Methods

We identified a total of 12 consecutive patients with underlying conduction abnormalities consistent with RBBB who were nonresponders on the basis of clinical and/or remodeling criteria. RBBB was diagnosed by conventional electrocardiographic criteria, including a terminal positive deflection in lead V ₁ with QRS duration >120 ms. We performed matching with 12 consecutive patients with LBBB who were nonresponders to CRT, with matching according to patients’ gender, age, cause of heart failure (ischemic vs nonischemic), QRS duration, and ejection fraction.

All subjects had previously implanted biventricular pacemakers with ICD because of advanced heart failure refractive to medical therapy, systolic dysfunction (left ventricular [LV] ejection fraction ≤ 35%), and prolonged QRS duration (≥120 ms). LV leads were implanted using fluoroscopy. LV lead position was confirmed by chest x-ray. Patients with anteriorly placed LV leads were excluded from the study groups.

All patients underwent standard transthoracic echocardiography (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway) using an ultrasound machine with a 2.5-MHz probe and digital storage capacity. All data were analyzed off-line by a single observer blinded to patient factors and pacing status. Chamber dimensions were assessed using 2-dimensional or M-mode measurements on the basis of current guidelines. The LV ejection fraction was calculated using the modified Simpson’s method.

All patients had an attempted atrioventricular (AV) delay optimization performed using echocardiography. The optimal AV interval was determined using mitral inflow pulsed-wave Doppler. On the basis of several described techniques, an optimal AV interval was chosen on the basis of dissociation of the E and A waves, with prevention of A-wave truncation, and maximal QA (from onset of Q wave to end of A wave) duration. After optimization, if indicated, the CRT device was programmed to nonfunctional pacing mode (VVI, backup 40 beats/min) to facilitate intrinsic conduction. After ≥5 minutes, images were acquired for CRT off comparison. All patients in the present study were in sinus rhythm throughout the examination, with satisfactory intrinsic conduction.

Mechanical dyssynchrony was assessed in all patients off-line with CRT off. Interventricular dyssynchrony was determined as the difference between preejection intervals from QRS onset to the beginning of ventricular ejection at pulmonary and aortic valve flow using pulse-wave Doppler. This was considered significant if >40 ms. Intraventricular dyssynchrony was also assessed using the tissue Doppler–derived longitudinal velocity opposing wall delay method, which measured the interval between the onset of the QRS complex and the peak of the systolic myocardial velocity in opposing basal segments. An opposing wall delay ≥65 ms in the 4-segment model was considered consistent with significant intraventricular mechanical dyssynchrony.

LV torsion and longitudinal strain were assessed off-line using dedicated software (EchoPAC PC version BT06; GE Healthcare, Milwaukee, Wisconsin) with CRT on and off. All patients underwent imaging at frame rates >50 frame/s and 3 cardiac cycles. Speckle-tracking software was used to calculate LV rotation (degrees) from the apical and basal short-axis views. During end-systolic frames, the endocardial border was manually traced, and the region of interest was obtained, which included the entire myocardium. Using the apex as a focus, counterclockwise rotation is positive and clockwise rotation is negative. LV torsion (or twist) was calculated as the difference between apical and basal rotation. Peak untwisting velocity (degrees per second) was also measured.

Longitudinal strain analysis was performed off-line using speckle tracking in the apical 4- chamber view to obtain septal and lateral strain curves with CRT on and off. Sample points were placed along the endocardium at end-systolic frames. The software package automatically generated strain curves after constructing a region of interest along the entire length of the LV wall and tracking the individual speckles. The duration of systole was obtained and measured as the interval between the Q wave and the termination of systolic flow as determined by pulse-wave Doppler in the LV outflow tract. The time (i.e., horizontal) axes of the individual strain curves were then standardized according to the percentage of the total systolic duration. The impact of biventricular pacing was assessed by calculating standardized strain curve differences by subtracting CRT off from CRT on data on a patient-by-patient basis.

All data are expressed as mean ± SD or as numbers and percentages. Mean measurements were compared using paired t tests, with significance set at p <0.05. All statistical analyses were performed using JMP for Macintosh version 7.0 (SAS Institute Inc., Cary, North Carolina).

To assess the impact of biventricular pacing in patients with RBBB or LBBB, areas under individual strain curve differences were calculated. The areas corresponding to systole and diastole on the basis of time curves were assessed. A single-sample t test was used to assess if the curves were significantly different from zero at the time points that corresponded to 100% and 200% of systolic duration, and an unpaired t test was used to assess if the curves were significantly different between groups at the same points.

Results

Per design, patients in the 2 groups (i.e., LBBB and RBBB) were similar with regard to age, gender, ischemic cause of heart failure, the ejection fraction, 2-dimensional measurements, and volumes. Baseline characteristics of all patients are listed in Table 1 . Two patients in each group had mitral regurgitation that was believed to be at least moderate to severe (3+ or higher) on the basis of current guidelines. Each group was composed of 7 patients sent for assessment of nonresponse on the basis of clinical and/or persistently decreased ejection fraction, whereas 5 were sent for AV optimization alone. On the basis of volumetric criteria, each of these 5 patients in each group sent for AV optimization alone could be considered nonresponders as defined by a simple volumetric definition (failure of end-systolic volume to decrease by 15% 6 months after implantation). Mean time to assessment after implantation was similar in the 2 groups. There were no differences in QRS duration between the 2 groups (160 ms in the LBBB group vs 155 ms in the RBBB group, p = 0.67). Of all patients with RBBB, 83% (n = 10) had concurrent left anterior hemiblock (LAHB), with 8 of these patients also having PR intervals >200 ms and hence trifascicular block. All patients were in sinus rhythm during the examination. Patients in the 2 groups had similar wall motion index scores (LBBB 2.65 ± 0.29 vs RBBB 2.64 ± 0.18, p = 0.84).When using a simple echocardiographic definition of scar (segments with ≤5-mm end-diastolic thickness with increased acoustic reflectance), the 2 groups had similar rates of left anterior descending coronary artery territory scar (33% in each group). Compared with the LBBB group, the RBBB group had a trend toward higher rates of right coronary artery (inferior wall) scar (50% vs 16%, p = 0.19) and less circumflex (posterior wall) scar (17% vs 33%, p = 0.64).

Table 1

Baseline Characteristics of Study Patients

Patient	Age (years)	Sex	Ischemic etiology	QRS morphology	QRS Duration (ms)	ACE/ ARB	Beta Blocker	NYHA class	Systolic BP	Diastolic BP	HR (bpm)	BNP (pg/mL)	Time (days) from implant	EF (%)	RVSP (mm Hg)	LVEDD (cm)	LVESD (cm)	LVEDV (mL)	LVESV (mL)
1	71	M	+	LBBB	156	+	+	2	123	55	73	345	652	28	43	6.2	5.2	242	174
2	70	M	+	LBBB	158	+	+	3	104	50	70	741	111	28	41	5.1	4.2	146	104
3	78	M	+	LBBB	172	+	+	3	113	55	60	690	94	32	27	6	5	206	140
4	61	F	0	LBBB	128	+	+	3	118	70	79	541	247	19	38	6.5	5.8	235	190
5	64	F	+	LBBB	130	0	+	3	109	65	64	602	157	20	60	6.6	6.1	284	227
6	59	M	+	LBBB	130	+	+	3	122	80	84	980	102	12	52	8.5	7.6	429	377
7	49	F	0	LBBB	142	+	+	3	140	90	91	317	344	20	35	6.1	5.1	187	150
8	67	M	0	LBBB	156	+	+	2	138	74	75	381	393	15	50	9.4	4.5	545	463
9	48	M	0	LBBB	230	+	+	3	150	94	95	590	600	10	39	9.2	8.9	508	457
10	65	F	0	LBBB	148	0	+	4	100	50	80	400	375	17	33	7.7	6.9	388	322
11	67	M	+	LBBB	150	+	+	2	135	68	72	232	502	20	40	6.7	6.1	260	208
12	66	M	+	LBBB	218	0	+	4	122	79	101	554	1354	11	35	6.4	5.5	237	211
13	65	M	+	RBBB	162	0	+	4	101	62	70	1050	132	23	27	6.6	5.7	327	251
14	65	M	+	RBBB	156	0	0	3	88	58	60	615	719	8	40	7.8	7	363	335
15	66	M	0	RBBB	166	+	+	3	88	49	90	2000	88	10	32	7.4	6.8	270	243
16	69	M	+	RBBB	192	0	0	3	108	55	65	491	96	14	40	5.6	4.8	244	204
17	54	M	+	RBBB	156	+	+	2	114	74	80	212	94	20	61	7.6	5.5	325	260
18	63	F	0	RBBB	140	+	+	3	133	74	63	805	498	12	50	6.7	6.3	375	333
19	66	M	+	RBBB	122	+	+	2	113	70	92	111	102	21	35	4.9	3.9	172	135
20	63	F	0	RBBB	150	+	+	3	108	62	75	65	110	21	48	4.7	4.2	104	83
21	65	M	+	RBBB	208	+	+	2	91	52	74	82	1575	20	32	8.1	7.3	352	280
22	66	F	0	RBBB	154	+	+	3	140	70	90	495	421	13	48	6.2	6	317	275
23	83	M	+	RBBB	120	+	+	2	114	65	66	902	1204	27	67	6.5	5.9	171	125
24	56	F	0	RBBB	131	+	+	3	110	55	71	70	374	11	38	7.8	7.6	375	335

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