Left ventricular mechanical dispersion by tissue Doppler imaging: a novel approach for identifying high-risk individuals with long QT syndrome

CLINICAL RESEARCH European Heart Journal (2009) 30, 330–337 doi:10.1093/eurheartj/ehn466 Arrhythmias Left ventricular mechanical dispersion by tissue Doppler imaging: a novel approach for identifying high-risk individuals with long QT syndrome Kristina Hermann Haugaa 1, Thor Edvardsen 1, Trond P. Leren 2, Jon Michael Gran3, Otto A. Smiseth 1, and Jan P. Amlie 1* Received 24 April 2008; revised 28 August 2008; accepted 29 September 2008; online publish-ahead-of-print 21 October 2008 See page 253 for the editorial comment on this article (doi:10.1093/eurheartj/ehn587) Aims The aim of this study was to investigate whether prolonged and dispersed myocardial contraction duration assessed by tissue Doppler imaging (TDI) may serve as risk markers for cardiac events (documented arrhythmia, syncope, and cardiac arrest) in patients with long QT syndrome (LQTS). ..................................................................................................................................................................................... Methods Seventy-three patients with genetically confirmed LQTS (nine double- and 33 single-mutation carriers with previous and results cardiac events and 31 single-mutation carriers without events) were studied. Myocardial contraction duration was prolonged in each group of LQTS patients compared with 20 healthy controls (P , 0.001). Contraction duration was longer in single-mutation carriers with previous cardiac events compared with those without (0.46 + 0.06 vs. 0.40 + 0.06 s, P ¼ 0.001). Prolonged contraction duration could better identify cardiac events compared with corrected QT (QTc) interval in single-mutation carriers [area under curve by receiver-operating characteristic analysis 0.77 [95% confidence interval (95% CI) 0.65– 0.89] vs. 0.66 (95% CI 0.52–0.79)]. Dispersion of contraction was more pronounced in single-mutation carriers with cardiac events compared with those without (0.048 + 0.018 vs. 0.031 + 0.019 s, P ¼ 0.001). ..................................................................................................................................................................................... Conclusion Dispersion of myocardial contraction assessed by TDI was increased in LQTS patients. Prolonged contraction duration was superior to QTc for risk assessment. These new methods can easily be implemented in clinical routine and may improve clinical management of LQTS patients. ----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords Long QT syndrome † Echocardiography † Ventricular arrhythmia † Myocardial contraction † Dispersion Introduction The long QT syndrome (LQTS) is a genetic disorder characterized by prolonged ventricular repolarization that predisposes to lifethreatening arrhythmias.1 The pathophysiology behind the arrhythmias in LQTS is not precisely defined. Possible mechanisms include early after-depolarizations (EADs) and dispersion of myocardial repolarization. Fifty years after its initial description,2 – 4 approaches for risk stratification are insufficiently defined. Risk stratification today is based on history of syncope, genotype, gender, and corrected QT (QTc) interval.1,5 Prolonged QTc is a marker of prolonged action potential duration which is associated with a prolonged left ventricular (LV) contraction.6 – 8 Electrocardiogram (ECG) has limited abilities to detect regional differences in LV electrical pattern. A relationship between motion abnormalities of the LV * Corresponding author. Tel: þ47 23072766, Fax: þ47 23073530, Email: Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2008. For permissions please email: . The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact . 1 Department of Cardiology, Rikshospitalet University Hospital, University of Oslo, N-0027 Oslo, Norway; 2Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway; and 3Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway 331 LV mechanical dispersion by TDI Methods Long QT syndrome patients Seventy-three patients with molecularly defined LQTS were included in this study (Figure 1). None of the LQTS patients had structural heart disease of other origin or were ventricularly paced. All 73 LQTS mutation carriers were genotyped: 44 LQT1, 18 LQT2, 1 LQT3, 1 LQT5, and nine double-mutation carriers. Double-mutation carriers were considered a separate category and were analysed separately. Long QT syndrome single-mutation carriers Sixty-four patients were single-mutation carriers of an LQTS-associated mutation. Of the single-mutation carriers, 33 (52%) had a history of documented arrhythmia, syncope, or cardiac arrest, here defined as ‘symptomatic’. All symptomatic and three asymptomatic single-mutation carriers received therapy with beta-blockers (n ¼ 36). In addition to beta-blocker therapy, three single-mutation carriers were treated with an ICD and three with atrial pacemaker. In addition, six single-mutation carriers were studied with ECG and echocardiography but deemed ineligible for inclusion. One of these six was an LQT1 patient who received chemotherapy owing to malignant disease and developed cardiomyopathy with reduced LV function. Five asymptomatic mutation carriers ,15 years of age were ineligible for inclusion. We could not exclude future cardiac events in these young individuals and their status as asymptomatic in this study would therefore be inaccurate. Long QT syndrome double-mutation carriers, Jervell and Lange-Nielsen syndrome Nine patients were double-mutation carriers of an LQTS-associated mutation and had clinically Jervell and Lange-Nielsen syndrome (JLNS) with additional deafness. All JLNS patients had experienced repeated cardiac events and were treated with beta-blockers. In addition, one JLNS patient was treated with left sympathetic denervation, two with an ICD, and three with atrial pacemaker. Control groups Healthy individuals Twenty healthy individuals were age- and sex-matched and recruited from hospital staff. All had normal clinical examination, ECG, QTc, and echocardiography. Individuals on beta-blocker therapy Since 64% of the LQTS patients were on beta-blocker therapy, we included 18 (...truncated)