How to diagnose the cause of sudden cardiac arrest

Sudden cardiac death or sudden cardiac arrest (SCA) is defined as natural death that occurs within an hour of the onset of acute symptoms or during sleep due to a primary cardiac cause. Most cases of SCA are attributable to coronary artery disease, with occult cardiomyopathy or inheritable arrhythmic syndromes accounting for a minority of SCA. Diagnosing the cause of SCA has potential implications for the patient and the family, and demands a comprehensive approach. This review summarizes the potential causes of SCA and outlines a systematic diagnostic approach to the SCA survivor. (Cardiol J 2011; 18, 2: 210-216

The diagnostic role of T wave morphology biomarkers in congenital and acquired long QT syndrome: A systematic review

Introduction: QTc prolongation is key in diagnosing long QT syndrome (LQTS), however 25%–50% with congenital LQTS (cLQTS) demonstrate a normal resting QTc. T wave morphology (TWM) can distinguish cLQTS subtypes but its role in acquired LQTS (aLQTS) is unclear. Methods: Electronic databases were searched using the terms “LQTS,” “long QT syndrome,” “QTc prolongation,” “prolonged QT,” and “T wave,” “T wave morphology,” “T wave pattern,” “T wave biomarkers.” Whole text articles assessing TWM, independent of QTc, were included. Results: Seventeen studies met criteria. TWM measurements included T-wave amplitude, duration, magnitude, Tpeak-Tend, QTpeak, left and right slope, center of gravity (COG), sigmoidal and polynomial classifiers, repolarizing integral, morphology combination score (MCS) and principal component analysis (PCA); and vectorcardiographic biomarkers. cLQTS were distinguished from controls by sigmoidal and polynomial classifiers, MCS, QTpeak, Tpeak-Tend, left slope; and COG x axis. MCS detected aLQTS more significantly than QTc. Flatness, asymmetry and notching, J-Tpeak; and Tpeak-Tend correlated with QTc in aLQTS. Multichannel block in aLQTS was identified by early repolarization (ERD30%) and late repolarization (LRD30%), with ERD reflecting hERG-specific blockade. Cardiac events were predicted in cLQTS by T wave flatness, notching, and inversion in leads II and V5, left slope in lead V6; and COG last 25% in lead I. T wave right slope in lead I and T-roundness achieved this in aLQTS. Conclusion: Numerous TWM biomarkers which supplement QTc assessment were identified. Their diagnostic capabilities include differentiation of genotypes, identification of concealed LQTS, differentiating aLQTS from cLQTS; and determining multichannel versus hERG channel blockade

Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2

The heart rhythm disorder long QT syndrome (LQTS) can result in sudden death in the young or remain asymptomatic into adulthood. The features of the surface electrocardiogram (ECG), a measure of the electrical activity of the heart, can be equally variable in LQTS patients, posing well-described diagnostic dilemmas. Here we report a correlation between QT interval prolongation and T-wave notching in LQTS2 patients and use a novel computational framework to investigate how individual ionic currents, as well as cellular and tissue level factors, contribute to notched T waves. Furthermore, we show that variable expressivity of ECG features observed in LQTS2 patients can be explained by as little as 20% variation in the levels of ionic conductances that contribute to repolarization reserve. This has significant implications for interpretation of whole-genome sequencing data and underlies the importance of interpreting the entire molecular signature of disease in any given individua

ARTICLE Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2

The heart rhythm disorder long QT syndrome (LQTS) can result in sudden death in the young or remain asymptomatic into adulthood. The features of the surface electrocardiogram (ECG), a measure of the electrical activity of the heart, can be equally variable in LQTS patients, posing well-described diagnostic dilemmas. Here we report a correlation between QT interval prolongation and T-wave notching in LQTS2 patients and use a novel computational framework to investigate how individual ionic currents, as well as cellular and tissue level factors, contribute to notched T waves. Furthermore, we show that variable expressivity of ECG features observed in LQTS2 patients can be explained by as little as 20% variation in the levels of ionic conductances that contribute to repolarization reserve. This has significant implications for interpretation of whole-genome sequencing data and underlies the importance of interpreting the entire molecular signature of disease in any given individual