Table 4.

Future directions and unmet needs

Question	Significance	Future Directions
Does using a HF risk score to identify individuals for preventive interventions reduce incident HF?	Important to identify patients that will gain the greatest benefit from early use of emerging preventive therapies	Trials comparing a clinical risk score-based strategy of management including subsequent use of biomarkers, imaging, and interventions focused on HF prevention compared with usual care
Does intensive lifestyle intervention in high-risk adults reduce incident HF?	Programs like the diabetes prevention program have shown significant benefits for risk factor management, and a similar framework needs to be explored with HF prevention	Creation and implementation of an intensive lifestyle program focused on adults at high-risk for HF with longitudinal follow-up to determine efficacy
When should biomarker or imaging-based screening be started in individuals with highly prevalent risk alleles to identify subclinical cardiac dysfunction?	The V122I TTR variant and the MYBPC3 deletion variant are present in nearly 4% of the African American and South Asian populations, respectively	Longitudinal cohort studies of young to middle-aged African American and South Asian adults with genetic data and contemporary cardiac imaging
In adults with TTR risk alleles, does initiation of TTR-specific therapies or aggressive risk factor modification during the subclinical phase prevent onset of HF?	Interaction of TTR risk alleles with clinical risk factors is not known; rationale for early use of TTR-specific therapies is based on the underlying pathophysiology and may significantly reduce morbidity and mortality	Large longitudinal cohorts studies to evaluate the interaction between TTR risk alleles and clinical risk factors; clinical trials of TTR-specific therapies in patients with TTR risk alleles and Stage B HF
How should HF risk be assessed in individuals with different risk enhancing features?	Clinical risk scores validated in the general population have not been specifically evaluated in these populations and disease-specific characteristics may need to be added to the score to improve its performance	Use of multicenter registries, specialized cohort studies, and electronic health record data to identify large enough cohorts for these more rare risk enhancing diseases