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) <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<0.001), E:A ratio and Tei index higher(all P<0.001), and t-IVT longer (P<0.001) in patients with events. Low FS [0.66 (0.50–0.87),P<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<0.001), E/e’ ratio (r=-0.49, p<0.001), t-IVT (r=-0.44, p<0.001),Tei index (r=-0.43, p<0.001) and NYHA class (r=-0.53, p<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 (<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<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<0.001) and Tei index (r=-0.43,p<0.001) but not with any of the other clinical or echocardiographic parameters. Group Ipatients (<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(>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<0.001) and with Tei index (r=0.7,p<0.001), E/A ratio (r=-0.6, p<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<0.001), E/Aratio (r=-0.56, p<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.

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: 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

International Telemetering Conference Proceedings / October 21, 2002 / Town & Country Hotel and Conference Center, San Diego, California / The Nova HYPERMOD demodulator operates in three modes, the classic pulse-code modulation/frequency modulation (PCM/FM), sometimes known as continuous phase frequency shift keying (CPFSK) mode, shaped offset quadrature phase shift keying (SOQPSK) mode, and continuous phase modulation (CPM) mode. Of interest to this paper is SOQPSK mode which is a waveform similar to the Advanced Range Telemetry (ARTM) Tier I waveform, Feher’s Quadrature Phase Shift Keying, B version (FQPSK-B) revision (Rev) A1. Also considered is another variant, FQPSK-JR. This paper will outline the cross compatibility and resynchronization speed of these waveforms based upon ARTM-adopted demodulator performance tests. The results of these laboratory tests comparing the HYPERMOD demodulator, the enhanced Tier I demodulator, and the current Tier I reference demodulator, both from RF Networks, will be presented.

No transporte de vídeo e áudio para aplicações de TV digital com recepção em terminais móveis podem ser utilizadas redes de distribuição de conteúdo baseadas em pacotes. Essas redes tornam o transporte dos sinais mais flexível. Entretanto, podem adicionar atrasos e variações de atraso, prejudicando o sincronismo dos fluxos de informação e, conseqüentemente, a apresentação das mídias. Nesta dissertação foi proposto um framework para avaliação e testes de sincronismo, desenvolvido para estudar a influência das perturbações causadas por redes de dados ou por remultiplexações no sincronismo de programas MPEG2. O framework possibilita o controle dos parâmetros de QoS da rede de distribuição utilizada para transmitir pacotes de um fluxo de transporte (MPEG2 Transport Stream) e permite avaliar a influência desses parâmetros no sincronismo do fluxo. Adicionalmente, foram implementados mecanismos de ressincronização do fluxo de transporte no framework, de forma a minimizar os efeitos dessas perturbações na rede. Verificou-se que os métodos implementados reduzem os efeitos de variações de atraso da rede e ressincronizam o fluxo de transporte transmitido, de forma que a variação de atraso nas amostras da referência de tempo do fluxo (Program Clock Reference . PCR) volta aos níveis anteriores (sem aplicação de variação de atraso na rede). / Content distribution packet networks can be used in video and audio transport for TV applications with reception in mobile terminals. These networks make signal transport more flexible. Nevertheless, they may add delay and jitter, damaging the synchronism of the information streams and, consequently, the media presentation. In this dissertation, a framework was proposed for synchronism test and evaluation. It was developed to study the influence of disturbances caused by data networks or remultiplexations in the synchronism of MPEG2 programs. The framework enables the control of QoS parameters of the distribution network used to transmit packets from a MPEG2 transport stream and allows the evaluation of the influence of these parameters in the synchronism of the streams. Furthermore, transport stream resynchronization mechanisms were implemented in the framework, minimizing the effects of these disturbances in the network. It was observed that the methods implemented reduce the effects of jitter in the network and resynchronize the transport stream transmitted, in a way that the jitter in the time reference samples (Program Clock Reference . PCR) of the stream returns to previous levels (without applying jitter in the network).

Introdução. Sabe-se que a terapia de ressincronização cardíaca (TRC) aumenta a capacidade ao esforço e reduz a ativação simpática em pacientes com insuficiência cardíaca (IC). Por outro lado, existem evidências de que o treinamento físico (TF) melhora o controle neurovascular, tolerância ao exercício e qualidade de vida dos pacientes com IC. Neste estudo, nós testamos a hipótese de que o TF associado à TRC diminuiria a atividade nervosa simpática muscular (ANSM) e a vasoconstrição periférica. Adicionalmente, esta associação de TRC e TF melhoraria a função cardíaca, consumo de oxigênio pico e qualidade de vida nesses pacientes. Métodos. Vinte e oito pacientes com IC submetidos há um mês de TRC e fração de ejeção < 35% foram consecutivamente e aleatoriamente divididos em dois grupos: treinados (TRCt, n=14, 54 ± 4 anos) e não-treinados (TRCs, n=14, 57 ± 1 anos). Um grupo de indivíduos controles saudáveis também foi incluído no estudo (n=11, 43 ± 4 anos). A ANSM foi avaliada diretamente pela técnica de microneurografia. O fluxo sanguíneo muscular foi avaliado pela técnica de pletismografia de oclusão venosa. A capacidade física foi avaliada pelo teste cardiopulmonar, a função cardíaca pelo ecocardiograma e a qualidade de vida pelo questionário Minnesota Living with Heart Failure. O TF foi realizado em esteira ergométrica por 40 minutos, 3 vezes por semana, durante 4 meses. Resultados. No período pré-intervenção, a ANSM foi significativamente maior (p=0,01) nos pacientes com IC quando comparados com os indivíduos saudáveis. O fluxo sanguíneo muscular não foi diferente entre os grupos estudados (p=0,24). Após quatro meses de treinamento físico, a ANSM foi reduzida (65 ± 7 vs 43 ± 8 disparos/100batimentos, p < 0,001), atingindo níveis semelhantes àqueles observados nos indivíduos saudáveis (43 ± 8 vs 31 ± 3 disparos/100batimentos, p=0,44). Além disso, o TF associado a TRC aumentou o FSM (1,63 ± 0,14 vs 1,85 ± 0,12 ml/min/100ml, p=0,02), a fração de ejeção (28 ± 3 vs 33 ± 4%, p=0,04) e a capacidade funcional (18,5 ± 1,1 vs 21,5 ± 1,7 ml/kg/min, p=0,04), o que não foi observado no grupo TRCs. Não houve alteração significativa na qualidade de vida dos pacientes (26 ± 4 vs 20 ± 4, p=0,11). Conclusão. O treinamento físico associado à TRC melhora expressivamente o controle neurovascular, a função cardíaca e a capacidade física em pacientes com IC. Estes achados destacam a importância da inclusão do treinamento físico no tratamento de pacientes com IC submetidos à TRC / Background. Cardiac Resynchronization Therapy (CRT) is known to increase exercise capacity and decrease sympathetic activation in HF. On the other hand, there is evidence that exercise training improves neurovascular control, physical capacity and quality of life in HF patients. We tested the hypothesis that exercise training (ET) associated with CRT would reduce muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction in chronic heart failure patients. In addition, the association of CRT and ET would improve cardiac function, peak oxygen consumption and quality of life in these patients. Methods. Twenty-eight HF patients submitted a month of CRT, EF < 35%, with CRT for 1 month were consecutively and randomly divided into two groups: Exercise-trained (CRTt, n=14, 54 ± 4 years old) and untrained (CRTs, n=14, 57 ± 1 years old). A control group was also involved in the study (n=11, 43 ± 4 years). MSNA was directly evaluated by microneurography technique and forearm blood flow by venous occlusion plethysmography. Peak VO2 was determined by cardiopulmonary exercise test, cardiac function by echocardiography and quality of life by Minnesota Living with Heart Failure questionnaire. ET consisted of three 40-minute exercise sessions per week on a treadmill for four months. Results. Baseline MSNA was significantly higher (p=0.01) in heart failure patients when compared with healthy controls. The forearm blood flow was not different between groups (p=0.24). After four months of ET, MSNA was significantly reduced (65±7 vs 43±8 bursts/100 heart beats, p < 0.001) reaching levels similar to those observed in healthy subjects (43±8 vs. 31±3 bursts/100 heart beats, p=0.44). Furthermore, ET associated with CRT increased forearm blood flow (1.63±0.14 vs. 1.85±0.12 ml/min/100ml, p=0.02), EF (28±3 vs. 33±4%, p=0.04) and peak VO2 (18.5±1.1 vs 21.5 ± 1.7 ml/kg/min, p=0.04), which was not observed in the CRTs. There was not significant changes in the quality of life of patients (26 ± 4 vs. 20 ± 4, p=0.11). Conclusions. ET associated with CRT improves neurovascular control, cardiac function and functional capacity in heart failure patients. These findings highlight the importance of including ET in the treatment of heart failure patients submitted to CRT

O objetivo deste estudo foi avaliar o efeito da ressincronização da ovulação, iniciada 24 dias após a primeira IATF, sobre a área do corpo lúteo (CL), a concentração plasmática de progesterona (P4) e a taxa de prenhez. Exp.1 526 novilhas Brangus com idades entre 24 e 26 meses, foram submetidas a um programa de IATF no início da estação de acasalamento. O protocolo de sincronização para a primeira IATF começou com a inserção de um implante intra-vaginal contendo 750 mg de P4 e a administração de 2 mg de benzoato de estradiol (BE) intramuscular (i.m.) no dia -9 (D-9). Depois de sete dias (D-2), os implantes de P4 foram removidos, e 150 μg de D-cloprostenol (PGF), i.m., e 1 mg de cipionato de estradiol (CE), i.m., foram administrados. A IATF foi realizada entre 48 e 54 horas após a remoção do implante de P4 (D0). Vinte e quatro dias após a primeira IATF (D24), as novilhas foram divididas aleatoriamente nos seguintes grupos experimentais: controle (n = 167, sem tratamento), BE (n = 208, 1 mg de BE, i.m.) e hCG (n = 151, 1000 UI de hCG, i.m.). Novilhas dos grupos BE e hCG receberam um novo implante intra-vaginal contendo 750 mg de P4 na D24. No dia 31 (D31), os implantes de P4 foram removidos e o diagnóstico de prenhez foi realizado por ultrassonografia. As taxas de prenhez da primeira IATF no D31 foram 58,7% (98/167), 53,4% (111/208) e 52,9% (80/151), respectivamente, para os grupos controle, BE e hCG. Novilhas diagnosticadas como não gestantes receberam 150 μg de PGF, i.m., e 1 mg de CE, i.m., sendo a segunda IATF realizada 48 a 54 horas após a remoção do implante (D33). No D31, os subgrupos de novilhas prenhes de cada grupo experimental foram aleatoriamente divididos, sendo realizado exame por ultrassonografia para determinar a área do CL e coleta de uma amostra de sangue para determinar a concentração sérica de P4: Controle (n = 13), BE (n = 26), e hCG (n = 24). A área de CL foi significativamente maior (P<0,05) no grupo hCG (3,42±0,76 cm2), em comparação aos grupos de BE (2,44±0,57 cm2) e controle (2,61±0,61 cm2). Da mesma forma, a concentração sérica de P4 foi significativamente maior (P<0,05) no grupo hCG (12,43±3,48 ng/ml) em comparação aos grupos BE (6,92±3,04 ng/ml) e controle (7,29±2,45 ng/ml). O uso do BE e do hCG em programas de ressincronização da ovulação 24 dias após a IATF não interferiu na taxa de prenhez da primeira IATF. É provável que o mecanismo de ação do BE não afete a atividade do CL, a produção de P4, e consequentemente, não tenha efeito negativo na manutenção da prenhez em protocolos de ressincronização da ovulação. O tratamento com hCG resultou no aumento da área de CL e da produção de P4, porém, este efeito não favoreceu a taxa de prenhez da primeira IATF. Exp.2 184 novilhas Brangus com idade entre 24 a 26 meses e peso corporal médio de 361±29,2 kg foram submetidas a dois programas de IATF. O protocolo de sincronização para a primeira IATF foi o mesmo utilizado no Exp.1. Vinte e quatro dias após a primeira IATF (D24), as novilhas foram aleatoriamente divididas conforme os hormônios utilizados para ressincronização, formando os seguintes grupos experimentais: BE (n = 83, 1 mg de BE, i.m.) e hCG (n = 101, 1000 UI de hCG, i.m.). Novilhas dos grupos BE e hCG receberam um novo dispositivo intravaginal contendo 750mg de progesterona no D24. No D31, os implantes foram removidos e o diagnóstico de gestação por ultrassonografia foi realizado. As taxas de prenhez da primeira IATF no D31 foram de 63,9% (53/83) e 64,9% (65/101), respectivamente, para os grupos BE e hCG. Novilhas diagnosticadas como não gestantes (n=66) receberam 150 μg de PGF, i.m., e 1 mg de CE, im; a segunda IATF foi realizada no D33. Trinta dias após a segunda IATF (D63), foi realizado o segundo diagnóstico de gestação. As perdas gestacionais entre o D31 e D63, das novilhas prenhes da primeira IATF foram 9,4% (5/53) e 6,2% (4/65) respectivamente para os grupos BE e hCG. As taxas de prenhez da segunda IATF foram 40,0% (12/30) e 22,2% (8/36), respectivamente, para os grupos BE e hCG. As taxas de prenhez acumulada para os grupos BE e hCG foram, respectivamente, 72,3% (60/83) e 68,3% (69/101). O uso do BE e hCG para ressincronização da ovulação 24 dias após a primeira inseminação não afetou a taxa de prenhez da primeira IATF. As taxas de prenhez obtidas na segunda IATF foram inferiores às expectativas, considerando a resposta da primeira IATF. Entretanto, as taxas de prenhez acumulada foram similares e satisfatórias para os primeiros 33 dias da estação de acasalamento. / The aim of this study was to evaluate the effect of resynchronization of ovulation, which began 24 days after the first TAI, on the corpus luteum area (CL), plasma progesterone production (P4) and pregnancy rates. Exp.1 526 Brangus heifers between 24 and 26 months of age were submitted to a TAI program at the beginning of the breeding season. The protocol synchronization for the first TAI started with the insertion of an intravaginal implant containing 750 mg progesterone (P4) and the administration of 2 mg of estradiol benzoate (EB) intramuscular (i.m.) on day -9 (D-9). After seven days (D-2), P4 implants were removed, and 150 μg D-cloprostenol (PGF), and 1 mg estradiol cypionate (EC), were administered, i.m. The TAI was carried out between 48 and 54 hours after removal of the P4 implant (D0). Twenty-four days after the first TAI (D24), heifers were divided randomly into the following groups: control (n = 167, untreated), EB (n = 208, 1 mg EB, i.m.) and hCG (n = 151, 1000 IU hCG, i.m.). Heifers of the EB and hCG groups received a new intravaginal implant containing 750 mg of P4 on D24. On day 31 (D31), P4 implants were removed and the pregnancy diagnosis was performed by ultrasonography. Pregnancy rates for the first TAI, on D31, were 58.7% (98/167), 53.4% (111/208) and 52.9% (80/151), respectively, for the control, EB and hCG groups. Non-pregnant heifers received 150 μg PGF, i.m., and 1 mg EC, i.m., and the second TAI was performed 48 to 54 hours after removal of the P4 implant (D33). On D31, subgroups of pregnant cows from each experimental groups were randomly divided to determine the surface area of the CL by ultrasound and blood samples were collected to determine P4 concentrations: control (n = 13), BE (n = 26), and hCG (n = 24). The surface area of the CL was significantly higher (P<0.05) in the hCG group (3.42±0.76 cm2) compared to the EB (2.44±0.57 cm2) and control (2.61±0.61 cm2) groups. Also, P4 concentrations were significantly higher (P<0.05) in the hCG group (12.43±3.48 ng/mL) compared to the EB groups (6.92±3.04 ng/mL) and control (7.29±2.45 ng/mL). The use of EB and hCG in ovulation resynchronization programs 24 days after TAI did not affect the pregnancy rates of the first TAI. It is likely that EB mechanism of action does not affect the activity of the CL and P4 production, consequently having no negative effect on the maintenance of pregnancy. Nevertheless, the hCG treatment on D24 increased the area of CL and P4 plasma levels, but this effect neither improves nor compromised pregnancy rate of the first TAI. Exp.2 184 aged 24-26 months Brangus heifers old with mean body weight of 361±29.2 kg were submitted to two consecutive TAI programs. The synchronization protocol to the first TAI was the same as in Exp.1. Twenty-four days after the first TAI (D24), heifers were randomly divided according to the hormones used for resynchronization, according to the following groups: BE (n = 83, 1 mg EB, i.m.) and hCG (n = 101, hCG 1000 IU, i.m.). Heifers of the EB and hCG groups received a new intravaginal device containing 750 mg of progesterone on D24. On D31, P4 implants were removed and pregnancy diagnosis was performed by ultrasonography. The first TAI pregnancy rates on D31 were 63.9% (53/83) and 64.9% (65/101), respectively, for the EB and hCG groups. Heifers diagnosed as open received 150 μg PGF, i.m., and 1 mg EC, i.m.; the second TAI was performed on D33. Thirty days after the second TAI (D63), the second pregnancy diagnosis was performed. Pregnancy loss rates from D31 to D63 were 9.4% (5/53) and 6.2% (4/65) respectively for the EB and hCG groups. Heifers diagnosed as open received 150 μg PGF, i.m., and 1 mg EC, i.m.; the second TAI was performed on D33. Thirty days after the second TAI (D63), the second pregnancy diagnosis was performed. Pregnancy loss rates from D31 to D63 were 9.4% (5/53) and 6.2% (4/65) respectively for the EB and hCG groups. Pregnancy rates for the second TAI were 40.0% (12/30) and 22.2% (8/36), for the EB and hCG groups respectively. The cumulative pregnancy rates for EB and hCG groups were, respectively, 72.3% (60/83) and 68.3% (69/101). The use of hCG and EB for resynchronization of ovulation 24 days after the first insemination did not affect pregnancy rates of the first TAI. Pregnancy rates obtained in the second TAI were below expected values, considering the first TAI response. However, cumulative pregnancy rates were similar and satisfactory for the first 33 days of the breeding season.