Cardiac Alternans: Mechanisms and Clinical Utility in Arrhythmia Prevention

Kulkarni, Kanchan; Merchant, Faisal M.; Kassab, Mohamad B; Sana, Furrukh; Moazzami, Kasra; Sayadi, Omid; Singh, Jagmeet P.; Heist, E. Kevin; Armoundas, Antonis A.

doi:10.1161/jaha.119.013750

Cited by 31 publications

(21 citation statements)

References 163 publications

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“…TWA burden was observed to be higher during atrial pacing at faster HR, which is consistent with previous findings and known restitution mediated mechanisms of TWA onset (Ng et al, 2007;Merchant et al, , 2013aKulkarni et al, 2019). Hence, the lack of significant effects of LLTS on TWA burden during atrial pacing compared to sinus rhythm could be attributed to higher baseline levels of alternans.…”

Section: Discussionsupporting

confidence: 90%

“…Microvolt TWA is a surrogate marker for susceptibility to VT/VF, leading to SCD (Merchant et al, , 2013a(Merchant et al, , 2015Kulkarni et al, 2019). Favorable modulation of VT/VF susceptibility by LLTS in a population at high risk for VT/VF such as patients with ICM may be a surrogate for potential benefit in a larger number of patients at risk for VT/VF.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…T-wave alternans, a manifestation of repolarization alternans (RA), has been associated with an increased risk of ventricular arrhythmias and SCD ( 1 ). Etiological hypotheses center around alternation of intracellular calcium (Ca 2+ ) concentration, either as a result of or as a driver of abnormalities in action potential duration, amplitude, or cellular sarcolemma currents in every other cardiac cycle ( 2 ). Localized cardiac alternans may lead to increased spatial dispersion of refractoriness (DR) and discordance of action potential duration in adjacent areas of the myocardium, which forms substrate for unidirectional conduction block and re-entrant arrhythmia ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Autonomic Modulation for Treatment of Repolarization Alternans and Refractory Ventricular Electrical Storm

et al. 2021

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Macroscopic T-wave alternans (TWA) is a rare finding on surface electrocardiogram and has been associated with an increased risk of impending sudden cardiac death. We highlight a case of macroscopic TWA in a patient with markedly prolonged QTc interval preceding ventricular electrical storm, which was refractory to medical management. Autonomic modulation of the stellate ganglion resulted in improvement in both TWA and QTc interval. ( Level of Difficulty: Advanced. )

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“…This suggests that significantly elevated levels of TWA may serve as a predictor of impending arrhythmias. Indeed, we have shown that TWA is a short‐ 23 , 24 , 25 , 26 and long‐term 27 , 28 predictor of susceptibility to ventricular tachyarrhythmias.…”

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confidence: 89%

“… 43 , 44 , 56 , 57 Therefore, maintaining a constant DI n ,

in Equation 2 , eliminates the pacing relation between APD and DI, thus eliminating feedback (Figure 1 ). Although other theories for the mechanisms of alternans onset have been proposed, 3 , 10 , 23 , 58 this restitution‐based mechanism of alternans formation remains the most predominant in the context of periodic pacing. 18 , 59 …”

Section: Electrical Restitution and Feedbackmentioning

confidence: 99%

Clinical Potential of Beat‐to‐Beat Diastolic Interval Control in Preventing Cardiac Arrhythmias

Kulkarni

Walton

Armoundas

et al. 2021

JAHA

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Life‐threatening ventricular arrhythmias and sudden cardiac death are often preceded by cardiac alternans, a beat‐to‐beat oscillation in the T‐wave morphology or duration. However, given the spatiotemporal and structural complexity of the human heart, designing algorithms to effectively suppress alternans and prevent fatal rhythms is challenging. Recently, an antiarrhythmic constant diastolic interval pacing protocol was proposed and shown to be effective in suppressing alternans in 0‐, 1‐, and 2‐dimensional in silico studies as well as in ex vivo whole heart experiments. Herein, we provide a systematic review of the electrophysiological conditions and mechanisms that enable constant diastolic interval pacing to be an effective antiarrhythmic pacing strategy. We also demonstrate a successful translation of the constant diastolic interval pacing protocol into an ECG‐based real‐time control system capable of modulating beat‐to‐beat cardiac electrical activity and preventing alternans. Furthermore, we present evidence of the clinical utility of real‐time alternans suppression in reducing arrhythmia susceptibility in vivo. We provide a comprehensive overview of this promising pacing technique, which can potentially be translated into a clinically viable device that could radically improve the quality of life of patients experiencing abnormal cardiac rhythms.

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Cardiac Alternans: Mechanisms and Clinical Utility in Arrhythmia Prevention

Cited by 31 publications

References 163 publications

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

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

Autonomic Modulation for Treatment of Repolarization Alternans and Refractory Ventricular Electrical Storm

Clinical Potential of Beat‐to‐Beat Diastolic Interval Control in Preventing Cardiac Arrhythmias

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