1. Diminished Left Ventricular Dyssynchrony and Impact of Resynchronization in Failing Hearts With Right Versus Left Bundle Branch Block J Am Coll Cardiol 2007;50:1484–90 Melissa J. Byrne, PhD, Robert H. Helm, MD, Samantapudi Daya, MD, Nael F. Osman, PhD, Henry R. Halperin, MD, MA, FAHA, Ronald D. Berger, MD, PhD, David A. Kass, MD, FAHA, Albert C. Lardo, PhD, FACC, FAHA Baltimore, MD

2. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Background Background: Cardiac resynchronization therapy (CRT) is effective for treating failing hearts with conduction delay and discoordinate contraction. Most data pertain to left (LBBB) versus right bundle branch (RBBB) delays. With RBBB, the lateral wall contracts early so biventricular (BiV) pre-excitation may not be needed. Furthermore, the magnitude of dyssynchrony and impact of CRT in RBBB remains largely unknown. Objectives: We compared mechanical dyssynchrony and impact of CRT in failing hearts with pure RBBB versus LBBB.

3. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Methods Dogs with tachypacing induced heart failure (HF) combined with right or left bundle branch radiofrequency ablation were studied. Basal dyssynchrony and effects of single and BiV CRT on left ventricular (LV) function were assessed by tagged magnetic resonance imaging (MRI) and pressure-volume catheter, respectively. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply.

4. J Am Coll Cardiol 2007;50:1484–90 Methods Strain derived form tagged-MRI was used to calculate the circumferential uniformity index (CURE, 0 → 1 is dyssynchronous → synchronous) and to quantify the degree of LV synchrony. Statistical analysis was performed by 1-way analysis of variance (ANOVA) to test for differences between percent change from baseline for RBBB-HF and LBBB- HF animals with respect to CURE, maximum derivative of LV pressure (dP/dtmax), standard deviation of time to peak strain, and ejection fraction (EF).

5. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Baseline Characteristics Normal *RBBB - HFLBBB - HFANOVA QRS (msec) 46±2.5110 ± 4.1 †113 ± 4.0 †< 0.0001 CURE 0.97±0.010.80 ± 0.03 ||0.58 ± 0.09 ‡0.002 +dP/dt max 2301±890.0928.0± 66.1 ‡981.7 ± 73.9 §0.005 LV EF (%) 51.8±2.832.6 ± 7.5 ‡25.1 ± 3.8 §0.005 RV EF (%) 49.1±3.215.5 ± 1.6 †25.1 ± 3.2 †<0.0001 * previously reported control animals, † p < 0.0001 as compared with baseline, ‡ p < 0.005 as compared with baseline, § p < 0.048 as compared with baseline, || p = 0.044 as compared with LBBB - HF

6. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Strain Plots Comparing LV Dyssynchrony in Failing Hearts with RBBB and LBBB Strain Septal Posterior Lateral Anterior LBBB RBBB Septal Posterior Lateral Anterior Base Apex Base Apex 307 msec 46 msec Time after onset of contraction Septal Posterior Lateral Anterior

7. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Comparison of Region Strain in Failing Hearts with RBBB and LBBB * p < 0.001 as compared with septum; † p < 0.030 as compared with septum; ‡ p < 0.001 as compared with lateral wall; § p < 0.535 as compared with lateral wall. Time to peak strain (% of r-r interval) Sept. Post. Lat. Ant. LBBB-HF Standard Deviation of Time to peak strain (msec) p < 0.001 RBBB LBBB RBBB-HF 0 10 20 30 40 * * † Time to peak strain (% of r-r interval) * § ‡ §

8. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Comparison of Global Strain in Failing Hearts with RBBB and LBBB Mechanical activation maps derived using tagged-MRI. CURE ranges from 0→1 with 0 being most dyssynchronous and 1 being perfectly synchronous. Early Activated Late Activated Septal LateralSeptal Lateral CURE = 0.53 LBBB-HF CURE = 0.79 RBBB-HF

9. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Functional and Mechanical Response to Various Modes of CRT in Failing Hearts with RBBB * p < 0.007 compared with baseline; † p < 0.047 compared with baseline; ‡ p < 0.005 compared with LV-only pacing; § p < 0.015 compared with LV-only pacing. ‡ * -20 -10 0 10 20 30 CURE dP/dtmax Stroke Work Tau * Percent change from baseline † † † § ‡ ‡ * ‡ † Bi-V pacing LV-only pacing RV single site pacing

10. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 Subgroup Analysis Comparing Modes of CRT in RBBB-HF All values expressed as a percent change from baseline ± standard error of mean; † p < 0.042 as compared with baseline; ‡ p < 0.015 as compared with baseline; § p < 0.003 as compared with baseline; p < 0.034 as compared with RV septal pacing. RV Single Site PacingBiV Pacing RV septal RV freewall RV apical ANOVA LV+RV septal LV+RV freewall LV+RV apical ANOVA CURE11.0 ± 4.9 †4.5 ± 2.010.6 ± 4.70.8263.3 ± 1.59.7 ± 4.01.2 ± 0.50.678 dP/dt max 4.3 ± 1.95.4 ± 2.7 †3.0 ± 1.20.6515.1 ± 2.3 ‡5.1 ± 2.1 §4.8 ± 2.0 †0.905 SW 4.6 ± 2.14.0 ± 1.8-4.4 ± 1.80.0464.5 ± 2.09.3 ± 3.7 §0.1 ± 0.020.121 Tau 8.8 ± 3.9 †-0.2 ± 0.1-3.0 ± 1.40.1196.3 ± 2.812.8 ± 5.726.3 ± 11.70.169 RVEF 39.8 ± 17.890.1 ± 40.256.5 ± 25.2 ║0.02950.3 ± 22.561.1 ± 27.3 †54.9 ± 24.50.151

11. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1484–90 The magnitude of cardiac dyssynchrony in failing hearts with RBBB is considerably less than those with LBBB Though CRT improves dyssynchrony in failing hearts with RBBB, this effect is smaller than observed in hearts with LBBB In RBBB conduction delay, there is little to no advantage of BiV over RV single-site pacing to improve LV synchrony and both modes can enhance RV ejection fraction.Conclusions