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

Figures

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  Figure 1. Representative action potential traces demonstrating the functional difference between periodic pacing (A) and constant diastolic interval (DI) pacing (B). In periodic pacing, the duration between consecutive stimuli (basic cycle length [BCL]) is constant from beat to beat, creating a partial dependence of the DI on the preceding action potential duration (APD) (DIn=BCL−APDn) (ie, feedback). Feedback elimination can be achieved by controlling and maintaining a constant DI on a beat‐by‐beat basis, hence eliminating the inherent dependence of the DI on the preceding APD.

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  Figure 2. Action potential duration (APD) as a function of basic cycle length (BCL) (or diastolic interval [DI]) for a single‐cell ionic model paced with periodic pacing and constant DI pacing with 0% and 2.5% heart rate variability (HRV). BCLstart and BCLend denote the start and end of APD alternans, respectively. Reproduced with permission from McIntyre et al43 ©2014, Elsevier.

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  Figure 3. Application of constant diastolic interval (DI) pacing to ventricular cable model using human kinetics. A, Dynamical response of the human ventricular cable model for periodic pacing (constant basic cycle length [BCL]) and constant DI pacing at varying cable lengths (L). BCLeq represents the calculated BCL for each DI (DI+ action potential duration [APD]=BCLeq). Colors represent different electrical responses: normal 1:1 conduction (dark blue), spatially concordant alternans (SCA) (light blue), spatially discordant alternans (SDA) (yellow), and conduction block (CB) (red). Darker or lighter color shade denotes alternans amplitude being larger or smaller than 50 ms, respectively. B, Representative traces of APD corresponding to beats 49 (red) and 50 (blue) along the 3‐cm length of the cable exhibiting alternans (BCL=185 ms) during periodic pacing. C, Representative traces of APD corresponding to beats 6 (red) and 7 (blue) along the length of the cable during constant DI pacing. No onset of alternans was observed. Reproduced from Zlochiver S, Johnson C, Tolkacheva E. Constant DI pacing suppresses cardiac alternans formation in numerical cable models. Chaos. 2017;27:093903, with the…

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  Figure 4. Schematic of the ex vivo whole heart optical mapping system with real‐time closed‐loop diastolic interval (DI) control. A, The optical mapping setup records optical videos during periodic and constant DI pacing for offline processing and analysis. B, The real‐time DI control system detects instantaneous T waves on a beat‐by‐beat basis using volume‐conducted ECG and applies electrical stimuli after a predetermined fixed TR interval. CAM indicates camera. DAQ indicates data acquisition board.

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  Figure 5. Experimental evaluation of constant diastolic interval (DI) pacing using ex vivo optical mapping of isolated whole rabbit hearts. A, Representative 2‐dimensional (2D) action potential duration (APD) maps depicting the change in APD with basic cycle length (BCL) for 2 consecutive beats during periodic pacing, for the left ventricle (LV). Corresponding 2D alternans maps denote the onset of spatial alternans (blue) at a BCL of 130 ms (BCL onset highlighted by red box). Action potential traces at a BCL of 200 ms (filled diamond) demonstrate 1:1 APD response at steady state and 2:2 APD response, alternans, at a BCL of 130 ms (asterisk). Mean diastolic interval (<DI>) corresponding to BCL onset was ≈41 ms.40 B, Representative 2D APD maps depicting the change in APD with DI for 2 consecutive beats during constant DI pacing. Corresponding 2D alternans maps show the absence of spatial alternans. Action potential traces at DIs of 90 (filled diamond) and 40 (asterisk) ms demonstrate steady state 1:1 APD response, highlighting the absence of temporal alternans during constant DI pacing. Green box highlights the DI equivalent to the <DI> during BCL onset for periodic pacing. C, Summary…

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  Figure 6. Representative example demonstrating the use of T‐wave triggered pacing to suppress spontaneously occurring alternans during acute myocardial ischemia. Alternans voltage and Kscore are plotted for 2 intracardiac bipolar leads (CS4LV3 and CS4LV9) during angioplasty balloon‐induced, coronary artery occlusion, which demonstrates spontaneous alternans at baseline. Alternans suppression pacing is delivered from the right atrium (amplitude, 5 mA; width, 5 ms; coupling to T wave, 155±40 ms). When triggered pacing is discontinued, both the alternans voltage and Kscore increase to the baseline level during sinus rhythm. Transitions from baseline to triggered pacing ON to triggered pacing OFF occur correspondingly at times marked by solid vertical black lines, whereas the colored horizontal lines during each intervention indicate the mean value of the alternans voltage/Kscore during that intervention. T‐wave triggered pacing results in a significant reduction of spontaneous T‐wave alternans during acute ischemia (alternans voltage, ≈0.63‐fold average reduction compared with baseline, P<0.0001; Kscore, ≈0.32‐fold average reduction compared with baseline, P<0.0001). Discontinuation of T‐wave…