Table 1
Prevalence of improvement from observational cohorts and subgroup analyses of clinical trials.* Modified from Gulati and Udelson.17 EF: left ventricular ejection fraction; HFrEF: heart failure with reduced ejection fraction; DCM: dilated cardiomyopathy; ACE: angiotensin-converting enzyme inhibitor; BB: beta blocker; ARB: angiotensin receptor blocker; MRA: mineralocorticoid receptor antagonist; ARNI: angiotensin receptor/neprilysin inhibitor.
| FIRST AUTHOR | PUBLICATION YEAR | STUDY SIZE (N) | POPULATION | BASELINE THERAPIES (> 70%) | IMPROVEMENT EF CUTOFF | FREQUENCY OF IMPROVEMENT (%) |
|---|---|---|---|---|---|---|
| Cioffi18 | 2004 | 110 | Chronic HFrEF (EF < 40%) | Digoxin, diuretics | > 51% | 18% |
| McNamara19 | 2011 | 373 | Recent onset DCM & myocarditis (EF ≤ 40%) | ACE, BB | ≥ 50% | 25% |
| Merlo20 | 2011 | 242 | Chronic DCM | ACE, BB, digoxin | Increase ≥ 10% or ≥ 50% | 37% |
| Wilcox21 | 2012 | 3,994 | Chronic HFrEF (EF ≤ 35%) | ACE, BB | Increase > 10% | 29% |
| Dunlay22 | 2012 | 674 | Chronic HF (EF < 50%) | Not given | ≥ 50% | 39% |
| Merlo24 | 2015 | 408 | DCM (EF < 50%) | ACE/ARB, BB | ≥ 50% | 15% |
| Florea9 | 2016 | 4,410 | Chronic HFrEF (EF < 35%) | ACE, diuretics | > 40% | 9% |
| Kalogeropoulos25 | 2016 | 2,166 | Chronic HFrEF (EF ≤ 40%) | ACE/ARB, BB | > 40% | 16% |
| Lupon26 | 2017 | 940 | Chronic HF (EF < 45%) | ACE/ARB, BB, diuretics | ≥ 45% | 25% |
| Agra Bermejo27 | 2018 | 242 | Chronic HFrEF (EF ≤ 40%) | ACE/ARB, BB, diuretics | > 40% | 52% |
| Chang28 | 2018 | 318 | African-American, Chronic HFrEF (EF < 35%) | ACE/ARB, BB, diuretics | > 40% | 19% |
| Ghimire29 | 2019 | 3,124 | Chronic HFrEF (EF ≤ 40%) | ACE, BB | Increase ≥ 10% | 38% |
| He30 | 2021 | 9,491 | Meta-analysis Chronic HFrEF | Varied | Varied | 23% |
| Zhang31 | 2021 | 1,160 | Chronic HFrEF (EF < 40%) | ACE/ARB, BB, MRA† | > 40% & increase ≥ 10% | 25% |
| Yang32 | 2022 | 262 | Chronic HFrEF (EF ≤ 40%) | BB, MRA | > 40% & increase ≥ 10% | 46% |
| Goh33 | 2023 | 407 | Chronic HFrEF (NICM; EF ≤ 40%) | ACE/ARB, BB | > 40% & increase ≥ 10% | 34% |
| Liu34 | 2023 | 573 | Chronic HFrEF (EF ≤ 40%) | ACE/ARB/ARNI, BB | > 40% & increase ≥ 10% | 37% |
| Mohebi36 | 2023 | 416 | Chronic HFrEF (EF < 35%) | ARNI, BB | ≥ 35% | 61% |
| Romero35 | 2024 | 1,307 | Chronic HFrEF (EF ≤ 40%) | ACE/ARB/ARNI | > 40% & increase ≥ 10% | 39% |
[i] *Select studies presented and not intended to be an exhaustive list.
†MRA only > 70% in persistent HFrEF patients
Figure 1
Categorization of frequently encountered myocardial insults in clinical practice. The outer ring represents pathobiologic insults that can result in left ventricular ejection fraction reduction. The middle ring represents either treatments that can result in left ventricular reverse remodeling (LVRR) or scenarios where LVRR can occur if the insult is removed. Used with permission from Hellawell and Marguiles.1 ALM: acute lymphocytic myocarditis; CPAP: continuous positive airway pressure; RAAS: renin-angiotensin-aldosterone system; LVAD: left ventricular assist device; MVR: mitral valve repair/replacement; AVR: aortic valve replacement; CSD: cardiac support device; CRT: cardiac resynchronization therapy
Table 2
Clinical predictors of myocardial recovery. Used with permission from Wilcox et al.14 LV: left ventricular; HF: heart failure; LBBB: left bundle branch block; Echo: echocardiography; CRT: cardiac resynchronization therapy; CMR: cardiac MRI; LGE: late gadolinium enhancement; NT-proBNP: N-terminal pro-b-type natriuretic peptide; sST2: solute suppression of tumorigenicity 2
| PREDICTOR CATEGORY | PREDICTORS OF REVERSE LV REMODELING |
|---|---|
| Clinical parameters | Nonischemic etiology |
| Shorter duration of HF | |
| Female sex | |
| No LBBB | |
| LBBB in CRT | |
| Genetic factors | Pathogenic gene variants not involving structural cytoskeletal proteins or Z-disk proteins |
| Echo/CMR imaging | Greater contractility on strain imaging LGE absence |
| Biomarkers | Lower NT-proBNP |
| Lower troponin | |
| Lower sST2 | |
| Galectin-3, emerging biomarkers (mimecan, miRNAs, orexin) |