Daily Cardiology Research Analysis
A cluster-randomized trial (STEEER-AF) showed that educating healthcare professionals improved adherence to atrial fibrillation rhythm-control guidelines but did not significantly improve stroke-prevention adherence. A Nature Cardiovascular Research study introduced a drug-tunable AAV expression system (DreAM) responsive to risdiplam, enabling up to 2,000-fold, reversible, and repeatable control of cardiac gene therapy expression. A prospective multicentre MINOCA cohort demonstrated that early C
Summary
A cluster-randomized trial (STEEER-AF) showed that educating healthcare professionals improved adherence to atrial fibrillation rhythm-control guidelines but did not significantly improve stroke-prevention adherence. A Nature Cardiovascular Research study introduced a drug-tunable AAV expression system (DreAM) responsive to risdiplam, enabling up to 2,000-fold, reversible, and repeatable control of cardiac gene therapy expression. A prospective multicentre MINOCA cohort demonstrated that early CMR changed diagnosis and/or management in 63% and facilitated deprescription of dual antiplatelet therapy with a number-needed-to-test of 3.
Research Themes
- Implementation science to improve AF guideline adherence
- Drug-tunable gene therapy control in cardiology
- CMR to refine MINOCA diagnosis and deprescribe DAPT
Selected Articles
1. Education of healthcare professionals to improve guideline adherence in atrial fibrillation: the STEEER-AF cluster-randomized clinical trial.
Across 70 centers (N=1,732), a 16-week structured education program for clinicians improved guideline adherence for rhythm control (adjusted risk ratio 1.51; 95% CI 1.04–2.18; P=0.03) but not for stroke prevention (adjusted risk ratio 1.10; 95% CI 0.97–1.24; P=0.13). Patient-reported integrated AF management improved by 5.1% (95% CI 1.4%–8.9%; P=0.01).
Impact: This is a multinational cluster-RCT directly testing an implementation strategy to close evidence-to-practice gaps in AF care, with measurable adherence and patient-centered outcomes.
Clinical Implications: Structured professional education can meaningfully improve rhythm-control guideline adherence and integrated AF care. Stroke prevention adherence may require different or additional strategies beyond education.
Key Findings
- Rhythm-control guideline adherence improved (adjusted risk ratio 1.51; 95% CI 1.04–2.18; P=0.03).
- No significant improvement in stroke-prevention adherence (adjusted risk ratio 1.10; 95% CI 0.97–1.24; P=0.13).
- Integrated AF management improved by 5.1% versus control (95% CI 1.4%–8.9%; P=0.01).
Methodological Strengths
- Cluster-randomized controlled design across six countries and 70 centers.
- Pre-specified, guideline-based Class I and III adherence measures and adjusted analyses.
Limitations
- No significant effect on stroke-prevention adherence despite education.
- Follow-up limited to 6–9 months; durability and clinical event impact not assessed.
Future Directions: Test multi-component implementation strategies (e.g., audit-feedback, EHR decision support, patient engagement) to improve stroke-prevention adherence and evaluate downstream clinical events.
2. The drug-elicitable alternative splicing module for tunable vector expression in the heart.
DreAM enables risdiplam-responsive, dose-dependent control of AAV transgene expression with up to 2,000-fold induction, with reversible and repeatable activation at approximately 2-day temporal resolution. Incorporation into a cardiomyocyte-specific, liver-detargeted AAV9 vector allowed transient activation of a cardiac regeneration factor.
Impact: This introduces a clinically actionable, small-molecule-tunable switch for cardiac gene therapy, addressing a key safety-efficacy limitation of AAV-based therapeutics.
Clinical Implications: A drug-tunable AAV platform could enable safer, personalized dosing of cardiac gene therapies, allowing on-demand activation, reversibility, and mitigation of off-target effects using an FDA-approved agent.
Key Findings
- Risdiplam activated DreAM-controlled AAV expression with up to ~2,000-fold induction in a dose-dependent manner.
- Temporal control achieved with approximately 2-day resolution; activation was reversible and repeatable.
- Embedding DreAM in a cardiomyocyte-specific, liver-detargeted AAV9 vector enabled transient activation of a cardiac regeneration factor.
Methodological Strengths
- Demonstrated dose-dependent, reversible, and repeatable control using a clinically approved small molecule.
- Organ- and cell-type–targeted vector context (cardiomyocyte-specific, liver-detargeted AAV9) for translational relevance.
Limitations
- Preclinical proof-of-concept; long-term safety, immunogenicity, and off-target splicing effects in humans remain untested.
- Quantitative performance across diverse cardiac disease models and large animals requires further validation.
Future Directions: Evaluate DreAM in large-animal cardiac models, characterize long-term safety and immunogenicity, and integrate with therapeutic transgenes to enable dose-finding and adaptive control in first-in-human studies.
3. Clinical impact of cardiac magnetic resonance imaging in myocardial infarction with non-obstructive coronary arteries: a prospective multicentre cohort study.
In 320 MINOCA patients, CMR changed diagnosis and/or management in 63% and significantly increased diagnostic certainty (median 6/10 pre-CMR to 8/10 post-CMR). Early CMR (≤14 days), absent atheroma on angiography, and low pre-CMR certainty predicted impact. Among those initially placed on DAPT, the number-needed-to-test for deprescription was 3.
Impact: Prospective, practice-embedded evidence that CMR meaningfully alters diagnosis and management in MINOCA, including deprescribing DAPT with a low number-needed-to-test, directly informs clinical pathways.
Clinical Implications: Early CMR should be integrated into MINOCA workup to refine diagnosis, increase diagnostic certainty, and avoid unnecessary DAPT exposure when no culprit is identified.
Key Findings
- CMR changed clinical diagnosis and/or management in 63% (95% CI 57%–68%; p<0.001).
- Diagnostic certainty increased from median 6/10 to 8/10 after CMR (p<0.0001).
- Early CMR (≤14 days), absent atheroma, and low pre-CMR certainty predicted impact; number-needed-to-test for DAPT deprescription was 3.
Methodological Strengths
- Prospective multicentre design with pre-specified pre/post assessments.
- Multivariable logistic regression identified predictors of diagnostic/management impact.
Limitations
- Clinical event outcomes were not the primary focus; follow-up duration for hard endpoints not detailed.
- Generalizability may vary with local imaging expertise and timing of CMR.
Future Directions: Randomized evaluation of early CMR-guided care pathways versus usual care in MINOCA with clinical outcomes and cost-effectiveness; integration of tissue characterization to tailor antithrombotic therapy.