HRT is a baroreflex-mediated biphasic reaction of heart rate in response to premature ventricular beats [
22]. Generally, abnormal HRT is widely accepted to be indicative of potential autonomic dysfunction or impaired baroreflex sensitivity in patients due to variety of disorders; it may also reflect changes in autonomic nervous system induced by different therapeutic modalities such as drugs, revascularization, or cardiac resynchronization therapy [
15,
23]. More importantly, impaired HRT has been demonstrated in identifying patients at high risk for all-cause mortality and sudden death, particularly in post-infarction and congestive heart failure patients [
24]. Notably, HRT have a higher specificity and sensitivity as compared to some other detection methods since it is a bi-physiological response of the interaction between sinus and ventricular contraction that reflect the sensitive outcome of extremely weak endogenous stimuli triggering reflex regulation [
25,
26]. In recent decades, increasing number of clinical applications in HRT have gained global popularity as well as considerable successes, and it has been previously described as an independent predictor of mortality in patients with cardiovascular diseases [
27,
28].
Generally, HRT is described as the acceleration and subsequent deceleration of sinus rate [
29]. Abnormal HRT has a well-established role in the stratification of post-infarction and heart failure in patients [
30]. However, current emphasis on the medical application of HRT is far from perfect, and its function has not been fully assessed. In this study, we evaluated the relationships between HRT parameters and prognosis in CHF patients to explore the predictive values of HRT parameters in the development and progression of CHF. This study revealed that CHF patients exhibited a significant reduction in HRT levels with higher TO levels and lower TS levels than the healthy subjects, suggesting that the HRT levels may be closely related to the development and progression of CHF. Although the exact reasons for HRT reduction in patients with CHF are not fully understood, a potential explanation could be that CHF patients may suffer from myocardial deformation or damages in the terminal receptors, and abnormal sympathetic and vagal afferent stimulation, which may lead to dullness of baroreflex, cause decreased HRT or disappearance of HRT after VPBs in patients with organic heart disease [
31]. Sredniawa et al. demonstrated that CHF patients were associated with more abnormal average values of HRT parameters, as a marker of the autonomic regulation in the heart, might play important roles in the progression toward end-stage heart failure or all-cause mortality of CHF patients [
18]. Analysis of HRT is an easy and innocuous way to assess the parasympathetic nervous system, and it can be used as a prognostic marker both in ischemic heart disease and heart failure; in some cases, it even has a better correlation than LVEF [
32]. We also found a significant difference in HRT
1/2 rate between CHF patients and healthy controls. Furthermore, CHF patients with NYHA grade IV had a higher positive rate of HRT
1/2 than those with NYHA grade II/III, revealing that HRT was correlated with the severity of CHF. The observation of more depressed HRT in patients with advanced NYHA functional class is also consistent with previous reports and studies [
33]. In addition, our study also found statistical differences in TS, LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor group; significant differences in TS among the three groups were also observed. Moreover, correlation analyses indicated that both the TS and TO were significantly correlated with SDNN and that only TS was significantly correlated with LVEF. These findings revealed that TS could be considered as a stronger predictor of hospitalization for worsening heart failure and death in CHF patients than LVEF, SDNN and RHR. The mechanisms of the decreased TS in CHF patients are not clear; it is likely that the TS is more susceptible to CHF events because it correlates with both the left ventricular function and the cardiac autonomic status [
34]. Consistent with our results, a previous study suggested that the TS appears to be a more suitable prognostic marker for CHF death and hospitalization than LVEF and SDNN, which further confirmed that HRT serves great predictive value in the prognosis of CHF [
35]. Univariate survival analysis demonstrated that age (≥65), LVEF (≤30%), SDNN (≤100 ms), RHR (≥75 bpm), HRT
1 and HRT
2 were associated with poor prognosis of CHF patients. Multivariate Cox regression analysis indicated that LVEF (≤30%), HRT
2, SDNN and RHR were independent risk factors for poor prognosis of CHF patients. Among these risk factors, HRT
2 (the combination of abnormal TO and TS) was the strongest predictor of CHF with a high hazard risk of 5.12 after CHF and remained highly significant after adjustment for LVEF and other clinical risk factors. The combination of abnormal TO and TS may result in tachycardia which would cause decreased heart efficiency in increased myocardial oxygen consumption, decreased myocardial perfusion during myocardial relaxation and diastolic, thereby leading to myocardial injury and aggravating or worsening heart failure [
36]. Nevertheless, some limitations of this study should be acknowledged. Firstly, a lack of image analysis software to automatically identify and analyze the matched VPBs, as well as HRT, limited the accuracy in the prognostic significance of HRT in CHF patients. Secondly, HRT level is easily affected by various factors, therefore certain limitations still remain in the sensitivity, specificity and positive predictive value of HRT in CHF patients. Thirdly, due to the short follow-up time and the relatively small sample size, the correlation between HRT and CHF requires further verification.