1357147 - Deficit in myocardial contractile function and adipose-related systemic and local inflammation

Systemic inflammation and epicardial adipose tissue accumulation are among several biological processes that result in impaired left ventricular (LV) distensibility in patients with heart failure and preserved ejection fraction [1]. Myocardial global longitudinal strain (GLS) detects early deficits in cardiac distensibility with greater sensitivity than LV ejection fraction (EF) [2, 3]. However, whether GLS can guide clinical management based on detection of local tissue derangement as a source of impaired LV distensibility remains uninvestigated. Therefore, this study aims to determine the relationship between GLS and systemic and local epicardial tissue markers of inflammation, epicardial fat fraction, and severity of heart failure based on New York Heart Association (NYHA) classification in patients with normal LV systolic function undergoing open-heart surgery.

Methods: We recruited 20 patients that underwent coronary artery bypass grafting and aortic valve replacement with diastolic dysfunction and normal LVEF ≥ 55%. The decreased myocardial contractile function was defined as median GLS ³ -18%.  Patients underwent fasting blood testing such as C-reactive protein (CRP), white blood cell (WBC) count, and lactate dehydrogenase (LDH)). Cardiac function and thoracic depo-specific FF were calculated from MR and epicardial adipose volume from CT images. At the time of surgery, an epicardial tissue specimens were harvested for lipidome and transcriptome analysis in twenty-two subjects. Logistic regression analyses were performed to evaluate significance level between variables.

Results: Half of our obese obese (mean BMI 31±4 kg/m2) patients exhibited decreased myocardial contractile function with GLS ≥ -18% (range from -10% to -18%) (Figure 1). Moreover, patients with decreased GLS demonstrated significantly increased systemic biomarkers of inflammation such as LDH, CRP, and WBC compared with patients with normal GLS. In addition, patients with decreased GLS demonstrated a significantly increased epicardial fat fraction (mean 82 ± 4 versus 70 ±11, p=0.01) and decreased epicardial tissue phosphatidylethanolamines (PE) [PE 36 (p=0.01) and PE 38 (p=0.01)] respectively than patients with GLS < -18%. Furthermore, an analysis of the epicardial tissue demonstrated an enrichment for genes involved in the complement pathway and innate immunity in the impaired contractile function group (p adjusted value = 0.026 using benjamini correction). However, these genes did not account for multiple comparisons. Clinically, patients with normal GLS endorsed predominantly NYHA Class I (70%) and II (30%) symptoms, while patients with decreased GLS endorsed NYHA Class II, (60%) Class III (20%), and Class IV (10%) symptoms.

Conclusion:

Deficit in myocardial contractile function correlates with increased systemic and epicardial tissue pro-inflammatory markers implicating inflammation that may facilitate phenotyping of patients across the spectrum of functional impairment based on NYHA classification.