Analysis of clinical features of heart failure in children with cardiomyopathy and improved ejection fraction.

Background: The prognosis of children with heart failure varies considerably. After treatment, left ventricular ejection fraction (LVEF) can be improved in some children. The aim of this study was to analyze the clinical features of children with heart failure accompanied by cardiomyopathy and recovered ejection fraction [heart failure with recovered ejection fraction (HFrecEF)] and to identify the predictors of improved LVEF. Methods: Children diagnosed with heart failure in Beijing Anzhen Hospital Affiliated to Capital Medical University from 2018 to 2021 were retrospectively enrolled. According to the baseline and change of LVEF, the patients were divided into two groups: a reduced ejection fraction (HFrEF) group and an HFrecEF group. The t-test was used to evaluate the difference between the two groups. The predictive factors of ejection fraction improvement were analyzed with a logistic regression model. Results: A total of 72 children were included in this study, including 31 (43.1%) in the HFrEF group and 41 (56.9%) in the HFrecEF group. Compared with children in the HFrEF group, children in the HFrecEF group were younger and had faster resting heart rates, lower creatinine, lower suppression of tumorigenicity 2 (ST2) expression, a lower platelet-to-lymphocyte (PLT:LYM) ratio, and smaller left atrial diameter. After a mean follow-up of 35.87 months, 26 cases returned to normal ejection fraction. In the HFrEF group, sudden cardiac death occurred in two cases, and four cases received heart transplantation. Logistic analysis showed that virus infection [odds ratio (OR) =1.279; 95% confidence interval (CI): 0.374-4.379; P=0.007], low ST2 expression (cutoff value =1.89 ng/mL: OR =1.042; 95% CI: 1.007-1.082; P=0.032), and treatment with intravenous immunoglobulin (IVIG) (OR =5.077; 95% CI: 1.458-17.684; P=0.011) were predictors of improvement in LVEF in patients with heart failure after treatment. Conclusions: In some patients with HFrecEF, LVEF eventually returned to normal. The combination of viral infection, low ST2 expression, and the application of IVIG therapy were found to be independent predictors of LVEF improvement in patients with heart failure after treatment.

Predicting factors for omitting beta-blockers in patients with tachycardia-induced cardiomyopathy after successful catheter ablation for atrial fibrillation.

Tachycardia induces a reduction in the left ventricular ejection fraction (LVEF), which is defined as tachycardia-induced cardiomyopathy (TIC). Conversion to and maintenance of sinus rhythm by catheter ablation can improve LVEF in patients with TIC due to atrial fibrillation (AF). Beta-blockers are mandatory for the treatment of heart failure with reduced LVEF(HFrEF), but the necessity of beta-blockers in TIC patients even after catheter ablation remains unclear. We examined the effect of beta-blockers on cardiac function in TIC patients after catheter ablation. We retrospectively analyzed 124 patients with a history of heart failure and an LVEF of ≤ 50% who underwent catheter ablation for AF. TIC was defined as a ≥ 10% improvement in the baseline LVEF and an improvement to an LVEF of ≥ 50% at 6 months after ablation. Patients with other cardiomyopathy diagnosed before the ablation were excluded. LVEF was significantly increased with the reductions of the left ventricular and left atrial volumes at the 6-month follow-up in all 80 patients with TIC. No beta-blockers were prescribed during the post-ablation follow-up in 21 patients with TIC. The absolute values of and changes in the echocardiographic parameters between before and after ablation were not significantly different between patients with and without beta-blockers after the ablation. A simple score using the history of hospitalization for heart failure and use of beta-blockers or diuretics prior to ablation was useful in identifying TIC patients who did not need prescription of beta-blockers after catheter ablation. LVEF similarly improved in both patients with and without prescription of beta-blockers after the ablation. Beta-blockers may not need to be prescribed after successful catheter ablation for AF in LVEF of ≤ 50% patients without other cause of cardiomyopathy diagnosed before the ablation, a history of hospitalization for heart failure and prescription of beta-blockers and diuretics before the ablation.

Treatment with catheter ablation for patients with arrhythmia-induced cardiomyopathy caused by atrial fibrillation promises a good prognosis.

Clinical outcomes after catheter ablation in patients with reduced left ventricular (LV) ejection fraction (EF) and atrial fibrillation (AF) remain unclear. This study aimed to explore the clinical outcomes of patients with arrhythmia-induced cardiomyopathy (AIC) and the influence of pharmacological treatment on clinical outcomes in patients with AIC after the procedure. Ninety-six patients with AF with a reduced LVEF (LVEF < 50%, 66.7 ± 10.9 years; 72 males) underwent AF ablation. AIC was defined as patients whose LVEF recovered ≥ 50% after catheter ablation (n = 67) and patients whose LVEF remained reduced were defined as non-AIC (n = 29). During a median follow-up of 25 (13-40) months, Kaplan-Meier analysis demonstrated that patients with AIC were associated with less frequent cardiovascular death (p = 0.025) and hospitalization for worsening heart failure (p < 0.001) than those without AIC. Freedom from AF recurrence was similar between the two groups (p = 0.47). In multivariate analysis, the LV end-diastolic diameter (p = 0.0002) and the CHA2DS2-VASc scores (p = 0.0062) were independent predictors of AIC. Among the 67 patients with AIC, no significant differences in baseline characteristics, except for LV chamber size and cryoballoon use, were observed between patients with AIC with (n = 31) and without renin-angiotensin system (RAS) inhibitors (n = 36). In the Kaplan-Meier analysis, cardiovascular death, hospitalization for worsening heart failure, and AF recurrence after catheter ablation did not differ between patients treated with and without RAS inhibitors (all p > 0.05). Catheter ablation in patients with AIC due to AF is associated with a good post-procedural prognosis.IRB information The study was approved by the Research Ethics Committee of the University of Fukui (No. 20220151) and clinical trial registration (UMIN000050391).

Outcome of mitral repair combined with Cox-maze procedure for atrial functional mitral regurgitation with heart failure with recovered ejection fraction.

OBJECTIVES: Atrial functional mitral regurgitation (AFMR) in patients with heart failure with recovered ejection fraction has received insufficient attention. This study analysed the prognosis and outcomes of mitral valve (MV) repair combined with the Cox-maze procedure. METHODS: A prospective cohort study of patients with AFMR with left ventricular ejection fraction (LVEF) <40% was conducted. All patients received guideline-directed medical therapy. Those with recovered ejection fraction underwent MV repair combined with the Cox-maze procedure. Mortality, atrial fibrillation (AF) recurrence, mitral regurgitation (MR) and postoperative tricuspid regurgitation were assessed using the inverse probability weighting (IPW) method. RESULTS: In total, 312 patients were enrolled in this study between 2010 and 2019, 247 of whom underwent MV repair combined with the Cox-maze procedure [full recovery (LVEF > 50%): n = 132, partial recovery (LVEF of 40-50%): n = 115]. IPW-adjusted survival of patients with LVEF ≥50% and LVEF 40-50% showed no significant difference [hazard ratio (HR): 2.18, 95% confidence interval: 0.46-10.38, P = 0.33]. However, patients with LVEF ≥50% had better IPW-adjusted long-term freedom from recurrent MR [HR: 2.44 (1.28-4.63), P = 0.0065] and AF recurrence [HR: 1.85 (1.06-3.21), P = 0.030] than those with LVEF of 40-50%. CONCLUSIONS: MV repair combined with the Cox-maze procedure was effective and feasible in patients with severe AFMR with heart failure with recovered ejection fraction. Additionally, patients with LVEF ≥50% after guideline-directed medical therapy undergoing these combined procedures had better long-term freedom from recurrent AF and MR than those with LVEF of 40-50%.

Heart Failure With Recovered Ejection Fraction in Patients With Nonischemic Cardiomyopathy: Characteristics, Outcomes, and Long-term Follow-up.

BACKGROUND: Duration of recovery and long-term outcomes have not been well-described in a large cohort of patients with heart failure with recovered ejection fraction (HFrecEF) owing to nonischemic cardiomyopathy. The aim of the study was to characterize the duration of recovery and long-term outcomes of patients with HFrecEF. METHODS AND RESULTS: We performed a retrospective analysis of our institution's databases. Only patients with nonischemic cardiomyopathy, a chronic HF diagnosis, and a previous left ventricular ejection fraction (LVEF) of ≤35% who had a subsequent LVEF of ≥50% were considered to have recovery. Patients with an LVEF of ≤35% who did not recover served as the comparison group. Included were 2319 patients with an LVEF of ≤35%, of whom 465 (20% [18.4%-21.7%]) met the above criteria for recovery (HFrecEF group). Recovery in the HFrecEF group was temporary in most cases, with 50% of patients experiencing a decline in LVEF to <50% within 3.5 [interquartile range 2.4-4.9] years after the day of recovery. Age and sex adjusted death and hospitalization were lower in the HFrecEF group than the HFrEF group (HR 0.29 [interquartile range 0.20-0.41] for death and 0.44 [interquartile range 0.32-0.60] for HF hospitalization, P < .0001 for both). Longer recovery was associated with better survival, with patients spending >5 years in recovery (LVEF of ≥50%) displaying the highest survival rates (83% alive at 10 years after recovery). Survival after recurrence of LV dysfunction was longer for those whose recovery duration was >1 year. CONCLUSIONS: Patients with nonischemic HFrecEF display a unique clinical course. Although recovery is temporary in most cases, patients with HFrecEF display lower mortality and hospitalization rates, with the more durable the recovery of LV systolic function, the longer survival can be anticipated.

Reverse Atrial Remodeling in Heart Failure With Recovered Ejection Fraction.

Background Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior-inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. Conclusions In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure.

HbA1c level is associated with the development of heart failure with recovered ejection fraction in hospitalized heart failure patients with type 2 diabetes.

BACKGROUND: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in hospitalized HFrEF patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 463 hospitalized T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after around 12 months. Patients who had an absolute EF improvement ≥10% and a second EF > 40% were classified into HFrecEF, and those who did not meet these criteria were defined as persistent HFrEF. RESULTS: During the 12-month follow-up, 44.5% of T2DM patients developed HFrecEF. Patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.5% [IQR 5.8% âˆ¼ 7.2%] vs. 6.7% [IQR 6.1% âˆ¼ 7.8%], P = 0.003), especially in HF of an ischemic etiology. HbA1c levels were inversely correlated with changes in EF during follow-up. After multivariate adjustment, every 1% increase in HbA1c conferred a 17.4% (OR: 0.826 [95% CI 0.701-0.968]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c ≤ 6.2%), those with poor glycemic control (HbA1c > 7.1%) had a 52.0% (OR: 0.480 [95% CI 0.281-0.811] decreased likelihood of HFrecEF. CONCLUSIONS: This study demonstrates that uncontrolled HbA1c level is associated with compromised development of HFrecEF in T2DM patients with HF, especially in those with an ischemic etiology.

Heart Failure with Improved Ejection Fraction: Insight into the Variable Nature of Left Ventricular Systolic Function.

The progress of contemporary cardiovascular therapy has led to improved survival in patients with myocardial disease. However, the development of heart failure (HF) represents a common clinical challenge, regardless of the underlying myocardial pathology, due to the severely impaired quality of life and increased mortality comparable with malignant neoplasms. Left ventricular ejection fraction (LVEF) is the main index of systolic function and a key predictor of mortality among HF patients, hence its improvement represents the main indicator of response to instituted therapy. The introduction of complex pharmacotherapy for HF, increased availability of cardiac-implantable electronic devices and advances in the management of secondary causes of HF, including arrhythmia-induced cardiomyopathy, have led to significant increase in the proportion of patients with prominent improvement or even normalization of LVEF, paving the way for the identification of a new subgroup of HF with an improved ejection fraction (HFimpEF). Accumulating data has indicated that these patients share far better long-term prognoses than patients with stable or worsening LVEF. Due to diverse HF aetiology, the prevalence of HFimpEF ranges from roughly 10 to 40%, while the search for reliable predictors and genetic associations corresponding with this clinical presentation is under way. As contemporary guidelines focus mainly on the management of HF patients with clearly defined LVEF, the present review aimed to characterize the definition, epidemiology, predictors, clinical significance and principles of therapy of patients with HFimpEF.

Insulin Resistance Is Associated With Heart Failure With Recovered Ejection Fraction in Patients Without Diabetes.

Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2-IR). The median HOMA2-IR level was 1.05 (interquartile range [IQR], 0.67-1.63) in our cohort of patients with HF who were nondiabetic. During follow-up, 121 (odds ratio [OR], 46.2% [95% CI 40.2-52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2-IR levels (0.92 [IQR, 0.61-1.37] versus 1.14 [IQR, 0.75-1.78], P=0.007), especially in nonischemic HF. Log2-transformed HOMA2-IR was inversely correlated to improvements in EF (Pearson's r=-0.25, P<0.001). After multivariable adjustment, a doubling of HOMA2-IR was associated with a 42.8% decreased likelihood of HFrecEF (OR, 0.572 [95% CI, 0.385-0.827]). Conclusions This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.

Clinical predictors of improvement in left ventricular ejection fraction in U.S. veterans with heart failure.

Background: Our understanding of the factors associated with improvement of LVEF and a heart failure with improved EF (HFimpEF) phenotype remains incomplete. Methods: We conducted a retrospective study using a national database of patients followed in the Veterans Affairs (VA) health system with serial assessment of left ventricular ejection fraction (LVEF) by echocardiography. We identified US veterans with a new diagnosis of heart failure with: (i) LVEF of <40 % in the 12 months prior to diagnosis, and (ii) follow-up LVEF assessment at least 6 months after their diagnosis. We defined HFimpEF as a final LVEF of ≥40 %. Results: Among the 106,414 US veterans with an initial LVEF of <40 % in this analysis, 39,994 (37.6 %) had a final EF of >40 % after a median follow up of 5 years. Multivariate regression analysis identified several factors that were independently associated with LVEF improvement including female sex, younger age, higher BMI, and a history of specific comorbid conditions such as hypertension, valve disease, atrial fibrillation, connective tissue disease, liver disease, and malignancy (p < 0.001). Conversely, a history of ischemic heart disease and peripheral arterial disease, as well as specific racial backgrounds (Black and Hispanic) were associated with lower rates of LVEF improvement. The model c-statistic for predicting LVEF improvement was 0.70. Conclusions: This large, detailed dataset facilitated an analysis of a large number of variables that significantly associated with HFimpEF; however, their combined discriminatory value for LVEF improvement remained modest, underscoring the complexity of the gene-environment-treatment interactions that govern LV function.

The Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers Is Associated with the Recovered Ejection Fraction in Patients with Dilated Cardiomyopathy.

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown to prevent left ventricular remodeling and improve outcomes of patients with heart failure (HF). This study aimed to investigate whether the use of ACEi/ARB could be associated with HF with recovered ejection fraction (HFrecEF) in patients with dilated cardiomyopathy (DCM).We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM between 2003 and 2014 from the clinical personal record, a national database of the Japanese Ministry of Health, Labour and Welfare. Patients with left ventricular ejection fraction (LVEF) < 40% were included. Eligible patients were divided into two groups according to the use of ACEi/ARB. A propensity score matching analysis was employed. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow-up.Out of 5,955 patients with DCM and LVEF < 40%, propensity score matching yielded 830 pairs. The mean age was 58.8 years, and 1,184 (71.3%) of the patients were male. The primary outcome was observed more frequently in the ACEi/ARB group than in the no ACEi/ARB group (57.0% versus 49.3%; odds ratio 1.36; 95% confidence interval (CI) 1.12-1.65; P = 0.002). Subgroup analysis revealed that the use of ACEi and ARB was associated with recovery of LVEF regardless of atrial fibrillation. The change in LVEF from baseline to 3 years of follow-up was greater in the ACEi-ARB group (14.9% ± 0.6% versus 12.3% ± 0.5%; P = 0.001).The use of ACEi/ARB is associated with HFrecEF in patients with DCM and reduced LVEF.

Beta-Blocker Use Is Associated With Prevention of Left Ventricular Remodeling in Recovered Dilated Cardiomyopathy.

Background Withdrawal of optimal medical therapy has been reported to relapse cardiac dysfunction in patients with dilated cardiomyopathy (DCM) whose cardiac function had improved. However, it is unknown whether beta-blockers can prevent deterioration of cardiac function in those patients. We examined the effect of beta-blockers on left ventricular ejection fraction (LVEF) in recovered DCM. Methods and Results We analyzed the clinical personal record of DCM, a national database of the Japanese Ministry of Health, Labor and Welfare, between 2003 and 2014. Recovered DCM was defined as a previously documented LVEF <40% and a current LVEF ≥40%. Patients with recovered DCM were divided into 2 groups according to the use of beta-blockers. A one-to-one propensity case-matched analysis was used. The primary outcome was defined as a decrease in LVEF >10% at 2 years of follow-up. Of 5370 eligible patients, 4104 received beta-blockers. Propensity score matching yielded 1087 pairs. Mean age was 61.9 years, and 1619 (74.5%) were men. Mean LVEF was 49.3±8.2%, and median B-type natriuretic peptide was 46.6 (interquartile range, 18.0-118.1) pg/mL. The primary outcome was observed less frequently in the beta-blocker group than in the no-beta-blocker group (19.6% versus 24.0%; odds ratio [OR], 0.77; 95% CI, 0.63-0.95; P=0.013). Subgroup analysis demonstrated that female patients (women: OR, 0.54; 95% CI, 0.36-0.81; men: OR, 0.88; 95% CI, 0.69-1.12; P for interaction=0.040) were benefited by beta-blockers. Conclusions Beta-blocker use could prevent deterioration of left ventricular systolic function in patients with recovered DCM.

Cardiac reverse remodelling and health status in patients with chronic heart failure.

AIMS: This study aims to assess long-term changes in left ventricular ejection fraction (LVEF) together with echocardiographic markers of cardiac remodelling and their association with prognosis and patient-reported quality of life (QoL). METHODS AND RESULTS: We conducted a retrospective analysis of serial echocardiograms performed between January 2009 and December 2019 in 1089 patients (median age 63 years, 71.0% men) enrolled in the Mazankowski Heart Function Clinic Registry who had at least two echocardiograms separated by ≥12 months. We classified the patients into four subgroups by their baseline and LVEF trajectories: persistent heart failure with reduced ejection fraction (persistent HFrEF, n = 364), recovered ejection fraction (HFrecEF, n = 325), transient recovery in ejection fraction (HFtrecEF, n = 117), and preserved ejection fraction (HFpEF, n = 283); 4490 echocardiograms were included in the present analysis, with 4.1 ± 1.8 echocardiograms available per patient during follow-up. Reductions in echocardiographic markers of cardiac remodelling, including LVIDd [adjusted odds ratio (aOR): 2.22, 95% confidence interval (CI) 1.75-2.86], LVIDs (aOR: 2.44, 95% CI 2.00-2.94), left ventricular mass index (aOR: 1.15, 95% CI 1.09-1.22), E/e' ratio (aOR: 1.15, 95% CI 1.02-1.30), left atrial volume index (aOR: 1.10, 95% CI 1.03-1.16), along with an increase in the maximum recommended daily dose of renin-angiotensin system inhibitors (aOR: 1.04, 95% CI 1.01-1.07) and mineralocorticoid-receptor antagonists (aOR: 1.06, 95% CI 1.01-1.11) at 2 years, strongly predicted the HFrecEF classification, which was further sustained at 5 years of follow-up. However, changes in these parameters were mostly absent in patients experiencing only a transient recovery in LVEF (HFtrecEF), closely resembling patients with persistent HFrEF. In the multivariable analysis, HFrecEF patients had lower risk of all-cause mortality alone [adjusted hazard ratio (aHR): 0.46, 95% CI 0.23-0.93], and composite all-cause (aHR: 0.59, 95% CI 0.49-0.73), cardiovascular (aHR: 0.47, 95% CI 0.36-0.61), and heart failure (aHR: 0.50, 95% CI 0.35-0.70) related hospitalizations with mortality than patients with persistent HFrEF. QoL assessed through the shortened Kansas City Cardiomyopathy Questionnaire-12 at the end of follow-up was greater in patients with HFrecEF by 5.2, 12.4, and 9.4 points than persistent HFrEF, HFtrecEF, and HFpEF, respectively. CONCLUSIONS: Patients with HFrecEF experienced progressive normalization in echocardiographic markers of cardiac remodelling characterized by reductions in left ventricular dimensions and mass in tandem with reductions in left atrial volume and E/e' ratio, which is associated with better prognosis and QoL.

Left Atrial Strain Associated with Functional Recovery in Patients Receiving Optimal Treatment for Heart Failure.

BACKGROUND: Heart failure with recovered ejection fraction (HFrecEF) has been reported in several previous studies to have a better prognosis than heart failure with reduced ejection fraction (HFrEF). However, the factors associated with HFrecEF have not been identified. The aim of this study was to test the hypothesis that left atrial (LA) strain could help identify patients with recovered ejection fraction (EF) among those with heart failure (HF) with low EF on admission. METHODS: One hundred consecutive patients hospitalized for the first time for new-onset HF were enrolled. Patients were clinically diagnosed with HFrEF on admission (left ventricular EF < 40%) and received optimal treatment for HF. Twenty-eight patients improved to HFrecEF during 6 months of follow-up. RESULTS: Regarding clinical background, there were significantly more women and a lower rate of atrial fibrillation in the HFrecEF group than in the HFrEF group. In a multivariate logistic regression analysis, LA strain was an independent predictor of HFrecEF, even after adjustment for gender and left ventricular EF (odds ratio: 4.06; 95% CI: 2.04-8.07; P < .001). A cutoff value of 10.8% for LA strain showed high sensitivity (96%) and specificity (82%) in identifying HFrecEF in patients with HF presenting with low EF on admission. During a follow-up period of 24 ± 13 months, 31 patients (31%) had cardiovascular death or readmission for HF. Patients with reduced LA strain (<10.8%) had significantly shorter event-free survival than those with preserved LA strain (P = .02). CONCLUSIONS: LA strain is a useful indicator for predicting HFrecEF and should be considered as a routine measurement in patients with HFrEF on admission.

Heart Failure With Recovered Left Ventricular Ejection Fraction: JACC Scientific Expert Panel.

Reverse left ventricular (LV) remodeling and recovery of LV function are associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction. A growing body of evidence suggests that even among patients who experience a complete normalization of LV ejection fraction, a significant proportion will develop recurrent LV dysfunction accompanied by recurrent heart failure events. This has led to intense interest in understanding how to manage patients with heart failure with recovered ejection fraction (HFrecEF). Because of the lack of a standard definition for HFrecEF, and the paucity of clinical data with respect to the natural history of HFrecEF patients, there are no current guidelines on how these patients should be followed up and managed. Accordingly, this JACC Scientific Expert Panel reviews the biology of reverse LV remodeling and the clinical course of patients with HFrecEF, as well as provides guidelines for defining, diagnosing, and managing patients with HFrecEF.

Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy.

BACKGROUND: The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear. OBJECTIVES: The aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy. METHODS: In this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure-related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months. RESULTS: Eighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias. CONCLUSIONS: The incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822).

Long-term and clinical profile of heart failure with recovered ejection fraction in a non-tertiary hospital. / Características y evolución de la insuficiencia cardiaca con función sistólica recuperada en un hospital no terciario.

INTRODUCTION: Heart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference. METHODS: We analysed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital. RESULTS: A total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ2 11.5, P=0.001], hazard ratio 0.37, 95% confidence interval [CI]: 0.21-0.67, P=0.002). Aetiology of deaths was not mainly secondary to HF. Younger age of 68 years (odds ratio [OR] 0-98, 95% CI: 0.96-0,99; P=0.025), ischemic origin (OR 1.12, 95% CI: 1.01-1.21; P=0.003) and use of aldosterone antagonists (OR 1.89, 95% CI: 1.09-3.26; P=0.023) were the variables independently associated to normalisation of EF. CONCLUSION: HF with recovered EF is a frequent phenomenon. It has a more favourable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients.

Baseline Longitudinal Strain Predicts Recovery of Left Ventricular Ejection Fraction in Hospitalized Patients With Nonischemic Cardiomyopathy.

Background Heart failure ( HF ) with "recovered" ejection fraction ( HF rec EF ) is an emerging phenotype, but no tools exist to predict ejection fraction ( EF ) recovery in acute HF . We hypothesized that indices of baseline cardiac structure and function predict HF rec EF in nonischemic cardiomyopathy and reduced EF . Methods and Results We identified a nonischemic cardiomyopathy cohort with EF <40% during the first HF hospitalization (n=166). We performed speckle-tracking echocardiography to measure longitudinal, circumferential, and radial strain, and the average of these measures (myocardial systolic performance). HF rec EF was defined as follow-up EF ≥40% and ≥10% improvement from baseline EF . Fifty-nine patients (36%) achieved HF rec EF (baseline EF 26±7%; follow-up EF 51±7%) within a median of 135 (interquartile range 58-239) days after the first HF hospitalization. Baseline demographics, biomarker profiles, and comorbid conditions (except lower chronic kidney disease in HF rec EF ) were similar between HF rec EF and persistent reduced- EF groups. HF rec EF patients had smaller baseline left ventricular end-systolic dimension (3.6 versus 4.8 cm; P<0.01), higher baseline myocardial systolic performance (9.2% versus 8.1%; P=0.02), and improved survival (adjusted hazard ratio 0.27, 95% confidence interval 0.11, 0.62). We found a significant interaction between baseline left ventricular end-systolic dimension and absolute longitudinal strain. Among patients with left ventricular end-systolic dimension >4.35 cm, higher absolute longitudinal strain (≥8%) was associated with HF rec EF (unadjusted odds ratio=3.9, 95% CI )confidence interval 1.2, 12.8). Incorporation of baseline indices of cardiac mechanics with clinical variables resulted in a predictive model for HF rec EF with c-statistic=0.85. Conclusions Factors associated with achieving HF rec EF were specific to cardiac structure and indices of cardiac mechanics. Higher baseline absolute longitudinal strain is associated with HF rec EF among nonischemic cardiomyopathy patients with reduced EF and larger left ventricular dimensions.

Heart Failure with Myocardial Recovery - The Patient Whose Heart Failure Has Improved: What Next?

In an important number of heart failure (HF) patients substantial or complete myocardial recovery occurs. In the strictest sense, myocardial recovery is a return to both normal structure and function of the heart. HF patients with myocardial recovery or recovered ejection fraction (EF; HFrecEF) are a distinct population of HF patients with different underlying etiologies, demographics, comorbidities, response to therapies and outcomes compared to HF patients with persistent reduced (HFrEF) or preserved ejection fraction (HFpEF). Improvement of left ventricular EF has been systematically linked to improved quality of life, lower rehospitalization rates and mortality. However, mortality and morbidity in HFrecEF patients remain higher than in the normal population. Also, persistent abnormalities in biomarker and gene expression profiles in these patients lends weight to the hypothesis that pathological processes are ongoing. Currently, there remains a lack of data to guide the management of HFrecEF patients. This review will discuss specific characteristics, pathophysiology, clinical implications and future needs for HFrecEF.