PubMed · 11552238
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H Leinonen. 1998. [The heart's function as a pump].. https://pubmed.ncbi.nlm.nih.gov/11552238/
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BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a heritable trait with marked variability in expression and outcomes. Our aims were to discover new genetic loci associated with HCM and to test the effect of a new polygenic risk score (PRS) on incidence, phenotype and outcomes stratified by genotype status. METHODS: A discovery genome-wide association study (GWAS) was performed on 2284 HCM cases and 4525 controls. Two fixed-effects meta-analyses combined our discovery GWAS with single-trait and multi-trait results from a published study. Discovered loci underwent comprehensive bioinformatic analysis including functional and druggability annotations. A PRS using loci from the two meta-analyses was evaluated for association with HCM diagnosis in 411 213 individuals from UK Biobank (UKBB); imaging phenotypes in individuals without HCM; a composite endpoint (including all-cause mortality and transplantation); and sudden cardiac death (SCD) in 1756 HCM cases. PRS analyses were stratified by genotype status. RESULTS: Three loci were found in the discovery GWAS (BAG3, FHOD3 and novel locus PPP1R3A). In the meta-analyses, 70 unique loci were identified, four novel (MYPN, YWHAE, NOS1AP and OBSCN). Bioinformatic analyses identified NOS1AP as a candidate HCM gene. A new PRS was significantly associated with HCM diagnosis (HR=3.19, 95% CI 2.46 to 4.14 for top 5% vs lower 95%; HR=1.88, 95% CI 1.72 to 2.06 per SD increase). Significant associations were found between PRS and greater left ventricular (LV) wall thickness and higher LV ejection fraction in UKBB participants without HCM. Genotype-negative HCM cases in the top 20% of the PRS distribution had an increased risk of SCD (HR=2.72, 95% CI 1.03 to 7.17). CONCLUSIONS: We report novel HCM loci. A new PRS predicted the risk of HCM development and associated imaging characteristics in the UKBB and outcomes in an HCM cohort.
Septic Cardiomyopathy (SCM) is a syndrome of acute cardiac dysfunction in septic patients, unrelated to cardiac ischemia. Multiomics studies including transcriptomics and proteomics have provided new insights into the mechanisms of SCM. In here, a rat model of SCM was established by intraperitoneal injection of lipopolysaccharide (LPS). Biomarkers of SCM were characterized via a multi-omics analysis. The differentially expressed (DE) mRNAs predominantly appeared in pathways linked to the immune response, inflammatory response, and the complement and coagulation cascades, while DE proteins were mainly enriched in pathways associated with the complement and coagulation cascades. On this basis, the integrated analysis was performed between transcriptome and proteome. The potential biomarkers were further verified by RT-qPCR and WB. The current proteotranscriptomic research has furnished a valuable dataset and fresh perspectives that will enhance our comprehension of the development of SCM. This, in turn, is expected to expedite the formulation of novel approaches for the prevention and management of SCM in patients.
In patients with heart failure (HF), low peak oxygen consumption (VO(2)) and prolonged QT interval or enhanced QT variability are associated with poor prognosis. Whether HF severity or left ventricular (LV) loading conditions can influence repolarization length is unknown. Survival, QTc interval, peak VO(2), clinical, laboratory, echocardiographic, and invasive hemodynamic data were analyzed in 154 transplant candidates; mortality was examined after a mean follow-up of 4.3 +/- 1.8 years. The relation between the QTc interval and other variables was examined using multivariate analysis and multiple correlation coefficients. Patients were stratified by peak VO(2) to study its relation with peak VO(2), mortality, loading conditions, and QTc intervals. Mean ejection fraction was 10 +/- 9%; mean cardiac index was 2.06 +/- 0.7 L/min/m(2). Seventy-one patients (47%) were dead at the end of study. Mortality and nonfatal ventricular arrythmias were higher (p <0.01) in patients with lower peak VO(2) and longer QTc intervals (p <0.001). An inverse correlation was found between QTc interval length and peak VO(2) (r = -0.790, p <0.0001). No correlation was found between QTc interval and LV loading conditions or the other analyzed variables. Thus, repolarization length measured by the QTc interval is inversely correlated with HF severity measured by peak VO(2) and is independent of LV loading conditions in patients with severe HF.