MARTINO MARTINELLI FILHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- Myocardial function reclassification: Echocardiographic strain patterns in patients with chronic Chagas cardiomyopathy and intraventricular dyssynchrony(2022) ATHAYDE, Guilherme A. T.; BORGES, Bruno C. C.; PINHEIRO, Andreia O.; SOUZA, Aline L.; OLIVEIRA, Camila P.; MARTINS, Sergio A. M.; TEIXEIRA, Ricardo A.; SIQUEIRA, Sergio F.; PORTER, Thomas Richard; MATHIAS JR., Wilson; MARTINELLI FILHO, MartinoBackground: We aimed to identify, among Chronic Chagas Cardiomyopathy (CCC) patients with left ventricular dysfunction (LVD) and non-left bundle branch block (non-LBBB), subgroups with different functional and mechanical patterns of global longitudinal strain (GLS) and intraventricular dyssynchrony (IVD) at rest and after exercise stress test, and reclassify them using a new echocardiographic approach. Methodology: In this single-center cross-sectional study, 40 patients with CCC, left ventricular ejection fraction (LVEF) <= 35% and non-LBBB underwent rest echocardiography and then treadmill exercise stress echocardiography with GLS and IVD analysis. The sample was divided into four groups, based on GLS and IVD significant variation between rest and exercise: GLS + IVD+ (9 patients); GLS + IVD- (9 patients); GLS-IVD+ (10 patients); GLS-IVD- (10 patients). Results: At rest, median LVEF was 28% (21.3%-33%) and GLS (-7% (-5%/-9.3%), were not different among groups. The average response of GLS was an increase of 0.74% over rest values, and the average response of IVD was a decrease of 6.9 ms. Group GLS-IVD+ presented more dyssynchrony at rest (p = 0.01). Left atrial (LA) volume (higher in GLS-IVD-) (p = 0.022) and TAPSE (higher in GLS + IVD+) (p = 0.015) were also different among groups at baseline. Of the 40 patients evaluated, 27 (67.5%) had very severe LVD (GLS < -8%). In addition, among these patients, 11 patients had contractile reserve after undergoing stress echocardiography. Conclusions: In patients with CCC, severe LVD and non-LBBB, the evaluation of GLS and IVD between rest and exercise was able to reclassify myocardial function and to identify subgroups with contractile reserve and significant dyssynchronopathy.
article 5 Citação(ões) na Scopus Comparação entre a ecocardiografia 2D e 3D na avaliação do remodelamento reverso após a TRC(2011) HOTTA, Viviane Tiemi; MARTINELLI FILHO, Martino; MADY, Charles; MATHIAS JR., Wilson; VIEIRA, Marcelo Luiz CamposBackground: Echocardiography is a useful method for screening and assessing response to cardiac resynchronization therapy (CRT). 3D echocardiography has already established its role in the evaluation of ventricular volumes and ejection fraction (LVEF) with excellent correlation of results when compared with magnetic resonance imaging (MRI). Objective: To compare the evaluation of ventricular volumes (LVDV, LVSV), LVEF, and LV mass before and after CRT by 2D echocardiography and three-dimensional echocardiography. Methods: We evaluated 24 patients with heart failure (HF), functional class (FC) III or IV (NYHA), sinus rhythm QRS >= 120 ms, during an optimized therapy for HF undergoing CRT. We conducted electrocardiogram (ECG), clinical evaluation, 2D and 3D echocardiography before, three and six months after CRT. The comparison between the techniques was performed using Pearson's correlation (r). Results: At baseline, the correlation between methods was 0.96 for evaluation of LVDV, 0.95 for evaluation of LVSV, 0.87 for LVEF and 0.72 for LV mass. After three months of CRT, the correlation between methods for analysis of LVDV was 0.96, 0.95 for LVSV, 0.95 for LVEF, and 0.77 for LV mass. After six months of CRT, the correlation between 2D and 3D echocardiography for analysis of LVDV was 0.98, 0.91 for LVSV, 0.96 for LVEF, and 0.85 for LV mass. Conclusion: This study reported was a reduction of LVDV, LVSV, besides improvement in LVEF after CRT. There was an excellent correlation between the 2D and 3D echocardiography for evaluation of ventricular volumes and LVEF, and a good correlation between methods for evaluation of left ventricular mass before and after CRT. (Arq Bras Cardiol 2011; 97(2) : 111-121)- Complications after Surgical Procedures in Patients with Cardiac Implantable Electronic Devices: Results of a Prospective Registry(2016) SILVA, Katia Regina da; ALBERTINI, Caio Marcos de Moraes; CREVELARI, Elizabeth Sartori; CARVALHO, Eduardo Infante Januzzi de; FIORELLI, Alfredo Inacio; MARTINELLI FILHO, Martino; COSTA, RobertoBackground: Complications after surgical procedures in patients with cardiac implantable electronic devices (CIED) are an emerging problem due to an increasing number of such procedures and aging of the population, which consequently increases the frequency of comorbidities. Objective: To identify the rates of postoperative complications, mortality, and hospital readmissions, and evaluate the risk factors for the occurrence of these events. Methods: Prospective and unicentric study that included all individuals undergoing CIED surgical procedures from February to August 2011. The patients were distributed by type of procedure into the following groups: initial implantations (cohort 1), generator exchange (cohort 2), and lead-related procedures (cohort 3). The outcomes were evaluated by an independent committee. Univariate and multivariate analyses assessed the risk factors, and the Kaplan-Meier method was used for survival analysis. Results: A total of 713 patients were included in the study and distributed as follows: 333 in cohort 1, 304 in cohort 2, and 76 in cohort 3. Postoperative complications were detected in 7.5%, 1.6%, and 11.8% of the patients in cohorts 1, 2, and 3, respectively (p = 0.014). During a 6-month follow-up, there were 58 (8.1%) deaths and 75 (10.5%) hospital readmissions. Predictors of hospital readmission included the use of implantable cardioverter-defibrillators (odds ratio [OR] = 4.2), functional class III--IV (OR = 1.8), and warfarin administration (OR = 1.9). Predictors of mortality included age over 80 years (OR = 2.4), ventricular dysfunction (OR = 2.2), functional class III-IV (OR = 3.3), and warfarin administration (OR = 2.3). Conclusions: Postoperative complications, hospital readmissions, and deaths occurred frequently and were strongly related to the type of procedure performed, type of CIED, and severity of the patient's underlying heart disease.
- Cardiac resynchronization therapy restores muscular metaboreflex control(2019) SPAGGIARI, Caio V.; KUNIYOSHI, Ricardo R.; ANTUNES-CORREA, Ligia M.; GROEHS, Raphaela V.; SIQUEIRA, Sergio F. de; MARTINELLI FILHO, MartinoIntroduction The muscular metaboreflex, whose activation regulates blood flow during isometric and aerobic exercise, is blunted in patients with heart failure (HF), and cardiac resynchronization therapy (CRT) may restore this regulatory reflex. Objective To evaluate metaboreflex responses after CRT. Methods Thirteen HF patients and 12 age-matched healthy control subjects underwent the following evaluations (pre- and post-CRT implantation in the patient group): (a) heart rate, blood pressure, and forearm blood flow measurements; (b) muscle sympathetic nerve activity (MSNA) evaluation; and (c) peak oxygen consumption (VO2peak). Examinations were performed at rest, during moderate isometric exercise (IE), and during forearm ischemia (metaboreflex activation). The primary outcome was the increment in MSNA during limb ischemia compared to the rest moment (Delta MSNA rest to metaboreflex activation). Results After CRT, rest MSNA decreased in the HF participants: 50.4 +/- 9.2 bursts/min pre-CRT vs 34.0 +/- 14.4 bursts/min post-CRT, P = .001, accompanied by an improvement in systolic blood pressure and in rate-pressure product. MSNA during limb ischemia decreased: 56.6 +/- 11.5 bursts/min pre-CRT vs 43.6 +/- 12.7 bursts/min post-CRT, P = .001, and the Delta MSNA rest to metaboreflex activation increased: 0% (interquartile range [IQR)], -7 to 9) vs 13% (IQR, 5-30), P = .03. An augmentation of mean blood pressure during limb ischemia post-CRT was noticed: 94 mmHg (IQR, 81-104) vs 110 mmHg (IQR, 100-117), P = .04. CRT improved VO2peak, and this improvement was correlated with diminution in Delta MSNA pre- to post-CRT at rest moment (r(s) = -0.74, P = .006). Conclusion CRT provides metaboreflex sensitization and MSNA enhancement. The restoration of sympathetic responsiveness correlates with the improvement in functional capacity.
- Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy(2022) BROCHET, Pauline; IANNI, Barbara Maria; LAUGIER, Laurie; FRADE, Amanda Farage; NUNES, Joao Paulo Silva; TEIXEIRA, Priscila Camillo; MADY, Charles; FERREIRA, Ludmila Rodrigues Pinto; FERRE, Quentin; SANTOS, Ronaldo Honorato Barros; KURAMOTO, Andreia; CABANTOUS, Sandrine; STEFFEN, Samuel; STOLF, Antonio Noedir; POMERANTZEFF, Pablo; FIORELLI, Alfredo Inacio; BOCCHI, Edimar Alcides; PISSETTI, Cristina Wide; SABA, Bruno; CANDIDO, Darlan da Silva; DIAS, Fabricio C.; SAMPAIO, Marcelo Ferraz; GAIOTTO, Fabio Antonio; MARIN-NETO, Jose Antonio; FRAGATA, Abilio; ZANIRATTO, Ricardo Costa Fernandes; SIQUEIRA, Sergio; PEIXOTO, Giselle De Lima; RIGAUD, Vagner Oliveira-Carvalho; BACAL, Fernando; BUCK, Paula; ALMEIDA, Rafael Ribeiro; LIN-WANG, Hui Tzu; SCHMIDT, Andre; MARTINELLI, Martino; HIRATA, Mario Hiroyuki; DONADI, Eduardo Antonio; PEREIRA, Alexandre Costa; RODRIGUES JUNIOR, Virmondes; PUTHIER, Denis; KALIL, Jorge; SPINELLI, Lionel; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.
- Efficacy, Safety, and Performance of Isolated Left vs. Right Ventricular Pacing in Patients with Bradyarrhythmias: A Randomized Controlled Trial(2019) CREVELARI, Elizabeth Sartori; SILVA, Katia Regina da; ALBERTINI, Caio Marcos de Moraes; VIEIRA, Marcelo Luiz Campos; MARTINELLI FILHO, Martino; COSTA, RobertoBackground: Considering the potential deleterious effects of right ventricular (RV) pacing, the hypothesis of this study is that isolated left ventricular (LV) pacing through the coronary sinus is safe and may provide better clinical and echocardiographic benefits to patients with bradyarrhythmias and normal ventricular function requiring heart rate correction alone. Objective: To assess the safety, efficacy, and effects of LV pacing using an active-fixation coronary sinus lead in comparison with RV pacing, in patients eligible for conventional pacemaker (PM) implantation. Methods: Randomized, controlled, and single-blinded clinical trial in adult patients submitted to PM implantation due to bradyarrhythmias and systolic ventricular function >= 0.40. Randomization (RV vs. LV) occurred before PM implantation. The main results of the study were procedural success, safety, and efficacy. Secondary results were clinical and echocardiographic changes. Chi-squared test, Fisher's exact test and Student's t-test were used, considering a significance level of 5%. Results: From June 2012 to January 2014, 91 patients were included, 36 in the RV Group and 55 in the LV Group. Baseline characteristics of patients in both groups were similar. PM implantation was performed successfully and without any complications in all patients in the RV group. Of the 55 patients initially allocated into the LV group, active-fixation coronary sinus lead implantation was not possible in 20 (36.4%) patients. The most frequent complication was phrenic nerve stimulation, detected in 9 (25.7%) patients in the LV group. During the follow-up period, there were no hospitalizations due to heart failure. Reductions of more than 10% in left ventricular ejection fraction were observed in 23.5% of patients in the RV group and 20.6% of those in the LV group (p = 0.767). Tissue Doppler analysis showed that 91.2% of subjects in the RV group and 68.8% of those in the LV group had interventricular dyssynchrony (p = 0.022). Conclusion: The procedural success rate of LV implant was low, and the safety of the procedure was influenced mainly by the high rate of phrenic nerve stimulation in the postoperative period.
- A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy(2018) MARTINELLI FILHO, Martino; PEIXOTO, Giselle de Lima; SIQUEIRA, Rgio Freitas de; MARTINS, Sergio Augusto Mezzalira; NISHIOKA, Silvana Angelina D'orio; PEDROSA, Anisio Alexandre Andrade; TEIXEIRA, Ricardo Alkmim; SANTOS, Johnny Xavier dos; COSTA, Roberto; KALIL FILHO, Roberto; RAMIRES, Jose Antonio FranchiniAims Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. Methods and results This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. Conclusion This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.
article 3 Citação(ões) na Scopus Long Distance Runner with Dilated Cardiomyopathy and Excellent Performance(2011) MATOS, Luciana Diniz Nagem Janot de; AZEVEDO, Luciene Ferreira; BRUM, Patrcia Chakur; SOSA, Eduardo Argentino; MARTINELLI, Martino; NEGRAO, Carlos Eduardoarticle 0 Citação(ões) na Scopus Hyper-response Evaluated by 3D Echocardiography after Cardiac Resynchronization Therapy(2011) HOTTA, Viviane Tiemi; VIEIRA, Marcelo Luiz Campos; RASSI, Daniela do Carmo; NISHIOKA, Silvana Angelina D'orio; MARTINELLI FILHO, Martino; MATHIAS JR., WilsonCardiac resynchronization therapy consists of a promising treatment for patients with severe heart failure, but about 30% of patients do not exhibit clinical improvement with this procedure. However, approximately 10% of patients undergoing this therapy may have hyperresponsiveness, and three-dimensional echocardiography can provide an interesting option for the selection and evaluation of such patients.- Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms(2022) BROCHET, Pauline; IANNI, Barbara; NUNES, Joao P. S.; FRADE, Amanda F.; TEIXEIRA, Priscila C.; MADY, Charles; FERREIRA, Ludmila R. P.; KURAMOTO, Andreia; PISSETTI, Cristina W.; SABA, Bruno; CANDIDO, Darlan D. S.; DIAS, Fabricio; SAMPAIO, Marcelo; MARIN-NETO, Jose A.; FRAGATA, Abilio; ZANIRATTO, Ricardo C. F.; SIQUEIRA, Sergio; PEIXOTO, Giselle D. L.; RIGAUD, Vagner O. C.; BUCK, Paula; ALMEIDA, Rafael R.; LIN-WANG, Hui Tzu; SCHMIDT, Andre; MARTINELLI, Martino; HIRATA, Mario H.; DONADI, Eduardo; JUNIOR, Virmondes Rodrigues; PEREIRA, Alexandre C.; KALIL, Jorge; SPINELLI, Lionel; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) >= 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.