Association of biomarkers and risk scores with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus

Background: Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). We sought the extent to which clinical scores (ARIC-HF, WATCH-DM), natriuretic peptides (NTpBNP) and troponin (hs-TnT) were associated with subclinical LV dysfunction (LVD). These associations could inform the ability of these tests to identify which patients should undergo echocardiography.

Methods: Participants with T2DM were prospectively recruited from three community-based populations. ARIC-HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP and hs-TnT were measured using an electro-chemiluminescence assay. All underwent a comprehensive echocardiogram. We calculated the sensitivity and specificity of clinical scores and biomarkers to identify abnormal global longitudinal strain (GLS ≥ -16%)), diastolic function (E/e' ≥ 14 or e' < 8 cm/s), left atrial volume index (LAV > 34 ml/m²) and LV hypertrophy (LV mass index > 88 g/m² (F) > 102 g/m²(M)).

Results: Of 804 participants (median age 69 years [inter-quartile range (IQR) 65-73], 36% female), clinical scores suggested significant HF risk (median ARIC-HF 8% [IQR 4-12]; WATCH-DM 10 points [IQR 8-12]), and the median NTpBNP was 50 pg/mL [IQR 25-101] and hs-TnT 9.6 pg/mL [IQR 6.8-13.6]. Abnormal GLS was present in 126 (17%), elevated E/e' in 114 (15%), impaired e' in 629 (78%), increased LAV in 351 (44%) and LV hypertrophy in 113 (14%). After adjustments for age, body-mass index, and renal function, each standard deviation increase in NTpBNP was associated with a GLS increase of 0.32 (p < 0.001) and hs-TnT increase by 0.26 (p < 0.001). Similar trends were observed with ARIC-HF (standardised β = 0.22, p < 0.001) and WATCH-DM (standardised β = 0.22, p < 0.001) in univariable analyses. However, none of the risk assessment tools provided satisfactory discrimination for abnormal GLS (AUC 63%), diastolic indices (e' AUC 54-61%) or LV mass (AUC 59-67%). At a sensitivity of 90%, there was an unacceptably low (< 50%) specificity.

Conclusion: Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LVD.