| 1. |
- Cortez, Daniel, et al.
(author)
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Quantitative T-wave morphology assessment from surface ECG is linked with cardiac events risk in genotype-positive KCNH2 mutation carriers with normal QTc values
- 2019
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In: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 30:12, s. 2907-2913
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Journal article (peer-reviewed)abstract
- Introduction: Long QT syndrome (LQTS) mutation carriers have elevated the risk of cardiac events even in the absence of QTc prolongation; however, mutation penetrance in patients with normal QTc may be reflected in abnormal T-wave shape, particularly in KCNH2 mutation carriers. We aimed to assess whether the magnitude of a three-dimensional T-wave vector (TwVM) will identify KCNH2-mutation carriers with normal QTc at risk for cardiac events. Methods: Adult LQT2 patients with QTc < 460 ms in men and <470 ms in women (n = 113, age 42 ± 16 years, 43% male) were compared with genotype-negative family members (n = 1007). The TwVM was calculated using T-wave amplitudes in leads V6, II, and V2 as the square root of (TV62 + TII2 + (0.5*TV2)2). Cox regression analysis adjusted for gender and time-dependent beta-blocker use was performed to assess cardiac event (CE) risk, defined as syncope, aborted cardiac arrest, implantable cardioverter-defibrillator therapy, or sudden death. Results: Dichotomized by median of 0.30 mV, lower TwVM was associated with elevated CE risk compared to those with high TwVM (HR = 2.95, 95% CI, 1.25-6.98, P =.014) and also remained significant after including sex and time-dependent beta-blocker usage in the Cox regression analysis (HR = 2.64, 95% CI, 1.64-4.24, P <.001). However, these associations were found only in women but not in men who had low event rates. Conclusion: T-wave morphology quantified as repolarization vector magnitude using T-wave amplitudes retrieved from standard 12-lead electrocardiogram predicts cardiac events risk in LQT2 women and appears useful for risk stratification of KCNH2-mutation carriers without QTc prolongation.
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| 2. |
- Dorsey, E. Ray, et al.
(author)
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Deep Phenotyping of Parkinson's Disease
- 2020
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 10:3, s. 855-873
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Research review (peer-reviewed)abstract
- Phenotype is the set of observable traits of an organism or condition. While advances in genetics, imaging, and molecular biology have improved our understanding of the underlying biology of Parkinson's disease (PD), clinical pheno-typing of PD still relies primarily on history and physical examination. These subjective, episodic, categorical assessments are valuable for diagnosis and care but have left gaps in our understanding of the PD phenotype. Sensors can provide objective, continuous, real-world data about the PD clinical phenotype, increase our knowledge of its pathology, enhance evaluation of therapies, and ultimately, improve patient care. In this paper, we explore the concept of deep phenotyping-the comprehensive assessment of a condition using multiple clinical, biological, genetic, imaging, and sensor-based tools-for PD. We discuss the rationale for, outline current approaches to, identify benefits and limitations of, and consider future directions for deep clinical phenotyping.
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| 3. |
- Platonov, Pyotr G., et al.
(author)
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Atrial Fibrillation in Long QT Syndrome by Genotype
- 2019
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In: Circulation: Arrhythmia and Electrophysiology. - 1941-3084. ; 12:10
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Journal article (peer-reviewed)abstract
- BACKGROUND: Long QT syndrome (LQTS) is caused by the abnormal function of ion channels, which may also affect atrial electrophysiology and be associated with the risk of atrial fibrillation (AF). However, large-scale studies of AF risk among patients with LQTS and its relation to LQTS manifestations are lacking. We aimed to assess the risk of AF and its relationship to the LQTS genotype and the long-term prognosis in patients with LQTS. METHODS: Genotype-positive patients with LQTS (784 LQT1, 746 LQT2, and 233 LQT3) were compared with 2043 genotype-negative family members. Information on the occurrence of AF was based on physician-reported ECG-verified events. Multivariate Cox proportional hazards regression analyses were performed for ages 0 to 60 and after 60 years (reflecting an early and late-onset of AF) to assess the risk of incident AF by genotype and the relationship of AF to the risk of cardiac events defined as syncope, documented torsades de pointes, and aborted cardiac arrest or sudden cardiac death. RESULTS: In patients followed from birth to 60 years of age, patients with LQT3 had an increased risk of AF compared with genotype-negative family members (hazard ratio=6.62; 95% CI, 2.04-21.49; P<0.001), while neither LQT1 nor LQT2 demonstrated increased AF risk. After the age of 60 years, patients with LQT2 had significantly lower risk of AF compared with genotype-negative controls (hazard ratio=0.07; 95% CI, 0.01-0.53, P=0.011). AF was a significant predictor of cardiac events in patients with LQT3 through the age of 60 (hazard ratio=5.38; 95% CI, 1.17-24.82; P=0.031). CONCLUSIONS: Our data demonstrate an increased risk of early age AF in patients with LQT3 and also indicate a protective effect of the LQT2 genotype in it's association with a decreased risk of AF after the age of 60.
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| 4. |
- Platonov, Pyotr G., et al.
(author)
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Risk Stratification of Type 2 Long-QT Syndrome Mutation Carriers with Normal QTc Interval : The Value of Sex, T-Wave Morphology, and Mutation Type
- 2018
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In: Circulation: Arrhythmia and Electrophysiology. - 1941-3149. ; 11:7
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Journal article (peer-reviewed)abstract
- Background: Long-QT (LQT) syndrome mutation carriers have higher risk of cardiac events than unaffected family members even in the absence of QTc prolongation. Changes in T-wave morphology may reflect penetrance of LQT syndrome mutations. We aimed to assess whether T-wave morphology may improve risk stratification of LQT2 mutation carriers with normal QTc interval. Methods: LQT2 mutation carriers with QTc <460 ms in men and <470 ms in women (n=154) were compared with unaffected family members (n=1007). Baseline ECGs recorded at age ≥18 years underwent blinded assessment. Flat, notched, or negative T waves in leads II or V5 were considered abnormal. Cox regression analysis was performed to assess the association between T-wave morphology, the presence of mutations in the pore region of KCNH2, and the risk of cardiac events defined as syncope, aborted cardiac arrest, defibrillator therapy, or sudden cardiac death. Sex-specific associations were estimated using interactions terms. Results: LQT2 female carriers with abnormal T-wave morphology had significantly higher risk of cardiac events compared with LQT2 female carriers with normal T waves (hazard ratio, 3.31; 95% confidence interval, 1.68-6.52; P=0.001), whereas this association was not significant in men. LQT2 men with pore location of mutations have significantly higher risk of cardiac events than those with nonpore mutations (hazard ratio, 6.01; 95% confidence interval, 1.50-24.08; P=0.011), whereas no such association was found in women. Conclusions: The risk of cardiac events in LQT2 carriers with normal QTc is associated with abnormal T-wave morphology in women and pore location of mutation in men. The findings further indicate sex-specific differences in phenotype and genotype relationship in LQT2 patients.
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