Left atrial strain is a predictor of left ventricular systolic and diastolic reverse remodelling in CRT candidates.

AIMS: The left atrium (LA) has a pivotal role in cardiac performance and LA deformation is a well-known prognostic predictor in several clinical conditions including heart failure with reduced ejection fraction. The aim of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on both LA morphology and function and to assess the impact of LA reservoir strain (LARS) on left ventricular (LV) systolic and diastolic remodelling after CRT. METHODS AND RESULTS: Two hundred and twenty-one CRT-candidates were prospectively included in the study in four tertiary centres and underwent echocardiography before CRT-implantation and at 6-month follow-up (FU). CRT-response was defined by a 15% reduction in LV end-systolic volume. LV systolic and diastolic remodelling were defined as the percent reduction in LV end-systolic and end-diastolic volume at FU. Indexed LA volume (LAVI) and LV-global longitudinal (GLS) strain were the main parameters correlated with LARS, with LV-GLS being the strongest determinant of LARS (r = -0.59, P < 0.0001). CRT induced a significant improvement in LAVI and LARS in responders (both P < 0.0001). LARS was an independent predictor of both LV systolic and diastolic remodelling at follow-up (r = -0.14, P = 0.049 and r = -0.17, P = 0.002, respectively). CONCLUSION: CRT induces a significant improvement in LAVI and LARS in responders. In CRT candidates, the evaluation of LARS before CRT delivery is an independent predictor of LV systolic and diastolic remodelling at FU.

Echocardiographic view and feature selection for the estimation of the response to CRT.

Cardiac resynchronization therapy (CRT) is an implant-based therapy applied to patients with a specific heart failure (HF) profile. The identification of patients that may benefit from CRT is a challenging task and the application of current guidelines still induce a non-responder rate of about 30%. Several studies have shown that the assessment of left ventricular (LV) mechanics by speckle tracking echocardiography can provide useful information for CRT patient selection. A comprehensive evaluation of LV mechanics is normally performed using three different echocardioraphic views: 4, 3 or 2-chamber views. The aim of this study is to estimate the relative importance of strain-based features extracted from these three views, for the estimation of CRT response. Several features were extracted from the longitudinal strain curves of 130 patients and different methods of feature selection (out-of-bag random forest, wrapping and filtering) have been applied. Results show that more than 50% of the 20 most important features are calculated from the 4-chamber view. Although features from the 2- and 3-chamber views are less represented in the most important features, some of the former have been identified to provide complementary information. A thorough analysis and interpretation of the most informative features is also provided, as a first step towards the construction of a machine-learning chain for an improved selection of CRT candidates.

Characterization of Responder Profiles for Cardiac Resynchronization Therapy through Unsupervised Clustering of Clinical and Strain Data.

BACKGROUND: The mechanisms of improvement of left ventricular (LV) function with cardiac resynchronization therapy (CRT) are not yet elucidated. The aim of this study was to characterize CRT responder profiles through clustering analysis, on the basis of clinical and echocardiographic preimplantation data, integrating automatic quantification of longitudinal strain signals. METHODS: This was a multicenter observational study of 250 patients with chronic heart failure evaluated before CRT device implantation and followed up to 4 years. Clinical, electrocardiographic, and echocardiographic data were collected. Regional longitudinal strain signals were also analyzed with custom-made algorithms in addition to existing approaches, including myocardial work indices. Response was defined as a decrease of ≥15% in LV end-systolic volume. Death and hospitalization for heart failure at 4 years were considered adverse events. Seventy features were analyzed using a clustering approach (k-means clustering). RESULTS: Five clusters were identified, with response rates between 50% in cluster 1 and 92.7% in cluster 5. These five clusters differed mainly by the characteristics of LV mechanics, evaluated using strain integrals. There was a significant difference in event-free survival at 4 years between cluster 1 and the other clusters. The quantitative analysis of strain curves, especially in the lateral wall, was more discriminative than apical rocking, septal flash, or myocardial work in most phenogroups. CONCLUSIONS: Five clusters are described, defining groups of below-average to excellent responders to CRT. These clusters demonstrate the complexity of LV mechanics and prediction of response to CRT. Automatic quantitative analysis of longitudinal strain curves appears to be a promising tool to improve the understanding of LV mechanics, patient characterization, and selection for CRT.

Left ventricular strain for predicting the response to cardiac resynchronization therapy: two methods for one question.

AIMS: Myocardial work (manually controlled software) and integral-derived longitudinal strain (automatic quantification of strain curves) are two promising tools to quantify dyssynchrony and potentially select the patients that are most likely to have a reverse remodelling due to cardiac resynchronization therapy (CRT). We sought to test and compare the value of these two methods in the prediction of CRT-response. MATERIALS AND RESULTS: Two hundred and forty-three patients undergoing CRT-implantation from three European referral centres were considered. The characteristics from the six-segment of the four-chamber view were computed to obtain regional myocardial work and the automatically generated integrals of strain. The characteristics were studied in mono-parametric and multiparametric evaluations to predict CRT-induced 6-month reverse remodelling. For each characteristic, the performance to estimate the CRT response was determined with the receiver operating characteristic (ROC) curve and the difference between the performances was statistically evaluated. The best area under the curve (AUC) when only one characteristic used was obtained for a myocardial work (AUC = 0.73) and the ROC curve was significantly better than the others. The best AUC for the integrals was 0.63, and the ROC curve was not significantly greater than the others. However, with the best combination of works and integrals, the ROC curves were not significantly different and the AUCs were 0.77 and 0.72. CONCLUSION: Myocardial work used in a mono-parametric estimation of the CRT-response has better performance compared to other methods. However, in a multiparametric application such as what could be done in a machine-learning approach, the two methods provide similar results.

Prediction of response to cardiac resynchronization therapy using a multi-feature learning method.

We hypothesized that a multiparametric evaluation, based on the combination of electrocardiographic and echocardiographic parameters, could enhance the appraisal of the likelihood of reverse remodeling and prognosis of favorable clinical evolution to improve the response of cardiac resynchronization therapy (CRT). Three hundred and twenty-three heart failure patients were retrospectively included in this multicenter study. 221 patients (68%) were responders, defined by a decrease in left ventricle end-systolic volume ≥15% at the 6-month follow-up. In addition, strain data coming from echocardiography were analyzed with custom-made signal processing methods. Integrals of regional longitudinal strain signals from the beginning of the cardiac cycle to strain peak and to the instant of aortic valve closure were analyzed. QRS duration, septal flash and different other features manually extracted were also included in the analysis. The random forest (RF) method was applied to analyze the relative feature importance, to select the most significant features and to build an ensemble classifier with the objective of predicting response to CRT. The set of most significant features was composed of Septal Flash, E, E/A, E/EA, QRS, left ventricular end-diastolic volume and eight features extracted from strain curves. A Monte Carlo cross-validation method with 100 runs was applied, using, in each run, different random sets of 80% of patients for training and 20% for testing. Results show a mean area under the curve (AUC) of 0.809 with a standard deviation of 0.05. A multiparametric approach using a combination of echo-based parameters of left ventricular dyssynchrony and QRS duration helped to improve the prediction of the response to cardiac resynchronization therapy.

Prognostic Usefulness of Myocardial Work in Patients With Heart Failure and Reduced Ejection Fraction Treated by Sacubitril/Valsartan.

The noninvasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (major adverse cardiovascular events [MACEs]). This study aimed to evaluate the short- and medium-term effect of Sacubitril/Valsartan treatment on MW parameters and the prognostic value of MW in this specific group of patients. Seventy-nine patients with HFrEF (mean age: 66 ± 12 years; LV ejection fraction: 28% ± 9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan. Sacubitril/Valsartan significantly increased myocardial constructive work (CW) (1023 ± 449 vs 1424 ± 484 mm Hg%, p <0.0001) and myocardial work efficiency (WE) [87 (78to 90) vs 90 (86 to 95), p <0.0001]. During FU (2.6 ± 0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LV ejection fraction and WE, global myocardial constructive work (CW) was the only predictor of MACEs [hazard ratio [HR] 0.99 (0.99 to 1.00), p = 0.04]. A CW <910 mm Hg identified patients at particularly increase risk of MACEs [HR 11.09 (1.45 to 98.94), p = 0.002, log-rank test p <0.0001]. In conclusion, in patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan allows the prediction of MACEs.