“…Research is needed to predict outcomes and biochemical consequences when therapies are tapered down based on disease characteristics in order to personalise therapy, as well as to predict the small number of patients with dilated cardiomyopathy who relapse suddenly after doing well on treatment for some years. 25 Careful consideration will need to be given to which clinicians take the lead on medicines optimisation and de-escalation. Hospital or primary care pharmacists could have a key role, as they will be able to take a more holistic view of the patient's overall medication list.…”
The current treatment landscape for heart failure is predominantly stratified using ejection fraction. Established drug combinations and devices such as cardiac resynchronisation therapy are available for heart failure with reduced ejection fraction (HFrEF), but medical options for heart failure with preserved ejection fraction (HFpEF) have, until recently, been lacking.A major advance in recent years has been the discovery of effective therapies for HFpEF, including sodium-glucose co-transporter 2 (SGLT2) inhibitors and perhaps also the mineralocorticoid receptor antagonist, spironolactone. For patients with atrial fibrillation and heart failure, the benefit of rhythm control with either radiofrequency ablation or medical therapy is uncertain. Targeted therapies for the small proportion of patients with transthyretin cardiac amyloidosis are available, while antifibrotics seem promising for a larger proportion of patients.For patients with HFrEF, additional treatment options have emerged in the past 10 years. The angiotensin receptor–neprilysin inhibitor (ARNI) combination sacubitril–valsartan and SGLT-2 inhibitors reduce mortality and improve life expectancy in symptomatic patients with HFrEF and at least mildly elevated plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP). The oral soluble guanylate cyclase stimulator vericiguat and cardiac myosin activator omecamtiv mecarbil are not yet licensed in the UK but may provide further treatment options, perhaps in more select groups of patients.Whether all patients with a prior diagnosis of HFrEF who are now in heart failure remission should continue all therapies at maximum tolerated dose indefinitely remains a dilemma. Individualised de-escalation of therapy remains controversial due to the risk of relapse but is occasionally trialled, particularly in patients with a triggering factor such as pregnancy. The ultimate aim is a personalised treatment plan—based on disease phenotype and trajectory—that minimises the risk of relapse and maximises the individual’s quality of life.
“…Research is needed to predict outcomes and biochemical consequences when therapies are tapered down based on disease characteristics in order to personalise therapy, as well as to predict the small number of patients with dilated cardiomyopathy who relapse suddenly after doing well on treatment for some years. 25 Careful consideration will need to be given to which clinicians take the lead on medicines optimisation and de-escalation. Hospital or primary care pharmacists could have a key role, as they will be able to take a more holistic view of the patient's overall medication list.…”
The current treatment landscape for heart failure is predominantly stratified using ejection fraction. Established drug combinations and devices such as cardiac resynchronisation therapy are available for heart failure with reduced ejection fraction (HFrEF), but medical options for heart failure with preserved ejection fraction (HFpEF) have, until recently, been lacking.A major advance in recent years has been the discovery of effective therapies for HFpEF, including sodium-glucose co-transporter 2 (SGLT2) inhibitors and perhaps also the mineralocorticoid receptor antagonist, spironolactone. For patients with atrial fibrillation and heart failure, the benefit of rhythm control with either radiofrequency ablation or medical therapy is uncertain. Targeted therapies for the small proportion of patients with transthyretin cardiac amyloidosis are available, while antifibrotics seem promising for a larger proportion of patients.For patients with HFrEF, additional treatment options have emerged in the past 10 years. The angiotensin receptor–neprilysin inhibitor (ARNI) combination sacubitril–valsartan and SGLT-2 inhibitors reduce mortality and improve life expectancy in symptomatic patients with HFrEF and at least mildly elevated plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP). The oral soluble guanylate cyclase stimulator vericiguat and cardiac myosin activator omecamtiv mecarbil are not yet licensed in the UK but may provide further treatment options, perhaps in more select groups of patients.Whether all patients with a prior diagnosis of HFrEF who are now in heart failure remission should continue all therapies at maximum tolerated dose indefinitely remains a dilemma. Individualised de-escalation of therapy remains controversial due to the risk of relapse but is occasionally trialled, particularly in patients with a triggering factor such as pregnancy. The ultimate aim is a personalised treatment plan—based on disease phenotype and trajectory—that minimises the risk of relapse and maximises the individual’s quality of life.
“…Combining data from clinical assessment as well as advanced imaging and biomarkers may enable the characterization of ongoing disease processes and prediction of the risk of relapse (Fig. 3 ) [ 4 , 45 ]. Fig.…”
Section: How Can Disease Etiology and Underlying Disease Activity Inf...mentioning
confidence: 99%
“…With the advent of effective disease-modifying therapies, left ventricular reverse remodeling (LVRR) is currently observed in at least 40% of patients with non-ischemic dilated cardiomyopathy (DCM) and is associated with improved prognosis [ 3 ]. Indeed, the trajectory of the left ventricular ejection fraction (LVEF) offers important insight into the clinical course and outcome of patients with HF [ 4 ]. A number of pivotal investigations in the last decade have shed light on the clinical profile and outcome of patients with previously reduced LVEF that improves to > 40%.…”
Purpose of Review
With the widespread implementation of contemporary disease-modifying heart failure therapy, the rates of normalization of ejection fraction are continuously increasing. The TRED-HF trial confirmed that heart failure remission rather than complete recovery is typical in patients with dilated cardiomyopathy who respond to therapy. The present review outlines key points related to the management and knowledge gaps of this growing patient group, focusing on patients with non-ischaemic dilated cardiomyopathy.
Recent Findings
There is substantial heterogeneity among patients with normalized ejection fraction. The specific etiology is likely to affect the outcome, although a multiple-hit phenotype is frequent and may not be identified without comprehensive characterization. A monogenic or polygenic genetic susceptibility is common. Ongoing pathophysiological processes may be unraveled with advanced cardiac imaging, biomarkers, multi-omics, and machine learning technologies. There are limited studies that have investigated the withdrawal of specific heart failure therapies in these patients. Diuretics may be safely withdrawn if there is no evidence of congestion, while continued therapy with at least some disease-modifying therapy is likely to be required to reduce myocardial workload and sustain remission for the vast majority.
Summary
Understanding the underlying disease mechanisms of patients with normalized ejection fraction is crucial in identifying markers of myocardial relapse and guiding individualized therapy in the future. Ongoing clinical trials should inform personalized approaches to therapy.
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