Effects of shensongyangxin capsule on heart rate turbulence and heart rate variability in chronic heart failure

Sudden cardiac death (SCD), caused mainly by ventricular tachycardia and ventricular fibrillation, still remains a big clinical challenge in chronic heart failure (CHF). Owing mainly to their strong prognostic efficiency and easy detection, heart rate variability (HRV) and heart rate turbulence (HRT) are widely used in recent years as the predictors for the risk of SCD.1,2 Shensongyangxin capsule, which was approved in China, is proved to have anti-arrhythmic action in many clinical settings including CHF. This study aimed to assess the antiarrhythmic effects of shensongyangxin capsule in CHF, as detected by HRV and HRT, in patients with CHF. METHODS Subjects Sixty-six CHF patients secondary to ischemic cardiomyopathy (n=31), dilated cardiomyopathy (n=19), hypertensive heart disease (n=16) without previous treatment were enrolled in this study. The inclusion criteria were aged >18 years and left ventricular ejection fraction (LVEF) <40%. The New York Heart Association (NYHA) heart function classes were class II in 15 patients (male 9 and female 6), class III in 35 patients (male 18 and female 17), and class IV in 16 patients (male 10 and female 6). Groups and treatment All subjects were randomly divided into two groups: the study group (n=32) treated with 4.8 g of shensongyangxin capsule daily in three divided doses in combination with routine pharmacotherapy according to guidelines of CHF, and the control group (n=34) treated with routine pharmacotherapy alone. The mean time of follow-up was 6 months. Measurement of HRT and HRV HRT consists mainly of turbulence onset (TO) and turbulence slope (TS), and TO was obtained according to the following formula: TO=(RR1+RR2)-(RR-2+RR-1)/(RR-2+ RR-1) ×100%, and TS was defined as the maximum positive slope of a regression line calculated from any sequence of 5 subsequent sinus-rhythm RR intervals within the first 20 sinus-rhythm intervals occurring after a premature ventricular complex (PVC). HRV consisted of time domain and frequency domain. Time domain included following parameters: (1) Standard deviation of all normal-to-normal intervals (SDNN); (2) Standard deviation of mean of all normal-to-normal intervals in all consecutive 5-minute segments of the entire recording (SDANN (ms)); (3) The root mean square of successive differences between adjacent normal-to-normal intervals (rMSSD (ms)); (4) The percentage of R-R intervals with more than 50 ms variation (pNN50). In frequency domain, low-frequency (LF, 0.04-0.15 Hz), high-frequency (HF, 0.15-0.4 Hz), and LF/HF ratio were main parameters. Echocardiography Left ventricular end-diastolic diameter (LVDD) was recorded with 2 D-directed M-mode echocardiography and LVEF was measured using Simpson's method. Clinical end points The end points included all cause mortality, ventricular tachycardia defined as episodes of 3 or more successive ventricular complexes and ventricular fibrillation, paroxysmal atrial fibrillation, and stroke. Statistical analysis All data were processed using SPSS 11.5 (SPSS Inc., USA). The quantitative variables were expressed as mean ± standard deviation (SD) and the qualitative variables as frequencies and percentages. The t test was used for comparison of mean between two groups. The chi-square analysis was used for comparison between categorical variables. A P value of <0.05 was regarded as denotation of statistically significant difference. RESULTS There was no significant difference in mean age, gender, body mass index (BMI), LVEF and LVDD and etiology between the two groups (P>0.05). The patients were well matched on NYHA classes between the two groups (P>0.05). The patients of both groups were well matched on the use of routine medications. Six (18.8%) in study group and 8 (23.5%) in control group stopped angiotensin converting enzyme inhibitor (ACEI) and took angiotensin receptor blocker (ARB) due to constant cough. One (3.1%) in study group and 2 (5.9%) in control group did not continue ACEI and ARB to the end of study because of obvious hypotension. All patients of study group continued taking the shensongyangxin capsule to the end of the study without side effects and complications that prompted stopping it. After treatment, HR and TO significantly decreased in both groups (P<0.05), and TS, pNN50, SDNN, rMSSD, LF, LF/HF significantly increased (P<0.05), while SDANN and HF significantly increased only in study group (P<0.05), yet there was no statistically significant difference in SDANN and HF in control group between before and after treatment (P>0.05), though the data appeared to have a tendency of increase. After treatment, there were statistically significant differences in the changes of HR, TO, TS, pNN50, SDNN, SDANN, LF, HF between two groups (P<0.05), whist the difference in rMSSD and LF/HF between two groups appeared to be insignificant (P>0.05) (Tables 1, 2).Table 1: HR, HRT and HRV before and after treatmentTable 2: Changes in HR, HRT and HRV after treatmentCompared with the control group, the study group had a lower occurrence rate of VT and paroxysmal atrial fibrillation (2 (6.3%) vs. 9 (26.5%), P<0.05). There was no significant difference in the gross mortality, VF and the occurrence rate of stroke between two groups (P>0.05) DISCUSSION Our study showed that routine pharmacotherapy could decrease HR and TO, and increase TS, pNN50, SDNN, rMSSD, LF, LF/HF, and shensongyangxin capsule, when combined with routine pharmacotherapy, could significantly further normalize the HRV and HRT and reduce the incidences of VT and AF, with more significant changes in parameters such as HR, TO, TS, pNN50, SDNN, SDANN, LF and HF, indicating that shensongyangxin capsule could bring definite electrophysiological benefit to patients with CHF. HRV is the physiological phenomenon of variation in the time interval between heartbeats. HRT has a strong and independent prognostic value for identifying postinfarction patients at high risk for death. The recovery of HRT could be produced after effective treatment including beta-blockers, ACEIs, or cardiac resynchronization therapy. Therefore, HRT might also be used as both a promising tool to identify patients who might benefit from implantation of a cardioverter-defibrillator and a treatment target to guide pharmacotherapy of HF. 3 Studies showed that shensongyangxin capsule could stabilize the cellular membrane, prolong potential action, block the reentry, and whereby effectively treat arrhythmia. Studies also showed that it could reduce and prevent the occurrence of arrhythmia, and could be recommended in the treatment of HF because of its safety and low toxicity and good compliance.