BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by risk of polymorphic ventricular tachycardia (pVT) and sudden death during stress. Experimental CPVT models show that delayed afterdepolarization (DAD)-induced triggered activity is the initiating mechanism of pVT, whereas an increase in transmural dispersion of repolarization (TDR) controls degeneration of pVT to ventricular fibrillation. U-wave and T-wave peak to T-wave end interval (TPE) are regarded as electrocardiographic counterparts of DAD and TDR, respectively. OBJECTIVE: We tested hypotheses that patients with CPVT might show abnormal U-waves and TPE intervals and that beta-blockers could suppress appearance of these repolarization abnormalities. METHODS: We reviewed Holter recordings from 19 CPVT patients with a RyR2 mutation (P2328S or V4653F) and from 19 healthy unaffected subjects to record U-waves and TPE intervals as well as to measure beta-blockers' effects on ventricular repolarization by use of an automated computerized program. RESULTS: The maximal U-wave to T-wave amplitude ratio was 0.8 +/- 0.6 in CPVT patients and 0.4 +/- 0.3 in unaffected subjects (P = .009). Patients with most ventricular extrasystoles had a higher U-wave to T-wave amplitude ratio than those with fewest extrasystoles. Treatment with beta-blockers decreased U-wave amplitude at high heart rates. CPVT patients had longer TPE intervals than unaffected subjects at high heart rates, and beta-blocker treatment shortened their TPE intervals. CONCLUSION: Present data support the hypothesis that U-waves associate with the DAD-triggered extrasystolic activity in CPVT patients. Patients with a RyR2 mutation show increased TPE at high heart rates. Beta-blocker treatment suppresses observed repolarization abnormalities in CPVT patients.
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by risk of polymorphic ventricular tachycardia (pVT) and sudden death during stress. Experimental CPVT models show that delayed afterdepolarization (DAD)-induced triggered activity is the initiating mechanism of pVT, whereas an increase in transmural dispersion of repolarization (TDR) controls degeneration of pVT to ventricular fibrillation. U-wave and T-wave peak to T-wave end interval (TPE) are regarded as electrocardiographic counterparts of DAD and TDR, respectively. OBJECTIVE: We tested hypotheses that patients with CPVT might show abnormal U-waves and TPE intervals and that beta-blockers could suppress appearance of these repolarization abnormalities. METHODS: We reviewed Holter recordings from 19 CPVT patients with a RyR2 mutation (P2328S or V4653F) and from 19 healthy unaffected subjects to record U-waves and TPE intervals as well as to measure beta-blockers' effects on ventricular repolarization by use of an automated computerized program. RESULTS: The maximal U-wave to T-wave amplitude ratio was 0.8 +/- 0.6 in CPVT patients and 0.4 +/- 0.3 in unaffected subjects (P = .009). Patients with most ventricular extrasystoles had a higher U-wave to T-wave amplitude ratio than those with fewest extrasystoles. Treatment with beta-blockers decreased U-wave amplitude at high heart rates. CPVT patients had longer TPE intervals than unaffected subjects at high heart rates, and beta-blocker treatment shortened their TPE intervals. CONCLUSION: Present data support the hypothesis that U-waves associate with the DAD-triggered extrasystolic activity in CPVT patients. Patients with a RyR2 mutation show increased TPE at high heart rates. Beta-blocker treatment suppresses observed repolarization abnormalities in CPVT patients.
Authors: Eyal Nof; Bernard Belhassen; Michael Arad; Zahurul A Bhuiyan; Charles Antzelevitch; Raphael Rosso; Rami Fogelman; David Luria; Dalia El-Ani; Marcel M A M Mannens; Sami Viskin; Michael Eldar; Arthur A M Wilde; Michael Glikson Journal: Heart Rhythm Date: 2011-05-26 Impact factor: 6.343
Authors: Mette Nyegaard; Michael T Overgaard; Mads T Søndergaard; Marta Vranas; Elijah R Behr; Lasse L Hildebrandt; Jacob Lund; Paula L Hedley; A John Camm; Göran Wettrell; Inger Fosdal; Michael Christiansen; Anders D Børglum Journal: Am J Hum Genet Date: 2012-10-05 Impact factor: 11.025
Authors: Kirsi Kujala; Jere Paavola; Anna Lahti; Kim Larsson; Mari Pekkanen-Mattila; Matti Viitasalo; Annukka M Lahtinen; Lauri Toivonen; Kimmo Kontula; Heikki Swan; Mika Laine; Olli Silvennoinen; Katriina Aalto-Setälä Journal: PLoS One Date: 2012-09-04 Impact factor: 3.240