Os efeitos da utilização da terapia de ressincronização cardíaca (TRC) em pacientes com cardiopatia chagásica (CCC) são pouco conhecidos. O objetivo desse trabalho foi comparar o efeito dessa terapia em pacientes com CCC e não-chagásica. Foram estudados, retrospectivamente, todos os pacientes submetidos à ressincronização cardíaca, associados ou não ao cardioversor-desfibrilador implantável (CDI) no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo no período de julho de 2007 a dezembro de 2017. Para comparar a mesma variável em dois momentos diferentes foi utilizado Teste de Wilcoxon. Para a comparação de proporções foi utilizado o teste exato de Fisher. A análise de sobrevida foi feita utilizando-se o método de Kaplan-Meier com o \"Long rank test\" para comparar a sobrevida entre os grupos. Para a análise das variáveis associadas à mortalidade pós-implante utilizou-se a análise de regressão de Cox. Noventa e oito pacientes foram incluídos e divididos em três grupos de cardiopatia: chagásica (CCC) com 42 pacientes (42,9%); isquêmicos (ISQ) com 13 (13,3%) e nãoisquêmico não-chagásico (NINC) com 43 (43,9%). Os pacientes que receberam implante de TRC foram 71,4% e TRC associado ao CDI foram 28,5%. Não havia diferença estatisticamente significativa entre os grupos na avaliação das características clínicas, exceto pela predominância de pacientes do gênero masculino no grupo ISQ. Em relação aos bloqueios de condução intraventriculares, havia menor quantidade de bloqueio de ramo esquerdo (BRE) espontâneo e maior quantidade de BRE induzido no grupo CCC. As demais características eletrocardiográficas e ecocardiográficas eram semelhantes entre os grupos. A sobrevida de pacientes que recebem a TRC foi baixa após 48 meses de implante, independentemente do tipo de miocardiopatia e a despeito da melhora significativa da classe funcional e estreitamento do QRS dos pacientes. Todavia, a sobrevida em pacientes chagásicos foi significativamente menor quando comparada as demais miocardiopatias. Ademais, a melhora da fração de ejeção do ventrículo esquerdo (FEVE) e a redução do diâmetro diastólico final do ventrículo esquerdo (DDFVE) ocorreram significativamente apenas no grupo NINC. O aumento da idade, FEVEreduzida, presença de atraso da condução intraventricular não especificada (ACINE) e de bloqueio de ramo direito (BRD) e baixa classe funcional estão associadas a maior risco de morte após implante. As taxas de complicações cirúrgicas foram baixas em todos os grupos. A taxa de óbito cirúrgico é compatível com a gravidade desses pacientes. Conclui-se que a CCC apresenta resposta clínica à TRC, mas a mortalidade após 48 meses é maior que em outras cardiopatias. / The effects of using cardiac resynchronization therapy (CRT) in patients with Chagas\' heart disease (CCC) are poorly understood. The objective of this study was to compare the effect of this therapy in patients with CCC and non-Chagas\' disease. We retrospectively studied all patients submitted to cardiac resynchronization associated or not with the implantable cardioverter defibrillator (ICD) at the Clinical Hospital of Ribeirão Preto Medical School at the São Paulo University from July 2007 to December 2017. We use Wilcoxon\'s test to compare the same variable in two different times. Fisher\'s exact test was used to compare proportions. Survival analysis was done using the Kaplan-Meier method with the Long rank test to compare survival between groups. Cox regression analysis was used to analyze the variables associated with post-implantation mortality. Ninety-eight patients were included and divided into three groups: cardiopathy: chagasic (CCC) with 42 patients (42.9%); ischemic (ISQ) with 13 patients (13.3%) and non-ischemic non-chagasic (NINC) with 43 (43.9%). The patients who received CRT implantation were 71.4% and CRI associated CRT were 28.5%. There was no statistically significant difference between the groups in the assessment of clinical characteristics, except for the predominance of male patients in the ISQ group. In relation to intraventricular conduction blockades, there was a lower amount of spontaneous left bundle branch block (LBBB) and greater amount of LBBB induced in the CCC group. The other electrocardiographic and echocardiographic characteristics were similar between groups. The survival of patients receiving CRT was low after 48 months of implantation, regardless of the type of cardiomyopathy and despite significant improvement in functional class and QRS narrowing of patients. However, survival in chagasic patients was significantly lower when compared to other cardiomyopathies. In addition, the improvement of left ventricular ejection fraction (LVEF) and the reduction of the left ventricular end-diastolic dimension (LVEDF) occurred significantly only in the NINC group. Increased age, reduced LVEF, presence of unspecified intraventricular conduction delay and left bundle branch block, and low functional class are associated with a higher risk of death after implantation. Therates of surgical complications were low in all groups. The surgical death rate is compatible with the severity of these patients. It is concluded that CCC presents a clinical response to CRT, but mortality after 48 months is higher than in the other cardiopathies.

INTRODUÇÃO: A terapia de ressincronização cardíaca (TRC) é procedimento já incorporado às diretrizes do tratamento da insuficiência cardíaca crônica grave. Os efeitos sobre a repolarização ventricular são controversos e seu comportamento ainda precisa ser melhor definido por meios não invasivos. OBJETIVO: Analisar o comportamento da repolarização ventricular, através do mapeamento eletrocardiográfico de superfície (MES), em pacientes sob TRC. MÉTODOS: Foram estudados 52 pacientes sob TRC com indicação classe I das Diretrizes Brasileiras de Dispositivos Cardíacos Eletrônicos Implantáveis-2007, com idade média 58,8±12,3 anos, 31 homens, FEVE:27,5±9,2 e QRS:181,5±24,2ms. Foram excluídos os que não eram classe I e também os que usavam amiodarona, portadores de fibrilação atrial, marcapasso ou CDI prévios. O MES de 87 derivações (59 no tórax anterior e 28 no dorso) foi realizado em ritmo sinusal (BASAL) e sob efeito do ressincronizador (BIV) Através de medidas semiautomáticas foram obtidos o intervalo QT, QTc médio e a dispersão de QT (DQT) global das 87 derivações, nos dois modos de estimulação, em cada paciente. As mesmas medidas foram realizadas e comparadas nas três regiões discriminadas pelo MES (VD, Septo e VE). Caracterizamos assim, o comportamento global e regional do QT e sua dispersão na TRC. Utilizamos os testes t Student pareado e ANOVA para comparações múltiplas. Nível de significância de p< 0,05. RESULTADOS: O comportamento global do QTmédio foi sensivelmente menor em BIV que no BASAL (424,4±38,7 x 455,8±46,5ms; p<0,001), assim como o QTc médio (460,7±42,3 x 483,8±41,4ms; p<0,05) e a DQT (61,2±26,2 x 74,9±28,7ms; p<0,05). O QTmédio foi semelhante nas 3 regiões nos modos BASAL e BIV (p=ns), porém o QTc médio nas regiõess VD e VE mostrou-se significantemente menor no modo BASAL. Sob BIV, essa diferença foi notavelmente menor na região do VD. A DQT, em região do VE, por sua vez, foi significantemente menor em relação ao Septo, nos dois modos (BASAL: 40,5±23,1 x 55,7±28,7ms, p<0,01 e BIV: 30,6±20,4 x 47,1±20,2ms, p<0,001). A variação de efeito (D%) da TRC determinou redução do QTmédio nas 3 regiões (VD: p=0,0014; Septo: p=0,0001 e VE: p=0,0018), enquanto a DQT reduziu-se em VD: p=0,04 e VE: p=0,023. Em região septal, a redução da DQT não atingiu significância, embora tenha mostrado a mesma tendência de resposta. CONCLUSÃO: O Mapeamento Eletrocardiográfico de Superfície detectou redução global e regional dos valores da repolarização ventricular, através da análise do QTm, QTcm e DQT, por efeito da terapia de ressincronização cardíaca em pacientes com insuficiência cardíaca grave e BRE / BACKGROUND: Cardiac resynchronization therapy (CRT) is an already established procedure, which became part of the guidelines for severe chronic heart failure treatment. Its effects upon the ventricular repolarization are controversial, therefore CRT response still remains to be better defined by noninvasive methods. OBJECTIVE: The aim of this study was to analyze the ventricular repolarization response by body surface potential mapping (BSPM) in patients undergoing CRT. METHODS: Fifty-two patients undergoing CRT, mean age 58.8±12.3 years, 31 male, LVEF 27.5±9.2 and QRS duration 181.5±14.2ms, with indication class I of the 2007Guidelines for Implantable Electronic Cardiac Devices of the Brazilian Society of Cardiology, were studied. Those who were not in class I and/or in use of amiodarone, with atrial fibrillation, or with previous pacemaker or ICD, were excluded. Eighty-seven-lead BSPM examination (59 leads on the anterior chest and 28 on the back) was performed in sinus rhythm (BASELINE), and in biventricular pacing (BIV) with the resynchronization device on. Global values of QT and mean QTc intervals, and QT dispersion (DQT) were semiautomatically measured in all patients in the two pacing modes. Same measurements were made and compared in the three regions (RV, Septum and LV) discriminated by BSPM maps. Thus we characterized the global and regional QT response and its dispersion under CRT. t-Student paired test and ANOVA were used for multiple comparisons. Significance level: p<.05. RESULTS: The global mean QT response was considerably smaller in BIV pacing than in BASELINE (424.4±38.7 x 455.8±46.5ms; p<.001), and so were the mean QTc (460.7±42.3 x 483.8±41.4ms; p<.05) and DQT (61.2±26.2 x 74.9±28.7ms; p<.05). Mean QT was similar across the three regions in both pacing modes (p=ns); however, mean QTc in RV and LV regions was found to be significantly smaller in BASELINE. In BIV pacing such difference was considerably smaller in the RV region. On the other hand, DQT value in the LV region was significantly smaller compared to the Septum region in both modes (BASELINE 40.5±23.1 x 55.7±28.7ms. p<.01; and BIV 30.6±20.4 x 47.1±20.2ms. p<.001). Variation of CRT effect (D%) determined reduction of mean QT in the three regions, RV (p=.0014); Septum (p=.0001); and LV (p=.0018), while DQT was reduced in RV (p=.04) and LV (p=.023) regions. DQT reduction in the septal region was not significant, although it showed the same trend of response. CONCLUSION: body surface potential mapping detected reduction of global and regional ventricular repolarization values by analyzing QTm, QTcm and DQT variables under the effect of cardiac resynchronization therapy, in patients with severe heart failure and LBBB

Os efeitos da utilização da terapia de ressincronização cardíaca (TRC) em pacientes com cardiopatia chagásica (CCC) são pouco conhecidos. O objetivo desse trabalho foi comparar o efeito dessa terapia em pacientes com CCC e não-chagásica. Foram estudados, retrospectivamente, todos os pacientes submetidos à ressincronização cardíaca, associados ou não ao cardioversor-desfibrilador implantável (CDI) no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo no período de julho de 2007 a dezembro de 2017. Para comparar a mesma variável em dois momentos diferentes foi utilizado Teste de Wilcoxon. Para a comparação de proporções foi utilizado o teste exato de Fisher. A análise de sobrevida foi feita utilizando-se o método de Kaplan-Meier com o \"Long rank test\" para comparar a sobrevida entre os grupos. Para a análise das variáveis associadas à mortalidade pós-implante utilizou-se a análise de regressão de Cox. Noventa e oito pacientes foram incluídos e divididos em três grupos de cardiopatia: chagásica (CCC) com 42 pacientes (42,9%); isquêmicos (ISQ) com 13 (13,3%) e nãoisquêmico não-chagásico (NINC) com 43 (43,9%). Os pacientes que receberam implante de TRC foram 71,4% e TRC associado ao CDI foram 28,5%. Não havia diferença estatisticamente significativa entre os grupos na avaliação das características clínicas, exceto pela predominância de pacientes do gênero masculino no grupo ISQ. Em relação aos bloqueios de condução intraventriculares, havia menor quantidade de bloqueio de ramo esquerdo (BRE) espontâneo e maior quantidade de BRE induzido no grupo CCC. As demais características eletrocardiográficas e ecocardiográficas eram semelhantes entre os grupos. A sobrevida de pacientes que recebem a TRC foi baixa após 48 meses de implante, independentemente do tipo de miocardiopatia e a despeito da melhora significativa da classe funcional e estreitamento do QRS dos pacientes. Todavia, a sobrevida em pacientes chagásicos foi significativamente menor quando comparada as demais miocardiopatias. Ademais, a melhora da fração de ejeção do ventrículo esquerdo (FEVE) e a redução do diâmetro diastólico final do ventrículo esquerdo (DDFVE) ocorreram significativamente apenas no grupo NINC. O aumento da idade, FEVEreduzida, presença de atraso da condução intraventricular não especificada (ACINE) e de bloqueio de ramo direito (BRD) e baixa classe funcional estão associadas a maior risco de morte após implante. As taxas de complicações cirúrgicas foram baixas em todos os grupos. A taxa de óbito cirúrgico é compatível com a gravidade desses pacientes. Conclui-se que a CCC apresenta resposta clínica à TRC, mas a mortalidade após 48 meses é maior que em outras cardiopatias. / The effects of using cardiac resynchronization therapy (CRT) in patients with Chagas\' heart disease (CCC) are poorly understood. The objective of this study was to compare the effect of this therapy in patients with CCC and non-Chagas\' disease. We retrospectively studied all patients submitted to cardiac resynchronization associated or not with the implantable cardioverter defibrillator (ICD) at the Clinical Hospital of Ribeirão Preto Medical School at the São Paulo University from July 2007 to December 2017. We use Wilcoxon\'s test to compare the same variable in two different times. Fisher\'s exact test was used to compare proportions. Survival analysis was done using the Kaplan-Meier method with the Long rank test to compare survival between groups. Cox regression analysis was used to analyze the variables associated with post-implantation mortality. Ninety-eight patients were included and divided into three groups: cardiopathy: chagasic (CCC) with 42 patients (42.9%); ischemic (ISQ) with 13 patients (13.3%) and non-ischemic non-chagasic (NINC) with 43 (43.9%). The patients who received CRT implantation were 71.4% and CRI associated CRT were 28.5%. There was no statistically significant difference between the groups in the assessment of clinical characteristics, except for the predominance of male patients in the ISQ group. In relation to intraventricular conduction blockades, there was a lower amount of spontaneous left bundle branch block (LBBB) and greater amount of LBBB induced in the CCC group. The other electrocardiographic and echocardiographic characteristics were similar between groups. The survival of patients receiving CRT was low after 48 months of implantation, regardless of the type of cardiomyopathy and despite significant improvement in functional class and QRS narrowing of patients. However, survival in chagasic patients was significantly lower when compared to other cardiomyopathies. In addition, the improvement of left ventricular ejection fraction (LVEF) and the reduction of the left ventricular end-diastolic dimension (LVEDF) occurred significantly only in the NINC group. Increased age, reduced LVEF, presence of unspecified intraventricular conduction delay and left bundle branch block, and low functional class are associated with a higher risk of death after implantation. Therates of surgical complications were low in all groups. The surgical death rate is compatible with the severity of these patients. It is concluded that CCC presents a clinical response to CRT, but mortality after 48 months is higher than in the other cardiopathies.

INTRODUÇÃO: A estimulação cardíaca artificial convencional em ponta do ventrículo direito é o tratamento de eleição para os quadros de bradicardia severa, contudo, apesar de excelente para corrigir a frequência cardíaca, favorece o surgimento de dissincronia ventricular mecânica, podendo agravar ou originar insuficiência cardíaca. Neste contexto, desde a década de 90 são utilizadas no Instituto Dante Pazzanese as estimulações septal (ou para-Hissiana) e bifocal de ventrículo direito (septal e apical). Postula-se que a estimulação em posição septal teria melhores resultados tanto em termos clínicos quanto às medidas elétricas e ecocardiográficas de função sistólica quando comparada à posição apical. Esta nova estimulação ainda não foi amplamente testada frente à estimulação convencional com as novas tecnologias de avaliação da sincronia cardíaca. MÉTODOS: Pacientes portadores de fibrilação atrial permanente, sem possibilidade de estimulação atrial, com disfunção sistólica leve ou moderada e bradicardia com indicação de marca-passo definitivo foram submetidos à implante de marca-passo bifocal de ventrículo direito com eletrodos em posição septal e apical em todos os casos. Os pacientes foram randomizados para estimulação unifocal por dois meses e a seguir submetidos à crossover no ponto de estimulação cardíaca. Após cada período de estimulação eram realizados eletrocardiograma e ecocardiograma transtorácico bidimensional com avaliação de parâmetros de sincronia do miocárdio ventricular. RESULTADOS: Foram incluídos 25 pacientes em cada grupo de estimulação na análise final do estudo. A estimulação em posição septal demonstrou uma menor duração do QRS estimulado (153 ± 12 ms vs. 174 ± 16 ms, p < 0,001) e melhor fração de ejeção do ventrículo esquerdo (44 ± 9% vs. 40 ± 8%, p < 0,001) quando comparada com a posição apical. A classe funcional (NYHA) também foi menor com a estimulação septal (1,8 ± 0,6 vs. 2,2 ± 0,7, p < 0,001). A avaliação da sincronia cardíaca evidenciou menos dissincronia interventricular (p < 0,001) e intraventricular com a estimulação septal (Septal to posterior delay: 33,1 ± 28,7 vs. 80,7 ± 46,2 ms, p < 0,001; Índice de Yu: 33,4 ± 8,6 ms vs. 50,2 ± 14,0 ms, p < 0,001; Strain radial: 78,8 ± 57,1 ms vs. 137,2 ± 50,2 ms, p < 0,001). CONCLUSÃO: A avaliação intrapaciente mostrou que, em comparação com a estimulação apical convencional, a estimulação em posição septal esteve associada à menor dissincronia cardíaca medida pela ecocardiografia, o que pode estar relacionado à melhor função sistólica do ventrículo esquerdo e consequentemente melhores resultados clínicos observados. / INTRODUCTION: Conventional artificial cardiac pacing in the right ventricle apex is the treatment of choice for severe bradycardia. Although it is excellent for correcting heart rate, it favors the onset of electromechanical ventricular dyssynchrony, which may aggravate or even lead to heart failure. In this context, the Septal (or para-Hissian) and bifocal (septal and apical) stimulation were used since the 90\'s in the Dante Pazzanese Institute. It was observed that the septal stimulation could have better results both in clinical terms and in the electrical and echocardiographic measurements of systolic function when compared to the apical stimulation. This new stimulation has not been yet extensively tested against conventional one with the new technologies of cardiac synchrony evaluation. METHODS: Patients with permanent atrial fibrillation, without possibility of atrial stimulation, with mild or moderate systolic dysfunction and bradycardia with indication of pacemaker were submitted to implantation of bifocal pacemaker in the right ventricle with electrodes in a septal and apical position in all cases. The patients were randomized to unifocal stimulation for two months and then underwent crossover, changing the point of cardiac stimulation. After each stimulation period, electrocardiogram and two-dimensional transthoracic echocardiography were performed with evaluation of ventricular myocardial synchrony parameters. RESULTS: Twenty-five patients were included in each stimulation group in the final analysis of the study. Septal pacing demonstrated a shorter duration of the QRS (153 ± 12 ms vs. 174 ± 16 ms, p < 0.001) and a better left ventricular ejection fraction (44 ± 9% vs. 40 ± 8%, p < 0.001) when compared to the apical position. NYHA functional class was also lower with septal pacing (1.8 ± 0.6 vs. 2.2 ± 0.7, p < 0.001). The cardiac synchrony evaluation showed less interventricular (p < 0.001) and intraventricular dyssynchrony with septal pacing (Septal to posterior delay: 33.1 ± 28.7 vs. 80.7 ± 46.2 ms, p < 0.001; Yu index: 33.4 ± 8.6 ms vs. 50.2 ± 14.0 ms, p < 0.001; Radial strain: 78.8 ± 57.1 ms vs. 137.2 ± 50.2 ms, p < 0.001). CONCLUSION: The intrapatient comparision showed that, compared to the apical conventional stimulation, the septal pacing was associated with lower cardiac dyssynchrony measured by echocardiography, which may be related to the better left ventricular systolic function and consequently better clinical results observed.

INTRODUÇÃO: Os benefícios na morbi-mortalidade obtidos pela terapia de ressincronização cardíaca (TRC) em pacientes com insuficiência cardíaca estão bem estabelecidos. Métodos invasivos e não invasivos têm sido utilizados para identificar aqueles que realmente se beneficiarão da TRC, mas 30% destes pacientes não apresentam melhora clínica/funcional. Poucos estudos avaliaram o comportamento elétrico dos pacientes submetidos à TRC. OBJETIVO: Utilizamos um método não invasivo, o mapeamento eletrocardiográfico de superfície (MES) para caracterizar o padrão da ativação elétrica ventricular em pacientes após a TRC. MÉTODOS: Estudamos 91 pacientes submetidos à TRC, com insuficiência cardíaca e bloqueio de ramo esquerdo (BRE), sendo 36 excluídos devido a FA (20), BRD (3), cardiopatias hipertrófica (3) e congênita (1) ou dependentes de marcapasso antes da TRC (9). Idade média:61±10 anos, FEVE:0,28±0,9, QRS:182±24ms, classe funcional NYHA: III(78%) e IV(22%). Com o ressincronizador ligado e desligado, todos realizaram o MES, o qual fornece 87 derivações simultâneas (58 anteriores e 29 posteriores). Os mapas isócronos obtidos pelo MES forneceram os tempos de ativação ventricular (TAV) global máximo e médio nas 87 derivações. Os TAVs obtidos foram regionalizados, sendo calculados os valores médios nas áreas do VD, do septo e do VE. Analisamos a diferença do TAV entre o VD e o VE, entre o septo e o VD e entre o septo e o VE, definidos como TAV Inter-Regional. Utilizados os testes de Mann-Whitney, Kruskall-Wallis, Fisher. Nível de significância: P0.05. RESULTADOS: O MES durante ritmo sinusal e BRE mostrou que os pacientes apresentavam prolongado TAV Global máximo e médio (138ms e 64,8ms, respectivamente) com significativa diferença Regional (54,5 x 56,4 x 95,9ms; p<0,0001; VD, septo e VE, respectivamente). A TRC reduziu o TAV Global máximo (138ms x 131ms; p=0,007) e o TAV Regional do VE (95,9 x 77,3ms; p=0,001). Houve aumento do TAV Regional do VD (54,5 x 78,9ms; p=0,001), sem alteração do TAV Regional do septo (56,4 x 59,6ms; p=ns). O comportamento do TAV Inter-Regional foi: Redução do TAV VE-VD (43,8 x 17,0ms; p=0,001) e do TAV septo-VE (42,6 x 16,3ms; p=0,001) e aumento do TAV septo-VD (6,9 x 16,0ms; p=0,002). CONCLUSÃO: O Mapeamento Eletrocardiográfico de Superfície possibilitou a caracterização detalhada da ativação elétrica ventricular de pacientes portadores de ressincronizador cardíaco através do comportamento elétrico global, regional e Inter-Regional durante ritmo sinusal com bloqueio de ramo esquerdo e estimulação biventricular / INTRODUCTION: The benefits of lower morbidity and mortality obtained with cardiac resynchronization therapy (CRT) in patients with heart failure are already well established. Invasive and noninvasive methods have been used to identify those who will really benefit from CRT, however 30% of these patients do not improve clinically/functionally. Few studies evaluated the cardiac electrical development of patients undergoing CRT. OBJECTIVE: To obtain through the body surface potential mapping (BSPM), a noninvasive approach, characterization of the ventricular electrical activation development in patients after CRT. METHODS: We studied 91 patients with heart failure and left bundle-branch block (LBBB) who underwent CRT, 36 of whom were excluded for AF (20), RBBB (3), hypertrophic (3) or congenital (1) cardiomyopathy, or depended upon a pacemaker before CRT (9). Mean age was 61±10 years, LVEF 0.28±0.9, QRSd 182±24ms, NYHA functional class III(78%) and IV(22%). All underwent BSPM examination of 87 simultaneous leads (58 on the anterior chest, 29 on the back) with the resynchronization device on, then in intrinsic rhythm and LBBB (device off). The BSPM isochronal maps provided maximal and mean global ventricular activation times (VAT) for all the 87 leads. From VATs thus obtained, separate mean values for the RV, septum and LV areas were then calculated. VAT differences between RV-LV, septum-RV and septum-LV, were analyzed and denominated inter-regional VATs. Mann-Whitney, Kruskall-Wallis and Fisher statistics were used, with P.05 established as the significance level. RESULTS: During sinus rhythm/LBBB the BSPM showed patients evidencing prolonged maximal and mean global VATs (138ms and 64.8ms, respectively), with significant regional differences (54.5 vs 56.4 vs 95.9ms; RV, septum and LV, respectively; p<0.0001). CRT reduced the maximal global VAT (138ms vs 131ms; p=0.007) and the LV regional VAT (95.9 vs 77.3ms; p=0.001). The RV regional VAT increased (54.5 vs 78.9ms; p=0.001), with no alteration of the septum regional VAT (56.4 vs 59.6ms; p=ns). The inter-regional VAT developed as follows: decrease in VATLV-RV (43.8 vs 17.0ms; p=0.001) and VATseptum-LV (42.6 vs 16.3ms; p=0.001), and increase in VATseptum-RV (6.9 vs 16.0ms; p=0.002). CONCLUSION: The body surface potential mapping permitted a detailed characterization of the ventricular electrical activation of patients carrying a cardiac resynchronization device, by mapping the global, regional and inter-regional electrical activation development during sinus rhythm with left bundle-branch block, and in biventricular pacing

INTRODUÇÃO: Os benefícios na morbi-mortalidade obtidos pela terapia de ressincronização cardíaca (TRC) em pacientes com insuficiência cardíaca estão bem estabelecidos. Métodos invasivos e não invasivos têm sido utilizados para identificar aqueles que realmente se beneficiarão da TRC, mas 30% destes pacientes não apresentam melhora clínica/funcional. Poucos estudos avaliaram o comportamento elétrico dos pacientes submetidos à TRC. OBJETIVO: Utilizamos um método não invasivo, o mapeamento eletrocardiográfico de superfície (MES) para caracterizar o padrão da ativação elétrica ventricular em pacientes após a TRC. MÉTODOS: Estudamos 91 pacientes submetidos à TRC, com insuficiência cardíaca e bloqueio de ramo esquerdo (BRE), sendo 36 excluídos devido a FA (20), BRD (3), cardiopatias hipertrófica (3) e congênita (1) ou dependentes de marcapasso antes da TRC (9). Idade média:61±10 anos, FEVE:0,28±0,9, QRS:182±24ms, classe funcional NYHA: III(78%) e IV(22%). Com o ressincronizador ligado e desligado, todos realizaram o MES, o qual fornece 87 derivações simultâneas (58 anteriores e 29 posteriores). Os mapas isócronos obtidos pelo MES forneceram os tempos de ativação ventricular (TAV) global máximo e médio nas 87 derivações. Os TAVs obtidos foram regionalizados, sendo calculados os valores médios nas áreas do VD, do septo e do VE. Analisamos a diferença do TAV entre o VD e o VE, entre o septo e o VD e entre o septo e o VE, definidos como TAV Inter-Regional. Utilizados os testes de Mann-Whitney, Kruskall-Wallis, Fisher. Nível de significância: P0.05. RESULTADOS: O MES durante ritmo sinusal e BRE mostrou que os pacientes apresentavam prolongado TAV Global máximo e médio (138ms e 64,8ms, respectivamente) com significativa diferença Regional (54,5 x 56,4 x 95,9ms; p<0,0001; VD, septo e VE, respectivamente). A TRC reduziu o TAV Global máximo (138ms x 131ms; p=0,007) e o TAV Regional do VE (95,9 x 77,3ms; p=0,001). Houve aumento do TAV Regional do VD (54,5 x 78,9ms; p=0,001), sem alteração do TAV Regional do septo (56,4 x 59,6ms; p=ns). O comportamento do TAV Inter-Regional foi: Redução do TAV VE-VD (43,8 x 17,0ms; p=0,001) e do TAV septo-VE (42,6 x 16,3ms; p=0,001) e aumento do TAV septo-VD (6,9 x 16,0ms; p=0,002). CONCLUSÃO: O Mapeamento Eletrocardiográfico de Superfície possibilitou a caracterização detalhada da ativação elétrica ventricular de pacientes portadores de ressincronizador cardíaco através do comportamento elétrico global, regional e Inter-Regional durante ritmo sinusal com bloqueio de ramo esquerdo e estimulação biventricular / INTRODUCTION: The benefits of lower morbidity and mortality obtained with cardiac resynchronization therapy (CRT) in patients with heart failure are already well established. Invasive and noninvasive methods have been used to identify those who will really benefit from CRT, however 30% of these patients do not improve clinically/functionally. Few studies evaluated the cardiac electrical development of patients undergoing CRT. OBJECTIVE: To obtain through the body surface potential mapping (BSPM), a noninvasive approach, characterization of the ventricular electrical activation development in patients after CRT. METHODS: We studied 91 patients with heart failure and left bundle-branch block (LBBB) who underwent CRT, 36 of whom were excluded for AF (20), RBBB (3), hypertrophic (3) or congenital (1) cardiomyopathy, or depended upon a pacemaker before CRT (9). Mean age was 61±10 years, LVEF 0.28±0.9, QRSd 182±24ms, NYHA functional class III(78%) and IV(22%). All underwent BSPM examination of 87 simultaneous leads (58 on the anterior chest, 29 on the back) with the resynchronization device on, then in intrinsic rhythm and LBBB (device off). The BSPM isochronal maps provided maximal and mean global ventricular activation times (VAT) for all the 87 leads. From VATs thus obtained, separate mean values for the RV, septum and LV areas were then calculated. VAT differences between RV-LV, septum-RV and septum-LV, were analyzed and denominated inter-regional VATs. Mann-Whitney, Kruskall-Wallis and Fisher statistics were used, with P.05 established as the significance level. RESULTS: During sinus rhythm/LBBB the BSPM showed patients evidencing prolonged maximal and mean global VATs (138ms and 64.8ms, respectively), with significant regional differences (54.5 vs 56.4 vs 95.9ms; RV, septum and LV, respectively; p<0.0001). CRT reduced the maximal global VAT (138ms vs 131ms; p=0.007) and the LV regional VAT (95.9 vs 77.3ms; p=0.001). The RV regional VAT increased (54.5 vs 78.9ms; p=0.001), with no alteration of the septum regional VAT (56.4 vs 59.6ms; p=ns). The inter-regional VAT developed as follows: decrease in VATLV-RV (43.8 vs 17.0ms; p=0.001) and VATseptum-LV (42.6 vs 16.3ms; p=0.001), and increase in VATseptum-RV (6.9 vs 16.0ms; p=0.002). CONCLUSION: The body surface potential mapping permitted a detailed characterization of the ventricular electrical activation of patients carrying a cardiac resynchronization device, by mapping the global, regional and inter-regional electrical activation development during sinus rhythm with left bundle-branch block, and in biventricular pacing

Ένας μεγάλος αριθμός μελετών παρατήρησης καθώς και τυχαιοποιημένων ελεγχομένων κλινικών δοκιμών έχει πλέον τεκμηριώσει την ασφάλεια, την αποτελεσματικότητα, καθώς και τις μακροπρόθεσμες επιδράσεις της θεραπείας καρδιακού επανασυγχρονισμού (ΘΚΕ) σε ασθενείς με προχωρημένη καρδιακή ανεπάρκεια, επηρεασμένη συσταλτικότητα της αριστεράς κοιλίας (ΑΚ) και ευρύ σύμπλεγμα QRS. Οι περισσότερες τυχαιοποιημένες κλινικές μελέτες με ΘΚΕ αναφέρουν την αποτελεσματικότητα της θεραπείας αυτής σε περίοδο 3 έως 12 μηνών. Αντίθετα, τα δεδομένα σχετικά με την μακροπρόθεσμη έκβαση, ειδικά των ασθενών με προχωρημένη καρδιακή ανεπάρκεια (λειτουργική κλάση III και IV), είναι περιορισμένα και όχι εντελώς σαφή. Σε αντίθεση με τον πλούτο των δεδομένων που αφορούν την αποτελεσματικότητα της ΘΚΕ όμως, και τα οποία έχουν προέλθει από πολλαπλές κλινικές δοκιμές, οι αναφορές σχετικά με την απόδοση της ΘΚΕ στην κλινική πράξη (εκτός δηλαδή ερευνητικών πρωτοκόλλων) είναι σχετικά περιορισμένες και οι μελέτες μακροχρόνιας παρακολούθησης είναι ακόμα λιγότερες. Οι μελέτες που έχουν ασχοληθεί ειδικά με την ηχοκαρδιογραφική ανταπόκριση μετά από ΘΚΕ είναι ως επί το πλείστον μέρος μιας μεγαλύτερης κλινικής δοκιμής. Τόσο σε μελέτες στα πλαίσια κλινικών δοκιμών όσο και σε μελέτες παρατήρησης όμως, οι έρευνες έχουν επικεντρώσει κυρίως σε περιόδους παρακολούθησης 3 έως 6 μηνών, ενώ λίγα μόνο δεδομένα υπάρχουν πέραν των 12 μηνών. Η αντίστροφη αναδιαμόρφωση της ΑΚ, κυρίως κατά την άμεση περίοδο μετά την εμφύτευση, φαίνεται να είναι και ο ισχυρότερος προγνωστικός δείκτης επιβίωσης των ασθενών με καρδιακή ανεπάρκεια που λαμβάνουν ΘΚΕ. Ωστόσο, καθώς η ΑΚ συνεχίζει να αναδιαμορφώνεται και μετά την εμφύτευση, είναι ασαφές κατά πόσον η βραχυπρόθεσμη ευνοϊκή ανταπόκριση που παρατηρείται στο 60% -70% των ασθενών διατηρείται μακροπρόθεσμα. Η ηχοκαρδιογραφία παραμόρφωσης έχει χρησιμοποιηθεί για την εξαγωγή δεικτών καρδιακού δυσυγχρονισμού και την εκτίμηση της λειτουργίας της ΑΚ πριν την εμφύτευση συσκευής ΘΚΕ (αμφικοιλιακού βηματοδότη με ή χωρίς δυνατότητα απινιδωτή). Η ανταπό-κριση των δεικτών παραμόρφωσης της ΑΚ μπορεί να έχει σημαντικές προγνωστικές επιπτώσεις για τους ασθενείς που υποβάλλονται σε ΘΚΕ, λαμβάνοντας υπ’ όψιν ότι οι δείκτες παραμόρφωσης πρόσφατα εδείχθησαν να έχουν ισχυρότερη συσχέτιση με την πρόγνωση των ασθενών με καρδιακή ανεπάρκεια σε σχέση με το κλάσμα εξώθησης ή άλλους κλασσικούς δείκτες της λειτουργικής κατάστασης της ΑΚ. Παρ’ όλα αυτά, ελάχιστα ηχοκαρδιογραφικά δεδομένα υπάρχουν σχετικά με την ανταπόκριση των δεικτών παραμόρφωσης μετά από θεραπεία επανασυγχρονισμού, ενώ δεν υπάρχουν καθόλου στοιχεία πέραν των 6 μηνών. Σε αυτή τη μελέτη, εκτιμήσαμε τη μακροπρόθεσμη ανταπόκριση της λειτουργίας της ΑΚ, όπως αυτή καταγράφεται ηχο¬καρδιο¬γραφικά μετά από τουλάχιστον 12 μήνες παρακολούθησης, μετά από εμφύτευση συσκευής καρδιακού επανασυγχρονισμού με δυνατότητες απινιδωτή (CRT-D). Ο πρωτογενής μας στόχος ήταν να καταγράψουμε συστηματικά, χρησιμοποιώντας συμβατικούς αλλά και νεώτερους ηχοκαρδιογραφικούς δείκτες (απεικόνιση παρα-μόρφωσης), τη μακροπρόθεσμη ανταπόκριση της λειτουργίας της ΑΚ μετά από εμφύτευση συσκευής ΘΚΕ με δυνατότητες απινιδωτή (CRT device with defibrillator capacity, CRT-D) σε ασθενείς με προχωρημένη καρδιακή ανεπάρκεια οι οποίοι λαμβάνουν βέλτιστη φαρμακευτική αγωγή. Οι δευτερογενείς μας στόχοι ήταν (α) να καταγράψουμε τη μακροπρόθεσμη (>12 μήνες) ανταπόκριση του δυσσυγχρονισμού της ΑΚ, όπως αυτή καταγράφεται με ηχοκαρδιογραφική απεικόνιση παραμόρφωσης (β) να συσχετίσουμε τους δείκτες δυσσυγχρονισμού της ΑΚ πριν από την εμφύτευση με τη μακροπρόθεσμη ανταπόκριση της λειτουργίας της ΑΚ, και (γ) να συσχετίσουμε τους συμβατικούς και νεώτερους ηχοκαρδιογραφικούς δείκτες λειτουργίας της αριστεράς κοιλίας πριν από την εμφύτευση με τη μακροπρόθεσμη ανταπόκριση της λειτουργίας της ΑΚ. / Several observational studies and randomized controlled trials (RCTs) have demonstrated the safety, efficacy, and long-term effects of cardiac resynchronization therapy (CRT) in patients with advanced heart failure, reduced left ventricular systolic function, and wide QRS complex. Most clinical trials with CRT report efficacy within a 3-to-12 month time frame. However, data on long-term effects, especially for advanced heart failure patients with NYHA class III-IV, are limited and unclear. In contrast to the wealth of data on efficacy of CRT, reports on effectiveness of CRT in clinical practice (i.e. outside the context of RCTs) are limited and data on long-term effectiveness are scarce. Studies dealing with echocardio-graphic responses come largely from sub-studies of larger RCTs. However, both these sub-studies as well as observational studies have focused on short-term echocardiographic responses, whereas very limited data exist beyond 12 months. Reverse remodeling of the left ventricle in response to CRT in the immediate post-implant period is the strongest predictor of long-term prognosis in these patients. However, as the left ventricle continues to remodel long after CRT device implantation, it is unclear whether the initial favorable response observed in 60% to 70% of CRT recipients is maintained long term. Deformation echocardiography has been used to derive ventricular dyssynchrony indices and assess left ventricular function prior to CRT device implantation (biventricular pacemaker with or without defibrillator capacity). The response of myocardial deformation indices of the left ventricle may have important prognostic implications for CRT recipients, considering that deformation parameters have been shown to have a stronger association with prognosis compared with ejection fraction or other conventional indices of left ventricular function. Nevertheless, limited echocardiographic data exist on the response of myocardial deformation indices to CRT, whereas no data exist beyond 6 months post CRT. In this study, we have evaluated the long-term echocardiographic response of left ventricle to CRT after a minimum of 12 months of follow up after implantation of a CRT device with defibrillator capacity (CRT-D). Our primary aim was to systematically record, using both conventional and novel echocardiographic indices (myocardial deformation), the long-term (12 months or longer) response of the left ventricle after CRT-D device implantation in patients with advanced heart failure receiving optimal medical therapy. Our secondary aims were to (a) record the long-term response of left ventricular dyssynchrony assessed with myocardial deformation indices in these patients; (b) correlate left ventricular dyssynchrony indices before CRT-D device implantation with long-term response of the left ventricle, and (c) correlate both conventional and novel left ventricular function indices before implantation with long-term response of the left ventricle after CRT-D device implantation.

No description available.

The objective of this thesis is to evaluate the use of Doppler echocardiography markers ofglobal dyssynchrony [total isovolumic time (t-IVT)] in the following 6 studies: 1) Its prognostic role in predicting cardiac events in patients undergoing CABG surgery,compared with conventional global systolic and diastolic measurements. 2) Its additional value in predicting six minute walk test (6-MWT) in patients with leftventricular (LV) ejection fraction (EF) &lt;45%. 3) Its prognostic value in comparison with other clinical, biochemical and echocardiographicvariables in patients with chronic systolic heart failure (HF). 4) The relationship between 6-MWT and cardiac function measurements in a consecutivegroup of patients, irrespective of EF and to identify predictors of exercise capacity. 5) To investigate the effect of age on LV t-IVT and Tei index compared with conventionalsystolic and diastolic parameters. 6) To assess potential additional value of markers of global LV dyssynchrony in predictingcardiac resynchronization therapy (CRT) response in HF patients. Study I Methods: This study included 74 patients before routine CABG who were followed up for18±12 months. Results: At follow-up, 29 patients were hospitalized for a cardiac event or died. LV-ESD wasgreater (P=0.003), fractional shortening (FS) lower (p&lt;0.001), E:A ratio and Tei index higher(all P&lt;0.001), and t-IVT longer (P&lt;0.001) in patients with events. Low FS [0.66 (0.50–0.87),P&lt;0.001], high E:A ratio [l4.13 (1.17–14.60), P=0.028], large LV-ESD [0.19 (0.05–0.84),P=0.029], and long t-IVT [1.37 (1.02–1.84), P=0.035] predicted events and deaths. Conclusion: Despite satisfactory surgical revascularization, long t-IVT and systolicdysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABGcardiac events. Study II Methods: We studied 77 patients (60±12 year, and 33.3% females) with stable HF using 6-MWT.iii Results: E’ wave (r=0.61, p&lt;0.001), E/e’ ratio (r=-0.49, p&lt;0.001), t-IVT (r=-0.44, p&lt;0.001),Tei index (r=-0.43, p&lt;0.001) and NYHA class (r=-0.53, p&lt;0.001) had the highest correlationwith the 6-MWT distance. In multivariate analysis, only E/e’ ratio [0.800 (0.665-0.961),p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor 6-MWTperformance (&lt;300m). Conclusions: In HF, the higher the filling pressures and the more dyssynchronous the LV, thepoorer is the patient’s exercise capacity. Study III Methods: We studied 107 systolic HF patients; age 68±12 year, 25% females and measuredplasma NT-pro-BNP. Results: Over a follow-up period of 3718 months, t-IVT ≥12.3 sec/min, mean E/Em ratio≥10, log NT-pro-BNP levels ≥2.47 pg/ml and LV EF ≤32.5% predicted clinical events. Theaddition of t-IVT and NT-pro-BNP to conventional clinical and echocardiographic variablessignificantly improved the χ2 for the prediction of outcome from 33.1 to 38.0, (p&lt;0.001). Conclusions: Prolonged t-IVT adds to the prognostic stratification of patients with systolicHF. Study IV Methods: We studied 147 HF patients (61±11 year, 50.3% male) with 6-MWT.Results: The 6-MWT correlated with t-IVT (r=-0.49, p&lt;0.001) and Tei index (r=-0.43,p&lt;0.001) but not with any of the other clinical or echocardiographic parameters. Group Ipatients (&lt;300m) had lower Hb (p=0.02), lower EF (p=0.003), larger left atrium (p=0.02),thicker septum (p=0.02), lower A wave (p=0.01) and lateral wall a’ (p=0.047), longerisovolumic relaxation time (r=0.003) and longer t-IVT (p= 0.03), compared with Group II(&gt;300m). Only t-IVT ratio [1.257 (1.071-1.476), p=0.005], LV EF [0.947 (0.903-0.993),p=0.02], and E/A ratio [0.553 (0.315-0.972), p=0.04] independently predicted poor 6-MWTperformance. Conclusion: In HF, the limited 6-MWT is related mostly to severity of global LVdyssynchrony, more than EF or raised filling pressures. Study V Methods: We studied 47 healthy individuals (age 62±12 year, 24 female), arbitrarilyclassified into: M (middle age), S (seniors), and E (elderly). Results: Age strongly correlated with t-IVT (r=0.8, p&lt;0.001) and with Tei index (r=0.7,p&lt;0.001), E/A ratio (r=-0.6, p&lt;0.001), but not with global or segmental systolic function measurements or QRS duration. The normal upper limit of the t-IVT (95% CI) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively, being shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p&lt;0.001), E/Aratio (r=-0.56, p&lt;0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but notwith QRS. Conclusions: In normals, age is associated with exaggerated LV global dyssynchrony anddiastolic function disturbances, but systolic function remains unaffected. Study VI Methods: We studied 103 HF patients (67±12 year, 82.5% male) recruited for CRTtreatment. Results: Prolonged t-IVT [0.878 (0.802-0.962), p=0.005], long QRS duration [0.978 (0.960-0.996), p=0.02] and high tricuspid regurgitation pressure drop (TRPD) [1.047 (1.001-1.096),p=0.046] independently predicted response to CRT. A t-IVT ≥11.6 s/min was 67% sensitiveand 62% specific (AUC 0.69, p=0.001) in predicting CRT response. Respective values for aQRS ≥ 151ms were 66% and 62% (AUC 0.65, p=0.01). Combining the two variables had asensitivity of 67% but higher specificity of 88% in predicting CRT response. In atrialfibrillation (AF) patients, only prolonged t-IVT ≥11 s/min [0.690 (0.509-0.937), p=0.03]independently predicted CRT response with a sensitivity of 69% and specificity of 79% (AUC0.78, p=0.015). Conclusion: Combining prolonged t-IVT and broad QRS had higher specificity in predictingresponse to CRT, with the former the sole predictor of response in AF patients.

The definition of optimal selection criteria for maximizing the response rate to Cardiac Resynchronization Therapy (CRT) is still an issue under active debate. Recent clinical approaches propose a classification of patients into classes of mechanisms that could lead to heart failure and study their response to the therapy. In this line of research, the computation of a metric between the motion and deformation patterns of a given subject and well identified classes of CRT responders is considered in this thesis, as the basis of a new strategy to compute patient selection indexes. The thesis proposes first an improved design for the construction of statistical atlases of myocardial motion and deformation, and applies it to the characterization of populations of patients involved in CRT. The added-value of our approach is highlighted in a clinical study, applying the methodology to a large population of patients with a given pattern of dyssynchrony (septal flash) and understanding the link between its correction and CRT response. Finally, we propose a method to extend the analysis to the comparison of individuals to reference populations, either healthy or pathological, using manifold learning techniques to model a disease as progressive deviations from normality along a manifold structure, and demonstrate the potential of our method for inter-subject comparison in CRT patients. / La definición de un criterio óptimo para mejorar la respuesta a la Terapia de Resincronización Cardíaca (TRC) sigue siendo un debate abierto. Estudio clínicos recientemente publicados proponen clasificar pacientes según diversos mecanismos patofisiológicos que pueden inducir insuficiencia cardíaca y estudian su respuesta a la terapia. Siguiendo esta línea de investigación, esta tesis considera el cálculo de una distancia entre los patrones de movimiento y deformación de un individuo y las clases de respondedores a la TRC, siendo la base de una nueva estrategia para calcular índices para seleccionar pacientes. Esta tesis presenta primero un método para construir un atlas estadístico de movimiento y deformación miocárdica, y su aplicación posterior a la caracterización de poblaciones de potenciales candidatos a la TRC. El valor añadido de nuestro método se enfatiza en un estudio clínico, en el cual se aplica la metodología a una gran población de pacientes con un patrón específico de disincronía cardíaca (llamado septal flash), y se relaciona su corrección y la respuesta a la TRC. Finalmente, se extiende el método para comparar individuos a una población de referencia, sana o patológica, usando técnicas de manifold learning para representar una patología como una desviación progresiva de la normalidad, con una estructura no lineal específica, y se demuestra el potencial de nuestro método para comparar entre sí candidatos a la TRC.