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

The overall goal of this experiment is to describe a feasible and valid method to establish a chronic asynchronous heart failure model for studying benefits of cardiac resynchronization therapy. Rapid pacing together with left bundle branch ablation helps to establish a stable heart failure model for studying CRT performance, including echocardiographic parameters, molecular and biologic modifications. The key point of this technique is the left bundle branch ablation, where you prevent the cardiac function recovery on this continuation of rapid pacing.

We first had the idea for this method when we found a significant recovery from heart failure once the rapid pacing was terminated. The epicardial left ventricle lead implantation is performed by mister Yao Ruiming, technician from our laboratory who is expert at this procedure. After preparing the canine for the LV pacing electrode implantation, begin with a transverse incision from the left parasternal line at the fourth intercostal space in a right lateral decubitus position.

After a blunt dissection of the thoracic muscle, open the left pleural cavity at the fourth intercostal space using sharp dissection. Use a rib retractor to hold open the intercostal space. Next, carefully incise the lateral pericardium and open it using stay sutures to fully expose the LV lateral wall.

Then, using a 4-0 suture, secure the LV pacing electrode to the myocardium in one stich. Now, measure the electrode lead parameters. Check that the pacing threshold and other parameters are correct, and then proceed by removing the stay sutures and closing the pericardium with two stitches.

Now, use two pericostal sutures to approximate the fourth and fifth ribs using size 0 suture and close the intercostal fascia muscularis with five stitches of 2-0/T sutures. Be sure to inflate the lungs adequately before the last suture. Then, put the muscle layers back in place.

Next, build a subcutaneous tunnel above the deep fascia from precordial area to the left cervix. Then, pull the terminal pin at the lead through the tunnel and suture the lead around an insulation sleeve to the fascia. Embed the lead locally.

To complete the surgery, provide penicillin and close the two incisions. Implant the RA and RV pacing electrodes two weeks after the LV electrode implantation, by which time the animal should have recovered from the thoracotomy. Carry out the operation in a cardiac catheterization surgery room equipped with the fluoroscopy apparatus.

After preparing the animal for surgery, begin with a small vertical incision close to the preceding wound on the left side of the cervical area. Then, using blunt dissection, separate the fascia to expose the left external jugular vein. Be sure to carefully separate the vein from the connective tissues.

With the aid of stay sutures, cut a small hole on the vein using iris scissors. Then, using a vein pick, insert a passive J-shaped RA lead and active RV lead into the left external jugular vein. Now, under fluoroscopy, advance the RV lead to the lower right atrium or inferior vena cava.

Then withdraw the straight stylet from the RV lead and insert a J-shaped stylet. With the help of the J-shaped stylet, introduce the lead across the tricuspid valve and into the outflow tract. Then, slowly withdraw both the lead and the stylet, allowing the lead tip to prolapse toward the RV apex.

Now, replace the curved stylet with a straight one and advance the lead towards the apex. Then, slowly withdraw the stylet a little while keeping the RA lead directed toward the high anterior atrium. Slowly withdraw the straight stylet.

Then, retract the tip of the J-shaped lead into the appendage. A characteristic to-and-fro motion of the electrode with atrial activity may be observed. After obtaining satisfactory lead parameters and checking the stability of both leads, tighten the suture proximal to the venotomy.

Then, tie down both leads to the underlying deep fascia around the suture sleeves. Then, check the positioning of the leads under fluoroscopy before proceeding with the pulse generator implantation. For sham surgeries, skip this procedure.

To implant the pulse generator, first dissect bluntly with the aid of a curved clamp to make a pocket for the pulse generator near the venous entry just above the fascia layer and below the subcutaneous fat. Next, clean and dry the lead pins. Cover the terminal pin at the atrial lead with an insulating sleeve, then suture the lead to the floor of the pocket.

Then, insert the ventricular lead into a pacemaker pulse generator and tighten it with a distal connector pin past the set screws of the generator. Now, place the generator into the pocket and quell the redundant bleeds beneath the device. Then, secure the generator to the fascia using another suture to the tie-down hole.

Now, perform a fluoroscopic examination of the entire system and check for homeostasis. To complete the surgery, sprinkle 200, 000 units of penicillin into the pocket and suture the superficial fascia layer closed using 2-0/T sutures. Then, approximate the skin edges with both sutures.

Carry out the catheter ablation under the guidance of fluoroscopy. Have a multi-general electrophysiological recorder prepared for simultaneous surface and intracardiac electrogram recording. Shave the hair off the chest, back and right inguinal region.

Keep the animal in a supine position. The first surgical steps are to insert sheets into the femoral vein and femoral artery for catheter placement. This is described in detail in the text protocol.

To proceed, advance a six French steerable quadripolar catheter into the femoral vein and connect the end of the catheter to the recorder. Then, pass the catheter into the right atrium and across the tricuspid valve until it is clearly in the right ventricle. Using a right anterior oblique 30-degree view, withdraw the catheter across the tricuspid orifice until the atrial potential appears and it increases in amplitude.

When the atrial and ventricular potentials are approximately equal in size, a biphasic or triphasic deflection will appear between them. This represents the right side of His bundle potential. Now, introduce a number seven French formula meter tip steerable ablation catheter into the femoral artery to map the left bundle branch potential.

Then, connect the ablation catheter to the RF generator and the multichannel electrophysiological recorder. Using a right anterior oblique 30-degree view, pass the arterial catheter retrogradely across the aortic valve and advance it into the left ventricle. There, deflect the catheter tip toward the intraventricular septum where it should remain in contact with the septum.

Now, using a left anterior oblique 45-degree view, slowly withdraw the catheter along the septum until the left side of His bundle potential is recorded between the atrial and ventricular electrogram just below the aortic valve. Then, slightly advance the catheter along the septum and manipulate the tip to identify a discrete left bundle potential, which is recorded beneath the aortic valve. It is usually located one to one and a half centimeters inferior to left side of His bundle recording site.

When the potential to ventricular electrogram interval is 10 milliseconds or so shorter than the HV interval and the AV electrogram ratio of less than one to 10, then the left bundle potential has been identified. Next, perform the ablation with the RF generator unless it is a sham surgery. Deliver 500 kilohertz of unmodulated sine wave energy at 30 to 40 watts to achieve a target temperature of 60 degrees Celsius at the electrode-tissue interface.

When a typical LBBB QRS morphology appears on the surface electrogram, continue the energy application. Then, observe the surface electrogram for a stabilization period of 30 minutes. To complete the procedure, remove both catheters.

Then, remove the sheets and tighten the suture knots rapidly to prevent hemorrhaging. Lastly, provide penicillin and close the incisions. The typical surface and intracardiac electrogram in the course of catheter ablation shows the mean LVPV to be about ten milliseconds shorter than the baseline HV interval, and after the LBB ablation, the QRS duration is prolonged.

Baseline echocardiographic parameters showed no difference between the groups. After the experimental intervention, the heart failure group had an obvious deterioration in cardiac function from which no measured parameter improved over eight weeks of observation. However, with eight weeks of CRT, the left ventricle and diastolic volume returned to normal, as did the left ventricle and systolic volume.

CRT also returned the lost left ventricle ejection fraction. Longitudinal strain curves of six segments from each plain made by speckle tracking analysis showed a measurable increase in the dispersion of the time to peak longitudinal strain in the heart failure group. By contrast, the therapy corrected the asynchrony.

This was observable in the four-chamber view, the two-chamber view and in the long axis view. Furthermore, the heart failure animals presented a significantly lower aortic velocity time integral than the shams. This metric was significantly increased by the CRT.

Histology revealed a remarkable decrease in cardiomyocyte diameter and a significant increase in the collagen volume fraction in the heart failure group. However, eight weeks of CRT provided a significant restoration of these metrics, indicating that the therapy invoked remodeling of the tissue. After watching this video, you should have got a good understanding of how to establish a chronic heart failure with isolated LBBB for studying CRT benefits.

Following the left bundle branch ablation, apart from rapid pacing, we can still use some other method to induce heart failure such as a coronary ligation to induce an ischemic heart failure. This well established technique was paved the way for researches to study cardiovascular diseases in large animal models of heart failure.