Evaluation of Tp-e interval, Tp-e/QT ratio and index of cardiac-electrophysiological balance in patients with tinnitus

Background Tinnitus is a common auditory symptom. Dysfunction in the autonomic nervous system (ANS) is an essential part of the etiopathogenesis of tinnitus. ANS regulates heart rate and heart rhythm and can lead to ventricular repolarization changes, which can cause malignant ventricular arrhythmias. T wave peak-to-end T(p-e) interval and T(p-e)/QT ratio are known ventricular arrhythmia indexes, and the index of cardiac-electrophysiological balance (iCEB) is a novel index that can be used to predict the risk of malignant ventricular arrhythmia. The goal of the study was to investigate these ventricular arrhythmia indexes in patients with tinnitus. Methods The study population consisted of 240 patients with tinnitus and 240 healthy subjects. A standard 12-channel surface electrocardiogram was applied to both groups. T(p-e) interval, QT interval and QRS duration were determined. Corrected QT (QTc) was determined via Bazett’s formula. To predict ventricular arrhythmia, iCEB (QT/QRS), T(p-e)/QT, corrected iCEB (QTc/QRS) and T(p-e)/QTc values were determined and compared between groups. Results Compared to the control group, QT (376.46 ± 36.54 vs 346.52 ± 24.51 ms), QTc (426.68 ± 24.68 vs 390.42 ± 24.04 ms), T(p-e) (75.86 ± 14.68 vs 62.42 ± 8.64 ms), T(p-e)/QT (0.201 ± 0.06 vs 0.180 ± 0.01) and T(p-e)/QTc (0.177 ± 0.06 vs 0.159 ± 0.02) were significantly higher in patients with tinnitus (p < 0.001 for all). QT/QRS (3.92 ± 0.68 vs 3.56 ± 0.32) and QTc/QRS (4.44 ± 1.03 vs 4.01 ± 0.64) were also significantly higher in patients with tinnitus (p = 0.018 and p = 0.008, respectively). In addition, significant positive correlations were found between T(p-e), T(p-e)/QTc ratio and disease duration (r = 0.792, p < 0.001; r = 0.500, p < 0.001, respectively). Conclusion As a result, patients with tinnitus may have an increased risk of malignant ventricular arrhythmia.

Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias

The inherited mutation (R14del) in the calcium regulatory protein phospholamban (PLN) is linked to malignant ventricular arrhythmia with poor prognosis starting at adolescence. However, the underlying early mechanisms that may serve as prognostic factors remain elusive. This study generated humanized mice in which the endogenous gene was replaced with either human wild type or R14del-PLN and addressed the early molecular and cellular pathogenic mechanisms. R14del-PLN mice exhibited stress-induced impairment of atrioventricular conduction, and prolongation of both ventricular activation and repolarization times in association with ventricular tachyarrhythmia, originating from the right ventricle (RV). Most of these distinct electrocardiographic features were remarkably similar to those in R14del-PLN patients. Studies in isolated cardiomyocytes revealed RV-specific calcium defects, including prolonged action potential duration, depressed calcium kinetics and contractile parameters, and elevated diastolic Ca-levels. Ca-sparks were also higher although SR Ca-load was reduced. Accordingly, stress conditions induced after contractions, and inclusion of the CaMKII inhibitor KN93 reversed this proarrhythmic parameter. Compensatory responses included altered expression of key genes associated with Ca-cycling. These data suggest that R14del-PLN cardiomyopathy originates with RV-specific impairment of Ca-cycling and point to the urgent need to improve risk stratification in asymptomatic carriers to prevent fatal arrhythmias and delay cardiomyopathy onset.

Importance of electrocardiographic markers in predicting cardiac events in children

ECG is a common diagnostic tool in medical practice. Sudden cardiac death (SCD) is a rare but devastating event. The most common cause of SCD in the young is a primary arrhythmic event, which is often produced by malignant ventricular arrhythmia. Several electrocardiographic markers for ventricular repolarization and depolarization have been proposed to predict this arrhythmic risk and SCD in children. Although many of these parameters can easily be used in clinical practice, some of them need specific techniques for interpretation. In this review, we summarized the current knowledge regarding the clinical importance and the ability of these ECG parameters to predict adverse cardiac events in the pediatric population.

Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the TTN Gene

Background: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. Methods: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). Results: Median follow-up was 49 (18–105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P =0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04–3.44]; P =0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30–2.04]; P <0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis ( P =0.07). Conclusions: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.