IJCS | Volume 32, Nº2, May/June 2019

285 Rezende et al. Cardiac disorders in chronic hepatitis C Int J Cardiovasc Sci. 2019;32(3)283-289 Review Article effect. The third pathophysiological mechanism would be by induction of myocardial cellular apoptosis caused by mitochondrial disorders and fragmentation of the genomic DNA of the cell. 13 The emergence of hypofunctioning fibrotic areas during the myocardial healing process would lead to cardiac remodeling with progressive loss of ventricular systolic function, leading to heart failure, as well as a greater risk for severe ventricular arrhythmias and sudden death. 10 Despite this association and the evidence of potential mechanisms that justify the occurrence of DCM induced by HCV, there are still no studies proving this fact. Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM) is an inherited disease characterized by an increased LV mass. This inappropriate myocardial hypertrophy is related to an architectural disorder of the cardiac fibers and different degrees of fibrosis, being a substrate for malignant ventricular arrhythmias, a frequent cause of sudden death in this population. Several types of mutations have been identified in genes that decode the structural proteins of myocyte, such as myosin heavy chains, tropomyosin and troponin T. 14 In a multicenter study conducted by Matsumori in Japan in the early 1990s, serology for HCV was positive in 74 out of 697 patients diagnosed with HCM (10.6%), a result that contrasted with only 25 seropositives in 1,039 volunteering blood donors (2.5%). Another interesting fact in this survey was that the prevalence of HCV was higher in patients with HCM compared to the DCM population. 9 Among the clinical manifestations described in this study, arrhythmias and cardiac conduction disorders were present in nearly half of the patients. The factors that justify the association of HCM and HCV infection have not been reported. Advanced liver disease As we saw in the introduction to this article, about 20% of the individuals with chronic hepatitis C will develop cirrhosis. In cirrhotic patients, hepatic dysfunction and portal hypertension may lead to hemodynamic, neurohumoral and inflammatory disorders that affect cardiac function. 15 Cirrhotic cardiomyopathy is characterizedby increased cardiac output, autonomic disorders that influence the response to physiological or pharmacological stimuli, systolic and diastolic dysfunction and electrical abnormalities, without any other cause of heart disease being identified to justify the findings described. Myocardial hypertrophy is often observed and an association with fibrosis increases the risk of ventricular arrhythmias. 16 Paradoxically, some authors report that abnormalities related to liver cirrhosis could have a “protective” effect to the risk of coronary artery disease and acute coronary events. Such factors would be attributed to hepatic dysfunction and hemodynamic effects of portal hypertension, such as worsening of coagulation, presence of thrombocytopenia and platelet dysfunction, blood pressure decreased due to lower peripheral vascular resistance, abnormal lipid metabolism causing a decrease in cholesterol levels and increased levels of estrogen. 15 However, a lower incidence of coronary events in this population is controversial and, in the case of patients infected with HCV, the risk of atherosclerotic disease could be increased by other factors not well known, as previously reported. Autonomic dysfunction is also an important marker of cirrhotic cardiomyopathy. Increased sympathetic activity and the renin-angiotensin-aldosterone system contribute to increased cardiac output, sodium and water retention and consequent increase in blood volume, associated with a reduction in peripheral vascular resistance due to the greater release of nitric oxide in the peripheral circulation, besides influencing ventricular remodeling with greater hypertrophy and worsening of the systolic and diastolic functions. The hyperadrenergic state facilitates the release of cytokines and the stimulation of cellular apoptosis, increasing myocardial impairment. 15 One of the main disorders caused by cirrhotic cardiomyopathy is the relative hypoxemia caused by vasodilation of the pulmonary arterial bed (Hepatopulmonary Syndrome). A significant increase in the diameter of the pulmonary capillaries produced by a higher concentration of nitric oxide in the arteriolar and pulmonary capillary beds would allow the passage of several erythrocytes simultaneously in the alveolar exchange area, leading to a lower oxygenation of these, resembling the right-left shunt effect. On the other hand, increased production of vasoconstricting agents in the splanchnic circulation could cause the so-called portopulmonary hypertension — initially reversible — but with the development of endothelial hyperplasia, local thrombosis and vessel obstruction, this pulmonary arterial hypertension becomes irreversible. 17