A Simple Score to Identify Super-Responders to Sacubitril/Valsartan in Ambulatory Patients With Heart Failure

Yang

Front. Cardiovasc. Med.

et al. 2021

Introduction: Left ventricular reverse remodeling (LVRR) is associated with decreased cardiovascular mortality and improved cardiac survival and also crucial for therapeutic options. However, there is a lack of an early prediction model of LVRR in first-diagnosed dilated cardiomyopathy.Methods: This single-center study included 104 patients with idiopathic DCM. We defined LVRR as an absolute increase in left ventricular ejection fraction (LVEF) from >10% to a final value >35% and a decrease in left ventricular end-diastolic diameter (LVDd) >10%. Analysis features included demographic characteristics, comorbidities, physical sign, biochemistry data, echocardiography, electrocardiogram, Holter monitoring, and medication. Logistic regression, random forests, and extreme gradient boosting (XGBoost) were, respectively, implemented in a 10-fold cross-validated model to discriminate LVRR and non-LVRR, with receiver operating characteristic (ROC) curves and calibration plot for performance evaluation.Results: LVRR occurred in 47 (45.2%) patients after optimal medical treatment. Cystatin C, right ventricular end-diastolic dimension, high-density lipoprotein cholesterol (HDL-C), left atrial dimension, left ventricular posterior wall dimension, systolic blood pressure, severe mitral regurgitation, eGFR, and NYHA classification were included in XGBoost, which reached higher AU-ROC compared with logistic regression (AU-ROC, 0.8205 vs. 0.5909, p = 0.0119). Ablation analysis revealed that cystatin C, right ventricular end-diastolic dimension, and HDL-C made the largest contributions to the model.Conclusion: Tree-based models like XGBoost were able to early differentiate LVRR and non-LVRR in patients with first-diagnosed DCM before drug therapy, facilitating disease management and invasive therapy selection. A multicenter prospective study is necessary for further validation.Clinical Trial Registration:http://www.chictr.org.cn/usercenter.aspx (ChiCTR2000034128).

Section: Discussionsupporting

confidence: 94%

“…Moreover, we also found that a single clinical index cannot predict LVRR well, which indicated that LVRR is a consequence of coaction of several factors. (20,36).…”

Section: Discussionmentioning

confidence: 99%

Early Prediction of Left Ventricular Reverse Remodeling in First-Diagnosed Idiopathic Dilated Cardiomyopathy: A Comparison of Linear Model, Random Forest, and Extreme Gradient Boosting

Yang

Front. Cardiovasc. Med.

et al. 2021

“…The criteria proposed in this paper are based on large registries evaluating biohumoral 5 or echocardiographic 23 effects of ARNI and have been used in other studies. 40 Furthermore, the response to treatment is also supported by CPET data, which had not been included in the preliminary established criteria of ARNI response in our study. Beyond ARNI, sodium‐glucose co‐transporter 2 inhibitors (SGLT2i) are known to reduce NT‐proBNP levels and improve cardiac function and prognosis.…”

Section: Discussionsupporting

confidence: 61%

“…Moreover, there is no univocal definition of ARNI efficacy. The criteria proposed in this paper are based on large registries evaluating biohumoral 5 or echocardiographic 23 effects of ARNI and have been used in other studies 40 . Furthermore, the response to treatment is also supported by CPET data, which had not been included in the preliminary established criteria of ARNI response in our study.…”

Section: Discussionmentioning

confidence: 94%

Haemodynamic forces predicting remodelling and outcome in patients with heart failure treated with sacubitril/valsartan

et al. 2023

AimsA novel tool for the evaluation of left ventricular (LV) systo‐diastolic function through echo‐derived haemodynamic forces (HDFs) has been recently proposed. The present study aimed to assess the predictive value of HDFs on (i) 6 month treatment response to sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) patients and (ii) cardiovascular events.Methods and resultsEighty‐nine consecutive HFrEF patients [70% males, 65 ± 9 years, LV ejection fraction (LVEF) 27 ± 7%] initiating sacubitril/valsartan underwent clinical, laboratory, ultrasound and cardiopulmonary exercise testing evaluations. Patients experiencing no adverse events and showing ≥50% reduction in plasma N‐terminal pro‐B‐type natriuretic peptide and/or ≥10% LVEF increase over 6 months were considered responders. Patients were followed up for the composite endpoint of HF‐related hospitalisation, atrial fibrillation and cardiovascular death. Forty‐five (51%) patients were responders. Among baseline variables, only HDF‐derived whole cardiac cycle LV strength (wLVS) was higher in responders (4.4 ± 1.3 vs. 3.6 ± 1.2; p = 0.01). wLVS was also the only independent predictor of sacubitril/valsartan response at multivariable logistic regression analysis [odds ratio 1.36; 95% confidence interval (CI) 1.10–1.67], with good accuracy at receiver operating characteristic (ROC) analysis [optimal cutpoint: ≥3.7%; area under the curve (AUC) = 0.736]. During a 33 month (23–41) median follow‐up, a wLVS increase after 6 months (ΔwLVS) showed a high discrimination ability at time‐dependent ROC analysis (optimal cut‐off: ≥0.5%; AUC = 0.811), stratified prognosis (log‐rank p < 0.0001) and remained an independent predictor for the composite endpoint (hazard ratio 0.76; 95% CI 0.61–0.95; p < 0.01), after adjusting for clinical and instrumental variables.ConclusionsHDF analysis predicts sacubitril/valsartan response and might optimise decision‐making in HFrEF patients.

Chinese medicine and natural products

“…HF is characterized by cardiac remodeling, which includes the accumulation of compensatory structural and functional alterations to alleviate ventricular wall stress. 26 Autophagy occurs in hypoxic cells 27 and organs during cardiovascular diseases, such as HF, 28 suggesting its stimulation under ischemic conditions. The data of the present study showed that autophagy are activated following OGD exposure in H9c2 cells.…”

Section: Discussionmentioning

confidence: 99%

Wenyang-Yiqi Granule Suppresses Oxygen-Glucose Deprivation-Induced Cardiomyocyte Autophagy Through Mammalian Target of Rapamycin Activation in H9c2 Cells

Gao

Lei

Han

et al. 2023

Background Wenyang-Yiqi Granule (WYYQ) is a four-component herbal formula, widely used to treat heart failure in China. It is known to regulate autophagy, but the mechanism(s) are unknown. Methods H9c2 cells were treated with WYYQ for 24 hours prior to oxygen-glucose deprivation (OGD). Expressions of the autophagy markers Beclin-1 and light chain 3 (LC3) were evaluated via quantitative polymerase chain reaction analysis. Protein levels of Beclin-1, LC3, p62, and mammalian targets of rapamycin (mTOR) were determined by Western blot analysis. Transmission electron microscopy was used to explore the effects of WYYQ on autophagosome formation. Results Treatment with WYYQ dramatically restrained OGD-induced autophagy, which was characterized by an inhibition of Beclin-1 and increased LC3 mRNA expression. In addition, WYYQ decreased the expression of Beclin-1 and the ratio of LC3-II/LC3-I; however, the abundance of p62 was enhanced at the protein level. Manipulation of the LC3-II/LC3-I ratio, p62 abundance, and autophagosome formation in response to WYYQ were associated with mTOR activity. Conclusions These findings show that WYYQ plays a protective role during hypoxic-ischemic stress through the suppression of excessive autophagy, which may be partially explained by its effects on mTOR. These data provide novel insight into the cardioprotective effects of WYYQ during cardiomyocyte autophagy.