Towards development of pacing protocol to mimic physiological heart rate Virendra V. Kakade1, Stephen D. McIntyre2, Elena G. Tolkacheva3

Departments of Electrical Engineering1, Mathematics2, Biomedical Engineering3

University of Minnesota Introduction Alternans, the beat-to-beat variation of action potential duration (APD), has been implicated as a substrate for ventricular fibrillation, which may lead to sudden cardiac death. Currently, the restitution hypothesis, based on periodic pacing was used to predict alternans formation in the heart. Periodic pacing introduces feedback in the heart by making the diastolic interval depend on the preceding APD. However, in vivo, the heart exhibits heart rate variability (HRV) which modulates feedback and may lead to failure of the restitution hypothesis.

Aim To develop physiologically relevant pacing protocols based on ECG analysis leading to an improvement of the current restitution hypothesis.

Methods We analyzed ECG data (2 minutes each) belonging to patients from Diseased (Myocardial Infarction, n=6) and healthy (n=8) categories from PhysioNet online database [1]. Various metrics related to heart rate variability were evaluated.

Measurements AVGRR : Average RR interval DI : Diastolic Interval SDRR : Standard deviation of RR interval APD : Action Potential Duration HRV: SDRR /AVGRR BCL : Basic Cycle Length

ECG Analysis of Diseased Patients

Patient AVGRR (ms) SDRR (ms) HRV (%)

S0306 975.8 60.9 6.2

S0303 771.5 34.5 4.5

S0292 874.3 39.3 4.5

S0304 888.9 22.6 2.5

S0308 839.2 27.4 3.3

S0452 1047.5 46.0 4.4

S0457 1044.0 67.7 6.5

S0460 1113.8 69.4 6.2

944.3±42.1* 45.98±6.42* 4.76±1.45*

Patient AVGRR (ms) SDRR (ms) HRV (%)

Twa18 699.7 19.6 2.80

Twa38 711.7 18.5 2.60

Twa31 710.0 13.8 1.94

Twa11 786.0 20.8 2.64

Twa20 814.8 25.7 3.16

Twa42 824.0 34.5 4.19

757±23.25* 22.15±2.92* 2.89±0.75*

Conclusion We propose two new protocols to mimic HRV. Our data indicate that the healthy category may be represented by the constant BCL pacing protocol; whereas, the diseased category may be represented by the constant DI pacing protocol in numerical simulations.

References 1. Goldberger AL, Amaral LAN, Glass L, Hausdorff JM, Ivanov PCh,

Mark RG, Mietus JE, Moody GB, Peng C-K, Stanley HE. PhysioBank, PhysioToolkit, and PhysioNet: Components of a New Research Resource for Complex Physiologic Signals. Circulation 101(23):e215-e220,2000

2. McIntyre SD, Mori Y., Tolkacheva EG Local onset of voltage and calcium alternans in the heart, ASME Dynamic Systems and Control Conference, 2011

δ=0 regular pacing

δ Є [0,1] pacing with random variation HRV=0.02

Constant BCL pacing protocol [2] BCL = BCL0 ± BCL0 * HRV *δ

Feedback Present

δ=0 regular pacing

δ Є [0,1] pacing with random variation HRV=0.02

Constant DI pacing protocol [2] DI = DI0 ± DI0 * HRV *δ

Feedback Absent

Acknowledgements This study was supported in part by the NSF Grant PHY 0957468.

APD ↔ RT DI ↔ TR RR ↔ BCL

nn RTRRTR

Connection between APD, DI, and ECG

Alternans

ECG

APDAPD

DIDI

ECG

AVGSD

AVGSD Feedback

1:1 Response

nn APDBCLDI

Periodic Pacing

HEALTHY

DISEASED

HRV in ECG illustrated by variation in RR intervals

Feedback

Sn : Stimulus

* indicates statistically different data at the p=0.05 level.

* indicates statistically different data at the 0.05 level

Histogram of RR intervals

Feedback evaluated from ECG

ECG analysis of Healthy Patients