Left atrial remodeling and novel biomarkers in obese patients with heart failure with preserved ejection fraction compared to type-2-diabetics and obese controls: a cardiac magnetic resonance study

Abstract Background Elevated filling pressures and subsequent left atrial (LA) dilation are common findings in heart failure with preserved ejection fraction (HFpEF), reflecting a chronic state of the disease and holding prognostic value. HFpEF is thought to develop through a long-term pro-inflammatory state triggered by comorbidities, such as obesity and type 2 diabetes mellitus (T2DM). Emerging biomarkers have shown associations with structural remodeling, but also increased myocardial stiffness. Purpose To elucidate the relationship between LA volume and function, and prognostic biomarkers (NT-proBNP, BNP-32, IL1R1, Galectin-3, and Pentraxin-3) in an obese cohort with T2DM or HFpEF and T2DM, versus healthy obese controls. Methods We conducted a prospective cohort study of 35 obese participants, divided into three groups: T2DM (n=16), HFpEF with T2DM (NYHA II-III, n=13), and healthy obese controls (n=6). Each subject underwent comprehensive CMR at a 3T scanner to assess LA strain and volume. Atrial strain was assessed on 2- and 4-chamber view cine images by experienced CMR investigators using dedicated software. Routine labs and serum levels of biomarkers were measured. If labs or images were repeated, the average was calculated. Statistical significance was determined through ANOVA and student’s t-test for group comparisons and Pearson correlation for associations between LA parameters and biomarker levels. Results Cohorts were evenly matched in terms of demographics, vital signs, and ventricular volumes and functions, as depicted in Table 1. Only one patient in the HFpEF subgroup reported history of atrial fibrillation. Both minimum and maximum LA volumes were significantly elevated in the HFpEF group compared to the T2DM and control groups (p < 0.018). LA strain (conduit, reservoir, and booster) was notably compromised in the HFpEF cohort, contrasting with the obese T2DM group where LA strain values did not differ significantly from those observed in obese controls (Figure 1). Biomarker analysis revealed a marked increase of NT-proBNP, BNP-32, Galectin-3, and Pentraxin-3 in the HFpEF cohort. In the HFpEF cohort, IL1R1 was the only biomarker that was strongly associated with higher left ventricular enddiastolic (r=0.69, p=0.003) and endsystolic volumes (r=0.75, p=0.009). Moreover, IL1R1 was the only biomarker associated with atrial functional changes (booster strain, r=-0.57, p=0.043) in the HFpEF patients. Our findings indicate that ILR1 plays a crucial role in the cardiometabolic (obesity-T2DM) HFpEF phenotype, with its activation leading to advanced cardiac remodeling. Conclusion Obese HFpEF patients with T2DM showed severely altered left atrial morphology and function compared to those that are only obese or obese with T2DM. Moreover, our findings revealed that atrial remodeling in this population is driven by pro-fibrotic inflammatory pathways.Characteristics of the study cohortLeft atrial strain analysis