Studium of the clinical impact of different forms of cardiac resynchronization therapy by patients with chronic heart failure MUDr. Lucie Burianová ABSTRACT: Introduction: Biventricular (BiV) pacing decreases mortality and improves quality of life of patients with severe heart failure. Haemodynamic and short time clinical studies suggest that isolated leftventricular pacing could have the same effect. Aims: Compare the effect of BiV and leftventricular pacing by subjects with dilated cardiomyopathy and severe heart failure with the attention to signs of dyssynchrony and remodelation of the left chamber. In methodical substudy compare the results of left chamber volumes and ejection fraction (EF LK) measured by CT angiography and 2-dimensional echocardiography with use of contrast agent (K-ECHO). Methods: Patients indicated for cardiac resynchronization therapy were randomized for either BiV or leftventricular pacing. After implantation of the device they were examinated clinically and by echocardiography every 3 months in the period of one year. Four years from the onset of the study the major adverse events in both groups were evaluated. The results of left chamber volumes and EF LK measured by K-ECHO and CT angiography were compared. Results: We enrolled 33 patients. We found clinical improvement in both...

Abstract Background: Implantable cardioverter-defibrillator (ICD) surgery in patients with implanted left ventricular assist devices (LVAD) is associated with an increased risk of bleeding complications because of the need to ensure that these patients are adequately anticoagulated. Our study aimed to evaluate the safety of our new strategy of uninterrupted oral anticoagulation compared to heparin-bridging during the surgical interval. Methods: Between January 2009 and January 2020, 116 patients with LVAD underwent ICD surgery. Since January 2015, 60 patients were operated under continued sufficient oral anticoagulation with a vitamin k antagonist (VKA group). Fifty-six patients underwent a heparin-bridging regimen (heparin group). Demographics, perioperative data, complications, and mortality were analyzed. Results: Bleeding complications attributable to the surgical intervention occurred more often (19.6% vs. 10.0%, p = 0.142) and at a higher rate of re-exploratory surgery (14.3% vs. 5.0%, p = 0.088) in the heparin group without reaching statistical significance. Moreover, the heparin group patients' postoperative total length of stay was 10 days longer (17.8 ± 23.8 days vs. 8.3 ± 9.5 days, p = 0.007). There were no procedure-related deaths, no thromboembolic events, and no LVAD-related thrombosis. Conclusion: Our strategy of uninterrupted oral anticoagulation is safe and results in a reduction by more than half the number of days in hospital without an increase in adverse events.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui vise à rétablir le synchronisme de contraction du ventricule gauche chez les patients souffrant d’insuffisance cardiaque. Aujourd’hui encore, plus de 30% de ces patients ne répondent pas au traitement de resynchronisation. Afin de mieux comprendre les effets de la CRT sur la fonction cardiaque, un resynchronisateur biventriculaire a été implanté chez des chiens sains et des chiens atteints d’insuffisance cardiaque. Les fonctions ventriculaires gauche et droite ont été étudiées selon différents modes de resynchronisation. Les résultats de cette étude confirment premièrement que la durée du complexe QRS n’est pas un marqueur approprié dans l’optimisation de la CRT. Les résultats démontrent également qu’une optimisation individualisée de la CRT est nécessaire afin de maximiser l’effet de la thérapie sur le ventricule gauche et que la modulation du délai de resynchronisation a un impact significatif sur la fonction ventriculaire droite. Plus précisément, la fonction systolique du ventricule droit est optimale lors d’une activation précoce de l’électrode gauche. / Cardiac resynchronization therapy (CRT) was introduced to reestablish the synchronism in left ventricular of heart failure patients. At the present time, more than 30% of these patients do not respond to the resynchronization treatments. In order to better understand the effect of CRT on the cardiac function, a biventricular pacemaker was implanted in healthy dogs and in dogs with induced heart failure. Results from this study show that using the QRS duration in order to optimize CRT is not recommended. In addition, they confirm that an individualized optimization of the CRT is necessary to maximize the effect of the therapy on the left ventricle and that the modulation of the resynchronization delay has a significant impact on the right ventricular function. More precisely, right ventricular systolic function is optimal with an early activation of the left electrode.

Introdução: A terapia de ressincronização cardíaca (TRC) é um tratamento recomendado pelas principais diretrizes mundiais para pacientes com insuficiência cardíaca congestiva (ICC), disfunção ventricular esquerda (FE <= 35%), com tratamento otimizado e distúrbio da condução intraventricular, principalmente pelo ramo esquerdo. Entretanto, 30%-40% dos pacientes selecionados não respondem ao tratamento. As razões desse insucesso não são completamente conhecidas. Existe, portanto, necessidade de desenvolvimento de índices multifatoriais para melhor selecionar e acompanhar a evolução e o prognóstico destes pacientes. Objetivo: Elaborar modelos preditores de risco de óbito cardíaco ou transplante (Tx), em diferentes fases da TRC. Métodos e Casuística: Estudo observacional, prospectivo e analítico, com inclusão de 116 pacientes, entre 01/2008 a 03/2013, sendo 69,8% do sexo masculino, com CF III (68,1%) e IV ambulatorial (31,9%), com BRE em 71,55% e com idade de 64,89 ± 11,18 anos e fração de ejeção (FE) de 29%. Avaliações foram feitas no período pré-implante (tempo 1), 6-12 meses (tempo 2) e 18-24 meses (tempo 3) e correlacionadas com a mortalidade cardíaca/Tx no final do seguimento. Foram estudadas variáveis clínicas, eletrocardiográficas e ecocardiográficas e realizadas análises de regressão de Cox e regressão logística, com a construção da curva ROC. As curvas de sobrevidas foram realizadas pelo método de Kaplan-Meier e comparadas pelo log-rank. Modelos e escores foram elaborados pelas pontuações do \"hazard ratio\", utilizado como variável independente no modelo de regressão logística. Resultados: Ocorreram 29 (25%) óbitos/Tx durante o seguimento de 34,09 ± 17,9 meses. A mortalidade cardíaca/Tx foi de 16,3 % (19 pacientes). Seis pacientes foram transplantados durante o tempo do estudo. No período préimplante (tempo 1), a presença de disfunção de ventrículo direito (VD), FE < 25% e o uso de altas doses de diuréticos (dois ou mais comprimidos de furosemida) mostraram-se com valor independente, com aumento de risco de óbito cardíaco/Tx de 3,9; 4,8 e 5,9 vezes, respectivamente. No tempo 2 (1° ano), as variáveis disfunção de VD, altas doses de diuréticos e internações por ICC foram as variáveis significativas, com aumento de risco 3,5; 5,3 e 12,5 respectivamente. No tempo 3 (2° ano), as variáveis disfunção de VD e classe funcional III/IV foram significativas no modelo multivariado de Cox, com aumento de risco de 12,1 e 7,7. As acurácias dos modelos foram 84,6%; 93% e 90,5%, respectivamente. Conclusão: Os modelos preditores de óbito cardíaco desenvolvidos a partir de variáveis clínicas e ecocardiográficas, obtidas em diferentes fases da TRC, mostraram boa acurácia e podem ajudar na seleção, seguimento, definição de resposta e aconselhamento destes pacientes / Introduction: Cardiac resynchronization therapy (CRT) is indicated for patients with congestive heart failure (CHF), ejection fraction (EF) <= 35%, and bundle branch block. However, 30%-40% do not respond to CRT. Therefore, there is a need to develop multifactorial indexes to better select and follow these patients. Objective: This work aims to develop predictive models for the risk of cardiac death or transplantation (Tx) at different stages of CRT. Methods: We performed a prospective observational study of 116 patients, 69.8% males, functional class (FC) III (68.1%) and IV (31.9%), LBBB in 71.55%, age 64.89 ± 11.18 years. We studied clinical, electrocardiographic, and echocardiographic variables and performed Cox and logistic regression with ROC and Kaplan- Meier curves. Results: The cardiac mortality was 16.3% (19 patients) in the 34.09 ± 17.9 follow-up months. Pre-implantation, the right ventricular dysfunction (RVD), EF <25%, and the use of high doses of diuretics (HDD) increased risk of cardiac death or Tx of 3.9, 4.8, and 5.9 fold, respectively, and in the first year, the variables RVD, HDD, and hospitalizations for CHF increased risk of death of 3.5, 5.3, and 12.5, respectively. In the 2nd year, the variables RVD and FC III / IV (NYHA) were significant in the multivariate Cox model. The accuracies of the models were 84.6%, 93%, and 90.5%, respectively. Conclusions: Cardiac death predictive models were developed in different stages of CRT, and were based on the analysis of simple clinical and echocardiographic variables. The models showed good accuracy and can help in the selection and follow-up of these patients

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui vise à rétablir le synchronisme de contraction du ventricule gauche chez les patients souffrant d’insuffisance cardiaque. Aujourd’hui encore, plus de 30% de ces patients ne répondent pas au traitement de resynchronisation. Afin de mieux comprendre les effets de la CRT sur la fonction cardiaque, un resynchronisateur biventriculaire a été implanté chez des chiens sains et des chiens atteints d’insuffisance cardiaque. Les fonctions ventriculaires gauche et droite ont été étudiées selon différents modes de resynchronisation. Les résultats de cette étude confirment premièrement que la durée du complexe QRS n’est pas un marqueur approprié dans l’optimisation de la CRT. Les résultats démontrent également qu’une optimisation individualisée de la CRT est nécessaire afin de maximiser l’effet de la thérapie sur le ventricule gauche et que la modulation du délai de resynchronisation a un impact significatif sur la fonction ventriculaire droite. Plus précisément, la fonction systolique du ventricule droit est optimale lors d’une activation précoce de l’électrode gauche. / Cardiac resynchronization therapy (CRT) was introduced to reestablish the synchronism in left ventricular of heart failure patients. At the present time, more than 30% of these patients do not respond to the resynchronization treatments. In order to better understand the effect of CRT on the cardiac function, a biventricular pacemaker was implanted in healthy dogs and in dogs with induced heart failure. Results from this study show that using the QRS duration in order to optimize CRT is not recommended. In addition, they confirm that an individualized optimization of the CRT is necessary to maximize the effect of the therapy on the left ventricle and that the modulation of the resynchronization delay has a significant impact on the right ventricular function. More precisely, right ventricular systolic function is optimal with an early activation of the left electrode.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui diminue la mortalité et améliore la qualité de vie des patients atteints d’insuffisance cardiaque et présentant un dyssynchronisme de la contraction ventriculaire gauche. Malgré le succès de cette thérapie, plus de 30% des patients ne présentent pas l’amélioration désirée. Plusieurs études portant sur le synchronisme électrique ou mécanique de la contraction ont été effectuées mais peu d’entres elles se sont attardées sur le couplage électromécanique à l'échelle macroscopique. Ce projet a comme objectif d’observer le comportement électromécanique des ventricules canins en présence d’un resynchronisateur cardiaque. Un logiciel a été développé pour permettre l’analyse des informations provenant de la cartographie endocardique sans contact et de la ventriculographie isotopique tomographique chez 12 sujets canins insuffisants. Pour observer la réponse mécanique suite à l’activation électrique, nous avons premièrement recalé les surfaces issues des 2 modalités. Ensuite, nous avons défini les limites du cycle cardiaque, analysé les signaux électriques et les courbes de déplacement de la paroi endocardique. Le début de la contraction est défini par un déplacement radial de 10% vers le centre du ventricule. Les résultats démontrent que la durée d’activation du ventricule gauche et la largeur du QRS augmentent en présence d’une stimulation externe et que les délais électromécaniques sont indépendants dans les modes de stimulation étudiés (sinusal, LVbasal, RVapex ou BIV) avec une moyenne de 84,56±7,19 ms. Finalement, nous avons noté que la stimulation basolatérale procure une fonction cardiaque optimale malgré une durée prolongée du QRS. / Cardiac Resynchronization Therapy (CRT) is known to decrease mortality rate and improve the quality of life for patients suffering from heart failure with left ventricular contraction dyssynchrony. However, it has been shown that 30% of patients do not respond to this therapy. Many studies have investigated the electrical or mechanical synchronism of contraction but few have studied the activation contraction coupling on a macroscopic level. The objective of this study is to observe the left ventricle’s electromechanical behaviour under biventricular stimulation. A software has been developed to analyse the data coming from non-contact mapping and blood pool SPECT for 12 dogs with heart failure. In order to observe the mechanical response following an electrical activation, we have registered 3D surfaces generated by the 2 modalities. Afterward, we defined the cardiac cycle limits, and we analyzed electrical signals as well as endocardial wall displacement curves where the onset of contraction was defined as a 10% inward radial displacement. Results show that both duration of left ventricular activation and QRS increase with pacing and that electromechanical delays are independent of stimulation mode (mean value 84,56 ± 7,19 ms). Finally, we observed that basolateral stimulation shows the best improvement for left ventricular function while presenting a long QRS duration.

Synchronous contraction and relaxation of the myocardium is required to optimize cardiac function. Regional timing of contraction and relaxation is dyssynchronous in many patients with heart failure. Cardiac resynchronization therapy (CRT) is a highly successful treatment for dyssynchronous heart failure. Patients are currently selected for CRT using surface electrocardiogram QRS duration as a measure of dyssynchrony. However, up to 30% of patients selected for CRT show no improvement. This poor response rate may in part be explained by the poor correlation between mechanical dyssynchrony and QRS duration. Thus, better methods to quantify mechanical dyssynchrony in the heart may improve the poor CRT response rate. The overall goal of this project was to develop better methods to diagnose dyssynchrony in the left ventricle (LV). We developed two new methods with different approaches. The first method improved upon existing tissue-Doppler based echocardiographic diagnosis of dyssynchrony by utilizing a cross-correlation (XC) function to quantify dyssynchrony during post-processing as opposed to the quantitatively simplistic time-to-peak analysis that is currently utilized. The second method utilized standard cine cardiac magnetic resonance (CMR) images to quantify the dyssynchrony in the flow of blood within the LV, which may represent a more direct, physiologically relevant measure of dyssynchrony. Specific aim 1 demonstrated that the new XC delay parameters can be quantified accurately with a stationary region of interest and therefore require significantly less post-processing time to calculate compared to the time-to-peak dyssynchrony parameters. Specific aim 2 showed that XC delays are superior to existing time-to-peak dyssynchrony parameters at discriminating patients with LV dyssynchrony from those with normal function. The time-to-peak parameters showed dyssynchrony in approximately half of the normal, healthy volunteers while the XC delay parameters had nearly perfect diagnostic accuracy. The results of specific aim 3 showed that XC delays could diagnose acute, pacing-induced dyssynchrony in young, healthy children with 79% accuracy while the time-to-peak parameters showed accuracies of 71%, 57% and 57%. Specific aim 4 showed that CMR-based quantification of LV internal flow can be used to discriminate patients with dyssynchronous heart failure from normal controls with 95% accuracy.

Introdução: A terapia de ressincronização cardíaca (TRC) é um tratamento recomendado pelas principais diretrizes mundiais para pacientes com insuficiência cardíaca congestiva (ICC), disfunção ventricular esquerda (FE <= 35%), com tratamento otimizado e distúrbio da condução intraventricular, principalmente pelo ramo esquerdo. Entretanto, 30%-40% dos pacientes selecionados não respondem ao tratamento. As razões desse insucesso não são completamente conhecidas. Existe, portanto, necessidade de desenvolvimento de índices multifatoriais para melhor selecionar e acompanhar a evolução e o prognóstico destes pacientes. Objetivo: Elaborar modelos preditores de risco de óbito cardíaco ou transplante (Tx), em diferentes fases da TRC. Métodos e Casuística: Estudo observacional, prospectivo e analítico, com inclusão de 116 pacientes, entre 01/2008 a 03/2013, sendo 69,8% do sexo masculino, com CF III (68,1%) e IV ambulatorial (31,9%), com BRE em 71,55% e com idade de 64,89 ± 11,18 anos e fração de ejeção (FE) de 29%. Avaliações foram feitas no período pré-implante (tempo 1), 6-12 meses (tempo 2) e 18-24 meses (tempo 3) e correlacionadas com a mortalidade cardíaca/Tx no final do seguimento. Foram estudadas variáveis clínicas, eletrocardiográficas e ecocardiográficas e realizadas análises de regressão de Cox e regressão logística, com a construção da curva ROC. As curvas de sobrevidas foram realizadas pelo método de Kaplan-Meier e comparadas pelo log-rank. Modelos e escores foram elaborados pelas pontuações do \"hazard ratio\", utilizado como variável independente no modelo de regressão logística. Resultados: Ocorreram 29 (25%) óbitos/Tx durante o seguimento de 34,09 ± 17,9 meses. A mortalidade cardíaca/Tx foi de 16,3 % (19 pacientes). Seis pacientes foram transplantados durante o tempo do estudo. No período préimplante (tempo 1), a presença de disfunção de ventrículo direito (VD), FE < 25% e o uso de altas doses de diuréticos (dois ou mais comprimidos de furosemida) mostraram-se com valor independente, com aumento de risco de óbito cardíaco/Tx de 3,9; 4,8 e 5,9 vezes, respectivamente. No tempo 2 (1° ano), as variáveis disfunção de VD, altas doses de diuréticos e internações por ICC foram as variáveis significativas, com aumento de risco 3,5; 5,3 e 12,5 respectivamente. No tempo 3 (2° ano), as variáveis disfunção de VD e classe funcional III/IV foram significativas no modelo multivariado de Cox, com aumento de risco de 12,1 e 7,7. As acurácias dos modelos foram 84,6%; 93% e 90,5%, respectivamente. Conclusão: Os modelos preditores de óbito cardíaco desenvolvidos a partir de variáveis clínicas e ecocardiográficas, obtidas em diferentes fases da TRC, mostraram boa acurácia e podem ajudar na seleção, seguimento, definição de resposta e aconselhamento destes pacientes / Introduction: Cardiac resynchronization therapy (CRT) is indicated for patients with congestive heart failure (CHF), ejection fraction (EF) <= 35%, and bundle branch block. However, 30%-40% do not respond to CRT. Therefore, there is a need to develop multifactorial indexes to better select and follow these patients. Objective: This work aims to develop predictive models for the risk of cardiac death or transplantation (Tx) at different stages of CRT. Methods: We performed a prospective observational study of 116 patients, 69.8% males, functional class (FC) III (68.1%) and IV (31.9%), LBBB in 71.55%, age 64.89 ± 11.18 years. We studied clinical, electrocardiographic, and echocardiographic variables and performed Cox and logistic regression with ROC and Kaplan- Meier curves. Results: The cardiac mortality was 16.3% (19 patients) in the 34.09 ± 17.9 follow-up months. Pre-implantation, the right ventricular dysfunction (RVD), EF <25%, and the use of high doses of diuretics (HDD) increased risk of cardiac death or Tx of 3.9, 4.8, and 5.9 fold, respectively, and in the first year, the variables RVD, HDD, and hospitalizations for CHF increased risk of death of 3.5, 5.3, and 12.5, respectively. In the 2nd year, the variables RVD and FC III / IV (NYHA) were significant in the multivariate Cox model. The accuracies of the models were 84.6%, 93%, and 90.5%, respectively. Conclusions: Cardiac death predictive models were developed in different stages of CRT, and were based on the analysis of simple clinical and echocardiographic variables. The models showed good accuracy and can help in the selection and follow-up of these patients

This thesis deals with the analysis of high-frequency ECG, namely by parameters for the determination of cardiac asynchrony from the amplitude envelopes ultra-high-frequency ECG. In the theoretical part is described the conventional and high-frequency ECG, procedure of their scanning and parameters of the acquired record. Also is described the electrical conduction system of the heart and its blockade. This issue is followed by chapters about cardiac asynchrony and its treatments by biventricular pacemaker – resynchronization therapy. The chapter about resynchronization includes a description of the methods used for the indication for therapy based on conventional and high-frequency ECG. In the practical part are proposed new parameters for determining heart asynchrony from high-frequency ECG, programmed their detection in environment MATLAB and described realization of detection and obtained results. In the last part of thesis is described statistical evaluation of data and is decided about suitability of use the proposed parameters.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui diminue la mortalité et améliore la qualité de vie des patients atteints d’insuffisance cardiaque et présentant un dyssynchronisme de la contraction ventriculaire gauche. Malgré le succès de cette thérapie, plus de 30% des patients ne présentent pas l’amélioration désirée. Plusieurs études portant sur le synchronisme électrique ou mécanique de la contraction ont été effectuées mais peu d’entres elles se sont attardées sur le couplage électromécanique à l'échelle macroscopique. Ce projet a comme objectif d’observer le comportement électromécanique des ventricules canins en présence d’un resynchronisateur cardiaque. Un logiciel a été développé pour permettre l’analyse des informations provenant de la cartographie endocardique sans contact et de la ventriculographie isotopique tomographique chez 12 sujets canins insuffisants. Pour observer la réponse mécanique suite à l’activation électrique, nous avons premièrement recalé les surfaces issues des 2 modalités. Ensuite, nous avons défini les limites du cycle cardiaque, analysé les signaux électriques et les courbes de déplacement de la paroi endocardique. Le début de la contraction est défini par un déplacement radial de 10% vers le centre du ventricule. Les résultats démontrent que la durée d’activation du ventricule gauche et la largeur du QRS augmentent en présence d’une stimulation externe et que les délais électromécaniques sont indépendants dans les modes de stimulation étudiés (sinusal, LVbasal, RVapex ou BIV) avec une moyenne de 84,56±7,19 ms. Finalement, nous avons noté que la stimulation basolatérale procure une fonction cardiaque optimale malgré une durée prolongée du QRS. / Cardiac Resynchronization Therapy (CRT) is known to decrease mortality rate and improve the quality of life for patients suffering from heart failure with left ventricular contraction dyssynchrony. However, it has been shown that 30% of patients do not respond to this therapy. Many studies have investigated the electrical or mechanical synchronism of contraction but few have studied the activation contraction coupling on a macroscopic level. The objective of this study is to observe the left ventricle’s electromechanical behaviour under biventricular stimulation. A software has been developed to analyse the data coming from non-contact mapping and blood pool SPECT for 12 dogs with heart failure. In order to observe the mechanical response following an electrical activation, we have registered 3D surfaces generated by the 2 modalities. Afterward, we defined the cardiac cycle limits, and we analyzed electrical signals as well as endocardial wall displacement curves where the onset of contraction was defined as a 10% inward radial displacement. Results show that both duration of left ventricular activation and QRS increase with pacing and that electromechanical delays are independent of stimulation mode (mean value 84,56 ± 7,19 ms). Finally, we observed that basolateral stimulation shows the best improvement for left ventricular function while presenting a long QRS duration.