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Background The 6-minute walk test (6MWT) independently predicts congestive heart failure (CHF) severity, death and heart failure hospitalizations, but must be administered in clinic by qualified staff on a pre-measured course. As part of the Health eHeart Study we sought to develop and validate a self-administered 6MWT mobile application (SA-6MWTapp) for independent use at home by patients. Methods and Results We performed a validation study of a SA-6MWTapp in 103-participants. In phase one (n=52), we developed a distance estimation algorithm for the SA-6MWTapp by comparing step counts from an Actigraph and measured distance on a pre-measured 6MWT course to step counts and estimated distance obtained simultaneously from our SA-6MWTapp (best estimation algorithm, r = 0.89 [95% CI 0.78 – 0.99]). In phase two, 32 participants (including those with CHF and pHTN) used the SA-6MWTapp independently in clinic and the distance estimated by the SA-6MWTapp was compared to the measured distance (r = 0.83 [95% CI 0.79-0.92]). In phase three, 19 patients with CHF and pHTN consecutively enrolled from clinic, performed 3.2 ±1 SA-6MWTapp tests per week at home over 2 weeks. Distances estimated from the SA-6MWTapp during home 6MWTs were highly repeatable (coefficient of variation = 4.6%) and correlated with in-clinic measured distance (r = 0.88 [95% CI 0.87-0.89]). Usability surveys performed during the second (in-clinic) and third (at-home) phases demonstrated that the SA-6MWTapp was simple and easy to use independently. Conclusions A self-administered 6MWTapp is easy to use and yields accurate repeatable measurements in the clinic and at home.

BACKGROUND Persistent severe left ventricular (LV) systolic dysfunction after myocardial infarction (MI) is associated with increased mortality and is a class I indication for implantation of a cardioverter-defibrillator. OBJECTIVES We developed models and assessed independent predictors of LV recovery to >35% and ≥50% after 90-day follow-up in patients presenting with acute MI and severe LV dysfunction.. METHODS Our multicenter prospective observational study enrolled participants with ejection fraction (EF) of ≤35% at the time of MI (n = 231). Predictors for EF recovery to >35% and ≥50% were identified after multivariate modeling and validated in a separate cohort (n = 236). RESULTS In PREDICTS, 43% of patients had persistent EF ≤35%, 31% had an EF of 36% to 49%, and 26% had an EF ≥50%. The model that best predicted recovery of EF to >35%, included EF at presentation, length of stay, prior MI, lateral wall motion abnormality at presentation, and peak troponin. The model that best predicted recovery of EF to ≥50%, included EF at presentation, peak troponin, prior MI, and presentation with ventricular fibrillation or cardiac arrest. After predictors were transformed into point scores, the lowest point scores predicted a 9% and 4% probability of EF recovery to >35% and ≥50%, respectively, whereas profiles with the highest point scores predicted an 87% and 49% probability of EF recovery to >35% and ≥50%. CONCLUSIONS In patients with severe systolic dysfunction following acute MI with an EF ≤35%, 57% had EF recovery to >35%. A model using clinical variables present at the time of MI can help predict EF recovery.

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue regarding the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17th 2016 represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions.