A novel electrocardiographic index for the diagnosis of diastolic dysfunction

Contains fulltext : 128595.pdf (publisher's version ) (Open Access)BACKGROUND: Although the assessment of diastolic dysfunction (DD) is an integral part of routine cardiologic examinations, little is known about associated electrocardiographic (ECG) changes. Our aim was to investigate a potential role of ECG indices for the recognition of patients with DD. METHODS AND RESULTS: ECG parameters correlating with echocardiographic findings of DD were retrospectively assessed in a derivation group of 172 individuals (83 controls with normal diastolic function, 89 patients with DD) and their diagnostic performance was tested in a validation group of 50 controls and 50 patients. The patient group with a DD Grade 1 and 2 showed longer QTc (422+/-24ms and 434+/-32ms vs. 409+/-25ms, p<0.0005) and shorter Tend-P and Tend-Q intervals, reflecting the electrical and mechanical diastole (240+/-78ms and 276+/-108ms vs. 373+/-110ms, p<0.0001; 409+/-85ms and 447+/-115ms vs. 526+/-119ms, p<0.0001). The PQ-interval was significantly longer in the patient group (169+/-28ms and 171+/-38ms vs. 153+/-22ms, p<0.005). After adjusting for possible confounders, a novel index (Tend-P/[PQxAge]) showed a high performance for the recognition of DD, stayed robust in the validation group (sensitivity 82%, specificity 93%, positive predictive value 93%, negative predictive value 82%, accuracy 88%) and proved a substantial added value when combined with the indexed left atrial volume (LAESVI, sensitivity 90%, specificity 92%, positive predictive value 95%, negative predictive value 86%, accuracy 91%). CONCLUSIONS: A novel electrocardiographic index Tend-P/(PQxAge) demonstrates a high diagnostic accuracy for the diagnosis of DD and yields a substantial added value when combined with the LAESVI

Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval

Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10-8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.The Pharmacogenomics Journal advance online publication, 5 March 2013; doi:10.1038/tpj.2013.4