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

Branching out:CRT beyond current concepts

Patients suffering from heart failure and delay in electrical activation of the heart can be treated with cardiac resynchronization therapy (CRT). This treatment restores the synchronous contraction of the two large cardiac chambers (ventricles) using a pacemaker. In this PhD thesis some relatively unexplored facets of CRT are investigated. One of these facets concerns the effects of CRT on electrical recovery of the cardiac cells (repolarization). A good and more or less simultaneous repolarization is important in the prevention of arrhythmias. Measurements in patients showed that important changes in the part of the electrocardiogram that represents repolarization already occurred within two weeks of starting CRT. Using a computer model, we demonstrated that these changes were indicative of more simultaneous repolarization. Moreover, we found that a bigger change in repolarization was linked to a larger improvement in cardiac function. These results can contribute to (research into) better treatment of patients with heart failure

Advanced electrocardiography in myocardial electrical remodeling : insights from cardiovascular magnetic resonance imaging

The electrocardiogram (ECG) is a common diagnostic tool in cardiology thanks to its high accessibility and low cost. However, in several cardiovascular diagnoses, including left ventricular hypertrophy (LVH), current conventional ECG measures and criteria have a poor diagnostic performance. LVH is associated with hypertension and diabetes, but is often missed by the standard 12-lead ECG. LVH is typically diagnosed by non-invasive imaging methods. Cardiovascular magnetic resonance (CMR) is the gold standard for diagnosing LVH. Advanced-ECG (A-ECG) is a term used to describe a combination of advanced ECG analysis methods, and has been shown to be of diagnostic and prognostic utility. The aims of this thesis were to investigate the ability of A-ECG to diagnose LVH, using CMR as reference, as well as investigating the prognostic ability of A-ECG measures with regards to morbidity and mortality. We found that increased extracellular volume fraction by CMR reduces voltage measures of conventional ECG criteria for LVH, including the Sokolow-Lyon index and Cornell indices. This may explain the limited sensitivity of the ECG in detecting LVH. We further investigated different patterns of LVH based on the relation between increased mass and wall thickness, and found that the different patterns differ on their electrocardiographic manifestation by A- ECG. Furthermore, A-ECG had a higher diagnostic performance compared to conventional ECG LVH criteria. The ECG detects electrical changes, while LVH represents a structural change. Therefore, the electrical changes associated with LVH may be better referred to as left ventricular electrical remodeling (LVER). LVER, defined as the A-ECG measure spatial QRS-T angle exceeding the upper limit of normal, was found to have a higher accuracy in diagnosing LVH compared to conventional ECG LVH criteria. We also found that patients with LVER have a worse prognosis compared to patients without LVER. Lastly, we optimized a score based on ECG and CMR measures, respectively, to predict morbidity and mortality, and found that ECG and CMR are both strong and independent predictors of events. In conclusion, conventional ECG criteria lack sensitivity in detecting LVH, which may be explained by increased extracellular volume fraction or different structural patterns in LVH. A-ECG has a higher diagnostic accuracy than conventional ECG criteria for LVH and is prognostic beyond CMR measures. Lastly, we suggest that LVER should be used when electrical changes in LVH are addressed

The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy.

The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non-specific in DCM, the recently acquired knowledge of the genotype-phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG-based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves

Relationship between electrocardiographic findings and cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy

Background-\u2014The new designation of arrhythmogenic cardiomyopathy defines a broader spectrum of disease phenotypes, which include right dominant, biventricular, and left dominant variants. We evaluated the relationship between electrocardiographic findings and contrast-enhanced cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy. Methods and Results-\u2014We studied a consecutive cohort of patients with a definite diagnosis of arrhythmogenic cardiomyopathy, according to 2010 International Task Force criteria, who underwent electrocardiography and contrast-enhanced cardiac magnetic resonance. Both depolarization and repolarization electrocardiographic abnormalities were correlated with the severity of dilatation/dysfunction, either global or regional, of both ventricles and the presence and regional distribution of late gadolinium enhancement. The study population included 79 patients (60% men). There was a statistically significant relationship between the presence and extent of T-wave inversion across a 12-lead ECG and increasing values of median right ventricular (RV) end-diastolic volume (P55 ms in the right precordial leads (V1-V3) was associated with higher RV volume (P=0.014) and lower RV ejection fraction (P=0.053). Low QRS voltages in limb leads predicted the presence (P=0.004) and amount (P<0.001) of left ventricular late gadolinium enhancement. Conclusions-\u2014The study results indicated that electrocardiographic abnormalities predict the arrhythmogenic cardiomyopathy phenotype in terms of severity of RV disease and left ventricular involvement, which are among the most important determinants of the disease outcome