Name: benefits of cardiac resynchronization therapy in an asynchronous heart failure model induced by left bundle branch ablation and rapid pacing
Uploaded: 2017-12-11T13:00:00
Description: Watch this Scientific Journal Video about Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing at JoVE.com

This work is funded by National Natural Science Foundation of China (81671685) and Shanghai Commission of Health and Family Planning (No. 201440538)

Fifteen male beagle dogs (12 to 18 months old, weighing around 10.0-12.0 kg) were purchased and subjected to experiments. All procedures were performed in compliance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (Publication No. 85-23, revised 1996) and were approved by the Animal Care Committee in Zhongshan Hospital, Fudan University. Figure 1 shows the schematic workflow for all protocol steps.
1. Pre-s...

<ol>
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Dilated cardiomyopathy constitutes a major cause of CHF, which is characterized by ventricular dilation, systolic dysfunction with reduced LVEF, and abnormalities of diastolic filling11. Since chronic tachycardia-mediated HF is a recognized clinical condition, rapid pacing of either atrium or ventricle for at least 3 to 4 weeks serves as a frequently used animal model to induce CHF11. Hemodynamic changes occur as soon as 24 h after rapid pacing, with continued deterioration...

Advanced chronic HF is a leading cause of mortality for various cardiovascular diseases. A subset of patients with congestive heart failure (CHF) also develop ventricular conduction discoordination that aggravates symptoms and prognosis. CRT, also referred to as biventricular pacing, has been introduced as an alternative therapy for these patients for over 20 years1,2. Unfortunately, about 20-40% of the patients show poor response to CRT. Since then, many studies have been carried out in order to maximize CRT response3. It is now well recognized that patients with LBBB could benefit more from CRT than those with non-LBBB4, since an LBBB pattern causes a larger magnitude of cardiac dyssynchrony due to asymmetry in the freedom of wall movement between septal and lateral walls. Meanwhile recent studies have begun exploring changes in gene expression and molecular remodeling associated with CRT5. Accompanying the structural reverse remodeling induced by CRT, cellular and molecular reversion to a normal level is of great interest6. Hence, it is essential to establish an optimal model of CHF with isolated LBBB for studying CRT benefits.
Chronic, rapid ventricular pacing was once used to produce CHF in a canine model. RV pacing could undoubtedly produce delayed LV contraction as a model of the LBBB-like contraction pattern. However, this type of functional asynchrony with an intact conduction system may not emulate anatomical LBBB and is not considered an appropriate model for studying CRT performance, the essence of which is to coordinate impaired electrical activation and myocardial contraction. Rapid restoration of LV contractility and partial recovery of LV dimensions after cessation of pacing were also reported7.
Experimental studies have induced chronic LBBB by RF ablation to establish asynchronous ventricular contraction8. A combination of reduction in global pump function and regional invalid mechanical work could exacerbate CHF by generating cardiac inefficiency as well as cardiac remodeling at the tissue, cellular, and molecular levels. In LBBB hearts, workload is lowest in the septum and highest in the LV lateral wall. As a consequence, cardiac remodeling is most pronounced in the lateral wall9. The purpose of the present study is: (i) to advance a stable and chronic HF model with interventricular and intraventricular mechanical asynchrony by means of rapid RV pacing in combination with LBB ablation; (ii) to confirm dyssynchronous HF in our model and CRT benefits in coordinating contraction by two-dimensional speckle tracking echocardiography and aVTI; and (iii) to preliminarily explore cellular reverse remodeling elicited by CRT.

<table>
	<tbody>
		<tr>
			<td>Closed iv catheter system (0.9mm&#215;25mm)</td>
			<td>Becton Dickinson Medical</td>
			<td>5264442</td>
			<td>Used as venous retention needle</td>
		</tr>
		<tr>
			<td>Sodium pentobarbital</td>
			<td>Sigma-Aldrich Company</td>
			<td>130205</td>
			<td>For anesthesia</td>
		</tr>
		<tr>
			<td>Pet clipper</td>
			<td>Wuhan Shernbao pet supplies Co., Ltd.</td>
			<td>PGC-660</td>
			<td>For hair shaving</td>
		</tr>
		<tr>
			<td>Electrocardiograph</td>
			<td>Shanghai photoelectric medical electronic instrument Co., Ltd.</td>
			<td>ECG-6511</td>
			<td>For electrocardiogram recording</td>
		</tr>
		<tr>
			<td>Echocardiograph</td>
			<td>GE-Vingmed Ultrasound Company</td>
			<td>VIVID E9</td>
			<td>For echocardiographic assessment</td>
		</tr>
		<tr>
			<td>EchoPAC software</td>
			<td>GE healthcare</td>
			<td>Version201</td>
			<td>Offline analysis</td>
		</tr>
		<tr>
			<td>Laryngoscope</td>
			<td>Shanghai Medical Instrument Co., Ltd</td>
			<td></td>
			<td>Orotracheal intubation</td>
		</tr>
		<tr>
			<td>Endotracheal tube</td>
			<td>SIMS Portex Inc, UK</td>
			<td>274093</td>
			<td>Orotracheal intubation</td>
		</tr>
		<tr>
			<td>Volume cycled respirator</td>
			<td>Newport Corporation</td>
			<td>C100</td>
			<td>Artificial ventilation</td>
		</tr>
		<tr>
			<td>HeartStart XL Defibrillator/Monitor</td>
			<td>Philips Medical Systems</td>
			<td>M4735A</td>
			<td>Electrocardiogram monitor during operation</td>
		</tr>
		<tr>
			<td>Benzalkonium Bromide Tincture</td>
			<td>Shanghai Yunjia Pharmaceutical Co., Ltd.</td>
			<td>H31022694</td>
			<td>Used for skin disinfection</td>
		</tr>
		<tr>
			<td>Rib retractor</td>
			<td>Shanghai Medical Instrument Co., Ltd.</td>
			<td></td>
			<td>For thoracotomy</td>
		</tr>
		<tr>
			<td>4-0 suture</td>
			<td>Shanghai Pudong Jinhuan Medical Products Co., LTD.</td>
			<td>24L1005</td>
			<td>Suture of LV epicardial electrode</td>
		</tr>
		<tr>
			<td>2-0/T suture</td>
			<td>Shanghai Pudong Jinhuan Medical Products Co., LTD.</td>
			<td>11M0505</td>
			<td>Suture of pacing leads, fascia, vessels, etc.</td>
		</tr>
		<tr>
			<td>0-suture</td>
			<td>Shanghai Pudong Jinhuan Medical Products Co., LTD.</td>
			<td>11P0501</td>
			<td>Skin suture</td>
		</tr>
		<tr>
			<td>penicillin powder</td>
			<td>North China Pharmaceutical Co., Ltd.</td>
			<td>F6034105</td>
			<td></td>
		</tr>
		<tr>
			<td>DSA X-ray machine</td>
			<td>Philips</td>
			<td>Allura Xper FD10</td>
			<td>X-ray for fluoroscopy</td>
		</tr>
		<tr>
			<td>LV pacing electrode</td>
			<td>Medtronic, Inc.</td>
			<td>LBT 4965</td>
			<td></td>
		</tr>
		<tr>
			<td>RV pacing electrode</td>
			<td>St. Jude Medical</td>
			<td>Tendril 1888</td>
			<td></td>
		</tr>
		<tr>
			<td>RA pacing electrode</td>
			<td>St. Jude Medical</td>
			<td>IsoFlex 1642T</td>
			<td></td>
		</tr>
		<tr>
			<td>Pacemaker pulse generator</td>
			<td>Medtronic, Inc.</td>
			<td>Enpulse E2DR01</td>
			<td>For rapid RV pacing</td>
		</tr>
		<tr>
			<td>CRT pulse generator</td>
			<td>St. Jude Medical</td>
			<td>Anthem PM 3212</td>
			<td>For CRT performance</td>
		</tr>
		<tr>
			<td>Multi-channel electrophysiologic recorder</td>
			<td>GE Medical Systems</td>
			<td>2003232-004</td>
			<td>For surface and intracardiac electrogram</td>
		</tr>
		<tr>
			<td>Catheter input module</td>
			<td>GE Medical Systems</td>
			<td>301-00202-08</td>
			<td>Multiple pole switches for stimulation or recording</td>
		</tr>
		<tr>
			<td>Radiofrequency generator</td>
			<td>Johnson-Johnson Company</td>
			<td>ST-4460</td>
			<td>For RF current delivery</td>
		</tr>
		<tr>
			<td>Cordless return electrode</td>
			<td>Covidien</td>
			<td>E7509</td>
			<td>For current circuit formation</td>
		</tr>
		<tr>
			<td>Cordis 6-Fr sheath</td>
			<td>Johnson-Johnson Company</td>
			<td>504-606X</td>
			<td>Access for mapping catheter</td>
		</tr>
		<tr>
			<td>Cordis 7-Fr sheath</td>
			<td>Johnson-Johnson Company</td>
			<td>504-607X</td>
			<td>Access for mapping and ablation catheter</td>
		</tr>
		<tr>
			<td>6-Fr quadripolar catheter</td>
			<td>Johnson-Johnson Company</td>
			<td>F6QRA005RT</td>
			<td>Mapping catheter</td>
		</tr>
		<tr>
			<td>7-Fr 4mm-tip steerable ablation catheter</td>
			<td>St. Jude Medical</td>
			<td>402823</td>
			<td>Mapping and ablation catheter</td>
		</tr>
		<tr>
			<td>Prucka Cardio-Lab&#174;2000</td>
			<td>GE Medical Systems</td>
			<td>6.9.00.000</td>
			<td>Software package for electrogram recording</td>
		</tr>
		<tr>
			<td>Heparin</td>
			<td>Haitong Pharmaceutical Co., Ltd</td>
			<td>160505</td>
			<td>Anticoagulant during catheter ablation</td>
		</tr>
		<tr>
			<td>Digital image analysis system</td>
			<td>Leica Microsystems</td>
			<td>Qwin V3</td>
			<td>For histologic analysis</td>
		</tr>
	</tbody>
</table>

benefits of cardiac resynchronization therapy in an asynchronous heart failure model induced by left bundle branch ablation and rapid pacing

It is now well recognized that heart failure (HF) patients with left bundle branch block (LBBB) derive substantial clinical benefits from cardiac resynchronization therapy (CRT), and LBBB has become one of the important predictors for CRT response. The conventional tachypacing-induced HF model has several major limitations, including absence of stable LBBB and rapid reversal of left ventricular (LV) dysfunction after cessation of pacing. Hence, it is essential to establish an optimal model of chronic HF with isolated LBBB for studying CRT benefits. In the present study, a canine model of asynchronous HF induced by left bundle branch (LBB) ablation and 4 weeks of rapid right ventricular (RV) pacing is established. The RV and right atrial (RA) pacing electrodes via the jugular vein approach, together with an epicardial LV pacing electrode, were implanted for CRT performance. Presented here are the detailed protocols of radiofrequency (RF) catheter ablation, pacing leads implantation, and rapid pacing strategy. Intracardiac and surface electrograms during operation were also provided for a better understanding of LBB ablation. Two-dimensional speckle tracking imaging and aortic velocity time integral (aVTI) were acquired to validate the chronic stable HF model with LV asynchrony and CRT benefits. By coordinating ventricular activation and contraction, CRT uniformed the LV mechanical work and restored LV pump function, which was followed by reversal of LV dilation. Moreover, the histopathological study revealed a significant restoration of cardiomyocyte diameter and collagen volume fraction (CVF) after CRT performance, indicating a histologic and cellular reverse remodeling elicited by CRT. In this report, we described a feasible and valid method to develop a chronic asynchronous HF model, which was suitable for studying structural and biologic reverse remodeling following CRT.

Successful LBB Ablation:
Figure 2 represents a typical surface and intracardiac electrogram in the course of catheter ablation. The mean LBP-V measured is 18.8 &#177;2.8 ms, which was about 10 ms shorter than the baseline H-V interval (28.8 &#177;2.6 ms, p &#60;0.01). The QRS duration prolonged from 59.2 &#177;6.8 ms to 94.2 &#177;8.6 ms (p &#60;0.01) after LBB ablation. The loss of t...

Watch this Scientific Journal Video about Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing at JoVE.com

Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing

The establishment of a chronic asynchronous heart failure (HF) model by rapid pacing combined with left bundle branch ablation is presented. Two-dimensional speckle tracking imaging and aortic velocity time integral are applied to validate this stable HF model with left ventricular asynchrony and the benefits of cardiac resynchronization therapy.

It is now well recognized that heart failure (HF) patients with left bundle branch block (LBBB) derive substantial clinical benefits from cardiac ...

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