1. Dr Eric Prystowsky Director Clinical Electrophysiology Laboratory St Vincent Hospital, Indianapolis Dr Leslie Saxon Chief, Electrophysiology Laboratory and Implantable Device Services University of California in San Francisco San Francisco, CA Dr Angelo Auricchio Director, Cardiac Catheterization Laboratory University of Magdeburg Magdeburg, Germany The EP show: biventricular pacing in CHF

2. While only 5-10% of advanced heart failure patients have traditional indications for bradycardia pacemakers, many of them have conduction disease – prolonged PR intervals or bundle branch blocks. In early, non-randomized trials, programming the AV delay to about 100 ms in standard RA and RV pacemakers in decompensated class IV heart failure patients resulted in dramatic improvements in pump function. In controlled clinical trials, no universal right-sided delay was found to improve pump function. Pacing in heart failure

3. A subset of patients with marked prolongation of their PR interval and mitral regurgitation may benefit from an ultra-short AV delay in the range of 100 ms. It was also thought that the 30% of patients with dilated heart failure who have a left bundle branch block might benefit from pre-excitation, reducing the delay in left sided activation contraction. Current studies in biventricular stimulation are now ongoing. Improving left- and right-sided delays

4. In an original substudy, patients with class III and IV heart were implanted with ventricular resynchronizers (VRs). They were treated for 1- month with pacing, 1-month with the VR turned off (without the patient’s knowledge), and a further 1-month with stimulation. Investigators measured heart rate, heart rate variability, and oxygen consumption. A second study looked at left ventricular pacing alone compared to biventricular pacing. PATH-CHF Pacing therapies for congestive heart failure

5. Measurement of acute hemodynamic responses revealed 2 different patient populations with regard to the effect on the QRS complex. Patients with a wide QRS complex, wider than 150 ms, all behave as responders. Other patients may not respond acutely to any shortening of the AV delay, and may even demonstrate substantial hemodynamic worsening. PATH-CHF Pacing therapies for congestive heart failure

6. A lead may be passed through the coronary sinus and into the venous system, obviating the need for screw-in epicardial lead implants. Approximately 5-10% of patients have some anatomical aberrancy and cannot be implanted using the transvenous approach. The ability to lodge the lead in the terminal vessels to get adequate LV pacing down far enough off the AV groove is also an issue. This technology still needs refinement so that these leads can be implanted widely and safely. Biventricular pacing Transvenous approach to epicardial pacing

7. To date, the patients who improve the most have the widest QRS intervals and more advanced heart failure. In these patients, improvements in VO 2 and walking distance up to 20-25% have been noted. Early echo data shows that chronic pacing for as short as 3 months prevents the progressive remodeling of the ventricle. Insufficient data currently exist regarding the effects of pacing in right bundle branch block. Pacing as therapy for CHF

8. Pacing as preventive therapy for CHF “I guess the question Leslie is throwing on the table, and I've heard it from others, and I think it's intriguing…if you take somebody who has class II heart failure with a left bundle, or left IVCD, and prophylactically pace them, will you prevent the development of class III failure?” Dr Eric Prystowsky Director Clinical Electrophysiology Laboratory St Vincent Hospital, Indianapolis

9. The COMPANION trial looks at mortality and hospitalization in CHF patients using biventricular stimulation alone, or biventricular therapy coupled with an ICD, compared to standard drug therapy. The MUSTIC trial (Multisite Stimulation in Cardiomyopathy) randomized 58 heart failure patients into 2 study arms using a cross-over, single-blinded design. The first arm started with BVP, the second with no BVP - after 3 months the pacing modes were switched. Additional randomized trials in biventricular pacing

10. MUSTIC trial results (i) BVP vs no BVPPercentage change p value Distance walked in 6-minute period * + 23%0.0001 Peak VO 2 (mL/min/kg) † + 8%0.0158 Quality of life † + 30%0.0002 Overall results of BVP vs no BVP BVP biventricular pacing * primary endpoint † secondary endpoint

11. The MUSTIC trial had a 5% mortality rate during the 6-month crossover period. 2 deaths were classified as sudden death: 1 occurred after 26 days in the BVP mode, 1 occurred after switching the pacemaker from inactive to active mode. The third death was due to heart failure decompensation. No data have yet shown that biventricular pacing promotes arrhythmic death. MUSTIC trial results (ii)

12. The PACMAN trial is a randomized trial with 2 arms, comparing biventricular stimulation versus no stimulation over time. Therapy is maximized for ACE inhibitors, beta-blockers and diuretics. Endpoints include improvement in exercise capacity, oxygenation and changes in total comorbidities. Follow-up will be at least 1 year per patient. PACMAN trial