skip to main content

Title: Clinical Potential of Beat‐to‐Beat Diastolic Interval Control in Preventing Cardiac Arrhythmias
Abstract 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.  more » « less
Award ID(s):
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Journal of the American Heart Association
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    As a leading cause of death in 325,000 adults per year in the United States, a significant proportion of sudden cardiac arrest (SCA) result from arrhythmias. To better understand the onset of arrhythmias and its potential treatment with more rapid and effective control approaches, a two-dimensional 50 × 50 cellular automata (CA) model is used in this study to illustrate the propagation of electrical waves across its tissue, and a constant diastolic interval (DI) control mechanism is adopted to help stabilize and prevent cardiac arrhythmias. Simulations of various scenarios including normal conduction and spiral waves in the presence of scar, normal conduction and alternans under control conditions are shown. The results validate that the CA model and constant DI control method are very efficient and effective in the study of dynamics and control of cardiac arrhythmias. 
    more » « less
  2. Dual voltage-calcium fluorescence optical recordings are increasingly appealing to characterize complex spa-tiotemporal cardiac dynamics within ex-vivo whole-heart ex-perimental preparations. Synchrony among voltage and calcium signals allows us to unveil novel multi-scale and multi-physics couplings at the ventricular scale and quantify features that define the intrinsic nonlinearities of the observed phenom-ena. Within such a complex scenario, we propose a rigorous methodological analysis comparing and contrasting multiple cardiac alternans onset and evolution indicators for rabbit pacing-down restitution protocols. We introduce a novel integral index quantified upon voltage and calcium signals, validated against well-accepted post-processing analyses, and generalized in terms of statistical restitution curves obtained under four different thermal states. Our study suggests that such a novel indicator can further advance our predictability on alternans onset, linking the concurrent evolution to an innovative quan-tification of the characteristic length obtained for both voltage and calcium at different thermal states. 
    more » « less
  3. Abstract

    Heart rhythm assessment is indispensable in diagnosis and management of many cardiac conditions and to study heart rate variability in healthy individuals. We present a proof-of-concept system for acquiring individual heart beats using smart speakers in a fully contact-free manner. Our algorithms transform the smart speaker into a short-range active sonar system and measure heart rate and inter-beat intervals (R-R intervals) for both regular and irregular rhythms. The smart speaker emits inaudible 18–22 kHz sound and receives echoes reflected from the human body that encode sub-mm displacements due to heart beats. We conducted a clinical study with both healthy participants and hospitalized cardiac patients with diverse structural and arrhythmic cardiac abnormalities including atrial fibrillation, flutter and congestive heart failure. Compared to electrocardiogram (ECG) data, our system computed R-R intervals for healthy participants with a median error of 28 ms over 12,280 heart beats and a correlation coefficient of 0.929. For hospitalized cardiac patients, the median error was 30 ms over 5639 heart beats with a correlation coefficient of 0.901. The increasing adoption of smart speakers in hospitals and homes may provide a means to realize the potential of our non-contact cardiac rhythm monitoring system for monitoring of contagious or quarantined patients, skin sensitive patients and in telemedicine settings.

    more » « less
  4. Electrode-based electrical stimulation underpins several clinical bioelectronic devices, including deep-brain stimulators and cardiac pacemakers. However, leadless multisite stimulation is constrained by the technical difficulties and spatial-access limitations of electrode arrays. Optogenetics offers optically controlled random access with high spatiotemporal capabilities, but clinical translation poses challenges. Here we show tunable spatiotemporal photostimulation of cardiac systems using a non-genetic platform based on semiconductor-enabled biomodulation interfaces. Through spatiotemporal profiling of photoelectrochemical currents, we assess the magnitude, precision, accuracy and resolution of photostimulation in four leadless silicon-based monolithic photoelectrochemical devices. We demonstrate the optoelectronic capabilities of the devices through optical overdrive pacing of cultured cardiomyocytes (CMs) targeting several regions and spatial extents, isolated rat hearts in a Langendorff apparatus, in vivo rat hearts in an ischaemia model and an in vivo mouse heart model with transthoracic optical pacing. We also perform the first, to our knowledge, optical override pacing and multisite pacing of a pig heart in vivo. Our systems are readily adaptable for minimally invasive clinical procedures using our custom endoscopic delivery device, with which we demonstrate closed-thoracic operations and endoscopic optical stimulation. Our results indicate the clinical potential of the leadless, lightweight and multisite photostimulation platform as a pacemaker in cardiac resynchronization therapy (CRT), in which lead-placement complications are common. 
    more » « less
  5. Abstract Aims

    The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts.

    Methods and results

    We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel.


    We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.

    more » « less