Search

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.

International audience; 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.

International audience; Identification of asymptomatic patients at higher risk for suffering cardiac events remains controversial and challenging in Brugada syndrome (BS). In this work, we proposed an ECG-based classifier to predict BS-related symptoms, by merging the most predictive electrophysiological features derived from the ventricular depolarization and repolarization periods, along with autonomic-related markers. The initial feature space included local and dynamic ECG markers, assessed during a physical exercise test performed in 110 BS patients (25 symptomatic). Morphological, temporal and spatial properties quantifying the ECG dynamic response to exercise and recovery were considered. Our model was obtained by proposing a two-stage feature selection process that combined a resampled-based regularization approach with a wrapper model assessment for balancing, simplicity and performance. For the classification step, an ensemble was constructed by several logistic regression base classifiers, whose outputs were fused using a performance-based weighted average. The most relevant predictors corresponded to the repolarization interval, followed by two autonomic markers and two other makers of depolarization dynamics. Our classifier allowed for the identification of novel symptom-related markers from autonomic and dynamic ECG responses during exercise testing, suggesting the need for multifactorial risk stratification approaches in order to predict future cardiac events in asymptomatic BS patients. Graphical abstract Pipeline for feature selection and predictive modeling of symptoms in Brugada syndrome.

International audience; OBJECTIVE: The physiological mechanisms involved in cardio-respiratory responses to sleep apnea events are not yet fully elucidated. A model-based approach is proposed to analyse the acute desaturation response to obstructive apneas. METHODS: An integrated model of cardio-respiratory interactions was proposed and parameters were identified, using an evolutionary algorithm, on a database composed of 107 obstructive apneas acquired from 10 patients (HYPNOS clinical study). Unsupervised clustering was applied to the identified parameters in order to characterize the phenotype of each response to obstructive apneas. RESULTS: A close match was observed between simulated oxygen saturation (SaO2) and experimental SaO2 in all identifications (median RMSE = 1.3892%). Two clusters of parameters, associated with different dynamics related to sleep apnea and periodic breathing were obtained. CONCLUSION AND SIGNIFICANCE: The proposed patient and event-specific model-based analysis provides understanding on specific desaturation patterns, consequent to apnea events, with potential applications for personalized diagnosis and treatment.

International audience; An original integrated model of cardio-respiratory interactions is presented in this paper with the objective of studying the acute physiological responses evoked by obstructive sleep apnea events in adults. A comprehensive sensitivity analysis of the model is proposed during the simulation of a 20 s obstructive apnea episode using the Morris' screening method and local sensitivity analysis. The more relevant parameters are related to the following mechanisms of the physiology: (i) the fraction of oxygen in inspired air, (ii) metabolic rates (oxygen consumption rate, CO2 production rate); (iii) chemoreflex (gains and time constants) (iv) respiratory mechanics (lung compliance and unstressed volume of air in the alveoli). These results highlight significant physiological variables that may be particularly useful for the development of novel diagnostic and therapeutic strategies, integrating a virtual patient approach.

This paper proposes the integration and analysis of a closed-loop model of the baroreflex and cardiovascular systems, focused on a time-varying estimation of the autonomic modulation of heart rate in Brugada syndrome (BS), during exercise and subsequent recovery. Patient-specific models of 44 BS patients at different levels of risk (symptomatic and asymptomatic) were identified through a recursive evolutionary algorithm. After parameter identification, a close match between experimental and simulated signals (mean error = 0.81%) was observed. The model-based estimation of vagal and sympathetic contributions were consistent with physiological knowledge, enabling to observe the expected autonomic changes induced by exercise testing. In particular, symptomatic patients presented a significantly higher parasympathetic activity during exercise, and an autonomic imbalance was observed in these patients at peak effort and during post-exercise recovery. A higher vagal modulation during exercise, as well as an increasing parasympathetic activity at peak effort and a decreasing vagal contribution during post-exercise recovery could be related with symptoms and, thus, with a worse prognosis in BS. This work proposes the first evaluation of the sympathetic and parasympathetic responses to exercise testing in patients suffering from BS, through the recursive identification of computational models; highlighting important trends of clinical relevance that provide new insights into the underlying autonomic mechanisms regulating the cardiovascular system in BS. The joint analysis of the extracted autonomic parameters and classic electrophysiological markers could improve BS risk stratification. © 2018 Elsevier B.V.

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.

Objective: Purposes of this work were i) to develop an in silico model of tumor response to radiotherapy, ii) to perform an exhaustive sensitivity analysis in order to iii) propose a simplified version and iv) to predict biochemical recurrence with both the comprehensive and the reduced model. Methods: A multiscale computational model of tumor response to radiotherapy was developed. It integrated the following radiobiological mechanisms: oxygenation, including hypoxic death; division of tumor cells; VEGF diffusion driving angiogenesis; division of healthy cells and oxygen-dependent response to irradiation, considering, cycle arrest and mitotic catastrophe. A thorough sensitivity analysis using the Morris screening method was performed on 21 prostate computational tissues. Tumor control probability (TCP) curves of the comprehensive model and 15 reduced versions were compared. Logistic regression was performed to predict biochemical recurrence after radiotherapy on 76 localized prostate cancer patients using an output of the comprehensive and the reduced models. Results: No significant difference was found between the TCP curves of the comprehensive and a simplified version which only considered oxygenation, division of tumor cells and their response to irradiation. Biochemical recurrence predictions using the comprehensive and the reduced models improved those made from pre-treatment imaging parameters (AUC = 0.81 $\pm$ 0.02 and 0.82 $\pm$ 0.02 vs. 0.75 $\pm$ 0.03, respectively). Conclusion: A reduced model of tumor response to radiotherapy able to predict biochemical recurrence in prostate cancer was obtained. Significance: This reduced model may be used in the future to optimize personalized fractionation schedules.

Funding Acknowledgements Type of funding sources: None. Background Despite having all a systolic heart failure and broad QRS, patients proposed for cardiac resynchronization therapy (CRT) are highly heterogeneous and it remains extremely complicated to predict the impact of the device on left ventricular (LV) function and outcomes. Objectives We sought to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic data on the left ventricular (LV) remodeling and prognosis of CRT-candidates by the application of machine learning (ML) approaches. Methods 193 patients with systolic heart failure undergoing CRT according to current recommendations were prospectively included in this multicentre study. We used a combination of the Boruta algorithm and random forest methods to identify features predicting both CRT volumetric response and prognosis (Figure 1). The model performance was tested by the area under the receiver operating curve (AUC). We also applied the K-medoid method to identify clusters of phenotypically-similar patients. Results From 28 clinical, electrocardiographic, and echocardiographic-derived variables, 16 features were predictive of CRT-response; 11 features were predictive of prognosis. Among the predictors of CRT-response, 7 variables (44%) pertained to right ventricular (RV) size or function. Tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with a very good prediction of both CRT response (AUC 0.81, 95% CI: 0.74-0.87) and outcomes (AUC 0.84, 95% CI: 0.75-0.93) (Figure 1, Supervised Machine Learning Panel). An unsupervised ML approach allowed the identifications of two phenogroups of patients who differed significantly in clinical and parameters, biventricular size and RV function. The two phenogroups had significant different prognosis (HR 4.70, 95% CI: 2.1-10.0, p Conclusions Machine learning can reliably identify clinical and echocardiographic features associated with CRT-response and prognosis. The evaluation of both RV-size and function parameters has pivotal importance for the risk stratification of CRT-candidates and should be systematically assessed in patients undergoing CRT. Abstract Figure 1

International audience; 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.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Hospital university of Rennes INSERM - LTSI Background Non-invasive estimation of myocardial work by trans-thoracic echocardiography is a novel tool to analyze myocardial contraction efficiency during systole. Two methods are described, on using Left ventricular (LV) strain and a LV pressure estimation, and another with only LV strain integrals. The present study analyzes their utility in prediction of CRT-response. Methods and results: 243 patients implanted by a CRT according to current recommendations were retrospectively included in hospital university of Rennes. All patients had a complete trans-thoracic echocardiography at implantation and at 6-moths follow-up. Responders were defined as having a 15% decrease in indexed LV end-systolic volume at follow-up compared to baseline. Baseline characteristics are described in table 1. 25.1% were non-responders. In this group, there were more men, more ischemic cardiomyopathies with more dilated LV. Strain signals ware analyzed only in the most informative loop, the apical 4 cavities. Myocardial work estimation with LV pressure estimation was previously described. The 3 different integral of strain signal were represented in figure 1. According to ROC curves, myocardial work (particularly wasted work in septal wall with AUC = 0.718 ± 0.04) estimated with LV pressure estimation is better than strain integrals to predict LV positive remodeling (best AUC 0.631 ± 0.040) after CRT-implantation. Conclusion Left ventricular pressure estimation give useful information on top of strain curves for prediction for CRT-response. Table 1 Responders n = 182 Non-responders n = 61 Men (%) 109 (59.9%) 52 (85%) Ischemic cardiomyopathy (%) 42 (23.1%) 34 (55.7%) LVEF (%) 28 ± 6 28 ± 7 GLS (%) -9 ± 3 -7 ± 3 LVEDD (mm) 62 ± 8 67 ± 7 LVEDVi (ml/m2) 85 ± 34 88 ± 30 LVEF Left ventricular ejection fraction; GLS: global longitudinal strain; LVEDD: left ventricular end-diastolic diameter; LVEDVi: left ventricular end diastolic volume index Abstract Figure 1

International audience; Introduction Variability of arterial blood pressure (ABP) has been associated with intraventricular hemorrhage in very preterm neonates (VPT) and may predict other brain lesions assessed at term-equivalent of age (TEA). Methods This was a prospective single-center study including VPT with early invasive continuous ABP monitoring and assessed at TEA using brain magnetic resonance imaging (TEA-MRI). The association between early mean ABP (MABP) and TEA-MRI findings was modeled by multivariate logistic regression analysis using covariates selected by the LASSO method. Results Among 99 VPT, the LASSO procedure selected consecutive periods of lowest MABP of 30 min on day 1 (d1) and 10 min on day 2 (d2) as the most relevant durations to predict TEA-MRI findings (OR [95% CI], 1.11 [1.02-1.23], p = 0.03 and 1.13 [1.01-1.27], p = 0.03, respectively). ROC curve analysis showed optimal thresholds at 30.25 mmHg on d1 and 33.25 mmHg on d2. This significant association persisted after adjustment with covariates including birthweight, gestational age, sex, and inotrope exposure. Final models selected by LASSO included the decile of the birthweight and lowest MABP for 30 min on d1 and 10 min on d2, for which the areas under the ROC curve were 74% and 75%, respectively. Conclusion Early continuous ABP monitoring may predict brain TEA-MRI findings in VPT. Impact Early arterial blood pressure monitoring may contribute to predicting brain damage upon MRI at term-equivalent of age for infants born very preterm. Careful blood pressure continuous monitoring in very preterm infants may identify infants at risk of long-term brain damage. Umbilical artery catheterization provides the best option for continuously monitoring arterial blood pressure in very preterm infants.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): ANR - Maestro project Background Stratification of aortic stenosis patients remains challenging and robust indices are required. Myocardial work assessment is a new afterload independent alternative to evaluate left ventricular function. Although, this method was developed in patients with normal aortic valve. We previously developed an integrated cardiovascular system simulated by a computational model to estimate non-invasively myocardial work in aortic stenosis patients* (figure 1A). In the present study, we tested our model in a prospective population of AS patients. Method and results 9 patients with severe AS (aortic valve area < 1cm2) were included. A complete trans-thoracic echocardiography with a non-invasive blood pressure by brachial artery cuff were realized immediately before a left heart catheterization to have an invasive left ventricular pressure. Myocardial work is then calculated with non-invasive and invasive LV pressure combined to LV strain curves. For constructive and wasted work, root mean squared between invasive and estimated measures were respectively r2 = 0.92 and r2 = 0.94 (figure 1B) Conclusion The proposed model is efficient to estimate non-invasively myocardial work indices in AS-patients. These afterload independent indices could permit in future to better stratify this population. *Owashi KP, Hubert A and al. Model-based estimation of left ventricular pressure and myocardial work in aortic stenosis. PlosOne 2020. Mar 3;15(3):e0229609 Abstract Figure 1

Funding Acknowledgements Type of funding sources: None. Objective The best modality to assess diastolic function in CRT-candidates is an object of debate and the relationship between diastolic function, CRT-response and survival are not clearly understood. Purpose of the study: 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 193 patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Patients were stratified according to DD grades (grade I to III). CRT-response was defined as a reduction of left ventricular (LV) end-systolic volume >15% at 6-month follow-up (FU). The primary endpoint was defined as a composite of heart transplantation, LV assisted device implantation or all-cause death during FU. Results During FU, 132 (68%) patients were CRT-responders. CRT delivery was associated with diastolic function degradation in non-responders. Grade I DD was able to predict CRT-response with a sensitivity, specificity and accuracy of 70%, 65%, and 63%, respectively. After a median period of 35 months, the primary endpoint occurred in 29 (15%) patients. Grade I DD was associated with a better outcome [HR 0.26 95% CI: (0.10-0.66)], independently from ischemic cardiomyopathy, LV dyssynchrony and CRT-response (Table 1). Non-responders with grade II or grade III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06) Figure 1. Conclusions Grade I DD is associated with LV remodelling after CRT and is an independent predictor of prognosis in CRT candidates. Abstract Figure.

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 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.

Background 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 analyze left ventricular function. Purpose We propose a new semi-automated method to calculate SVL area and explore the added value of this index for diastolic function assessment. Methods 50 patients (25 amyloidosis, 25 HFpEF) were included in the study and compared with 25 healthy control subjects. All patients underwent standard echocardiography. SVL area were also assessed. Results 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 Conclusion Strain-volume loops 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. Figure 1 Funding Acknowledgement Type of funding source: None

Background Although patients with typical left bundle branch block (LBBB) show greater efficacy of cardiac resynchronization therapy (CRT), there is a wide range of responses to CRT with a subset of patients showing little or no improvement. Recently, it has been shown that combination of echo-based parameters of LV dyssynchrony and QRS duration helped to improve the prediction of the response to CRT. However, the interpretation of features extracted from echocardiography could be difficult due the complexity of mechanisms involved in cardiac contraction. Computational modelling could help to improve the interpretation of myocardial strains in LBBB patients before implantation. Purpose Purpose of the study is to propose a patient-specific model-based approach in order to assist the analysis of myocardial strains and to improve the interpretability of echo-based parameters. Methods The proposed model of the cardiovascular system integrates four main sub-models: 1) cardiac electrical system, 2) right and left atrium, 3) multi-segment right and left ventricles and 4) systemic and pulmonary circulations. Patient-specific simulations of myocardial strains were obtained by coupling the computational model and the clinical data to a parameter identification algorithm (Figure 1, upper panel). The proposed approach was evaluated on data obtained from 10 LBBB patients, including ischaemic (n=5) and non-ischaemic (n=5) cardiomyopathy. The localisation of scar was determined by cardiac MRI. Bull's-eye representations of the electrical activation time and contractility levels were analysed. Results The comparison between simulated and experimental strains for the 10 subjects reflects a satisfying adaptation of the model to different strain morphologies. The mean errors between real and synthesized signals are equal to 3.72±0.91. The lower panel of Figure 1 presents simulated (black line) and experimental (red line) myocardial strain signals for selected LBBB patients with a lateral ischaemia, anterior ischaemia and non-ischaemia. The bull's-eye representations of electrical activation delay and contractility levels, estimated from the model-based approach, for ischemic and non-ischemic LBBB is included in the figure. Contractility bull's-eye results allow ischaemic and non-ischaemic cases distinction, where low levels of contractility could be associated with damaged tissues. Conclusion Identified parameters show significant electrical conduction, mechanical activation delays for the LBBB patient. Hypocontractile myocardial segments were successfully localized from the model-based approach in both ischemic and non-ischemic patients. Funding Acknowledgement Type of funding source: None

Background The relationship between diastolic dysfunction (DD) and outcome after CRT is debated. Purpose Purpose of this study was to evaluate the role of DD in predicting all-cause mortality in heart failure patients undergoing CRT. Methods One-hundred ninety-three patients (age: 67±11 years, QRS width: 167±21 ms, LVEF 28±8%) 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 according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging. A reduction of LV end-systolic volume >15% at 6-month follow-up (FU) identified CRT-responders and was observed in 132 (68%) patients. Results During a median 35 months FU, 29 (15%) patients died. Through multivariable analysis, coronary artery disease, NYHA functional class and grade I DD were shown to be independent predictors of prognosis (Table 1). Grade I DD was associated with a longer survival rate in both responders and non responders (Figure 1). Non responders with grade II-III DD had the worse outcome (HR 12.5 [3.56–44.04], p Conclusions Better diastolic function at baseline is associated with an improved survival after CRT implantation, independently of CRT-response. Funding Acknowledgement Type of funding source: None

International audience; This paper proposes a patient-specific model-based estimation of myocardial strain signals and the evaluation of echo-based parameters, adapted to patients with left bundle branch block (LBBB). The left ventricle (LV) was divided into 16 segments in order to evaluate concurrently different regions at the ventricular contraction process. For each LV segment, some parameters, associated with the active and passive components of the cardiac muscle, the electro-mechanical driving function and the electrical depolarization time, were identified using evolutionnary algorithms. The proposed approach was evaluated on data obtained from 3 LBBB patients. From patient-specific simulations, we also analysed electrical activation delay and myofiber contractility in LV segments. A close match was observed between experimental and simulated myocardial strain curves for all the subjects. The root mean square error (RMSE) is equal to 2.87(± 1.00), 2.49(± 0.55) and 3.63(± 0.81) for the anterior ischemic, the lateral ischemic and the non-ischemic LBBB patients, respectively. The proposed patient-specific model-based approach may be a useful tool for understanding LV mechanical dyssynchrony and identifying patients suitable for cardiac resynchronization therapy (CRT). © 2020 Creative Commons; the authors hold their copyright.

International audience; 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.

International audience; The objective of the current study was to propose a sensitivity analysis of a 3D left ventricle model in order to assess the influence of parameters on myocardial mechanical dispersion. A finite element model of LV electro-mechanical activity was proposed and a screening method was used to evaluate the sensitivity of model parameters on the standard deviation of time to peak strain. Results highlight the importance of propagation parameters associated with septal and lateral segments activation. Simulated curves were compared to myocardial strains, obtained from echocardiography of one healthy subject and one patient diagnosed with intraventricular dyssynchrony and coronary artery disease. Results show a close match between simulation and clinical strains and illustrate the model ability to reproduce myocardial strains in the context of intraventricular dyssynchrony.

Brugada syndrome (BS) is a genetic pathology that might cause sudden cardiac death (SCD) in patients with a structurally normal heart. Repolarization disorders have been postulated as a potential substrate for triggering cardiac arrhythmia in BS, that usually occur at rest or during sleep. In this paper, we have characterized ventricular repolarization markers during sleep on patients suffering from BS. To this end, standard 12-lead ECG recordings were analyzed in a population of 110 BS patients (25 symptomatic). The QT and the T-wave peak to T-wave end intervals (respectively QT and Tpe) were assessed from lead V5. The linear relationship between these markers and the instantaneous heart rate period (RR interval) are determined during each hour and for the whole sleep period. From the models obtained, corrected QT and Tpe measures were then estimated for each patient at 60 beats/min (QT 60 and Tpe 60 ) and at the mean heart rate observed during the involved time interval ($Q{T_{\overline {{\mathbf{HR}}} }}$ and $Tp{e_{\overline {{\mathbf{HR}}} }}$). Results show larger values for symptomatic patients in all markers, with significant differences with respect to the asymptomatic group in the case of Tpe (Tpe 60 : p = 0.0012; Tpe HR : p = 0.0014). Moreover, the temporal profiles of these markers reveal major differences among BS subgroups during the last 3 hours of sleep, where symptomatic patients presented increased QT 60/HR (p = 0.01) and T pe 60/HR (p < 0.001), as compared to the initial sleep hours. We conclude that BS patients present different repolarization properties according to their symptomatology, especially during the final stage of sleep.

Aims. 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 after cardiac resynchronization therapy (CRT). Also, we sought to test the respective value of automatically extracted parameters from left ventricular (LV) strain curves recorded in apical 4-chamber view as compared to the other echocardiographic views. Methods and results; This is a machine learning study based on a dataset of 161 patients who were treated by CRT according to current ESC-guidelines. The longitudinal strain curves of the 6 LV-segments of the left ventricle were plot for the three different apical views. Several features as times or integrals were extracted as previously published. These features were classified by importance using the out-of-bag method(fig1). Half of the most important features come from the 4-chamber view and a third from the 2-chamber view. The correlation between the most important features was studied to determine the relationship between them. Almost all the features from the 2-chamber and apical long-axis views are correlated with others and generally with one acquired from the 4-chamber view. Conclusion The high number of important features indicate the relevance of the 4-chamber as unique view for applying machine learning approaches on strain curves. Optimizing selection of patients for CRT should be possible just on the dataset coming from one apical 4-chamber view. Abstract 539 Figure. fig1

Background The noninvasive assessment of myocardial work by pressure-strain loops (PSL) analysis is a recently introduced tool to estimate myocardial performance. PSL analysis cannot be applied to patients having an obstacle to LV ejection, as in the case of aortic stenosis (AS), because of the difficulty to estimate left ventricular (LV) pressure. The purpose of this work is to propose a non-invasive model-based estimation of the left ventricular pressure curve in AS patients in order to evaluate myocardial work indices. Methods Twelve patients with moderate-to-severe AS underwent cardiac catheterization to acquire the LV pressure (Pexp-LV). All patients underwent a standard trans-thoracic echocardiography to extract regional myocardial strain curves and estimate the aortic valve area (AVA). Systolic and diastolic arterial pressures were also measured. The proposed cardiovascular system (CVS) model is composed of four main coupled sub-models simulating: i) cardiac electrical activities, ii) cardiac cavity, iii) the systemic and pulmonary circulation, and iv) cardiac valves (Figure 1, upper panel). A 2-step parameter identification strategy, based evolutionary algorithms, was implemented to learn LV parameters from Pexp-LV and to estimate patient-specific model-based LV pressure curves (Pmodel-LV) starting from parameters obtained from non-invasive hemodynamics. Global myocardial constructive work (GCW) and myocardial wasted work (GWW) were calculated using Pexp-LV and Pmodel-LV. Results A close match was observed between Pexp-LV and Pmodel-LV, with a mean total relative error of 12.27% (range 5.9% to 17.40%). When considering GCW and GWW, global correlation was equal to 0.92 (p Conclusions A model-based approach can be used to estimate LV pressure and myocardial work indices in patients with AS, and be provide a promising tool for the assessment of myocardial performance in patients with AS Funding Acknowledgement Type of funding source: None

International audience; Purpose - The area of left ventricular (LV) pressure-strain loop (PSL) is used as an index of regional myocardial work. The purpose of the present work is to compare the main segmental PSL markers and the derived global work indices, when they are calculated using an estimated pressure signal or an observed pressure signal.Methods and results - In nine patients implanted with a bi-ventricular pace-maker (CRT), LV pressure was invasively measured in five conditions: CRT-off, LV-pacing, right ventricular-pacing and two different CRT-pacing. For each condition, systolic blood pressure was measured by brachial artery cuff-pressure and transthoracic echocardiography loops were recorded simultaneously. The error and relative root mean square error (rRMSE) between measured and estimated pressure were calculated for each patient and each configuration. Correlation coefficient (R2) and Bland-Altman (BA) analysis were performed for PSL area and work indices. A total of 43 different haemodynamic conditions were compared (774 segmental PSL). The global rRMSE between estimated and measured LV-pressure was 12.3 mmHg. The estimated and measured segmental LV-PSL were strongly correlated, with an R2 of 0.98. BA analysis shows that the mean bias for the estimation of segmental LV-PSL area is 86.0 mmHg.%. A significant bias effect with linearly increasing error with pressure values is observed. R2 ≥ 0.88 and a mean bias in BA analysis ≤41.4 mmHg.% was observed for the estimation of global myocardial work indices.Conclusion - The non-invasive estimation for LV pressure-strain loop area and the global myocardial work indices obtained from LV-PSL strongly correlates with invasive measurements.

International audience; 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 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, 25.11 vs 47.5, P 1,057 mm Hg% (OR = 9.49; P = .002), and WW > 384 mm Hg% (OR = 16.24, P 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.

Background The relationship between diastolic dysfunction (DD) and outcome after CRT is debated. The purpose of this study was to evaluate the role of DD in predicting all-cause mortality in heart failure patients undergoing CRT. Methods One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms, LVEF 28 ± 8%) 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 according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging. A reduction of LV end-systolic volume > 15% at 6-month follow-up (FU) identified CRT-responders and was observed in 132 (68%) patients. Results During a median 35 months FU, 29 (15%) patients died. Through multivariable analysis, coronary artery disease [HR 2.21 (1.00–4.89) P = 0.05], NYHA [HR 2.92 (1.45–5.87), P = 0.003] and grade I DD [HR 0.34 (0.13–0.89)] were shown to be independent predictors of prognosis ( Table 1 ). Grade I DD was associated with a longer survival rate in both responders and non-responders ( Fig. 1 ). Non-responders with grade II-III DD had the worse outcome [HR 12.5 (3.56–44.04), P Conclusion Better diastolic function at baseline is associated with improved survival after CRT implantation, independently of CRT-response.

Background Non-invasive estimation of myocardial work by transthoracic echocardiography is a novel tool to analyse myocardial contraction efficiency during systole. Two methods are described, on using Left ventricular (LV) strain and a LV pressure estimation, and another with only LV strain integrals. The present study analyses their utility in prediction of CRT-response. Methods and results In total, 243 patients implanted by a CRT according to current recommendations were retrospectively included in hospital university of Rennes. All patients had a complete transthoracic echocardiography at implantation and at 6-moths follow-up. Responders were defined as having a 15% decrease in indexed LV end-systolic volume at follow-up compared to baseline. Baseline characteristics are described in Table 1 ; 25.1% were non-responders. In this group, there were more men, more ischemic cardiomyopathies with more dilated LV. Strain signals were analysed only in the most informative loop, the apical 4 cavities. Myocardial work estimation with LV pressure estimation was previously described. The 3 different integral of strain signal were represented in Fig. 1 . According to ROC curves, myocardial work (particularly wasted work in septal wall with AUC = 0.718 ± 0.04) estimated with LV pressure estimation is better than strain integrals to predict LV positive remodelling (best AUC 0.631 ± 0.040) after CRT-implantation. Conclusion Left ventricular pressure estimation give useful information on top of strain curves for prediction for CRT-response.

Background Patients undergoing cardiac resynchronisation therapy are heterogeneous. Therefore, the prediction of CRT-response and outcome is challenging. The aim of this study was to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic variables on the left ventricular (LV) remodelling and prognosis of CRT-candidates by the application of machine-learning (ML) approaches. Methods In total, 193 patients undergoing CRT (mean age 67 ± 11 years, QRS width: 167 ± 21 msec) were prospectively included in this multicentre study. We used a combination of the Boruta algorithm and random forest methods (RF) to identify features predicting both CRT-volumetric response and prognosis. The model performance was tested by the area under the receiver-operating curve (AUC). We also applied the K-medoid method to identify clusters of phenotipically-similar patients. Results From 28 clinical, electrocardiographic, and echocardiographic-derived variables, 16 features were predictive of CRT-response, and 11 features were predictive of prognosis. Among the predictors of CRT-response, 6 variables (38%) pertained to right ventricular (RV) size or function. The tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with a very good prediction of both CRT-response (AUC: 0.81, 95% CI: 0.74–0.87) and outcome (AUC 0.84, 95% CI: 0.75–0.93) ( Fig. 1 A–B). An unsupervised ML approach allowed the identifications of two phenogroups of patients who differed significantly in clinical parameters, biventricular size and RV function and had significantly different prognosis (log-rank P Table 1 ). Conclusions ML can reliably identify clinical and echocardiographic features associated with CRT-response and prognosis. Our results underscore the value of the assessment of RV-size and function parameters for the risk stratification of CRT-candidates.

Background: Inflammatory adhesions result from an inflammatory response of the peritoneum during an intra-abdominal inflammatory process secondary to thermal or mechanical injury, infection, radiation, ischemia, dissection, abrasion or foreign body reaction. Adhesions produce consequences such as: infertility, intestinal obstruction, and pelvic-abdominal pain. The objective of this study is to evaluate the effects of Meloxicam, a selective cyclooxygenase-2 inhibitor, on the formation of postoperative peritoneal adhesions in an experimental animal model. Methods: Twenty female Wistar rats were submitted to laparotomy. Postoperative peritoneal adhesions were induced by scorching the serous surface of the colon. The animals were randomly divided into two experimental groups: one group received Meloxicam intramuscularly for 7 days, and the other served as a control group. They were sacrificed and evaluated at 15 days. Results: In the animals given Meloxicam, it was observed that a decrease in number (p = 0.018), severity (p = 0.004), extension (p = 0.011), density (p = 0.023), degree of inflammation (p = 0.002), vascular proliferation (p = 0.004) and fibrosis (p = 0.029) of adhesions, compared to the control group. Conclusion: In conclusion, this study demonstrated that the administration of Meloxicam intramuscularly significantly decreases the formation of postoperative peritoneal adhesions and, therefore, may be useful in their prevention. The effects of Meloxicam could not only be due to its anti-inflammatory action, but also to its effects on the expression of the Vascular Endothelial Growth Factor.

International audience; Aims: Assessment of left ventricular (LV) volumes and ejection fraction (LVEF) with cardiac imaging is important in the selection of patients for cardiac resynchronization therapy (CRT). Several observational studies have explored the role of imaging-derived LV dyssynchrony parameters to predict the response to CRT, but have yielded inconsistent results, precluding the inclusion of imaging-derived LV dyssynchrony parameters in current guidelines for selection of patients for CRT. Methods: The EuroCRT is a large European multicentre prospective observational study led by the European Association of Cardiovascular Imaging. We aim to explore if combing the value of cardiac magnetic resonance (CMR) and echocardiography could be beneficial for selecting heart failure patients for CRT in terms of improvement in long-term survival, clinical symptoms, LV function, and volumes. Speckle tracking echocardiography will be used to assess LV dyssynchrony and wasted cardiac work whereas myocardial scar will be assessed with late gadolinium contrast enhanced CMR. All data will be measured in core laboratories. The study will be conducted in European centres with known expertise in both CRT and multimodality cardiac imaging.

Symptoms such as ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest, especially during sleep, suggesting that the autonomic nervous system (ANS) function may be relevant in the arrhythmogenesis of the disease. The aim of this work was to assess the ANS response captured by a non-linear heart rate variability (HRV) measure in 69 patients diagnosed with BS, who underwent a standardized physical stress test. Heart rate complexity (HRC) was evaluated by the power-law scaling analysis (Beta slope) during rest, exercise, recovery and rest post-recovery, in order to discriminate between symptomatic and asymptomatic BS patients. Symptomatic patients showed a significant reduction in HRC in comparison to asymptomatic subjects, after exertion (p=0.015); during the whole recovery period (p=0.023), and, in particular within the passive recovery phase (p=0.025), as well as during rest post-recovery (p=0.022). Based on these results, symptoms could be associated with a lower ANS complexity during the stress test stages where parasympathetic activity is predominant. Therefore, the proposed HRV indicators could be of help in the risk stratification of asymptomatic patients.

Aim This work aims to evaluate a novel semi-automatic tool for the assessment of volume-strain loops by transthoracic echocardiography (TTE). The proposed method was evaluated on a typical model of left ventricular (LV) diastolic dysfunction: the cardiac amyloidosis. Method 18 patients with proved cardiac amyloidosis were compared to 19 controls, from a local database. All TTE were performed using Vivid E9 or E95 ultrasound system. The complete method includes several steps: 1) extraction of LV strain full traces from apical 4 and 2 cavities views, 2) estimation of LV volume from these two traces by spline interpolations, 3) resampling of LV strain curves, determined for the same cardiac beat, (in apical 4-, 2- and 3- cavities views) as a function of pre-defined percentage increments of LV-volume and 4) calculation of the LV volume-strain loop area. (Figure 1, panel B) Results (Table 1): LVEF was similar between both groups whereas global longitudinal strain was significantly lower in amyloidosis group (−14.4 vs −20.5%; p Table 1 Amyloidosis (N=18) Controls (N=19) p Global strain-volume loop area (%.mL) 36.5±21.3 120.0±54.2 Figure 1 Conclusion LV volume-strain loop area appears a very promising new tool to assess semi-automatically diastolic function. Future applications will concern the integration of LV volume-strain loop area as novel feature in machine-learning approach.

The present study aimed to further unravel the effects of nasal continuous positive airway pressure (nCPAP) on the cardiovascular and respiratory systems in the neonatal period. Six-hour polysomnographic recordings were first performed in seven healthy newborn lambs, aged 2–3 days, without and with nCPAP application at 6 cmH2O (nCPAP-6), in randomized order. The effects of nCPAP-6 on heart rate variability, respiratory rate variability, and cardiorespiratory interrelations were analyzed using a semiautomatic signal processing approach applied to ECG and respiration recordings. Thereafter, a cardiorespiratory mathematical model was adapted to the experimental conditions to gain further physiological interpretation and to simulate higher nCPAP levels (8 and 10 cmH2O). Results from the signal processing approach suggest that nCPAP-6 applied in newborns with healthy lungs: 1) increases heart rate and decreases the time and frequency domain indices of heart rate variability, especially those representing parasympathetic activity, while increasing the complexity of the RR-interval time series; 2) prolongs the respiratory cycle and expiration duration and decreases respiratory rate variability; and 3) slightly impairs cardiorespiratory interrelations. Model-based analysis revealed that nCPAP-6 increases the heart rate and decreases respiratory sinus arrhythmia amplitude, in association with a reduced parasympathetic efferent activity. These results were accentuated when simulating an increased CPAP level. Overall, our results provide a further understanding of the effects of nCPAP in neonates, in the absence of lung disease.NEW & NOTEWORTHY Application of nasal continuous positive airway pressure (CPAP) at 6 cmH2O, a level very frequently used in newborns, alters heart and respiratory rate variability, as well as cardiorespiratory interrelations in a full-term newborn model without lung disease. Moreover, whereas nasal CPAP at 6 cmH2O decreases parasympathetic efferent activity, there is no change in sympathetic efferent activity.

International audience; 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: 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.

Aim This work aims to evaluate a novel semi-automatic tool for the assessment of volume-strain loops by transthoracic echocardiography (TTE). The proposed method was evaluated on a typical model of left ventricular (LV) diastolic dysfunction: the cardiac amyloidosis. Method Seventeen patients with proved cardiac amyloidosis and 18 patients with heart failure with preserved ejection fraction (HFpEF) were compared to 19 controls, from a local database. All TTE were performed using Vivid E9 or E95 ultrasound system (General Electrics Healthcare, Horten, Norway). The complete method includes several steps: 1) extraction of LV strain full traces from apical 4 and 2 cavities views, 2) estimation of LV volume from these two traces by spline interpolations, 3) resampling of LV strain curves, determined for the same cardiac beat, (in apical 4-, 2- and 3- cavities views) as a function of pre-defined percentage increments of LV-volume and 4) calculation of the LV volume-strain loop area. ( Fig. 1 , panel A) Results ( Table 1 ): LVEF was similar between all groups whereas global longitudinal strain was significantly lower in amyloidosis group than controls (−14.4 vs. −20.5%; P Fig. 1 , panel B, HFpEF in green). This area was better correlated with mean e’ (r = 0.650, P Conclusion LV volume-strain loop area appears a very promising new tool to assess semi-automatically diastolic function.

Implantable accelerometers have been already proposed for the continuous monitoring of heart wall motion. Although a number of markers extracted from cardiac accelerometry have been associated with contractility, they are mainly based on uniaxial (1D) sensors, that not always reflect this relationship consistently. In this work, 3D-acceleration signals obtained from sensors located at the left ventricle (LV) of two anesthetized pigs were acquired at baseline and during dobutamine infusion, along with LV pressure. For each cardiac cycle, the reference contractility was estimated as the maximal LV pressure first derivative $(dP/dt_{max})$ . The peak of maximum energy (PE) and the peak of acceleration (PA) were computed for each accelerometry axis and for the acceleration modulus. Different polynomial curves were fitted to scatterplots representing $dP/dt_{max}$ vs. each extracted feature, in order to quantify fitting qualities. Three-dimensional features, and particularly PE, seemed to better represent contractility. Based on results, inotropism seems to be quadratically related to acceleration-based features, which may lead to more reliable LV contractility estimates when based on 3D data.

International audience

International audience; 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

International audience; Ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest and especially during sleep, suggesting that changes in the autonomic modulation may play an important role in arrhythmogenesis. The autonomic response to exercise and subsequent recovery was evaluated on 105 patients diagnosed with BS (twenty-four were symptomatic), by means of a time-frequency heart rate variability (HRV) analysis, so as to propose a novel predictive model capable of distinguishing symptomatic and asymptomatic BS populations. During incremental exercise, symptomatic patients showed higher HFnu values, probably related to an increased parasympathetic modulation, with respect to asymptomatic subjects. In addition, those extracted HRV features best distinguishing between populations were selected using a two-step feature selection approach, so as to build a linear discriminant analysis (LDA) classifier. The final features subset included one third of the total amount of extracted autonomic markers, mostly acquired during incremental exercise and active recovery, thus evidencing the relevance of these test segments in BS patients classification. The derived predictive model showed an improved performance with respect to previous works in the field (AUC= 0.92 +/- 0.01; Se= 0.91 +/- 0.06; Sp= 0.90 +/- 0.05). Therefore, based on these findings, some of the analyzed HRV markers and the proposed model could be useful for risk stratification in Brugada syndrome.

A novel integrated model of cardio-respiratory interactions is presented in this paper with the objective of understanding the acute physiological response due to events of sleep apneas and hypopneas in adults. A formal sensitivity analysis is proposed, focused on the chemoreflex and metabolism gas exchange components of this model, during the simulation of a 20-seconds obstructive apnea episode. During apnea, the most influent parameters were those related to metabolic rates. After the apnea, the most relevant parameters were the one related with the the amplitude gains of the central and peripheral chemoreflex. A first qualitative comparison has shown a close behaviour between experimental and simulated cardiorespiratory responses to apnea. These results highlight the influent components of chemoreflex control and the metabolic rates and provides key information towards the definition of patient-specific parameters.

The etiology of Brugada syndrome (BS) is complex and multifactorial, making risk stratification in this population a major challenge. Since changes in the autonomic modulation of these patients are commonly related to arrhythmic events, we analyze in this work whether the response to head-up tilt (HUT) testing on this population may provide useful, complementary information for risk stratification. In order to perform this analysis, a coupled physiological model integrating the cardiac electrical activity, the cardiovascular system and the baroreceptors reflex control of the autonomic function, in response to HUT is proposed. A sensitivity analysis was performed, based on a screening method, evidencing the influence of cardiovascular parameters on blood pressure and of baroreflex regulation on heart rate. The most sensitive parameters have been identified on a set of 20 subjects (8 controls and 12 BS patients), so as to assess subject-specific model parameters. According to the results, controls showed an increased sympathetic modulation after tilting, as well as a reduced left ventricular contractility was observed in symptomatic, with respect to asymptomatic BS patients. These results provide new insights regarding the autonomic mechanisms regulating the cardiovascular system in BS which might be used as a complementary source of information, along with classical electrophysiological parameters, for BS risk stratification.

Objective Ventricular arrhythmias in Brugada syndrome (BS) mainly occur at rest, especially during nighttime, suggesting that parasympathetic activity at night may play an important role in the arrhythmogenesis of the disease. This study examined and compared the autonomic function of symptomatic and asymptomatic BS patients overnight. Approach We analyzed various heart rate variability (HRV) and heart rate complexity (HRC) markers in a clinical series including 87 BS patients, where 23 were symptomatic. Main results Statistically significant differences were found in markers MIRR, SDNN, SDANN, [Formula: see text] and SampEn, suggesting that symptomatic patients may be related to lower heart rate variability and complexity values, as well as to greater circadian fluctuations overnight. Significance The results provide further evidence for the role of autonomic imbalance in the pathophysiology of BS, highlighting the relevance of nighttime analysis to the unmasking of significant ANS changes. Based on these outcomes, the role of HRV and HRC assessment at night could be a step forward towards the understanding of BS and the risk for the occurrence of symptoms in these patients, with a potential future impact on therapeutic strategies.

Although previous studies have suggested that the analysis of mechanical dyssynchrony can improve prediction of response to cardiac resynchronization therapy (CRT), current guidelines still neglect the value of left ventricular (LV) mechanical dyssynchrony assessed by imaging techniques

Background Recent studies have shown that myocardial constructive work (CW) assessed by pressure strain loops (PSLs) is an independent predictor of cardiac resynchronization therapy response (CRT + ). Purpose of the study To assess the role of global myocardial CW in the prediction of long-term outcome of patients undergoing CRT. Methods 2D-standard and speckle-tracking echocardiography were performed in 166 CRT candidates (mean age: 66 ± 10 years, males: 69%, QRS duration: 165 ± 19 ms) before CRT implantation and at 6-month follow-up. Left-ventricular (LV) end-systolic volume reduction > 15% at 6-month follow-up defined CRT + and occurred in 48 (29%) patients. Results After a median FU of 4 years (range: 1.3–5 years), all-cause death occurred in 28 patients (17%), cardiac death in 14 patients (8%). At multivariable Cox-regression analysis, including age, ischemic etiology, septal flash, and CRT + , CW and age were the only prognostic predictors. A CW ≤ 888 mmHg% (AUC 0.71, P = 0.007 and AUC 0.67, P = 0.004 for cardiac and all-cause mortality) was associated with an increased cardiac and all-cause mortality risk. Conclusions The estimation of left-ventricular CW by PSLs curves is a relatively novel tool, which allows the prediction of long-term prognosis in CRT candidates.

International audience; Aim Modulation of ST-segment elevation (STE) and tachyarrhythmic events by the autonomic nervous system (ANS) has been reported in patients with Brugada syndrome (BS). This study examined and compared the autonomic characteristics and STE in symptomatic vs. asymptomatic patients with BS. Methods and result We studied 40 symptomatic and 78 asymptomatic patients (mean age = 46.1 ± 13.7 years; 88 men) who underwent 24 h, 12-lead electrocardiograms, and exercise and a head-up tilt tests. Heart rate variability was examined and STE was measured at 5 points between 100 and 140 ms after the onset of 1 min averaged QRS complexes, and the type 1 Brugada pattern was automatically identified. 'Type 1 Brugada burden' was the percentage of averaged type 1 complexes. All measurements were made over 24 h, and during day and night times. During daytime, the variation coefficients of standard deviation of normal-to-normal intervals were 39.0 ± 12.3 vs. 34.1 ± 14.5 ms (P< 0.05) and high frequency normalized units were 39.9 ± 16.9 vs. 33.9 ± 16.2% (P< 0.05) in symptomatic vs. asymptomatic patients, respectively. ST-segment elevation was similar in symptomatic and asymptomatic patients at all time points. The type 1 Brugada burden in V2 was 38.7 ± 33.6% in the symptomatic vs. 24.3 ± 35.2% in the asymptomatic sample, a statistically non-significant difference. Conclusion This analysis of ANS did not identify sensitive predictors of arrhythmic events in patients with BS. We observed, however, greater fluctuations in sinus node response to ANS in symptomatic patients. The type 1 Brugada electrocardiographic pattern was not as reliable a predictor of arrhythmic risk as previously reported. © Published on behalf of the European Society of Cardiology. All rights reserved.