Relationship of NT-proBNP with echocardiographic abnormalities and functional status in diabetic cardiomyopathy

In a prespecified analysis of ARISE-HF among patients with diabetic cardiomyopathy but no symptomatic HF, elevated NT-proBNP levels were associated with worse health status and reduced functional capacity but not with structural cardiac abnormalities.

This summary is based on the publication of Gouda P, Liu Y, Butler J, et al. - Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical siabetic cardiomyopathy. Cardiovasc Diabetol. 2024 Aug 2;23(1):281. doi: 10.1186/s12933-024-02378-w

Introduction and methods

Background

Patients with diabetes are at risk of developing cardiomyopathy, even in the absence of traditional risk factors for HF such as hypertension, coronary artery disease, and valvular heart disease [1]. Early recognition of patients with diabetic cardiomyopathy but no overt HF symptoms is important to slow down progression to symptomatic HF. However, the relationship between natriuretic peptides, structural cardiac abnormalities, and functional capacity in this population has not yet been established.

Aim of the study

The study aim was to evaluate the associations between NT-proBNP levels, echocardiographic findings, health status and activity, and functional capacity in patients with diabetic cardiomyopathy.

Methods

This was a prespecified subgroup analysis of the ARISE-HF (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure) trial, an ongoing, placebo-controlled, double-blind, phase 3 RCT in which the efficacy of AT-001, a novel aldose reductase inhibitor, was evaluated in 691 patients with well-controlled T2D and evidence for ≥1 of the following criteria: (1) abnormal cardiac structure or function, (2) elevated cardiac biomarkers (NT-proBNP ≥50 ng/L or hs-cTnT ≥6 ng/L), and (3) reduced exercise capacity (defined as a peak oxygen uptake (VO₂) ≤75% of predicted normal value) [2]. Patients had cardiac dysfunction but no overt HF symptoms (stage B HF). Key exclusion criteria included symptomatic HF, LVEF <40%, or use of loop diuretics. The study drug did not improve exercise capacity compared with placebo [3].

In the current analysis, baseline data of echocardiography, laboratory investigations, and health and functional assessments from 685 study participants (99.1%) with a baseline NT-proBNP measurement were included. Median baseline NT-proBNP level was 71 ng/L (Q1–Q3: 33–135).

Main results

• No significant associations were observed between baseline NT-proBNP levels (either assessed as quartiles or continuous variables) and echocardiographic parameters including global longitudinal strain, LVEF, LV mass index, left atrial volume index, ratio of early mitral inflow velocity to septal/early diastolic mitral annular velocity (E/e’), or right ventricular systolic pressure.
• However, after adjustment for known confounders, such as age, sex, and blood pressure, NT-proBNP levels were mildly correlated with LVEF (rho=−0.11; P=0.02).
• NT-proBNP levels (assessed as continuous variables) were correlated with the KCCQ – Overall Summary Score (rho=–0.10; P=0.007), KCCQ – Clinical Summary Score (rho=–0.14; P<0.001), KCCQ – Physical Limitation Score (rho=–0.13; P<0.001) and Physical Activity Scale in the Elderly (PASE) score (rho=–0.12; P=0.004).
• However, after adjustment for known confounders, the correlations for the KCCQ – Overall Summary Score and PASE score were no longer significant.
• With regard to cardiopulmonary exercise testing, NT-proBNP levels (assessed as continuous variables) were correlated with the exercise duration (rho=–0.28; P<0.001), peak VO₂ (rho=–0.26; P<0.001), and ratio of minute ventilation/carbon dioxide production (rho=0.12; P=0.002).

Conclusion

In this prespecified subgroup analysis of the ARISE-HF trial among patients with diabetic cardiomyopathy and stage B HF, elevated NT-proBNP levels were associated with worse health status and reduced functional capacity but not with structural cardiac abnormalities on echocardiography. According to the authors, their “findings suggest that, regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals.” Still, “the temporal relationship between NT-proBNP, cardiac structural abnormalities, and functional capacity remains unclear.”

Find this article online at Cardiovasc Diabetol.

References

1. Stanton AM, Vaduganathan M, Chang L-S, Turchin A, Januzzi JL, Aroda VR. Asymptomatic diabetic cardiomyopathy: an underrecognized entity in type 2 diabetes. Curr Diab Rep. 2021;21:1–11.
2. Januzzi JL Jr, Butler J, Del Prato S, Ezekowitz JA, Ibrahim NE, Lam CS, et al. Rationale and design of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart failure trial (ARISE-HF) in patients with high-risk diabetic cardiomyopathy. Am Heart J. 2023;256:25–36.
3. Januzzi James L, Butler J, Del Prato S, Ezekowitz Justin A, Ibrahim Nasrien E, Lam Carolyn SP, et al. Randomized trial of a selective aldose reductase inhibitor in patients with diabetic cardiomyopathy. J Am Coll Cardiol. 2024;84(2):137–48. https://doi.org/10.1016/j.jacc.2024.03.380.