Sérgio Freitas de Siqueira

Conventional Versus Biventricular Pacing in Heart Failure and Bradyarrhythmia: The COMBAT Study

BACKGROUND Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. METHODS AND RESULTS COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2 max)). Sixty patients were enrolled, and the mean follow-up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2 max) were not significantly different. Death occurred more frequently with RVP. CONCLUSION In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode.

Biventricular Pacing Improves Clinical Behavior and Reduces Prevalence of Ventricular Arrhythmia in Patients with Heart Failure

PURPOSE To analyze the influence of biventricular pacing (BP) on clinical behavior, ventricular arrhythmia (VA) prevalence, and left ventricular ejection fraction (LV EF) by gated ventriculography. METHODS Twenty-four patients with left bundle branch block (LBBB) and NYHA class III and IV underwent pacemaker implantation and were randomized either to the conventional or BP group, all receiving BP after 6 months. RESULTS Sixteen patients were in NYHA class IV (66.6%) and 8 were in class III (33.4%). After 1-year follow-up, 14 patients were in class II (70%) and 5 were in class III (25%). Two sudden cardiac deaths occurred. A significant reduction in QRS length was found with BP (p=0.006). A significant statistical increase, from a mean of 19.13 +/- 5.19% (at baseline) to 25.33 +/- 5.90% (with BP) was observed in LVEF Premature ventricular contraction prevalence decreased from a mean of 10,670.00 +/- 12,595.39 SD or to a mean of 3,007.00 +/- 3,216.63 SD PVC/24 h with BP (p<0.05). Regarding the hospital admission rate over 1 year, we observed a significant reduction from 60. To 16 admissions with BP (p<0.05). CONCLUSION Patients with LBBB and severe heart failure experienced, with BP, a significant NYHA class and LVEF improvement. A reduction in the hospital admission rate and VA prevalence also occurred.

Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease

BACKGROUND Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. METHODS AND RESULTS We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. CONCLUSIONS Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.

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

BACKGROUND 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.

COMBAT--conventional versus multisite pacing for bradyarrhythmia therapy: rationale of a prospective randomized multicenter study.

COMBAT is a prospective, multicenter, randomized, blinded clinical study, with crossover design. The main objective is the comparative evaluation of atrio‐biventricular versus conventional atrioventricular stimulation (atrio and right ventricle) in patients with heart failure and bradycardia as the primary indication for pacemaker implantation. After successful atrio‐biventricular system implantation, patients will be randomized into two groups: group A—atrioventricular conventional pacing and group B—atrio‐biventricular pacing. Both groups will be programmed in DDD mode with AV delay optimized by echocardiogram. After 3 months, New York Heart Association functional class, ventricular arrhythmia density and complexity, echocardiography outcomes, 6‐min hall walk distance, quality of life and peak oxygen consumption will be assessed in all patients. Then, all patients will crossover to the other pacing regimen, with an additional AV delay adjustment by echo. Patients will be followed up for another 3 months at the end of which all evaluations will be repeated. Patients will then crossover back to their original pacing regimen for a further 3 months. At the end of this 9‐month period, patients will be reprogrammed according to their optimal pacing regime.

Neurohumoral behavior in recipients of cardiac pacemakers controlled by a closed-loop autonomic nervous system-driven sensor.

The purpose of a sensor‐driven pacing system is to physiologically correct chronotropic incompetence (CI). The aim of this study was to evaluate the changes in heart rate provided by a sympathetically driven pacemaker (PM) compared with normal sinus function (NSF). Nine men and six women (age 37–80 years) with AV block and a PM controlled by a closed‐loop system were studied. Group I included eight patients with CI, and group II included seven patients with NSF. All patients underwent Valsalva maneuver and tilt table testing with measurements of plasma catecholamines and renin activity. Pacing was initially programmed in the DDDC mode at a lower rate (60 ppm) and upper rate limit (0.85 × [220 ‐ age]), then in DDDR in group I and VVIR in group II. The second phase of the study consisted of nitroglycerin and phenylephrine infusions, and the third phase of physiological provocative maneuvers. The second and third phases were performed in three patients from each group with sensor activity On and Off. In group I, heart rate changed during tilt only in the DDDR mode. In group II, heart rate changes were comparable in both modes. Catecholamine levels in group I were higher during DDDC than during DDDR pacing (P < 0.05). In group I, heart rate did not change during phases II and IV of the Valsalva maneuver in the DDDC mode, but behaved nearly physiologically after sensor activation. A late and a paradoxical response to nitroglycerin was observed in groups I and II and to phenylephrine in group I. During physiological maneuvers, significantly greater variations in heart rate were observed during DDDR than during DDDC pacing. Sympathetic SDP provides physiological modulations of the heart rate were provided by a sympathetically driven pacing system in patients with AV block and CI.

Cardiomiopatia hipertrófica: importância dos eventos arrítmicos em pacientes com risco de morte súbita

OBJECTIVE: To evaluate, in patients with hypertrophic cardiomyopathy and risk for SCD who underwent implantable cardioverter-defibrillator (ICD) implantation: a- the occurrence of arrhythmic events; b- the occurrence of clinical events and their correlation with arrhythmic events; c- the occurrence of ICD shock therapy and clinical and functional correlations; d- clinical and functional predictors of prognosis. METHODS: Twenty six patients with hypertrophic cardiomyopathy and risk factors for SCD undergoing ICD implantation from May, 2000 to January, 2004 (mean follow-up = 20 months) were studied. Fourteen patients (53.8%) were females and the mean age was 42.7 years. ICD was indicated for primary prevention of sudden cardiac death in 16 patients (61.5%), and for secondary prevention in 10 patients (38.5%). Twenty patients (76.9%) presented syncope prior to ICD implantation; half of them were related to ventricular fibrillation or sustained ventricular tachycardia, 15 (57.7%) had a history of familial sudden death, 12 patients (46.2%) had nonsustained ventricular tachycardia on the 24-hour Holter monitoring, and five (19.2%) had an interventricular septal thickness greater than 30 mm. RESULTS: Four shock therapies were recorded by the ICD in potentially lethal arrhythmias (three patients with sustained ventricular tachycardia and one patient with ventricular fibrillation) during the follow-up. One death occurred, probably due to a thromboembolic stroke. Four patients had recurrence of syncope with no arrhythmic event recorded by the ICD. The statistical analysis showed a significant difference in early ICD shock therapy in patients whose interventricular septal thickness was greater than 30 mm. CONCLUSION: 1- occurrence of arrhythmic events in 50% of the patients; most of them (62%) were ventricular tachycardia, whether sustained (31%) or nonsustained (31%); in the remaining patients paroxysmal supraventricular tachycardia was observed. 2- recurrent syncope in the minority of the patients (16%), however not associated with the presence of arrhythmic events. 3- the presence of an interventricular septal thickness greater than 30 mm in the echocardiogram was associated with early shock therapy (p = 0.003). 4- absence of clinical or functional predictors.

Silent Atrial Fibrillation in Elderly Pacemaker Users: A Randomized Trial Using Home Monitoring

Pacemaker with remote monitoring (PRM) may be useful for silent atrial fibrillation (AF) detection. The aims of this study were to evaluate the incidence of silent AF, the role of PRM, and to determine predictors of silent AF occurrence.

Cardiac pacing in hypertrophic cardiomyopathy: a cohort with 24 years of follow-up

BACKGROUND The benefits of heart stimulation in hypertrophic cardiomyopathy (HCM) patients have been questioned. Research work available in Brazil on those benefits is scarce. OBJECTIVE To describe the indication, clinical response, complications and survival time related to pacemaker implant in HCM patients. METHODS Thirty-nine hypertrophic cardiomyopathy patients were studied (41% males) and submitted to pacemaker implant from May, 1980 through November, 2003. RESULTS Twenty-seven patients presented obstructive hypertrophic cardiomyopathy, and 12, non-obstructive. Mean age was 46.4 years of age (range 14-77), with follow-up of 6.4+/-4.1 years. Major indications for implant were: spontaneous or induced atrioventricular block (54%), refractoriness to therapeutic conduct associated to high gradient (33%), support for drug therapy to treat bradychardia (8%), and atrial fibrillation prevention (5%). Functional class was shown to improve from 2.41+/-0.87 to 1.97+/-0.92 (p=0.008), and symptoms referred were reduced. No change was made in drug therapy administration. No procedure-related deaths were reported. Although shown to be safe, the procedure was not free from complications (6 patients--15.4%). Three deaths occurred in the follow-up period--the three of them were atrial fibrillation female patients, with evidence of functional deterioration. A close association was observed between clinical condition worsening and the onset of atrial fibrillation or flutter. CONCLUSION Cardiac pacing in HCM patients was successful, with evidence of symptoms relief in obstructive HCM patients. No functional improvement was observed in non-obstructive patients.

Endocarditis Secondary to Microsporidia Giant Vegetation in a Pacemaker User

A 60-year-old white man was admitted with a 2-week history of shivering and fever (38°C). He had had a dual-chamber pacemaker implanted in 1996 because of complete atrioventricular block, with an elective pulse generator replaced 3 months before admission. Medications taken on a daily basis included amiodarone for atrial fibrillation rhythm control and atenolol for hypertension. His blood pressure was normal; his heart rate was 80 bpm; and he was febrile (38.5°C). Chest auscultation revealed a systolic murmur at the left and right sternal borders with respiratory shifting in the heart sound, not previously described in this patient. ECG showed a normally functioning pacemaker (Figure 1). Chest x-ray was normal (Figure 2), as were renal function and differential white cell count. Figure 1. Twelve-lead surface ECG showed a normally functioning dual-chamber pacemaker. Figure 2. A, Frontal anterior-posterior chest x-ray showed a pacemaker in the right infraclavicular region with no other abnormality. B, Normal frontal posterior-anterior chest x-ray after surgical intervention. Endocarditis was confirmed by a transesophageal echocardiography …A 60-year-old white man was admitted with a 2-week history of shivering and fever (38°C). He had had a dual-chamber pacemaker implanted in 1996 because of complete atrioventricular block, with an elective pulse generator replaced 3 months before admission. Medications taken on a daily basis included amiodarone for atrial fibrillation rhythm control and atenolol for hypertension. His blood pressure was normal; his heart rate was 80 bpm; and he was febrile (38.5°C). Chest auscultation revealed a systolic murmur at the left and right sternal borders with respiratory shifting in the heart sound, not previously described in this patient. ECG showed a normally functioning pacemaker (Figure 1). Chest x-ray was normal (Figure 2), as were renal function and differential white cell count. Figure 1. Twelve-lead surface ECG showed a normally functioning dual-chamber pacemaker. Figure 2. A, Frontal anterior-posterior chest x-ray showed a pacemaker in the right infraclavicular region with no other abnormality. B, Normal frontal posterior-anterior chest x-ray after surgical intervention. Endocarditis was confirmed by a transesophageal echocardiography …