Center for Cardiological Innovation

Oct 1, 2014

Center Directors Thor Edvardsen and Kristina Haugaa got their article published in European Heart Journal

Center Director Thor Edvardsen and Center Director of Cardiology Research Kristina Haugaa published in renowned European Heart Journal, online edition, with their journal article titled: Electromechanical window negativity in genotyped long-QT syndrome patients: Relation to arrhythmia risk.

The European Heart Journal has an impactfactor of 14.723, with annually increasing importance. Its a weekly published peer-reviewed journal and also the Official Journal of the European Society of Cardiology, aiming to publish the highest quality clinical and research material on all aspects of cardiovascular medicine.
Picture: Cover for October Issue, 2014

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INTRODUCTION

The congenital long-QT syndromes (LQTS) are caused by mutations in genes encoding for cardiac ion-channel subunits or ion-channel-associated proteins. To date, at least 15 different genes have been causally implicated.¹ Long-QT syndromes-related ion-channel defects predispose to cardiac action-potential prolongation and accentuate regional and temporal dispersion of repolarization. Genotype-specific pro-arrhythmic conditions can exacerbate repolarization dispersion and lead to the occurrence of afterdepolarizations, premature ventricular ectopic beats, and re-entrant excitation. These mechanisms can precipitate torsades de pointes (TdP) in susceptible LQTS patients, but their exact contribution to arrhythmogenesis remains often obscure. Additional mechanisms, including mechano-electrical triggers, appear relevant, but remain to be fully elucidated.

ABSTRACT

AIM:
Prolonged and dispersed left-ventricular (LV) contraction is present in patients with long-QT syndrome (LQTS). Electrical and mechanical abnormalities appear most pronounced in symptomatic individuals. We focus on the 'electromechanical window' (EMW; duration of LV-mechanical systole minus QT interval) in patients with genotyped LQTS. Profound EMW negativity heralds torsades de pointes in animal models of drug-induced LQTS.

METHODS AND RESULTS:
We included 244 LQTS patients from three centres, of whom 97 had experienced arrhythmic events. Seventy-six matched healthy individuals served as controls. QT interval was subtracted from the duration of Q-onset to aortic-valve closure (QAoC) midline assessed non-invasively by continuous-wave echocardiography, measured in the same beat. Electromechanical window was positive in controls but negative in LQTS patients (22 ± 19 vs. -43 ± 46 ms; P < 0.0001), being even more negative in symptomatic than event-free patients (-67 ± 42 vs. -27 ± 41 ms; P < 0.0001). QT, QTc, and QAoC were longer in LQTS subjects (451 ± 57, 465 ± 50, and 408 ± 37 ms, P < 0.0001). Electromechanical window was a better discriminator of patients with previous arrhythmic events than resting QTc (AUC 0.77 (95% CI, 0.71-0.83) and 0.71 (95% CI, 0.65-0.78); P = 0.03). In multivariate analysis, EMW predicted arrhythmic events independently of QTc (odds ratio 1.25; 95% CI, 1.11-1.40; P = 0.001). Adding EMW to QTc for risk assessment led to a net reclassification improvement of 13.3% (P = 0.03). No EMW differences were found between the three major LQTS genotypes.

CONCLUSIONS:
Patients with genotype-positive LQTS express EMW negativity, which is most pronounced in patients with documented arrhythmic events.


Representative electromechanical window calculations in the same beat during continuous-wave Doppler echocardiography of the left ventricular-outflow tract. (Left panel) Electromechanical window positivity (yellow bar) in a healthy individual. (Middle panel) Electromechanical window negativity (red bar) in an asymptomatic long-QT syndrome subject. (Right panel) Profound electromechanical window negativity in a symptomatic patient. Q-onset to aortic-valve closure, interval from initiation of QRS to aortic-valve closure; EMW, electromechanical window; RV, right ventricle; LV, left ventricle; LA, left atrium; Ao, ascending aorta.

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