Classification Model of Heart Transplant Outcomes Based on Features of Left Ventricular Functional Geometry

The function of the transplanted heart can be significantly affected by acute allograft rejection, chronic rejection, high blood pressure. These factors may induce cardiac remodelling with further adverse consequences for the patients. Dynamic change in the configuration of the left ventricle (LV) from end diastole to end systole (LV functional geometry) is an important factor of the heart pump function. The objective of this study is to evaluate the time dependent changes in parameters of LV functional geometry in the transplanted heart and to assess relations between the changes and adverse outcomes of the heart transplantation (HT). We used linear discriminant analysis (LDA) to build classification models based on either the standard echocardiographic parameters of LV systolic function and global longitudinal strain (GLS) or LV function geometry indexes. The training set for model building included data from patients with different degrees of systolic dysfunction. Using the models, we retrospectively classified data from 31 patients after orthotropic HT. In contrast to the LDA models based on the standard echocardiographic characteristics and GLS, the model based on the LV functional geometry data showed high accuracy in predicting allograft rejection and development of the heart failure in the HT patients. © 2018 Creative Commons Attribution

Ремоделирование сердца недоношенных детей

Epidemiological studies consistently have suggested an association between low birth weight and increased rate of cardiovascular morbidity and mortality in adult life. Preterm birth, as one of the leading causes of the low birth weight, is associated with cardiovascular remodeling which consists of changes in heart chambers geometry and contraction-relaxation mode, ventricular hypertrophy, arterial wall structure and density changes. Several types of preterm birth are discussed: prematurity, associated with placental insufficiency and fetal growth restriction, preterm leaking of amniotic fluid, and twin pregnancy. DNA methylation process under the influence of epigenetic factors of the intrauterine and early postnatal development is suggested as a one of the main mechanism of cardiovascular remodeling in preterm infants. The other mechanisms of cardiovascular remodeling are discussed in terms of the modern intrauterine programming concept. The early diagnostics and prevention of cardiovascular diseases in preterm born children are discussed. The treatment during prenatal and early postnatal periods as well as prevention of the remodeling causes could diminish and even reverse the development of the negative cardiovascular events and diseases in later life according to the so called concept of “one thousand days opportunities window”. © 2020 Izdatel'stvo Meditsina. All rights reserved.Работа выполнена при финансовой поддержке ФГБОУ ВО УГМУ Минздрава России в рамках госзадания ИИФ УрО РАН (тема № АААА-А18-118020590031-8) и поддержана постановлением Правительства РФ от 16.03.2013 № 211 (соглашение 02.A03.21.0006)

Impact of inter-ventricular lead distance on cardiac resynchronization therapy outcomes

Cardiac resynchronization therapy (CRT) has been shown as an essential treatment of patients with heart failure, leading to improvements in symptoms, left ventricular (LV) function, and survival. However, up to 30% of appropriately selected patients remain non-responders to CRT. The aim of our study was to test a hypothesis on the impact of lead positioning in the ventricular walls on CRT response in patients with advanced chronic heart failure with and without pre-operative inter and intra-ventricular myocardial dyssynchrony. We examined 53 guideline-selected CRT candidates. Response to CRT was defined in 6 months after implantation of CRT devices. All patients underwent standard and Doppler echocardiography for assessment of LV function and mechanical dyssynchrony. Individual right ventricular (RV) and LV lead tip position, inter-lead distance, and the horizontal and vertical components were measured on the radiograph images with using an automated custom made software Our results showed that the RLV inter-lead distance is an essential parameter correlated with the CRT outcomes. A logistic model comprising the RLV inter-lead distance with parameters of dyssynchrony demonstrated a high predictive power for odds of CRT success. © 2017 IEEE Computer Society. All rights reserved.Research was supported by Act 211 Government of the Russian Federation, agreement № 02.A03.21.0006 and Program of the RAS Presidium #I.33П

Evaluation of the Long-term Effectiveness of Cardiac Resynchronization Therapy

Aim. To determine quantitative criteria for assessing the therapeutic benefits and the most informative time frames after cardiac resynchronization therapy (CRT) to assess its long-term effectiveness (1, 2, 3 years of follow-up) based on retrospective analysis. To assess the CRT effectiveness, parameters of left ventricular (LV) reverse remodeling and signs characterizing the clinical CRT response were considered. Material and methods. This single-center, retrospective, non-randomized study included data from 278 patients with implanted CRT devices. Quantitative criteria for assessing CRT effectiveness were determined using a two-step cluster analysis of patients 1, 2, and 3 years after CRT by LV reverse remodeling parameters. Results. In the dataset with satisfactory division accuracy, after the first year, two clusters were identified, which are conventionally named as “non-responders” and “responders”. Two and three years after therapy, patients were classified into three clusters: “non-responders”, “responders” and “super-responders”. For the obtained clusters, we found cutoff values for LV reverse remodeling parameters, which can be used as criteria for response to therapy. The study identified the most informative time frames for assessing the postoperative CRT effectiveness 1, 2, 3 years after the surgery. At the same time, the clinical response to therapy is manifested earlier in comparison with the reverse LV remodeling. Despite the high divisibility of patients into responders and non-responders, predictive models of CRT effectiveness created using the available data from standard diagnostic protocols for heart failure patients have insufficient accuracy to be used for making decisions on therapy appropriateness. This circumstance indicates the need to receive additional data to improve the forecasting quality. Conclusion. The study revealed a period for assessing the clinical response and changes in LV reverse remodeling after CRT surgery, which is important for the optimal choice of postoperative therapy. It has been shown that in most cases, one year after surgery is sufficient to assess the clinical response, and the process of LV reverse remodeling can last up to two years on average. When assessing the CRT effectiveness by reverse remodeling, along with a change in LV end-systolic volume (ESV), it is necessary to take into account LV end-diastolic volume (EDV) changes. The change in LV ejection fraction showed a significantly lower value among the analyzed parameters in assessing the CRT effectiveness. Based on the cluster classification of patients, a dividing rule was established for responders and non-responders in the first and second years after surgery with an accuracy of 97%: a decrease in LV ESV and EDV by 9% or more compared to preoperative values. © 2021, Silicea-Poligraf. All rights reserved.Relationships and Activities. This work was supported by a Russian Science Foundation grant № 19-14-00134

Evaluation of the long-term effectiveness of cardiac resynchronization therapy

Aim. To determine quantitative criteria for assessing the therapeutic benefits and the most informative time frames after cardiac resynchronization therapy (CRT) to assess its long-term effectiveness (1, 2, 3 years of follow-up) based on retrospective analysis. To assess the CRT effectiveness, parameters of left ventricular (LV) reverse remodeling and signs characterizing the clinical CRT response were considered.Material and methods. This single-center, retrospective, non-randomized study included data from 278 patients with implanted CRT devices. Quantitative criteria for assessing CRT effectiveness were determined using a two-step cluster analysis of patients 1, 2, and 3 years after CRT by LV reverse remodeling parameters.Results. In the dataset with satisfactory division accuracy, after the first year, two clusters were identified, which are conventionally named as “non-responders” and “responders”. Two and three years after therapy, patients were classified into three clusters: “non-responders”, “responders” and “super-responders”. For the obtained clusters, we found cutoff values for LV reverse remodeling parameters, which can be used as criteria for response to therapy.The study identified the most informative time frames for assessing the postoperative CRT effectiveness 1, 2, 3 years after the surgery. At the same time, the clinical response to therapy is manifested earlier in comparison with the reverse LV remodeling.Despite the high divisibility of patients into responders and non-responders, predictive models of CRT effectiveness created using the available data from standard diagnostic protocols for heart failure patients have insufficient accuracy to be used for making decisions on therapy appropriateness. This circumstance indicates the need to receive additional data to improve the forecasting quality.Conclusion. The study revealed a period for assessing the clinical response and changes in LV reverse remodeling after CRT surgery, which is important for the optimal choice of postoperative therapy. It has been shown that in most cases, one year after surgery is sufficient to assess the clinical response, and the process of LV reverse remodeling can last up to two years on average.When assessing the CRT effectiveness by reverse remodeling, along with a change in LV end-systolic volume (ESV), it is necessary to take into account LV end-diastolic volume (EDV) changes. The change in LV ejection fraction showed a significantly lower value among the analyzed parameters in assessing the CRT effectiveness. Based on the cluster classification of patients, a dividing rule was established for responders and non-responders in the first and second years after surgery with an accuracy of 97%: a decrease in LV ESV and EDV by 9% or more compared to preoperative values

Evaluation of interventricular delay during cardiac resynchronization therapy in patients with quadripolar systems in long-term postoperative follow-up

Aim. To assess the association between changes in interventricular delay (IVD) and response to cardiac resynchronization therapy (CRT) during 24-month postoperative period in patients with quadripolar left ventricular leads.Material and methods. This retrospective non-randomized study included data from 48 patients with implanted CRT devices with quadripolar left ventricular (LV) leads, examined 3, 6, 12, 24 months after operation. CRT responders were considered patients with a decrease in end-systolic volume (ESV) by more than 10% compared with preoperative. To test the hypothesis about the rationale for choosing the maximum IVD when installing the LV lead, the group of patients was divided into two subgroups as follows: one with the maximum IVD (IVDmax, n=24), the other — without this condition (n=24).Results. A correlation was found between changes in IVD and ESV, as well as ejection fraction (EF) in the period of 6, 12 and 24 months after implantation compared to baseline. In the subgroup with IVDmax, the shortening of IVD in the postoperative period is higher at each considered period compared to the second subgroup, and in general, there is a more pronounced decrease in IVD over 24 months. At the same time, 3, 6, 12 months after surgery, patients with IVDmax show a significantly greater decrease in ESV and, accordingly, a greater increase in EF. Prognostic models of CRT response in the long term after implantation were created. Significant predictors were the initial IVD, changes in IVD in the early postoperative period and IVDmax selection. At the same time, not a single factor, taken separately, made it possible to separate responders and non-responders.Conclusion. A greater shortening of the IVD corresponds to a greater decrease in LV ESV and EDV, as well as a greater increase in EF in the long-term postoperative period. The choice of quadripolar LV lead in accordance with the maximum IVD is accompanied by a decrease in the proportion of non-responders, a more pronounced decrease in electrical ventricular dyssynchrony and an improvement in systolic function

Evaluation of interventricular delay during cardiac resynchronization therapy in patients with quadripolar systems in long-term postoperative follow-up

Aim. To assess the association between changes in interventricular delay (IVD) and response to cardiac resynchronization therapy (CRT) during 24-month postoperative period in patients with quadripolar left ventricular leads. Material and methods. This retrospective non-randomized study included data from 48 patients with implanted CRT devices with quadripolar left ventricular (LV) leads, examined 3, 6, 12, 24 months after operation. CRT responders were considered patients with a decrease in end-systolic volume (ESV) by more than 10% compared with preoperative. To test the hypothesis about the rationale for choosing the maximum IVD when installing the LV lead, the group of patients was divided into two subgroups as follows: one with the maximum IVD (IVDmax, n=24), the other — without this condition (n=24). Results. A correlation was found between changes in IVD and ESV, as well as ejection fraction (EF) in the period of 6, 12 and 24 months after implantation compared to baseline. In the subgroup with IVDmax, the shortening of IVD in the postoperative period is higher at each considered period compared to the second subgroup, and in general, there is a more pronounced decrease in IVD over 24 months. At the same time, 3, 6, 12 months after surgery, patients with IVDmax show a significantly greater decrease in ESV and, accordingly, a greater increase in EF. Prognostic models of CRT response in the long term after implantation were created. Significant predictors were the initial IVD, changes in IVD in the early postoperative period and IVDmax selection. At the same time, not a single factor, taken separately, made it possible to separate responders and non-responders. Conclusion. A greater shortening of the IVD corresponds to a greater decrease in LV ESV and EDV, as well as a greater increase in EF in the long-term postoperative period. The choice of quadripolar LV lead in accordance with the maximum IVD is accompanied by a decrease in the proportion of non-responders, a more pronounced decrease in electrical ventricular dyssynchrony and an improvement in systolic function. © 2022, Silicea-Poligraf. All rights reserved.Russian Science Foundation, RSF: 19-14-00134Relationships and Activities. The study was supported by the RSF grant № 19-14-00134

Machine Learning Prediction of Cardiac Resynchronisation Therapy Response From Combination of Clinical and Model-Driven Data

Background: Up to 30–50% of chronic heart failure patients who underwent cardiac resynchronization therapy (CRT) do not respond to the treatment. Therefore, patient stratification for CRT and optimization of CRT device settings remain a challenge. Objective: The main goal of our study is to develop a predictive model of CRT outcome using a combination of clinical data recorded in patients before CRT and simulations of the response to biventricular (BiV) pacing in personalized computational models of the cardiac electrophysiology. Materials and Methods: Retrospective data from 57 patients who underwent CRT device implantation was utilized. Positive response to CRT was defined by a 10% increase in the left ventricular ejection fraction in a year after implantation. For each patient, an anatomical model of the heart and torso was reconstructed from MRI and CT images and tailored to ECG recorded in the participant. The models were used to compute ventricular activation time, ECG duration and electrical dyssynchrony indices during intrinsic rhythm and BiV pacing from the sites of implanted leads. For building a predictive model of CRT response, we used clinical data recorded before CRT device implantation together with model-derived biomarkers of ventricular excitation in the left bundle branch block mode of activation and under BiV stimulation. Several Machine Learning (ML) classifiers and feature selection algorithms were tested on the hybrid dataset, and the quality of predictors was assessed using the area under receiver operating curve (ROC AUC). The classifiers on the hybrid data were compared with ML models built on clinical data only. Results: The best ML classifier utilizing a hybrid set of clinical and model-driven data demonstrated ROC AUC of 0.82, an accuracy of 0.82, sensitivity of 0.85, and specificity of 0.78, improving quality over that of ML predictors built on clinical data from much larger datasets by more than 0.1. Distance from the LV pacing site to the post-infarction zone and ventricular activation characteristics under BiV pacing were shown as the most relevant model-driven features for CRT response classification. Conclusion: Our results suggest that combination of clinical and model-driven data increases the accuracy of classification models for CRT outcomes. Copyright © 2021 Khamzin, Dokuchaev, Bazhutina, Chumarnaya, Zubarev, Lyubimtseva, Lebedeva, Lebedev, Gurev and Solovyova.This work was supported by Russian Science Foundation grant no. 19-14-00134