In this episode of Behind the Science, Adith Arun and Dr. Neal K Lakdawala discuss the recent phase 2A trial of Danicamtiv in patients with dilated cardiomyopathy (DCM). They explore the study's design, patient cohorts, clinical implications, and the importance of genetic testing and patient-reported outcomes. The conversation also touches on the future of gene therapy in cardiomyopathy and ongoing studies like Kinship DCM.

Takeaways:

• The trial tested a myosin activator to improve cardiac function.
• Patients with sarcomeric dysfunction may benefit most from Danicamtiv.
• LVEF improvements varied across genetic cohorts in the study.
• Clinical thresholds for treatment response are crucial in rare diseases.
• Patient-reported outcomes like KCCQ are essential for assessing treatment efficacy.
• Genetic testing for DCM is underutilized in clinical practice.
• Gene therapy is emerging as a potential treatment for cardiomyopathy.
• The Kinship DCM study aims to further investigate Danocamtiv's effects.
• Understanding differential efficacy and toxicity is vital for future treatments.
• The field of cardiomyopathy is at an exciting juncture with ongoing research.

In JACC's inaugural Behind the Science episode, Adith Arun, sits down with senior author Barry A. Borlaug, MD, to discuss his latest study published in JACC's December 16, 2025 issue, examining tricuspid regurgitation (TR) across the full spectrum of HFpEF. The study found that TR is common even in early HFpEF, with ventricular secondary TR (VSTR) representing the predominant pattern (≈26% vs. ≈8% ASTR). VSTR was closely associated with pulmonary vascular disease, greater right atrial enlargement, and significantly higher risks of HF hospitalization and mortality. The study also highlighted the limitations of using atrial fibrillation to define ASTR—nearly 46% of patients categorized as ASTR had no prior AFib. Importantly, clinically meaningful TR was observed even in exercise-only HFpEF, reinforcing the value of exercise hemodynamic testing for earlier detection.

Join JACC Associate Editor Emily Bucholz, MD, PhD, MPH, and author Rebecca Josowitz, MD, PhD as they discuss key findings from this JACC paper on placental malperfusion in congenital heart disease (CHD). The paper, published in JACC's November 11 issue, highlights future research directions, including identifying at-risk populations, developing imaging and molecular biomarkers, and exploring potential in utero therapies. This brief interview offers a compelling look at the intersection of fetal cardiology and placental biology.

JACC continues its partnership with TCT 2025 in our latest interview, featuring JACC: Associate Editor Yousif Ahmad, MBBS, PhD, and author Shamir R. Mehta, MD, MSc. Listen here as they discuss this randomized, double-blind trial presented at TCT 2025 and published in JACC. Mehta et al demonstrate that intracoronary low-dose alteplase did not improve outcomes in STEMI patients with large thrombus burden and may increase arrhythmic risk. Together with prior studies, STRIVE closes the chapter on adjunctive intracoronary fibrinolysis as a strategy to improve outcomes during primary PCI.

JACC is proud to present research from the PROCTOR trial, and in this video interview with JACC Associate Editor Yousif Ahmad, MD and author Ruben W. de Winter, MD, review the randomized study comparing PCI of native coronary arteries versus saphenous vein grafts in patients with prior CABG. Contrary to expectations, the trial found that at one year, patients treated with vein graft PCI had significantly lower rates of major adverse cardiovascular events than those treated with native vessel PCI, challenging current guideline recommendations and highlighting the need for longer-term follow-up.

JACC continues its collaboration with TCT 2025 in this interview featuring JACC Associate Editor Celina M. Yong, MD, MBA, MSc, FACC, and lead investigator Professor Chao Gao, MD, PhD. The discussion spotlights the 3-year results of the REC-CAGEFREE I randomized trial comparing drug-coated balloons (DCB) with drug-eluting stents (DES) for de novo coronary lesions. Published in JACC and presented at TCT 2025, the findings reveal that while DCBs remained inferior to DES at 3 years, the outcome gap narrowed over time, primarily driven by elective revascularizations rather than death or MI. Professor Gao also explores bleeding risk, antiplatelet therapy patterns, bailout stenting rates, and where DCBs may find their optimal role, particularly in small vessel disease and high bleeding-risk patients.

In this episode, Dr. Makoto Mori, Associate Editor at JACC and Assistant Professor of Cardiac Surgery at Yale, interviews Dr. Paul Sorajja, lead author of the SUMMIT MAC Trial. They discuss the groundbreaking results of this study, which explores the use of the Tendyne transcatheter mitral valve replacement (TMVR) device in patients with severe mitral annular calcification (MAC)—a group traditionally challenging to treat surgically. Dr. Sorajja shares key findings, including high technical success rates, effective screening protocols, and significant improvements in patient outcomes. This conversation highlights a major advancement in structural heart disease treatment and its implications for clinical practice.

JACC's November 4 issue features the High Blood Pressure Guideline surrounded by a series of expert commentaries. In this video interview, JACC Deputy Editor Erica S. Spatz, MD, FACC, speaks with author Anand Vaidya, MD MMSc. Listen in for an insider view of the evolving understanding of primary aldosteronism in light of the 2025 high blood pressure guidelines. Dr. Vaidya emphasizes that primary aldosteronism may be a common, modifiable contributor to hypertension—potentially affecting up to 25% of patients—and advocates for simplified diagnostic approaches and broader use of mineralocorticoid receptor antagonists to improve outcomes.

The High Blood Pressure Guideline is paired with expert commentaries in JACC's November 4 issue. In this video interview focusing on one of the commentaries, JACC Deputy Editor Erica S. Spatz, MD, FACC, talks with author Daichi Shimbo, MD, about the importance of out-of-office blood pressure monitoring. They discuss the latest guidelines, which give home and ambulatory monitoring the highest recommendation, and explore practical strategies for implementation, including validated devices, patient education, and data integration into clinical workflows.

JACC continues to provide context and highlight important content for readers, and our November 4 issue features the High Blood Pressure Guideline surrounded by a series of expert commentaries. In this video interview discussing the commentary on preeclampsia, JACC Deputy Editor Erica S. Spatz, MD, FACC, speaks with author Vesna D. Garovic, MD, PhD about the complexities of hypertensive disorders in pregnancy, particularly preeclampsia. Dr. Garovic emphasizes the heterogeneity of preeclampsia, the need for earlier and more nuanced blood pressure management, and the importance of postpartum follow-up to mitigate long-term cardiovascular and renal risks for women.