Dear #FunctionNotFailure community, Thank you for the gift of being apart of this remarkable family. 💜 Onwards we go, focusing on community, science, impact, perseverance and innovation. 📈 @HFSA @robmentz @ShashankSinhaMD @DrMarthaGulati @j_alvarezgarcia @EMDeFilippisMD @SantosGallegoMD @AndrewJSauer @noshreza @JasonKatzMD @KSharmaMD @mpsotka @orlyvardeny @ngilotraMD @heartofthemater

Having a reason to get up in the morning cuts your risk of dying by more than half. A 2019 JAMA study of nearly 7,000 adults found that people with the strongest sense of purpose had the lowest mortality, and the effect was independent of wealth, health, exercise, and depression. Purpose does not mean ambition. It means feeling that your daily actions matter to something beyond yourself. A grandparent raising a garden. A retired teacher who tutors. A caregiver who shows up every morning. The research does not measure achievement. It measures the feeling that what you do connects to something. The biological pathway runs through every system the body uses to stay alive. People with a sense of purpose sleep better, have lower inflammatory markers, take their medications, show up for screenings, and maintain social ties. Each of those individually lowers mortality. Together, they compound into a survival advantage that is larger than the sum of its parts. The opposite is also in the data. People who lose purpose, through retirement without a replacement, the death of a spouse, or the end of a career they defined themselves by, show a rapid decline in health that cannot be explained by aging alone. The body seems to treat purposelessness as a signal that the organism is no longer needed. Nobody writes "sense of purpose" on a prescription pad. The research says it belongs there. pubmed.ncbi.nlm.nih.gov/3112…

🫀 Heart transplantation is entering a new era! This State-of-the-Art review explores advances reshaping the field: individualized LVAD vs transplant decisions, DCD & HCV+ donors, and new organ preservation strategies expanding the donor pool. 🔗 bit.ly/45xVQXm 🧵👇

New @JCardFail Focus Issue 📘 This month's issue explores heart transplantation, from DCD transplantation to heart allocation reform and personalized immunosuppression. 🔗 Explore the September Focus Issue: onlinejcf.com/current#

New focus issue @JCardFail on 🫀transplantation is just 🔥🔥🔥 led by @EMDeFilippisMD @rcstarling @KiranKhush1 - it’s relevant, provocative, and just so easy to read. Don’t miss it!! 👇🏽👇🏽👇🏽 onlinejcf.com/current

A lot of disappointments in CV trials lately. 😳 so sorry to see this announcement today: HERMES and ATHENA has also been stopped due to "the low likelihood of a different outcome from ZEUS." firstwordpharma.com/story/79… @mvaduganathan @markcpetrie20 @lamcardio @robmentz

Hi all, The Lp(a) HORIZON trial has released topline data and, quite shockingly, missed its primary endpoint. In other words, lowering Lp(a) in patients with prior MI, stroke or peripheral arterial disease, who were otherwise very well treated for LDL-C, blood pressure, diabetes and other risk factors, did not reduce the primary cardiovascular endpoint. We obviously need to see the full data before making firm conclusions, and I don’t want to speculate too much without the details. But this is a big enough result that it is worth summarizing what we know, what we don’t know, and what this may mean for our patients after 20+ years of trying to test the “Lp(a) hypothesis.” What we know: 1-There are hundreds if not thousands of genetic, epidemiologic and Mendelian-randomization studies showing that elevated Lp(a) is associated with MI, stroke, peripheral arterial disease and aortic stenosis. That body of evidence is very strong. 2-However, much of those data come from community-based populations, often before the era of intensive LDL-C lowering and modern secondary prevention. 3-There has been much less information about how much residual risk Lp(a) carries in someone who has already had an event and is then treated very aggressively. 4-HORIZON may have had some of the best-treated patients of any recent cardiovascular outcomes trial. Baseline LDL-C was about 65 mg/dL, a measured LDL-C contains the cholesterol carried on Lp(a), so in reality, 15-20 points lower. 5-In patients with very high Lp(a), if you correct LDL-C for Lp(a)-cholesterol, the actual LDL-C carried by LDL particles may have been closer to 45–50 mg/dL, perhaps even lower in some patients. 6-This raises a very basic question: Can you still demonstrate a major incremental benefit from lowering another apoB-containing particle when the underlying LDL burden has already been driven this low? What we don’t know: 1-What was the actual corrected LDL-C in these patients? I think it would be extremely informative to directly measure Lp(a)-C and calculate corrected LDL-C. This may tell us a lot about the biological setting in which pelacarsen was being tested. 2- What was the OxPL status? Our prior work has suggested that much of the pro-inflammatory biology associated with Lp(a) is related to its enrichment in oxidized phospholipids. Did OxPL fall? Did patients with higher OxPL derive more benefit? Was Lp(a) concentration actually identifying the patients with the most pathogenic particles? 3- Did we measure the right component of Lp(a) for trial inclusion? We generally measure molar particle concentration. But is molar concentration itself the main driver of risk, or is it partly a surrogate for what the particle carries? Cholesterol? Triglycerides? Oxidized phospholipids? Other proteins? Could two patients with the same Lp(a) concentration have very different Lp(a)-mediated risk? I think this question deserves much more attention. 3- Were the genetic data telling us exactly what we thought they were telling us? The genetic data are extremely compelling, but genetics reflect lifelong exposure. A clinical trial treats patients late in life, often after decades of arterial injury and after an event has already occurred. Those are not necessarily the same experiment. Could there also be some unrecognized biology linked to the LPA locus that we have not completely accounted for? That possibility should at least be considered. 3- Does very low LDL-C modify the Lp(a) risk relationship? Maybe Lp(a) is particularly important when LDL-C is higher, but its contribution becomes smaller once LDL-C is driven to very low levels. Again, we need the data. 4- Does aspirin or other antiplatelet therapy reduce part of the risk associated with Lp(a)? Lp(a) has potentially important prothrombotic effects. Almost everyone in a trial like HORIZON is receiving contemporary antiplatelet therapy. Could that blunt one component of the risk associated with Lp(a)? 5- Why are these patients still having events? This may be one of the most interesting questions of all. These are patients with LDL-C around 65 mg/dL, and perhaps corrected LDL-C substantially lower, yet cardiovascular events continue to occur. What is driving that residual risk? Inflammation? Thrombosis? Plaque burden that is already too advanced? Other lipoprotein characteristics? Something we are not measuring? 6- Do we need to re-examine some basic assumptions about atherosclerosis? We have spent decades focusing heavily on the quantity of circulating lipoproteins. But perhaps lipoproteins are relatively benign until they undergo biological modification in the artery wall. Oxidation may be one of those key modifications. For some patients, the answer may be to remove more particles from the circulation. For others, perhaps the better approach is to prevent their oxidation or block the downstream biological effects of oxidized lipids. The recent difficulties with anti-inflammatory approaches, including IL-6 inhibition, make these mechanistic questions even more interesting. 7- Was there something specific about pelacarsen, the degree or timing of Lp(a) lowering, advanced disease, trial duration, background therapy or patient selection that mitigated a potential benefit? We simply don’t know yet. That is why the detailed results will be so important. What does this mean for patients today? If you have already had an MI, stroke or PAD, the immediate lesson is very clear: 1- Get all of your established risk factors treated aggressively. 2- Get LDL-C/apoB very low. 3- Control blood pressure. 4- Control diabetes. 5- Don’t smoke. 6- Use appropriate antiplatelet and other guideline-directed therapies. HORIZON shows us what modern secondary prevention should look like. If you have elevated Lp(a) but have never had an event, the genetic and epidemiologic data still suggest increased lifetime risk. Until the other 4 outcome trials read out, I would continue to treat every modifiable risk factor aggressively. We should wait for those trials before drawing broad conclusions about the entire field. I think the story of Lp(a) therapy is beginning, not ending. We also need to show tremendous respect and gratitude to the patients who participated in HORIZON and to the investigators and companies that invested enormous resources to actually test the Lp(a) hypothesis, to the ultimate benefit to peole with elevated Lp(a) to best guide how to manage risk. More to come as we go forward.

I've been MIA on SoME fronts...taking some time to go inward & recalibrate. Still, wanted to share our Aug Ed page @JCardFail on something I'm always working on...embracing uncertainty. It may resonate w/our trainees waiting on interviews as well as graduating ones taking on new jobs. Wishing everyone compassion and grace...as we all navigate the ongoing challenge of embracing uncertainty 🙏 onlinejcf.com/article/S1071-…

📉 Treating high blood pressure is one of the best ways to prevent HF ❤️ ✅ Standard control (<140): ~50% less HF 
🚀 Intensive/SPRINT (<120): adds ~38% more 
💥 Combined: ~69% ↓ 🇺🇸 Nationwide, Rx and going intensive could prevent ~167,000 HF cases/year in eligible adults

👉Just published in @NEJM: STAREE Trial ☝️At last, robust randomized evidence on statins for primary prevention in older adults. 🔹 9,971 adults ≥70 years, without cardiovascular disease, diabetes, or dementia 🔹 Atorvastatin 40 mg vs placebo 🔹 Median follow-up: 5.9 years 🔹 Baseline LDL-C: ~127 mg/dL NEJMoa2607314.pdf 👉Key findings: 🔹 30% reduction in major cardiovascular events HR 0.70 (95% CI 0.61–0.82; P<0.001) 🔹 NNT = 37 over 5.9 years 🔹 MI: HR 0.57 🔹 Coronary revascularization: HR 0.57 🔹 Benefit was also observed in participants ≥75 years 👉Importantly: 🔹 No increase in dementia (HR 1.03) 🔹 No significant effect on all-cause mortality 🔹 No improvement in overall disability-free survival 🔹 Serious adverse events were similar between groups. ☝️Bottom line: Age alone should not be a reason to withhold LDL-C lowering. Even in healthy adults ≥70 years, lowering LDL-C translates into substantial cardiovascular benefit. @society_eas @nationallipid 🔗nejm.org/doi/full/10.1056/NE…

🫀 #REACT at #ESCCongress #Hotline How early does atherosclerosis really begin? 16,808 adults, age 18–70 without known ASCVD underwent coronary, carotid & femoral imaging 🔎 Silent atherosclerosis: 57.1% overall ➡️ Already present in ~1 in 13 adults aged 18–29 ➡️ ~9 in 10 by age 60–70! 💃🏻Women: steep rise during midlife, around menopausal transition; men developed atherosclerosis ~5–10 years earlier 🫀Atherosclerosis begins decades before clinical events—and often before conventional risk scores identify high risk. REACT should make us think about prevention much earlier Next question: can imaging-guided early intervention actually prevent progression and events? Or should we just work to prevent CVD in everyone? 📄 @NEJM nejm.org/doi/full/10.1056/NE… #ASCVD #Prevention #WomensHeartHealth #CVPrev

This is simply outstanding! What wonderful mentors @mchonig @pnatarajanmd 👏🏽👏🏽👏🏽 to let a medical student present and she was outstanding!

Of the major age-related diseases (cardiovascular, cancer, neurodegenerative) heart is the most preventable with lifestyle factors and medications. It's about to become far more preventable! @Drroxmehran and I teamed up for this @JACCJournals perspective A "once-in-a-generation opportunity" jacc.org/doi/10.1016/j.jacc.…

To understand the biology of aging, extending healthspan and promoting longevity, females should be prioritized for research. The reproduction resilience hypothesis @CellCellPress @BuckInstitute cell.com/cell/fulltext/S0092…

Thank you @DrHelenECollin1 for including me on this important paper. Understanding the impact of sleep disruptions on the cardiometabolic health of pregnant women provides insights to potential CV changes and need to be further studied #cardioobstetrics @TheLancet @HMethodistCV @valeriaduarteMD @khurramn1 @WilliamZoghbi

Hear from the guest editors leading The New Frontier of Heart Function in Women as they share their excitement for this upcoming focus issue. 📅 Submissions open through Sept. 15th: bit.ly/4fC1NZh #WomensHeartHealth #HeartFailure #CallForPapers

What’s in name? #PMOS 🆚 PCOS: should translate into recognizing this is not a gynecological condition but rather affecting the cardio metabolic health of the women it affects & translate into improved treatment

New from the @ACCinTouch:2026 ACC Clinical Guidance on Adult Immunizations as Part of CV Care. Honored to serve as Vice Chair of this effort. Evidence growing that vaccines influence CV risk reduction not just infection prevention. In press @JACCJournals jacc.org/doi/10.1016/j.jacc.…

New science alert! Do AF, diabetes, or obesity change the benefits of aspirin withdrawal after HM3 LVAD?💖 This ARIES-HM3 analysis says no. Bleeding decreased without increases in stroke or thrombosis, even in these higher-risk subgroups.🩸 🔗bit.ly/4gbLxhI

New HFpEF consensus pathway lays out clear approach: 💠SGLT2i + (ns)MRA, unless contraindicated 💠+GLP1, if obese 💠Consider ARNI 💠AVOID BB as able CKM GL give framework in context of comorbidities. 🚨Need to make sure we don't delay effective therapies down the decision tree!🚨

In a recent @forbeshealth feature, Roxana Mehran, MD,shares her expert perspective on the FDA's approval of Lipfendrahis and what it means for patients, their cholesterol management, and why individualized treatment decisions remain essential. Read more: bit.ly/3Ruv7r9