IJCS | Volume 33, Nº4, July and August 2020

416 inhibitor should also be reviewed. Recently, Zhang et al. 35 demonstrated that sacubitril / valsartan reduced the concentration of pro-inflammatory cytokines and the neutrophil count, while increasing the lymphocyte count more than valsartan alone or placebo in patients with acute HF. This evidence supports the biological plausibility of the early administration of sacubitril / valsartan in patients with COVID-19, in order to maximize the anti-inflammatory effects of sacubitril and contain the effect of Angiotensin I in the lungs. 36 It should be noted, however, that there has been no clinical studies evaluating cardiovascular outcomes that support this practice. Therapeutics for COVID-19 and Cardiovascular Disease HFpEF patients with multiple comorbidities are at high risk of death in the case of SARS-CoV2 infection, therefore it is imperative that preventivemeasures be taken. To date, there is no vaccine to prevent COVID-19. The best prevention is to avoid exposure to the virus. The usual preventive measures that can reduce the risk of exposure include: wearing face masks; regular hand washing with soap or disinfection with hand sanitizer containing at least 70%alcohol; avoiding contactwith infectedpeople, keeping an adequate distance; and refraining from touching the eyes, nose andmouthwith unwashed hands. 37 In addition, patients with HFpEF should be vaccinated against pneumococcal pneumonia and influenza. Social isolation to prevent COVID-19 does not necessarily mean the adoption of a sedentary lifestyle. Patients with HFpEF in functional class II and III benefit from regular aerobic exercise to improve their functional capacity and diastolic function. 35 Whenever possible and within the precautions of respiratory contamination, exercise should be maintained. HFpEF patients use polypharmacy to control comorbidities such as angiotensin-converting enzyme (ACEI) inhibitors, diuretics, statins, oral hypoglycemic agents, and some medications that can reduce hospitalization due to HF decompensation, such as spironolactone, candesartan, nebivolol and sacubitril / valsartan, in female patients and with a left ventricular ejection fraction of less than 57%, as evidenced in the PARAGON-HF Study. 38,39 Such prior medications must be maintained in the pandemic and in the eventual contamination by the virus. The antiviral properties of chloroquine (CQ) were previously observed in HIV and other viruses. It has been postulated that CQ and Hydroxychloroquine (HCQ) inhibit endosomal maturation, a process by which endosomes are translocated from the cell to central hubs. In addition, CQ could prevent the viral replication of SARS-CoV1 in vitro. A follow-up study demonstrated comparable effectiveness of HCQ, a less toxic derivative, and suggested that the mechanism of decreased endosomal maturation did indeed apply to SARS-CoV2 infection in vitro. So far, the role of HCQ in COVID-19 has only been evaluated in non‑blind, non-randomized, and low-quality studies. At the time of writing this article, CQ and HCQ have clinical off-label use authorized by the Federal Council of Medicine. There are ongoing clinical trials which assess the in vivo outcome of this hypothetical property. In addition, CQ and HCQ prolong the QT interval, which increases the risk of a pro-arrhythmic effect. Significant caution should therefore be taken when initiating these agents in patients with a QTc interval >500ms, in those with congenital long QT syndrome, with structural heart disease, or under concomitant use of other QT interval prolonging agents. 14 In fact, a recently published observational study with more than 96 000 patients hospitalized for COVID-19 showed an increased risk of death with HCQ and CQ when used alone or in association with a macrolide. 40 ChloroquineandHydroxychloroquinecardiomyopathy There are case reports which relate the use of CQ and HCQ with the onset of diastolic and systolic ventricular dysfunction, dilated cardiomyopathy, pu lmona r y hype r t en s i on s e c onda r y t o l e f t ventricular dysfunction, atrioventricular blocks, and ventricular tachyarrhythmias. In most cases, reversibility is observed after drug withdrawal. Diagnostic confirmation is given by the presence of cytoplasmic curvilinear bodies on electron microscopy of the cardiac muscle added to the clinical history of using CQ or HCQ, and the absence of other factors. 41-44 A possible genetic predisposition is speculated such as the polymorphism of α-galactosidase A, the genetic basis of Fabry's disease. Both CQ / HCQ cardiomyopathy and Fabry disease have clinical and histological similarities. 45 Mesquita et al. HFpEF and COVID-19 Int J Cardiovasc Sci. 2020; 33(4):412-418 Viewpoint