Cellular and Molecular Aspects of Dyssynchrony and Resynchronization

Kirk, Jonathan A.; Kass, David A.

doi:10.1016/j.hfc.2016.07.003

Cited by 16 publications

(7 citation statements)

References 116 publications

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“…Development of implantable pacing devices for mice has been long recognized as essential for fundamental research of conduction system disorders and heart failure as well as investigation of the adverse effects from chronic pacing. 3 The clinical significance of open questions regarding aberrant conduction has driven several prior attempts to engineer devices appropriate for mice, but none to date has been capable of long-term continuous pacing for more than several days. Previously, key pitfalls have been the lack of sufficient battery life and high surgical implant mortality.…”

Section: Discussionmentioning

confidence: 99%

“…2 Since not all patients respond to cardiac pacing in the same way, many important biological questions about the underlying mechanisms of pacing-induced cardiomyopathy and cardiac resynchronization therapies remain open. 3 This highlights the potential for future innovations in pacing techniques that may improve clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Cardiac pacing strategies have been used in larger animals to develop models of atrial fibrillation or sudden death, 4, 5 but similar approaches have not been possible to test in mice due to the lack of available technologies for chronic pacing in these small animals. 3 The ability to pace genetically modified mice will enable many important investigations in the field of cardiac electrophysiology and heart failure. 3 Prior attempts to create fully implantable pacemakers for mice have been limited to less than 1 week in pacing duration due to limited battery performance and technical restrictions of the device technologies.…”

Section: Introductionmentioning

confidence: 99%

“…3 The ability to pace genetically modified mice will enable many important investigations in the field of cardiac electrophysiology and heart failure. 3 Prior attempts to create fully implantable pacemakers for mice have been limited to less than 1 week in pacing duration due to limited battery performance and technical restrictions of the device technologies. 6, 7 Alternative solutions for pacing over longer time frames have required wireless power transmission, which allowed only brief intermittent pacing of mice under anesthesia, 7 or the use of exteriorized passive connects for tethered pacing in rats.…”

Section: Introductionmentioning

confidence: 99%

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A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse

Hulsmans

Aguirre

Bonner

et al. 2018

Circulation Research

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Rationale: Cardiac pacing is a critical technology for the treatment of arrhythmia and heart failure. The impact of specific pacing strategies on myocardial function is an area of intense research and high clinical significance. Mouse models have proven extremely useful for probing mechanisms of heart disease, but there is currently no reliable technology for long-term pacing in the mouse. Objective: We sought to develop a device for long-term pacing studies in mice. We evaluated the device for i) treating 3rd-degree atrioventricular block after macrophage depletion, ii) ventricular pacing-induced cardiomyopathy, and iii) high-rate atrial pacing. Methods and Results: We developed a mouse pacemaker by refashioning a 26 mm × 6.7 mm clinical device powered by a miniaturized, highly efficient battery. The electrode was fitted with a single flexible lead, and custom software extended the pacing rate to up to 1200 beats per minute. The wirelessly programmable device was implanted in the dorsal subcutaneous space of 39 mice. The tunneled lead was passed through a left thoracotomy incision and attached to the epicardial surface of the apex (for ventricular pacing) or the left atrium (for atrial pacing). Mice tolerated the implantation and both long-term atrial and ventricular pacing over weeks. We then validated the pacemaker’s suitability for the treatment of atrioventricular block after macrophage depletion in Cd11bDTR mice. Ventricular pacing increased the heart rate from 313±59 to 550 beats per minute (P<0.05). In addition, we characterized tachypacing-induced cardiomyopathy in mice. Four weeks of ventricular pacing resulted in reduced left ventricular function, fibrosis, and an increased number of cardiac leukocytes and endothelial activation. Finally, we demonstrated the feasibility of chronic atrial pacing at 1200 beats per minute. Conclusions: Long-term pacing with a fully implantable, programmable, and battery-powered device enables previously impossible investigations of arrhythmia and heart failure in the mouse.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse

Hulsmans

Aguirre

Bonner

et al. 2018

Circulation Research

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“…Conduction system disease with progression to complete AV block is a well-recognized complication of several neuromuscular disorders, including myotonic dystrophy. The presence of conduction disease characterized by first-degree AV block and underlying LBBB suggest a key pathogenic role of electrical dysynchrony in mediating the cardiomyopathy associated with DM1 11 . In patients with DM1, implantation of a permanent pacemaker is recommended even in asymptomatic patients with an abnormal resting ECG or with HV interval prolongation during electrophysiological study 12 .…”

Section: Discussionmentioning

confidence: 99%

Ventricular tachycardia in patients with type 1 myotonic dystrophy: a case series

Nikhanj

Sivakumaran

Miskew-Nichols

et al. 2019

European Heart Journal - Case Reports

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Background Type 1 myotonic dystrophy (DM1) is associated with a variety of cardiac conduction abnormalities and the frequent need for permanent pacing. However, the role of ventricular tachycardia (VT) and the implied risk of sudden cardiac death (SCD) is poorly understood. Case summary This study examined a 56-patient DM1 cohort of men and women, and identified five patients (two females and three males) with ventricular arrhythmias (8.9%). Patients were reviewed on a case-by-case basis, with their clinical presentation and management of VT and the associated cardiomyopathy indicated. Patient cardiac function was determined by 12-lead electrocardiogram, 48-h Holter monitor, and transthoracic echocardiography. These patients were therefore suitable candidates for implantable cardioverter-defibrillator implantation and received these devices; four of the five patients also received cardiac resynchronization therapy. Medical therapies included angiotensin converting enzyme inhibition, mineralocorticoid receptor antagonist, and following device implantation, beta-blocker therapy was initiated. Discussion Our case series demonstrates the prevalence of VT in patients with DM1 highlighting the associated risks of SCD in this patient population. The burden of ventricular arrhythmias, advanced conduction disease, and cardiomyopathy are best treated with a combination of device and medical therapies.

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Resynchronization Therapy for Patients with Congenital Heart Disease: Are We Ready for Prime Time?

Anjewierden

Aziz

2018

Curr Cardiol Rep

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CRT is a valuable tool in the treatment of heart failure in the setting of CHD. Current evidence points toward the ability of this therapy to increase hemodynamic parameters and reduce heart failure-related symptoms. Within the CHD population, patients with systemic left ventricles appear to benefit the most from CRT. Utilization of CRT in CHD has been technically difficult due to the complexity and variety of anatomic substrates. However, lateral thoracotomies and other advances have made implantation more feasible. The most up-to-date evidence continues to support the use of CRT in the heterogeneous population of CHD with careful and individualized patient selection. Further studies are needed to evaluate the utility of CRT for specific anatomic substrates within this population.

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Cellular and Molecular Aspects of Dyssynchrony and Resynchronization

Cited by 16 publications

References 116 publications

A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse

A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse

Ventricular tachycardia in patients with type 1 myotonic dystrophy: a case series

Resynchronization Therapy for Patients with Congenital Heart Disease: Are We Ready for Prime Time?

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