Harlan Krumholz, MD.

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Heart Failure

Don’t Blame Your Heart for Heart Failure

Perhaps the biggest cardiology story of the year, an entire issue of JACC now hypothesizes that heart failure with preserved ejection fraction (HFpEF) might actually be caused by visceral fat tissue that triggers cardiac weakening through adipokine signaling.

• HFpEF has traditionally been seen as a heterogeneous disorder related to comorbidities like obesity, hypertension, and diabetes, with an unclear cause of pathophysiology.
• Obesity is present in over 95% of HFpEF patients and tracks with disease severity, yet it has been viewed as a contributing factor rather than the cause.
• Adipokines are substances that are released by fat tissue and act as hormones to regulate body functions like appetite, metabolism, and inflammation.

The new unifying adiposity framework now proposes that visceral fat expansion causes secretion of an altered adipokine profile that leads to systemic inflammation alongside cardiac hypertrophy and fibrosis. The hypothesis organizes adipokines into three functional domains…

• Domain I adipokines are cardioprotective molecules suppressed by excess body fat, representing a critical protective pathway that becomes disabled.
• Domain II adipokines are also cardioprotective molecules but they are increased by the body as a compensatory response to body fat level.
• Domain III adipokines, which are heightened during high body fat and drive the inflammation, hypertrophy, and fibrosis effects directly causing HFpEF

Taking the hypothesis a step further, this means that HFpEF is the result of high body fat imbalances that promote the Domain III adipokines while suppressing Domain I adipokines  with Domain II.

Although we have yet to see a definitive adipokine study, the authors put together several converging lines of evidence supporting adipose tissue as the primary pathogenic driver of HFpEF. Some examples include…

• Obesity and calorie excess are the drivers of experimental HFpEF models, with visceral fat changes visible years before HF diagnosis specifically predicting HFpEF (but not HFrEF).
• Striking parallels exist between obesity and HFpEF in molecular, pathophysiological, and clinical features, with adipokine levels correlating with disease severity in both.
• Experimental interventions targeting only adipose tissue to modify specific adipokine secretion cause distant cardiac effects, changing cardiomyopathy progression.

The Takeaway

This unifying hypothesis fundamentally reframes HFpEF from a multi-cause cardiac disorder with obesity as one comorbidity to an adipose-driven endocrine disease. If future studies validate this hypothesis, it could transform HFpEF treatment and the conversation around how to prevent our hearts from failing.

Tempus Receives FDA 510(k) Clearance for Tempus ECG-Low EF

Tempus announces the expansion of its Tempus ECG-AI portfolio with Tempus ECG-Low EF, software intended for use to analyze 12-lead ECG recordings and detect signs associated with having a low left ventricular ejection fraction (LVEF less than or equal to 40%) in patients 40 years of age or older at risk of heart failure. It is not intended as a stand-alone diagnostic and positive results may suggest the need for further clinical evaluation. For Full Indications for Use, visit here.

Monebo’s Approach to Cardiac Health Monitoring

The heart works day and night, so your cardiac monitoring software should too. Learn about how Monebo’s latest innovation superimposes long-term monitoring results onto a 24-hour circadian cycle scale, creating a comprehensive map of circadian variations.

The Wire

• CHIP, CVD, and Aspirin: A recent JAMA study suggests aspirin provides no special benefit for primary cardiovascular prevention in older individuals with clonal hematopoiesis of indeterminate potential (CHIP). Researchers analyzed 9.4k adults from the ASPREE trial and found that CHIP was present in 23% of participants and was not associated with increased cardiovascular events, but was linked to higher bleeding risk. Meanwhile, aspirin showed no differential effects on cardiovascular outcomes or bleeding between those with and without CHIP.

• AHA Statement on Heart Rehab: The AHA released a statement affirming that cardiac rehabilitation improves cardiovascular health while reducing mortality and hospital readmissions. However, the statement also clarifies that women are significantly underrepresented in cardiac rehab due to lower referrals, comorbidities, societal obligations, and financial barriers. As a result, research gaps exist regarding CR efficacy in women, especially for specific conditions like spontaneous coronary artery dissection. The statement’s authors believe that improving outcomes will require automatic referrals and gender-sensitive design to enhance women’s cardiovascular health.

• AHA Statement on CAC Detection: Another AHA statement established that coronary artery calcium (CAC) detection improves cardiovascular risk stratification beyond traditional factors, but adoption remains limited despite guidelines recommending it for 17M+ Americans. According to the statement, opportunistic CAC detection using routine non-cardiac chest CT scans offers a solution without additional radiation or cost, while AI algorithms enable automated CAC quantification and reporting. Notably, three HeartLung Technologies–led studies were cited as evidence for the statement.

• Hello Heart’s Adherence AI: Hello Heart launched Nia, an AI heart health assistant for improving medication adherence. Nia provides 24/7 support, medication guidance, personalized insights, and evidence-based information as part of Hello Heart’s Medication Management suite. The assistant works alongside a connected pill box and licensed pharmacists to improve adherence while helping prevent costly hospitalizations and worsening symptoms.

• GRACE 3.0 Works for ACS: According to a recent Lancet study, the latest version of the Global Registry of Acute Coronary Events (GRACE 3.0) provides personalized risk assessment for non-ST-elevation acute coronary syndrome patients (NSTE-ACS). The updated GRACE 3.0 scoring system was validated using 609k NSTE-ACS patients, with machine learning models showing excellent performance for predicting in-hospital mortality (AUC 0.90) and 1-year mortality (AUC 0.84).

• CVD Risk in Your Eyes: Topcon Healthcare acquired Toku, an AI health technology company using retinal images to assess cardiovascular risk, biological aging, and chronic kidney disease. Toku’s platforms (CLAiR, BioAge, MyKidneyAI) analyze over 4.3M retinal images to identify disease risk years before symptoms appear. The new integration into Topcon’s Harmony platform will now enable scalable, non-invasive AI screening across primary care, eyecare, and telehealth globally.

• Lapsi’s Listening Stethoscope: Lapsi Health unveiled Keikku 2.0, a second-generation AI-powered smart stethoscope that also now offers medical scribe capabilities. The wireless device combines clinical auscultation with ambient AI to transcribe patient conversations, generate clinical notes with automated coding, and detect cardiac/respiratory abnormalities in real-time. The device is FDA Class II cleared and costs $350-400 with the ability to connect to smartphones. Beyond documentation, Keikku aims to become healthcare’s AI infrastructure through open API partnerships to enable third-party algorithms.

• DCD vs. DBD Heart for Kids: A new AHA study suggests that expanding donation after circulatory death (DCD) heart acceptance for pediatric candidates may improve transplant access without hurting outcomes. The study analyzed 2.5k pediatric heart transplant candidates to compare outcomes between those listed for donation after brain death (DBD) only versus DCD and found that only 3.9% were listed for DCD hearts. Among high-risk patients, DCD listing doubled transplant likelihood, shortened waitlist duration, eliminated waitlist mortality, and achieved comparable one-year survival to DBD-only listing.

• PCI and TAVR? No Problem: Researchers believe performing PCI and TAVR together could be safe and effective, though the timing of the two procedures is unclear. Researchers in Cardiovascular Revascularization Medicine compared outcomes for 200+ patients with severe aortic stenosis and coronary artery disease undergoing either staged PCI (7-45 days before TAVR) or simultaneous PCI/TAVR and found that both methods had comparable in-hospital mortality (4% staged vs. 2% simultaneous). After three years, simultaneous procedures showed 68 days longer mean survival time, fewer bleeding events, and reduced transfusions.

• Depression’s CVD Implications: Research presented at ECNP suggests depression could have cardiometabolic associations, potentially requiring tailored physical health monitoring approaches. Researchers examined nearly 6k Dutch adults without baseline cardiovascular disease or diabetes, tracking depressive symptom subtypes over seven years, finding that melancholic symptoms (early waking, reduced appetite) increased cardiovascular disease risk 1.5-fold but not diabetes risk. Meanwhile, energy-related symptoms (fatigue, excessive sleep, increased appetite) raised type 2 diabetes risk 2.7-fold but not cardiovascular risk.

• Waiting on the HF Polypill: It seems like the heart failure community is eager for a polypill treatment, even if no definitive studies have been released. According to a JACC: Advances study that surveyed patients about their HFrEF treatment, most patients don’t receive the current four-pillar guideline-directed medical therapy for HFrEF due to barriers including cost, dose titration challenges, and clinician hesitancy. The study then goes on to suggest that polypills may initially serve population-level versus precision-medicine needs, even though phase 3 trials are years away.

Changes in Heart Failure Management

Heart failure is a complex condition with high heart failure hospitalization and cardiovascular mortality rates, especially among patients with HFpEF and HFmrEF, for whom treatment options have been limited. Read how Bayer’s Dr. Alanna Morris-Simon discusses the changing treatment landscape and strategies for improving patient outcomes.

5,600 Ways to Improve Your Cardiac Ultrasound Workflow

AI-powered measurements can enhance the way you acquire and interpret cardiac ultrasound. Learn how AI-powered ultrasound can help you overcome everyday limitations in echo. Read Siemens Healthineers’ white paper on how its AI software provides 5,600+ automated measurements to help improve workflow efficiency, consistency, and clinical confidence.

The Hidden Costs of Delaying Cardiac MRI Adoption

Despite being the gold standard for functional cardiac imaging, many hospitals remain slow to adopt it. From missed revenue to lost patients, the impact goes far beyond the scan. Read about the real clinical and financial risks of falling behind.

The Resource Wire

• Us2.ai’s AI HF Now Possible with Handheld Echo: The latest research shows Us2.ai’s software can take handheld echocardiography beyond its standard applications. Read this EHJ study about how swiftly and accurately Us2.ai’s HF detection software detects LVEF, closely matching expert human analysis of standard cart based echocardiograms.

• Merge Hemo Expands to Puerto Rico: Merge partnered with Alpha Biomedical to bring Merge Hemo to Puerto Rico, marking the software’s first expansion outside the 50 U.S. states. Read more about the work Merge is doing to expand access to its award winning solutions beyond the United States.

• Explore Vitrea Advanced Visualization: Discover Canon Medical Healthcare IT’s suite of advanced imaging workflows designed to increase efficiency in cardiovascular imaging, and facilitate the assessment, diagnosis, and treatment of cardiovascular diseases. These cutting-edge tools support the delivery of faster, more accurate care while integrating seamlessly into clinical workflow.

• A New Era of Precision and Efficiency: Ready to enhance your cardiovascular imaging precision and efficiency? See how Circle Cardiovascular Imaging’s new cvi42 6.3 platform is bringing CT and MR imaging under a single platform.

• PIA Medical Processes It All: Need an analysis like calcium scoring, strain or even FFR? PIA Medical began as a Core Lab and can handle creative cardiac research and clinical trials along with the full breadth of clinical analyses available today.

• The Largest Registry on Plaque Analysis in CAD: What if 50% of your CCTA patients could benefit from an adjustment to their treatment plan? Read more about Heartflow’s DECIDE registry that demonstrates how Heartflow Plaque Analysis using its Plaque Staging software empowers physicians with clinical insights that lead to real-world impact.

The Industry Wire

1. Trump Administration issues expanded guidance for IVF treatment.
2. Trump puts pressure on pricing for weight-loss drugs.
3. Amazon One Medical debuts pediatric telehealth service.
4. States scramble for shares of $50B rural health fund.
5. FDA releases list of drugs getting expedited review.
6. Microsoft targets nurses with new Dragon Copilot features.
7. Prospect Medical to sell troubled Crozer Health in Pennsylvania.
8. Philadelphia health system to lay off 650 workers. 
9. Which U.S. health systems are doing well? 
10. Terminated CDC workers fight back against firings.