The significance of residual inflammation in mortality risk stratification for Takotsubo syndrome: Evaluating CRP measurement alongside the InterTAK Prognostic Score

Abstract

Introduction

Initially described as a benign acute cardiomyopathy, Takotsubo syndrome (TTS) has been linked to elevated mortality rates during both the acute phase and long-term follow-up. Emerging evidence suggests that unresolved myocardial inflammation may contribute to this adverse prognosis.

Objective

This study aimed to evaluate the incremental prognostic utility of C-reactive protein (CRP) in conjunction with the InterTAK Prognosis score for stratifying long-term mortality in TTS.

Method

A retrospective analysis was conducted on data from a multicenter registry encompassing 307 patients diagnosed with Takotsubo syndrome (TTS) between 2008 and 2020. Patients were stratified into quartiles based on the InterTAK Prognosis score. The discriminatory potential of C-reactive protein (CRP) in predicting long-term mortality was assessed. The primary endpoint was defined as all-cause mortality within 1 year.

Results

Stepwise increase of CRP at discharge that corresponds to INTERTAK quartiles was observed: 9.5 mg/L (25th percentile) in the first quartile, 15.8 mg/L (median) in the second quartile, 25.3 mg/L (75th percentile) in the third quartile, and 41.2 mg/L (maximum) in the fourth quartile. Receiver operating characteristic curves (ROC) analysis revealed that CRP value at discharge was predictive of one-year mortality (area under the curve [AUC] = 0.81; 95% confidence interval [CI] = 0.68–0.90) with an optimal threshold set at 33 mg/L (Sensitivity: 65%; Specificity: 87%). When considering the InterTAK score, the incorporation of CRP at discharge with a cut-off of 33 mg/L exhibited a significant enhancement in the prediction of one-year mortality in “intermediate” risk (25% vs. 1%; P = 0.008) or “very high” risk (40% vs. 10%; P = 0.02) patients. Receiver operating characteristic (ROC) curves indicated a tendency for the area under the curve (AUC) to increase when considering the CRP value at discharge (AUC 0.85 vs. 0.79, P = 0.06). While the improvement in AUC did not attain statistical significance, discrimination improved from “acceptable” (AUC [0.7–0.8]) for the original InterTAK Prognosis score to “excellent” (AUC [0.8–0.9]) (Fig. 1).

Conclusion

In Takotsubo syndrome, the persistence of inflammatory burden at hospital discharge emerged as an independent predictor of one-year mortality, augmenting the predictive capacity of the conventional INTERTAK Prognosis score.