Microvolt t-wave alternans its clinical significance in the assessment of the risk of sudden cardiac death among patients with hypertrophic cardiomyopathy

Summary Some patients with hypertrophic cardiomyopathy (HCM) are at significant risk of premature sudden death. Identification of the risk factors may enable effective prevention of adverse cardiac events in these patients. Assessment of the microvolt T-wave alternans (MTWA) is a recognized non-invasive diagnostic test used in risk stratification of sudden cardiac death (SCD). However, the number of reports on the frequency of occurrence of MTWA in HCM is small. Aim: Evaluation of the prognostic value of MTWA in predicting the risk of arrhythmic events (sudden cardiac death, documented VT/VF, appropriate ICD discharge) in patients with HCM. Material and methods 122 patients with HCM underwent detailed clinical assessment and ECG- and echocardiographic examination. They underwent 24-hour ambulatory ECG monitoring, and the following elements were analysed: 1) arrhythmias, 2) heart rate variability (HRV) and the QT segment, 3) the presence of ventricular late potentials (LP), 4) heart rate turbulence (HRT). MTWA assessment was made during a test on a treadmill (Cambridge Heart). In accordance with the adopted criteria, the test was interpreted as negative, positive or indeterminate. Subsequently, positive and indeterminate results were described collectively as MTWA(+) and negative results as MTWA(−). Then the patients were divided into two groups: Group 1 – 57 patients (46,7%) with MTWA(−), and Group 2 – 65 patients (53,2%) with MTWA(+). In order to stratify the risk, the following were adopted as composite primary endpoints: sudden cardiac death or hospitalization for life-threatening arrhythmias (VT/VF), and appropriate ICD discharge. Results The mean follow-up period of the patients was 57±8 months; during that time, events that met the criteria for the endpoint occurred in 16 patients. On the basis of univariate analysis, 10 variables with a significant influence on the occurrence of an event were selected (unexplained syncope, NT-proBNP values elevated above 411 pg/ml, size of the left atrium over 44mm, diastolic thickness of the interventricular septum over 25 mm, the presence of MTWA(+), the QRS width >90 msec, QTc >467 msec, QTd >70 msec, SDNN <110 msec, and sinus rhythm turbulence parameters TS <2,9 ms/2RR). These variables were then included in a multivariate analysis. The model from a Cox regression analysis showed that the presence of unexplained syncope (HR=1,4), MTWA(+) (HR=1,5), size of the left atrium over 44mm (HR=5), and the thickness of the interventricular septum over 25 mm (HR=1,5) increased the risk of sudden events. Conclusions 1) Patients with hypertrophic cardiomyopathy had a significant percentage of positive results of the microvolt T-wave alternans test (MTWA+), 2) Positive MTWA test result in patients with hypertrophic cardiomyopathy can help to identify patients at risk of sudden cardiac death. FUNDunding Acknowledgement Type of funding sources: None.

Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure

Aims: Microvolt T-wave alternans (TWA), an oscillation in T-wave morphology of the electrocardiogram (ECG), has been associated with increased susceptibility to ventricular tachy-arrhythmias, while vagus nerve stimulation has shown promising anti-arrhythmic effects in in vivo and ex vivo animal studies. We aimed to examine the effect of non-invasive, acute low-level tragus stimulation (LLTS) on TWA in patients with ischemic cardiomyopathy and heart failure.Methods: 26 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and chronic stable heart failure, previously implanted with an automatic implantable cardioverter defibrillator (ICD) device with an atrial lead (dual chamber ICD or cardiac resynchronization therapy defibrillator), were enrolled in the study. Each patient sequentially received, (1) Sham LLTS (electrode on tragus, but no stimulation delivered) for 5 min; (2) Active LLTS at two different frequencies (5 and 20 Hz, 15 min each); and (3) Active LLTS, during concomitant atrial pacing at 100 bpm at two different frequencies (5 and 20 Hz, 15 min each). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 μs, frequency 5/20 Hz, amplitude 1 mA lower than the discomfort threshold). TWA burden was assessed using continuous ECG monitoring during sham and active LLTS in sinus rhythm, as well as during atrial pacing.Results: Right atrial pacing at 100 bpm led to significantly heightened TWA burden compared to sinus rhythm, with or without LLTS. Acute LLTS at both 5 and 20 Hz, during sinus rhythm led to a significant rise in TWA burden in the precordial leads (p < 0.05).Conclusion: Acute LLTS results in a heart-rate dependent increase in TWA burden.

Electrophysiological Mechanisms Underlying T-Wave Alternans and Their Role in Arrhythmogenesis

T-wave alternans (TWA) reflects every-other-beat alterations in the morphology of the electrocardiogram ST segment or T wave in the setting of a constant heart rate, hence, in the absence of heart rate variability. It is believed to be associated with the dispersion of repolarization and has been used as a non-invasive marker for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death as numerous studies have shown. This review aims to provide up-to-date review on both experimental and simulation studies in elucidating possible mechanisms underlying the genesis of TWA at the cellular level, as well as the genesis of spatially concordant/discordant alternans at the tissue level, and their transition to cardiac arrhythmia. Recent progress and future perspectives in antiarrhythmic therapies associated with TWA are also discussed.

Investigating two kinds of cellular alternans and corresponding TWA induced by impaired calcium cycling in myocardial ischemia

<abstract> <sec><title>Background</title><p>The utility of T wave alternans (TWA) in identifying arrhythmia risk has been demonstrated. During myocardial ischemia (MI), TWA could be induced by cellular alternans. However, the relationship between cellular alternans patterns and TWA patterns in MI has not been investigated thoroughly.</p> </sec> <sec><title>Methods</title><p>We set MI conditions to simulate alternans. Either prolonging Ca²⁺ release or increasing spark-induced sparks (secondary sparks) can give rise to different patterns of APD alternans and TWA. In addition, different ischemic zones and reduced conduction velocity are also considered in one dimensional simulation.</p> </sec> <sec><title>Results</title><p>Delay of Ca²⁺ release can produce discordant Ca²⁺-driven alternans in single cell simulation. Increasing secondary sparks leads to concordant alternans. Correspondingly, morphology and magnitude of TWA vary in two different cellular alternans. Epi ischemia results in alternans concentrating in the first half of T wave. Endo and transmural ischemia lead to fluctuations in the second half of T wave. In addition, slowing conduction velocity has no effect on TWA magnitude.</p> </sec> <sec><title>Conclusion</title><p>Specific ionic channel dysfunction and ischemic zones affect TWA patterns.</p> </sec> </abstract>