Ricardo Alkmim Teixeira

Cardiac Damage from Chronic Use of Chloroquine: A Case Report and Review of the Literature

Chloroquine has been widely used in rheumatological treatment, but potential severe side effects require careful follow-up. Cardiac damage is not a common consequence, but its clinical relevance has not yet been described. We report the case of a 58-year-old woman with rheumatoid arthritis, in whom chronic chloroquine use resulted in major irreversible cardiac damage. She presented with syncopal episodes due to complete atrioventricular block confirmed by electrophysiological study whose changes were concluded to be irreversible and a permanent pacemaker was indicated. Endomyocardial biopsy was also performed to search for histopathological and ultrastructural cardiac damage. We also reviewed the 22 cases of chloroquine-induced cardiopathy described to date as well as its pathophysiology.

Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus.

AIMS To perform a comprehensive evaluation of heart rhythm disorders and the influence of disease/therapy factors in a large systemic lupus erythematosus (SLE) cohort. METHODS AND RESULTS Three hundred and seventeen consecutive patients of an ongoing electronic database protocol were evaluated by resting electrocardiogram and 142 were randomly selected for 24 h Holter monitoring for arrhythmia and conduction disturbances. The mean age was 40.2 ± 12.1 years and disease duration was 11.4 ± 8.1 years. Chloroquine (CQ) therapy was identified in 69.7% with a mean use of 8.5 ± 6.7 years. Electrocardiogram abnormalities were detected in 66 patients (20.8%): prolonged QTc/QTd (14.2%); bundle-branch block (2.5%); and atrioventricular block (AVB) (1.6%). Age was associated with AVB (P = 0.029) and prolonged QTc/QTd (P = 0.039) whereas anti-Ro/SS-A and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were not (P > 0.05). Chloroquine was negatively associated with AVB (P = 0.01) as was its longer use (6.1 ± 6.9 vs. 1.0 ± 2.5 years, P = 0.018). Time of CQ use was related with the absence of AVB [odds ratio (OR) = 0.103; 95% confidence interval (CI) = 0.011-0.934, P = 0.043] in multiple logistic regression. Holter monitoring revealed abnormalities in 121 patients (85.2%): supraventricular ectopies (63.4%) and tachyarrhythmia (18.3%); ventricular ectopies (45.8%). Atrial tachycardia/fibrillation (AT/AF) were associated with shorter CQ duration (7.05 ± 7.99 vs. 3.63 ± 5.02 years, P = 0.043) with a trend to less CQ use (P = 0.054), and older age (P < 0.001). Predictors of AT/AF in multiple logistic regression were age (OR = 1.115; 95% CI = 1.059-1.174, P < 0.001) and anti-Ro/SS-A (OR = 0.172; 95% CI = 0.047-0.629, P = 0.008). CONCLUSIONS Chloroquine seems to play a protective role in the unexpected high rate of cardiac arrhythmias and conduction disturbances observed in SLE. Further studies are necessary to determine if this antiarrhythmic effect is due to the disease control or a direct effect of the drug.

Arrhythmias in systemic lupus erythematosus

Cardiac involvement is present in more than half of the patients with Systemic Lupus Erythematosus (SLE). However, studies on the prevalence of arrhythmias in this disease and laboratory correlations predictive of their development do not exist. It seems possible that the classic second mortality peak is related to arrhythmias, mainly due to the sudden nature of those deaths. Autoimmune process, atherosclerotic complications, and even adverse effects secondary to the treatment of this disorder (chloroquine cardiotoxicity) seem to be the main pathophysiological mechanisms of those disturbances. The direct participation of autoantibodies, such as anti-Ro/SSA and anti-RNP, is still controversial. All types of AV blocks (AVB), intraventricular conduction disturbances, and sick sinus syndrome have already been described in this disease. Tachycardias identified more often include sinus tachycardia, atrial fibrillation, and atrial ectopies. Long QT syndrome and the presence of late potentials in signal-averaged ECG have also been described in SLE patients and they can be associated with increased mortality rates. Cardiac toxicity secondary to chloroquine could be responsible for several types of arrhythmias. However, few cases of fascicular block evolving to complete AV block have been described. Since these adverse effects are rarely reported, the beneficial anti-inflammatory and immune properties support the use of antimalarials in this disease. A complete cardiologic evaluation should include the conduction system and must be carried out in all SLE patients to identify arrhythmias, therefore preventing symptoms and also sudden cardiac death.

Predictors of death in chronic Chagas cardiomyopathy patients with pacemaker

BACKGROUND 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 24months. All patients underwent a clinical and device assessment, 12-lead electrocardiography and echocardiography. RESULTS During the median follow-up of 1.9years (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 ≥150ms (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). The model 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.

A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy

Aims 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.