Long-term survival in refractory angina: predictors and the role of high-sensitive troponin

Background/Introduction Approximately 10% of patients with chronic coronary syndrome (CCS) experience refractory angina (RA), a condition that remains uncontrolled despite optimal medical therapy and myocardial revascularization. The annual mortality rate in these patients has been shown to be around 4%, nearly double of that observed in other CCS studies involving complex multivessel disease amenable to revascularization. However, there is a lack of multicenter studies evaluating long-term mortality in RA and identifying the main risk predictors. High-sensitivity troponin T (hs-cTnT) is a biomarker that has already proven useful in predicting outcomes in CCS and RA patients in shorter follow-up periods. Purpose To evaluate the long-term mortality of patients with RA and identify its main predictors. Methods We prospectively enrolled 104 patients referred to a specialized RA outpatient clinic who provided consent for plasma sample collection at baseline (70.2% male, age 62.8 ± 9.8 years; left ventricular ejection fraction 52.0 ± 13.4%) between October 2008 and September 2013. The primary endpoint was all-cause mortality. Mortality data were obtained through medical records and phone contact until February 2025. Survival curves were constructed using the Kaplan-Meier method, and factors associated with mortality were analyzed using univariate Cox proportional regression followed by multivariate analysis. Results Over a median follow-up of 11 years, 52 deaths occurred, resulting in an estimated cumulative mortality rate of 50%, with an annual mortality rate of 4.5%. Significant predictors of death, identified in both univariate and multivariate analyses, included age, left ventricular ejection fraction, and hs-cTnT levels (Table). Other factors such as diabetes mellitus, more extensive coronary disease, limiting angina, and ischemia were not associated with increased mortality. Notably, among patients with undetectable plasma levels of hs-cTnT, no deaths occurred over more than 8 years of follow-up. In contrast, patients with hs-cTnT levels above the 99th percentile showed a higher mortality rate from the earliest months of observation, with this trend continuing over more than 10 years of follow-up (Figure). Conclusion Patients with refractory angina have a significantly higher mortality rate compared to other CCS patients who are candidates for revascularization. The most important predictors of death include left ventricular dysfunction and hs-cTnT levels. Low levels of this biomarker are strongly associated with a favorable long-term prognosis, emphasizing the potential role of hs-cTnT in patient risk stratification.