Detection of Hepatitis C Virus RNA from the Heart of Patients with Hypertrophic Cardiomyopathy

doi:10.1006/bbrc.1996.0803

Biochemical and Biophysical Research Communications

Volume 222, Issue 3, 24 May 1996, Pages 678-682

https://doi.org/10.1006/bbrc.1996.0803 Get rights and content

Abstract

We investigated hepatitis C virus (HCV) infection in 35 patients with hypertrophic cardiomyopathy and 40 patients with ischemic heart disease who were consecutively admitted to our hospital. Frequency of positive anti-HCV antibody was significantly higher in patients with hypertrophic cardiomyopathy (6 of 35 patients, 17.1%) than that in patients with ischemic heart disease (1 of 40 patients, 2.5%, p = 0.036). In three of these six patients with hypertrophic cardiomyopathy, HCV RNA was detected in myocardial tissue. In two of these three patients, HCV RNA was detected from biopsy and autopsy specimens of the ventricles, but not in the serum, suggesting that HCV may replicate in myocardial tissue and may be relevant to ventricular hypertrophy. Thus, HCV infection may play a role in the development of hypertrophic cardiomyopathy.

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Citation Excerpt :
Unlike HCV antibody-positivity, HCV RNA-positivity was not a determinant factor for SV dysfunction or poor long-term survival (Figure. 3, Table 4). Interestingly, the previous study showed that HCV RNA was detected in the myocardial tissue of hypertrophic cardiomyopathy patients but not in their serum.23 HCV RNA was found in serum in 3 out of 7 patients with ischemic heart disease, who had HCV RNA-positive carotid plaque.24
It was reported that hepatitis C virus (HCV) antibody-positivity adversely affects cardiac function. As the screening for HCV began in 1992, we hypothesized that HCV antibody-positive rate would be high in adult congenital heart disease (ACHD) patients who underwent heart surgery before 1992 and adversely affected cardiac function and long-term prognosis. We retrospectively enrolled 243 ACHD patients (mean age 25.9 years) who underwent cardiac surgery before 1992 and visited our hospital from 1995 to 2015. We compared clinical characteristics including cardiac function and long-term prognosis between HCV antibody-positive (n = 48) and antibody-negative (n = 195) patients. The composite end point (CEP) included cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation. The prevalence of reduced systemic ventricular ejection fraction <50% was significantly higher in the HCV antibody-positive group compared with the HCV antibody-negative group (17 vs 5.4%, p = 0.014). During a mean follow-up period of 10.1 years (interquartile range 6 to 14 years), the CEP was noted in 51 patients. Kaplan-Meier analysis showed the HCV antibody-positive group had significantly poor event-free survival than the HCV antibody-negative group (log-rank, p = 0.002). In contrast, HCV ribonucleic acid-positivity was not a significant predictor of the CEP in the HCV antibody-positive group (log-rank, p = 0.442). Furthermore, the HCV antibody-positivity was significantly associated with the CEP in both univariable and multivariable Cox regression models (hazard ratio 2.37, 95% confident interval 1.32 to 4.15, p = 0.005 and 1.96, 1.06 to 3.63, p = 0.032, respectively). In conclusion, these results suggest that more attention should be paid to HCV antibody-positivity in the management of ACHD patients.
Pegylated Interferon-α Plus Ribavirin Therapy Improves Left Ventricular Diastolic Dysfunction in Patients With Chronic Hepatitis C Attaining Sustained Virological Response
2018, American Journal of the Medical Sciences
Citation Excerpt :
Recent studies have shown that off-target effects of combination therapy are involved in a wide spectrum of toxicities affecting various organ systems including the cardiovascular system,6,10,11 whereas, other studies have reported no adverse effect of combination therapy with pegIFN/RBV on the cardiac function of patients infected with HCV.12 Robust studies have identified HCV infection as an insidious disease predisposing patients to the risk of developing clinical and subclinical cardiovascular disease,13-19 and our previous study demonstrated evidence of left ventricular diastolic dysfunction (LVDD) in chronically HCV-infected individuals.20 Emerging evidence also indicates that infection with HCV increases the risk of cardiovascular disease and the potential effect of viral eradication can improve cardiovascular outcomes in the clinical setting.21
Pegylated interferon (pegIFN) in combination with ribavirin (RBV) has successfully improved the rate of sustained virological response (SVR) in chronic hepatitis C virus (HCV) infected individuals, which reduces the progression of the chronic liver disease. However, the influence of combination therapy (pegIFN/RBV) on cardiac function has yielded ambiguous results. The present study aimed to evaluate the effects of combination therapy with pegIFN/RBV on cardiac function of HCV-infected individuals with SVR.
Cardiac function was assessed and correlated in 142 treatment-naïve patients with HCV infections by determining cardiac biomarkers and echocardiography before treatment and for 24 weeks post-treatment.
An SVR was achieved by 50.7% of all patients. Serum N-terminal pro-B-type natriuretic peptide levels were significantly higher in all patients before treatment and decreased significantly 24 weeks post-treatment in the SVR group (62.84 [36.98-102.73] versus 22.87 [15.64-56.92] pg/mL, P < 0.01). Peak early diastolic annular velocity (E′) was significantly lower (7.69 ± 2.48 versus 9.74 ± 2.68 cm/s, P < 0.001) and E/E′ was higher (10.04 ± 2.51 versus 8.18 ± 2.31, P < 0.001) in all patients with SVR. However, there were no statistically significant differences in biomarkers and echocardiographic parameters for patients without SVR. In addition, multivariate analysis identified age (odds ratio [OR] = 1.076; 95% CI: 1.031-1.125; P < 0.001), NT-proBNP (OR = 1.122; 95% CI: 1.002-1.248; P = 0.015), and SVR (OR = 0.532; 95% CI: 0.214-0.895; P = 0.023) as statistically significant independent variables associated with left ventricular diastolic dysfunction.
The present study showed no adverse effects of combination therapy on cardiac function of HCV-infected individuals with SVR. Subsequent viral eradication resulted in improvement of left ventricular diastolic dysfunction.
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Citation Excerpt :
Furthermore, the higher frequency of antigens from hepatitis B and C in DCMs, especially in idiopathic DCM compared to donated hearts, also raises the possibility of a causal relationship between these microorganisms and DCM. In a Japanese population [30–32], it was reported a higher frequency of hepatitis C virus in patients with DCM and hypertrophic cardiomyopathy, however, another series did not demonstrate the same results [33], suggesting technical or geographical influence over these findings. Alternatively, the presence of infectious agents could be secondary to another initial process and even so could contribute for the pathophysiological pathway.
Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM).
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The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies.
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Citation Excerpt :
Also, some of the cases of dilated cardiomyopathy have the same gene mutations of hypertrophic cardiomyopathy. Although myocarditis is believed to be the major cause of dilated cardiomyopathy, myocarditis is often associated with hypertrophic cardiomyopathy which is caused by a viral infection such as hepatitis C virus [10–13], or by cardiac sarcoidosis as discussed below [14]. Therefore, one etiology is not consistent with one phenotype of cardiomyopathy.
Hepatitis C virus (HCV) is the cause of many different forms of heart disease worldwide, and yet few cardiologists are aware of it as an etiology of heart disease, or its treatment. The burden of HCV-derived heart diseases is global, with a higher prevalence in Asia, Africa, and low- and middle-income countries. Our study showed that in more than 10% of Japanese patients, their cardiomyopathies are associated with HCV infection. More recently, we found in the USA that up to 15% of patients with heart failure with myocarditis have associated HCV infection. In contrast, in China 79% of patients with hepatocellular cancer and 37% of hepatitis C patients have heart disease, as detected by measuring a proven and sensitive biomarker of heart disease, NT-proBNP. In Pakistan, 17% of hepatitis C patients have heart diseases, as measured by this metric.
Based on these data, 3% of 6.6 billion (198 million) persons worldwide are infected with HCV, and 17–37% (34–73 million) persons are suffering from HCV-derived heart diseases. These figures may be comparable to the number of patients with hepatitis C. HCV infection causes only hepatitis in some patients, only heart diseases in some patients, and both hepatitis and heart diseases in other patients.
A global network is required to establish methods to detect heart diseases caused by infectious agents. Other goals for the network are the expansion of preventive and therapeutic programs in underprivileged countries.
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¹: Corresponding author: 54 Kawaracho Shogoin, Sakyo-ku, Kyoto 606, Japan. Fax: 81-75-751-6477.

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Regular ArticleDetection of Hepatitis C Virus RNA from the Heart of Patients with Hypertrophic Cardiomyopathy

Abstract

Regular Article
Detection of Hepatitis C Virus RNA from the Heart of Patients with Hypertrophic Cardiomyopathy