Daily Cardiology Research Analysis
Analyzed 182 papers and selected 3 impactful papers.
Summary
Two randomized clinical trials from JAMA Cardiology deliver opposing conclusions on conduction system pacing versus biventricular pacing for cardiac resynchronization in HFrEF with LBBB, underscoring the need for careful patient selection and further trials. Separately, a pan-European HF risk model (SCORE2-HF) shows excellent discrimination and region-specific calibration to estimate 10- and 30-year incident heart failure risk in adults without prior CVD.
Research Themes
- Cardiac resynchronization strategies: conduction system pacing vs biventricular pacing
- Long-term risk prediction for incident heart failure in primary prevention
- Trial-to-trial heterogeneity and its impact on guideline translation
Selected Articles
1. Long-Term Outcomes of Left Bundle-Branch Pacing vs Biventricular Pacing in Heart Failure: The HeartSync-LBBP Randomized Clinical Trial.
In 200 patients with HFrEF and LBBB, LBBP reduced the composite of all-cause death or heart failure hospitalization versus BiVP over a median 36 months (HR 0.26). All-cause mortality did not differ, but HF hospitalization and super-response rates favored LBBP.
Impact: This rigorously conducted multicenter RCT suggests LBBP may outperform BiVP for hard outcomes in CRT-eligible HFrEF with LBBB, potentially reshaping first-line resynchronization strategy.
Clinical Implications: For patients with HFrEF and LBBB undergoing CRT, LBBP may reduce HF hospitalizations and the composite of death/HFH compared with BiVP. Given opposing RCT findings in similar populations, centers should individualize approach, ensure operator expertise, and await confirmatory multicenter trials.
Key Findings
- Primary composite of death or HF hospitalization was lower with LBBP vs BiVP (8% vs 28%; HR 0.26, 95% CI 0.12-0.57).
- HF hospitalization alone was reduced with LBBP (7% vs 28%; HR 0.23, 95% CI 0.10-0.52).
- Super-response (LVEF increase ≥15% or to ≥50%) occurred more often with LBBP (55% vs 36%).
Methodological Strengths
- Multicenter randomized design with 36-month median follow-up
- Hard clinical endpoints and prespecified echocardiographic response definitions
Limitations
- All sites in a single country may limit generalizability
- Open-label design and no significant difference in all-cause mortality
Future Directions: Head-to-head multinational RCTs with standardized implant techniques and crossover adjudication are needed to reconcile discordant CRT trials and define subgroups deriving maximal benefit from LBBP.
IMPORTANCE: Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking. OBJECTIVE: To evaluate the long-term clinical outcomes of LBBP and BiVP. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 to December 2024. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to receive either LBBP or BiVP. MAIN OUTCOMES AND MEASURES: The primary end point was the time to death from any cause or heart failure hospitalization (HFH). The secondary end points included all-cause death, HFH, echocardiographic response (absolute increase in LVEF ≥5%), and super response (absolute increase in LVEF ≥15% or improvement of LVEF to ≥50%) rates. RESULTS: Of the 200 included patients, 136 were male and 64 were female. The success rate was 98% in the LBBP group and 94% in the BiVP group (P = .28). The median follow-up duration was 36 (range, 33-39) months. The primary end point of time to death or HFH was significantly lower in the LBBP group compared with BiVP (8% vs 28%; hazard ratio [HR], 0.26; 95% CI, 0.12-0.57; P < .001). There was no significant difference in all-cause mortality between the groups (2.0% vs 5.0%; HR, 0.40; 95% CI, 0.08-2.04; P = .25). However, LBBP significantly reduced the risk of HFH (7.0% vs 28.0%; HR, 0.23; 95% CI, 0.10-0.52; P < .001). The echocardiographic response rates were similar in both groups (86.0% vs 81.0%; P = .34) but the super-response rate was higher in the LBBP group (55.0% vs 36.0%; P < .007). CONCLUSIONS AND RELEVANCE: In this study, LBBP was superior to BiVP in reducing the risk of death or HFH in patients with LBBB and severely reduced LVEF. Further trials are warranted in this patient population. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2000036554.
2. Conduction System vs Biventricular Pacing in Heart Failure: The PhysioSync-HF Randomized Clinical Trial.
In a 14-center RCT of 173 HFrEF patients with LBBB, CSP (preferentially left bundle-branch area pacing) was inferior to BiVP for a hierarchical composite outcome at 12 months and failed noninferiority. LVEF improved in both groups but more with BiVP, though CSP incurred lower direct medical costs.
Impact: This well-executed randomized noninferiority trial counters other recent findings, highlighting heterogeneity in CSP outcomes and the need to refine indications and technique before broad adoption.
Clinical Implications: Routine first-line CSP in HFrEF with LBBB is not supported by these data. Programs adopting CSP should ensure robust operator expertise, careful patient selection, and shared decision-making while awaiting larger, harmonized trials.
Key Findings
- CSP failed noninferiority and was inferior to BiVP for the hierarchical composite at 12 months (OR 2.36, 95% CI 1.37-4.06).
- LVEF increased in both arms but more with BiVP (mean difference 3.8%, 95% CI 0.3%-7.3%).
- CSP showed lower direct medical costs (~$7090 less at 12 months) despite inferior clinical composite outcome.
Methodological Strengths
- Investigator-initiated multicenter randomized noninferiority design with hierarchical composite endpoint
- Predefined noninferiority margin and comprehensive clinical, functional, and economic outcomes
Limitations
- 12-month follow-up may miss late divergences in outcomes
- Open-label design; CSP techniques and learning curves may vary across centers
Future Directions: Standardize CSP implantation protocols, stratify by conduction disease and scar burden, and conduct longer-term, adequately powered multicountry RCTs to reconcile divergent results.
IMPORTANCE: Conduction system pacing (CSP) is a promising and potentially cost-effective alternative to biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB), but its impact on heart failure (HF) outcomes remains uncertain. OBJECTIVE: To compare CSP vs BiVP on an HF-related outcome in patients with HFrEF and LBBB. DESIGN, SETTING, AND PARTICIPANTS: PhysioSync-HF (Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure) was an investigator-initiated, multicenter, noninferiority randomized clinical trial enrolling participants from November 2022 to December 2023 with 12 months of follow-up at 14 hospitals across all regions of Brazil. Adults with symptomatic HFrEF (New York Heart Association NYHA] classes II through III), left ventricular ejection fraction (LVEF) of 35% or less, and LBBB (QRS duration ≥130 milliseconds) were eligible for inclusion. Data were analyzed from May to August 2025. INTERVENTION: Patients were randomized 1:1 to either CSP (preferentially left bundle-branch area pacing) or BiVP. MAIN OUTCOMES AND MEASURES: The primary outcome was a hierarchical composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. The prespecified noninferiority margin for the odds ratio (OR) was 1.2. RESULTS: A total of 173 patients (median [IQR] age, 62 years [56-68]; 86 female patients [49.7%]; 115 (66.5%) with dilated cardiomyopathy; median [IQR] LVEF, 26% [22%-31%]; median [IQR] QRS, 180 milliseconds [170-200]) were included. At 12 months, CSP failed to meet noninferiority and was inferior to BiVP for the primary end point (OR, 2.36; 95% CI, 1.37-4.06; P = .99 for noninferiority; P = .002 for between-group difference). The time-to-event composite of death, HF hospitalizations, or urgent HF visits was higher in CSP (hazard ratio, 2.35; 95% CI, 0.99-5.61). Mean (SD) LVEF increased to 35% (12%) with CSP and 39% (12%) with BiVP (mean difference, 3.8%; 95% CI, 0.3%-7.3%). Relative to baseline, both groups had comparable improvements in QRS duration, Kansas City Cardiomyopathy Questionnaire Overall Summary Score, NYHA class, and natriuretic peptide levels. Total direct medical cost related to the procedure and heart failure care was the equivalent of $7090 (95% CI, $5779-$8648) lower in patients randomized to CSP at 12 months. CONCLUSIONS AND RELEVANCE: In patients with HFrEF and LBBB, CSP was inferior to BiVP for a composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. These findings do not support the routine use of CSP as the first-line resynchronization strategy in this population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05572736.
3. Prediction of incident heart failure in individuals without prior cardiovascular disease: the SCORE2-HF risk model.
SCORE2-HF, derived from 611,778 individuals and recalibrated with >36 million records, showed high discrimination (C-indices 0.827–0.874) and region-specific calibration to estimate 10- and 30-year incident HF risk in adults over 40 without prior CVD. Risk estimates meaningfully varied by conventional risk factors and European risk regions.
Impact: This large-scale, externally validated, region-calibrated HF risk model fills a gap in primary prevention by enabling individualized HF risk estimation using routinely collected variables.
Clinical Implications: Clinicians can integrate SCORE2-HF to identify higher-risk individuals for intensified lifestyle and medical prevention strategies, particularly in European settings where regional calibration aligns estimates to contemporary incidence.
Key Findings
- Sex-specific, competing risk-adjusted models achieved C-indices of 0.827, 0.839, and 0.874 in three external cohorts.
- Models were recalibrated using >36 million individuals across four European risk regions for 10- and 30-year HF incidence.
- Risk estimates varied substantially by smoking, T2DM, hypertension, BMI>30 kg/m2, age, and regional risk strata.
Methodological Strengths
- Derivation from 25 prospective cohorts with competing-risk adjustment and sex-specific modeling
- Extensive recalibration to contemporary incidence and robust external validation in >1.3 million individuals
Limitations
- Heterogeneity in cohort measurements and endpoints across countries
- Generalizability outside Europe and to underrepresented ancestries may be limited
Future Directions: Incorporate biomarkers and imaging where available, extend validation to non-European and diverse ancestry cohorts, and evaluate clinical impact of SCORE2-HF–guided prevention.
BACKGROUND AND AIMS: Heart failure (HF) presents a significant and growing public health challenge. The aim of this study was to develop and validate SCORE2-HF, a model for HF risk estimation in European adults aged over 40-years without previous cardiovascular disease. METHODS: Using data from 25 prospective cohorts (14 countries, 611 778 individuals, 21 818 incident HF events) the sex-specific, competing risk-adjusted SCORE2-HF models were derived including age, smoking status, systolic blood pressure, antihypertensive treatment, body mass-index (BMI), estimated glomerular filtration rate, and type 2 diabetes mellitus (T2DM), including age at diagnosis and glycated haemoglobin. Using Europe-wide statistics from the World Health Organization and linked health records from five countries (>36 million individuals, 515 466 incident HF events) models were recalibrated to contemporary 10-year and 30-year HF incidence in four European risk regions. SCORE2-HF was validated using data from three further cohorts (three countries; 1 336 824 participants; 36 841 incident HF-events). RESULTS: In the three external validation cohorts, C-indices (95% confidence interval) were 0.827 (0.824-0.829), 0.839 (0.827-0.850) and 0.874 (0.863-0.884). SCORE2-HF risks varied importantly by individual's risk factors, and risk region. For example, in the low-risk region, the average 10-year risk for 70-year-old individuals with zero versus four adverse risk factors (smoking, T2DM, hypertension and BMI >30 kg/m2), was 8% versus 24% in men and 6% versus 20% in women. By contrast, in the very high-risk region, average SCORE2-HF risk with four adverse risk factors was 59% in 70-year-old men or women. CONCLUSIONS: SCORE2-HF - a model derived, recalibrated and validated to estimate 10-year and 30-year risk of incident HF across European countries - may enhance the identification of individuals at higher risk of developing HF.