Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

Background:Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence.Objective:To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias.Method:Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram).Results:GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028).Conclusion:The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.

Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

Background: Gender can influence post-infarction cardiac remodeling. Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. Results: MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Conclusions: Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.

Effects of Exercise Training on Heart Rate Variability in Chagas Heart Disease

Background: Heart rate variability (HRV) is a marker of autonomic dysfunction severity. The effects of physical training on HRV indexes in Chagas heart disease (CHD) are not well established. Objective: To evaluate the changes in HRV indexes in response to physical training in CHD. Methods: Patients with CHD and left ventricular (LV) dysfunction, physically inactive, were randomized either to the intervention (IG, N = 18) or control group (CG, N = 19). The IG participated in a 12-week exercise program consisting of 3 sessions/week. Results: Mean age was 49.5 ± 8 years, 59% males, mean LVEF was 36.3 ± 7.8%. Baseline HRV indexes were similar between groups. From baseline to follow-up, total power (TP): 1653 (IQ 625 - 3418) to 2794 (1617 - 4452) ms, p = 0.02) and very low frequency power: 586 (290 - 1565) to 815 (610 - 1425) ms, p = 0.047) increased in the IG, but not in the CG. The delta (post - pre) HRV indexes were similar: SDNN 11.5 ± 30.0 vs. 3.7 ± 25.1 ms. p = 0.10; rMSSD 2 (6 - 17) vs. 1 (21 - 9) ms. p = 0.43; TP 943 (731 - 3130) vs. 1780 (921 - 2743) Hz. p = 0.46; low frequency power (LFP) 1.0 (150 - 197) vs. 60 (111 - 146) Hz. p = 0.85; except for high frequency power, which tended to increase in the IG: 42 (133 - 92) vs. 79 (61 - 328) Hz. p = 0.08). Conclusion: In the studied population, the variation of HRV indexes was similar between the active and inactive groups. Clinical improvement with physical activity seems to be independent from autonomic dysfunction markers in CHD.

Value of the Qrs-T Angle in Predicting the Induction of Ventricular Tachyarrhythmias in Patients with Chagas Disease

Background:The QRS-T angle correlates with prognosis in patients with heart failure and coronary artery disease, reflected by an increase in mortality proportional to an increase in the difference between the axes of the QRS complex and T wave in the frontal plane. The value of this correlation in patients with Chagas heart disease is currently unknown.Objective:Determine the correlation of the QRS-T angle and the risk of induction of ventricular tachycardia / ventricular fibrillation (VT / VF) during electrophysiological study (EPS) in patients with Chagas disease.Methods:Case-control study at a tertiary center. Patients without induction of VT / VF on EPS were used as controls. The QRS-T angle was categorized as normal (0-105º), borderline (105-135º) or abnormal (135-180º). Differences between groups for continuous variables were analyzed with the t test or Mann-Whitney test, and for categorical variables with Fisher's exact test. P values < 0.05 were considered significant.Results:Of 116 patients undergoing EPS, 37.9% were excluded due to incomplete information / inactive records or due to the impossibility to correctly calculate the QRS-T angle (presence of left bundle branch block and atrial fibrillation). Of 72 patients included in the study, 31 induced VT / VF on EPS. Of these, the QRS-T angle was normal in 41.9%, borderline in 12.9% and abnormal in 45.2%. Among patients without induction of VT / VF on EPS, the QRS-T angle was normal in 63.4%, borderline in 14.6% and abnormal in 17.1% (p = 0.04). When compared with patients with normal QRS-T angle, those with abnormal angle had a fourfold higher risk of inducing ventricular tachycardia / ventricular fibrillation on EPS [odds ratio (OR) 4; confidence interval (CI) 1.298-12.325; p = 0.028]. After adjustment for other variables such as age, ejection fraction (EF) and QRS size, there was a trend for the abnormal QRS-T angle to identify patients with increased risk of inducing VT / VF during EPS (OR 3.95; CI 0.99-15.82; p = 0.052). The EF also emerged as a predictor of induction of VT / VF: for each point increase in EF, there was a 4% reduction in the rate of sustained ventricular arrhythmia on EPS.Conclusions:Changes in the QRS-T angle and decreases in EF were associated with an increased risk of induction of VT / VF on EPS.

Reproducibility of Left Ventricular Mass by Echocardiogram in the ELSA-Brasil

Background: Echocardiography, though non-invasive and having relatively low-cost, presents issues of variability which can limit its use in epidemiological studies. Objective: To evaluate left ventricular mass reproducibility when assessed at acquisition (online) compared to when assessed at a reading center after electronic transmission (offline) and also when assessed by different readers at the reading center. Methods: Echocardiographers from the 6 ELSA-Brasil study investigation centers measured the left ventricular mass online during the acquisition from 124 studies before transmitting to the reading center, where studies were read according to the study protocol. Half of these studies were blindly read by a second reader in the reading center. Results: From the 124 echocardiograms, 5 (4%) were considered not measurable. Among the remaining 119, 72 (61%) were women, mean age was 50.2 ± 7.0 years and 2 had structural myocardial abnormalities. Images were considered to be optimal/ good by the reading center for 110 (92.4%) cases. No significant difference existed between online and offline measurements (1,29 g, CI 95% −3.60-6.19), and the intraclass correlation coefficient between them was 0.79 (CI 95% 0.71-0.85). For images read by two readers, the intraclass correlation coefficient was 0.86 (CI 95% 0.78-0.91). Conclusion: There were no significant drifts between online and offline left ventricular mass measurements, and reproducibility was similar to that described in previous studies. Central quantitative assessment of echocardiographic studies in reading centers, as performed in the ELSA-Brasil study, is feasible and useful in clinical and epidemiological studies performed in our setting.

Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure

In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis.

Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

AbstractBackground:Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy.Objective:To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy.Methods:The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased.Results:A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation.Conclusion:In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5).

Ergospirometry and Echocardiography in Early Stage of Heart Failure with Preserved Ejection Fraction and in Healthy Individuals

AbstractBackground:Heart failure with preserved ejection fraction is a syndrome characterized by changes in diastolic function; it is more prevalent among the elderly, women, and individuals with systemic hypertension (SH) and diabetes mellitus. However, in its early stages, there are no signs of congestion and it is identified in tests by adverse remodeling, decreased exercise capacity and diastolic dysfunction.Objective:To compare doppler, echocardiographic (Echo), and cardiopulmonary exercise test (CPET) variables - ergospirometry variables - between two population samples: one of individuals in the early stage of this syndrome, and the other of healthy individuals.Methods:Twenty eight outpatients diagnosed with heart failure according to Framingham’s criteria, ejection fraction > 50% and diastolic dysfunction according to the european society of cardiology (ESC), and 24 healthy individuals underwent Echo and CPET.Results:The group of patients showed indexed atrial volume and left ventricular mass as well as E/E’ and ILAV/A´ ratios significantly higher, in addition to a significant reduction in peak oxygen consumption and increased VE/VCO2 slope, even having similar left ventricular sizes in comparison to those of the sample of healthy individuals.Conclusion:There are significant differences between the structural and functional variables analyzed by Echo and CPET when comparing two population samples: one of patients in the early stage of heart failure with ejection fraction greater than or equal to 50% and another of healthy individuals.