Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients: the Aldo-DHF randomized controlled trial

Objectives To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF). Background O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies. Methods This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e′ 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82–298). Pearson’s correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months. Results The O3I was below (< 8%), within (8–11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = − 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = − 0.12, p = 0.017), triglycerides (r = − 0.117, p = 0.02), non-HDL-C (r = − 0.101, p = 0.044), body-mass-index (r = − 0.149, p = 0.003), waist circumference (r = − 0.121, p = 0.015), waist-to-height ratio (r = − 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity (β = 15.614, p < 0,001), maximal aerobic capacity (β = 0.399, p = 0.005) and LVEF (β = 0.698, p = 0.007) at 12 months. Conclusions Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Graphic abstract Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8–11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art (https://smart.servier.com) licensed by a Creative Commons Attribution 3.0 Unported License.

552 Natural history of bivalvular functional regurgitation

Introduction Bivalvular functional regurgitation (BVFR) defined as concomitant mitral and tricuspid insufficiency has not been described or systematically assessed before. The present study therefore sought to define incidence, impact and natural history of BVFR in heart failure with reduced ejection fraction (HFrEF) to provide the foundation for risk assessment and directions for potential treatment strategies. Methods We enrolled 1021 consecutive patients with HFrEF under guideline-directed medical therapy and performed comprehensive echocardiographic and neurohumoral profiling. Mitral and tricuspid regurgitation was quantified by an integrated approach comprising valve morphology, width of the proximal regurgitant jet, proximal flow convergence, and pulmonary venous flow. All-cause mortality during a five-year follow up served as the primary endpoint. Results Thirty percent of patients suffered from moderate or severe BVFR. Long-term mortality increased with the presence and severity of FR with severe BVFR representing the highest risk-subset (P &lt; 0.001). Severe BVFR patients were more symptomatic and displayed an adverse remodeling and neurohumoral activation pattern (all P &lt; 0.05). Severe BVFR was associated with excess mortality (Figurel 1, Panel A) independently of clinical (adj.HR 1.52, 95%CI 1.39-1.84;P &lt; 0.001) and echocardiographic (adj.HR 1.31, 95%CI 1.11-1.54;P = 0.001) confounders, guideline-directed medical therapy (adj. HR 1.55, 95%CI 1.35-1.79;P &lt; 0.001) and neurohumoral activation (adj.HR 1.31, 95%CI 1.07-1.59;P = 0.009). Moderate BVFR (n = 99) comprised equal baseline characteristics and similar risk as isolated severe FR. (Figure 1, Panel B) (HR 0.95, 95%CI 0.69-1.30;P = 0.73). Conclusion This long-term outcome study shows the multi-faceted nature of FR and defines BVFR as an important clinical entity associated with impaired functional class, adverse cardiac remodeling and excess risk of mortality. Moderate BVFR conveys similar risk as isolated severe FR reflecting the deleterious impact of the global regurgitant load on the failing heart and the need of an integrated understanding for risk-assessment. Abstract 552 Figure 1 (Panel A and B)