Cardio-respiratory coupling and myocardial recovery in heart failure with reduced ejection fraction.

INTRODUCTION: The interaction between the cardiovascular and respiratory systems in healthy subjects is determined by the autonomic nervous system and reflected in respiratory sinus arrhythmia. Recently, another pattern of cardio-respiratory coupling (CRC) has been proposed linking synchronization of heart and respiratory system. However, CRC has not been studied precisely in heart failure (HF) with reduced ejection fraction (EF) (HFrEF) according to the myocardial recovery. METHODS: 10-min resting electrocardiography measurements were performed in persistent HFrEF patients (n=40) who had a subsequent left ventricular EF (LVEF) of ≤ 40 %, HF with recovered EF patients (HFrecEF) (n=41) who had a subsequent LVEF of > 40 % and healthy controls (n=40). Respiratory frequency, respiratory rate, CRC index, time-domain, frequency-domain and nonlinear heart rate variability indices were obtained using standardized software-Kubios™. CRC index was defined as respiratory high-frequency peak minus heart rate variability high-frequency peak. RESULTS: Respiratory rate was positively correlated with high-frequency (HF) peak (Hz) in both persistent HFrEF group (p<0.001) and HFrecEF group (p<0.001), while respiratory rate was negatively correlated with HF power (ms2) in the healthy controls (p<0.05). CRC index was lowest in the persistent HFrEF group followed by HFrecEF and was high in healthy controls (0.008 vs 0.012 vs 0.056 Hz, p=0.03). CONCLUSION: CRC index was lowest in patients with impaired myocardial recovery, which indicates that cardio-respiratory synchrony is stronger in persistent HFrEF. This may represent a higher HF peak (Hz)/lower HF power (ms2) and abnormal sympathovagal balance in persistent HFrEF group compared to healthy controls. Further work is underway to tests this hypothesis and determine the utility of CRC index in HF phenotypes and its utility as a potential biomarker of response with neuromodulation.

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.

Heart Failure with Recovered Ejection Fraction in Patients with Vinculin Loss-of-function Variants.

Predictors of myocardial recovery in heart failure (HF) are poorly understood. We explored if vinculin (VCL) variants are associated with myocardial recovery in dilated cardiomyopathy (DCM). Six infants with DCM with a VCL loss-of-function (LOF) variant were identified. Median age at diagnosis was 2 months, median LV ejection fraction was 24%, and median LV end-diastolic diameter z-score was 10.8. All patients received HF medications. Five patients (83%) showed normalization of LV function at a median age of 2.7 years. One patient progressed to end-stage HF requiring heart transplant. This case series identified a unique phenotype of HF with reduced ejection fraction at presentation that evolved to HF with recovered EF in over 80% of infant DCM cases with LOF VCL variants. These findings have prognostic implications for counseling and management of VCL-associated DCM and highlight a possible genetic basis for HF with recovered ejection fraction.

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.

The Prognostic Value of Anemia in Patients with Preserved, Mildly Reduced and Recovered Ejection Fraction.

Data on the relevance of anemia in heart failure (HF) patients with an ejection fraction (EF) > 40% by subgroup-preserved (HFpEF), mildly reduced (HFmrEF) and the newly defined recovered EF (HFrecEF)-are scarce. Patients with HF symptoms, elevated NT-proBNP, EF ≥ 40% and structural abnormalities were registered in the HFpEF-HFmrEF database. We described the outcome of our HFpEF-HFmrEF cohort by the presence of anemia. Additionally, HFrecEF patients were also selected from HFrEF patients who underwent resynchronization and, as responders, reached 40% EF. Using propensity score matching (PSM), 75 pairs from the HFpEF-HFmrEF and HFrecEF groups were matched by their clinical features. After PMS, we compared the survival of the HFpEF-HFmrEF and HFrecEF groups. Log-rank, uni-and multivariate regression analyses were performed. From 375 HFpEF-HFmrEF patients, 42 (11%) died during the median follow-up time of 1.4 years. Anemia (HR 2.77; 95%CI 1.47-5.23; p < 0.01) was one of the strongest mortality predictors, which was also confirmed by the multivariate analysis (aHR 2.33; 95%CI 1.21-4.52; p = 0.01). Through PSM, the outcomes for HFpEF-HFmrEF and HFrecEF patients with anemia were poor, exhibiting no significant difference. In HFpEF-HFmrEF, anemia was an independent mortality predictor. Its presence multiplied the mortality risk in those with EF ≥ 40%, regardless of HF etiology.