IJCS | Volume 32, Nº2, May/June 2019

286 Rezende et al. Cardiac disorders in chronic hepatitis C Int J Cardiovasc Sci. 2019;32(3)283-289 Review Article Spe c i a l a t t en t i on shou l d be g i ven t o t he e l e c t r ophy s i o l og i c a l d i s o r de r s i n c i r r ho t i c cardiomyopathy. Previous studies have reported cardiac arrhythmias as the main clinical manifestation in patients with cardiac abnormalities related to HCV infection and in patients with liver cirrhosis due to any etiology. The increase in the QT interval is the most frequently observed abnormality, with an incidence of up to 50% in this population, apparently more pronounced the greater the activity of the disease and the worse the liver function. 18 Specifically in the case of hepatitis C, QT increase may be higher in patients coinfected with HIV. 19 Long QT has been described as a predictor of mortality in liver cirrhosis. 16 The use of some common drugs in cirrhotic patients is also related to increased QT interval. An example are the fluoroquinolones used in the treatment of spontaneous bacterial peritonitis. Similarly, in HIV coinfected patients, the associated antiretroviral therapy has also been described as a cause of significant QT interval increase. 20 The onset of severe ventricular arrhythmias, such as polymorphic ventricular tachycardia (Torsade de pointes) associated with long QT, may be a rare cause of sudden death in this population. Inaddition toventricular arrhythmias, supraventricular tachyarrhythmias such as atrial fibrillation and flutter are more often diagnosed in cirrhotic patients. Lee et al., 21 found that the presence of hepatic cirrhosis is an independent predictor for the occurrence of atrial fibrillation (AF), especially in the population younger than 65. However, although the presence of AF is related to higher mortality in the general population, this arrhythmia had no correlation with higher mortality in the cirrhotic group, which could be explained by the high proportion of deaths in this group, about five times higher compared to the control group. 21 Atrioventricular and intraventricular conduction disorders are also described in these patients with a higher prevalence in the general population. 16 However, the findings related to autonomic dysfunction with chronotropic deficit are the main abnormalities related to heart rhythm. The explanation for this fact is mainly the progressive loss of sensitivity of cardiac beta- adrenergic receptors, despite the high sympathetic tone in cirrhosis. In addition, decreased response to beta-adrenergic stimulus would also be related to the involvement of other elements of sympathetic signal transduction, including the receptor itself, G protein and adenylyclase activity, decreasing AMPc levels. 22 Other studies reported that the chronotropic incompetence observed in physical or pharmacological stress response tests could be a predictor of cardiovascular events (myocardial infarction and heart failure) in cirrhotic patients that had a liver transplant. 23,24 The treatment of cardiac disorders in cirrhotic patients presents some peculiarities in comparison to other forms of myocardiopathies. The use of non- cardioselective beta-blockers (e.g. propranolol) can prevent the bleeding of esophageal varices, decrease the risk of severe arrhythmias associated with increased QT interval and improve diastolic dysfunction, playing an important role in decreasing the deleterious effects of hyperadrenergic state. The use of angiotensin- converting enzyme inhibitors may prevent cardiac remodeling and arrhythmias such as atrial fibrillation and should be used with caution because of the risk of hypotension, since these patients already have a lower peripheral vascular resistance. Aldosterone inhibitors, such as spironolactone, have a better effect on blood volume reduction than loop diuretics in this population, and also contribute to the reduction of myocardial fibrosis. Liver transplant may reverse most of the cardiac abnormalities mentioned. 15 Treatment of hepatitis C Interferon and Ribavirin Interferon (IFN) has several biological properties which mainly include antiviral, immunomodulatory and antiproliferative actions. Alpha-IFN (produced by leukocytes), widely used in the treatment of patients with hepatitis C, has several side effects, including cardiac abnormalities that are rare but may represent a greater risk of serious complications. 25 In the early 1990s, Sonnenblik et al. published a record of 44 patients with cardiac complications related to IFN therapy, including 58% incidence of arrhythmias, 21% of acute coronary syndromes, 12% of cardiomyopathies and 9% of other manifestations, including pericarditis. Of the 25 patients that presented arrhythmias, two had severe ventricular tachyarrhythmias and one had sudden death. Of the eight patients with acute myocardial infarction, six died. 26 The introduction of alpha interferon pegylate (peginterferon) allowed to increase the interval of subcutaneous administration of IFN to once a week, instead of three times a week in the previous treatment. The association of peginterferon with ribavirin added