Harlan M. Krumholz
H-index:
209
Here is my substack on the topic: Fat, Reframed.
neverdelegateunderstanding.substack.com/p/fat-reframed
neverdelegateunderstanding.substack.com/p/fat-reframed
Fat, Reframed
A Turning Point in Heart Disease
neverdelegateunderstanding.substack.com
@jaccjournals.bsky.social is the place for ideas that may change our thinking; spark dialogue; and contribute to progress in advancing global cardiovascular health.
HFpEF is one of medicine’s biggest puzzles.
Maybe the answers lie not in the heart alone, but in the cross-talk between fat and myocardium.
Read the full JACC Adipokine Spotlight and join the conversation.
🔗 www.jacc.org/toc/jacc/cur...
#JACC #HFpEF #Cardiology #AdipokineHypothesis
Maybe the answers lie not in the heart alone, but in the cross-talk between fat and myocardium.
Read the full JACC Adipokine Spotlight and join the conversation.
🔗 www.jacc.org/toc/jacc/cur...
#JACC #HFpEF #Cardiology #AdipokineHypothesis
JACC: Vol 86, No 16
JACC. 2025 Oct, 86 (16) 1231–1233.
www.jacc.org
The issue invites disagreement and testing.
Some cases of HFpEF may not fit the model.
But frameworks like this push the field forward—helping us ask sharper questions and design better studies.
Some cases of HFpEF may not fit the model.
But frameworks like this push the field forward—helping us ask sharper questions and design better studies.
Themes emerge:
• It’s about fat distribution, not just BMI.
• Adipokines act through endocrine-paracrine signaling.
• Sex, race, and metabolic context all shape expression and risk.
• New therapies (GLP-1RA, SGLT2i) may restore adipokine balance.
• It’s about fat distribution, not just BMI.
• Adipokines act through endocrine-paracrine signaling.
• Sex, race, and metabolic context all shape expression and risk.
• New therapies (GLP-1RA, SGLT2i) may restore adipokine balance.
To deepen the discussion, we invited experts across cardiology and metabolism to weigh in:
• Erica Spatz: A Turning Point
• Carolyn Lam & Dalane Kitzman: From Pariah to Paradigm
• Subodh Verma & Deepak Bhatt: Parsing the Adipokine Axis
• Faiez Zannad, Jennifer Ho, Robert Mentz, and others.
• Erica Spatz: A Turning Point
• Carolyn Lam & Dalane Kitzman: From Pariah to Paradigm
• Subodh Verma & Deepak Bhatt: Parsing the Adipokine Axis
• Faiez Zannad, Jennifer Ho, Robert Mentz, and others.
As Editor-in-Chief, I wrote about why JACC published it:
Because progress in medicine requires ideas that connect disciplines and challenge assumptions.
🧠 “Ideas Worth Testing: The Adipokine Hypothesis.”
www.jacc.org/doi/10.1016/...
Because progress in medicine requires ideas that connect disciplines and challenge assumptions.
🧠 “Ideas Worth Testing: The Adipokine Hypothesis.”
www.jacc.org/doi/10.1016/...
Ideas Worth Testing: The Adipokine Hypothesis
www.jacc.org
In this 25,000-word State-of-the-Art Review, Packer unites >1,800 references to build a testable framework explaining how dysfunctional adipose tissue could underlie HFpEF.
It’s bold, ambitious—and worth debating.
It’s bold, ambitious—and worth debating.
Dr. Milton Packer proposes that hypertrophied, inflamed fat cells secrete molecules—adipokines—that drive cardiac remodeling, inflammation, and fibrosis.
In other words: HFpEF may begin in fat, not the heart.
In other words: HFpEF may begin in fat, not the heart.
After decades of disappointment in HFpEF, a new idea is shaking things up.
Could heart failure with preserved EF actually be an adipose-driven disease?
JACC’s latest issue explores “The Adipokine Hypothesis.”
@jaccjournals.bsky.social
🔗 www.jacc.org/toc/jacc/cur...
Could heart failure with preserved EF actually be an adipose-driven disease?
JACC’s latest issue explores “The Adipokine Hypothesis.”
@jaccjournals.bsky.social
🔗 www.jacc.org/toc/jacc/cur...
Physician certification should not be an ordeal; it is in vast need of improvement.
My @jaccjournals.bsky.social Journals Editor’s Page explores how we can modernize physician certification to be relevant, humane, and effective.
🔗 www.jacc.org/doi/10.1016/...
My @jaccjournals.bsky.social Journals Editor’s Page explores how we can modernize physician certification to be relevant, humane, and effective.
🔗 www.jacc.org/doi/10.1016/...
Rethinking Physician Certification: A Call for a Modern, Meaningful Standard
www.jacc.org
In this Editor’s Page, I outline why we believe authors can use AI tools to improve scientific writing—if they fully own what they submit.
At JACC, we won’t stigmatize responsible use of AI. But we will insist on accountability.
jacc.org/doi/10.1016/...
@jaccjournals.bsky.social
At JACC, we won’t stigmatize responsible use of AI. But we will insist on accountability.
jacc.org/doi/10.1016/...
@jaccjournals.bsky.social
Tools, Not Ghosts: Artificial Intelligence, Writing, and Responsibility
Download article citation: If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.
jacc.org
In this Editor’s Page, I outline why we believe authors can use AI tools to improve scientific writing if they fully own what they submit.
At JACC,we won’t stigmatize responsible use of AI. We will insist on accountability.
www.jacc.org/doi/10.1016/...
@jaccjournals.bsky.social @yalemed.bsky.social
At JACC,we won’t stigmatize responsible use of AI. We will insist on accountability.
www.jacc.org/doi/10.1016/...
@jaccjournals.bsky.social @yalemed.bsky.social
Tools, Not Ghosts: Artificial Intelligence, Writing, and Responsibility
Download article citation: If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.
www.jacc.org
For anyone who has wanted a clear, authoritative summary of inflammation and cardiovascular disease, and where the science is heading, here it is.
The 2025 ACC Scientific Statement on Inflammation and Cardiovascular Disease. @jaccjournals.bsky.social www.jacc.org/doi/10.1016/...
The 2025 ACC Scientific Statement on Inflammation and Cardiovascular Disease. @jaccjournals.bsky.social www.jacc.org/doi/10.1016/...
Inflammation and Cardiovascular Disease: 2025 ACC Scientific Statement: A Report of the American College of Cardiology
www.jacc.org
This is an extraordinary report from @ihmeuw.bsky.social and published in @jaccjournals.bsky.social; it demonstrates that cardiovascular disease is a global scourge. And we are failing to leverage what we know to save lives. www.jacc.org/doi/10.1016/...
Reposted by Harlan M. Krumholz
Congratulations to @uvmlarnermed.bsky.social medical student, Sarah Krumholz, for winning the Outstanding Research Publication award for her study in REGARDS investigating risk of hypertension by sRAGE level! Very well deserved!
Her paper: pubmed.ncbi.nlm.nih.gov/40708351/
Her paper: pubmed.ncbi.nlm.nih.gov/40708351/
The next leap is computable quality.
Living, real-time intelligence from routine clinical data that will:
-Support accountability
-Fuel improvement
-Accelerate discovery
Living, real-time intelligence from routine clinical data that will:
-Support accountability
-Fuel improvement
-Accelerate discovery
But most current measures fail this test.
Registries = richer than claims but costly, delayed, and not built for improvement
Claims = coarser, even more delayed
Neither delivers what clinicians need at the point of care.
Registries = richer than claims but costly, delayed, and not built for improvement
Claims = coarser, even more delayed
Neither delivers what clinicians need at the point of care.
Door-to-balloon time proved what’s possible.
When hospitals had real-time feedback, mortality for STEMI dropped—without new drugs or devices.
The lesson?
👉 Quality improves when data are timely, trusted, and actionable.
When hospitals had real-time feedback, mortality for STEMI dropped—without new drugs or devices.
The lesson?
👉 Quality improves when data are timely, trusted, and actionable.
Quality measurement was once a breakthrough.
But today it’s too slow, too costly, and too disconnected from daily care.
It’s time to reinvent it.
🆕 My Editor’s Page in JACC: www.jacc.org/doi/epdf/10....
@jaccjournals.bsky.social @yalemed.bsky.social
But today it’s too slow, too costly, and too disconnected from daily care.
It’s time to reinvent it.
🆕 My Editor’s Page in JACC: www.jacc.org/doi/epdf/10....
@jaccjournals.bsky.social @yalemed.bsky.social
Computable Quality
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www.jacc.org
New @JACCJournals: Guiding the AI Revolution in CV Medicine
I lay out 5 operational principles—from rigorous validation to bias reduction—to make AI safe, equitable & impactful in cardiology.
➡️ www.jacc.org/doi/10.1016/...
@jaccjournals.bsky.social @yalemed.bsky.social @yaleschoolofmed.bsky.social
I lay out 5 operational principles—from rigorous validation to bias reduction—to make AI safe, equitable & impactful in cardiology.
➡️ www.jacc.org/doi/10.1016/...
@jaccjournals.bsky.social @yalemed.bsky.social @yaleschoolofmed.bsky.social
Guiding the AI Revolution in Cardiovascular Medicine:
www.jacc.org
by Eric J. Topol — Reposted by Harlan M. Krumholz
A conversation on Healthy Aging with @hmkyale.bsky.social and @thehowie.bsky.social @yaleschoolofmed.bsky.social
insights.som.yale.edu/podcasts/hea...
insights.som.yale.edu/podcasts/hea...
Eric Topol: The Keys to Healthy Aging
Howie and Harlan are joined by physician, scientist, and author Eric Topol to discuss his new book, Super Agers: An Evidence-Based Approach to Longevity; the potential of individualized polygenic risk...
insights.som.yale.edu
Reposted by Harlan M. Krumholz, Eric J. Topol
“Everyone thinks their genes are the cause for them getting an age-related disease, it’s actually your immune system.” - @erictopol.bsky.social the author of Super Agers on #HealthandVeritas podcast
pod.link/1588414491/e... @thehowie.bsky.social @hmkyale.bsky.social
pod.link/1588414491/e... @thehowie.bsky.social @hmkyale.bsky.social
pod.link
Biology, not blame.
That’s the message from #ESCCongress.
Fat is not just storage, it’s an organ.
Its signals may drive heart failure and more.
Read my take: Fat, Reframed: A Turning Point in Heart Disease.
substack.com/home/post/p-... @jaccjournals.bsky.social @yaleschoolofmed.bsky.social
That’s the message from #ESCCongress.
Fat is not just storage, it’s an organ.
Its signals may drive heart failure and more.
Read my take: Fat, Reframed: A Turning Point in Heart Disease.
substack.com/home/post/p-... @jaccjournals.bsky.social @yaleschoolofmed.bsky.social
Fat, Reframed
A Turning Point in Heart Disease
substack.com
Reposted by Harlan M. Krumholz
1/4
Rehabilitation can ⬆️ Functional Independence and ⬇️ Long-term Cognitive Impairment among #ICU survivors. But how often do hospitals deliver it?
Led by @yalemedicine.bsky.social resident Jose Victor, our paper bit.ly/41p9fPT in @accpchest.bsky.social provides insights
Rehabilitation can ⬆️ Functional Independence and ⬇️ Long-term Cognitive Impairment among #ICU survivors. But how often do hospitals deliver it?
Led by @yalemedicine.bsky.social resident Jose Victor, our paper bit.ly/41p9fPT in @accpchest.bsky.social provides insights
by Harlan M. Krumholz — Reposted by Nicholas A. Christakis
New @JACCJournals Editor’s Page: A Disquieting Plateau
🫀 Cardiovascular mortality progress has stalled
📉 In some areas, it’s reversing
💡 We must confront what’s happening on our watch—and what comes next
👉 authors.elsevier.com/a/1lfjn2d9GI...
#CardioTwitter #HealthEquity @jaccjournals.bsky.social
🫀 Cardiovascular mortality progress has stalled
📉 In some areas, it’s reversing
💡 We must confront what’s happening on our watch—and what comes next
👉 authors.elsevier.com/a/1lfjn2d9GI...
#CardioTwitter #HealthEquity @jaccjournals.bsky.social
In my new Substack post...
Did you know air pollution can raise blood pressure?
I break down a just-published JACC trial testing HEPA filters in homes near highways—and what it means for heart health.
@jaccjournals.bsky.social
👉 neverdelegateunderstanding.substack.com/p/00314b6f-e...
Did you know air pollution can raise blood pressure?
I break down a just-published JACC trial testing HEPA filters in homes near highways—and what it means for heart health.
@jaccjournals.bsky.social
👉 neverdelegateunderstanding.substack.com/p/00314b6f-e...
Never Delegate Understanding
Making health and science understandable. Click to read Never Delegate Understanding, by Harlan Krumholz, a Substack publication. Launched 3 days ago.
neverdelegateunderstanding.substack.com
Can a HEPA filter protect the heart?
My latest JACC #DeepDive explores a new trial of in-home air filtration—what it found, why the effect size matters, and how it fits into decades of research on air pollution and CVD risk.
🎧 www.jacc.org/digital-cont...
@jaccjournals.bsky.social
My latest JACC #DeepDive explores a new trial of in-home air filtration—what it found, why the effect size matters, and how it fits into decades of research on air pollution and CVD risk.
🎧 www.jacc.org/digital-cont...
@jaccjournals.bsky.social
Podcast Episode: Environmental Exposure as Intervention: HEPA Filtration and Blood Pressure Near Traffic Corridors | JACC Deep Dive
In this Deep Dive, Editor-in-Chief Dr. Harlan Krumholz explores a pragmatic, randomized crossover trial testing whether in-home HEPA filtration can reduce blood pressure in adults living near high-traffic roadways. The findings offer early insights into how targeted environmental interventions may influence cardiovascular risk—especially among individuals with elevated baseline systolic blood pressure.
www.jacc.org
🎙️ New JACC This Week podcast!
This issue features:
🔹 CSPACE RCT — CSP vs RV pacing in AV block
🔹 HEPA filtration & blood pressure
🔹 FLAVOUR 6-year follow-up—FFR vs IVUS
🔹 Editor’s Page: excess CV mortality in Black Americans
🎧 Listen: www.jacc.org/digital-cont...
@jaccjournals.bsky.social
This issue features:
🔹 CSPACE RCT — CSP vs RV pacing in AV block
🔹 HEPA filtration & blood pressure
🔹 FLAVOUR 6-year follow-up—FFR vs IVUS
🔹 Editor’s Page: excess CV mortality in Black Americans
🎧 Listen: www.jacc.org/digital-cont...
@jaccjournals.bsky.social
Podcast Episode: Pacing Strategies, Air Quality, and the Path to Equity | JACC This Week
In this week's JACC Deep Dive podcast, Dr. Harlan Krumholz highlights new science with direct clinical implications: a randomized trial showing conduction system pacing outperforms RV pacing in AV block, a pragmatic study suggesting HEPA filtration may modestly lower blood pressure, and long-term data from FLAVOR comparing FFR and IVUS-guided PCI. Also featured are a state-of-the-art review on heart failure therapy implementation, a brief report refining NT-proBNP thresholds for pre–heart failure, and an updated JACC Report Card revealing persistent cardiovascular mortality disparities among Black Americans.
www.jacc.org