Great presentation by @ZhiYu_ACGT presenting our work with A. Vromman, P. Libby, @Dr_RajatGupta, & colleagues on the downstream proteomic consequences of clonal hematopoiesis across proteomic platforms along with murine validation hashtag #AHA25

Our analysis of CHIP (clonal hematopoiesis of indeterminate potential) and risk of heart failure in ~420,000 @uk_biobank participants led by rising ⭐️ @Sflynn4242 @mghmedres now in @JAMACardio simultaneous w/ #AHA25 jamanetwork.com/journals/jam… (1/4)

Fantastic job with the presentation @WongChrisX - very excited to share this good news that randomization to caffeinated coffee ⬇️#Afib, to have this presented as a LBCT @AHAScience, and published in @JAMANetwork Two caveats for all to consider lest we hear, “But you guys said caffeine was all ‘good’!”: 1. This study was specific to #Afib. In our prior CRAVE trial, acute caffeinated coffee was associated with ⬆️#PVCs nejm.org/doi/full/10.1056/NE… 2. These data should NOT be extrapolated to higher dose or synthetic caffeinated products and especially energy drinks, which case reports suggest may cause #Afib @pnatarajanmd @PrashSanders @DrMarthaGulati @drjohnm @UCSFCardiology @UCSFHospitals @UCSF

Excited to participate in a ph1 RCT of novel oral NLRP3i (selnoflast) with @david_place_ @kparuchuri P. Libby & colleagues @genentech being developed for inflammatory CVD risk #AHA25

Thanks to @gregorymmarcus! Although maybe no more than this 1cup today @AHAScience @DrMarthaGulati ☕️

DECAF: In an open-label multi-national RCT of N=200 pts with persistent AF consuming avg ~1cup coffee per day, maintaining coffee consumption led to *reduced* AF/AFL recurrence vs abstinence! jamanetwork.com/journals/jam… @JAMA_current @gregorymmarcus #AHA25 ☕️

DARE-AF: In an open-label RCT of 200 individuals living in China undergoing AF ablation, and without SGLT2i Rx current indications, dapagliflozin vs placebo did not lead to a reduction in AF recurrence risk ahajournals.org/doi/abs/10.1… @CircAHA #AHA25

PISCES: Among 1228 pts on HD, 4g omega-3 fatty acids vs corn oil placebo led to reduction in serious CV events (HR 0.57!). nejm.org/doi/full/10.1056/NE… @NEJM This is on the background of null STRENGTH (4g omega-3 carboxylic acids vs corn oil in high CV risk pts jamanetwork.com/journals/jam…) & numerous other null EPA/DHA vs placebo CV outcomes trials. Given the numerous EPA/DHA trials assessing CV outcomes, should we apply multiple hypothesis-correction when interpreting a positive trial? The effect estimate is large and hard to ignore. The side effect rate did not appear to be greater in the omega-3 fatty acid vs placebo comparison. So should we then recommend omega-3 fatty acids to pts on HD to reduce CV risk? The OTC fish oils are lower dose and of varying formulations. REDUCE-IT (nejm.org/doi/full/10.1056/NE…) has suggested that dose and formulation may be particularly relevant for omega-3 fatty acid supplements for CV outcomes. So this trial does not show that OTC fish oils are cheap and effective interventions for pts on HD. Pts at HD are at high CV risk despite standard interventions. So it’s plausible that observations of other interventions may not generalize. As with everything, further study is needed. #KidneyWeek #AHA25

Congrats to the amazing @MGBResearchNews colleague @pnatarajanmd recipient of the #AHA25 the Genomic and Epidemiology Mid-Career Research Award!

📢 Adding evolocumab to lipid-lowering therapy significantly reduced the risk of a first major CV event in patients without prior heart attack or stroke. More from @pnatarajanmd at #AHA25 ⬇️

In my view, people don’t give APOC3 nearly as much credit as they give PCSK9. Honestly, APOC3 inhibition might end up being far more life-transforming. Before PCSK9 inhibitors, we already had statins that revolutionized LDL-C lowering. PCSK9 added value, but its market impact was modest. For triglycerides (TGL), though, we’ve had nothing truly effective. APOC3 inhibition changes that — its impact on TGL reduction is absolutely transformative.

Excellent cardiometabolic LBCT wrap-up by @CBallantyneMD! Precision Medicine 4.0 will include longitudinal risk assessment starting with genetics! #AHA25

VESALIUS-CV: among high-risk pts *without* prior events, evolocumab (PCSK9 mAb) led 45mg/dl lower LDL-C & 25% RRR of a *first* major CV events. Secondary analyses indicated 20% reduction in all-cause mortality! nejm.org/doi/full/10.1056/NE… @NEJM #AHA25 My thoughts on “primary prevention.” Many will quibble that this isn’t primary prevention because most had CAC. But the prospect of treating patients with medicines who have never had an event & not necessarily making them feel better requires a demonstration of benefit for major outcomes. Pretty much all ASCVD trials focus on preventing recurrent events. Hats off to the investigators, @Amgen, trial participants to moving earlier in the disease course. Bold and important. Current guidelines stratify secondary prevention to very high risk ASCVD (those with major events and risk factors) as a group for the most potent LDL-C-lowering. However, these data suggest high risk primary prevention deserves similarly most potent LDL-C-lowering.

Coverage in @washingtonpost with comments from me and others on this scientific breakthrough washingtonpost.com/science/2… #AHA25 @AHAScience

A scientific first! ANGPTL3 in vivo gene editing in a ph1 trial is feasible & appears to lower LDL-C by 50% and TGs by 55% among individuals with resistant hyperlipidemia. nejm.org/doi/full/10.1056/NE… @NEJM #AHA25 Efficacy appears similar to zodasiran (ANGPTL3 siRNA) (nejm.org/doi/full/10.1056/NE…) This is a remarkable demonstration about how genetic discovery is driving both therapeutic hypotheses/targets but the medicines themselves. The role of in vivo gene editing for lipids with comparable efficacy to other strategies requires further investigation.

When I was a medical student, I vividly recall taking care of very very sick patients with acute pancreatitis in the ICU. Remarkable to see how APOC3 inhibition (here, olezarsen) is now shown to be a highly effective therapy for severe hypertriglyceridemia, esp among those with prior pancreatitis to reduce risk for acute pancreatitis (NNT 20 for all and 4 for those with prior) & yield remission (up to ~50%) for hypertriglyceridemia. Congrats @marstonMD @TIMIStudyGroup! nejm.org/doi/full/10.1056/NE… #AHA25 @NEJM

Combo triple agonist for FGF21 R/ Glucagon R/ GLP1 R lowers triglycerides by 69% v placebo among individuals with severe hypertriglyceridemia in a ph2 trial of N=79 #AHA25

🌍 South Asians = 25% of the world 🧪 But just 3.2% of major #CVD trial participants This gap puts a high-risk population at even greater risk. How can we close it? 🔗 ow.ly/Op5250Xf2mn #JACCAsia #HealthEquity #ClinicalTrials @pnatarajanmd @NishantUppal7 @DLBHATTMD