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JACC Deep Dive explores the methodology, interpretation, and impact of key studies published in JACC.
20 Episodes
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Dr. Harlan Krumholz reviews the STEP trial, which studied over 8,500 older adults in China to compare intensive versus standard blood pressure control. The trial found that lowering systolic blood pressure to 110–130 mm Hg significantly reduced major cardiovascular events by 26% without added safety risks, confirming benefits previously shown in the SPRINT trial. A six-year follow-up revealed a lasting "legacy effect," showing that starting intensive treatment earlier produced enduring cardiovascular protection even after pressures equalized. The key takeaway: early, sustained, and carefully monitored intensive control is safe, effective, and time-sensitive—each year of delay means missed opportunities to prevent heart attacks and strokes.
In this episode of JACC Deep Dive, Editor-in-Chief Dr. Harlan Krumholz explores groundbreaking findings from the CLEAR-IE registry—the largest study to date on percutaneous mechanical aspiration (PMA) for right-sided infective endocarditis. He discusses the procedure's feasibility, outcomes, and its role alongside surgery, offering insights into how PMA may reshape treatment options for high-risk patients.
In this JACC Deep Dive, Dr. Harlan Krumholz highlights a study by Ikemura et al. that used data from the ISCHEMIA trial to model how angina symptoms evolve over three years in patients with stable coronary disease treated either invasively or conservatively. The study identified six distinct symptom trajectories, showing that while most patients improved over time, those undergoing revascularization were more likely to experience rapid and complete symptom relief. However, the benefit was not uniform—patients with frequent baseline angina saw the greatest improvement, and some had persistent symptoms regardless of treatment. These findings underscore the importance of personalized, shared decision-making based on a patient's likely symptom trajectory rather than a binary treatment choice.
In this JACC Deep Dive, Dr. Harlan Krumholz discusses a pre-specified analysis from the SUMMIT trial, which evaluated the effects of tirzepatide in patients with heart failure with preserved ejection fraction (HFpEF) and obesity, both with and without type 2 diabetes. The study found that tirzepatide significantly improved symptoms, function, and reduced heart failure events, with similar benefits regardless of diabetes status, though weight loss was slightly less in those with diabetes. Importantly, cardiac structural improvements (LV mass and pericardial fat regression) were also similar across both groups, suggesting benefits beyond weight loss alone. The trial's strengths included its integrated design and imaging substudy, though limitations such as modest imaging power and baseline group differences were noted. Clinically, the results support using tirzepatide in HFpEF patients with obesity, regardless of diabetes status, as the benefits remain robust.
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.
In this episode of JACC Deep Dive, Dr. Harlan Krumholz explores new insights from a post hoc analysis of the MASTER DAPT trial, highlighting the real-world burden of ischemic and bleeding events in high bleeding risk patients after PCI. By examining recurrent—not just first—events, the study sheds light on how abbreviated dual antiplatelet therapy (DAPT) impacts total clinical outcomes. Key findings include reduced bleeding without increased ischemic risk and a notable clustering of ischemic events following bleeding. This analysis advances the conversation around patient-centered endpoints and the evolving science of recurrent event modeling in cardiology.
In this episode of JACC Deep Dive, KACC Editor-in-Chief Harlan M. Krumholz, MD, SM, FACC, explores a post hoc analysis of the HELIOS-B trial, which examined whether echocardiographic parameters can track treatment response in transthyretin amyloid cardiomyopathy (ATTR-CM) patients treated with vutrisiran. The study found that changes in cardiac function correlated with clinical outcomes, suggesting a role for serial imaging in personalized care. Behind the scenes, reviewers were particularly intrigued by the potential of echocardiographic markers—especially global longitudinal strain—as surrogate endpoints, while also noting the exploratory nature of the findings and the need for further validation.
JACC focuses in again on Lipids in our June 3 issue, bringing critical insights into emerging targeted therapies. In the June 3 Deep Dive, editor-in-chief Harlan M. Krumholz, MD, SM, FACC, reviews the INTERASPIRE study by Ray et al, reviewing implications, key findings, and a thoughtful summary and analysis of the reviewer findings.
Go behind the scenes with JACC as editor-in-chief Harlan M. Krumholz, MD, SM, FACC, talks about what 's caught his attention in the latest JACC issue on amyloid. In this paper by Sheikh et al, the authors did a pre-specified exploratory analysis from the HELIOS-B trial, evaluating vutrisiran in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The study showed that vutrisiran helped preserve or improve functional capacity and quality of life over 30 months, with consistent benefits across both monotherapy and tefamidis-treated patients. Waterfall plots illustrated the full spectrum of individual patient responses, revealing meaningful improvements in many while underscoring variability in outcomes. The analysis emphasized this heterogeneity, supporting a move toward precision care in amyloidosis.
Join JACC Editor in Chief Harlan Krumholz, MD, SM, as he speaks about this ACC.25 presentation published in JACC. This fascinating study by Rohan Khera et al independently analyzed patient-level data from the SURMOUNT trials of tirzepatide for obesity. The study revealed striking individual variability in weight loss and metabolic response, even to a highly effective therapy—an insight powerfully illustrated through waterfall plots. Reviewers praised the transparent, sponsor-independent approach and the study's contribution to precision medicine, though they noted it was descriptive rather than predictive, underscoring the need for future research to identify what drives differential treatment response.
This JACC Deep Dive in our May 13 issue highlights new findings from the SUMMIT CKD study, showing that terzepatide improves symptoms, function, and weight in patients with HFpEF and obesity—regardless of kidney function. The analysis also underscores the importance of using both creatinine and cystatin C to better assess kidney health. Reviewers praised the study's methodological rigor and dual focus, while noting the need for larger, long-term trials to confirm renal outcomes.
In this JACC Deep Dive episode, Dr. Harlan Krumholz reviews the ADVANTAGE-AF trial, which evaluated pulse field ablation (PFA) as a treatment for persistent atrial fibrillation. The study demonstrated that PFA is a safe and effective approach, with strong symptomatic outcomes and a low complication rate, though questions remain about long-term durability and the need for more rigorous follow-up. PFA represents a promising innovation, but further randomized studies and extended monitoring will be essential to fully define its role in clinical practice.
In a Deep Dive in our May 13 issue, Editor-in-Chief Harlan Krumholz, MD, SM, FACC, discusses a study led by Barry Borlaug that investigates whether excess weight or metabolic dysfunction has a greater impact on heart failure with preserved ejection fraction (HFpEF). The findings showed that obesity—more than insulin resistance—was strongly associated with worse hemodynamic and functional outcomes. Reviewers praised the study's nuanced approach and use of invasive measures, while editorialists emphasized the ongoing importance of addressing both adiposity and metabolic health in HFpEF management.
In this JACC Deep Dive episode, Editor-in-Chief Dr. Harlan Krumholz discusses a major study on sudden cardiac arrest in young competitive athletes, highlighting survival rates, causes, and racial disparities. The study shows that survival improves dramatically with immediate AED use and has increased over time, emphasizing the need for widespread emergency preparedness and health equity efforts.. While progress has been made, ensuring universal access to CPR training and AEDs remains critical to saving lives.
In this in-depth analysis of the Altshock-2 trial (Study on Early Intra-aortic Balloon Pump Placement in Acute Decompensated Heart Failure Complicated by Cardiogenic Shock), Harlan M Krumholz, MD, FACC, goes deep into the study and its two related editorials. Listen here for this unique behind-the-scenes look at the review process, plus a thoughtful summary of the study and the two related editorials. All this content appears in JACC, in our special focus issue on cardiogenic shock.
In this JACC Deep Dive, Editor-in-Chief Harlan M. Krumholz, MD, SM, discusses a large real-world study by Min et al. examining heart failure with improved ejection fraction (HFimpEF) in over 24,000 patients. The study found that while EF improvement is common (30%), true remission is rare and relapse occurs in about 25% of cases—highlighting the need for continued guideline-directed medical therapy (GDMT) even after apparent recovery. Listen to the podcast, find out what reviewers and editors liked about the paper, and get more insight into our dedicated focus issue on heart failure.
JACC's July 29 issue explores why the ACURATE neo2 valve failed in its IDE trial, with a post-hoc analysis pointing to under-expansion in heavily calcified anatomies as a potential culprit. Though the valve is off the market, the findings raise critical questions about procedural success, device design, and future innovation in TAVR. Listen to our Deep Dive narrated by JACC Editor-in-Chief Harlan M. Krumholz, MD, SM, FACC, as he goes into the science behind the peer review.
In this JACC Deep Dive, JACC Editor in Chief Harlan M. Krumholz, MD, SM, explores a study led by Dr. Pradeep Natarajan that evaluates how well the new AHA PREVENT risk equations predict cardiovascular events across four major U.S. health systems. The study found wide variation in performance—PREVENT was well-calibrated at Penn Medicine but significantly underestimated risk at Mass General Brigham and Vanderbilt, particularly among women and minority groups. Reviewers praised the importance and rigor of the work but raised key questions about model calibration, fairness in outcome comparisons, and whether truly "plug-and-play" risk tools are realistic across diverse healthcare environments.
In this JACC Deep Dive, Harlan M. Krumholz, MD, SM, FACC reviews a study by Covani, et al that uses OCT imaging in over 1,500 ACS patients to show how increasing cardiovascular risk factor burden—like smoking, diabetes, and hypertension—is strongly associated with vulnerable plaque features such as thin caps, inflammation, and rupture. The findings were most pronounced in STEMI patients and reinforce the biological impact of cumulative risk. Reviewers found the core results intuitive but pushed for deeper mechanistic insights, leading to a stronger final paper with improved clarity, additional analyses, and a more nuanced understanding of how traditional risk factors shape plaque instability.
In this JACC Deep Dive, Harlan M. Krumholz, MD, SM, FACC, discusses a new study in the July 8 issue of JACC, authored by Saket Girotra MD, SM, et al. In the study, which links national registry and Medicare data, the authors found striking hospital-level variation in cardiac arrest rates and outcomes—and identified better nurse staffing as a key factor in both preventing arrests and improving survival. Behind the scenes, the manuscript underwent multiple rounds of revision, with close collaboration between editors and authors to strengthen the analysis, add new visualizations, and clarify key takeaways. The study underscores the need to invest in systems and staffing that detect clinical deterioration before it becomes irreversible.
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