title: Recombinant interferon alpha treatment decreases heart rate variability indices and impairs exercise tolerance in patients with chronic hepatitis.
abstract: Complications of interferon (IFN) therapy include cardiac arrhythmias, impaired cardiac function and myocardial ischemia. Decreased heart rate variability (HRV) indices, impaired exercise tolerance and decreased left ventricular (LV) function are related to unfavorable outcome of heart disease. To investigate the effect of IFN therapy on HRV, exercise tolerance and cardiac function, 24-h ambulatory electrocardiographic monitoring (AECG), two-dimensional echocardiography, and exercise treadmill testing (ETT) was performed in 9 patients (age 56 +/- 9 years-old) with chronic hepatitis and without underlying heart disease before and after treatment with IFN (recombinant alpha 2b; 10 x 10(6) U/day for 4 weeks). HRV parameters consisted of standard deviation of RR interval (sdNN, ms), SDANN (ms), S.D. index (ms), rMSSD (ms), pNN50 (%) and frequency analysis of heart rate spectrum resulted in low (ms, 0.04-0.15 Hz), high (ms, 0.15-0.40 Hz) and total (ms, 0.01-1.00 Hz) frequency components. Ischemia was not detected by AECG or ETT, and LV function was normal after INF treatment in all patients. However, INF treatment resulted in a decrease in exercise tolerance time (449 +/- 94 s vs. 329 +/- 67 s, P < 0.05) and a decrease in several HRV parameters (S.D. index, 42 +/- 5 ms vs. 37 +/- 9 ms; rMSSD, 22 +/- 5 ms vs. 19 +/- 4 ms; pNN50, 4 +/- 3% vs. 2 +/- 1%; P < 0.05). Further, patients treated with INF tended to have a lower sdNN and total frequency spectra, although this difference did not reach the level of statistical significance. These data suggest that the arrhythmogenic effect of INF may be mediated by decreases in HRV and impairment of exercise tolerance even in patients without overt heart diseases. Further, INF therapy may be contraindicated in patients with predisposing severe cardiac disorders, including arrhythmias, ischemia and decreased LV function.
authors.affiliation: Division of Biomedical Engineering, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. bonpeit@ndmc.ac.jp
authors.forename: B
authors.initials: B
authors.lastname: Takase
authors.forename: A
authors.initials: A
authors.lastname: Hamabe
authors.forename: A
authors.initials: A
authors.lastname: Uehata
authors.forename: T
authors.initials: T
authors.lastname: Hujioka
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: F
authors.initials: F
authors.lastname: Ohsuzu
authors.forename: M
authors.initials: M
authors.lastname: Ishihara
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004452:Echocardiography; D004562:Electrocardiography / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006521:Hepatitis, Chronic / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins