Podcasts about arbs

THE LANCET 2003;362:767-771Background: Angiotensin II which plays a role in ventricular remodeling and progression of heart failure can be produced by pathways independent of angiotensin convening enzyme. Preliminary studies showed that the combination of angiotensin II blockers with angiotensin-converting enzyme inhibitors (ACEi) improves hemodynamics and reduces ventricular remodeling.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial sough to assess if adding the angiotensin-receptor blocker (ARB), candesartan, to ACEi could improve outcomes in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 40% or less within the previous 6 months, and NYHA class II, III or IV symptoms. Patients with NYHA class II symptoms had to have cardiac-related hospitalization within 6 months. Patients also had to have treatment with ACEi at a constant dose for at least 30 days.Exclusion criteria were not provided in the main manuscript.Baseline characteristics: Patients were recruited from 618 centers in 26 countries. The trial randomized 2,548 patients – 1,276 randomized to receive candesartan and 1,272 to receive placebo.The average age of patients was 64 years and 79% were men. The average left ventricular ejection fraction was 28%. Cardiomyopathy was ischemic in 62% of the patients. The NYHA class was II in 24% of the patients, III in 73% and IV in 3%.Approximately 48% had hypertension, 30% had diabetes, 56% had prior myocardial infarction, 9% had stroke, 27% had atrial fibrillation and 17% were current smokers.At the time of enrollment, 90% were taking a diuretic, 58% were taking digoxin, 55% were taking beta-blockers, 17% were taking spironolactone and all but two patients were taking ACEi.Procedures: The trial was double-blinded. Patients were assigned in a 1:1 ratio to receive candesartan starting at 4 or 8mg once daily or placebo. The treatment was doubled every two weeks to a target dose of 32mg once daily.After randomization, follow up occurred at 2, 4, and 6 weeks, 6 months and every 4 months thereafter.Endpoints: The primary outcome was a composite of cardiovascular death or heart failure hospitalizations. All deaths were classified as cardiovascular unless there was a clear non-cardiac cause.Analysis was performed based on the intention-to-treat principle. The estimated sample size to have 80% power at 5% alpha was 2,300 patients. The sample size calculation assumed 16% relative risk reduction in the primary outcome with candesartan assuming an 18% annual event rate in the placebo arm.Results: The median follow up time was 41 months. The mean candesartan daily dose was 24mg at 6 months.Candesartan reduced the primary endpoint of cardiovascular death or heart failure hospitalizations (37.9% vs 42.3%, adjusted HR: 0.85, 95% CI: 0.75 – 0.96; p= 0.01). Candesartan reduced the individual components of the primary outcome - (23.7% vs 27.3%; p= 0.021) for cardiovascular death and (24.2% vs 28.0%; p= 0.018) for heart failure hospitalizations. There was no significant reduction in all-cause death (29.5% with candesartan vs 32.4%; p= 0.105). The number of patients who had any hospitalization was similar in both groups (66.8% with candesartan vs 67.5%; p= 0.7), however, the total number of hospitalizations was lower with candesartan (2,462 vs 2,798; p= 0.023).Serum creatinine at least doubled in 7% of the patients in the candesartan group vs 6% in the placebo group. In the subset of patients taking spironolactone, serum creatinine at least double in 11% of the patients taking candesartan compared to 4% of the patients taking placebo.Hyperkalemia, defined as serum potassium of 6 mmol/L or higher, occurred in 3% of the patients in the candesartan group vs 1% in the placebo group. In the subset of patients taking spironolactone, hyperkalemia occurred in 4% of the patients taking candesartan compared to 1% of the patients taking placebo.There were two cases of angioedema in the candesartan group and three in the placebo group. All patients were taking an ACEi.There were no significant subgroup interactions, including in patients taking both beta-blockers and ACEi at baseline.Conclusion: In patients with systolic heart failure, adding candesartan to an ACEi reduced the primary composite outcome of cardiovascular death or heart failure hospitalizations with a number needed to treat of approximately of 23 patients over 41 months of follow up. The total number of all-cause hospitalizations was reduced by 336 with candesartan. All-cause death was not significantly reduced with candesartan.While the results of the trial appear impressive, the high number of adverse outcomes with candesartan in patients taking spironolactone is concerning. Spironolactone led to significant reduction in all-cause mortality in patients with systolic heart failure, as seen in the RALES trial, and should be prioritized over adding candesartan. Notably, fewer than 20% of patients in the trial were on spironolactone at baseline; if more had been, the incremental benefit of candesartan would likely have been reduced due to an increased risk of adverse effects from triple neurohormonal blockade (ACEi, ARBs, and mineralocorticoid receptor antagonists). Furthermore, spironolactone acts by blocking the aldosterone receptor, which is downstream in the renin–angiotensin–aldosterone system. Since candesartan blocks angiotensin II upstream in the same pathway, simultaneous inhibition at multiple points may lead to diminishing benefit.Finally, the differences observed in the subgroup of patients on beta-blockers between this trial and Val-HeFT remain unclear and may simply reflect the play of chance. As we previously discussed, patients receiving both an ACEi and beta-blockers had worse outcomes with valsartan in the Val-HeFT trial.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

In this episode of PT Snacks podcast, host Kasey explores the importance of understanding common hypertension and cholesterol medications encountered in outpatient orthopedic settings. Kasey discusses the effects of beta blockers, ACE inhibitors, ARBs, calcium channel blockers, diuretics, and statins on patients' response to exercise. The episode covers potential side effects, red flags, and practical tips for physical therapists, highlighting the significance of a holistic approach to patient care. Additional resources and special offers through MedBridge are also mentioned.00:00 Welcome to PT Snacks Podcast00:56 Importance of Pharmacology in PT02:09 Understanding Blood Pressure Medications04:31 Cholesterol Medications and Their Effects05:34 Red Flags and Patient Management Tips06:51 Additional Resources and ConclusionRelevant MedBridge Courses1. Exercise and Drug Interactions by Kenneth L. Miller - Overview: Understand how various medications interact with exercise. Covers physiology, drug metabolism, and exercise prescription. 2. Pharmacology for Rehabilitation: Considerations for the Aging Adult by Andrew Opett - Overview: Explores the effects of drugs like antihypertensives and statins, especially in older adults.Support the showWhy PT Snacks Podcast?This podcast is your go-to for bite-sized, practical info designed for busy, overwhelmed Physical Therapists and students who want to build confidence in their foundational knowledge without sacrificing life's other priorities. Stay Connected! Never miss an episode—hit follow now! Got questions? Email me at ptsnackspodcast@gmail.com or leave feedback HERE. Join the email list HERE On Instagram? Find unique content at @dr.kasey.hankins! Need CEUs Fast?Time and resources short? Medbridge has you covered: Get over $100 off a subscription with code PTSNACKSPODCAST: Medbridge Students: Save $75 off a student subscription with code PTSNACKSPODCASTSTUDENT—a full year of unlimited access for less!(These are affiliate links, but I only recommend Medbridge because it's genuinely valuable.) Optimize Your Patient Care with Tindeq Looking for a reliable dynamometer to enhance your clinical measurements? Tindeq ...

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on Sacubitril/Valsartan vs ACE Inhibitors or ARBs: A Systematic Review and Meta-Analysis of Randomized Trials

We hear from Caroline — SEND Advisor to the Special Partnership Trust — on how her schools are using and adapting our Planning Framework for Pupils with SEND. Interviewee: Caroline Jewell, SEND Advisor to the Special Partnership Trust Caroline is SEND Advisor to the Special Partnership Trust, having worked previously as a Headteacher. Based in the South West of England, the trust is made up of ten SEN schools and ARBs. Since it was founded in 2016, the trust has championed a collaborative and innovative approach to education, and this extends to their PSHE education programme.    Interviewer: Jenny Fox, Senior Subject Specialist Jenny is one of the Senior Subject Specialists at the PSHE Association. She has a Masters in Teaching and Learning, and led PSHE education and Citizenship in two London schools, including a school with Specialist Resourced Provision for Autism.

Learn more about becoming an Insider on our website: https://www.benbikman.comThis week in The Metabolic Classroom lecture, Ben focuses on the relationship between hypertension medications and metabolic health, providing a critical examination of their mechanisms and metabolic implications.He begins by highlighting the role of insulin resistance as a common root cause of both hypertension and metabolic disorders. Ben explains that while hypertension medications such as diuretics, beta blockers, ACE inhibitors, ARBs, and calcium channel blockers are often prescribed, they each have unique effects on insulin sensitivity and glucose metabolism, which can either mitigate or exacerbate metabolic dysfunction. Notably, some classes of these medications, like ARBs, may improve insulin sensitivity, while others, like beta blockers and diuretics, can impair it, leading to heightened risks for type 2 diabetes.Ben underscores the importance of addressing the root causes of hypertension—namely, insulin resistance—through lifestyle interventions like low-carbohydrate diets and fasting, which improve both blood pressure and metabolic health. He emphasizes the need for personalized treatment plans that consider the metabolic side effects of medications, advocating for strategies that tackle insulin resistance as a primary approach to improving overall health.Show Notes/References:For complete show notes and references referred to in this episode, we invite you to become a Ben Bikman “Insider” subscriber. As a subscriber, you'll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben, ad-free Metabolic Classroom Podcast episodes, show notes and references, Ben's Research Reviews Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more about becoming an Insider on our website: https://www.benbikman.comBen's favorite yerba maté and fiber supplement: https://ufeelgreat.com/usa/en/c/InsulinIQBen's favorite meal-replacement shake: https://gethlth.com (discount: BEN10)Ben's favorite electrolytes (and more): https://redmond.life (discount: BEN15)Ben's favorite allulose source: https://rxsugar.com (discount: BEN20)Ben's favorite health check-up for women: https://choosejoi.co/drben15 (discount: DRBEN15)Ben's favorite health check-up for men: https://blokes.co/drben15 (discount: DRBEN15)Ben's favorite exogenous ketone: https://www.americanketone.com (discount: Ben10)Other products Ben likes: https://www.amazon.com/shop/benbikmanphd#MetabolicHealth #Hypertension #BloodPressure #DrBenBikman #InsulinResistance #MetabolicScience #FatCellBiology #Diuretics #BetaBlockers #ACEInhibitors #CalciumChannelBlockers #BloodPressureMedications #HealthTips #DASHDiet #InsulinSensitivity #FatCells #KetogenicDiet #LowCarbLiving #HealthyLifestyle #HeartHealth Hosted on Acast. See acast.com/privacy for more information.

$5 Q-BANK: https://patreon.com/highyieldfamilymedicine Intro 0:30, Hypertension classifications 1:45, Lifestyle modifications 3:00, Thiazide diuretics 4:16, ACE Inhibitors and ARBs 5:59 Calcium channel blockers 8:15, Beta blockers 9:36, Mineralocorticoid receptor antagonists 10:49, Goal-directed medical therapy 12:49, Resistent hypertension 15:37, Other antihypertensives 16:38, Hypertensive emergency 20:33, Hypertension in pregnancy 23:00, Primary hyperaldosteronism 24:38, Renal artery stenosis 26:24, Cushing syndrome 27:22 Pheochromocytoma 28:53, Obstructive sleep apnea 30:26, Coarctation of the aorta 31:30, Practice questions 32:30

Sounds like a nifty musical group, but "Crochet and the White Sox Arbs" is the focus right now for this front office. The price for the All-Star pitcher is set, and only some teams can provide the ask. We'll explain why Chris Getz is in his element with this move. Meanwhile the team is already dropping arbitration eligible players, and the salary clearing makes sense at this stage of the offseason. Chris Lanuti and his buddy Ed Siebert sit at his 9-foot homemade oak bar in a basement on the South Side of Chicago to discuss their favorite team - The Chicago White Sox in a podcast "For Fans, By Fans!" Listen. Subscribe. Share. Call 708-459-8406 and leave your comments and questions for the next episode! SUBSCRIBE NOW​ on Apple Podcasts, Spotify, everywhere podcasts can be found and always at SoxInTheBasement.com!

Busking has long been a way for musicians to gain performance experience and garner a following. Busking in the streets of Melbourne CBD with their heartfelt performance is a new group of Filipino musicians (Birch, Zyra and Arbs) who call themselves “After Hours”. - Ang busking ay matagal nang naging paraan para sa mga musikero na magkaroon ng karanasan sa pagganap at makakuha ng mga followers. Makikita ang bagong grupong "After Hours" na sina Birch, Zyra at Arbs na nagtatanghal sa mga kalye ng Melbourne CBD.

Episode 49 – Abnormal Repetitive Behaviours in Dogs – What You Need To Know!   Abnormal Repetitive Behaviours in dogs are challenging to diagnose and treat. Their genetic and heritable nature, the large number of physical medical differential diagnoses and their ritualistic and invariant nature can make them difficult to live with and their treatment really requires the help and support of an expert!   In this episode you will learn: 1.      The definition of Abnormal Repetitive Behaviours 2.      The big 5 groups of ARBs 3.      What we need to think about when it comes to physical medical rule outs 4.      What breeds are predisposed 5.      How to treat these patients   Here are some of the resources Dr Katrin mentions in this episode: 1.      Moon-Fanelli, A. A., Dodman, N. H., & Cottam, N. (2007). Blanket and flank sucking in Doberman Pinschers. Journal of the American Veterinary Medical Association, 231(6), 907–912. https://doi.org/10.2460/javma.231.6.907   2.      Dodman, N. H., Karlsson, E. K., Moon-Fanelli, A., Galdzicka, M., Perloski, M., Shuster, L., Lindblad-Toh, K., & Ginns, E. I. (2010). A canine chromosome 7 locus confers compulsive disorder susceptibility. Molecular Psychiatry, 15(1), 8–10. https://doi.org/10.1038/mp.2009.111 We really hope you enjoy this episode; it is packed with so much information!   If you liked this episode of the show, The Pet Behaviour Chat, please LEAVE A 5-STAR REVIEW, like, share, and subscribe!   Facebook Group: Join The Pet Behaviour Community on Facebook   You can CONNECT with me: Website: Visit my website Trinity Veterinary Behaviour Instagram: Follow Trinity Veterinary Behaviour on Instagram Trinity Veterinary Behaviour Facebook: Join us on Trinity Veterinary Behaviour's Facebook page Trinity Veterinary Behaviour YouTube: Subscribe to Trinity Veterinary Behaviour on YouTube LinkedIn Profile: Connect with me on LinkedIn   Thank you for tuning in!

Guideline evolution is driven by ongoing research; recent studies like PeriOperative ISchemic Evaluation-3 Trial (POISE-3) and trials such as OPtimisation of Peri-operaTive CardIovascular Management to Improve Surgical outcomE II (OPTIMISE II) trial may influence recommendations on hemodynamic management and the use of tranexamic acid. Future guidelines are expected to integrate machine learning models for risk prediction, addressing complex patient phenotypes and interactions. Discontinuation vs. continuation of renin–angiotensin system inhibition before non-cardiac surgery: the SPACE trial has challenged existing practices regarding the discontinuation of ACE inhibitors or ARBs, highlighting the dynamic nature of medical guidelines and the continuous incorporation of new evidence to enhance patient care. Presented by Andy Cumpstey and Joff Lacey with Mark Edwards, Consultant in Anaesthesia and Perioperative Medicine, University Hospital Southampton Honorary Senior Clinical Lecturer, University of Southampton and John Whittle, Clinical Academic working in Perioperative Translational Medicine at UCL and Honorary Consultant in Perioperative Medicine, Anaesthesia and Critical Care at University College Hospitals London. -- More on POISE-3 here: https://clinicaltrials.gov/study/NCT03505723 More on OPTIMISE II here: https://optimiseii.org/ More on the SPACE trial here: https://doi.org/10.1093/eurheartj/ehad716  

We're taking a short summer break, but we'll be back at the end of August with brand new episodes.  Lose your heart to NephMadness 2022! Dr. Joel Topf (@kidney_boy) and Dr. Sadiya Khan (@HeartDocSadiya) tackle the NephMadness 2022 Cardiorenal Syndrome region, leading us through the pathophysiology of cardiorenal syndrome, how to approach the creatinine “bump” with diuresis, managing patients with diuretic resistance, and more. Claim CME for this episode at curbsiders.vcuhealth.org! Episodes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | thecurbsiders@gmail.com | Free CME! Show Segments Intro, disclaimer, guest bios Guest one-liners, Introduction to Nephmadness 2022 Case #1 from Kashlak: acute decompensated heart failure with elevated creatinine Definition and pathophysiology of cardiorenal syndrome Use of home ACE-is/ARBs and SGLT-2 inhibitors in cardiorenal syndrome Case #2 from Kashlak: the creatinine bump with diuresis Approach to the creatinine bump with diuresis Tips for the volume exam Interpreting cardiac biomarkers in patients with chronic kidney disease Case #3 from Kashlak: diuretic resistance Maximizing loop diuretic efficacy Sequential nephron blockade Use of hypertonic saline Outro Credits Producer, Writer, Show Notes, Infographics: Malini Gandhi Cover Art:  Beth Garbitelli Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP    Reviewer: Emi Okamoto MD, FACP Executive Producer: Beth Garbitelli Showrunner: Matthew Watto MD, FACP Editor: Clair Morgan of nodderly.com Guest: Dr. Joel Topf MD, Dr. Sadiya Khan MD Sponsor: Beginly Health Ready to take control of your job search? Visit beginlyhealth.com/curbsiders to get started.  Sponsor: Locumstory Tune in to The Locumstory Podcast on Spotify, Apple, or Google podcasts. Sponsor: Freed You can try Freed for free right now by going to freed.ai. And listeners of Curbsiders can use code CURB50 for $50 off their first month.

CardioNerds Dr. Rick Ferraro, Dr. Gurleen Kaur, and Dr. Maryam Barkhordarian discuss the evidence and data supporting SGLT inhibition for cardiovascular and kidney health outcomes with expert faculty Dr. Muthu Vaduganathan. They discuss the role of SGLT inhibitors in different populations, including those with diabetes mellitus, heart failure, CKD, and myocardial infarction. Show notes and audio editing by CardioNerds Academy Fellow Dr. Maryam Barkhordarian. This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan The benefit of SGLT inhibition extends beyond diabetes, and improves cardiovascular and kidney health outcomes independent of diabetes in appropriate patient populations. SGLT inhibition decreases cardiovascular mortality and heart failure hospitalization independent of left ventricular ejection fraction. SGLT inhibitors reduce clinically relevant events such as dialysis and transplantation in CKD patients irrespective of etiology and are now a cornerstone for the prevention of CKD progression. The introduction of polypills in heart failure can simplify GDMT implementation. Show notes - The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan How did SGLT inhibitors transition from “diabetes medication” to guideline-directed cardiovascular medicine? Most therapies in cardiology were developed for a particular purpose and ended up being indicated for a vastly different reason. The SGLT-2 inhibitors are no different. Cardiovascular safety concerns about diabetes medications led to a mandate to conduct cardiovascular outcomes trials for all novel diabetes medications. This federal requirement shed light on the cardiovascular benefits of SGLT inhibitors in patients with diabetes. These initial trials showed that not only are these medications safe but also, surprisingly, proved their role in preventing heart failure and delaying progression of chronic kidney disease. What are the mechanisms of action of SGLT-2 and SGLT-1/2 inhibitors? The central mechanism(s) of how these medications confer health outcomes benefits patients is/are not well understood. The main organ involved in the action of SGLT-2 inhibitors is the kidney at the level of the proximal tubule, impacting the cardiovascular system by handling salt and water and improving kidney efficiency. Conversely, SGLT-1/2 inhibitors also act at the level of the gut, the predominant location of the SGLT-1 cotransporter. Their effects on the cardiovascular system are secondary, given there is no SGLT-1 or -2 cotransporters in the myocardium. These secondary effects can be impacted through blood pressure reduction, volume regulation, improved glycemic control, etc. to overall improve cardiovascular status. Whatever the underlying mechanisms, the empirical data for their use is strong and growing. What is the role of SGLT inhibitors in preventing CKD progression? RAAS inhibitors (ACE inhibitors and ARBs) have been the cornerstone of CKD management for the past two to three decades. SGLT inhibitors have been the first add-on to this background therapy. Four trials, DAPA-CKD, EMPA-CKD, CREDENCE, and the SCORED, investigated the effects of SGLT-2 and SGLT-1/2 inhibitors in patients with CKD with or without diabetes. The outcomes of these trials include modifying the course of CKD and reducing events such as dialysis initiation and transplantation. These effects were regardless of participants' diabetic status, CKD etiology, or individual patient profile.

We're taking a short summer break, but we'll be back at the end of August with brand new episodes. Master common hypertension scenarios in the clinic! Our guest Dr. Jordy Cohen (@jordy_bc) will lead us through the FAQs of outpatient hypertension management, including making a diagnosis of hypertension, managing blood pressure in patients with chronic kidney disease, working up refractory hypertension, and more. Claim CME for this episode at curbsiders.vcuhealth.org! Credits ● Writer: Matthew Watto, MD, FACP ● Producers: Matthew Watto, MD, FACP and Malini Gandhi ● Show Notes, Infographic, and Cover Art: Malini Gandhi ● Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP ● Reviewer: Emi Okamoto MD ● Executive Producer: Beth Garbitelli ● Showrunner: Matthew Watto MD, FACP ● Editor: Clair Morgan of nodderly.com ● Guest: Jordy Cohen MD Show Segments ● Intro, disclaimer, guest bio ● Guest one-liner, Picks of the Week* ● Case from Kashlak: New diagnosis of hypertension ● How to make a diagnosis of hypertension ● When to start anti-hypertensive medication ● Initial blood pressure regimen ● Case from Kashlak: White coat hypertension ● Case from Kashlak: Hypertension in chronic kidney disease ● ACEis and ARBs in chronic kidney disease ● Diuretics in chronic kidney disease ● Case from Kashlak: Refractory hypertension ● History and initial workup for refractory hypertension ● Treatment of primary hyperaldosteronism ● Outro

N Engl J Med 2024;390:1372-1381Background: Beta-blockers are prescribed to the majority of patients with acute myocardial infarction. The bulk of evidence supporting this practice comes from trials published in the 1980s - BHAT and ISIS-I. Since the publication of these seminal trials, the care of patients with acute myocardial infarction has significantly changed with improvement in antiplatelet therapy, the addition of high-intensity statins and renin–angiotensin–aldosterone system antagonists in addition to early revascularization for STEMI patients. Furthermore, myocardial injury is now detected based on high-sensitivity troponin assays which can detect smaller myocardial infarctions. Therefore, there is a lack of evidence whether beta-blockers provide benefit for patients with acute myocardial infarction in the current era.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.The Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) trial sought to assess whether long-term oral beta-blocker treatment improves outcomes in patients with acute myocardial infarction and preserved left ventricular ejection fraction.Patients: Eligible patients were adults, 1 to 7 days after myocardial infarction who underwent coronary angiography and echocardiography. Patients were required to have obstructive coronary artery disease on coronary angiography defined as stenosis of ≥50%, a fractional flow reserve of ≤0.80, or an instantaneous wave-free ratio of ≤0.89 at any time point before randomization. Left ventricular Ejection fraction on echocardiogram had to be ≥50%. Patients were excluded if they had contraindications to beta-blockers or if the treating physician determined that treatment with beta-blockers is indicated for other conditions.Baseline characteristics: The trial randomized 2,508 patients to the beta-blockers group and 2,512 patients to the control group. The average age of patients was 65 years with 78% being men. About 20% were current smokers, 46% had hypertension, 14% had diabetes, 7% had prior myocardial infarction and < 1% had prior heart failure.The index event was STEMI in 35% of the patients. About 96% underwent percutaneous coronary intervention. The median heart rate was 74 bpm and the median systolic blood pressure was 151 mm Hg.Medications at discharge included aspirin in 97% of the patients, P2Y12 inhibitors in 96%, ACEi or ARBs in 80% and statins in 99%.Procedures: Patients were randomized 1:1 to receive metoprolol succinate (first choice), bisoprolol (second choice) or no beta-blockers. The target doses were at least 100 mg daily for metoprolol succinate and at least 5 mg daily for bisoprolol. Patients in the control group were discouraged from using beta-blockers; they did not receive placebo. If a patient was on beta-blocker therapy at the time of enrollment and was randomly assigned to the no–beta-blocker group, the beta-blocker had to tapered off over a period of 2 to 4 weeks.Endpoints: The primary end point was a composite of death from any cause or new myocardial infarction. Secondary end points were death from any cause, death from cardiovascular causes, myocardial infarction, hospitalization for atrial fibrillation as primary diagnosis, and heart failure hospitalization. There were three safety endpoints: 1- Hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker, 2- hospitalization for asthma or chronic obstructive pulmonary disease as a primary diagnosis and 3- hospitalization for stroke.Data on clinical end points were not centrally adjudicated but rather obtained from the SWEDEHEART registry and the Swedish Population Registry.Statistical analysis was performed based on the intention-to-treat principle. Before trial initiation, the estimated event rate in the control group was 7.2%/ year and at least 16.7% lower event rate in the beta-blocker group was considered clinically meaningful. During the trial, the actual event rate in control group was 3%/ year. Given this event rate, a 25% lower event rate in the beta-blocker group was considered clinically meaningful. A total of 379 primary end point events were needed in order to have 80% power at a two-sided alpha of 0.05, to detect the 25% lower event rate with beta-blockers. The estimated number of patients needed was about 5,000.Results: Among the patients who attended the SWEDEHEART registry, 1500/1831 (81.9%) of the beta-blocker group were still taking beta-blockers after 11 to 13 months; compared to 269/ 1886 (14.3%) in the no beta-blocker group.After a median follow up time of 3.5 years, beta-blockers did not the reduce the composite primary endpoint compared to no beta-blockers (7.9% vs 8.3%, HR: 0.96; 95% CI, 0.79 - 1.16; p= 0.64). There were no significant differences in death from any cause (3.9% vs 4.1%), death from cardiovascular causes (1.5% vs 1.3%), myocardial infarction (4.5% vs 4.7%), hospitalization for atrial fibrillation (1.1% vs 1.4%) or hospitalization for heart failure (0.8% vs 0.9%).Safety endpoints were also not significantly different between both groups; 3.4% vs 3.2% for the bradyarrhythmia, syncope or hypotension endpoint, 0.6% in both groups for the hospitalization for asthma or COPD endpoint and 1.4% vs 1.8% for hospitalization for stroke.There were no significant subgroup interactions.Conclusion: In patients with acute myocardial infarction who underwent coronary angiography and had preserved left ventricular systolic function, treatment with beta-blockers did not improve outcomes over a 3.5-year follow-up. Events were infrequent in the trial; 1.4% for cardiovascular death, 4.6% for recurrent myocardial infarction and 0.8% for hospitalization for heart failure. The low event rate in this population in the current era makes it difficult to demonstrate additional benefit with more therapies.The open-label design of the study may have introduced performance bias; however, this bias is expected to favor beta-blockers given the superiority design of the study. Another limitation, as noted by the authors, is that outcomes were obtained from the SWEDEHEART registry and the Swedish Population Registry and were not centrally adjudicated. However, this is expected to affect both groups equally.We believe the divergent results between this trial and older beta-blocker trials in myocardial infarction patients such as BHAT and ISIS-1 which were published in the 1980s, is due to the significant improvement in the management of acute myocardial infarction over time including improved medical therapy in addition to early revascularization for STEMI patients. This improved patient care has led to significantly lower mortality rates over time. For instance, all-cause death in the control arm of REDUCE-AMI is significantly lower than that of BHAT and ISIS-1, at 4.1% vs 9.8% and 11.9%, respectively. This is despite REDUCE-AMI having a longer follow-up period of 3.5 years compared to 2.1 years and 1 year in the earlier trials.In conclusion, this study does not provide evidence that beta-blockers improve outcomes for patients with acute myocardial infarction and preserved ejection fraction in the contemporary era.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

NEJM 2021:385:1845-55.Background Over two decades had passed since the publications of the seminal trials comparing ACE inhibitors with placebo in post-MI patients with LV dysfunction and congestive heart failure (SAVE, AIRE and TRACE). The VALIANT trial, published in 2003, found that the ARB drug Valsartan was as effective as Captopril in improving survival and reducing cardiovascular morbidity in this patient population. Thus, for many years, a cornerstone of managing post-MI patients with LV dysfunction and heart failure involved afterload reduction with ACE inhibitors or ARBs.Then in 2014, the landscape of heart failure management changed with the publication of the PARADIGM-HF trial which found that Entresto, a drug combining the ARB Valsartan and the neprilysin inhibitor Sacubitril, significantly reduced death and heart failure hospitalizations. We will review PARDIGM-HF later since it enrolled patients with chronic, stable heart failure and not post-MI patients. The rationale for the combination drug is that it simultaneously blocks the renin-angiotensin system and inhibits of the breakdown of several vasoactive peptides including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), serving to enhance vasodilation and reduce blood volume.The PARADISE-MI trial sought to test the hypothesis that early initiation of Sacubitril-Valsartan in post-MI patients with LV dysfunction and congestive heart failure would reduce cardiovascular death or incident heart failure compared to the ACE inhibitor Ramipril.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Adults without a history of heart failure who had a spontaneous MI within 0.5 to 7 days before presentation who had either a LVEF of /= 70 years, diabetes, previous MI, eGFR

Arbs for Blood Pressure? Favorite Foods to Carb Up, Highest Protein Per Meal? Favorite Foods For Contest Carb Up? TIME STAMPS BELOW Coaches Skip Hill, Andrew Berry, Scott McNally - Blood Sweat & Gear Coaching QA 245

In this episode, I divide losartan and Cozaar into syllables, tell you which syllables to emphasize, and share my sources. The written pronunciations can be helpful, so you can see them below and in the show notes on thepharmacistsvoice.com.   The purpose of my pronunciation episodes is to provide the intended pronunciations of drug names from reliable sources so you feel more confident saying them and less frustrated learning them.    Losartan = loe-SAR-tan, emphasize SAR (source: USP Dictionary Online)   Cozaar = CO-zar, emphasize CO (patient information on Organon's website)   If you know someone who needs to learn how to say losartan and Cozaar, please share this episode with them. Subscribe to/follow this podcast for all future episodes.    Thank you for listening to episode 272 of The Pharmacist's Voice ® Podcast!   To read the FULL show notes, visit https://www.thepharmacistsvoice.com.  Click the Podcast tab, and select episode 272.   Subscribe to or follow The Pharmacist's Voice ® Podcast to get each new episode delivered to your podcast player and YouTube every time a new one comes out!     Apple Podcasts   https://apple.co/42yqXOG  Spotify  https://spoti.fi/3qAk3uY  Amazon/Audible  https://adbl.co/43tM45P YouTube https://bit.ly/43Rnrjt   Links from this episode USP Dictionary Online (aka “USAN”)  **Subscription-based resource USP Dictionary's (USAN) pronunciation guide (Free resource on the American Medical Association's website) Patient Information for Cozaar ® via Organon's website accessed April 1, 2024 The Pharmacist's Voice Podcast Episode 269, pronunciation series episode 28 (tirzepatide) The Pharmacist's Voice Podcast Episode 267, pronunciation series episode 27 (atorvastatin)  The Pharmacist's Voice Podcast Episode 265, pronunciation series episode 26 (omeprazole) The Pharmacist's Voice Podcast Episode 263, pronunciation series episode 25 (PDE-5 inhibitors) The Pharmacist's Voice Podcast Episode 259, pronunciation series episode 24 (ketorolac) The Pharmacist's Voice ® Podcast episode 254, pronunciation series episode 23 (Paxlovid) The Pharmacist's Voice ® Podcast episode 250, pronunciation series episode 22 (metformin/Glucophage) The Pharmacist's Voice Podcast ® episode 245, pronunciation series episode 21 (naltrexone/Vivitrol) The Pharmacist's Voice ® Podcast episode 240, pronunciation series episode 20 (levalbuterol) The Pharmacist's Voice ® Podcast episode 236, pronunciation series episode 19 (phentermine)  The Pharmacist's Voice ® Podcast episode 228, pronunciation series episode 18 (ezetimibe) The Pharmacist's Voice ® Podcast episode 219, pronunciation series episode 17 (semaglutide) The Pharmacist's Voice ® Podcast episode 215, pronunciation series episode 16 (mifepristone and misoprostol) The Pharmacist's Voice ® Podcast episode 211, pronunciation series episode 15 (Humira®) The Pharmacist's Voice ® Podcast episode 202, pronunciation series episode 14 (SMZ-TMP) The Pharmacist's Voice ® Podcast episode 198, pronunciation series episode 13 (carisoprodol) The Pharmacist's Voice ® Podcast episode 194, pronunciation series episode 12 (tianeptine) The Pharmacist's Voice ® Podcast episode 188, pronunciation series episode 11 (insulin icodec)  The Pharmacist's Voice ® Podcast episode 184, pronunciation series episode 10 (phenytoin and isotretinoin) The Pharmacist's Voice ® Podcast episode 180, pronunciation series episode 9 Apretude® (cabotegravir) The Pharmacist's Voice ® Podcast episode 177, pronunciation series episode 8 (metoprolol)  The Pharmacist's Voice ® Podcast episode 164, pronunciation series episode 7 (levetiracetam) The Pharmacist's Voice ® Podcast episode 159, pronunciation series episode 6 (talimogene laherparepvec or T-VEC)  The Pharmacist's Voice ® Podcast episode 155, pronunciation series episode 5 Trulicity® (dulaglutide)  The Pharmacist's Voice ® Podcast episode 148, pronunciation series episode 4 Besponsa® (inotuzumab ozogamicin) The Pharmacist's Voice ® Podcast episode 142, pronunciation series episode 3 Zolmitriptan and Zokinvy The Pharmacist's Voice ® Podcast episode 138, pronunciation series episode 2 Molnupiravir and Taltz The Pharmacist's Voice ® Podcast episode 134, pronunciation series episode 1 Eszopiclone and Qulipta

On this podcast episode, I discuss some of the most common antihypertensive drug interactions you need to know. One major interaction I discuss is the trifecta of a diuretic, an ACE or ARB, and an NSAID. This combination significantly increases the risk for acute renal failure. Nitrates aren't classically referred to as an antihypertensive but they can definitely cause some problems when combined with PDE5 Inhibitors. Lithium can interact with 3 blood pressure medication classes. ACEIs, ARBs, and diuretics can all increase the risk for lithium toxicity.

Special guest Luke Laffin, MD, FACC, the Co-Director, Center for Blood Pressure Disorders with the Department of Cardiovascular Medicine at the Cleveland Clinic joins us to talkabout first-line meds for hypertension.Listen in as they discuss nuances regarding selection of a first-line medication for the treatment of hypertension.You'll also hear practical advice from panelists on TRC's Editorial Advisory Board:Andrea Darby Stewart, MD, Associate Director, Honor Health Family Medicine Residency Program and Clinical Professor of Family, Community & Occupational Medicine at the University of Arizona College of Medicine - PhoenixDouglas S. Paauw, MD, MACP, Professor of Medicine at the University of Washington School of MedicineFor the purposes of disclosure, Dr. Luke Laffin reports relevant financial relationships with CRISPR Therapeutics [hyperlipidemia], Eli Lilly [obesity], Medtronic [hypertension] (honorarium); Arrowhead [hyperlipidemia], AstraZeneca [hyperlipidemia], Mineralys Therapeutics [hypertension] (grants/research support).The other speakers have nothing to disclose. All relevant financial relationships have been mitigated.TRC Healthcare offers CE credit for this podcast. Log in to your Pharmacist's Letter or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.The clinical resources mentioned during the podcast are part of a subscription to Pharmacist's Letter and Prescriber Insights: Chart: Treatment of HypertensionChart: Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme InhibitorsChart: Comparison of Calcium Channel BlockersChart: Comparison of Commonly Used DiureticsIf you're not yet a Pharmacist's Letter or Prescriber Insights subscriber, find out more about our product offerings at trchealthcare.com. Follow or subscribe, rate, and review this show in your favorite podcast app. You can also reach out to provide feedback or make suggestions by emailing us at ContactUs@trchealthcare.com.

Episode 154: Heart Failure and GDMTDr. Malave explains the four main medications that are part of the guideline-directed medical therapy of heart failure with reduced ejection fraction. Dr. Arreaza added comments and questions.  Written by Maria Fernanda Malave, MD. Edits by Hector Arreaza, MD.  You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Brief introduction: Heart failure (HF) is a common condition that affects about 23 million people in the world, and it is estimated that 50% of cases are due to heart failure with reduced ejection fraction (HFrEF). It is a major public health concern because of the high morbidity and mortality with a 5-year survival rate of 25% after hospitalization due to HFrEF.In recent years, the management of HFrEF has evolved due to increased evidence in favor of certain medications. Guideline-directed medical therapy (GDMT) is the foundation of medical therapy for these patients, and it is the result of multiple randomized controlled trials and reviews favoring four main drug classes: 1. renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors -ACEi- and angiotensin receptor blockers -ARB), 2. evidence-based β-blockers, 3. mineralocorticoid inhibitors, and 4. sodium-glucose cotransporter 2 inhibitors -SGLT-2i-. The benefit of this therapy is mostly seen when these four groups of medications are used in conjunction. During this episode, we will provide some key elements about the prescription of these medications, but this is only an overview, and you are invited to continue learning from reputable sources.Definitions: HF is defined as the impairment of the heart to meet the metabolic demands of the body. It can be caused by multiple conditions that interfere with the filling up of the heart or conditions that prevent an effective ejection of blood out of the heart. Classification of HFrEF: Based on the EF by echocardiogram, heart failure can be classified as:Heart failure with preserved ejection fraction (HFpEF) when the EF is 50% or more.Heart failure with mildly reduced ejection fraction when EF ranges between 41-49%.Heart failure with reduced ejection fraction (HFrEF) when EF is 40% or less.GDMT: Once we make the diagnosis of HF, it is key to educate our patients and re-educate them every single visit about the importance of guideline-directed medical therapy (GDMT) and lifestyle modifications, because this can change the prognosis and exacerbation rates. Many patients think that since they are feeling well after starting GDMT they can stop it, but that's going to increase exacerbations, hospitalizations, and decrease quality of life. Key points to discuss with patients.First, discuss that GDMT are disease-modifying drugs that regulate the neurohormonal system to stop the progression of the disease. We should explain to our patients that medications should be taken despite feeling well. Also, patients should be educated about regular follow-ups and medication titration. We can even instruct our patients about increasing their furosemide dose if they observe signs of overload, such as a weight increase of 2-3 kgs in 3-4 days, tight rings, socks or bracelets, also Paroxysmal nocturnal dyspnea, dyspnea on exertion, and more.  Second, lifestyle modifications such as: quit smoking and alcohol. Additionally, in general, water restriction between 1.2-1.5L daily, salt restriction (there is no official recommendation about how many grams, but in general we recommend less than 2g daily). Third, it is highly recommended to do aerobic exercise that produces mild dyspnea since this improves cardiovascular capacity and decreases hospitalization risk. Patients should be encouraged to have their annual influenza vaccine and pneumococcal vaccine according to their own immunization schedule. According to the AFP journal, in September 2022, researchers found a clinically and statistically significant reduction in all-cause mortality for patients who received an influenza vaccine right after an MI, with a number needed to treat of 50, the effectivity of the vaccine may vary by season.GDMT, groups of medications:What are the basic medications any patient with HF should be on? At least, patients should be on angiotensin receptor blockers ARBs/ACEIs and Beta-blockers. Let's keep in mind that beta-blockers should be given cautiously in cases of exacerbation, but in general low doses are safe. We also have the angiotensin receptor/neprilysin inhibitors (ARNIs), a group of medications whose representative is the combination of sacubitril/valsartan, aka Entresto®. This medication should be the target once ARBs/ACEIs are tolerated. ARBs/ACEIs/ARNIs should be discontinued in the setting of advanced CKD, with a GFR of 30 or less. This applies to other medications used in HF such as SGLT-2 and mineralocorticoid receptor antagonist (MRA, such as spironolactone/eplerenone). Remember that SGLT-2 inhibitors should be started regardless diabetes status, and BB are safe in the setting of CKD. We also have other groups that are considered safe in patients with advanced CKD such as hydralazine/isosorbide dinitrate (combined or not), which are used in African Americans whose BP and HF symptoms do not improve with maximally tolerated dose of ARBs/ACEIs + BB.Ivabradine: Let's not forget about ivabradine, which is an SA node inhibitor like BB. Patients need to meet criteria such as a maximally tolerated dose of beta-blocker, heart rate of a least 70 or more and being on normal sinus rhythm to be started on this medication. Ivabradine does not improve survival as BB do, so even though they are not contraindicated in HF exacerbation, BB are still preferred since ivabradine does not decrease mortality.Titration and follow-ups in the HF management:-ARBs/ACEIs/ARNIs should be titrated approx. Q2 weeks until the maximally tolerated dose is achieved, ARNI should be titrated up Q2-4weeks. With these medications, we should monitor BP, potassium levels and Glomerular Filtration Rate (GFR). -BB can also be titrated up Q2weeks until the maximally tolerated dose is achieved. HR, BP and signs of congestion should be observed in patients on BB. Same for hydralazine/isosorbide, with BP follow-up. -MRA, such as spironolactone/eplerenone, these meds can be added in patients who remain symptomatic despite maximally tolerated doses of “ARBs or ACEIs or ARNIs” plus Beta-blockers. For MRA, potassium level, and GFR should be monitored every 2-3 days after initiation, 7 days after titration, monthly for 3 months, and then Q3 months. To start a patient on MRA, K+ must be lower than 5.Patients with HF should be followed up at least in a 2-week interval either via telephone, telemedicine, or clinic visit to assess symptoms, vital signs, bloodwork and to perform a physical exam. Monitoring EF: After 3-6 months of the patient´s stabilization, we should reorder an echo, EKG, BNP and Basic Metabolic Panel. The ejection fraction improves in all patients after GDMT initiation and compliance, and in some patients, this improvement is very significant, so we need to reassess EF after stabilization. Comorbidities: Also, let´s keep in mind that most of the patients have associated comorbidities such as Afib, diabetes, valve disease, or anemia. These comorbidities must be addressed either by starting anticoagulation, adjusting anti-diabetes medications, starting iron, or referring to cardiology if a valve replacement is needed.When to refer to Cardiology? Some patients will qualify for device therapy (ICD) as a primary prevention for ventricular arrhythmias that can degenerate either into torsades or ventricular fibrillation. These patients must be symptomatic, at least in 3 months of maximally tolerated GDMT, and EF between 30-35%. Symptomatic

On this episode, I discuss aliskiren pharmacology, adverse effects, drug interactions, and much more. Aliskiren should not be used with ACE Inhibitors or ARBs. I discuss why that is in this episode. Aliskiren has a long enough half-life at approximately 24 hours so it is recommended to only take this once daily. Hyperkalemia is a major concern with aliskiren. It is important to monitor potassium levels and renal function.

Injectable, long-acting therapy is a new frontier for hypertension management. Join host, Geoff Wall, as he evaluates zilebesiran, a hepatic angiotensinogen blocker for blood pressure control for up to six months. The GameChangerZilebesiran blocks the final production of angiotensinogen at the hepatic level making it safer from a renal perspective than the ACEis or ARBs. A single subcutaneous injection provides therapy for up to six months. HostGeoff Wall, PharmD, BCPS, FCCP, BCGPProfessor of Pharmacy Practice, Drake UniversityInternal Medicine/Critical Care, UnityPoint Health ReferenceDesai AS, Webb DJ, Taubel J, et al. Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension. N Engl J Med. 2023 Jul 20;389(3):228-238. doi: 10.1056/NEJMoa2208391. PMID: 37467498.https://www.nejm.org/doi/full/10.1056/NEJMoa2208391 Pharmacist Members, REDEEM YOUR CPE HERE! Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)CPE Information Learning ObjectivesUpon successful completion of this knowledge-based activity, participants should be able to:1. Describe the mechanism of action of Zilebesiran2. Discuss possible advantages and disadvantages of this drug in the treatment of hypertension0.05 CEU/0.5 HrUAN: 0107-0000-23-323-H01-PInitial release date: 10/16 /2023Expiration date: 10/16/2024Additional CPE details can be found here.Follow CEimpact on Social Media:LinkedInInstagramDownload the CEimpact App for Free Continuing Education + so much more!

We're taking a short summer break, but we'll be back in September with brand-new episodes. Can't wait? Join our Kashlak family at patreon.com/curbsiders for access to twice-monthly bonus episodes… there are already 9 of them available to feed your brain hole! Yummy! Master common hypertension scenarios in the clinic! Our guest Dr. Jordy Cohen (@jordy_bc) will lead us through the FAQs of outpatient hypertension management, including making a diagnosis of hypertension, managing blood pressure in patients with chronic kidney disease, working up refractory hypertension, and more. Free CME for this episode at curbsiders.vcuhealth.org Patreon | Episodes | Subscribe | Spotify | YouTube | Newsletter | Contact | Swag! | CME Credits Writer: Matthew Watto, MD, FACP Producers: Matthew Watto, MD, FACP and Malini Gandhi Show Notes, Infographic, and Cover Art: Malini Gandhi Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP    Reviewer: Emi Okamoto MD Executive Producer: Beth Garbitelli Showrunner: Matthew Watto MD, FACP Editor: Clair Morgan of nodderly.com Guest: Jordy Cohen MD CME Partner: VCU Health CE The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit. See info sheet for further directions. Note: A free VCU Health CloudCME account is required in order to seek credit. Show Segments Intro, disclaimer, guest bio Guest one-liner, Picks of the Week* Case from Kashlak: New diagnosis of hypertension How to make a diagnosis of hypertension When to start anti-hypertensive medication Initial blood pressure regimen Case from Kashlak: White coat hypertension Case from Kashlak: Hypertension in chronic kidney disease ACEis and ARBs in chronic kidney disease Diuretics in chronic kidney disease Case from Kashlak: Refractory hypertension History and initial workup for refractory hypertension Treatment of primary hyperaldosteronism Outro Sponsor: Green Chef Go to GreenChef.com/60curb and use code 60curb to get 60% off plus free shipping.

Dette afsnit er en liveoptagelse fra Empire Bio, hvor vi talte om og så Barry Jenkins' prisvindende fænomenale film fra 2016, Moonlight. Dramaet 'Moonlight' er historien om den unge mand, Chiron, fortalt gennem tre definerende nedslag: barndom, ungdom og voksenliv. Fra en ludfattig barndom med grov mobning og en opvækst, hvor vold og spørgsmål om seksualitet presser sig på til et voksenliv, hvor han må genforhandle sin identitet og tage ejerskab over sit eget liv.'Moonlight' er skrevet og instrueret af Barry Jenkins. Han vandt en Oscar for bedste adapterede manuskript, og selve filmen modtog den prestigefyldt Oscar for bedste film i 2017.Til at snakke om Moonlight har vi inviteret to überseje film-professionelle og yderst kyndige typer med os i dag: Elombe brice Parfait & Kristian Arbs. Vi taler blandt andet om, hvordan Moonlight især blev fremhævet for måden den formåede at hæve sig over den stereotypiserende skildring af både tilværelsen i det amerikanske ghetto og en kærlighedsrelation mellem to sorte mænd. En skildring, der er båret af en særdeles fremragende, nærværende og levende skuespilpræstation. Har I set Moonlight, og hvad har gjort særligt indtryk hos jer?

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines were recently updated with a focus on kidney health in patients with diabetes.  The updated guidelines include recommendations on screening, prevention, and treatment of chronic kidney disease (CKD), including the use of SGLT2 inhibitors, finerenone, and ACE inhibitors or ARBs.  The written commentary posted on the iForumRx website provides a succinct summary of the Top Ten Things Every Clinician Should Know. Guest Authors:  Kara Olstad, PharmD; Gurminder Sanghera, BSc, PharmD; and Darren Grabe, PharmD Music by Good Talk

Welcome to another enlightening episode of our podcast, where we delve into the latest medical research to bring you insights that can enhance your understanding and practice. This episode focuses on four intriguing studies: STUDY #1: We begin with a fascinating study comparing the responses of an AI chatbot and physicians to medical questions posted on a Reddit forum. The results might surprise you and prompt a rethink on how AI can assist in routine physician duties. Ayers JW et al. Comparing physician and artificial intelligence chatbot responses to patient questions posted to a public social media forum. JAMA Intern Med 2023 Apr 28; [e-pub]. (https://doi.org/10.1001/jamainternmed.2023.1838)   STUDY #2: Next, we delve into the POISE-3 trial, which examined the effects of hypotension-avoidance versus hypertension-avoidance strategies in noncardiac surgery. The findings could have significant implications for the management of patients with hypertension undergoing surgery. Marcucci M et al. Hypotension-avoidance versus hypertension-avoidance strategies in noncardiac surgery: An international randomized controlled trial. Ann Intern Med 2023 Apr 25; 176:605. (https://doi.org/10.7326/M22-3157)   STUDY #3: Our third study is the IRONMAN trial, which investigated the effects of intravenous ferric derisomaltose in patients with heart failure and iron deficiency. The results provide further support for the benefit of iron repletion in this population. Kalra PR et al. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): An investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet 2022 Dec 17; 400:2199. (https://doi.org/10.1016/S0140-6736(22)02083-9)   STUDY #4: Finally, we discuss a subgroup analysis of the AFFIRM-AHF trial, exploring the association between hemoglobin levels and the efficacy of intravenous ferric carboxymaltose in patients with acute heart failure and iron deficiency. The findings shed light on the role of hemoglobin levels in the treatment outcomes of these patients. Filippatos G et al. Association between hemoglobin levels and efficacy of intravenous ferric carboxymaltose in patients with acute heart failure and iron deficiency: An AFFIRM-AHF subgroup analysis. Circulation 2023 Apr 13; [e-pub]. (https://doi.org/10.1161/CIRCULATIONAHA.122.060757)   This episode promises to be a treasure trove of knowledge, offering insights into the role of AI in medicine, the management of hypertension in surgery, the importance of iron repletion in heart failure, and the influence of hemoglobin levels on treatment outcomes. So, grab your headphones and join us as we navigate these captivating studies. Don't miss this opportunity to enhance your understanding and make a difference in patients' lives. See you there! For shownotes, visit us at https://www.medmastery.com/podcasts/cardiology-podcast.  

In this episode we explore ways in which the extracellular matrix can be manipulated, including the story of doxycycline, TGF-beta in Marfan syndrome and whether beta blockers can reduce vascular events in vascular EDS. ·        Intro 0:12 ·        Review of previous episode 0:28 ·        In this episode 2:26 ·        The pressure against the vessels 4:06 ·        The pressure against the wall 8:44 ·        Matrix metalloproteinases 10:16 ·        Tadpole study – collagen breakdown 10:35 ·        Tetracycline antibiotics 14:05 ·        Rat model – periodontal disease and hydroxyproline 14:24 ·        Chemically modified tetracyclines 20:14 ·        Mouse model – tetracycline use 22:00 ·        Tetracyclines and other autoimmune conditions 23:22 ·        Marfan syndrome 24:45 ·        Fibrillin and Marfan syndrome 28:48 ·        TGF-beta 29:36 ·        Mouse model – Marfan syndrome and fibrillin 31:14 ·        ARBs and TGF-beta 33:51 ·        TGF-beta and vascular EDS 37:25 ·        Back to the mouse model 38:38 ·        Protein kinase C 39:56 ·        Summary 40:26 Disclosures: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Bowen CJ, et al. J Clin Invest. 2020;130:686-698. Brooke BS. Lancet. 2010;doi:10.1016/S0140-6736(10)61155-5 Dietz HC, et al. Am J Med Genet C Semin Med Genet. 2005;doi:10.1002/ajmg.c.30068. Dubacher N, et al. Cardiovasc Res. 2020;116:457-465. Golub LM, et al. SAGE. 1998;doi:10.1177/08959374980120010501. Gross J, et al. PNAS. 1962;doi:10.1073/pnas.48.6.1014 Habashi JP, et al. Science. 2006;312:117-121. Morissette R, et al. Circ Cardiovasc Genet. 2014;7:80-88. Mullen M, et al. Lancet. 2019;394:2263-2270. Neptune ER, et al. Nat Genet. 2003;33:407-411.

This month on Episode 45 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the February 3rd and February 17th issues of Circulation Research. This episode also features an interview with Dr Hind Lal and Dr Tousif Sultan from the University of Alabama at Birmingham about their study Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation.   Article highlights:   Pi, et al. Metabolomic Signatures in PAH   Carnevale, et al. Thrombosis TLR4-Mediated in SARS-CoV-2 Infection   Cai, et al. Macrophage ADAR1 in AAA   Koide, et al. sEVs Accelerate Vascular Calcification in CKD   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cynthia St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today I'm going to be highlighting the articles from our February 3rd and 17th issues of Circulation Research. I'm also going to have a chat with Dr Hind Lal and Dr Tousif Sultan from the University of Alabama at Birmingham about their study, Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. But before I get to the interviews, here are a few article highlights.   Cindy St. Hilaire:        The first article I want to highlight comes from the laboratory of Dr Peter Leary at the University of Washington, and the title is Metabolomic Signatures Associated With Pulmonary Arterial Hypertension Outcomes. Pulmonary Arterial Hypertension or PAH is a rare but life-threatening disease in which progressive thickening of the walls of the lung's blood vessels causes increased blood pressure and that increased blood pressure ultimately damages the heart's right ventricle.   Interestingly, progression to heart failure varies considerably among patients, but the reasons why there is variability are not well understood. To find out, this group turned their attention to patient metabolomes, which differ significantly from those of healthy people and thus may also change with severity. Blood samples from 117 PAH patients were analyzed for more than a thousand metabolites by mass spectrometry and the patient's progress was followed for the next three years. 22 patients died within a three-year period and 27 developed significant right ventricle dilation. Other measures of severity included pulmonary vascular resistance, exercise capacity and levels of BNP, which is a metric of heart health. Two metabolic pathways, those relating to polyamine and histidine metabolism, were found to be linked with all measures of severity suggesting a key role for them in disease pathology. While determining how these pathways influence disease as a subject for further study, the current findings may nevertheless lead to new prognostic indicators to inform patient care.   Cindy St. Hilaire:        The next article I want to discuss is coming from our February 3rd issue of Circulation Research and this is coming from the laboratory of Dr Francisco Violi at the University of Rome and the title is Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2 Infection. Thrombosis can be a complication of COVID-19 and it is associated with poor outcomes, including death. However, the exact mechanism by which the virus activates platelets, which are the cells that drive thrombosis, is not clear. For one thing, platelets do not appear to express the receptor for SARS-CoV-2. They do however, express the TLR4 receptor and that's a receptor that mediates entry of other viruses as part of the immune response. And TLR4 is ramped up in COVID-19 patient platelets. This group now confirms that, indeed, SARS-CoV-2 interacts with TLR4, which in turn triggers thrombosis.   The team analyzed platelets from 25 patients and 10 healthy controls and they found that the platelet activation and thrombic activity were both boosted in the patient samples and could not be blocked using a TLR4 inhibitor. Additionally, immunoprecipitation and immunofluorescent experiments further revealed colocalization between the virus protein and the TLR4 receptor on patient platelets. The team went on to show that the signaling pathway involved reactive oxygen species producing factors p47phox and Nox2, and that inhibition of phox 47, like that of the TLR4 receptor itsel,f could prevent platelet activation. As such, this study suggests that inhibiting either of these proteins may form the basis of an antithrombotic treatment for COVID-19.   Cindy St. Hilaire:        The third article I want to highlight is coming from the lab of Shi-You Chen at University of Missouri and the title of this article is ADAR1 Non-Editing Function in Macrophage Activation and Abdominal Aortic Aneurysm. Macrophage activation plays a critical role in abdominal aortic aneurysm development, or AAA development. Inflammation is a component of this pathology; however, the mechanisms controlling macrophage activation and vascular inflammation in AAA are largely unknown. The ADAR1 enzyme catalyzes the conversion of adenosine to inosine in RNA molecules and thus this conversion can serve as a rheostat to regulate RNA structure or the gene coding sequence of proteins. Several studies have explored the role of ADAR1 in inflammation, but its precise contribution is not fully understood, so the objective of this group was to study the role of ADAR1 in macrophage activation and AAA formation.   Aortic transplantation was conducted to determine the importance of nonvascular ADAR1 in AAA development and dissection and angiotensin II infusion of ApoE knockout mice combined with a macrophage specific knockout of ADAR1 was used to study the role of ADAR1 macrophage specific contributions to AAA formation and dissection. Allograft transplantation of wild type abdominal aortas to ADAR1 haploinsufficient recipient mice significantly attenuated AAA formation. ADAR1 deficiency in hematopoietic stem cells also decreased the prevalence and the severity of AAA and it also inhibited macrophage infiltration into the aortic wall. ADAR1 deletion blocked the classic macrophage activation pathway. It diminished NF-κB signaling and it enhanced the expression of a number of anti-inflammatory microRNAs. Reconstitution of ADAR1 deficient but not wild type human monocytes to immunodeficient mice blocked the aneurysm formation in transplanted human arteries. Together these results suggest that macrophage ADAR1 promotes aneurysm formation in both mouse and human arteries through a novel mechanism of editing the microRNAs that target NF-κB signaling, which ultimately promotes vascular inflammation in AAA.     Cindy St. Hilaire:        The last article I want to highlight is also from our February 17th issue of Circulation Research and it is coming from the lab of Shintaro Mandai at Tokyo Medical and Dental University and the title of the article is Circulating Extracellular Vesicle Propagated MicroRNA signatures as a Vascular Calcification Factor in Chronic Kidney Disease. Chronic Kidney Disease or CKD accelerates vascular calcification in part by promoting the phenotypic switching of vascular smooth muscle cells to osteoblast like cells. This study investigated the role of circulating small extracellular vesicles or SUVs from the kidneys in promoting this osteogenic switch. CKD was induced in rats and in mice by an adenine induced tubular interstitial fibrosis and serum from these animals induced calcification in in vitro cultures of A-10 embryonic rat smooth muscle cells. Intraperitoneal administration of a compound that prevents SEV biosynthesis and release inhibited thoracic aortic calcification in CKD mice under a high phosphorus diet. In Chronic Kidney Disease, the microRNA transcriptome of SUVs revealed a depletion of four microRNAs and the expression of the microRNAs inversely correlated with kidney function in CKD patients.   In vitro studies found that transected microRNA mimics prevented smooth muscle cell calcification in vitro. In silico analyses revealed that VEGF-A was a convergent target of all four microRNAs and leveraging this, the group used in vitro and in vivo models of calcification to show the inhibition of the VEGF-A, VEGFR-2 signaling pathway mitigated calcification. So in addition to identifying a new potential therapeutic target, these SUV propagated microRNAs are a potential biomarker that can be used for screening patients to determine the severity of CKD and possibly even vascular calcification.   Cindy St. Hilaire:        Today I have with me Dr Hind Lal who's an associate professor of medicine at the University of Alabama Birmingham and his post-doctoral fellow and the lead author of the study Dr Tousif Sultan. And their manuscript is titled Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. And this article is in our February 3rd issue of Circulation Research. So thank you both so much for joining me today.   Tousif Sultan:              Thank you.   Hind Lal:                     Thank you for taking time.   Cindy St. Hilaire:        So ponatinib, it's a tyrosine kinase inhibitor and from my understanding it's the only treatment option for a specific group of patients who have chronic myelogenous leukemia and they have to harbor a specific mutation. And while this drug helps to keep these patients alive essentially, it's extremely cardiotoxic. So cardiotoxicity is somewhat of a new field. So Dr Lal, I was wondering how did you get into this line of research?    Hind Lal:                    So I was fortunate enough to be in the lab of Dr Tom Force and he was kind of father of this new area, now is very developed, it's called cardio-oncology. On those days there were basically everything started in cardio-oncology. So I just recall the first tyrosine kinase approved by FDA was in 2000 and that was... Imagine and our paper came in Nature Medicine 2005 and discovering there is... so to elaborate it a little bit, the cancer therapy broadly divided in two parts. One is called non-targeted therapy like chemotherapy, radiations, et cetera, and then there are cytotoxic drugs. So those cytotoxic drugs because they do not have any targeted name on it so they are, cardiotoxic are toxic to any organ was very obvious and understanding. When these targeted therapy came, which is mainly kinase inhibitor are monoclonal antibodies. So these are targeted to a specific pathway that is activated only in the cancer cells but not in any other cells in the body so they were proposed as like magic bullets that can take off the cancer without any cardiotoxity or minimal side effects. But even in the early phase like 2005 to 2010, these came out, these so-called targeted, they are not very targeted and they are not also the magic bullets and they have serious cardiotoxicity.   Cindy St. Hilaire:        And so what's the mechanism of action of ponatinib in the leukemia and how does that intersect with the cardiovascular system?   Hind Lal:                     Yeah, so this is very good question I must say. So what we believe at this point because, so leukemia if you know is driven by the famous Philadelphia chromosome, which is a translicational gene, one part of human chromosome nine and one part of human chromosome 22 and they translocate make a new gene which is BCR-ABL gene. And because it was discovered in Philadelphia UPENN, is named that Philadelphia chromosome, which is very established mechanism, that's how CML is driven. But what we have discovered that the cardiotoxicity driven by totally, totally different from the ponatinib is one of the inflammatory So it's kind of goodening. So this question is so good. One kind of toxicity is called on-target, when toxicity is mediated by the same mechanism, what is the mechanism of the drug to cure the cancer? So in that case your absolute is minimal because if you manipulate that, the drug's ability to cure the cancer will be affected but if the toxicity and the efficacy is driven by two different mechanism, then as in case of ponatinib seems like it's NLRP3 and inflammasome related mechanism. So this can be managed by manipulating this pathway without hampering the drug efficacy on the cancer.   Cindy St. Hilaire:        So what exactly is cardiotoxicity and how does it present itself in these patients?   Hind Lal:                     So these drugs like ponatinib, they call broader CVD effects. So it's not just cardiac, so they also in hypertensives and atherosclerosis and thrombosis, those kind of thing. But our lab is primarily focused on the heart. So that's why in this paper we have given impresses on the heart. So what we believe at this point that ponatinib lead to this proinflammatory pathway described in this paper, which is just 108A9-NLRP3-IL-1β and this inflammatory pathway lead to a cytokine storm very much like in the COVID-19 and these cytokine storms lead to excessive myocarditis and then finally cardiac dysfunction.   Cindy St. Hilaire:        Is the cytokine storm just local in the cardiac tissue or is it also systemic in the patients? Is cardiotoxicity localized only or is it a more systemic problem?   Tousif Sultan:              I would like to add in this paper we have included that we look this cytokine things and explain blood circulation, bone marrow. So the effect is everywhere, it's not local. So we didn't check other organs, maybe other organs also being affected with the ponatinib treatment.   Cindy St. Hilaire:        And what's the initial phenotype of a patient has when they start to get cardiotoxicity, what's kind of like a telltale symptom?   Hind Lal:                     So good thing that in recent years cardio-oncology developed. So initially the patient that were going for cancer treatment, they were not monitored very closely. So they only end up in cardiology clinic when they are having some cardiac events already. So thanks to the lot of development and growth in the cardio-oncology field, now most patients who going for a long-term cancer treatment, they are closely monitored by cardiology clinics.   Cindy St. Hilaire:        Got it. So they can often catch it before a symptom or an event. That's wonderful.   Hind Lal:                     Yeah, so there's a lot of development in monitoring.   Cindy St. Hilaire:        Wonderful. So you were really interested in figuring out why ponatinib induces cardiotoxicity and you mentioned that really up until now it's been very difficult to study and that's because of the limitation of available murine models. If you just inject a wild type mouse with ponatinib, nothing happens really. So what was your approach to finding relatively good murine models? How did you go about that?   Hind Lal:                     So this is the top scientific question you can ask. So like science, the field is try and try again. So initially this is the first paper with the ponatinib toxicity using the real in vivo models. Any paper before this including ours studies published, they were done on the cellular model in hiPSC, that isolated cardiomyocytes. So you directly putting the ponatinib directly the isolated cells. So this is first case when we were trying to do in vivo, maybe other attempt in vivo but at least not published. So first we also treated the animals with ponatinib and that failed, we don't see any cardiotoxic effect. And then when we going back to the literature, the clinical data is very, very clear from pharmacovigilance that ponatinib is cardiotoxic in humans. So when we're not able to see any phenotype in mouse, we realize that we are not mimicking what's happening in the humans.   So we certainly missing something. Now once again I quote this COVID-19, so many people get infected with COVID-19 but people are having preexisting conditions are on high risk to developing CVD. So there was some literature on that line. So we use this very, very same concept that if there is preexisting conditions, so likely who'd have developing future cardiac event will be more. So we use two model in this paper one atherosclerosis model which is APoE null mice mice, another is tag branding which is pressure overload model for the heart and as soon as we start using what we call comorbidity model like patient is having some preexisting conditions and we very clearly see the robust defect of ponatinib on cardiac dysfunction.   Cindy St. Hilaire:        Yeah, it's really, really well done and I really like that you use kind of two different models of this. Do you think it's also going to be operative in maybe like the diabetic mirroring models? Do you think if we expand to other comorbidities, you might also recapitulate the cardiotoxicity?   Hind Lal:                     So you got all the best questions.   Cindy St. Hilaire:        Thank you. I try.   Hind Lal:                     So because this is CML drug and lot of the risk factor for cardiovascular and cancer are common and even metabolic disease. So most of the time these patients are elderly patients and they're having metabolic conditions and most of the time they have blood pressure or something CVD risk factors. So I agree with you, it'll be very relevant to expand this to the diabetes or metabolic models, but these were the first study, we put all our focus to get this one out so news is there then we can expand the field adding additional models et cetera. But I agree with you that will be very logical next step to do.   Cindy St. Hilaire:        Yeah. And so I guess going back to what you know from the human study or the clinical trials or the human observations, are different populations of patients with CML more predisposed to cardio toxicity than others or is that not known yet?   Hind Lal:                     So one other area called pharmacovigilance. So what pharmacovigilance does patient all over the world taking these drugs. So WHO have their own vigilance system and FDA have their own, so it's called BG-Base for the WHO and it's called the FAERS for the FDA. So one can go back in those data sets and see if X patient taking this Y drug and what kind of symptoms or adverse effect they are seeing and if these symptoms are associated with something else. So there is data that if patients having CVD risk factor, they are more prone to develop ponatinib induced cardiac events. But it needs more polish like you asked the just previous question, diabetes versus maybe blood pressure means hypertension, atherosclerosis, or thrombosis. So it has not been delineated further but in a one big bucket if patients are having CVD risk factor before they are more prone and more likely to develop the cardiac events.   Cindy St. Hilaire:        So after you established that these two murine models could pretty robustly recapitulate the human phenotype, what did you do next? How did you come upon the S100A8/A9-NLRP3-IL-1β signaling circuit? How did you get to that?   Hind Lal:                     So in basic science work, whenever we do mouse is called until we get there is cardiac dysfunction, it's called phenotype, right? So mouse had a cardiac phenotype. So next step is, "Why? What is leading to that phenotype?" That's what we call mechanism. So there the best idea to fit the mechanism is using one of the unbiased approaches like you do unbiased proteomics, unbiased RNC analysis, something like this that will analyze the entire transcript like RNC and say, "Okay, these pathway are," then you can do further analysis that will indicate these pathway are different, are altered. So in this case we used RNC analysis and it came out that this yes A8 and yes A9, 100A8 and nine, they were the most upregulated in this whole set. And thereafter we were very lucky. So we started this study at Vanderbilt, where my lab was and thereafter we very lucky to move here and found Sultan who had a lot of experience with this inflammation and immune system and then Sultan may add something on this so he'll be the better person to say something on this.   Tousif Sultan:              So after our RNC analysis, so we got this S100A8 and nine as top hit with the ponatinib treatment. So then we validated this finding with our flow cytometric, qRT PCR aand then we started which pathway is going to release cytokine and all that. So we found that is NLRP3 inflammasome.   Cindy St. Hilaire:        Yeah and well and I guess maybe step back, what is S100A8/A9? What are those? Tousif Sultan:              Yeah, S10A8/A9 is a calcium binding protein. So that's also called alarmin and they basically binds with the pathogen associated pattern and other TLR2 like receptors and then start inflammatory pathway to release cytokine and all that and it's stable in heterodimer form. So S100A8 heterodimer with A9 and then bind with TLR and a start in this inflammatory pathway.   Cindy St. Hilaire:        And what type of cell is that happening in? Is that happening in the immune cells only or is it also in the cardiomyocyte, or...?   Tousif Sultan:              Yeah, we have included all this data. So from where this alarmin is coming with ponatinib treatment, so literature also suggested that neutrophils and monocytes, those cells are the potential to release the alarmin. So here we also found these two type of cells, neutrophils and monocytes. They release huge alarmin with the treatment of ponatinib.   Cindy St. Hilaire:        And so really taking this really neat mechanism to the next level, you then tried attenuating it by using broad anti-inflammatory steroid dexamethasone but also by targeting these specific components, the NLRP and the S100A specific inhibitors and they worked well. It worked really nicely. Does your data show that any of these therapies work better than the other and then are these viable options to use in humans?   Hind Lal:                     Yeah, we have some data in the paper. Are very broad which help a lot in COVID patients, far very acute infections. So in this case, situation is very different cause most of CML patients will going to take ponatinib for lifelong, there is no remission, right? So in those case, its certainly not a very attractive option. We have shown data in the paper that dexamethasone help with the heart but lead to some metabolic changes. So we have compared those with the NLRP3 inhibitors, those metabolic alterations, dexa versus the NLRP3 inhibitors, CY-09. And we demonstrated that targeting is specifically with paquinimod, our NLRP3 inhibitor CY-09, feel better. It can still rescue the cardiac phenotype without having those adverse effect on metabolic parameters.   Cindy St. Hilaire:        That's wonderful. Do you think though that because you have to take ponatinib for life, that long-term NLRP inhibition would also cause problems or...?   Hind Lal:                     So because not every patient who taking ponatinib would develop the cardiac phenotype, right? Which is like a 10%, 12%, patient developing cardiac dysfunction. So I think someone like I strongly believe paquinimod, which is inhibitor of S100A9, will be really good option or at least we have enough data that make us nail for at least a small clinical trial. And we quickly moving on that. At UAB we have our clinical cardio-oncology program and we are already in touch with the director for the clinical cardio-oncology program. So what we trying to do in that small trial is if one of the standard therapy for heart like beta blocker or ARBs inhibitor, is there any preference like one work better than the other in the standard care? So first we doing that project, then we obviously looking forward if one small clinical trial can be done with paquinimod. I strongly believe it should be helpful.   Cindy St. Hilaire:        That is wonderful. And so do you think... There's other chemotherapeutic agents or probably even other non-cancer drugs that cause cardiotoxicity, do you think this mechanism, this pathway, this S100A-NLRP-IL-1β axis is operative in all cardiotoxicities or do you think it's going to be very specific to the ponatinib?   Hind Lal:                     So it's certainly not all, but it'll be certainly more than ponatinib. So in our lab we are using another kinase inhibitor, which is osimertinib and it's not published yet, but now we know that it's also cardiotoxic because it's taking metabolic root or energetics disruption but not this pro-inflammatory part, but we're doing another project which is strep pneumonia induced cardiac dysfunction, which is called pneumonia. So strep pneumoniae, which leads to the pneumonia ,and lot patient die because of the failing heart we see here in the hospitals and we see these pathways operational over there and we gearing up to do clinical trial on that aspect as well, but it's not generalized like all kind of heart will have the same mechanism.   Cindy St. Hilaire:        It's wonderful to see you're already taking those next steps towards really kind of bringing this to a translational/clinical study. So what was the most challenging aspect of this study?   Tousif Sultan:              The challenging aspect, ponatinib is a kinase inhibitor and that was surprising for us how it's activating immune cells. Generally kinase inhibitors, inhibits all the cells like that. So that was challenging. So we repeated it many times did in vitro experiment to confirm that. So we just added, just treated in vitro immune cells with the ponatinib and confirmed it. So that was little challenging.   Cindy St. Hilaire:        So what's next? You mentioned you're going to try some clinical trials, early stage clinical trials. What's next mechanistically, what do you want to go after?   Hind Lal:                     So what we are doing next and we are very, very eagerly trying to do that. So what it was done, we used the cardiac comorbidity models, but as you know, anybody who will take ponatinib will have cancer, right? So we strongly believe that we miss one factor. There was no cancer on these. So that is very logical next step. What that will allow us to do, what rescue experiment we'll have done in this paper. So we saw, "Okay, this rescue the cardiac phenotype, which is taken care of now," but very same time, we not able to demonstrate that this is happening without hurting the cancer efficacy. So if we have the dual comorbid mouse, which have CML a real thing and we have cardiac thing, then that will allow us to demonstrate, "Okay, we got something that can take care of the cardiac problem without hurting the efficacy on the cancer." And it will be best if you also help little bit to more potentiate the cancer efficacy.   Cindy St. Hilaire:        Yes. Excellent. Well, congratulations on a beautiful study, really exciting findings. Dr Lal and Dr Sultan, thank you so much for taking the time to talk with me today.   Tousif Sultan:              Thank you so much.   Hind Lal:                     Well thank you, Cynthia. We really appreciate your time. Thank you for having us.   Cindy St. Hilaire:        Yeah, it was great.   Cindy St. Hilaire:        That's it for our highlights from the February 3rd and February 17th issues of Circulation Research. Thank you so much for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and Instagram with the handle @CircRes and #DiscoverCircRes. Thank you to our guests, Dr Hind Lal and Dr Tousif Sultan. This podcast is produced by Ishara Ratnayake, edited by Melissa Stoner and supported by the editorial team at Circulation Research. Some of the copy text for the highlighted articles was provided by Ruth Williams. I'm your host, Dr Cynthia St. Hilaire, and this is Discover CircRes, you're on-the-go source for most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2023. And the opinions expressed by the speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahajournals.org.  

Hypertension treatments are really about a few drug classes: ACEIs and ARBs, Beta Blockers, Calcium Channel Blockers, Diuretics, and a few more. This episode has a few mnemonics and a focus on prefixes and suffixes that will help you remember them.  Need more help; you can find many of my mnemonics books on Audible that you might be able to get your first for free if you've never had one before.  https://www.audible.com/pd/Memorizing-Pharmacology-Mnemonics-Audiobook/B07DLGC8MP?source_code=AUDFPWS0223189MWT-BK-ACX0-118296&ref=acx_bty_BK_ACX0_118296_rh_us  

Dr. Ebell and Dr. Wilkes discuss the POEM titled ' Use of ACEIs and ARBs in advanced chronic kidney disease does not worsen, and may improve, renal outcomes '

The second of the RAAS system blockers! Very similar to the ACE Inhibitors with a little twist. "And all the Sartans assembled........."

On this episode, I discuss indapamide pharmacology, adverse effects, drug interactions, and pharmacokinetics. I discuss how indapamide differs from other thiazide diuretics. Particularly, I discuss indapamide compared to hydrochlorothiazide. Frequent urination, hypokalemia, and dehydration are all possible risks with indapamide. Pay attention to medications that can increase the risk for acute renal failure when added to indapamide. NSAIDs, ACEIs, ARBs, and other diuretics can increase this risk.

1. Are you wondering if you still need to care for your landscape plants? Julio and I will tell you what you need to know. 2. We'll tell you what to do to winterize your pond. 3. Caroline called the Bloomers in the Garden Hotline and told us about her beautiful Gardenia growing outdoors. 4. Our buddy Harold from Staten Island called the Bloomers in the Garden Hotline and asked about snow this winter on his large arborvitae. 5. If you're thinking about pruning your dogwood tree, "Drop this Pruners!" 

On this podcast episode, I discuss valsartan pharmacology, adverse effects, drug interactions, and much more. Valsartan is a fairly common ARB. I mostly see losartan and valsartan used as the most common ARBs in hypertension management. Valsartan has a longer half-life than losartan which is why we can often get away with once daily dosing compared to losartan which sometimes requires twice daily. Hyperkalemia is a major concern with ARBs like valsartan. Trimethoprim and spironolactone are two medications that can increase this risk.

Robert Lefkowitz: A Funny Thing Happened on the Way to Stockholm Robert Lefkowitz is James B. Duke Professor of Medicine and Professor of Biochemistry and Chemistry at the Duke University Medical Center. His group spent 15 difficult years developing techniques for labeling the receptors with radioactive drugs and then purifying the four different receptors that were known and thought to exist for adrenaline. In 1986 Bob and his team transformed the understanding of what had become known as G protein coupled receptors, when he and his colleagues cloned the gene for the beta2-adrenergic receptor. Today, more than half of all prescription drug sales are of drugs that target either directly or indirectly the receptors discovered by Bob and his trainees. These include amongst many others beta blockers, angiotensin receptor blockers or ARBs and antihistamines. He has received numerous honors and awards, including the National Medal of Science, the Shaw Prize, the Albany Prize, and the 2012 Nobel Prize in Chemistry. He was elected to the National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences. He is the author with Randy Hall of A Funny Thing Happened on the Way to Stockholm: The Adrenaline Fueled Adventures of an Accidental Scientist. In this conversation, Bob and I explore the important nature of mentoring in his success — and how he has in turn utilized mentoring to support so many colleagues and students. We discuss the importance of building careers around problems versus techniques and other key principles that effective mentors adopt. Plus, we explore the key of ownership of work and using fun as an indicator to follow. Key Points Success is rarely accidental. Most people with extraordinary accomplishments had outstanding mentors along the way. Teach people to build their careers around problems, not techniques. The crucial job of a mentor is to keep things in focus for the person you are mentoring — both in their current work and their careers. People achieve the most motivation when they have ownership over their work. A key measure of striking the right guidance between ownership and guidance is whether or not everybody is having fun. Resources Mentioned A Funny Thing Happened on the Way to Stockholm: The Adrenaline Fueled Adventures of an Accidental Scientist* by Robert Lefkowitz Interview Notes Download my interview notes in PDF format (free membership required). Related Episodes What You Gain By Sponsoring People, with Julia Taylor Kennedy (episode 398) How to Know What You Don't Know, with Art Markman (episode 437) How to Lead and Retain High Performers, with Ruth Gotian (episode 567) Discover More Activate your free membership for full access to the entire library of interviews since 2011, searchable by topic.

In the second episode of our hypertension series, Taylor  and Dr. Gallagher discuss lifestyle modifications and medications used in the treatment of high blood pressure.Share your reactions and questions with us at  Speak Pipe . We might feature you on a future episode!=== Outline ===1. Introduction2. Chapter 1: Setting goals3. Chapter 2: Lifestyle modifications4. Chapter 3: Initiating Pharmacotherapy5. Chapter 4: Adherence to Medications6. Conclusion=== Learning Points ===Most patients with hypertension would benefit from having a low blood pressure, regardless of the degree of lowering.Recognize that asking patients to start medications can be a large ask for a patient, especially if they are otherwise healthy and have several other conditions to manage. Lifestyle modifications—such as reducing salt intake and drinking water—may lower blood pressure to some degree. However, finding such “low-hanging fruit” in lifestyle modifications is difficult, and providers should not shy away from pharmacotherapies. Firstline therapies for lowering blood pressure include long-acting calcium channel blockers, ACE inhibitors/ARBs, and diuretics. Optimizing a patient's regimen may require a combination of therapies, and combination pills may be effective in improving adherence.=== Our Expert(s) ===Benjamin Gallagher, MD, FACP is an Assistant Professor of Clinical Medicine (General Medicine) at Yale School of Medicine.=== References ===2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-e248.Ostchega Y, Fryar CD, Nwankwo T, Nguyen DT. Hypertension prevalence among adults aged 18 and over: United States, 2017–2018. NCHS Data Brief, no 364. Hyattsville, MD: National Center for Health Statistics. 2020.SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 373(22):2103–16. 2015.Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure-lowering treatment on cardiovascular outcomes and mortality: 14 – Effects of different classes of antihypertensive drugs in older and younger patients: Overview and meta-analysis. J Hypertens 36(8):1637–47. 2018.=== Recommended Reading ===Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM; American Heart Association. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006 Feb;47(2):296-308. doi: 10.1161/01.HYP.0000202568.01167.B6. PMID: 16434724.=== About Us ===The Primary Care Pearls (PCP) Podcast is created in collaboration with faculty, residents, and students from the Department of Internal Medicine at the Yale School of Medicine. The project aims to create accessible and informative podcasts about core primary care topics centered around real patient stories.Hosts: Josh Onyango, Maisie OrsilloProducers: Helen Cai, Kevin Wheelock, Danish ZaidiLogo and name: Eva ZimmermanTheme music and Editing: Josh OnyangoOther background music: Dan Lebowitz, penguinmusic, future mono, Jesse Gallagher, VYEN, madriFan, Instagram: @pcpearlsTwitter: @PCarePearlsListen on most podcast platforms: linktr.ee/pcpearls

Marfan Syndrome is a rare genetic heart disease, but still affects over a million people worldwide. It causes swelling of the main blood vessel of the heart, which can even tear if major surgery is not performed - usually when the patient is in their 20s or 30s. Researchers form Oxford University worked with teams all over the world to combine results from several trials involving almost 1500 patients - the most powerful study of its kind - and found that two widely available medicines, angiotensin receptor blockers and beta-blockers, work both separately and in combination to slow the rate of expansion of the blood vessel, potentially delaying the need for surgery and the risk of tearing by a decade or more if the drugs are taken together long term. In this interview, Alex Pitcher, MD and William E. Boden MD, FACC, FAHA, with Sun Moon Kim MD FSCAI FACC, discuss the ESC Late-Breaker: MTT: Assessing the Effects of ARBs and Beta-Blockers in Marfan Syndrome.

For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources:  ·Newsletter Sign Up·Jubilee website·PrevMed's website·PrevMed's Rumble channel·PrevMed's YouTube channel·PrevMed's Facebook page·PrevMed's Instagram·PrevMed's LinkedIn·PrevMed's Twitter ·PrevMed's Pinterest

On today's episode: Standard opening and joke, but with a new sponsorship from Panacea Financial!   Pod Episode is on an interesting study from last month on management of hyperkalemia with patients on ACE/ARBs that I thought was super interesting and very relevant to primary care.  Hope you agree!

James Dainard is co-founder and managing partner at Heaton Dainard Real Estate and Intrust Funding LLC. He is currently a co-host on one of the BiggerPockets podcast series. As a seasoned real estate investor, James leads the development and execution of corporate strategies, marketing, and property acquisitions at Heaton Dainard Real Estate. His decade of experience investing in multi-family and single-family units in the Puget Sound region has guided Heaton Dainard with over a billion dollars in sales and over 3,000 transactions directly to investors. Flipping houses remains one of the most well-known strategies in today's real estate industry, and for good reason: fix and flip homes can potentially offer attractive profit margins for real estate investors who know what they're doing. Unfortunately, many beginner investors make the mistake of assuming that the only important part of flipping a house is the renovation itself; in actuality, success will also depend on how good of a deal you secure when purchasing a property. Consequently, finding fix and flip deals is one of the hardest aspects of the job. Tune in for today's episode where James shares some his insights about fixing and flipping houses with us. Episode links: JamesDainard.com IntrustFunding.com HeatonDainard.com https://www.instagram.com/jdainflips/?hl=en  --- Transcript Before we jump into the episode, here's a quick disclaimer about our content. The Remote Real Estate Investor podcast is for informational purposes only, and is not intended as investment advice. The views, opinions and strategies of both the hosts and the guests are their own and should not be considered as guidance from Roofstock. Make sure to always run your own numbers, make your own independent decisions and seek investment advice from licensed professionals.   Michael: Hey everyone, welcome to another episode of the Remote Real Estate Investor. I'm Michael Albaum and today with me, I have James Dainard with Heaton Dainard Real Estate and James is the co-founder and managing principal of that company. They do apartment syndication, hard money lending, fix and flips and also have a brokerage among many other things. So James is gonna be talking to us today about the fix and flip market, what he's been doing and how it's changing, and what we as investors should be thinking about as we get into this market. So let's get into it.   James what is going on, man, thanks for coming on the podcast and hanging out with me. I appreciate it.   James: Yeah, I'm excited to be here. It's anytime I get to talk real estate's always a win.   Michael: I know, I know and it's crazy that we like get paid for it. It's kind of a joke, you know?   James: Yeah. I'm still waiting to see the big checks. But all right, I'll keep doing real estate until that somehow I figured that part out.   Michael: I'm right there with you, man. For anyone who doesn't know your background, know your name that your company give us a quick and dirty insight who you are, where you come from? What is it you're doing real estate today?   James: Yeah, I'm James Dainard. So I'm out of the Pacific Northwest. We've been an active investment company at the Seattle, Washington for the last 18 years now. So I started doing this when I was a senior in college actually knocking doors for an investment company and then once I graduated, we kind of just start building companies, one after the other, went through a pretty nasty weather. Well, the month that we opened our business was the month that the whole real estate market fell apart in 2007, and eight. So it's, we're very seasoned investors, we're active guys in Seattle, we typically do we have a brokerage that does about 200 fix and flip properties a year with our clients and then we do about an additional 50 ourselves and then we land hard money up in Seattle, Washington, just short term financing and then we're big apartments indicators as well. So we own about 2000 doors in the Seattle market. Very, very active, very active guys. We like to stay busy, we work and then also, and now we started doing it now we're putting out a lot of different types of educational stuff for people on project already and then on the market for bigger pockets with any podcast channel. So always expanding, always doing more things. But we're, we're guys that like to talk about what we're doing not about theories. It's like, whatever, whatever we're actually got our hands on. That's usually what we're talking about.   Michael Love it, love it. Well, James, I love to focus the conversation today on fix and flip, since I think it's something a lot of our audience members are really interested in and it's just a super unique time, seemingly in the market as a whole. So give us a little bit of insight. Are you doing anything different now than you were six months or 12 months ago with regard to fix and flip?   James: Oh, yeah, we are doing things completely different and you know, and I think one thing that investors always need to know is the market goes up and downs, it's changing all the times and so what you're doing, and this is why the fix and flip business can be so challenging. Again, we've been doing this for about 18 years, and we've been in four different types of markets, you know, we had, or five, you know, 2006, through eight was crazy hot like it was now maybe not quite as hot as this last one. We had the crash where we were flipping in a declining market where the market was crashing 10% every month, basically, there was like the it was just the walls were coming in on every project and then we were in a flat market 14 to 18 or 17 and then you know, this last 24 months had been pretty crazy with the appreciation and in the last 24 months, you had to do things completely different to make money and a lot of that had to do with like timing, purchasing the right location and also interest rates as interest rates were really low, the pricing was soaring and so now we're in that whole new, it's a whole new market again, you know, cost of money has gone up about 35 to 40% and it's slowed everything down.   So as flippers, what we've had to do is instead of just trying to secure a deal in the right location with low inventory, we're really checking the numbers and how we underwrite things is vastly different than we would do. Six months ago, like six months ago, we were looking for that high data point and interpreting where the market was going to kind of factor in a little bit of appreciation on the exit, which will allow us to buy in a slimmer margin. Now what we're doing is we're buying at cheaper, larger spreads because we don't think the market is going to get the depreciation and we're being very fine tuned on our comparables, we just have to really dig into everything and we only will use current market data because the rates are sky, they're moving around so much. So we only pull comparable data from what when the interest rates were in impact. So like, right now, we're only going back 30 days on our sales, we won't look at anything 60 to 90 days old, because it was just a different market at that point in time. So but yes, you always have to change, you have to change what you're doing on a regular basis. So we're buying differently, we're underwriting way tighter, we're looking for bigger walk and margins are being super conservative on our ARBs and then also, we're rebuilding our whole construction team as well to get more cost efficient.   Michael: Interesting, so when you talk about like underwriting things differently or buying differently, give us a little bit of insight, like what does that mean and like, how are you actually doing that?   James: So underwriting it's so key when you're looking at any investment, right? It's going to tell you a what it's worth stabilized. It's going to tell you if you're buying a property, what's your rent projection? What's your cash on cash return and with fix and flip the two major you know, I mean, the three major things and when you're underwriting fix and flip is a the performer what is the numbers telling you in the deal is that a good enough cash on cash return or return that you're happy with? The second most important thing is understanding your rehab costs and accounting for those correctly, because that's going to really dictate whether you're going to make money or not and right now, because we're in this volatile market, where we have cost of monies going up, the labor market is still a little bit messed up right now to where it's hard to get guys, the site materials are still more expensive, it's harder to find supply chain issues. So what we're doing in that market is we're adding 10 to 15% contingencies to every budget as we're underwriting, we also re snap out our budgets every 60 to 90 days to keep up with the cost. Whereas four years ago, we had to do it once a year, like update it, get our numbers down, but it's so rapid that we have to move things around and so we're staying on top of our construction budgets and then lastly, that valuing that asset for highest and best use, we're looking at how do you rapid return on each deal, because you can look at a deal and skin it three different ways.   You can go really heavy and go for the big margin, you can do it really light and go for a small margin, which you're in and out of the deal and get a good cash on cash return in a small amount of time. But we're being we're just spending a lot of times digging into comparables, we're staying very tight on our radiuses to make sure that we're staying inside of our neighborhoods, because you know, neighbor as the market cools down, things like schools, neighborhoods, neighbors, all these things, negative impacts, they affect the values a lot more, you know, the last 24 months, you could buy a house on a little bit busier road or maybe have a little bit crunchy your neighbor and you could still sell it with no problem. But as it slows down inventory increases, those things become kind of major issues for sale. So we're, we're really deducting negative impact properties, we're taking five to 10% off those on values, you know, when we're looking at comparables, and then we're only going back 30 days, because we want to see what the buyers with the same cost of money what they can afford, that's what we need a price off of and then lastly, we're not going to that high, high end comp, we're trying to stay in the cluster and then putting together our rehab plan to fit in the cluster. We don't want to be this super nice, expensive house right now. We want to be the most updated, but in the affordable masses and that's what's been selling things fairly quickly for us. You know, the market is definitely cooled to where we're not getting a ton of people coming through these houses. But we have 50 listings right now a fix and flip properties, and we're still 60% pending and so things are still selling as long as you're putting the right plan in play.   Michael: Interesting, man, I think that makes a ton of sense and are you have you shifted? I know, you said you're not trying to do like the most fancy updated house anymore, is that something that you have done in the past?   James: Yeah, we do. You know, I like to go where it's hard, because those are the best margins and it's, you know, especially real estate has been this thing that's it's almost like Bitcoin, right? Like we're everybody wanted in at one time, the last 24 months and so what that does is when you're the masters coming into the market, it really compresses your margins and sometimes it just comes down to straight luck, like people made a lot of money just because they bought something and the market made it worth a lot more. Not because they bought the right thing, not because they put the right plan on it, it was just the market and so is as you're kind of going in, we would go after more expensive property. So like the last 12 to 18 months, because they're more expensive. They require a lot more rehab plans, they require a lot more liquidity and to be honest, when you're taking out hard money loans that are over a million dollars, they're expensive to hold and so the debt cost is really expensive and so we been in that area because there was lack of investors buying there, it got us about we were able to achieve about 50% higher margins in that space, because…   Michael: Just less competition...   James: Less competition… So that's we went from doing more cookies better deals like I used to flip about 100 120 homes a year myself and then as that got more and more compressed, I was like, Well, why am I doing all this work for small margins, I'm just rack like, it's just wear me out. So then we went to larger projects, to where we get we're focused, instead of doing 120, we're doing 40 to 50. So we've got to work a little smarter. But as that market cools down those, that's a very risky market to be in, because if there's a, you know, a 5% correction, on $3 million, that's, that's a, that's a huge hit on your bottom 150 grand, they can come right off the top, which can be a lot of your margin and so the more expensive properties we're being, we're making sure we're padding and with a lot more walk in margin on. The other thing about the more expensive ones we're staying, we're being more conservative on now, where we've been doing a lot of them, it's because they take a long time, so you're exposed to a lot more market conditions. You know, if the if the Fed continues to increase rates over the next six to nine months with, they're saying they will, that that value can swing dramatically over a nine month period, whereas 12 months ago, it was just swinging up.   So it was all when at that point and so we have started scaling back on the more expensive properties just because they're really high risk, or we're expecting that we get our margins up even further than they were before. The one thing I have seen is not a lot of people are buying them. So the margins are getting bigger and bigger and so there is like that magic number for us, we're trying to hit at least 50 to 60% cash on cash return on those deals, because the extra return allows for any kind of market dip at the same time. But the key right now, because the market conditions are changing, they're going to be continuing change, it's just get in and out in and out, get your deal, buy, stabilize it, sell it, rack your return move on to the next and so that's why we've kind of pulled out of that market, in addition to as the market starting to get a little bit more flatlined, and stable, a lot of investors have already exited, because they I mean, to be honest, they don't have the stomach for it, it because it's risky and so the margins have gotten bigger on the easier deals. So that's why we're also going back that way as well because you know, we don't want to work on a project for 12 to 18 months on some massive project if we don't have to. So we don't really pick the project based on like our own personal opinion, I would love to only do multimillion dollar flips, because I just enjoy them more I get I get to do more, I get to do cool things there. But I want to go with what financially makes sense and so you know, for us, that's why we're also rebuilding our construction team right now as we build a team to do higher end properties. But as we go back to cookie cutter, we have to, you know, we got to change out our staff, we have to change our contractors and that's what we're working on right now. We have full time staff, like we're cold calling contractors for finding new guys or meeting them on site, because we have to build that new bench for what we're trying to accomplish. Not every remodel is the same and not every guy is the same. So you have to be balanced with who you have as your resources.   Michael: Yeah, that makes total sense and because things are changing, so drastically, seemingly, and so quickly. I mean, do you ever think about like a plan B? If you can't flip the thing? Do whatever makes sense to put a tenant in place and hold it and almost burned the property or are you like, no, we're gonna fix and flip it and if we have to take a haircut on the exit, we will just move on to the next one?   James: Well, that's the dream deal, right? It's the it's the lowest risk deal, which is your burr style flip where you know, because the hard part about the expensive properties, you know, if I'm flipping a home, I got two going on right now where we paid roughly 1.5 for one and we pay 1.8 for another we're putting 750 grand 900 grand into both properties. So I can't keep that as a rental like that. If we leave 25% in, no, our mortgage is going to be 25 grand a month at that point and so you know, 20-25 grand, so that's just not going to pencil and so that's another reason why we're kind of backing off because you know, the best kind of deal you can buy right now like I just gotten contract, I have one that I close in seven days. I picked it up for 275, which is about 25% cheaper than we were paying nine months ago for these houses and so we already got the discount because the market starting there's more opportunities as people get nervous and but it's a perfect deal for low risk flipping, and these are ones that people should be if you're really nervous about the market, you should target these kinds of properties. So we're paying 275 It is a piece of garbage. It needs a ton of work. We're putting, we're putting like $135 a foot into this house, which is a lot for us for like a low rent model, but it's we've 100 It's 110,000 our budget for 700,700 square foot house. It's…, that deal works. It's just toast it's the you know the roof caved in. It's stacked full garbage to the ceiling, it's definitely good. Actually, if anyone was check it out, we're gonna we're gonna do a live walkthrough on it pretty soon.   Lots of weird things in the house but and the reason is so good is we're paying 275 with a rehab, we're going to be into it like 375 385, we can refi that deal even at high rates, if it's worth a solid 499 to five and a quarter five and a quarter is a definite number right now. But we've actually performed it at 499, because it's about seven months out. So we've reduced our value down based on where we think the rates are going to be. And that's the most important thing for mitigating risk. You know, you don't want to just look at the rates. Now, if you think they're going to be higher in six to nine months, you want to bring your ARV down a little bit, because that means that property is less affordable at that point and so we had a performance at 499, which is going to be roughly about a $50,000 profit after all hard cup money cost, sell costs in that and so that's going to end up being like a 60% cash on cash return with our lender interest funding, because then we do 15% down. So you know, we're coming in with like 60 to $70,000 down, we're going to make 50. So it's a great return. But let's say the market drops down at 450, we can still refinance that property and get almost 90% of our cash back on that loan to value because we can go up to 75% and our payments going to be roughly about 25 2600 annual rent for 2800 and so it's the perfect flip, because no matter what you either can rack your 70% cash on cash return by quick in and out deal and that's a lot of work for 50 grand, but it's very safe and that's why we bought it or if the market falls apart, which it definitely could you never know what can happen, then we can still refinance it, we can keep it and then hold it for two years and then sell it off later at that point, or, you know, our $200 in cash flow, let's say we decided to just keep it and that rates fall down to about 5%, five and a half to what they're usually around, our cash flow is not going to just be $200 a month, it's going to be around $800 a month. So you can you can target the cheaper, heavy fixer smaller houses, those are very good properties that because the price points are so low, they make it very interchangeable. So if you want to be safe in flipping, buying a burr is the best way to go. Because you know what refi out, you know will pay for itself and you have that 25% margin, which is your profit in the flip and so those are the best things you can target in this current market…   Michael: It makes total sense. Have you ever thought about like on this particular property seller financing at like nine or 10%?   James: Well, it's the problem is seller financing in that kind of scenario. Let's say we got that guy to finance us 90% and we just had to bring in 10%. At that point, I can get hard money loan three interest funding at 10% rate, you know, 10 to 12 and the loan balance…   Michael: Oh yeah, you're in it for the hard money…   James: And then we can also get a construction loan, which is going to triple our return expectations because if we pay and we do 10% down, so we give that guy 27,500 down, but then we have to come out of pocket with the rehab of 110 220, our cash on cash returns actually going to be reduced by 65% by not using a construction lender because with the construction lender, we only have to come up with the 15% of the total project. Whereas the other way, we're coming up with 10 and all the rehab and so that's the dangerous part about seller financing. seller financing works really well, if it's a light fixture in my opinion, or they're just giving you 100% financing with a closeout term at that point and so for me, I don't really care about rates I don't really care about cost of money, I just look up cash on cash return and whatever the highest cash on cash return is how I want to set the deal up for leverage.   Michael: Okay, makes total sense. James, like you are clearly an expert in the space and in your market and you are so laser focused, it seems and you know Seattle, like the back of your hand. What do you recommend to newer flippers, newer investors that want to get into this space that maybe don't have that level of expertise in their market that you do?   James: Start with baby steps, baby that's the biggest thing where people I've seen it where I've gotten myself in the most amount of trouble too is when I buy something I don't know and the rehab gets out of control and in what the last 24 months depreciation would save your butt. It didn't matter if you bought a deal and you didn't quite know what you're doing that it made you look good. Yeah, yeah, you everybody looked good, including myself like it just the margins were absurd and but if you don't know how to nail that plan, that's where you can get really out of control. Like if you spend 35% more on your budget and it goes way over your timeframes, that's going to eliminate your profit and you better steal to sell that for top dollar or you could be losing really quick and so the first thing you want to do is really take baby steps try to go for more cosmetics where you're not doing like adding bathrooms changing out things, low permit properties where you can do more cosmetic swap outs, tile flooring, doors, trim, minor things, maybe roof windows, that will keep it you can you can kind of isolate your cost a lot more. The other thing that you to do is you always can partner with investor to, you know, bring in like a general. So like right now what I'm actually doing because the markets risks here we're doing we're trying to figure out how to cut costs is we are now partnering also.   So instead of increasing staff to manage more projects, we're actually we're running some projects ourselves to where we're generally in the whole thing, then we are also partnering with generals now to where I'm giving away 30% of the deal to the general, but they are running the whole thing with my team, my team is gonna go get in the paint colors, the tile that design the layout, they handle everything A to Z, and they have a vested interest in it. So what we're doing is we're bringing in our resources that are starting to slow down on work, too and we're tying them into the deal because it requires less management, and it reduces the risk because the contractor who can charge you, whatever he wants for change orders right now is tied to the deal, too. So he's essentially charging himself, right and so partnering with the general is a good way to go partnering with another investor, you know, like I bought a flip property out in Scottsdale, Arizona in the last six months and I don't know, Scottsdale, I don't have the same resources. I don't have the same deal flow out there. So I had some extra capital. So I invested in a gal named Cara Beckman's flip and so I was she found the deal. She ran the project, I put up all the cash and we split the profit 50-50 and so there's other ways you can do you can partner with people with the right type of processes in play.   Michael: Yeah. I love it, I love it. When you're underwriting a deal, I mean, they're talking about the 70% rule and as you're underwriting a flip, are there some rules and guidelines that you live by, in today's market to help you kind of get a quick, quick glance at a property and know if it's a potential interest or not?   James: Yeah, so I always buy off cash on cash return, because it's that 70% rule can be hard. It's a great rule of thumb, right? Like, what's it worth, buy it, you want to be buying at, you know, purchase price and fix up at 70% of that total amount, right. So for all the listeners, if you're if you have property worth 100 grand, you're trying to buy it for 50, put 20 in and then you're at 70% at that point and it's not it's a good rule of thumb to do so like a lot of times, even when I'm surface writing a deal, I'll just take the ARV or the value of the property, I times it by 80% because I knock off all my landing costs, selling cost, subtract the rehab, subtract the purchase price, and then there's the profit at the end of the day. The one thing I don't like about that is the ARV can be so changed, though. Like it can be 70% one way and it cannot be the other way and so there's so many ways that you can do a deal. It's hard to put it in a standard box. Now I think if you're in more of a cookie cutter area, like if you're in track wrong track home bill, like if you're in like Central Florida, Texas, where they're all the same, it's easier to do but in Seattle, every street matters so much whether it's like high crime, or is it a better street where the schools are, the homes are really old, and they're all different. So the rehabs vary so much you can't standardize as much every project is its own beast and so that's why I go off cash on cash return. So when I'm looking at a deal, I'm always going okay, can I get around a 50% cash on cash return after all costs, and that's how I buy off of is that's my minimum expectation for short term investment. Like on buying holds, I'm always shooting for 10%. So like, as long as I know, my margin, that's how I underwrite correctly. Now the market will change what my margin expectations will be, though and so like 12 months ago, my cash on cash return on a flip, I was trying to get 35% with leverage in there and then it would kind of bump up with appreciation. So as the market slows down, I increase my return, if that keeps me fairly safe at that point.   Michael: And that makes total sense. You're just patting yourself additionally, in case something moves the wrong direction.   James: Yeah, it's no different than how we were buying the last 12 months. It's like we were buying on slimmer margins, because we thought there was a higher exit down the road and you know, so if you're in a really good market, you buy slim and if you were in a really, you know the market start transitioning, you start patting your performance or like even in the stock market, a lot of people were day trading, right? They're getting them in now, people kind of getting more settled in because the day trading can blow up in your face really quick. The short term is harder to do and so you're seeing a lot more people just invest in the long term because they're like, hey, I just want a stable return, try to beat inflation. But you know, as the market cools down, you get less trading in there a lot too. Yeah. But with the market cooling down, it has created some massive opportunities. So I mean, we're definitely buying property way cheaper than we were buying 90 days ago. Which is nice. It's we're getting back to like a normal system like we can buy it for this we rehab it and then we sell for this and we're gonna make roughly around this whereas last two years is like well, I don't know what's gonna happen we'll see could hit…   Michael: Yeah, anyone's guess is good. So James is like 50% cash on cash is like insane. saine insanely high, which is amazing and I have to imagine not all of your deals have hit that target. So can you give us a little bit of insight into one that maybe didn't go your way to help level set expectations for what the flippers?   James: Oh, yeah, you can very easily lose 50% In flipping too. I mean, the thing about flipping is, wherever one always needs to remember the things I have to remember is I'm an investor, I'm making a decision on risk and if I have the chance to make a 50% return, that's an extremely high return, especially in like a nine month period, right? That's on an annual basis. That's like 70% 75%, that means that that investment engine is extremely risky. Like you don't like there's a reason but like, CDs don't pay 30%. Very risky and I feel like sometimes people forget, like how high risk this business is and so you really got to stay on top of it. But yeah, I mean, we've had all sorts of deals go wrong over the I mean, the first major fixture I ever bought when I was 23. I 2008 happened right as I was selling it, and I got flatlined, I lost all my cash I'd saved in two years of wholesaling and so it can go away very, very quickly. But I mean, even recently, like we, I mean, we had a deal where we bought a home, we got its permit, we jacked up the house and then the city came back to us back in the plan review decided to change the whole plan on us, we had to put a new foundation in which ended up costing too much money in the house fell over. It basically just collapsed down and so we had to build a new house and so what it's like in that house, we've owned this property now for three years, because of the time in the restore and the new plan, right, and we know what we're doing and so it was just one of those things where everything that could have gone oh, and then our foundation company walked off with half of our deposit, it was just everything went wrong and we do this and we manage and we watch everything. But sometimes things just go wrong and that was one of them. Where it's a domino effect, it was like this went wrong, this went wrong, this went wrong and then you know, and so now we're listed on the market and if we sell it for full price, which we've been at for 75 days, we'll maybe break even after three years and you know, and who knows, we might take a haircut too. But that's just kind of part of the game. Like how I look at this, I don't look at this per deal. I look at this as I'm an investor.   So if I'm looking at the stock market, again, like if I look at my portfolio, I'm not looking at that one stock, I'm going how did this work over a 12 to 24 month period and so that's how we even look at our flips the last 12 to 24 months, like some are like the last 24 we made too much money. Now we're going to take a little bit of a haircut. But when we look at it, at the end of the day, it's still going to be a great return as long as we're buying and selling consistently. But we have definitely had I've had all sorts of bad things happen on where we've lost money usually comes down to bad hiring or bad contractors, where we've hired guys, we've worked with them for five, six years, the wheels come off and they disappear with our money. I've hired a fake contractor before where he hadn't legitimate fake IDs and licenses and a business law and he still had a business license still had a contract. That deal I definitely lost I think I lost like 80 grand on that house because he didn't eat it's not only he, he took my money did a bunch of the work was supposed to get permits, never got permits, I got red tagged. That's how I found out it was all a big scam and we had to rip the whole house, we basically had to restart backwards and redo it again. So not only did we pay him way too much money, we had to redo everything that he had done and so when you get in that situation, it's really hard to get out of that hole and you know, for me, I just say sometimes you got to take, you know, take a face to the face and keep moving forward, go and go that route. But yes, if you can make 50% returns, you can lose it just as fast.   Michael: Yeah and I think that's so important to remember because I know I'm totally guilty of it myself getting so enamored with these high returns and the big sexy projects and oh my god, how attractive it is and then when things go sideways, you're like, oh, I didn't really think this was gonna happen and you can get caught looking pretty quickly.   James: It's easy to get caught in this business. It's you know, it that's what everyone just has to remember is you got to constantly be refining it. Typically when you're a flipper or developer even a buy and hold strategist, right? You have to change your business plan every nine to 12 months, because the market will change cost of money is going to change market conditions are going to change rehabs going to change and so you have to keep changing as long as you move your chess pieces around and try to forecast it down a little bit. Then that's how you don't get really rocked. But, you know, at the end of the day, bad things happen. Sometimes just things don't go the way you want and you just have to keep moving forward and the most important thing is don't lock up like I back when I was newer. I would kind of lock up and try to figure out how to save the money and get the money back. But then you just waste time and you get bled out by a holding cost because you're paying 10 to 12% for hard money and so you start to be you almost are becoming, you're spending even more money by trying to pick up the money. So for me, I just try to keep it moving for that point.   Michael: Yeah, that makes a ton of sense. It's like almost counterintuitive, but when you look at the math, like numbers don't lie. That's really a really great point.   James: Yeah, you got to look at the whole picture. Like, what were your cost racking and how do you mitigate the risk at the end of it?   Michael: Yeah, love it James. This has been awesome, man. For people that want to reach out to you learn more about your business, learn more about what it is you do, where's the best place for them to do that?   James: Well, first, check us out on Bigger Pockets on the market podcast is an awesome podcast where we talk a lot about a lot of these strategies in forecasting and data, how we change our strategies with data, like what's going on in the market, where do we see the trends are and then the key is the change before they happen and so we talked about it there or you can check us out we do a ton of free real estate education on our YouTube channel @projectre or Instagram @ jdainflips. We were really just trying to get good information out to people. It's not really surfacey like we get we get into the issues like alright, this is what happened. This is what how we're fixing it, and it cost me this much and so we get very, very specific training on our social media pages.   Michael: So it's not just glamour shots of Lamborghinis, and cheques and that sort of thing.   James: Yeah, I haven't got I haven't gotten to that. I haven't got my spray tan all the way on yet.   Michael: In good time and good time.   James: Don't believe what you see on social media. It's no we're gonna show you the glamorous lifestyle of it. Flipping is not easy and we let you guys know what we're doing. I mean, even for us, right? We flipped over. We've been in over 3000 flips, stuff gets asked all the time to it's caught we you just have to work with other investors find out how to fix problems, and the best way you can do that is just communicate with everybody. Yeah, so definitely check us out.   Michael: I love it. Well, James, thank you so much again for coming on and hanging out with me. I really appreciate you.   James: Yeah, no, thanks for having me on, I appreciate it.   Michael: Absolutely take care of we'll chat soon.   All right, everyone. That was our episode. A big thank you to James for coming on super interesting stuff and can't wait to see how they continue to perform in the next six, nine and 12 months going forward. As always, if you like the episode, feel free to leave us a rating or review. We'd love to hear from you and we look forward to seeing on the next one. Happy investing…

This week, please join authors Mikhail Kosiborod and Christian Schulze and Editorialist Stefan Anker as they discuss the original articles "Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure: Results From the EMPULSE Trial" and "Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF)" and the editorial "SGLT2 Inhibitors: From Antihyperglycemic Agents to All-Around Heart Failure Therapy." Dr. Carolyn Lam:             Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley:           And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam:             I'm so excited about the feature discussion this week. It is a paired feature along with their editorial and it's all focused on SGLT2 inhibitors. The first, results from the EMPULSE trial, Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure; and the second, the EMPAG-heart failure trial, The Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients with Acute Heart Failure. Incredibly important topics, incredibly important discussion. Wait up for it. We're just going to tell you a little bit more about two other original papers in today's issue, and I'm going to go first, Greg. Is that okay? Dr. Greg Hundley:           You bet. Dr. Carolyn Lam:             Now, really interesting topic here. We have strong evidence supporting the effective blood pressure and cardiovascular disease risk lowering properties of healthy diet such as the DASH diet, Mediterranean diet, and so on and so on. But what about the diet consumed by a fifth of the entire world's population? The Chinese cuisine. Interestingly, today's paper addresses just that. This is from authors, Dr. Wu, from Peking University Clinical Research Institute and colleagues who performed a multicenter patient and outcome assessor blind randomized feeding trial among 265 participants with baseline systolic blood pressure of 130 to 159 in four major Chinese cuisines. And these are the Shandong, Huaiyang, Cantonese, and Szechuan cuisines, and here's how they did it. After a seven day run in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine based Chinese heart healthy diet for another 28 days. The primary outcome was systolic blood pressure. The study developed the first heart healthy Chinese diet that fits Chinese food culture and emphasizes its palatability by involving master shifts in developing the recipes. Dr. Greg Hundley:           Oh wow. Carolyn, this is really interesting, especially one fifth of the world's population in studying a heart healthy diet. So did it work? I can't wait to hear the results. Dr. Carolyn Lam:             Well, the change in systolic and diastolic blood pressure from baseline to the end of the study in the control group was five millimeters mercury and 2.8 millimeters mercury reduction, respectively. The net difference of change between the two groups in systolic and diastolic blood pressure were a reduction of 10 and almost four millimeters mercury, respectively. The effect size did not differ among cuisines, and so in summary, with a patient and assessor blind randomized feeding trial, this study really demonstrated that the blood pressure lowering effect of the Chinese heart health diet could indeed be substantial, and importantly, be compatible with medications while palatable and affordable in Chinese adults with high blood pressure, and so these results support the idea that food is medicine and will give many patients with high blood pressure the confidence to adopt heart healthy diets in their lifestyle treatment. Dr. Greg Hundley:           Wow, Carolyn, that is really an interesting article. So many of these articles today could all be features in and of themselves. That was just outstanding. Well, my next paper comes to us from the world of preclinical science, and it's from Dr. Sean Wu from Stanford University School of Medicine. So Carolyn, immune checkpoint inhibitors are monoclonal antibodies that are used to activate the immune system against tumor cells. Now, despite their therapeutic benefits, immune checkpoint inhibitors have the potential to cause immune mediated adverse events such as myocarditis, a rare but serious side effect with up to 50% mortality in affected patients. Now histologically, patients with immune checkpoint inhibitor of myocarditis have lymphocytic infiltrates in the heart implicating T-cell mediated mechanisms. However, the precise pathologic immune subsets and molecular changes in immune checkpoint inhibitor myocarditis are unknown. Dr. Carolyn Lam:             Wow. So insights into the etiology of these immune checkpoint associated myocarditis cases must be very important. So what did they find? Dr. Greg Hundley:           Right, Carolyn? So clonal cytotoxic, TEMRA CD8+ cells were found to be significantly increased in the blood of patients with immune checkpoint inhibitor myocarditis corresponding with an analogous increase in effector cytotoxic CD8+ cells in the blood and hearts of PD-1 deficient mice with myocarditis. These expanded effector CD8+ cells had unique transcriptional changes, including upregulation of the chemokines CCL5, CCL4, and CCL4L2, and they may serve as attractive diagnostic therapeutic targets for reducing life threatening cardiac immune related adverse events in immune checkpoint inhibitor treated cancer patients, and Carolyn, just like so many of our articles, there's a very nice accompanying editorial by Professor Gianluigi Condorelli that also offers an update on current research pertaining to non-systemic steroid therapy to treat immune mediated myocarditis. Well, Carolyn, how about we jump to some of the other articles in the issue? Dr. Carolyn Lam:             Oh, you bet, Greg. There's an exchange of letters between Drs. Madias and Knops regarding the article “Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: The Analysis of All Appropriate Therapy in the PRAETORIAN Trial.” Dr. Greg Hundley:           And also in the mail bag, Professor Mark has a Research Letter entitled “Effect of Empagliflozin on Kidney Biochemical and Imaging Outcomes in Patients with Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction, The SUGAR-DM-HF Study,” and our own Tracy Hampton has several synopses from articles published elsewhere in our piece on cardiovascular news. Well, how about we get onto that feature forum discussion, two papers, two editorialists. I can't wait. Dr. Carolyn Lam:             Me too. Let's go, Greg. Dr. Greg Hundley:           Welcome, listeners to this July 26th feature forum discussion. So remember, listeners, for forum discussions, we have several manuscripts that focus on a singular topic and we bring together the authors, our associate editors, and also an editorialist, and today, I want to introduce, we have with us Dr. Mikhail Kosiborod from Mid America Heart Institute in Kansas City, Missouri, Dr. Christian Shults from University Hospital Jena in Germany, Stefan Anker from Charité in Berlin, Germany, and our Associate Editors, Brendan Everett from Brigham and Women's Hospital in Boston, Massachusetts, and Justin Grodin from University of Texas Southwestern Medical Center in Dallas, Texas. Welcome, gentleman, and we'll start with you, Mikhail. Could you describe for us the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Mikhail Kosiborod:   Well, thanks very much, Greg. The background for the study, which was the secondary analysis of the EMPULSE trial was patients that are hospitalized with acute decompensated heart failure represent a very high risk group. We know that they have high risk of death and hospitalizations, and we also know that they have very poor health status that's very high burden of symptoms, physical limitations, and poor quality of life, and so addressing those treatment goals, trying to reduce the risk of clinical events like death and hospitalizations and improve the symptoms and physical limitations in this patient population are very important treatment goals. Now we previously demonstrated in the main results of the EMPULSE trials that using empagliflozin initiating empagliflozin SGLT2 inhibitor in this patient population as compared with placebo provided a significant total clinical benefit, which was a composite of total death, repeat hospitalizations for heart failure, or a change in a Kansas City cardiomyopathy questionnaire, which is a kind of a gold standard measure of patient's health status. What we tried to do in a much more granular fashion in this study is to understand the effects of empagliflozin as compared with placebo on this very important outcome, the Kansas City cardiomyopathy questionnaire, and we actually evaluate all of the key domains and composite symptoms, physical limitations, as well as quality of life. Dr. Greg Hundley:           Very nice, and Mikhail, can you describe for us what study population specifically, and then what was your study design? Dr. Mikhail Kosiborod:   Well, this was a population of patients that were hospitalized with heart failure and that EMPULSE was unique in its design because first of all, previous SGLT2 inhibitor trials mostly focused on patients with chronic heart failures that were in an outpatient setting, including prior trials of empagliflozin, and EMPULSE really focused on acutely hospitalized patient population, but it included patients regardless of ejection fraction. So as they were hospitalized with decompensated heart failure and reduced or preserved ejection fraction. They were enrolled regardless of if they had type 2 diabetes, they were enrolled essentially, regardless of kidney function, only patients with EGFR of less than 20 were excluded, and also importantly, was this study and a unique feature of the study in particular was that we enrolled patients whether they had acute de novo heart failure. That means that was a new diagnosis of heart failure that was bad enough for them to be hospitalized or worsening chronic heart failure requiring hospitalization. So it was really an all-comer trial for patients acutely hospitalized for heart failure. So we had just over 500 patients and they were randomized in the hospital. After a brief period of stabilization, we use empagliflozin, 10 milligrams daily or placebo and treated for 90 days, and the primary outcome at 90 days was a total clinical benefit that I described that was a composite, hierarchical composite of total death hospitalizations, repeat hospitalizations for heart failure and changing KCCQ. In this study, again, we focused predominantly on KCCQ, trying to understand the effects on health status, again, symptoms, physical limitations, and quality of life. Dr. Greg Hundley:           Excellent. And Mikhail, what were your study results? Dr. Mikhail Kosiborod:   Well, what we observed, a couple of things. One is we first examined the effects of empagliflozin on the primary endpoint across the range of KCCQ and baseline, and what we found was that regardless of the degree of symptomatic impairment and baseline, empagliflozin was consistent in providing them total clinical benefits that I described previously, and then kind of shifting to what I think is the most interesting findings, the effects of empagliflozin versus placebo on KCCQ, what we found was that as you would imagine in this population of patients that were acutely hospitalized with heart failures, that had very poor health status, very low KCCQ at baseline, and within the first 90 days, which was observation period, both groups of patients had substantial improvements in KCCQs. As one would expect after acutely decompensated episode of heart failure and treatment in a hospital, everyone got better. But patients treated with empagliflozin had significantly greater improvement in KCCQs than those that were treated with placebo, and that was first of all, a very substantial difference between the two groups. It was more than five points in favor of empagliflozin already at 15 days and was highly statistically significant, and it was maintained throughout the 90 day treatment period. So the fact that we saw both a clinical meaningful and statistically significant improvement in just 15 days, I think is a very important clinical message, and then finally, I guess what I will mention is these benefits of empagliflozin while main outcome we looked at was KCCQ total symptoms, we're focusing on the symptoms, but it was consistent when we looked at physical limitations as well as quality of life. So really, all key domains of KCCQ were impacted in a similar way. Dr. Greg Hundley:           Very nice. So in acute heart failure, marked symptomatic improvement after the administration of the SGLT2 inhibitor empagliflozin at 10 milligrams per day. Well, now listeners, we're going to turn to our associate editor, Dr. Brendan Everett, and Brendan, again, you have many papers come across your desk. What attracted you to this particular manuscript? Dr. Brendan Everett:      Well, thanks, Greg, and I think this manuscript caught my eye because of the importance of the clinical question, and Mikhail outlined why I think that was really relevant. So we understand that this class of medications or SGLT2 inhibitors have important effects on outcomes like re-hospitalization in patients with heart failure, and what was particularly striking about this paper is that it took patients rather than those with chronic heart failure, but as Mikhail mentioned, enrolled a patient population that was actually in the hospital, and I think this was an important frontier for this particular question about when to start the SGLT2 inhibitor and what kind of benefits there might be. Furthermore, I think the fact that they did not select the population based on ejection fraction was particularly striking, and of course, I think is remarkable, but now old news, they did not select on the presence or absence of diabetes as well. And so those three components really attracted me to the paper. I also think the outcome is one that really is valuable and worth exploring, and specifically, I'm talking about how patients feel on the medication after a hospitalization for heart failure. Appropriately, we focused on re-hospitalization for heart failure and cardiovascular death in prior trials in this space, and I think we need to embellish those findings or further deepen those findings with a perspective on how patients actually feel when they get the medication, and of course, it goes without saying that what's particularly important here also is that it was a randomized placebo controlled trial, and so the results have some element of internal validity that I think is really important. So those were the things, Greg, that really attracted my attention as I read the paper for the first time. Dr. Greg Hundley:           Thank you so much, Brendan. Well, listeners, we've got a second paper today and we're next going to hear from Dr. Christian Shults, and he also is focusing on really another aspect of the administration of empagliflozin in patients with acute heart failure and that pertains to the renal function of the patients. So Christian, could you describe for us the background pertaining to your study and what was the hypothesis that you were intending to address? Dr. Christian Schulze:     Thanks, Greg. Well, it's great to introduce all study here in this running. So our study impacted those in acute decompensated heart failure. The impact HF trial was a study based on the hypothesis that we wanted to test, whether empagliflozin has effects in acute decompensated heart failure, and we focused on the patient population that was not addressed in EMPULSE, patients that came to the ER and needed to be treated right away, and we wanted to know and this was our main hypothesis, but are the diuretic and [inaudible 00:17:11] effects of the SGLT2 inhibitor on this case, empagliflozin, actually had an impact on diuretic regimens and kidney functions since this is one of the main end points that limits treatment, and also is one of the outcomes of patients with acute decompensated heart failure in the hospital. Dr. Greg Hundley:           Very nice. And so Christian, what study design did you implement and who was included in your study population? Dr. Christian Schulze:     So we also used the randomized two arm study design. We included patients with acute decompensated heart failure independent of left ventricular ejection fraction. Patients needed to have an NT-proBNP of more than 500. The average NT-proBNP in fact was 4,300 in our entire patient population, and we included patients within 12 hours of presentation. So many of these patients have been recruited in the ER, they presented two hour cardiology heart failure service, and then were immediately randomized to the trial in the two arms, and we tested not 10 milligrams of empagliflozin. We actually tested 25 milligrams of empagliflozin based on in-house data that 25 milligrams potentially had a stronger diuretic effect compared to 10 milligrams. Dr. Greg Hundley:           And what did you find? Dr. Christian Schulze:     So we followed patients for five days. It was a relatively short period of time. It was designed to address the in-house phase of patients with acute decompensated heart failure. The mean duration of stay was 6.3 days in the hospital so this was exactly the time that we wanted to test. We had a 30 day endpoint for safety issues, and what we could see is that patients on 25 milligrams on empagliflozin on top of standard diuretic regimens and medical care had 25% higher diuretic outputs compared to patients in the placebo group. We also found no differences in markers of renal injury dysfunction, and could in fact confirm that after 30 days, patients in the empagliflozin group had a better EGFR compared to patients in the placebo group. On top, we saw a more rapid decrease in body weight and also a more profound decrease in NT-proBNT values. Dr. Greg Hundley:           And Christian, just for our listeners to put a little bit of this in perspective, what was the range of serum creatinine for the patients that were enrolled in your study? Dr. Christian Schulze:     So the main EGFR in the entire population was around 60 and the creatinine values were around 107 on average in the entire cohort. So this is a very typical population. We had around 30% of the population with de Novo heart failure, around 20 to 30% of the population was pre-treated for preexisting heart failure. So very typical population of patients with heart failure presenting to the emergency room. Dr. Greg Hundley:           And did you have any kind of lower level EGFR cutoff, I mean, for enrollment into this study? Dr. Christian Schulze:     So when we designed the trial, we actually still had the sub classification of diabetes or impaired glucose or homeostasis as an inclusion criteria. We dropped it before we started the trial because the data came out that this is actually, in fact, not a critical issue for patients with heart failure. So diabetes was not a subgroup in our trial and the lower limit of EGFR was actually a thoroughly defined protocol. Dr. Greg Hundley:           Very nice. Well, listeners, now we're going to turn to our second associate editor, Dr. Justin Grodin from University of Texas Southwestern Medical Center in Dallas, Texas, and Justin, similar to Brendan, and you see many papers come across your desk and so what attracted you to this particular paper by Christian and his colleagues? Dr. Justin Grodin:            Well, Greg, I think first and foremost, and I think very similar to Brendan, but I think what's always striking is if I may just take a step back, decompensated heart failure in the United States is the number one cause for hospitalization among Medicare beneficiaries. So I think really, the brunt and really the truly public health message of the disease is very important in the applicability, and even though that decompensated heart failures is one of the most common things that we ever encounter when we practice, internists, cardiologists, et cetera, we have very, very little clinical trial guidance that tells us how to decongest individuals when they're hospitalized with swelling and heart failure and a lot of these individuals can be quite ill, and we have some clinical trial data, but largely, we have a lot of negative studies or inconclusive studies in this space. So certainly, what drew me to this trial was definitely that context, and obviously, based on the mechanistic data with SGLT2 inhibitors, I think one of the natural questions, which Christian addresses, is that we know that up front, they do augment natriuresis. So I think it's very compelling to marry those two together because this is what many of us that use these medications regularly have been asking is whether or not they would have some efficacy in that regard, and then another thing that caught my eye and me as a cardiorenal investigator was, just as Christian highlighted, was we have a clinical trial that randomly assigned individuals, really that were ill and many of whom were not stabilized within 12 hours of presentation, and we're talking about patients that are coming into the hospital at all times during the day in and I think that's very remarkable that we have something with standard... We have a study with standardized assessments where we're really trying to ask a very practical, pragmatic question, which is do these therapies lower the sodium balance in individuals with decompensated heart failure, and I think what's important is largely, we've got a lot of medications that supplement loop diuretics, which are the class of drugs that the majority of us use, and we have a lot of other therapies that we use that really have very little data or poor data that guide us such as thiazide diuretics, carbonic and hydrase inhibitors, mineralocorticoid receptor antagonists, and so here, we have a clinical trial that asks a question that's on many people's minds. And then we do have very compelling, at least short term pragmatic and mechanistic data that does tell us that these individuals do have a greater natriuretic effect when empagliflozin is used as an adjunct to standardized loop diuretic therapy. So it's a very practical clinical question, and I think what's very important, and we could debate probably all day about the implications of GFR change and kidney function change while we're decongesting somebody with diuretics, but I think what's reassuring to all the clinicians is we really didn't see an effect on kidney function despite a greater natriuretic effect or enhanced diuretic effect, if you will, with the use of empagliflozin. Dr. Greg Hundley:           Very nice. Well, thank you, Justin. Listeners, now we have an editorialist and as you know, editorialists really help us put the scientific presentation of an original manuscript into the perspective of really the global theme of a topic, and we have Stefan Anker from Berlin, and Stefan, can you describe for us how do we put these two manuscripts and results that we've heard about really in the context now of moving forward with the use of SGLT2 inhibitors in the management of patients with acute decompensated heart failure? Dr. Stefan Anker:            Thank you so much. Really, I think these two papers, on the one hand, enhance our certainty about early use, and on the other hand, possibly show us that there might be even more to achieve by, on the one hand, moving even earlier with the application of SGLT2 inhibitors or possibly consider the higher dose. Now let's take one step back. These drugs were developed in type two diabetes and the first successful trial was the [inaudible 00:25:42] outcome trial. Many people have forgotten that this trial tested two doses and not only one, the 10 and the 25 milligram dose, and of course, with the success for improving kidney outcomes and heart failure hospitalization outcomes, we move forward into these two specialist areas, on the one hand, broadening it to the non-diabetic communities, but on the other end, narrowing it by focusing on the 10 milligram dose regardless of whether there is [inaudible 00:26:12]. And we basically now learn A, to use these drugs even earlier than we did in the big trials and we can now be sure to start their use in the hospital, and if you take the average change in quality of life results seen, you actually get a better result for the patient on quality of life when you start earlier than when you start late in the ambulatory studies where basically, in the chronic setting, maybe you have one and a half to two points difference. Here, you now have four and a half points in the study shown by Mikhail, and of course, it's also good to know that you can start this in any type of patient, regardless of their quality of life. The impact study from Christian, they basically moved it now even earlier, moving into the hospital space is possible based on EMPULSE. Moving it into the acute admission space is at least a consideration now based on what Christian here has shown. And he is actually addressing the one question I hear very often in my presentations about SGLT2 inhibitors, what about this 25 milligram dose? Is there a place for this in cardiology as well, and a possible place is shown here, not only that this is a safe thing to do, but also you get urinary output. Of course, we may in the future, want to see this compared, directly compared to the 10 milligram dose, but of course, the world is not created in one day, but needs more than one and so really, I think these two studies, on the one hand, address an important issue, when to start using them. On the other hand, show us a little bit of a glimpse to the future. Dr. Greg Hundley:           Very nice, Stefan, and listeners, we get to take advantage of having these authors, editors, and editorialists together and ask them what they see as the next study to be performed in this sort of sphere of research. So Mikhail, we'll start with you. In 30 seconds or less, what do you see as the next study to be performed in this arena of research? Dr. Mikhail Kosiborod:   I think, Greg, what we've learned recently, including from the EMPULSE trial, we have this population of patients in a hospital with heart failure's a huge issue as Justin mentioned, and until recently, we had very little [inaudible 00:28:31] for them beyond the usual kind of decongestion with loop diuretics and trying to make them feel better, but you look at outcome data. It really was a dearth of effective therapies that have meaningful impact on important outcomes. Now that's changing, SGLT2 inhibitors is one example. There are some other recent examples in this patient population, like a firm HF and iron deficient patients with heart failure. But the bottom line is it's no longer kind of a desert, if you will, of positive trials. We now have something we can do and I think what this proves is that we need to actually invest more, both in terms of resources and time to really do what we we're being able to do in other areas of heart failure and those patients with chronic, half and half where we can start developing pillars of therapy that can actually truly improve outcomes with this patient population and there is a lot going on that makes me optimistic that's going to be the case in the coming years. Dr. Greg Hundley:           Very nice. And Brendan? Dr. Brendan Everett:      Well, I think both trials mentioned today really pushed our understanding of this population forward. I think the biggest clinical question that I face when I'm caring for these patients is that we have four, at least, guideline directed therapies, right? We have beta blockers, we have ARBs, ACE inhibitors and ARNIs. We have mineral receptor antagonists and we have SGLT2 inhibitors. So which do we use in what order and how do we start them, and what kind of parameters do we use to guide us if we're limited either by renal function or by blood pressure or by some other factor. And we often, if not always, have one of those constraints that we're dealing with and so I would say the next step for me is trying to sort out which of these therapies and what order ought to be our highest priority for patients with acute decompensated heart failure as we move quickly from the acute decongestion stage towards discharge and a chronic therapy that will then be followed as an outpatient over the ensuing days and months. Dr. Greg Hundley:           Very nice. And Christian. Dr. Christian Schulze:     Thank you again, and Brandon pointed out very nicely. I mean, we have good evidence now for chronic heart failure treatment. We have the four columns of heart failure medical therapy. Questions that remain open is what do we do with all these patients that are now guideline medicated, come to the hospital with an acute decompensation? Should we carry on with the medication? Should we terminate and in particular, should be carry on with full dose, 50% dose of SGLT2 inhibitors, and the next question is, what dose should we use, in fact, for SGLT2 inhibitors? Is it in group effects or is sotagliflozin comparable to empagliflozin, and then is there a role for a step by scheme that we initially have in high dose therapy that we then downgrade to 10 milligrams on the chronic heart failure treatments, and then of course, quality of life is very important. We should ask this question also in this patient population that is early on treated, do we see benefits that carry on in the outpatient setting and do we see an effect of early treatment on long term benefits? Dr. Greg Hundley:           Justin? Dr. Justin Grodin:            Well, I would have to agree with all of my colleagues here on this call. I think all have raised really good points, but I think one very simple, and I'll echo some of Brendan's statements, but one very simple question is we know that when we decongest people and initiate a negative salt balance in the hospital for decompensated heart failure, we cause neurohormonal activation and there are a lot of downstream untoward effects from chronic decongestive therapies, and I think one of the more compelling things is we still yet have defined what is the best way to decongest individuals with swelling or volume overload in the hospital. Here, we have compelling studies with SGLT2 inhibitors for quality of life and really, the way patients feel. And this is really what's important to them, and then something very pragmatic to clinicians and let's make people pee more, but I think one of the compelling questions, and I don't know if it will be answered, is we have a lot of choices for supplemental therapies and different diuretic strategies when patients come in the hospital for decompensated heart failure, and I do think that these studies do move the needle with SGLT2 inhibitors. I think that's abundantly clear, but we still don't know what is the best way to dry out my patient or make my patient pee so that they feel better, but I do think that these studies do at least set the stage that there's some compelling advantages to SGLT2 inhibitors. Dr. Greg Hundley:           And then lastly, Stefan. Dr. Stefan Anker:            Thank you. Besides the detailed points mentioned by many, and Christian, totally support 25 versus 10 milligram, how long 25 milligram, if at all in the future. Besides this, I'm interested in the big picture question. So what about the post myocardial infarct congestion/heart failure situation, and there will be two trials in the next 18 to 24 months that report on this, and my pet kind of area is actually to treat heart failure where nobody thinks it is heart failure, and what I mean is for instance, advanced cancer patients, cardiac wasting cardiomyopathy. So the heart failure in sick cancer patients, and indeed, we are planning to do exactly that now in a study focusing on hospice care patients to really improve the quality of life, the very thing focus here on the EMPULSE trial. Dr. Greg Hundley:           Well, listeners, we want to thank our authors, Dr. Mikhail Kosiborod from Mid America Heart Institute in University of Missouri, and Christian Shults from the University Hospital in Jena, Germany. Also, our associate editors, Dr. Brendan Everett from Brigham and Women's Hospital in Boston, and Dr. Justin Grodin from University of Texas Southwestern in Dallas, Texas, and also, our editorialist, Dr. Stefan Anker from Charité in Berlin, Germany for bringing us these two manuscripts pertaining to two randomized clinical trials regarding the administration of the SGLT2 inhibitor, empagliflozin in acute heart failure, demonstrating first, marked improvement in heart failure symptoms and health related quality of life. And second, in those with estimated GFRs greater than 30 mls per minute, an augmentation of natriuresis in the setting of the co-administration of diuretics without deterioration in renal function. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Canagliflozin is an SGLT2 inhibitor. I discuss the pharmacology, dosing, adverse effects, and drug interactions of this medication. Canagliflozin reduces blood sugar, by facilitating its exit through the urine. This can increase the risk of genitourinary infections. A diuresis type effect can happen due to canagliflozin and this effect may be exacerbated by the use of thiazide and loop diuretics. Hyperkalemia has been reported with the use of canagliflozin; the risk for this is increased with the use of medications like ACE inhibitors, ARBs, and aldosterone antagonists.

How do you counsel patients on beta blockers? Is one beta-blocker better than the other? What is preferred: ACEi, ARBs or ARNIs? What are the pros and cons of each? How does spironolactone compare to eplerenone? When do you stop mineralocorticoid receptor antagonist? What are risks with SGLT2 inhibitors? How do you initiate GDMT? Which meds do you start first and in what order?Show notes, Transcript and References:  https://www.coreimpodcast.com/2022/05/11/5-pearls-on-guideline-directed-medical-therapy/Sponsor: https://go.amboss.com/GDMTGet CME-MOC credit with ACP: https://www.acponline.org/cme-moc/cme/internal-medicine-podcasts/core-im Time stamps:03:13 Pearl 112:14 Pearl 220:36 Pearl 326:42 Pearl 432:16 Pearl 5Tags: IM Core, CoreIM, heart failure with reduced ejection fraction, GDMT, treatment, cardiology

In this episode, we review new updates and key concepts from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. This guideline is newly published (April 2022) and is a full update of the 2013 guidelines and the 2017 focused update for heart failure. Key Concepts Heart failure is classified as HFrEF (heart failure with reduced ejection fraction = 50% with increased LV filling pressures). Most drug therapy recommendations are similar for HFrEF, HFimpEF, and HFmrEF whereas HFpEF therapies are different. The 2022 AHA/ACC/HFSA heart failure guidelines now recommend SGLT2 inhibitors, such as dapagliflozin and empagliflozin, in patients with HFrEF, HFmrEF, and HFpEF. The 2022 AHA/ACC/HFSA heart failure guidelines continue to prefer ARNi, such as sacubitril/valsartan (Entresto), over ACE inhibitors and ARBs in patients with HFrEF. Based on the PARAGON-HF trial, ARNi is also recommended in those with HFpEF albeit with a weak recommendation. Avoiding excessive dietary sodium is reasonable to reduce congestive symptoms in patients with heart failure; however, guidelines do not recommend a specific maximum intake nor does data support clinical outcome benefit with dietary sodium restriction. References Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published online ahead of print, 2022 Apr 1]. Circulation. 2022;101161CIR0000000000001063. doi:10.1161/CIR.0000000000001063. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063 Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial. Lancet. 2022;399(10333):1391-1400. doi:10.1016/S0140-6736(22)00369-5

Two very common types of blood pressure medicines, so called ACE inhibitors and ARBs, may improve survival for people with cancer of the pancreas, a new study finds. William Nelson, director of the Kimmel Cancer Center at Johns Hopkins, notes that this is an idea that's been around for a while. Nelson: What they found […]

March is National Kidney Month, which brings awareness to kidney health, which in turn is a global public health burden. For this last episode of Physician's Weekly podcast this March of 2022, we wanted to highlight a recent publication about the use of diuretics in patients with chronic kidney disease, or CKD, with a prevalence of 11% in the USA . Diuretics are useful in the management of most patients with CKD because they reduce ECF volume; lower blood pressure; potentiate the effects of ACE inhibitors, ARBs, and other antihypertensive agents; and reduce the risk of cardiovascular disease in CKD. Physician's Weekly's Senior Editor Martta Kelly interviews Dr. Alan S Go, of the Kaiser Permanente of Northern California, whose team looked at the effect of diuretics on renal outcomes among nearly 48K adults with chronic kidney disease. Loop and thiazide class diuretics are an important part of guideline-directed medical therapy for patients with CKD with hypertension, edema, metabolic acidosis and/or hyperkalemia. Yet diuretics can be also be associated with acute elevations in serum creatinine and electrolyte derangements. Whether diuretics result in direct kidney injury versus benign hemoconcentration of serum creatinine remains controversial, which was the rationale behind this large study. But first, March is also famous for MATCH DAY from the National Resident Matching Program (NRMP). Match Day is when domestic and international medical school students and graduates learn in which U.S. residency programs they will train. Naturally this is extremely important to the careers of all residents and it is coupled with high stress and anxiety, as well as questions about how best to prepare. Some recent participants set up a Resident-led platform, called Inside The Match, with information, help reviewing your applications, and a podcast series to provide everything you wanted to know about the residency match process but were too afraid to ask. Physician's Weekly interviews psychiatry resident and co-founder Simone Bernstein, previously recognized as a social entrepreneur in Forbes' 30 under 30 list. She is truly a mover and shaker!Enjoy listening!Additional reading:https://www.insidethematch.com/Fitzpatrick JK, Yang J, Ambrosy AP, Cabrera C, Stefansson BV, Greasley PJ, Patel J, Tan TC, Go AS. Loop and thiazide diuretic use and risk of chronic kidney disease progression: a multicentre observational cohort study. BMJ Open. 2022 Jan 31;12(1):e048755. Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

The following question refers to Section 4.7 and figure 16 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern Student Dr. Shivani Reddy, answered first by Fellow at Johns Hopkins Dr. Rick Ferraro, and then by expert faculty Dr. Roger Blumenthal.Dr. Roger Blumenthal is professor of medicine at Johns Hopkins where he is Director of the Ciccarone Center for the Prevention of Cardiovascular Disease. He was instrumental in developing the 2018 ACC/AHA CV Prevention Guidelines. Dr. Blumenthal has also been an incredible mentor to CardioNerds from our earliest days.The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #4 Ms. K.M. is a 40-year-old woman presenting to the outpatient clinic for a routine physical exam required for her employment as an airline stewardess. She states she has been in her usual good health but does experience occasional headaches and lightheadedness while in flight. On exam her BP was noted to be 170/90. The diagnosis of hypertension is confirmed during a subsequent clinic visit. What would be the most appropriate initial therapy recommendation(s) for Ms. K.M.?A. Initiate single drug therapy with a beta-blocker.B. Discuss and initiate lifestyle interventionsC. Initiate two-drug combination therapy with a thiazide-like diuretic, BB, CCB, or an ARB.D. Both B and C  Answer #4 The correct answer is D. Both B (lifestyle interventions) and C (initial combination therapy) are appropriate at this time. Lifestyle interventions are indicated for all patients with high-normal BP or hypertension because they can delay the need for drug treatment or complement the BP-lowering effect of drug treatment (Class 1). Moreover, most lifestyle interventions have health benefits beyond their effect on BP. Single-drug therapy will rarely achieve optimal BP control. Therefore, initial antihypertensive therapy with a combination of two drugs, preferably as a single-pill combination, is recommended for the management of HTN (Class 1). The only exceptions would be patients with a baseline BP close to the recommended target, who might achieve that target with a single drug, or very old (>80 years) or frail patients who may better tolerate a gentler reduction of BP. Five major classes of BP-lowering drug therapy have shown benefit in reducing CV events; angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs), and thiazide or thiazide-like diuretics. A combination of an ACE inhibitor or ARB with a CCB or thiazide/thiazide-like diuretic is the preferred initial therapy for most patients with hypertension (Class 1). For those in whom treatment requires escalation to three drugs, a combination of an ACE inhibitor or ARB with a CCB and a thiazide/thiazide-like diuretic should be used (Class 1). Resistant hypertension is defined as BP being uncontrolled despite treatment with optimal or best-tolerated doses of three or more drugs including a diuretic, and confirmed by ABPM or HBPM. Spironolactone is the most effective drug for lowering BP in resistant hypertension when added to existing treatment; however, the risk of hyperkalaemia is increased in patients with CKD. When spironolactone is not tolerated, amiloride, alpha-blockers, beta-blockers, or centrally acting drugs, such as clonidine, have evidence supporting their use. Renal denervation and device-based therapy may be considered for specific cases. Beta-blockers should be used when there is a specific indication (e.g. angina, post myocardial infarction, arrythmia, HFrEF, or as an alternative to an ACE inhibitor or ARB in women of child-bearing potential). Combinations of an ACE inhibitor and an ARB are not recommended because of no added ben...

Dr. Ebell and Dr. Wilkes discuss the POEM titled ' Lowering blood pressure does not decrease the risk of T2DM in persons with hypertension; ACEIs/ARBs do '

Lose your heart to NephMadness 2022! Dr. Joel Topf (@kidney_boy) and Dr. Sadiya Khan (@HeartDocSadiya) tackle the NephMadness 2022 Cardiorenal Syndrome region, leading us through the pathophysiology of cardiorenal syndrome, how to approach the creatinine “bump” with diuresis, managing patients with diuretic resistance, and more. *Claim free CME for this episode at curbsiders.vcuhealth.org! *Available within 24 hours of release. Episodes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | thecurbsiders@gmail.com | Free CME! Credits Producer, Writer, Show Notes, Infographics: Malini Gandhi Cover Art:  Beth Garbitelli Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP    Reviewer: Emi Okamoto MD, FACP Executive Producer: Beth Garbitelli Showrunner: Matthew Watto MD, FACP Editor: Clair Morgan of nodderly.com Guest: Dr. Joel Topf MD, Dr. Sadiya Khan MD Sponsor: ACP's Internal Medicine Board Review The Greater Chicago course, beginning on May 23rd  through May 27th     or Washington, D.C., on July 11th through July 15th New registrants will receive 6 months of access to the course recordings. Visit acponline.org/imbr2022 to register or learn more. Sponsor: SquareSpace Go to Squarespace.com for a free trial, and when you're ready to launch, go to squarespace.com/Curb to save 10% off your first purchase of a website or domain. Sponsor: Green Chef Go to GreenChef.com/curb130 and use code curb130 to get $130 off, plus free shipping! Sponsor: Masterworks Masterworks is giving listeners priority access to their newest offerings. Just head to masterworks.art/curbsiders  CME Partner: VCU Health CE The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.  Show Segments Intro, disclaimer, guest bios Guest one-liners, Introduction to Nephmadness 2022 Case #1 from Kashlak: acute decompensated heart failure with elevated creatinine Definition and pathophysiology of cardiorenal syndrome Use of home ACE-is/ARBs and SGLT-2 inhibitors in cardiorenal syndrome Case #2 from Kashlak: the creatinine bump with diuresis Approach to the creatinine bump with diuresis Tips for the volume exam Interpreting cardiac biomarkers in patients with chronic kidney disease Case #3 from Kashlak: diuretic resistance Maximizing loop diuretic efficacy Sequential nephron blockade Use of hypertonic saline Outro

Today on the Ether we have the LUNAomics chat about TradFi and DeFi interest rate arbs. Recorded on March 12th 2022. Make sure to check out our sponsors, Orbital Command, Luart, Talis, WeFund, and Glow Yield! We appreciate their support.