Effect of heart rate and autonomic tone on the QT interval.

Susmano, Armando

doi:10.1161/circ.66.2.7094254

Cited by 4 publications

(4 citation statements)

References 6 publications

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“…We assessed correlations of crude values of sex-pooled and sex-specific age, heart rate (RR interval), and QT intervals. Using stepwise linear regression model, we adjusted the QT intervals for age, sex, and RR-interval (16,17) and determined the beta coefficient, two-tailed P -value, and partial R 2 of the covariates in the model. In addition, we tested additional possible covariates, i.e.…”

Section: Methodsmentioning

confidence: 99%

High prevalence of four long QT syndrome founder mutations in the Finnish population

Marjamaa¹,

Salomaa²,

Newton‐Cheh³

et al. 2009

Annals of Medicine

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Aims Long QT syndrome (LQTS) is an inherited arrhythmia disorder with an estimated prevalence of 0.01%–0.05%. In Finland, four founder mutations constitute up to 70% of the known genetic spectrum of LQTS. In the present survey, we sought to estimate the actual prevalence of the founder mutations and to determine their effect sizes in the general Finnish population. Methods and results We genotyped 6334 subjects aged≥30 years from a population cohort (Health 2000 study) for the four Finnish founder mutations using Sequenom MALDI-TOF mass spectrometry. The electrocardiogram (ECG) parameters were measured from digital 12-lead ECGs, and QT intervals were adjusted for age, sex, and heart rate using linear regression. A total of 27 individuals carried one of the founder mutations resulting in their collective prevalence estimate of 0.4% (95% CI 0.3%–0.6%). The KCNQ1 G589D mutation (n=8) was associated with a 50 ms (SE 7.0) prolongation of the adjusted QT interval (P=9.0×10-13). The KCNH2 R176W variant (n=16) resulted in a 22 ms (SE 4.7) longer adjusted QT interval (P=2.1×10-6). Conclusion In Finland 1 individual out of 250 carries a LQTS founder mutation, which is the highest documented prevalence of LQTS mutations that lead to a marked QT prolongation.

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Section: Methodsmentioning

confidence: 99%

High prevalence of four long QT syndrome founder mutations in the Finnish population

Marjamaa¹,

Salomaa²,

Newton‐Cheh³

et al. 2009

Annals of Medicine

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“…Histograms of all the variables were reviewed for normality. Using a stepwise linear regression model, we adjusted the mean QT Nc intervals for age and gender [23, 24] and determined the beta coefficient, 2‐tailed P ‐value and partial R 2 for each covariate in the model. In addition, we tested additional covariates i.e.…”

Section: Methodsmentioning

confidence: 99%

Common candidate gene variants are associated with QT interval duration in the general population

Marjamaa

Newton‐Cheh

Porthan

et al. 2009

Journal of Internal Medicine

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Objectives QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. Because 30-40% of the QT-interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population-based sample. Methods We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5,043 Finnish individuals, using Sequenom MALDI-TOF mass spectrometry. ECG parameters were measured from digital 12-lead ECGs and QT intervals were adjusted for age, sex and heart rate with a nomogram (Nc) –method derived from the present study population. Results The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QTNc interval (p=3.6×10−11) in sex-pooled analysis. In agreement with previous studies, we replicated the association with QTNc interval with minor alleles of KCNH2 intronic SNP rs3807375 (1.6 ms (SE 0.4) or 0.08 SD, p=4.7×10−5), KCNH2 K897T (−2.6 ms (SE 0.5) or −0.14 SD, p=2.1×10−7) and NOSA1P variants including rs2880058 (4.0 ms (SE 0.4) or 0.22 SD, p=3.2×10−24) under additive models. Conclusions We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age-, sex- and heart rate-adjusted QT interval, and could thus modulate repolarization-related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.

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“…Previous work has shown that ventricular repolarization is strongly modulated by heart rate but also independently by autonomic nervous activity 20 and QT dynamics is thought to offer a more integrative measure of autonomic balance under stress than resting QT interval alone. 21 This is supported by multiple lines of evidence showing that abnormal QT dynamics is an independent predictor of cardiovascular mortality in cardiac patients.…”

Section: Discussionmentioning

confidence: 99%

Genetic Basis and Prognostic Value of Exercise QT Dynamics

Duijvenboden

Ramírez

Young

et al. 2020

Circ: Genomic and Precision Medicine

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Background: Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated. Methods: QT dynamics during exercise and recovery were derived in 56 643 individuals from UK Biobank without a history of cardiovascular events. Genome-wide association studies were conducted to identify genetic variants and bioinformatics analyses were performed to prioritize candidate genes. The prognostic value of QT dynamics was evaluated for cardiovascular events (death or hospitalization) and all-cause mortality. Results: Heritability of QT dynamics during exercise and recovery were 10.7% and 5.4%, respectively. Genome-wide association studies identified 20 loci, of which 4 loci included genes implicated in mendelian long-QT syndrome. Five loci did not overlap with previously reported resting QT interval loci; candidate genes included KCNQ4 and KIAA1755 . Genetic risk scores were not associated with cardiovascular events in 357 882 unrelated individuals from UK Biobank. We also did not observe associations of QT dynamics during exercise and recovery with cardiovascular events. Increased QT dynamics during recovery was significantly associated with all-cause mortality in the univariate Cox regression analysis (hazard ratio, 1.09 [95% CI, 1.05–1.13], P =2.28×10 -5 ), but the association was not significant after adjusting for clinical risk factors. Conclusions: QT interval dynamics during exercise and recovery are heritable markers but do not carry independent prognostic information for clinical outcomes in the UK Biobank, a population-based cohort. Their prognostic importance may relate to cardiovascular disease cohorts where structural heart disease or ischemia may influence repolarization dynamics. The strong overlap between QT dynamics and resting QT interval loci suggests common biological pathways; however, nonoverlapping loci suggests alternative mechanisms may exist that underlie QT interval dynamics.

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Effect of heart rate and autonomic tone on the QT interval.

Cited by 4 publications

References 6 publications

High prevalence of four long QT syndrome founder mutations in the Finnish population

High prevalence of four long QT syndrome founder mutations in the Finnish population

Common candidate gene variants are associated with QT interval duration in the general population

Genetic Basis and Prognostic Value of Exercise QT Dynamics

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