ABC | Volume 114, Nº4, April 2020

Short Editorial Short Editorial: Ser49Gly Beta1-adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure Antonio Carlos Pereira-Barretto 1,2, 3 Departamento de Cardiopneumologia da FMUSP, 1 São Paulo, SP – Brazil Instituto do Coração (InCor) do HCFMUSP - Serviço de Prevenção e Reabilitação, 2 São Paulo, SP – Brazil Hospital Santa Marcelina – Cardiologia, 3 São Paulo, SP – Brazil Short Editorial: Ser49Gly Beta1-adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure Mailing Address: Antonio Carlos Pereira-Barretto • Instituto do Coração, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Av Éneas de Carvalho Aguiar 44, Cerqueira Cesar, Postal Code 05403-000, São Paulo - Brazil E-mail: pereira.barretto@incor.usp.br Keywords Heart Failure/physiopathology; Heart Failure/mortality; Prognosis; Genetic,Polymorphism; Sympathetic Nervous System; Adrenergic beta-1; Receptor Agonists; Adrenergic beta-2; Receptor Agonists. Heart failure (HF) is a disease that develops into high morbidity/mortality. However, not all patients have a bad evolution. Symptomatic patients and those who require hospitalization for treatment comprise the group with the worst prognosis. Symptom intensity has shown to be a good predictor of prognosis. However, in less symptomatic patients, we have a much more limited capacity to identify those who will have a worse evolution. 1 In the article “Ser49Gly Beta1-adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure”, published in this issue, the authors discuss a current topic, in which they show that patient evolution is, at least in part, related to their genetic profile, and that this profile determines the intensity of HF and symptom development. 2 Neurohormonal stimulation has an important pathophysiological role in HF, and multicentric clinical trials have fully documented that the blockade of the overactivated renin-angiotensin-aldosterone and sympathetic systems modifies the disease evolution. And in this context, the role of the sympathetic nervous system is well established and possibly has the role of the greatest villain in the history of HF. The response to neurohormonal stimulation is not the same in all patients and the genetic polymorphism influences this response. The sympathetic activity is mediated by type 1 and type 2 beta-adrenergic receptors. 3 The genetic polymorphism of these receptors has been evaluated and the sympathetic activity differs according to the polymorphism. For the beta- 1 receptor, two polymorphisms have been more frequently studied: Ser19Gly and Arg389Gly and for the beta-2receptor, also two polymorphisms: Gly16Arg and Gln27Glu. 3 The beta-1 receptor polymorphism has been shown to play a role in the incidence of HF, response to beta‑blockers, echocardiographic outcomes, functional capacity, incidence of cardiac arrhythmia and the clinical evolution of patients. 2,3 However, most studies were carried out with small populations and the outcomes have not shown homogeneous results, although it has been possible to verify that the genetic constitution determines patient evolution, including treatment response. One can verify this fact, in relation to the beta-2 receptor polymorphism, in the FAST-Carvedilol study. When assessing survival, one can document that by analyzing patients considering the polymorphism, evaluating the DD-ID and II genotypes, the carriers of the polymorphism II had higher mortality than the DD and ID variants. However, the most interesting result was that patients II, when they received an optimized dose of carvedilol (> 50% of the target dose), showed a significant reduction in mortality, while in patients with the DD and ID variants, the dose did not change the evolution. 4 As the study result, we observed that group II treated with a low dose of carvedilol had a 6-fold greater chance of dying than the group that received an optimized dose of carvedilol. 4 In the same line of research, in the MERIT-HF study, when analyzing the Beta-1 receptor polymorphism, it was observed that there were patients receiving high doses of beta-blockers who did not respond to treatment, whereas others showed significant improvement. 3 In the BEST study, the genetic polymorphism was associated to the lack of response to the beta-blocker bucindolol. This was one of the few multicenter studies with a significant number of patients that prospectively analyzed the role of the polymorphism in the therapeutic response to a beta-blocker. The polymorphism was analyzed in this multicenter trial with more than 1,000 patients and showed that patients with the wild beta-1 receptor Gly389 polymorphism did not respond to treatment with bucindolol. On the other hand, those without this polymorphism had reduced mortality with bucindolol. 3 The researchers consider that the data on the polymorphism are not always consistent and that at the moment it is better not to use this tool to guide treatment. 2 However, its role in the evolution of HF patients continues to supply us with information, allowing a better understanding of this complex syndrome. The studies have shown that the adrenergic system response mediated by the genetic variants of central or peripheral adrenoceptors has a role in the physiology of HF. As already shown, this inter-individual variability even changes the prognosis of HF, with some patients showing more cardiac events despite the moderate DOI: https://doi.org/10.36660/abc.20200183 625