External validation and extension of the TIMI risk score for heart failure in diabetes for patients with recent acute coronary syndrome: An analysis of the EXAMINE trial

Abstract

Aims:The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure (HF) in Diabetes (TRS-HF DM ) prognosticates HF hospitalization in people with type 2 diabetes (T2D). This study aimed to externally validate and extend its use for those with recent acute coronary syndrome (ACS). Materials and Methods: The TRS-HF DM was externally validated in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial (n = 5380) and extended with natriuretic biomarkers. Missing data were multiply imputed. Initial TRS-HF DM variables were previous HF (2 points), atrial fibrillation (1 point), coronary artery disease (1 point), estimated glomerular filtration rate <60 ml/ min/1.73 m 2 (1 point), and urine albumin-to-creatinine ratio 30-300 mg/g (1 point) and >300 mg/g (2 points).Results: In total, HF hospitalization occurred in 193 (3.6%) patients. Based on the TRS-HF DM , 25% of patients were classified as intermediate risk (1 point), 30% were classified as high risk (2 points), 19% were classified as very-high risk (3 points) and 26% were classified as severe risk (≥4 points). Before model extension, discrimination (C-index 0.76, 95%ÁCI 0.73-0.80) and calibration (calibration slope 0.82, 95%ÁCI 0.65-1.0; calibration-in-the-large À0.15, 95%ÁCI À0.37-0.64) were moderate-to-good in individuals with T2D and recent ACS. The extension of TRS-HF DM with the addition of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) improved discrimination (C-index 0.82, 95%ÁCI 0.79-0.85) and calibration (calibration slope 0.84, 95%ÁCI 0.66-1.02; calibration-in-the-large À0.12, 95%ÁCI À0.33-0.081) for this higher-risk population. Conclusion:The TRS-HF DM with the extension of NT-ProBNP improves risk stratification and generalizes the use of the risk score for patients with T2D and ACS.Future validation studies in ACS populations may be warranted.

Prognostic models for heart failure in patients with type 2 diabetes: a systematic review and meta-analysis

“…Furthermore, TRS-HFDM was well calibrated in intermediate-risk cohorts but showed miscalibration in very high-risk and severe-risk populations. Of note, the addition of NT-proBNP to TRS-HFDM improved the reclassification of PwT2DM at very high CVD risk (Net Reclassification Index, NRI=24%) 34…”

“…TRS-HFDM is an integer-based model predicting the 4-year risk of HHF and includes five variables 19. TRS-HFDM was developed and validated in RCTs cohorts with established or at high CVD risk, demonstrating good discrimination (pooled C-statistic=0.75, 95% CI (0.69 to 0.81), 95% PI (0.58 to 0.87), low certainty) 19 32–34. Furthermore, TRS-HFDM was well calibrated in intermediate-risk cohorts but showed miscalibration in very high-risk and severe-risk populations.…”

S100A8/A9 as a prognostic biomarker with causal effects for post-acute myocardial infarction heart failure

“…As a result, other causal proteins may have been missed due to the low detection power in the initial screening step. Lastly, the urine albumin-creatinine ratio (UACR) is a prognostic marker of adverse HF outcomes in patients with ACS with type 2 diabetes 33 , 34 . We have not conducted this analysis because of the missing of UACR in present study.…”

Impact of Residential Social Deprivation on Prediction of Heart Failure in Patients With Type 2 Diabetes: External Validation and Recalibration of the WATCH-DM Score Using Real World Data

“…Many risk models do currently exist for predicting risk of HF in patients with T2DM. [7][8][9][10] However, the majority of these models have been derived from studies that may not reflect real-world population (clinical trial data or prospective studies). For example, the WATCH-DM (Weight [BMI], Age, hyperTension, Creatinine, HDL-C, Diabetes control [fasting plasma glucose], QRS Duration, MI, and CABG) risk score and Risk Equations for Complications of Type 2 Diabetes risk scores were developed using the ACCORD trial (Action to Control Cardiovascular Disease in Diabetes), while the Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HF DM ) was created using the SAVOR-TIMI (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes-Thrombolysis in Myocardial Infarction) 53 study.…”