Table.

Prioritized Research Opportunities for AF and HF

The Overlapping Pathophysiology Between AF and HF
1. To establish the risk profiles and prevalence of tachycardiomyopathy with lesser degrees of reversible LV dysfunction. This may be best accomplished through a curated cohort of patients with AF and non-ischemic HF in whom the following are characterized: biomarkers, fibrosis on cardiac MRI, cardiac structure on cardiac MRI and echo, genomic (methylation, transcriptomic, proteomic, etc.), and genetic profiles of cardiomyopathy and AF, peak VO2 testing, and patient-reported outcomes before and at 6 and 12 months after ablation to determine frequency and characteristics predicting meaningful improvement.
2. To conduct a randomized trial of intensive maintenance of volume status vs. usual care to reduce progression of HF and progression of paroxysmal to persistent AF as well as following AF ablation in adults with either HFrEF or HFpEF. Outcomes would include LVEF and LV dimensions in HFrEF, diastolic function and left atrial volume and patient-reported symptoms and function in both HFrEF and HFpEF.
3. To conduct randomized clinical trials of catheter ablation, antiarrhythmic drugs, and prevention in patients with AF and HF. To enhance the feasibility of such trials, pragmatic and other innovative trial designs should be leveraged.
Research to prevent HF in individuals with AF
1. Mechanistic studies are needed to elucidate the underlying pathobiology of cardiac remodeling, HFpEF, and HFrEF after AF onset.
2. Studies should focus on risk stratification of individuals with AF, and identification of at-risk individuals most likely to develop HFrEF or HFpEF, leveraging clinical, biochemical, imaging, or genomic/genetic data. Through detection of atrial and ventricular fibrosis and accurate measurement of hemodynamics, cardiac MRI specifically may be important in elucidating factors responsible for the development and progression of HF in AF patients.
3. Studies should focus on identifying preventive/therapeutic strategies to effectively reduce the risk of developing HFpEF and HFrEF in AF patients.
Research to prevent AF in individuals with HF
1. In randomized controlled trials, test whether treating early detected AF can improve event-free survival (stroke/systemic embolism, heart failure deterioration/hospitalization, mortality, dementia/cognitive decline) and patient-centered outcomes (quality of life, functional status, frailty). Also, the best treatment for early detected AF should be investigated and may include more aggressive rhythm control with available or novel antiarrhythmic drugs, catheter ablation, or device therapies.
2. Explore existing and new deeply-phenotyped HF cohorts to define HF subtypes with a high risk of AF and adverse outcomes based on multi-level information in order to highlight pathophysiological pathways for experimental work-up, improve screening efficiency, and identify targets for prevention. Characterize AF phenotypes that may be unique in HFpEF versus HFrEF.
3. Conduct randomized controlled trials comparing the effectiveness in preventing AF of standard and novel HF treatments (e.g., beta-blockers, cardiac resynchronization therapy) in HFrEF and HFpEF patients.
Research on symptom burden in AF versus HF
1. Determine if disease-specific, patient-reported outcome measures best determine the impact of AF and AF therapy on quality of life in order to define the best endpoints in AF and HF clinical trials, the most appropriate measures of clinical AF care quality, and the most accurate predictors of AF disease trajectory.
2. Study the effects of AF on cardiovascular function and symptoms in a spectrum of AF patients to determine how to discriminate between symptoms due to occult myocardial dysfunction or comorbidities versus AF.
3. Define clinically-important differences in disease-specific patient-reported outcome measures and their associations with age, sex, and race/ethnicity and the variability in health status across practices determining the proportion of this variability that is due to patient (e.g. socio-demographic, socio-economic, clinical comorbidities and disease severity) and practice characteristics (e.g. treatment).