Optimal Screening for Predicting and Preventing the Risk of Heart Failure Among Adults With Diabetes Without Atherosclerotic Cardiovascular Disease: A Pooled Cohort Analysis

Abstract

Background: The optimal approach to identify individuals with diabetes who are at a high risk for developing heart failure (HF) to inform implementation of preventive therapies is unknown, especially in those without atherosclerotic cardiovascular disease (ASCVD).

Methods: Adults with diabetes and no HF at baseline from 7 community-based cohorts were included. Participants without ASCVD who were at high risk for developing HF were identified using 1-step screening strategies: risk score (WATCH-DM [Weight, Age, Hypertension, Creatinine, HDL-C, Diabetes Control, QRS Duration, MI, and CABG] ≥12), NT-proBNP (N-terminal pro-B-type natriuretic peptide ≥125 pg/mL), hs-cTn (high-sensitivity cardiac troponin T ≥14 ng/L; hs-cTnI ≥31 ng/L), and echocardiography-based diabetic cardiomyopathy (echo-DbCM; left atrial enlargement, left ventricular hypertrophy, or diastolic dysfunction). High-risk participants were also identified using 2-step screening strategies with a second test to identify residual risk among those deemed low risk by the first test: WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, NT-proBNP/echo-DbCM. Across screening strategies, the proportion of HF events identified, 5-year number needed to treat and number needed to screen to prevent 1 HF event with an SGLT2i (sodium-glucose cotransporter 2 inhibitor) among high-risk participants, and cost of screening were estimated.

Results: The initial study cohort included 6293 participants (48.2% women), of whom 77.7% without prevalent ASCVD were evaluated with different HF screening strategies. At 5-year follow-up, 6.2% of participants without ASCVD developed incident HF. The 5-year number needed to treat to prevent 1 HF event with an SGLT2i among participants without ASCVD was 43 (95% CI, 29-72). In the cohort without ASCVD, high-risk participants identified using 1-step screening strategies had a low 5-year number needed to treat (22 for NT-proBNP to 37 for echo-DbCM). However, a substantial proportion of HF events occurred among participants identified as low risk using 1-step screening approaches (29% for echo-DbCM to 47% for hs-cTn). Two-step screening strategies captured most HF events (75-89%) in the high-risk subgroup with a comparable 5-year number needed to treat as the 1-step screening approaches (30-32). The 5-year number needed to screen to prevent 1 HF event was similar across 2-step screening strategies (45-61). However, the number of tests and associated costs were lowest for WATCH-DM/NT-proBNP ($1061) compared with other 2-step screening strategies (NT-proBNP/hs-cTn: $2894; NT-proBNP/echo-DbCM: $16 358).

Conclusions: Selective NT-proBNP testing based on the WATCH-DM score efficiently identified a high-risk primary prevention population with diabetes expected to derive marked absolute benefits from SGLT2i to prevent HF.

Keywords: biomarkers; heart failure; risk; type 2 diabetes mellitus.

Figure 1.. Sequential testing in the 2-step screening strategies.

The 2-step screening strategies were based on combining two tests as needed. Participants identified as high risk for developing heart failure based on the first test do not undergo further testing. A second test is performed only for participants who do not identify as high risk based on the first test.

Figure 2.. Five-year number needed to treat for prevention of an incident HF event using the treatment effect of an SGLT2i among participants with no history of ASCVD stratified by 1- (Panel A) and 2-step screening strategies (Panel B)

WATCH-DM: high risk = score ≥12, low risk = score <12; NT-proBNP: high risk ≥125 pg/mL, low risk <125 pg/mL; Hs-cTn: high-risk ≥14 ng/L for hs-cTnT or ≥31 ng/L for hs-cTnI, low-risk <14 ng/L for hs-cTnT or <31 ng/L for hs-cTnI; Echo-DbCM: high-risk = left atrial enlargement, left ventricular hypertrophy, or diastolic dysfunction, low-risk = no left atrial enlargement, left ventricular hypertrophy, and diastolic dysfunction; WATCH-DM / NT-proBNP: high risk = score ≥12 or NT-proBNP ≥125 pg/mL, low-risk = score <12 and NT-proBNP <125 pg/mL; NT-proBNP / hs-cTn: high-risk = NT-proBNP ≥125 pg/mL or hs-cTnT ≥14 ng/L or hs-cTnI ≥31 ng/L, low-risk = NT-proBNP <125 pg/mL and hs-cTn <14 ng/L and hs-cTnI <31 ng/L; NT-proBNP / echo-DbCM: high risk = NT-proBNP ≥125 pg/mL or left atrial enlargement, left ventricular hypertrophy, or diastolic dysfunction, low risk = NT-proBNP <125 pg/mL and no left atrial enlargement, left ventricular hypertrophy, and diastolic dysfunction. The black dotted line represents the upper end of the 95th percentile of the NNT⁵ to prevent 1 HF event with an SGLT2i among participants with history of ASCVD (n = 34). The error bars represent the standard error calculated using the 95% confidence interval. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; echo-DbCM, echocardiogram-based diabetic cardiomyopathy; HF, heart failure; hs-cTn, high-sensitivity cardiac troponin; NNT⁵, number needed to treat for 5 years; NT-proBNP, N-terminal pro-B-type natriuretic peptide; SGLT2i, sodium-glucose cotransporter 2 inhibitor.

Figure 3.. Proportion of HF events identified among high- and low-risk participants with no history of ASCVD stratified by 1- and 2-step screening strategies

See Figure 2 legend for description of groups and abbreviations. Data are presented as percentage (95% confidence interval).

Figure 4.. Five-year number needed to screen for prevention of an incident HF event using the treatment effect of an SGLT2i and additional cost of testing stratified by 2-step screening strategies

See Figure 2 legend for description of groups and abbreviations. Test quantity and cost are shown in Tables S2, S8. The error bars represent the standard error calculated using the 95% confidence interval.