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ACE-inhibitors (ACE-I) represent effective drugs more and more widely used in acute myocardial infarction (AMI) patients, in post AMI patients and mainly, today, in CHF patients.A complete review of the scientific literature and of all the randomized controlled clinical trials (RCTs), where ACE-I have been tested directly or in association with other drugs, have been performed. ACE-I effects on total mortality (TM) and arrhythmic mortality (AM) and other composite clinical endpoints have been evaluated. It is well known that frequent ventricular arrhythmias (VA) and a high incidence of sudden death (SD) can be documented in CHF patients; nevertheless a direct relationship between VA, TM, and AM has not been clearly demonstrated; neither beneficial effects, on the same endpoints, of the treatment and suppression of ambient VA in CHF. Conversely, sometimes clear negative effects on both TM and AM have been observed. According to individual studies and two recent complete and large metanalysis, ACE-I were unable to reduce AM, but they reduced TM. Furthermore, they can affect and modify many, if not all, of the triggering factors of VA and SD in this context. Differently from ACE-I, betablockers (BB) have been clearly associated with a reduction in TM and AM, in the same context. Thus, at present time, ACE-I, with or without BB, should be considered the standard therapy in all patients with CHF, if not contraindicated. Angiotensin II antagonists (AII-a) probably represent a comparably effective treatment, in all CHF patients and mainly in those patients, suffering from side effects or showing intolerance to ACE-I, but we are still lacking definitive data from RCTs. In many RCTs, conducted with traditional antiarrhythmic drug therapy (ADT), these drugs have been widely used, contributing probably, in a consistent way, to some of the positive results of these studies. All primary and some secondary implantable defibrillators (ICD) RCTs, in the prevention of SD, have included these drugs as the standard treatment of the underlying cardiac disease, with or without CHF. The same therapeutical strategy is regularly applied in all biventricular pacing (BP) RCTs, with or without the ICD. These trials are supposed to assess the reduction in TM and AM, preventing deterioration or progression of CHF and improving the quality of the patients' s life.Finally, according to these clinical evidences, in the last part of the review, we stress the need for a more widespread implementation of ACE-I and AII-a in treating CHF patients.

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Abstract Background Chagas disease (CD), a parasitic disease caused by Trypanosoma cruzi. Parasite persistence is crucial in the development and progression of Chagas cardiomyopathy that occurs in 30% of untreated patients. Methods and findings A cohort of 95 CD treated children, with at least 6 years post-treatment follow up, was evaluated. Median after treatmeant follow-up was 10 years. At the time of the last visit a group of non infected subjects were also included as a control for cardiological studies. During follow-up, the majority of treated subjects 59/61 (96%) achieved negative parasitemia by qPCR at the end of treatment. A decrease in T. cruzi antibodies titers were observed and seroconversion by two conventional serology tests (IHA, ELISA) occurred in 53/95 (56%). Holter showed alterations in 3/95 (3%) of treated patients: isolated ventricular extrasystoles and nocturnal sinus bradycardia (one patient); asymptomatic and vagal related 1st and 2nd degree AV block (one patient); and complete right bundle branch block (cRBBB) (one patient). Only the last one is probably related to CD involvement. 2D speckle tracking echocardiography was conducted in 79/95 (83%) patients and no alterations in myocardial contractility were observed. In the non infected group Holter evaluations showed similar non pathological results in 3/28 (10%) of subjects: isolated ventricular premature beats (2 patients); asymptomatic 2nd degree AV block with Wenckebach sequences during night time (one patient). 2D speckle tracking echocardiography was conducted in 25/28 (89%) with no alterations. Conclusions After long term follow-up of a cohort of treated children for CD, a good parasiticidal treatment effect and a low incidence of cardiological lesions, related to Chagas disease, were observed. These results suggest a protective effect of treatment on the development of cardiological lesions and strengthen the recommendation of early diagnosis and treatment of infected children. Trial registration ClinicalTrials.gov NCT04090489.