Screening for stage B heart failure in Type 2 diabetes: natriuretic peptide screening alone misses echocardiographic abnormalities

Abstract Background Heart failure (HF) often manifests as the first cardiac event in individuals with type 2 diabetes mellitus (T2DM). International guidelines recommend natriuretic peptide (NP) screening for stage B/ pre-HF in asymptomatic individuals with T2DM, with echocardiography reserved for those with elevated NPs ("NP-gated" echo approach). Whether this strategy misses individuals with echocardiographic abnormalities despite normal NPs is not fully understood. Purpose To assess the proportion of individuals with T2DM who will be classified as Stage B HF based on biomarker and echocardiography, using independent and combined screening approaches. Methods We utilised the Performance of NT-proBNP In risk Stratification for Cardiovascular Events and mortality in patients with diabetes [PISCES] study (n=765, mean age 62±9 years, 62% men), which enrolled patients with T2DM with no HF. All patients underwent laboratory-based N-terminal pro-B-type NP (NT-proBNP) testing and a point-of-care artificial intelligence echocardiography (Us2.ai). Abnormal echocardiography was defined as left ventricular ejection fraction <50%, left ventricular mass index ≥115(male) or ≥95g/m2(female), left atrial volume index>34 in sinus rhythm or >40mL/m2 in atrial fibrillation, relative wall thickness (RWT) >0.42, E/e' >9, peak tricuspid regurgitation velocity >2.8m/s, pulmonary arterial systolic pressure >35mmHg. Patients with T2DM were classified into either (1) Stage B(biomarker) with elevated NT-proBNP (≥125pg/mL) and normal echocardiography, or (2) Stage B(echo) with abnormal echocardiography and normal NT-proBNP, or (3) Stage B(biomarker+echo) with elevated NT-proBNP and abnormal echocardiography or (4) no abnormalities. Results Among asymptomatic patients with T2DM, the highest proportion of individuals were in Stage B(echo) (43%), followed by those with no abnormalities (37%), Stage B(biomarker+echo) (15%) and Stage B(biomarker) (5%). Patients with Stage B(echo) (vs. no abnormalities) were older (62.5 vs 59.8 years), had a higher prevalence of hypertension (78.4 vs. 72.4%), higher systolic blood pressure (135 vs. 128 mmHg), higher RWT and higher E/e’ (p<0.001 for all). Individuals in Stage B(biomarker+echo) (versus no abnormalities) were older, had a longer duration of T2DM, higher prevalence of hypertension, atrial fibrillation, prior CVD, highest NT-proBNP levels, lowest eGFR levels, and more echocardiography abnormalities (higher RWT and E/e’). Patients identified as Stage B(biomarker) (versus no abnormalities) had a longer duration of T2DM, higher NT-proBNP levels, higher prevalence of comorbidities and comparable echocardiographic measures. Conclusion Among asymptomatic patients with T2DM, a significant proportion have subclinical cardiac abnormalities despite a lack of diagnostic NP elevation. Instead of NP-gated echocardiography, an integrated approach using both NT-proBNP and AI echocardiography may improve the early detection of Stage B HF.