Long QT Syndrome

Signal averaged ECGs /Long QTsyndrome I 749 | Prognostic significance of the signal averaged electrocardiogram In patients with chronic coronary artery disease: analysis in the time domain and by spectral temporal mapping T. Hofmann, A. Burmeister1, T. Meinertz. UniversitSts-Krankenhaus Eppendorf, Medizinische Klinik, Abt. Kir Kardiotogie;' AK St Georg, II. Med. Klinik, Hamburg, Germany Late potentials (LP) in the signal averaged electrocardiogram (SA-ECG) have been Identified as prognostic determinants In pts. after recent myocardial infarction. However, the prognostic significance In "tow-risk" pts with chronic coronary artery disease has not been studied systematically. SAECG was recorded in a total of 698 pts. with angiographicaHy proven coronary artery disease and analyzed by time domain analysis (TDA) and by spectral temporal mapping (STM). Cardiac death or cardlopulmonary resuscitation due to ventricular tachycardia/fibrillation (= cardiac event) were used as the primary endpoint for follow-up (mean follow-up time 28 ± 3.7 months). 45 pts. (6 4%) died dunng follow-up, in 29 pts. autopsy data were available. A cardiac event occurred In 46 pts. (sudden death: n = 27, death from congestive heart failure/fatal myocardial Infarction: n = 11, cardlopulmonary resuscitation due to malignant ventricular arrhythmias: n = 8). An abnormal SA-ECG using TDA was found In 43% of pts. wtth a cardiac event, as compared to 21.7% in those without (p < 0.0005). The probability of a cardiac event during follow-up was 4.4% when TDA and STM were both normal, 9.5 and 10.2% when either STM or TDA were abnormal, and 28.5% when both were abnormal. In the following table different variables to predict a cardiac event during follow-up are summarized. (QRS-d duration of the averaged QRS complex, EF = left ventricular ejection fraction). TDA abnormal STM abnormal QRS-d > 120 ms EF<45% SensJtMty Specificity Pos.pred. accuracy Neg. pred. accuracy Odds ratio 43% 22% 37% 33% 79% 92% 88% 91% 13% 16% 18% 19% 95% 94% 95% 95% 2.0« 267 3 13 3.49 A QRS-d > 120 msec and an EF < 45% were the only Independent predictors of a cardiac event (Cox regression analysis). Logistic regression analysis using the latter 2 variables could predict a cardiac event with a sensitivity of 54% and a specificity of 88%. Conclusions: In pts. wfth chronic coronary artery disease, the duration of the averaged QRS complex and left ventricular ejection fraction are independent predictors of a cardiac event [ 7 5 0 | Wavelet analysis of the signal averaged electrocardiogram - prediction of arrhythmic events In post-Infarction patients T. Fetsch, G. Sierra, L Reinhardt, A. Martinez-Rublo, M. Borggrefe, G. Bretthardt University Hospital, Dept of CanBotogy and Inst. Res. Arteriosclerosis, MOnster, Germany The wavelet analysis (WA) represents a new mathematical approach to analyze the frequency content of time sequences encompassing the limitations of the Fast Fourier Transformation. We used the multi-resolution Daubechies wavelet decomposition of the signal averaged ECG (SAECG) Including QFlS, the ST segment and the T wave. The SAECG was decomposed Into 8 frequency bands. The total (tP) and the relative power (rP) of each band was calculated. In addition, the time domain parameters of late potential (LP) analysis were estimated for 25 and 40 Hz filtering. We studied SAECGs from 778 pts. suffering from acute myocardial Infarction (Ml) recorded 18 ± 9 days after Ml. In the follow-up period of 6 to 54 months (median 23 months) 42 serious arrhythmic events (AE) occurred. Results: No linear correlation was found between WA and LP parameters. The mean of the tP and rP In the frequency bands of 15.1 to 31.3 Hz and 3.8 to 7.6 Hz differed significantly In pts. with and without AE (p < 0.02 and p < 0.005). In LP analysis only RMS at both filter frequencies was significantly different in both groups (p = 0.025 and p = 0.033). In a muHfvariate analysis the rP In the bands between 3.8 and 31.3 Hz were most significant (p = 0.019 and p o 0.005) to separate the pts. wfth from those without AE. In LP analysis onfy the RMS at 25 and 40 Hz filtering showed a comparable significance (p = 0.025 and p = 0.033). In a discriminant model the rP in the bands between 3.8 and 31.3 Hz reached a sensitivity and specificity of 54% and 70% detecting pts. with AE In follow-up (predictive accuracy 69%). LP parameters reached 62%/60% and 54%/52% of sensitivity and specificity with a predictive accuracy of 54% and 52%, respectively- Thus, WA of the SAECG leads to results comparable or slightly better than the LP analysis in pts. with AE after myocardial infarction. 125 LONG QT SYNDROME | 751 | A mutatlonal hotspot In HERG associated with a severe form of long QT syndrome and notched T-waves I. Denjoy, E. Dausse 1 , M. Berthet 1 , X. AndrS-Fouet2, M. Bennaceur1, K. Schwartz1, P. Coumel, P. Guicheney1. Cardiology, Lariboisiere Hospital; 1 INSERM UR 153, Pttie-Salpitriere Hospital, Pans;2 Lyon, France Three specific mutated genes have been Identified for long QT syndrome (LOTS). We report on a new mutation in HERG, the morbid gene on chromosome 7, associated with a particular clinical presentation and T-wave pattern. Clinical evaluation including a 12-lead ECG was performed and blood samples were drawn after written consent In 24 members of a French LQTS family. The following parameters, corrected for heart rate by Bazetf s formula, were analyzed in lead II of the first ECG obtained: QTc (ms), QT onset-c (ms), QT peak-c (ms), T duration-c (ms), T ampfitude (mV). Subjects were considered as affected In case of: 1) syncope or torsade de pointes; 2) QTc > 460 ms. Five affected subjectB evidenced tight linkage to HERG and exclusion of all the other published loci. Single strand conformation analysis and direct sequencing were used to determine whether HERG was the mutated gene in this family. Results: Female affected subjects were more severely symptomatic than males with numerous syncopes or torsade de pointes occurring during emotion or while asleep, leading to sudden-death in 2 cases. All affected subjects evidenced a markedly prolonged QTc interval (508 ± 48 ms), with a broad based (329 ± 51 ms) and low amplitude T-wave (0.19 ± 0.07 mV). T-waves were deeply inverted in the right precordial leads and notched in the left precordial leads of all gene carriers, regardless of age, gender and betablocking therapy. A G to A transition at position 1681 resulted in the substitution of threonine for a highly conserved alanlne at codon 561 (Ala561Tnr) in the 5 affected subjects, altering the fifth membrane-spanning domain of the HERG protein. Conclusion: A new mutational hotspot was found in HERG associated with a severe form of LQTS and notched T-wave In all gene carriers. I 752 | A variant of congenital long QT syndrome, the Jervell Lange-Nielsen syndrome, maps not to HERG and SCN5A E. Schutze-Bahr1-2, W. Haverkamp1, M. Hordt1, H. Wiebusch 2 , M. Borggrefe \ G. (...truncated)