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Introduction: The characterization and selection of heart failure (HF) patients for cardiac resynchronization therapy (CRT) remain challenging, with around 30% non-responder rate despite following current guidelines. This study aims to propose a novel hybrid approach, integrating machine-learning and personalized models, to identify explainable phenogroups of HF patients and predict their CRT response., Methods: The paper proposes the creation of a complete personalized model population based on preoperative CRT patient strain curves. Based on the parameters and features extracted from these personalized models, phenotypes of patients are identified thanks to a clustering algorithm and a random forest classification is provided., Results: A close match was observed between the 162 experimental and simulated myocardial strain curves, with a mean RMSE of 4.48% (±1.08) for the 162 patients. Five phenogroups of personalized models were identified from the clustering, with response rates ranging from 52% to 94%. The classification results show a mean area under the curves (AUC) of 0.86 ± 0.06 and provided a feature importance analysis with 22 features selected. Results show both regional myocardial contractility (from 22.5% to 33.0%), tissue viability and electrical activation delays importance on CRT response for each HF patient (from 55.8 ms to 88.4 ms)., Discussion: The patient-specific model parameters' analysis provides an explainable interpretation of HF patient phenogroups in relation to physiological mechanisms that seem predictive of the CRT response. These novel combined approaches appear as promising tools to improve understanding of LV mechanical dyssynchrony for HF patient characterization and CRT selection., Competing Interests: Declaration of competing interest No conflict of interest exists. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Heart failure is a clinical syndrome with an increasing prevalence and incidence worldwide that impacts patients' quality of life, morbidity, and mortality. Implantable cardioverter-defibrillator and cardiac resynchronization therapy are pillars of managing patients with HF and reduced left ventricular ejection fraction. Despite the advances in cardiac imaging, the assessment of patients needing cardiac implantable electronic devices relies essentially on the measure of left ventricular ejection fraction. However, multi-modality imaging can provide important information concerning the aetiology of heart failure, the extent and localization of myocardial scar, and the pathophysiological mechanisms of left ventricular conduction delay. This paper aims to highlight the main novelties and progress in the field of multi-modality imaging to identify patients who will benefit from cardiac resynchronization therapy and/or implantable cardioverter-defibrillator. We also want to underscore the boundaries that prevent the application of imaging-derived parameters to patients who will benefit from cardiac implantable electronic devices and orient the choice of the device. Finally, we aim at providing some reflections for future research in this field., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Conflict of interest: none declared., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Heart failure with reduced ejection fraction (HFrEF) is a heterogeneous syndrome. In heart failure (HF) classifications, right ventricle (RV) function was for a long time unrecognized in favor of left ventricular ejection fraction (LVEF). The response to sacubitril/valsartan might differ according to phenotypes and the impact of right ventricular characteristics on this response remains controversial., Objectives: First, we applied clustering analysis in a HFrEF population undergoing sacubitril/valsartan treatment according to guidelines, to identify phenotypes and their associated clinical outcomes. Secondly, we evaluated RV-remodeling., Material and Methods: It is a prospective, observational, single-center study conducted on 108 symptomatic patients (mean age 66 ±12.8 years, 22.2% women). First, the clustering analysis was applied in a HFrEF population undergoing sacubitril/valsartan treatment, according to the guidelines, in order to identify phenotypes and clinical outcomes associated with them. Secondly, we evaluated RV-remodeling., Results: Two distinct clusters were identified. Among the differences between phenotypes, RV (tricuspid annular plane systolic excursion (TAPSE) 16 ±4 mm compared to 19 ±4 mm, p < 0.001; RV free wall strain -19 ±5% compared to -21 ±4%, p = 0.046; RV fraction area change (FAC) 31 ±9% compared to 38 ±9%, p < 0.001), LV-filling pressure (E-wave deceleration time 138 (median: 41) ms compared to 180 (median: 94) ms, p < 0.001; E/e' 16.7 (median: 8.0) ms compared to 13.0 (median: 9.7) ms, p = 0.02) and creatinine level (106 ±34 μmol/L compared to 90 ±19 μmol/L, p = 0.002) were substantially different at the initiation of therapy. Major adverse cardiac events (MACEs) or death occurred in 38 out of 107 patients: 51.1% in cluster 1 compared to 24.2% in cluster 2 (p = 0.0074). A significant improvement in RV-functional parameters was observed under treatment. The TAPSE improved and correlated with the change in left ventricular (LV) function. Yet, it did not correlate with systolic pulmonary artery pressure (sPAP) and LV end-diastolic diameter., Conclusions: The HFrEF phenotype characterized by more severe RV dysfunction has a worse prognosis during sacubitril/valsartan therapy. Both RVand LV functions significantly improve when the patient is treated with sacubitril/valsartan.

Objectives: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT)., Background: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT., Methods: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EF preserved ), 36% to 49% (EF mid ), and ≤35% (EF low ). Sixty-four patients underwent CRT and were re-examined after 6 months., Results: Septal work was successively reduced from controls, through EF preserved , EF mid , and EF low (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EF preserved and EF mid versus controls, and did not significantly correlate with LVEF in these groups. In EF low, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005)., Conclusions: In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT., Competing Interests: Funding Support and Author Disclosures Drs Sletten and Aalen were supported by grants from the Norwegian Health Association. Dr Larsen was a recipient of a clinical research fellowships form the South-Eastern Norway Regional Health Authority. Prof Voigt holds a personal research mandate of the Flemish Research Council. Prof Voigt and Dr Duchenne were further supported by a grant of the University of Leuven. Dr Smiseth is co-inventor, but since May 24, 2017 has had no financial relations to the patent “Method for myocardial segment work analysis,” which was used to calculate the myocardial work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose, (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) is characterized by a high rate of hospitalization and mortality (up to 84% at 5 years), which are similar to those observed for heart failure with reduced ejection fraction (HFrEF). These epidemiologic data claim for the development of specific and innovative therapies to reduce the burden of morbidity and mortality associated with this disease. Compared with HFrEF, which is due to a primary myocardial damage (eg ischemia, cardiomyopathies, toxicity), a heterogeneous etiologic background characterizes HFpEF. The authors discuss these phenotypes and specificities for defining therapeutic strategies that could be proposed according to phenotypes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response., Competing Interests: Declaration of Competing Interest Nothing to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Despite all having systolic heart failure and broad QRS intervals, patients screened for cardiac resynchronization therapy (CRT) are highly heterogeneous, and it remains extremely challenging to predict the impact of CRT devices on left ventricular function and outcomes. The aim of this study was to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic data on the left ventricular remodeling and prognosis of CRT candidates by the application of machine learning approaches., Methods: One hundred ninety-three patients with systolic heart failure receiving CRT according to current recommendations were prospectively included in this multicenter study. A combination of the Boruta algorithm and random forest methods was used to identify features predicting both CRT volumetric response and prognosis. Model performance was tested using the area under the receiver operating characteristic curve. The k-medoid method was also applied to identify clusters of phenotypically similar patients., Results: From 28 clinical, electrocardiographic, and echocardiographic variables, 16 features were predictive of CRT response, and 11 features were predictive of prognosis. Among the predictors of CRT response, eight variables (50%) pertained to right ventricular size or function. Tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with particularly good prediction of both CRT response (area under the curve, 0.81; 95% CI, 0.74-0.87) and outcomes (area under the curve, 0.84; 95% CI, 0.75-0.93). An unsupervised machine learning approach allowed the identification of two phenogroups of patients who differed significantly in clinical variables and parameters of biventricular size and right ventricular function. The two phenogroups had significantly different prognosis (hazard ratio, 4.70; 95% CI, 2.1-10.0; P < .0001; log-rank P < .0001)., Conclusions: Machine learning can reliably identify clinical and echocardiographic features associated with CRT response and prognosis. The evaluation of both right ventricular size and functional parameters has pivotal importance for the risk stratification of CRT candidates and should be systematically performed in patients undergoing CRT., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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.

Aims: Early diagnosis of heart failure with preserved ejection fraction (HFpEF) by determination of diastolic dysfunction is challenging. Strain-volume loop (SVL) is a new tool to analyse left ventricular function. We propose a new semi-automated method to calculate SVL area and explore the added value of this index for diastolic function assessment., Method and Results: Fifty patients (25 amyloidosis, 25 HFpEF) were included in the study and compared with 25 healthy control subjects. Left ventricular ejection fraction was preserved and similar between groups. Classical indices of diastolic function were pathological in HFpEF and amyloidosis groups with greater left atrial volume index, greater mitral average E/e' ratio, faster tricuspid regurgitation (P < 0.0001 compared with controls). SVL analysis demonstrated a significant difference of the global area between groups, with the smaller area in amyloidosis group, the greater in controls and a mid-range value in HFpEF group (37 vs. 120 vs. 72 mL.%, respectively, P < 0.0001). Applying a linear discriminant analysis (LDA) classifier, results show a mean area under the curve of 0.91 for the comparison between HFpEF and amyloidosis groups., Conclusion: SVLs area is efficient to identify patients with a diastolic dysfunction. This new semi-automated tool is very promising for future development of automated diagnosis with machine-learning algorithms., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT)., Methods and Results: In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70-0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81-0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120-150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18-0.74) and 0.21 (95% CI: 0.072-0.61), respectively., Conclusion: Assessment of myocardial work and septal viability identified CRT responders with high accuracy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Estimated plasma volume status (ePVS) has diagnostic and prognostic value in patients with heart failure (HF). However, it remains unclear which congestion markers (i.e., biological, imaging, and hemodynamic markers) are preferentially associated with ePVS. In addition, there is evidence of sex differences in both the hematopoietic process and myocardial structure/function., Method and Results: Patients with significant dyspnea (NYHA ≥ 2) underwent echocardiography and lung ultrasound within 4 h prior to cardiac catheterization. Patients were divided according to tertiles based on sex-specific ePVS thresholds calculated from hemoglobin and hematocrit measurements using Duarte's formula. Among the 78 included patients (median age 74.5 years; males 69.2%; HF 48.7%), median ePVS was 4.1 (percentile 25-75  = 3.7-4.9) mL/g in males (N = 54) and 4.8 (4.4-5.3) mL/g in females (N = 24). Patients with the highest ePVS had more frequently HF, higher NT-proBNP, larger left atrial volume, and higher E/e' (all p values < 0.05), but no difference in inferior vena cava diameter or pulmonary congestion assessed by lung ultrasound (all p values > 0.10). In multivariable analysis, higher E/e' and lower diastolic blood pressure were significantly associated with increased ePVS. The association between ePVS and congestion variables was not sex-dependent except for left-ventricular end-diastolic pressure, which was only correlated with ePVS in females (Spearman Rho = 0.53, p < 0.01 in females and Spearman Rho = - 0.04, p = 0.76 in males; p interaction  = 0.08)., Conclusion: ePVS is associated with E/e' regardless of sex, while only associated with invasively measured left-ventricular end-diastolic pressure in females. These results suggest that ePVS is preferably associated with left-sided hemodynamic markers of congestion.

Background: Heart failure (HF) readmission is common post-transcatheter aortic valve replacement (TAVR). Nonetheless, limited data are available regarding its predictors and clinical impact. This study evaluated the incidence, predictors, and impact of HF readmission within 1-year post-TAVR, and assessed the effects of the prescription of HF therapies at discharge on the risk of HF readmission and death., Methods: Patients included in the TAVR registry of a single expert center from 2009 to 2017 were analyzed. Competing-risk and Cox regressions were performed to identify predictors of HF readmission and death., Results: Among 750 patients, 102 (13.6%) were readmitted for HF within 1-year post-TAVR. Overall, 53 patients (7.1%) experienced late readmissions (>30 days post-TAVR), and 17 (2.3%) had multiple readmissions. In ≈30% of readmissions, no trigger could be identified. Predominant causes of readmissions were changes in medication/nonadherence and supraventricular arrhythmia. Independent predictors of HF readmission included diabetes mellitus, chronic lung disease, previous acute HF, grade III or IV aortic regurgitation, and pulmonary hypertension both at discharge from the index hospitalization but not HF therapies. Overall, HF readmission did not significantly impact all-cause mortality (hazard ratio [HR], 1.36 [95% CI, 0.99-1.85]). However, late (HR, 1.90 [95% CI, 1.30-2.78]) and multiple HF readmissions (HR, 2.10 [95% CI,1.17-3.76]) were significantly associated with all-cause mortality. Prescription of renin-angiotensin system inhibitors at discharge was associated with a lower rate of all-cause mortality, especially among patients receiving doses of 25% to <50% (HR, 0.67 [95% CI, 0.48-0.94]) and 75% to 100% (HR, 0.61 [95% CI, 0.37-0.98]) of the optimal daily dose., Conclusions: HF readmission is common within 1-year of TAVR. Late and multiple HF readmissions associate with an increased risk of long-term all-cause mortality. Baseline comorbidities (diabetes, chronic lung disease, previous acute HF) and echocardiographic findings at discharge (grade III or IV aortic regurgitation, pulmonary hypertension) identified patients at high risk of HF readmission.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling., Methods and Results: One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress-strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P < 0.05). Amongst all LV walls, the acute change in work in the septum and lateral wall of the four-chamber view correlated best and significantly with volumetric reverse remodelling (r = 0.62, P < 0.0001), with largest change seen in patients with most volumetric reverse remodelling. In multivariate linear regression analysis, including conventional parameters, such as pre-implant QRS morphology and duration, LV ejection fraction, ischaemic origin of cardiomyopathy, and the redistribution of work across the septal and lateral walls, the latter appeared as the strongest determinant of volumetric reverse remodelling after CRT (model R2 = 0.414, P < 0.0001)., Conclusion: The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Recent studies have shown that myocardial constructive work (CW) assessed by pressure-strain loops (PSLs) is an independent predictor of a volumetric response to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the role of CW in predicting the cardiac outcome of heart failure patients undergoing CRT., Methods: This is a retrospective study including 166 CRT candidates (ejection fraction [EF] ≤35%, QRS duration ≥120 milliseconds). Two-dimensional standard echocardiography and speckle-tracking echocardiography were performed before CRT and at 6-month follow-up. PSLs were used to assess myocardial CW., Results: After a median follow-up of 4 years (range 1.3-5 years), cardiac death occurred in 14 patients (8%). A multivariable Cox regression analysis including age, coronary artery disease, and septal flash showed that CW≤888 mm Hg% was the only independent predictor of cardiac mortality (hazard ratio 4.23, 95% CI 1.08-16.5, P = .03). After 6 months of CRT, a 15% reduction in left ventricular end-systolic volume was observed in 118 (71%) patients, and a CRT volumetric response was identified. Among CRT responders, the concomitant presence of CW ≤888 mm Hg% identified a subgroup of patients at high risk of cardiac death (P = .04 in the log-rank test). The addition of CW ≤888 mm Hg% to a model including age, coronary artery disease, septal flash, and CRT response caused a significant increase in model power for the prediction of cardiac death (χ 2 : 12.6 vs 25.7, P = .02)., Conclusions: The estimation of left ventricular CW by PSLs is a relatively novel tool that allows for the prediction of cardiac outcome in CRT candidates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Cardiac resynchronization therapy (CRT) plays a pivotal role in the management of patients with heart failure (HF) and wide QRS complex. However, the treatment is plagued by numerous non-responders. Aim of the study is to evaluate the role myocardial work estimated by pressure-strain loops (PSLs) in the comprehension of physiological mechanisms associated with CRT and in the prediction of CRT response., Methods and Results: Ninety-seven patients with symptomatic HF (ejection fraction: 27 ± 6%, QRS duration 164 ± 18 ms) undergoing CRT implantation according to current recommendations were retrospectively included in the study. Standard 2D and speckle tracking echocardiography were performed before CRT and at the 6-month follow-up (FU). PSL analysis allowed the calculation of global and regional myocardial constructive work (CW) and wasted work (WW). A > 15% reduction in left ventricular (LV) end-systolic volume at FU defined CRT-positive response (CRT-PR). At FU, 63 (65%) patients responded to CRT. Global CW (CWtot) was significantly increased in CRT-responders. At multivariate analysis, CWtot > 1057 mmHg% (OR 14.69, P = 0.005) and septal flash (OR 8.05, P = 0.004) were the only significant predictors of CRT-PR. CWtot was associated with the entity of CRT-induced myocardial remodelling in both ischaemic (r = -0.55, P < 0.0001) and non-ischaemic patients (r = 0.65, P < 0.0001). A CWtot < 1057 mmHg% identified 85% of non-responders with a positive predictive value of 88%., Conclusion: Patients with higher CWtot exhibit a favourable response to CRT. These data encourage further studies for the assessment of the myocardial substrate related to the functional response to CRT.

Background: Cardiac resynchronization therapy (CRT) in heart failure is plagued by too many nonresponders. The aim of the present study is to evaluate whether the estimation of myocardial performance by pressure-strain loops (PSLs) is useful for the selection of CRT candidates., Methods: Ninety-seven patients undergoing CRT were included in the study. Bidimensional and speckle-tracking echocardiography were performed before CRT and at the 6-month follow-up (FU). Conventional dyssynchrony parameters were evaluated. Left ventricular (LV) constructive work (CW) and wasted work (WW) were estimated by PSLs. Positive response to CRT (CRT+) was defined as ≥15% reduction in LV end-systolic volume at FU and was observed in 63 (65%) patients., Results: The addition of CW > 1,057 mm Hg% (area under the curve, 0.72, P < .0001) and WW > 384 mm  Hg% (area under the curve, 0.67, P = .005) to a baseline model including clinical, echocardiographic, and conventional dyssynchrony parameters significantly increased the model power (χ 2 , 25.11 vs 47.5, P < .0001). In this model, septal flash (odds ratio [OR] = 2.78; P = .001), CW > 1,057 mm Hg% (OR = 9.49; P = .002), and WW > 384 mm Hg% (OR = 16.24, P < .006) remained the only parameters associated with CRT+. The combination of CW > 1,057 mm Hg% and WW > 384 mm Hg% showed a good specificity (100%) and positive predictive value (100%) but a low sensitivity (22%), negative predictive value (41%), and accuracy (49%) for the identification of CRT+., Conclusions: The estimation of CW and WW by PSLs is a novel tool for the assessment of CRT patients. Although these parameters cannot be used by their own to select CRT candidates, they can provide further insights into the comprehension of dyssynchrony mechanisms and contribute to improving the identification of CRT responders., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Almost all attempts to improve patient selection for cardiac resynchronization therapy (CRT) using echo-derived indices have failed so far. We sought to assess: the performance of homemade software for the automatic quantification of integral 3D regional longitudinal strain curves exploring left ventricular (LV) mechanics and the potential value of this tool to predict CRT response., Methods: Forty-eight heart failure patients in sinus rhythm, referred for CRT-implantation (mean age: 65 years; LV-ejection fraction: 26%; QRS-duration: 160 milliseconds) were prospectively explored. Thirty-four patients (71%) had positive responses, defined as an LV end-systolic volume decrease ≥15% at 6-months. 3D-longitudinal strain curves were exported for analysis using custom-made algorithms. The integrals of the longitudinal strain signals (I L,peak ) were automatically measured and calculated for all 17 LV-segments., Results: The standard deviation of longitudinal strain peak (SDI L,peak ) for all 17 LV-segments was greater in CRT responders than non-responders (1.18% s -1 [0.96; 1.35] versus 0.83% s -1 [0.55; 0.99], p = 0.007). The optimal cut-off value of SDI L,peak to predict response was 1.037%.s -1 . In the 18-patients without septal flash, SDI L,peak was significantly higher in the CRT-responders., Conclusions: This new automatic software for analyzing 3D longitudinal strain curves is avoiding previous limitations of imaging techniques for assessing dyssynchrony and then its value will have to be tested in a large group of patients.

Cardiac resynchronization therapy (CRT) has had a major favourable impact on the care of patients with symptomatic heart failure, left ventricular ejection fraction<35% and enlarged QRS. Despite this, about 35% of patients who undergo CRT in accordance with current guidelines are "non-responders". Therefore, more accurate selection of CRT candidates would significantly improve patient benefit and decrease costs. In the past decade, some small non-randomized studies have shown that estimation of left ventricular dyssynchrony by echocardiography might be useful to ameliorate the selection of patients for CRT. These preliminary findings have been challenged by the results of large randomized surveys, such as the Prospect and EchoCRT trials, which demonstrated that no left ventricular mechanical dyssynchrony variable could accurately predict CRT response. In recent years, improvements in myocardial imaging techniques, and the potential of fusion imaging to facilitate our understanding of the physiological basis of dyssynchrony and plan lead delivery, have let us suppose that imaging might play a role in the future of CRT. The aim of the present paper is to provide an overview of recent advances in the field of imaging-guided CRT. The role of imaging in the assessment of CRT candidates, in guiding lead implantation, and in the optimization of CRT delivery will be addressed, together with the limitations of these new techniques., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Aims: The aim of this article is to assess the left atrial (LA) reservoir function in patients with severe aortic stenosis (AS) and to evaluate its impact on the recurrence of major adverse cardiac events (MACEs)., Methods and Results: About 128 patients (mean age 79 ± 9 years) with severe AS were included in the study. Global peak LA strain (PLAS) measured by two-dimensional speckle-tracking echocardiography (STE) during left ventricular (LV) systole represented the LA reservoir function. Overall death, hospitalization for cardiac cause, and worsening heart failure were defined as MACEs. With respect to the values observed in a control group of 20 healthy patients, PLAS resulted significantly reduced in AS. According to the multivariate linear regression analysis, LV global longitudinal strain, mitral E/e' ratio, and systolic pulmonary arterial pressure (sPAP) were the best correlates to PLAS. During follow-up, the predefined MACEs occurred in 39 patients. According to the multivariate Cox regression analysis, a PLAS <21% was a significant predictor of MACEs [hazard ratio (HR) 2.88, P = 0.04], as was coronary artery disease (HR 2.68, P = 0.004) and the New York Heart Association functional class (HR 2.08, P = 0.03)., Conclusion: In patients with severe AS, a global PLAS <21% is an independent predictor of prognosis. Given the combined influence of LV diastolic and systolic function and of LA performance on sPAP, the decline of PLAS might be considered a marker of global myocardial impairment in AS. Further studies are needed to confirm the critical role of LA relaxation in prognosis and to validate its relevance in routine clinical practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Introduction: Acutely decompensated heart failure (HF) in patients with diuretic resistance is often treated with extracorporeal ultrafiltration. Peritoneal ultrafiltration (PUF) has been proposed for the long-term management of severe HF after resolution of the acute episode. The aim of the present study was to evaluate the use of PUF in the treatment of chronic refractory HF in patients without end-stage renal disease. ♢, Methods: This multicenter (10 nephrology departments throughout Italy) retrospective observational study included patients with severe HF refractory to maximized drug treatment. The patients were proposed for PUF because they had experienced at least 3 hospital admissions in the preceding year for acutely decompensated HF requiring extracorporeal ultrafiltration. ♢, Results: Of the 48 study patients (39 men, 9 women; mean age 74 ± 9 years), 30 received 1 nocturnal icodextrin exchange, 5 required 2 daily exchanges, and 13 received 2 - 4 sessions per week of automated peritoneal dialysis. During the first year, renal function remained stable (initial: 20.8 ± 10.0 mL/min/1.73 m(2); end: 22.0 ± 13.6 mL/min/1.73 m(2)), while pulmonary artery systolic pressure declined to 40 ± 6.09 mmHg from 45.5 ± 9.18 mmHg (p = 0.03), with a significant concomitant improvement in New York Heart Association functional status. Hospitalizations decreased to 11 ± 17 days/patient-year from 43 ± 33 days/patient-year before the start of PUF (p < 0.001). The incidence of peritonitis was 1 episode in 45 patient-months. Patient survival was 85% at 1 year and 56% at 2 years. ♢, Conclusions: This study confirms the satisfactory results of using PUF for chronic HF in elderly patients.

The aim of the Best Practice guidelines on peritoneal ultrafiltration (UF) in patients with treatment-resistant advanced decompensated heart failure (TR-AHDF) is to achieve a common approach to the management of decompensated heart failure in those situations in which all conventional treatment options have been unsuccessful, and to stimulate a closer cooperation between nephrologists and cardiologists. The standardization of the case series of different centers would allow a better definition of the results published in the literature, without which they are nothing more than anecdotes. TR-AHDF is characterized by the persistence of severe symptoms even when all possible pharmacological and surgical options have been exhausted. These patients are often treated with methods that allow extracorporeal UF - slow continuous ultrafiltration (SCUF) and continuous renal replacement therapy (CRRT) - which have to be performed in hospital facilities. Peritoneal ultrafiltration (PUF) can be considered a treatment option in patients with TR-AHDF when, despite the fact that all treatment options have been used, patients meet the following criteria: • stage D decompensated heart failure (ACC/AHA classification); • INTERMACS level 4 decompensated heart failure; • INTERMACS frequent flyer profile; • chronic renal failure (estimated glomerular filtration rate <50 ml/min per 1.73 m2: KDOQI classification stage 3 chronic kidney disease); • no obvious contraindications to peritoneal UF. PUF treatment modes are derived from the treatment regimens proposed by various authors to obtain systemic UF in patients with severe decompensated heart failure, using manual and automated incremental peritoneal dialysis involving various glucose concentrations in addition to the single icodextrin exchange. These guidelines also identify a minimum set of tests and procedures for the follow-up phase, to be supplemented, according to the center's resources and policy, with other tests that are less routine or more complex also from a logistic/organizational standpoint, emphasizing the need for the patient's clinical and treatment program to involve both the nephrologist and the cardiologist. The pathophysiological aspects of a deterioration in kidney function in patients with decompensated heart failure are also considered, and the results of PUF in patients with decompensated heart failure reported in the various case series are reviewed.

Thyroid hormone (TH) has a fundamental role in cardiovascular homeostasis in both physiological and pathological conditions, influencing cardiac contractility, heart rate (HR), diastolic function and systemic vascular resistance (SVR) through genomic and non-genomic mediated effects. In heart failure (HF) the main alteration of thyroid function is referred to as "low-triiodothyronine (T3) syndrome" (LT3S) characterized by decreased total serum T3 and free T3 (fT3) with normal levels of thyroxine (T4) and thyrotropin (TSH). Even if commonly interpreted as an adaptive factor, LT3S may have potential negative effects, contributing to the progressive deterioration of cardiac function and myocardial remodeling in HF and representing a powerful predictor of mortality in HF patients. All these observations, together with the early evidence of the benefits of T3 administration in HF patients indicate that placebo-controlled prospective studies are now needed to better define the safety and prognostic effects of chronic treatment with synthetic TH in HF.

Context: Low-T(3) syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T(3) replacement therapy in patients with low-T(3) syndrome and ischemic or nonischemic dilated cardiomyopathy (DC)., Design: A total of 20 clinically stable patients with ischemic (n = 12) or nonischemic (n = 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66-77; median, 25-75th percentile) who underwent 3-d synthetic L-T(3) infusion (study group); the other 10 patients (average age 68 yr, range 64-71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T(3) (initial dose: 20 microg/m(2) body surface.d) or placebo infusion., Results: After T(3) administration, free T(3) concentrations increased until reaching a plateau at 24-48 h (3.43, 3.20-3.84 vs. 1.74, 1.62-1.93 pg/ml; P = 0.03) without side effects. Heart rate decreased significantly after T(3) infusion (63, 60-66 vs. 69, 60-76 beats per minute; P = 0.008). Plasma noradrenaline (347; 270-740 vs. 717, 413-808 pg/ml; P = 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P = 0.02), and aldosterone (175, 152-229 vs. 231, 154-324 pg/ml; P = 0.047) significantly decreased after T(3) administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T(3) administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114-158 ml/m(2) body surface; P = 0.02) and stroke volume (40, 34-44 vs. 35, 28-39 ml/m(2) body surface; P = 0.01) increased, whereas external and intracardiac workload did not change., Conclusions: In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T(3) administration.