| 1. |
- Costa, Jason, et al.
(författare)
-
Combined assessment of sex- and mutation-specific information for risk stratification in type 1 long QT syndrome
- 2012
-
Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 9:6, s. 892-898
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events. OBJECTIVE We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene. METHODS The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1051 individuals with LQT1 (450 men and 601 women) by the location and function of the LQT1-causing mutation (prespecified as mutations in the intracellular domains linking the membrane-spanning segments [ie, S2-S3 and S4-S5 cytoplasmic loops] involved in adrenergic channel regulation vs other mutations). RESULTS Multivariate analysis showed that during childhood (age group: 0-13 years) men had >2-fold (P < .003) increased risk for ACA/SCD than did women, whereas after the onset of adolescence the risk for ACA/SCD was similar between men and women (hazard ratio = 0.89 [P = .64]). The presence of cytoplasmic-loop mutations was associated with a 2.7-fold (P < .001) increased risk for ACA/SCD among women, but it did not affect the risk among men (hazard ratio 1.37; P = .26). Time-dependent syncope was associated with a more pronounced risk-increase among men than among women (hazard ratio 4.73 [P < .001] and 2.43 [P = .02], respectively), whereas a prolonged corrected QT interval (>= 500 ms) was associated with a higher risk among women than among men. CONCLUSION: Our findings suggest that the combined assessment of clinical and mutation location/functional data can be used to identify sex-specific risk factors for life-threatening events for patients with LQT1.
|
|
| 2. |
- Holmqvist, Fredrik, et al.
(författare)
-
Abnormal P-Wave Morphology Is a Predictor of Atrial Fibrillation Development and Cardiac Death in MADIT II Patients
- 2010
-
Ingår i: Annals of Noninvasive Electrocardiology. - 1082-720X. ; 15:1, s. 63-72
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several ECG-based approaches have been shown to add value when risk-stratifying patients with congestive heart failure, but little attention has been paid to the prognostic value of abnormal atrial depolarization in this context. The aim of this study was to noninvasively analyze the atrial depolarization phase to identify markers associated with increased risk of mortality, deterioration of heart failure, and development of atrial fibrillation (AF) in a high-risk population with advanced congestive heart failure and a history of acute myocardial infarction. Methods: Patients included in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) with sinus rhythm at baseline were studied (n = 802). Unfiltered and band-pass filtered signal-averaged P waves were analyzed to determine orthogonal P-wave morphology (prespecified types 1, 2, and 3/atypical), P-wave duration, and RMS20. The association between P-wave parameters and data on the clinical course and cardiac events during a mean follow-up of 20 months was analyzed. Results: P-wave duration was 139 +/- 23 ms and the RMS20 was 1.9 +/- 1.1 mu V. None of these parameters was significantly associated with poor cardiac outcome or AF development. After adjustment for clinical covariates, abnormal P-wave morphology was found to be independently predictive of nonsudden cardiac death (HR 2.66; 95% CI 1.41-5.04, P = 0.0027) and AF development (HR 1.75; 95% CI 1.10-2.79, P = 0.019). Conclusion: Abnormalities in P-wave morphology recorded from orthogonal leads in surface ECG are independently predictive of increased risk of nonsudden cardiac death and AF development in MADIT II patients. Ann Noninvasive Electrocardiol 2010;15(1):63-72
|
|
| 3. |
|
|
| 4. |
- Migdalovich, Dimitry, et al.
(författare)
-
Mutation and gender-specific risk in type 2 long QT syndrome: Implications for risk stratification for life-threatening cardiac events in patients with long QT syndrome
- 2011
-
Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 8:10, s. 1537-1543
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Men and women with type 2 long QT syndrome (LQT2) exhibit time-dependent differences in the risk for cardiac events. We hypothesized that data regarding the location of the disease-causing mutation in the KCNH2 channel may affect gender-specific risk in LQT2. OBJECTIVE This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information. METHODS The risk for life-threatening cardiac events from birth through age 40 years (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) was assessed among 1,166 LQT2 male (n = 490) and female (n = 676) patients by the location of the LQTS-causing mutation in the KCNH2 channel (prespecified in the primary analysis as pore-loop vs. non-pore-loop). RESULTS During follow-up, the cumulative probability of life-threatening cardiac events years was significantly higher among LQT2 women (26%) as compared with men (14%; P <.001). Multivariate analysis showed that the risk for life-threatening cardiac events was not significantly different between women with and without pore-loop mutations (hazard ratio 1.20; P = .33). In contrast, men with pore-loop mutations displayed a significant > 2-fold higher risk of a first ACA or SCD as compared with those with non-pore-loop mutations (hazard ratio 2.18; P = .01). Consistently, women experienced a high rate of life-threatening events regardless of mutation location (pore-loop: 35%, nonpore-loop: 23%), whereas in men the rate of ACA or SCD was high among those with pore-loop mutations (28%) and relatively low among those with non-pore-loop mutations (8%). CONCLUSION Combined assessment of clinical and mutation-specific data can be used for improved risk stratification for life-threatening cardiac events in LQT2.
|
|
