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

This editorial refers to ‘A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy’ by M. Martinelli Filho et al., on pages 1813–1818. Chagas disease was first described more than a century ago by Chagas1 and remains one of the major health challenges in South America, affecting more than 8 million people. However, the disease is no longer confined to South America and is emerging in the USA, Europe, Canada, Australia, and Japan. It has been estimated than more than 300 000 in the USA and more than 200 000 in Europe are infected by Trypanosoma cruzi, mainly due to population migration.2,3 In endemic areas, the disease is mainly transmitted to humans by a vector, a triatominae insect. Other modes of transmission are observed in the non-endemic areas.2 Large-scale vector control programmes and screening of blood donors have reduced new cases of the disease in some endemic areas such as Brazil.2 In most European countries, the disease is underappreciated with absence of screening programmes and limited access to treatment. Because of the increasing prevalence of the disease in Europe, physicians should be able to recognize and treat chronic Chagas disease.3 The majority of infected carriers remain asymptomatic in the indeterminate phase, but about 30 to 40% will develop cardiac and/or gastrointestinal involvement many years after infection.2 Chronic Chagas cardiomyopathy (CCC) is the most frequent and life-threatening form of the disease and observed in about 30% of the infected population. This type of heart disease has a wide spectrum of electrocardiographic abnormalities, most commonly right bundle branch block with or without left anterior hemiblock but also left bundle branch block (LBBB) in less than 10% of patients and other abnormalities such as sick sinus syndrome, AV block, atrial fibrillation, ventricular premature beats, ventricular tachycardia (VT), and sudden cardiac death. Sudden cardiac death generally is due to VT and ventricular fibrillation but also to systemic and pulmonary embolism. The most important clinical finding in patients with CCC is ventricular dysfunction that varies from mild to severe cardiac failure. Cardiac failure is the mechanism of death in about one-third of patients and the prognosis is worse than in ischaemic cardiomyopathy (ICM) and non- ICM.2–5 There are several mechanisms underlying the development of CCC including autonomic nervous system derangement, microvascular disturbances, parasite-dependent myocardial injury, and immune-mediated myocardial damage.6 These pathogenic mechanisms lead to progressive myocardial fibre destruction, fibrosis, inflammation, compensatory hypertrophy, and reduction in performance, with dilatation of the atria and both ventricles, and a progressive remodelling process.5 Cardiac resynchronization therapy (CRT) is an established therapeutic modality for patients with ICM and dilated cardiomyopathy (DCM) when associated with symptoms, LBBB and QRS duration >130 ms, and left ventricular ejection fraction (LVEF) <35%, despite adequate medical treatment (Class I recommendation).7 However, little is known about the effects of CRT in patients with CCC. There are no randomized studies, and very few observational reports in this condition. In this issue of Europace, Martinelli Filho et al.8 present data from a retrospective study of patients treated between January 2001 and December 2012, comparing the outcome of patients with CCC and those with DCM and ICM who underwent CRT. They studied 115 patients with CCC, 177 patients with DCM and 134 patients with ICM. The primary endpoint was all-cause mortality, and the secondary endpoints were the rate of non-advanced NYHA class 12 months after CRT implantation and echocardiogram changes evaluated at least 6 months after CRT. The primary endpoint mortality was met in 67/115 patients with CCC, in 71/177 patients with DCM, and 55/134 patients with ICM. The estimated annual mortality rates for DCM and ICM groups were 10.4% and 11.3%, respectively, compared to 25.4% in CCC patients. However, there were no differences in survival among patients with preserved functional class in the three groups (I–II NYHA), in contrast to the much higher mortality in the CCC group in patients with advanced NYHA class. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group. Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic results, although patients in the DCM group had increased LVEF and decreased LV end-diastolic diameter. This is an important and interesting study and is the largest published series describing patients with CCC treated with CRT. It is important to try to understand why such a large difference in mortality was observed among the different CM groups. The first point is that neither in this publication nor in prior literature was there a control group of CCC patients without CRT, therefore we really do not know whether CRT improved, worsened, or was neutral in its effects. One possible reason for the possible lack of benefit could be the amount of fibrosis that the CCC patients might have in the region where the LV lead is positioned. We already know that patients with CCC and advanced heart failure have a large amount of fibrosis2 and if the LV lead was positioned in a region of fibrosis there may be inadequate local capture or conduction. In the future, the amount and location of LV fibrosis on MRI should be investigated in patients with CCC, especially those destined to have CRT. The other important point is that the baseline characteristics of the CCC group were much different in many aspects compared to the other two groups. The CCC group had many more patients with atrial fibrillation and right ventricular dysfunction, and fewer patients on beta blockers. There was also a big difference in the CCC group and the type of intra-ventricular block, with a greater proportion of non-LBBB patients. All these factors will negatively impact the response to CRT, so it is not clear if all these baseline differences were responsible for the different mortality that was found in this study. In summary, the study of Martinelli Filho et al.8 showed that CCC patients who underwent CRT have worse prognosis compared to CRT-treated patients with DCM and ICM. Randomized prospective studies in CCC patients are clearly warranted to determine if there is any potential benefit of CRT in contrast to patients with others forms of CM for whom CRT is clearly advantageous in appropriately selected patients. Conflict of interest: none declared.