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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- Detection of Early Diffuse Myocardial Fibrosis and Inflammation in Chagas Cardiomyopathy with T1 Mapping and Extracellular Volume(2023) MELO, Rodrigo J. L.; ASSUNCAO, Antonildes N.; MORAIS, Thamara C.; NOMURA, Cesar H.; SCANAVACCA, Mauricio I.; MARTINELLI-FILHO, Martino; RAMIRES, Felix J. A.; FERNANDES, Fabio; IANNI, Barbara M.; MADY, Charles; ROCHITTE, Carlos E.Purpose: To evaluate myocardial T1 mapping and extracellular volume (ECV) parameters in different stages of Chagas cardiomyopathy and determine whether they are predictive of disease severity and prognosis.Materials and Methods: Prospectively enrolled participants (July 2013 to September 2016) underwent cine and late gadolinium enhancement (LGE) cardiac MRI and T1 mapping with a precontrast (native) or postcontrast modified Look-Locker sequence. The native T1 and ECV values were measured among subgroups that were based on disease severity (indeterminate, Chagas cardiomyopathy with preserved ejection fraction [CCpEF], Chagas cardiomyopathy with midrange ejection fraction [CCmrEF], and Chagas cardiomyopathy with reduced ejection fraction [CCrEF]). Cox proportional hazards regression and the Akaike information criterion were used to determine predictors of major cardiovascular events (cardioverter defibrillator implant, heart transplant, or death).Results: In 107 participants (90 participants with Chagas disease [mean age & PLUSMN; SD, 55 years & PLUSMN; 11; 49 men] and 17 age-and sex matched control participants), the left ventricular (LV) ejection fraction and the extent of focal and diffuse or interstitial fibrosis were correlated with disease severity. Participants with CCmrEF and participants with CCrEF showed significantly higher global native T1 and ECV values than participants in the indeterminate, CCpEF, and control groups (T1: 1072 msec & PLUSMN; 34 and 1073 msec & PLUSMN; 63 vs 1010 msec & PLUSMN; 41, 1005 msec & PLUSMN; 69, and 999 msec & PLUSMN; 46; ECV: 35.5% & PLUSMN; 3.6 and 35.0% & PLUSMN; 5.4 vs 25.3% & PLUSMN; 3.5, 28.2% & PLUSMN; 4.9, and 25.2% & PLUSMN; 2.2; both P < .001). Remote (LGE-negative areas) native T1 and ECV values were also higher (T1: 1056 msec & PLUSMN; 32 and 1071 msec & PLUSMN; 55 vs 1008 msec & PLUSMN; 41, 989 msec & PLUSMN; 96, and 999 msec & PLUSMN; 46; ECV: 30.2% & PLUSMN; 4.7 and 30.8% & PLUSMN; 7.4 vs 25.1% & PLUSMN; 3.5, 25.1% & PLUSMN; 3.7, and 25.0% & PLUSMN; 2.2; both P < .001). Abnormal remote ECV values (>30%) occurred in 12% of participants in the indeterminate group, which increased with disease severity. Nineteen combined outcomes were observed (median follow-up time: 43 months), and a remote native T1 value greater than 1100 msec was independently predictive of combined outcomes (hazard ratio, 12 [95% CI: 4.1, 34.2]; P < .001).Conclusion: Myocardial native T1 and ECV values were correlated with Chagas disease severity and may serve as markers of myocardial involvement in Chagas cardiomyopathy that precede LGE and LV dysfunction.
- Long-Term Follow-Up of Implantable Cardioverter-Defibrillator for Secondary Prevention in Chagas' Heart Disease(2012) MARTINELLI, Martino; SIQUEIRA, Sergio Freitas de; STERNICK, Eduardo Back; RASSI JR., Anis; COSTA, Roberto; RAMIRES, Jose Antonio Franchini; KALIL FILHO, RobertoAssessing the efficacy of implantable cardioverter-defibrillators (ICD) in patients with Chagas' heart disease (ChHD) and identifying the clinical predictors of mortality and ICD shock during long-term follow-up. ChHD is associated with ventricular tachyarrhythmias and an increased risk of sudden cardiac death. Although ChHD is a common form of cardiomyopathy in Latin American ICD users, little is known about its efficacy in the treatment of this population. The study cohort included 116 consecutive patients with ChHD and an ICD implanted for secondary prevention. Of the 116 patients, 83 (72%) were men; the mean age was 54 +/- 10.7 years. Several clinical variables were tested in a multivariate Cox model for predicting long-term mortality. The average follow-up was 45 +/- 32 months. New York Heart Association class I-II developed in 83% of patients. The mean left ventricular ejection fraction was 42 +/- 16% at implantation. Of the 116 patients, 58 (50%) had appropriate shocks and 13 (11%) had inappropriate therapy. A total of 31 patients died (7.1% annual mortality rate). New York Heart Association class III (hazard ratio [HR] 3.09, 95% confidence interval 1.37 to 6.96, p = 0.0064) was a predictor of a worse prognosis. The left ventricular ejection fraction (HR 0.972, 95% confidence interval 0.94 to 0.99, p = 0.0442) and low cumulative right ventricular pacing (HR 0.23, 95% confidence interval 0.11 to 0.49, p = 0.0001) were predictors of better survival. The left ventricular diastolic diameter was an independent predictor of appropriate shock (I-ER 1.032, 95% confidence interval 1.004 to 1.060, p = 0.025). In conclusion, in a long-term follow-up, ICD efficacy for secondary sudden cardiac death prevention in patients with ChHD was marked by a favorable annual rate of all-cause mortality (7.1%); 50% of the cohort received appropriate shock therapy. New York Heart Association class III and left ventricular ejection fraction were independent predictors of worse prognosis, and low cumulative right ventricular pacing defined better survival.
- CHronic use of Amiodarone aGAinSt Implantable cardioverter-defibrillator therapy for primary prevention of death in patients with Chagas cardiomyopathy Study: Rationale and design of a randomized clinical trial(2013) MARTINELLI, Martino; RASSI JR., Anis; MARIN-NETO, Jose Antonio; PAOLA, Angelo Amato Vincenzo de; BERWANGER, Otavio; SCANAVACCA, Mauricio Ibraim; KALIL, Roberto; SIQUEIRA, Sergio Freitas deBackground The implantable cardioverter defibrillator (ICD) is better than antiarrhythmic drug therapy for the primary and secondary prevention of all-cause mortality and sudden cardiac death in patients with either coronary artery disease or idiopathic dilated cardiomyopathy. This study aims to assess whether the ICD also has this effect for primary prevention in chronic Chagas cardiomyopathy (CCC). Methods In this randomized (concealed allocation) open-label trial, we aim to enroll up to 1,100 patients with CCC, a Rassi risk score for death prediction of >= 10 points, and at least 1 episode of nonsustained ventricular tachycardia on a 24-hour Holter monitoring. Patients from 28 centers in Brazil will be randomly assigned in a 1: 1 ratio to receive an ICD or amiodarone (600 mg/d for 10 days, then 200-400 mg/d until the end of the study). The randomization sequence will be generated by computer, and the members of the committees responsible for end point validation and data analysis will be blinded to study assignment. The primary end point is all-cause death, and enrolment will continue until 256 patients have reached this end point. Key secondary end points include cardiovascular death, sudden cardiac death, hospitalization for heart failure, and quality of life. We expect follow-up to last 3 to 6 years, and data analysis will be done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov number NCT01722942. Conclusion CHAGASICS is the first large-scale trial to assess the benefit of ICD therapy for the primary prevention of death in patients with CCC and nonsustained ventricular tachycardia, who have a moderate to high risk of death.
- Effects of Cardiac Resynchronization Therapy on Muscle Sympathetic Nerve Activity(2014) KUNIYOSHI, Ricardo R.; MARTINELLI, Martino; NEGRAO, Carlos E.; SIQUEIRA, Sergio F.; RONDON, Maria U. P. B.; TROMBETTA, Ivani C.; KUNIYOSHI, Fatima H. S.; LATERZA, Mateus C.; NISHIOKA, Silvana A. D'Orio; COSTA, Roberto; TAMAKI, Wagner T.; CREVELARI, Elizabeth S.; PEIXOTO, Giselle De Lima; RAMIRES, Jose A. F.; KALIL, RobertoIntroductionMuscle sympathetic nerve activity (MSNA) is an independent prognostic marker in patients with heart failure (HF). Therefore, its relevance to the treatment of HF patients is unquestionable. ObjectivesIn this study, we investigated the effects of cardiac resynchronization therapy (CRT) on MSNA response at rest and during exercise in patients with advanced HF. MethodsWe assessed 11 HF patients (51 3.4 years; New York Heart Association class III-IV; left ventricular ejection fraction 27.8 2.2%; optimal medical therapy) submitted to CRT. Evaluations were made prior to and 3 months after CRT. MSNA was performed at rest and during moderate static exercise (handgrip). Peak oxygen consumption (VO2) was evaluated by means of cardiopulmonary exercise test. HF patients with advanced NYHA class without CRT and healthy individuals were also studied. ResultsCRT reduced MSNA at rest (48.9 +/- 11.1 bursts/min vs 33.7 +/- 15.3 bursts/min, P < 0.05) and during handgrip exercise (MSNA 62.3 +/- 13.1 bursts/min vs 46.9 +/- 14.3 bursts/min, P < 0.05). Among HF patients submitted to CRT, the peak VO2 increased (12.9 +/- 2.8 mL/kg/min vs 16.5 +/- 3.9 mL/kg/min, P < 0.05) and an inverse correlation between peak VO2 and resting MSNA (r = -0.74, P = 0.01) was observed. ConclusionsIn patients with advanced HF and severe systolic dysfunction: (1) a significant reduction of MSNA (at rest and during handgrip) occurred after CRT, and this behavior was significantly superior to HF patients receiving only medical therapy; (2) MSNA reduction after CRT had an inverse correlation with O-2 consumption outcomes.
- Impact of diabetes mellitus on ischemic cardiomyopathy. Five-year follow-up. REVISION-DM trial(2018) HUEB, Thiago; ROCHA, Mauricio S.; SIQUEIRA, Sergio F.; NISHIOKA, Silvana Angelina D'Orio; PEIXOTO, Giselle L.; SACCAB, Marcos M.; LIMA, Eduardo Gomes; GARCIA, Rosa Maria Rahmi; RAMIRES, Jos Antonio F.; KALIL FILHO, Roberto; MARTINELLI FILHO, MartinoBackground: Patients with ischemic cardiomyopathy and severe left ventricular dysfunction have a worse survival prognosis than patients with preserved ventricular function. The role of diabetes in the long-term prognosis of this patient group is unknown. This study investigated whether the presence of diabetes has a long-term impact on left ventricular function. Methods: Patients with coronary artery disease who underwent coronary artery bypass graft surgery, percutaneous coronary intervention, or medical therapy alone were included. All patients had multivessel disease and left ventricular ejection fraction measurements. Overall mortality, nonfatal myocardial infarction, stroke, and additional interventions were investigated. Results: From January 2009 to January 2010, 918 consecutive patients were selected and followed until May 2015. They were separated into 4 groups: G1, 266 patients with diabetes and ventricular dysfunction; G2, 213 patients with diabetes without ventricular dysfunction; G3, 213 patients without diabetes and ventricular dysfunction; and G4, 226 patients without diabetes but with ventricular dysfunction. Groups 1, 2, 3, and 4, respectively, had a mortality rate of 21.6, 6.1, 4.2, and 10.6% (P < .001); nonfatal myocardial infarction of 5.3, .5, 7.0, and 2.6% (P < .001); stroke of .40, .45, .90, and .90% (P = NS); and additional intervention of 3.8, 11.7, 10.3, and 2.6% (P < .001). Conclusion: In this sample, regardless of the treatment previously received patients with or without diabetes and preserved ventricular function experienced similar outcomes. However, patients with ventricular dysfunction had a worse prognosis compared with those with normal ventricular function; patients with diabetes had greater mortality than patients without diabetes.
- 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.
- Effect of chronic kidney disease in ischemic cardiomyopathy Long-term follow-up-REVISION-DM2 trial(2019) HUEB, Thiago Ovanessian; LIMA, Eduardo Gomes; ROCHA, Mauricio S.; SIQUEIRA, Sergio F.; NISHIOKA, Silvana Angelina Dorio; PEIXOTO, Giselle L.; SACCAB, Marcos M.; GARCIA, Rosa Maria Rahmi; RAMIRES, Jose Antonio F.; KALIL FILHO, Roberto; MARTINELLI FILHO, MartinoA strong association exists between chronic kidney disease (CKD) and coronary artery disease (CAD). The role of CKD in the long-term prognosis of CAD patients with versus those without CKD is unknown. This study investigated whether CKD affects ventricular function. From January 2009 to January 2010, 918 consecutive patients were selected from an outpatient database. Patients had undergone percutaneous, surgical, or clinical treatment and were followed until May 2015. In patients with preserved renal function (n = 405), 73 events (18%) occurred, but 108 events (21.1%) occurred among those with CKD (n = 513) (P < .001). Regarding left ventricular ejection fraction (LVEF) <50%, we found 84 events (21.5%) in CKD patients and 12 (11.8%) in those with preserved renal function (P < .001). The presence of LVEF <50% brought about a modification effect. Death occurred in 22 (5.4%) patients with preserved renal function and in 73 (14.2%) with CKD (P < .001). In subjects with LVEF <50%, 66 deaths (16.9%) occurred in CKD patients and 7 (6.9%) in those with preserved renal function (P = .001). No differences were found in CKD strata regarding events or overall death among those with preserved LVEF. In a multivariate model, creatinine clearance remained an independent predictor of death (P < .001). We found no deleterious effects of CKD in patients with CAD when ventricular function was preserved. However, there was a worse prognosis in patients with CKD and ventricular dysfunction. Resgistry number is ISRCTN17786790 at .
- Improved relationship between left and right ventricular electrical activation after cardiac resynchronization therapy in heart failure patients can be quantified by body surface potential mapping(2013) SAMESIMA, Nelson; PASTORE, Carlos Alberto; DOUGLAS, Roberto Andres; MARTINELLI FILHO, Martino; PEDROSA, Anisio A.OBJECTIVES: Few studies have evaluated cardiac electrical activation dynamics after cardiac resynchronization therapy. Although this procedure reduces morbidity and mortality in heart failure patients, many approaches attempting to identify the responders have shown that 30% of patients do not attain clinical or functional improvement. This study sought to quantify and characterize the effect of resynchronization therapy on the ventricular electrical activation of patients using body surface potential mapping, a noninvasive tool. METHODS: This retrospective study included 91 resynchronization patients with a mean age of 61 years, left ventricle ejection fraction of 28%, mean QRS duration of 182 ms, and functional class III/IV (78%/22%); the patients underwent 87-lead body surface mapping with the resynchronization device on and off. Thirty-six patients were excluded. Body surface isochronal maps produced 87 maximal/mean global ventricular activation times with three regions identified. The regional activation times for right and left ventricles and their interregional right-to-left ventricle gradients were calculated from these results and analyzed. The Mann-Whitney U-test and Kruskall-Wallis test were used for comparisons, with the level of significance set at p <= 0.05. RESULTS: During intrinsic rhythms, regional ventricular activation times were significantly different (54.5 ms vs. 95.9 ms in the right and left ventricle regions, respectively). Regarding cardiac resynchronization, the maximal global value was significantly reduced (138 ms to 131 ms), and a downward variation of 19.4% in regional-left and an upward variation of 44.8% in regional-right ventricular activation times resulted in a significantly reduced inter-regional gradient (43.8 ms to 17 ms). CONCLUSIONS: Body surface potential mapping in resynchronization patients yielded electrical ventricular activation times for two cardiac regions with significantly decreased global and regional-left values but significantly increased regional-right values, thus showing an attenuated inter-regional gradient after the cardiac resynchronization therapy.
- Predictors of death in chronic Chagas cardiomyopathy patients with pacemaker(2018) PEIXOTO, Giselle de Lima; MARTINELLI FILHO, Martino; SIQUEIRA, Sergio Freitas de; NISHIOKA, Silvana Angelina D'Orio; PEDROSA, Anisio Alexandre Andrade; TEIXEIRA, Ricardo Alkmim; COSTA, Roberto; KALIL FILHO, Roberto; RAMIRES, Jose Antonio FranchiniBackground: Chronic Chagas cardiomyopathy (CCC) is the most serious and frequent manifestation of Chagas disease. Conduction abnormalities and bradycardia requiring pacemaker are common. The aim of this study was to determine the rate and predictors of death in CCC patients with pacemaker. Methods: In this single-center prospective cohort study we assessed the outcome of 396 CCC patients with pacemaker, followed-up for at least 24 months. All patients underwent a clinical and device assessment, 12-lead electrocardiography and echocardiography. Results: During the median follow-up of 1.9 years (Interquartile range 1.6-2.4), there were 65 (16.4%) deaths, yielding an annual mortality rate of 8.6%. The major cause was sudden death (33.8%), followed by heart failure (HF), 32.3%. All the investigated variables were examined as potential predictors of death. The final multivariate logistic regression model included five independent variables: advanced HF functional class (OR [odds ratio] 6.71; 95% confidence interval [95% CI] 1.95-23.2; P = 0.003), renal disease (OR 5.71; 95% CI 1.80-18.0; P = 0.003), QRS >= 150 ms (OR 2.80; 95% CI 1.08-7.27; P = 0.034), left atrial enlargement (OR 2.75; 95% CI 1.09-6.95; P = 0.032) and left ventricular ejection fraction = 43% (OR 2.31; 95% CI 1.07-4.97; P = 0.032). Themodel had good discrimination, confirmed by bootstrap validation (optimism-adjusted c-statistic of 0.78) and the calibration curve showed a proper calibration (slope = 0.972). Conclusions: CCC patients with pacemaker have a high annual mortality rate despite that the pacemaker related variables were not predictors of death. The independent predictors of death can help us to identify the poor prognosis patients.
- Global and Regional Ventricular Repolarization Study by Body Surface Potential Mapping in Patients with Left Bundle-Branch Block and Heart Failure Undergoing Cardiac Resynchronization Therapy(2012) DOUGLAS, Roberto A. G.; SAMESIMA, Nelson; FILHO, Martino M.; PEDROSA, Anisio A.; NISHIOKA, Silvana A. D.; PASTORE, Carlos A.Background: The controversial effects promoted by cardiac resynchronization therapy (CRT) on the ventricular repolarization (VR) have motivated VR evaluation by body surface potential mapping (BSPM) in CRT patients. Methods: Fifty-two CRT patients, mean age 58.8 +/- 12.3 years, 31 male, LVEF 27.5 +/- 9.2, NYHA III-IV heart failure with QRS181.5 +/- 14.2 ms, underwent 87-lead BSPM in sinus rhythm (BASELINE) and biventricular pacing (BIV). Measurements of mean and corrected QT intervals and dispersion, mean and corrected T peak end intervals and their dispersion, and JT intervals characterized global and regional (RV, Intermediate, and LV regions) ventricular repolarization response. Results: Global QTm (P < 0.001) and QTcm (P < 0.05) were decreased in BIV; QTm was similar across regions in both modes (P = ns); QTcm values were lower in RV/LV than in Intermediate region in BASELINE and BIV (P < 0.001); only RV/Septum showed a significant difference (P < 0.01) in the BIV mode. QTD values both of BASELINE (P < 0.01) and BIV (P < 0.001) were greater in the Intermediate than in the LV region. CRT effect significantly reduced global/regional QTm and QTcm values. QTD was globally decreased in RV/LV (Intermediate: P = ns). BIV mode significantly reduced global T peak end mean and corrected intervals and their dispersion. JT values were not significant. Conclusions: Ventricular repolarization parameters QTm, QTcm, and QTD global/regional values, as assessed by BSPM, were reduced in patients under CRT with severe HF and LBBB. Greater recovery impairment in the Intermediate region was detected by the smaller variation of its dispersion.