What we found for our new score
This large observational study first derived a long-term prognosis model for NICM heart failure patients implanted with CRT. The Alpha-score was based on the largest retrospective cohort of Chinese NICM patients with CRT. The risk score performed well in predicting the long-term prognosis of NICM patients based on the clinical characteristics and biomarkers; it showed good predictive ability for both all-cause mortality and heart failure hospitalization within the derivation and validation datasets. In addition, a simple easy-to-use application was developed for clinical risk stratification before CRT implantation and long-term follow-up, which can calculate the score any time and any place.
The published scores
Over the past decades, prior risk models [9, 10, 14-16]performed with good calibration and accuracy in derivation cohorts or western validation cohorts; however, Asian populations, especially Chinese participants, are rarely used for validation[17]. VALID-CRT [11]and ScREEN[8] scores were derived and validated in European multicenter studies, and EARRN [10] does not have a validation population.
The prevalence of ischemic heart failure in CRT candidates was over 50% in most studies [1, 7, 9, 10, 18] conducted in North America and Europe. However, the situation in Asia is significantly different regarding the subtype of CRT candidates[19-21]. Based on the Japan Cardiac Device Treatment Registry (JCDTR) database [21], the proportion of non-ischemic cardiomyopathy was up to 70%. Based on our previous studies, patients with NICM were also common at a rate of above 60% in China.[6, 22]
Previous studies showed that patients with a non-ischemic etiology had a better prognosis than patients with an ischemic etiology. A possible mechanism might be the favorable reverse remodeling and replacement of the myocardial fibrosis scar burden in the LV lead tip area [23, 24]. The different physiological mechanisms could lead to varied pathophysiology, differing clinical status and distinctive responses to device therapy between ischemic and non-ischemic cardiomyopathy. This was a negligible but significant reason for poor discrimination in many predictive models among CRT patients. The performance of risk models based on Western population might be modest in NICM patients with CRT; these scores are readily acceptable to clinicians based on common clinical risk factors, although it is suggested that recalibration based on different etiologies might improve the applicability of the scores for the NICM population.
Variables associated with the risk of all-cause mortality and heart failure exacerbation
The five identified baseline covariates in the Alpha-score are aligned with those identified in previous studies. Several earlier studies reported that inflammation and heart functional biomarkers were associated with heart failure outcomes. It is known that inflammation plays an important role in the pathogenesis and progression of heart failure[9, 25]. High sensitivity CRP (HsCRP), one of the circulating biomarkers of inflammation related to the severity of heart failure, is a sensitive predictor and is widely used to evaluate clinical outcomes[9, 26, 27]. Chi Cai, et al [19] indicated that the elevated baseline HsCRP level was an independent predictor of adverse survival and increased HF hospitalization. In contrast, some studies[28] showed that baseline level of HsCRP was not associated with long-term outcomes, and the sample size of those studies is relatively small. Similarly, in our study, elevated NT-proBNP levels have been shown to be an independent predictor of HF progression and mortality, which is in line with several earlier studies[16, 29, 30]
LBBB was traditionally a strong predictor of electrical LV discordance in numerous large trials[7, 31-34]. We have shown that non-LBBB patients who are CRT recipients tend to have poorer outcomes. Although the mechanism remains uncertain, the larger LA is associated with pulmonary hemodynamic alterations and LA dilatation dysfunction[7, 34-37].
Limitations of our study
This study has some limitations. First, as it is an observational, retrospective study, the baseline characteristics were based on medical records from Fuwai Hospital, and we had no data on serial measurements of biomarkers and echocardiography parameters. Therefore, our findings may not provide model prediction values for the CRT response. Second, the proportion of CRT-D patients in the validation dataset was relatively small, and the patient composition might limit the applicability of the Alpha-score to all CRT recipients. Third, data on final left ventricular lead location, cardiac magnetic resonance imaging for scar tissue and QRS duration after implantation were not collected prospectively. Finally, although the validation dataset was selected randomly in our cohort and determination was good, the potential clinical utility of the Alpha model for risk stratification requires a larger population and further investigation. Despite these limitations, this is the first and largest risk model for NICM patients with CRT in Asia. We believe that the Alpha-score could provide useful prognostic information on NICM among CRT recipients.