Cardiac contractility modulation therapy: Are there superresponders?

Al‐Ghamdi, Bandar; Shafquat, Azam; Mallawi, Yaseen

doi:10.1016/j.hrcr.2017.02.004

Cited by 7 publications

(4 citation statements)

References 16 publications

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“…We compared clinical drug concentration-dependent QT prolongation with in vitro drug concentration-dependent action potential duration prolongation (Blinova et al, 2019). In the future, 3D ECT data may be leveraged Frontiers in Physiology frontiersin.org to better understand CCM in patient-specific populations or cohorts using disease-specific models (e.g., clinical trial in a dish) (Strauss and Blinova, 2017;Fermini et al, 2018;Blinova et al, 2019), and to identify potential CCM super responders (Al-Ghamdi et al, 2017;Hesselson et al, 2022) before therapy is needed. Likewise, these data provide an in vitro tool to optimize CCM parameters and tailor said parameters to an individual patient using patient-specific 3D ECTs following clinical presentation.…”

Section: Various Ccm Electrical Signals Modulate 3d Ect Functionmentioning

confidence: 99%

Acute effects of cardiac contractility modulation stimulation in conventional 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte models

et al. 2022

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Cardiac contractility modulation (CCM) is a medical device therapy whereby non-excitatory electrical stimulations are delivered to the myocardium during the absolute refractory period to enhance cardiac function. We previously evaluated the effects of the standard CCM pulse parameters in isolated rabbit ventricular cardiomyocytes and 2D human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) monolayers, on flexible substrate. In the present study, we sought to extend these results to human 3D microphysiological systems to develop a robust model to evaluate various clinical CCM pulse parameters in vitro. HiPSC-CMs were studied in conventional 2D monolayer format, on stiff substrate (i.e., glass), and as 3D human engineered cardiac tissues (ECTs). Cardiac contractile properties were evaluated by video (i.e., pixel) and force-based analysis. CCM pulses were assessed at varying electrical ‘doses’ using a commercial pulse generator. A robust CCM contractile response was observed for 3D ECTs. Under comparable conditions, conventional 2D monolayer hiPSC-CMs, on stiff substrate, displayed no contractile response. 3D ECTs displayed enhanced contractile properties including increased contraction amplitude (i.e., force), and accelerated contraction and relaxation slopes under standard acute CCM stimulation. Moreover, 3D ECTs displayed enhanced contractility in a CCM pulse parameter-dependent manner by adjustment of CCM pulse delay, duration, amplitude, and number relative to baseline. The observed acute effects subsided when the CCM stimulation was stopped and gradually returned to baseline. These data represent the first study of CCM in 3D hiPSC-CM models and provide a nonclinical tool to assess various CCM device signals in 3D human cardiac tissues prior to in vivo animal studies. Moreover, this work provides a foundation to evaluate the effects of additional cardiac medical devices in 3D ECTs.

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Section: Various Ccm Electrical Signals Modulate 3d Ect Functionmentioning

confidence: 99%

Acute effects of cardiac contractility modulation stimulation in conventional 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte models

et al. 2022

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“…Previously Al-Ghamdi et al had presented the case of 35-year-old male patient with a history of dilated cardiomyopathy with exceptional good response to CCM therapy with increase of LVEF from 25 to 45%. 4 The question is whether there is group of patients who could be "super-responders" to CCM therapy. Mando et al in meta-analysis of four randomized controlled trials proved that CCM in patients with systolic HF and narrow QRS complexes was associated with decrease in HF symptoms assessed by Minnesota Living with Heart Failure Questionnaire (MLWHQ).…”

Section: Discussionmentioning

confidence: 99%

Dependence from cardiac contractility modulation -- a loss of modulation as a cause of heart failure exacerbation.

Wojtaszczyk,

Kaczmarek,

Ptaszynski

et al. 2024

Preprint

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“…The current delivered is much greater than the pulse delivered by pacing and is thought to modify the entry of calcium into the myocardium and improve contractility. The actual mechanism is unknown 17–19. The authors propose that this current allows capture of more myocardium by altering the resistance of insulating fibres or sensitising myocardial cells not captured by the altered native conduction system.…”

Section: Discussionmentioning

confidence: 99%

Pathophysiology of narrow complex dilated cardiomyopathy insight derived from the velocity equation: velocity = distance/time

et al. 2019

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The pathophysiology of narrow complex dilated cardiomyopathy is not defined, so therapeutic options are limited. By utilising the velocity equation, the pathophysiology of narrow complex cardiomyopathy allows above normal conduction propagation velocities. There are two pathophysiological theories that allow above normal conduction velocities and failure to capture the myocardium: (1)insulating fibres of the conduction system extending beyond the apex and (2) reduction of axon branching. A patient with narrow complex cardiomyopathy was subjected to graded increase in amplitude and pulse width pacing to overcome the failure of native conduction to capture the myocardium. Peak systolic strain maps demonstrated a progressive increase in apical contractility with increasing pulse width and amplitude. Ejection fraction improved from 17% to 31%. Understanding the pathophysiology of narrow complex cardiomyopathy leads to proposed therapies. One potential pacing therapy is multi-lead pacing at high amplitude and pulse width to capture myocardial cells not captured by native conduction.

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Cardiac contractility modulation therapy: Are there superresponders?

Cited by 7 publications

References 16 publications

Acute effects of cardiac contractility modulation stimulation in conventional 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte models

Acute effects of cardiac contractility modulation stimulation in conventional 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte models

Dependence from cardiac contractility modulation -- a loss of modulation as a cause of heart failure exacerbation.

Pathophysiology of narrow complex dilated cardiomyopathy insight derived from the velocity equation: velocity = distance/time

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