- Email: [email protected]
ECG risk stratification in genotyped patients with congenital long QT-syndrome
S222 P4-23
Heart Rhythm, Vol 2, No 5, May Supplement 2005 Table
EFFECT OF PULMONARY VEIN ISOLATION ON ATRIAL ARRHYTHMOGENIC SUBSTRATES IN ATRIAL FIBRILLATION Masahiro Ogawa, MD, Koichiro Kumagai, MD, Hiroo Noguchi, MD, Tomoo Yasuda, MD and Keijiro Saku, MD. Fukuoka University School of Medicine, Fukuoka, Japan. Background: It has been reported that pulmonary veins (PVs) have a major role in initiation or maintainance of atrial fibrillation (AF) and PV isolation is effective therapy to modify atrial arrhythmogenic substrates for AF elimination. However, its mechanism remains unclear. Methods and Results: We performed P-wave signal-averaged electrocardiography with P-wave-triggering method from the 12 standard electrocardiographic lead in 15 patients with paroxysmal or persistent atrial fibrillation. We measured maximum P-wave duration (PWD), minimum PWD, P wave dispersion among 12 leads and before and after PV isolation. Maximum and minimum PWD after PV isolation were significantly shorter than those before PV isolation (163.6 ⫾ 9.3 to 153.1 ⫾ 9.2 ms, P⬍ 0.0001, 141.6⫾ 9.8 to 135.9 ⫾ 9.3 ms, P⬍ 0.0001, respectively). P wave dispersion was significantly smaller than that before PV isolation (25.9 ⫾ 7.0 to 20.1 ⫾ 6.0 ms, P⬍ 0.0001). LP20 significantly increased after PV isolation compared with that before PV isolation (1.8 ⫾ 1.5 to 3.0 ⫾ 2.2 V, P⬍0.0001). Conclusion: Pulmonary vein isolation may contribute improvement of atrial arrhythmogenicity due to shortening and homogeneity of atrial depolarization and reduction of atrial conduction delay.
P4-24 ELECTROCARDIOGRAPHIC DIFFERENCES BETWEEN TIMOTHY SYNDROME AND LQT3 CHILDREN Li Zhang, MD, Katherine W. Timothy, BS, Charles Antzelevitch, PhD, Serge Sicouri, MD and G. Michael Vincent, MD. LDS Hospital, University of Utah, Salt Lake City, UT and Masonic Medical Research Laboratory, Utica, NY. Timothy syndrome (TS), the first identified calcium channel gene-mediated long QT syndrome due to a Cav1.2 gene mutation (G406R), causing multisystem dysfunction besides marked QT prolongation. The clinical outcome is so severe that 71% of TS children developed life-threatening episodes such as torsade de pointes, ventricular fibrillation or asystole, which led to the sudden death rate of 58% at the average age of 2.5 years. The ECG patterns observed in TS are thought to mimic those of LQT3 in that both affect the plateau phase of the action potential. This study sought to elucidate a gene-specific phenotype. Methods: Serial ECGs (n⫽85) of 11 TS (age range 0-5 yrs, 5 female), 12 LQT3 (0.25-5 yrs, 6 F) and 22 normal children (NLs, 0-5 yrs, 11 F) were evaluated for the ST-T patterns, heart rate (HR), PR interval, QRS duration, ST segment, and QT interval. Results: 1. TS children showed three phenotypes in their serial ECGs (Table): baseline ECG (8/11); ventricular bradycardia due to 2:1 AVB (P-rate 133⫾13 bpm, V-rate 66⫾7) with P wave on the markedly prolonged ST segment (P on ST) in 8/11; and ST/T alternans (4/11). 2. The AVB and bradycardia were worsened by beta-blocker medication in 5/11 of TS children. 3. Though longer than in NLs, ST segment and QT interval in LQT3 children were significantly shorter than that of TS. Conclusions: 1. “P on ST” with normal PR interval and QRS duration indicates 2:1 AVB is functional due to marked ST/QT prolongation in Timothy syndrome. 2. Bradycardia is predominant and beta-blocker medication is not suitable in this condition. 3. The unstable ECG patterns, marked ST/QT prolongation and bradycardia imply increased vulnerability to lethal ventricular arrhythmias, asystole and sudden death.
Compared to normal children, *p⬍0.01 and **p⬍0.001 respectively. P4-25 ECG RISK STRATIFICATION IN GENOTYPED PATIENTS WITH CONGENITAL LONG QT-SYNDROME Gerold Mo¨nnig, MD, Lars Eckardt, MD, Horst Wedekind, MD, Peter Milberg, MD, Paulus Kirchhof, MD, Gu¨nter Breithardt, MD, PhD and Eric Schulze-Bahr, MD. University Hospital Mu¨nster, Mu¨nster, Germany. Background: The QT interval in the surface ECG is one of the most often used risk stratifiers in patients with congenital long QT (LQT)-syndrome. Methods: In 200 consecutive genotyped LQT family members, the discriminative power of the QTc interval in all ECG leads between mutation carriers (age 35⫾19 years; LQT1: 35; LQT2: 52; LQT3: 2; LQT5: 13) and noncarriers (n⫽97; age 35⫾18 years)as well as LQT carriers with survived sudden cardiac arrest (high risk, n⫽16) and without (n⫽87) was studied using Receiver Operating Characteristic Analysis (ROC ⫽ area under curve). Additionally, the 10-year risk for events (syncope and sudden cardiac arrest) was calculated for QTc percentile in all individuals. Results: The discrimination was highest in lead II and lead V4/5 for both, identifying carriers and high risk patients (ROC range 0.83-0.87). In these leads, sensitivity and specificity was highest for suggested QTc cut-offs (440 and 500 msec1/2) for identification of LQT mutation carriers and high risk patients (between 68-81% and 79-83%, respectively). The estimated 10-year risk for events in QTc percentiles increased exponentially from 3 to 50% and was 42% for QTc⬎500 msec1/2 (figure). Conclusions: Based on these retrospective data, QTc may be helpful for family analysis and for risk stratification in patients with LQT syndrome. A single measurement should be obtained in lead II if measurable and then in left precordial leads (preferably V4/5) as a second choice with QTc cut-offs of 440 msec1/2 to identify LQT mutation carriers and 500 msec1/2 to identify those with risk for sudden cardiac arrest.
P4-26 QT INTERVAL VARIABILITY AND QT/RR RELATIONSHIP IN PATIENTS WITH POSTINFARCTION IMPAIRMENT OF THE LEFT VENTRICLE FUNCTION AND DIFFERENT TYPES OF VENTRICULAR ARRHYTHMIAS Krzysztof T. Szydlo, MD, PhD, Maria Trusz-Gluza, MD, PhD, Witold Orszulak, MD, PhD, Dagmara Urbanczyk, MD, PhD, Artur Filipecki, MD, PhD, Krystian Wita, MD, PhD and Jolanta Krauze, MD, PhD. Silesian Medical Academy, Katowice, Poland.
Heart Rhythm, Vol 2, No 5, May Supplement 2005 Table
EFFECT OF PULMONARY VEIN ISOLATION ON ATRIAL ARRHYTHMOGENIC SUBSTRATES IN ATRIAL FIBRILLATION Masahiro Ogawa, MD, Koichiro Kumagai, MD, Hiroo Noguchi, MD, Tomoo Yasuda, MD and Keijiro Saku, MD. Fukuoka University School of Medicine, Fukuoka, Japan. Background: It has been reported that pulmonary veins (PVs) have a major role in initiation or maintainance of atrial fibrillation (AF) and PV isolation is effective therapy to modify atrial arrhythmogenic substrates for AF elimination. However, its mechanism remains unclear. Methods and Results: We performed P-wave signal-averaged electrocardiography with P-wave-triggering method from the 12 standard electrocardiographic lead in 15 patients with paroxysmal or persistent atrial fibrillation. We measured maximum P-wave duration (PWD), minimum PWD, P wave dispersion among 12 leads and before and after PV isolation. Maximum and minimum PWD after PV isolation were significantly shorter than those before PV isolation (163.6 ⫾ 9.3 to 153.1 ⫾ 9.2 ms, P⬍ 0.0001, 141.6⫾ 9.8 to 135.9 ⫾ 9.3 ms, P⬍ 0.0001, respectively). P wave dispersion was significantly smaller than that before PV isolation (25.9 ⫾ 7.0 to 20.1 ⫾ 6.0 ms, P⬍ 0.0001). LP20 significantly increased after PV isolation compared with that before PV isolation (1.8 ⫾ 1.5 to 3.0 ⫾ 2.2 V, P⬍0.0001). Conclusion: Pulmonary vein isolation may contribute improvement of atrial arrhythmogenicity due to shortening and homogeneity of atrial depolarization and reduction of atrial conduction delay.
P4-24 ELECTROCARDIOGRAPHIC DIFFERENCES BETWEEN TIMOTHY SYNDROME AND LQT3 CHILDREN Li Zhang, MD, Katherine W. Timothy, BS, Charles Antzelevitch, PhD, Serge Sicouri, MD and G. Michael Vincent, MD. LDS Hospital, University of Utah, Salt Lake City, UT and Masonic Medical Research Laboratory, Utica, NY. Timothy syndrome (TS), the first identified calcium channel gene-mediated long QT syndrome due to a Cav1.2 gene mutation (G406R), causing multisystem dysfunction besides marked QT prolongation. The clinical outcome is so severe that 71% of TS children developed life-threatening episodes such as torsade de pointes, ventricular fibrillation or asystole, which led to the sudden death rate of 58% at the average age of 2.5 years. The ECG patterns observed in TS are thought to mimic those of LQT3 in that both affect the plateau phase of the action potential. This study sought to elucidate a gene-specific phenotype. Methods: Serial ECGs (n⫽85) of 11 TS (age range 0-5 yrs, 5 female), 12 LQT3 (0.25-5 yrs, 6 F) and 22 normal children (NLs, 0-5 yrs, 11 F) were evaluated for the ST-T patterns, heart rate (HR), PR interval, QRS duration, ST segment, and QT interval. Results: 1. TS children showed three phenotypes in their serial ECGs (Table): baseline ECG (8/11); ventricular bradycardia due to 2:1 AVB (P-rate 133⫾13 bpm, V-rate 66⫾7) with P wave on the markedly prolonged ST segment (P on ST) in 8/11; and ST/T alternans (4/11). 2. The AVB and bradycardia were worsened by beta-blocker medication in 5/11 of TS children. 3. Though longer than in NLs, ST segment and QT interval in LQT3 children were significantly shorter than that of TS. Conclusions: 1. “P on ST” with normal PR interval and QRS duration indicates 2:1 AVB is functional due to marked ST/QT prolongation in Timothy syndrome. 2. Bradycardia is predominant and beta-blocker medication is not suitable in this condition. 3. The unstable ECG patterns, marked ST/QT prolongation and bradycardia imply increased vulnerability to lethal ventricular arrhythmias, asystole and sudden death.
Compared to normal children, *p⬍0.01 and **p⬍0.001 respectively. P4-25 ECG RISK STRATIFICATION IN GENOTYPED PATIENTS WITH CONGENITAL LONG QT-SYNDROME Gerold Mo¨nnig, MD, Lars Eckardt, MD, Horst Wedekind, MD, Peter Milberg, MD, Paulus Kirchhof, MD, Gu¨nter Breithardt, MD, PhD and Eric Schulze-Bahr, MD. University Hospital Mu¨nster, Mu¨nster, Germany. Background: The QT interval in the surface ECG is one of the most often used risk stratifiers in patients with congenital long QT (LQT)-syndrome. Methods: In 200 consecutive genotyped LQT family members, the discriminative power of the QTc interval in all ECG leads between mutation carriers (age 35⫾19 years; LQT1: 35; LQT2: 52; LQT3: 2; LQT5: 13) and noncarriers (n⫽97; age 35⫾18 years)as well as LQT carriers with survived sudden cardiac arrest (high risk, n⫽16) and without (n⫽87) was studied using Receiver Operating Characteristic Analysis (ROC ⫽ area under curve). Additionally, the 10-year risk for events (syncope and sudden cardiac arrest) was calculated for QTc percentile in all individuals. Results: The discrimination was highest in lead II and lead V4/5 for both, identifying carriers and high risk patients (ROC range 0.83-0.87). In these leads, sensitivity and specificity was highest for suggested QTc cut-offs (440 and 500 msec1/2) for identification of LQT mutation carriers and high risk patients (between 68-81% and 79-83%, respectively). The estimated 10-year risk for events in QTc percentiles increased exponentially from 3 to 50% and was 42% for QTc⬎500 msec1/2 (figure). Conclusions: Based on these retrospective data, QTc may be helpful for family analysis and for risk stratification in patients with LQT syndrome. A single measurement should be obtained in lead II if measurable and then in left precordial leads (preferably V4/5) as a second choice with QTc cut-offs of 440 msec1/2 to identify LQT mutation carriers and 500 msec1/2 to identify those with risk for sudden cardiac arrest.
P4-26 QT INTERVAL VARIABILITY AND QT/RR RELATIONSHIP IN PATIENTS WITH POSTINFARCTION IMPAIRMENT OF THE LEFT VENTRICLE FUNCTION AND DIFFERENT TYPES OF VENTRICULAR ARRHYTHMIAS Krzysztof T. Szydlo, MD, PhD, Maria Trusz-Gluza, MD, PhD, Witold Orszulak, MD, PhD, Dagmara Urbanczyk, MD, PhD, Artur Filipecki, MD, PhD, Krystian Wita, MD, PhD and Jolanta Krauze, MD, PhD. Silesian Medical Academy, Katowice, Poland.