👤 Emeline M Van Craenenbroeck

We investigated the relationship between heart failure etiology and lipoprotein subfractions, and to explore their associations with left ventricular dimension and function in heart failure with reduced ejection fraction (HFrEF) patients. Cross-sectional investigation of serum lipoprotein subfractions from 205 HFrEF patients in the SMARTEX heart failure study. Serum levels of triglycerides, cholesterol, free cholesterol, phospholipids, lipoproteins (Apolipoproteins; A-1, A-2, and B), very-low-density (VLDL), intermediate-density (IDL), low-density (LDL), and high-density lipoprotein (HDL) were determined using Stable HFrEF patients [left ventricular ejection fraction (LVEF) ≤ 35%, NYHA class II-III], with ischemic (ICM, n = 119) or non-ischemic (NICM, n = 86) cardiomyopathy were studied. NICM patients had higher levels of 48 lipoproteins compared to ICM patients, including 29 LDL, 13 VLDL, and 6 HDL subfractions [p <0.05]. NICM patients had 22% higher cholesterol and 27% higher remnant cholesterol levels, with 24% more atherogenic ApoB containing subfractions (VLDL, IDL, LDL) (p <0.05). Heart failure etiology and statin treatment explained 23-24% of the variability in cholesterol, free cholesterol, and ApoB (p <0.001). Triglyceride content in some VLDL and LDL subfractions was weakly associated with left ventricular end-diastolic volume, end-diastolic diameter, ejection fraction, and S'. NICM patients had the highest atherosclerotic lipoprotein burden, attributed to elevated ApoB particles and partly due to less statin treatment. The triglyceride content of some VLDL and LDL subfractions was weakly associated with left ventricular structure and function. However, further research is needed to determine their prognostic significance before implementation into strategies for prevention and treatment. Show less

The importance of genetic testing for cardiomyopathies has increased in the last decade. However, in heart transplant patients with former cardiomyopathy, genetic testing in retrospect is not routinely performed. We hypothesize that the yield of genetic testing in this population is considerable, and will have a major impact for both patients and relatives. Patients that underwent heart transplantation (HTx) between 1995 and 2020 and were still in follow-up, were offered genetic testing if the primary etiology was non-ischemic cardiomyopathy. Next generation sequencing (NGS) of known cardiomyopathy genes was performed and variants were classified as variant of unknown significance (class 3), likely pathogenic (class 4) or pathogenic (class 5) variant. Of the 99 HTx patients in active follow-up, only 6 patients had a genetic diagnosis at the time of HTx. In this study, 31 selected patients with prior non-ischemic cardiomyopathy underwent genetic testing post HTx. 23/31 patients (74.2%) carried a variant that was classified as class 3 or higher. In 12/31 patients a class 4/5 variant (38.7%) was identified, and in 11/31 patients (35.5%) a class 3 variant. Class 5 Variants in TTN were the most prevalent (7/31), followed by class 5 variants in MYBPC3 (2/31). A positive family history was present in 21/31 (67.7%) and a second precipitating factor (e.g., alcohol abuse, pregnancy) was present in 17/31 patients (54.8%). Diagnostic yield of genetic testing was similar between patients with or without familial history and/or second hit. Through cascade screening 48 family members were screened for presence of a class 4/5 variant, of whom 19 (39.6%) were genotype positive, of whom 10 (52.6%) showed a cardiac phenotype. Appropriate follow-up was offered. Genetic testing for cardiomyopathy genes established a molecular diagnosis in 38.7% of patients post HTx. These results highlight the importance of genetic testing in this population as it is still often overlooked in patients that already underwent HTx in the past. Genetic testing is highly recommended, independent of family history or second precipitating factors, as it might identify relatives at risk. Show less