Heart Failure in Focus: 10 Studies That Redefined Care in 2025

Key highlights from the top heart failure papers of 2025 include:

• Prevention moves to the forefront: A landmark Lancet series issued a strong call to action for healthcare professionals, systems, and policymakers to prioritize primary prevention of HF. The authors stressed early identification of individuals at risk, detection of pre-HF using biomarkers, and implementation of lifelong preventive strategies to reduce the growing global HF burden.
• Iron deficiency treatment revisited: The FAIR-HF2 trial evaluated intravenous ferric carboxymaltose in patients with HFrEF and iron deficiency. While the complex statistical framework precluded definitive significance, the study added supportive evidence that iron repletion can reduce HF hospitalizations, with a safety profile comparable to placebo.
• Vericiguat and outcomes beyond hospitalization: The VICTOR trial showed that vericiguat did not significantly reduce the composite endpoint of cardiovascular death or HF hospitalization in stable HFrEF patients. However, cardiovascular mortality was lower with vericiguat, highlighting a potential survival benefit even in the absence of reduced hospitalization rates.
• Mortality insights from VICTOR: A dedicated mortality analysis revealed reductions in all-cause mortality, sudden cardiac death, and HF-related deaths with vericiguat. These findings reinforced the importance of evaluating cause-specific outcomes when assessing HF therapies.
• Digitalis makes a comeback: The DIGIT-HF trial revisited digitoxin nearly three decades after earlier digitalis trials. In patients with HFrEF receiving contemporary guideline-recommended therapy, digitoxin significantly reduced the combined risk of death or HF hospitalization, without an increase in adverse events, challenging long-standing safety concerns.
• Sudden cardiac death risk early after diagnosis: The SCD-PROTECT study highlighted a substantial risk of life-threatening ventricular arrhythmias in newly diagnosed HFrEF patients during early optimization of medical therapy. The findings supported the temporary use of wearable cardioverter-defibrillators in this vulnerable period.
• SGLT2 inhibitors initiated in hospital: The DAPA ACT TIMI-68 trial showed that starting dapagliflozin during HF hospitalization was safe. While the primary endpoint was neutral, pooled data confirmed early reductions in cardiovascular events and mortality, supporting in-hospital initiation of SGLT2 inhibitors.
• Treating before confirmation of HF: A large cohort study demonstrated that early initiation of SGLT2 inhibitors and mineralocorticoid receptor antagonists at the time of elevated natriuretic peptide detection could prevent HF hospitalization or death, even before echocardiographic confirmation.
• Challenges in therapy up-titration: The TITRATE-HF study showed that rapid initiation of quadruple therapy for HFrEF is feasible in real-world practice. However, achieving target doses remained uncommon, often due to clinical inertia rather than intolerance, underscoring the need for sustained follow-up and proactive titration.
• Questioning fluid restriction: The FRESH-UP trial found no meaningful benefit of fluid restriction on health status in chronic HF patients, while thirst distress was higher. These results challenge routine fluid restriction advice in stable HF.

In summary, the top heart failure papers of 2025 reflect a shift toward earlier prevention, faster initiation of effective therapies, and critical reassessment of established practices. Together, they point to a more proactive, patient-centered approach that may further improve survival and quality of life in heart failure.

Reference:

Bauersachs, J., Zieroth, S., & De Boer, R. A. The year in cardiovascular medicine 2025: The top 10 papers in heart failure. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaf1044