Acute Biomechanical Effects of Cardiac Contractility Modulation in Living Myocardial Slices from End-Stage Heart Failure Patients

Figures

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  Figure 1. (A) illustrates the LMS cultivation set-up. (B) shows definitions of excitatory and CCM pulse parameters and contractile measurements. AUC: area under the curve; CD: contraction duration; CD50: peak width at 50% of the maximum amplitude; Fmax: maximum contraction force; TTP: time to peak; TTR: time to relaxation; +dF/dt: steepest positive slope; −dF/dt: steepest negative slope.

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  Figure 2. CCM stimulation enhanced Fmax gradually for up to 3 min and then stabilized in LMS with positive inotropy (n = 42) from heart failure patients (n = 7). Typical contractile tracings were provided. Data are expressed as median and IQR, with added individual data points.

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  Figure 3. Biomechanical effects of increasing CCM pulse delay (10–200 ms) in LMS (CCM amplitude 80 mA, 21 ms duration). Increasing delay enhanced Fmax, AUC, +dF/dt, and −dF/dt, but did not alter TTP or TTR. Data are expressed as median and IQR, with added individual data points. Clustered Wilcoxon signed rank tests were used to compare contractile parameters for delay 10 ms (n = 60), 20 ms (n = 60), 30 ms (n = 60), 40 ms (n = 60), 50 ms (n = 55), 70 ms (n = 49), 100 ms (n = 55), 150 ms (n = 47), and 200 ms (n = 53). * p ≤ 0.05.

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  Figure 4. (A): Contractile tracings of HF-LMS with a negative, neutral, and positive inotropic response during CCM stimulation. (B–D): Inotropic response of HF-LMS to varying CCM stimulation parameters. A higher fraction of LMS showed a positive inotropic response with increasing CCM pulse delay, amplitude, and duration. Fractions were calculated for pulse delay 10 (n = 60), 20 (n = 60), 30 (n = 60), 40 (n = 60), 50 (n = 55), 70 (n = 49), 100 (n = 55), 150 (n = 47), and 200 ms (n = 53); pulse duration 11 (n = 48), 21 (n = 64), 31 (n = 59), and 41 ms (n = 58); pulse amplitude 1× (n = 54), 2× (n = 54), 3× (n = 56), and 4× threshold (n = 56).

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  Figure 5. (A): Partial reversal of the negative force-frequency relationship (FFR) with CCM stimulation. The number of included LMS at higher frequencies decreased from 57 to 24 due to exclusion of LMS when contractions did not capture all electrical stimuli. (B): The FFR of 24 LMS with capture of all pacing frequencies (30 to 180 bpm). (C,D) illustrate the Fmax of 24 LMS before and during CCM stimulation at 30 to 180 bpm, respectively.