Discussion
We present a prospective cohort of patients with heart failure and an indication for CRT where Chagas disease was the most frequent cause of cardiomyopathy. There was no loss of follow-up and use of evidence-based medical therapies was higher than most previous CRT-trials.9,10 Furthermore, the indication for CRT was consistent with guideline-based recommendations, with almost all patients presenting with LBBB (induced or spontaneous) and QRS> 150ms.
Patients undergoing the upgraded CRT implantation had similar clinical, echocardiographic and demographic characteristics when compared to the population of new CRT, only differing with a higher prevalence of Chagas’ disease. Unlike previous studies comparing de novo CRT vs upgraded, we found no difference regarding the prevalence of atrial fibrillation or QRS duration between both groups.5,11
Overall population was a high-risk one, with LVEF in average below 25% and most patients on NYHA class III or IV. In general, CRT was effective in improving systolic performance with a significant increase in LVEF. This left ventricular reverse remodeling occurred consistently in both groups, upgraded and de novo . This result is in line with a recently published meta-analysis that demonstrated similar rates of improvement in LVEF in patients undergoing upgraded and de novo -CRT.12
However, we observed a high overall mortality in 1-year follow-up of 30.1%, mainly in the upgraded-CRT group. In univariate analysis, Chagas disease and upgraded-CRT were directly associated with overall mortality in 1-year, and the main find of our study was that in the multivariate model, upgraded therapy was the solely variable associated with the outcome. This finding, and the excessive mortality-rate in the upgraded group, is consistent with the study of Vamos M et al, that followed 552 CRT implantations, including 177 upgrade procedures, and found a 1.65-fold increased mortality. Similarly, the cohort of Beca B et al, found a long-term mortality rate 2.86-fold increased. On the other hand, this data differs from previously mentioned meta-analysis, and the European CRT survey, that demonstrated that CRT upgrade is associated with similar risk for all-cause mortality compared to de novoresynchronization therapy.5,11-13
Some factors may justify these findings, firstly, it has been suggested that CRT upgrade procedures are associated with increased peri-procedural complications. In fact, all in-hospital deaths occurred in the upgraded-CRT group, and directly related to the procedure. Our sample size was not sufficient to test this hypothesis. Data comparing the rates of complications following CRT upgrade versus de novoCRT are limited and inconsistent. In a large European CRT Survey of 11088 patients, and 2396 (23.2%) upgrade procedures, overall peri-procedural complication rates were similar between upgraded-CRT andde novo CRT. In contrast, Cheung JW et al, using the United States National database, identified a significantly higher rate of complications in CRT upgrade patients compared to de novo CRT patients with a two-fold increased risk of in-hospital mortality.6,14
Other hypothesis is that patients in the upgrade group had more advanced heart disease and more comorbidities, and the indication for biventricular pacing may have been initiated too late. In our series, upgraded patients had similar baseline characteristics of advanced heart failure compared to de novo patients. However, despite the lack of statistical significance, upgraded patients had a trend to be older, with slightly lower left ventricular ejection fraction and higher prevalence of NYHA III and IV.
Finally, particularly in this heart failure population, Chagas disease might play a role in impairing patients survival. The pathophysiological and epidemiological characteristics of Chagas disease itself corroborate worse outcomes. Heart failure patients due to Chagas cardiomyopathy are known to have a worse prognosis compared to other etiologies, with a higher incidence of death from heart failure progression and arrhythmic death.15-17. Particularly in patients undergoing CRT, it has been consistently demonstrated that Chagas cardiomyopathy has a worse prognosis when compared to other heart failure etiologies. Martinelli et al showed that Chagas disease had a two-fold higher risk of death in one-year compared to the others dilated cardiomyopathy. Simirlaly, Passos, et al also demonstrated a worse prognosis in combined events in patients with Chagas cardiomyopathy after CRT.7,8
It is important to emphasize that, since intrinsic LBBB in Chagas heart disease is uncommon, and it is considered an arrhythmogenic cardiomyopathy characterized by a wide variety of abnormalities of the conduction, it is expected a higher incidence of upgraded-CRT implantation in this patients. In fact, in the cohort presented by Martinelli et al, there was a 73.9% incidence of induced-LBBB in Chagas’ disease patients undergoing CRT. In our study, 72.7% of patients undergoing upgraded-CRT implantation had Chagas cardiomyopathy.
This is the first study in which we are known to specifically address the impact of the upgraded-CRT on mortality in a population where Chagas disease is a prevalent cause of cardiomyopathy. In fact, in line with previous publications, Chagas’ disease was directly associated with an increase in short-term mortality after CRT implantation, however after multivariate analysis adjusted for potential confounders, it is suggested that this worse prognosis is due to the higher incidence of upgraded-CRT in this patients. Studies with larger cohorts of Chagas cardiomyopathy patients are necessary to confirm this hypothesis. Until then, considering the current scientific evidence, patients with heart failure secondary to Chagas disease and previous ventricular pacing, must have the indication for the upgrade procedure evaluated with great caution.
This study has some limitations. We emphasize the unicentric design of the study, which may impact in its external validity. Additionally, it is a non-randomized study that generates hypothesis and is exposed to confounding bias. Finally, the limited sample size makes the study vulnerable to type 1 error.