Daily Cardiology Research Analysis
Three impactful cardiology studies stood out today: a randomized trial (HELIOS-B) showing that the RNAi therapy vutrisiran reduces mortality and cardiovascular events in transthyretin amyloid cardiomyopathy; a SEQUOIA-HCM analysis indicating aficamten benefits even mildly symptomatic obstructive HCM; and a large cohort analysis linking long-term wearable-measured physical activity with lower incident atrial fibrillation risk.
Summary
Three impactful cardiology studies stood out today: a randomized trial (HELIOS-B) showing that the RNAi therapy vutrisiran reduces mortality and cardiovascular events in transthyretin amyloid cardiomyopathy; a SEQUOIA-HCM analysis indicating aficamten benefits even mildly symptomatic obstructive HCM; and a large cohort analysis linking long-term wearable-measured physical activity with lower incident atrial fibrillation risk.
Research Themes
- RNA interference therapy improves outcomes in ATTR cardiomyopathy
- Myosin inhibition benefits across symptom severity in obstructive HCM
- Wearable-derived physical activity and atrial fibrillation prevention
Selected Articles
1. Vutrisiran Improves Survival and Reduces Cardiovascular Events in ATTR Amyloid Cardiomyopathy: HELIOS-B.
In HELIOS-B (n=655), subcutaneous vutrisiran significantly reduced all-cause mortality, cardiovascular mortality, and heart failure-related events over up to 39–42 months of follow-up, with consistent benefits irrespective of baseline tafamidis use. These findings reinforce and extend prior efficacy signals, demonstrating durable survival and morbidity benefits in ATTR-CM.
Impact: This is a large randomized trial showing mortality reduction with an RNAi therapy in ATTR-CM, addressing a high-need population and potentially reshaping standard care.
Clinical Implications: Vutrisiran can be considered to reduce mortality and heart failure events in ATTR-CM, including in patients already on tafamidis; integration into guideline-directed therapy should be discussed.
Key Findings
- Reduced all-cause mortality vs placebo (HR 0.64; 95% CI 0.46–0.88).
- Reduced cardiovascular mortality vs placebo (HR 0.67; 95% CI 0.47–0.96).
- Lowered composite of CV mortality and CV events (HR 0.72; 95% CI 0.55–0.94).
- Decreased CV hospitalizations (RR 0.75), HF hospitalizations (RR 0.67), and urgent HF visits (RR 0.54).
- Benefits were consistent regardless of baseline tafamidis use.
Methodological Strengths
- Randomized, double-blind trial with large sample (n=655) and prespecified analyses.
- Long follow-up (DB 33–36 months plus up to 6 months OLE) with comprehensive CV endpoints.
Limitations
- Mortality analyses included up to 6 months of open-label extension, introducing potential bias.
- Generalizability may be limited to trial-eligible ATTR-CM populations.
Future Directions: Head-to-head or combination strategies with tafamidis, long-term safety surveillance, and evaluation across genotype and cardiac staging subgroups.
2. Efficacy of Aficamten in Patients with Obstructive Hypertrophic Cardiomyopathy and Mild Symptoms: Results from the SEQUIOA-HCM Trial.
In SEQUOIA-HCM, patients with mild oHCM symptoms derived significant improvements in pVO2, KCCQ, gradients, and NT-proBNP with aficamten, comparable to those with more advanced symptoms. Serious adverse events were infrequent, supporting consideration of aficamten earlier in the disease course.
Impact: Extends the therapeutic scope of myosin inhibition to less symptomatic oHCM, informing earlier intervention strategies.
Clinical Implications: Clinicians may consider aficamten for symptomatic relief and hemodynamic improvement even in mildly symptomatic oHCM, with monitoring for safety.
Key Findings
- pVO2 improvement at 24 weeks was similar between mild (+1.6 mL/kg/min) and more symptomatic (+1.8 mL/kg/min) groups (p=0.8).
- Secondary endpoints (NYHA class, resting/Valsalva gradient, NT-proBNP) did not differ significantly between groups.
- Both groups improved in KCCQ-CSS; the magnitude was greater in the advanced symptom group (p=0.02 interaction).
- Serious adverse events were infrequent across groups.
Methodological Strengths
- Randomized controlled trial framework with prospectively defined symptom strata.
- Multiple clinically relevant endpoints including exercise capacity, symptoms, hemodynamics, and biomarkers.
Limitations
- Subgroup analysis not powered for between-strata comparisons; risk of multiplicity.
- 24-week follow-up limits assessment of long-term durability and safety.
Future Directions: Longer-term outcomes, head-to-head comparisons with other myosin inhibitors, and evaluation of initiation thresholds in early oHCM.
3. Fitbit-measured physical activity is inversely associated with incident atrial fibrillation among All of Us participants.
Using one year of Fitbit accelerometry from 15,570 All of Us participants and five-year follow-up, higher moderate-to-vigorous physical activity was associated with lower incident atrial fibrillation, independent of clinical and genetic risk factors. This supports leveraging long-term wearable data to refine AF prevention strategies.
Impact: Demonstrates the preventive relevance of objectively measured, long-term free-living physical activity for AF risk—beyond short-term or self-reported assessments.
Clinical Implications: Encourage sustained moderate-to-vigorous activity and consider integrating wearable-derived metrics into AF risk stratification and lifestyle counseling.
Key Findings
- One-year Fitbit-based MVPA was inversely associated with five-year incident AF.
- Association persisted after adjustment for clinical and genetic risk factors.
- Study leverages long-term, free-living accelerometry rather than short-term or self-report.
Methodological Strengths
- Objective, long-term wearable accelerometry in free-living conditions.
- Cox modeling with adjustments including genetic risk, enhancing robustness.
Limitations
- Observational design limits causal inference and is susceptible to residual confounding.
- Cohort demographics and device adherence may limit generalizability.
Future Directions: Interventional trials leveraging wearable-guided activity prescriptions and mechanistic studies linking activity patterns to atrial substrate remodeling.