Maintaining Success for Patients With Dilated Cardiomyopathy and Remission of Heart Failure

Corresponding Author

H eart failure with improved ejection fraction, defined as attaining both a $10% improvement in left ventricular ejection fraction and to >40%, is increasingly recognized. 1 Before the use of quadruple disease-modifying therapy, reverse remodeling was observed in a third or more of patients with dilated cardiomyopathy (DCM). 2 The rate of heart failure with improved ejection fraction will now be even greater with contemporary therapy. There is great diversity within this broad spectrum of recovery, in terms of both normalization of cardiac function and resolution of symptoms, which are not always concordant. A proportion of patients will have remission of heart failure with reduced ejection fraction (HFrEFrem), defined by resolution of symptoms, normalization of left ventricular ejection fraction, and plasma concentrations of natriuretic peptides and by the ability to withdraw diuretic agents without recurrence of congestion. This is more frequent in DCM compared to ischemic heart failure. and myocardial work may be critical to maintaining remission ( Figure 1). Maintaining beta-blocker therapy may therefore be a cornerstone of sustaining remission by reducing myocardial work, particularly during periods of stress.

REMISSION BASED ON PHENOTYPE?
Initiation of disease-modifying therapy is key to improving outcomes among patients with persistent symptomatic HFrEF; more effective therapies and interventions will surely be added in years to come.
How to prioritize the initiation of a growing number of therapies at diagnosis is a challenge, and whether patients who achieve remission continue to benefit from all available therapies at the maximum tolerated doses indefinitely is unclear. Whether a simplified pharmacologic regimen based on beta blockers will be successful at maintaining remission once neurohormonal activation has been suppressed, acquired triggers have been removed, and a compensated state has been reached is unknown.
We believe that treatments that target the primary  Developing targeted approaches to maintaining heart failure remission will depend on characterizing the extent of ongoing myocardial susceptibility and balancing this against myocardial workload. Therapies may target different aspects of myocardial susceptibility or myocardial workload. Clinical trials should not only investigate the risks of therapeutic de-escalation but also the possible benefits and why these occur.

FUTURE RESEARCH
To turn a strategy of targeted, individualized therapy for HFrEFrem from an aspiration into a reality, a series of trials focusing on stratified therapy and based on disease phenotype and mechanism are required.
Initial studies may focus on the short-to mediumterm effects of the withdrawal of a single agent on myocardial mechanics and remodeling in patients who are perceived to have a low risk of relapse. Early identification of relapse and demonstration that remission can be restored derisks such trials from an individual patient perspective as well as for clinical services and research. These studies may then progress to larger noninferiority studies assessing the effects on longer-term clinical outcomes. Greater understanding of the likelihood of relapse and the mechanistic drivers will guide the decision-making process and enable more personalized selection of the therapies most likely to maintain remission. Large studies will be required to characterize relationships between disease heterogeneity, ongoing treatments, and disease outcomes. These insights will provide a foundation for developing effective and personalized approaches to long-term therapy that are sensitive to patients' preferences. Twitter: @bp_halliday, @imperialNHLI.