Baseline clinical characteristics
From the final 66 patients, 35 patient (53%) had HBP implantation, while the other 31 (47%) patients had LBBAP implantation (Table 1). There was no significant age difference between both groups, and only 2 patient (5.7%) from HBP group underwent the procedure as a resynchronization therapy for heart failure. More than half of the patients from each group had dual chamber pacemaker. A considerable number of patients from LBBAP group had a history of previous pacemaker implantation (67.7%, p=0.197). Both groups had a wide QRS complex duration at baseline (124.63 ± 33.36 ms in HBP vs. 121.94 ± 32.91 ms in LBBAP group, p=0.981).
Table 1. Baseline Characteristics
Baseline
|
HBP
n = 35
|
LBBAP
n = 31
|
p Value
|
Age (years)
|
57.00 ± 16.15
|
57.68 ± 17.45
|
0.404
|
Gender
|
0.047*
|
Male
|
21 (60.0%)
|
11 (35.5%)
|
|
Female
|
14 (40.0%)
|
20 (64.5%)
|
CSP indication
|
0.177
|
Symptomatic Bradycardia
Resynchronization therapy
|
33 (94.3%)
2 (5.7%)
|
31 (100%)
0 (0%)
|
|
Pacemaker chambers
|
0.258
|
Single
|
9 (25.7%)
|
12 (38.7%)
|
|
Dual
|
26 (74.3%)
|
19 (61.3%)
|
History of pacemaker
|
0.197
|
No history of pacemaker
|
19 (54.3%)
|
10 (32.3%)
|
|
Temporary Pacemaker
|
12 (34.3%)
|
16 (51.6%)
|
Permanent Pacemaker
|
4 (11.4%)
|
5 (16.1%)
|
QRS duration (ms)
|
124.63 ± 33.36
|
121.94 ± 32.91
|
0.981
|
CSP = conduction system pacing
*P value <0.05
Baseline echocardiography parameters
From the baseline data of echocardiography parameters measured before PPM implantation, majority of patients in either HBP or LBBAP group had a normal LA and LV size, with a higher mean of LVEF in HBP group (51.17 ± 13.87% vs. 45.58 ± 11.08%, p=0.078) (Table 2). Most patients had normal or mild degree of mitral regurgitation or tricuspid valves regurgitation along with low or intermediate probability of pulmonary hypertension.
QRS duration and echocardiographic parameters after pacemaker implantation
After pacemaker implantation, HBP group had a shorter mean QRS duration compared to LBBAP group (113.40 ± 17.06 ms vs 120.81 ± 12.12 ms, p=0.029) (Figure 2).
Table 2. Baseline Echocardiographic Parameters
Echocardiographic parameters
|
HBP
n = 35
|
LBBAP
n = 31
|
p Value
|
LA Size (mm)
|
38.86 ± 8.44
|
36.13 ± 10.07
|
0.236
|
LAVI (ml/m2)
|
41.63 ± 34.32
|
34.29 ± 20.27
|
0.302
|
LVEDd (mm)
|
48.54 ± 7.43
|
49.55 ± 9.09
|
0.623
|
LV dilatation
|
0.691
|
Yes
|
13 (37.1%)
|
13 (41.9%)
|
No
|
22 (62.9%)
|
18 (58.1%)
|
LA dilatation
|
0.805
|
Yes
|
17 (48.6%)
|
16 (51.6%)
|
No
|
18 (51.4%)
|
15 (48.4%)
|
LVEF (%)
|
51.17 ± 13.87
|
45.58 ± 11.08
|
0.078
|
EF
|
0.026*
|
Preserved EF
|
22 (62.9%)
|
11 (35.5%)
|
Reduced EF
|
13 (37.1%)
|
20 (64.5%)
|
Mitral regurgitation
|
0.739
|
No
|
23 (65.7%)
|
24 (77.4%)
|
Mild
|
9 (25.7%)
|
5 (16.1%)
|
Moderate
|
2 (5.7%)
|
1 (3.2%)
|
Severe
|
1 (2.9%)
|
1 (3.2%)
|
Tricuspid regurgitation
|
0.803
|
No
|
22 (62.9%)
|
21 (67.7%)
|
Mild
|
8 (22.9%)
|
7 (22.6%)
|
Moderate
|
4 (11.4%)
|
3 (9.7%)
|
Severe
|
1 (2.9%)
|
0 (0%)
|
Probability of pulmonary hypertension
|
0.962
|
Low
|
23 (65.7%)
|
20 (64.5%)
|
Intermediate
|
7 (20.0%)
|
7 (22.6%)
|
High
|
5 (14.3%)
|
4 (12.9%)
|
EF = ejection fraction; LAVI = left atrial volume index; LA = left atrium; LV = left ventricle; LVEDd = left ventricular end diastolic dimension; LVEF = left ventricular ejection fraction
Compared with baseline, the mean LVEDD in both groups were similar, while the mean of LAVI in HBP group was reduced (41.63 ± 34.32 ml/m2 to 37.11 ± 24.82 ml/m2, p=0.815) with a relatively similar value in LBBAP group (Table 3).
Table 3. QRS Duration and Echocardiographic Parameters after Pacemaker Implantation
Echocardiographic parameters
|
HBP
n = 35
|
LBBAP
n = 31
|
p Value
|
Mean follow up (months)
|
6.33
|
4.81
|
0.316
|
QRS duration (ms)
|
113.40 ± 17.06
|
120.81 ± 12.12
|
0.029*
|
Pacing selectivity
Selective
Nonselective
|
18 (51.4%)
17 (48.6%)
|
25 (80.6%)
6 (19.4%)
|
0.013*
|
LA Size (mm)
|
36.20 ± 7.02
|
37.29 ± 8.62
|
0.574
|
LAVI (ml/m2)
|
37.11 ± 24.82
|
35.87 ± 16.71
|
0.815
|
LVEDD (mm)
|
47.31 ± 7.86
|
47.55 ± 7.52
|
0.902
|
LV dilatation
|
0.579
|
Yes
|
6 (17.1%)
|
7 (22.6%)
|
|
No
|
29 (82.9%)
|
24 (77.4%)
|
LA dilatation
|
0.782
|
Yes
|
17 (48.6%)
|
14 (45.2%)
|
|
No
|
18 (51.4%)
|
17 (54.8%)
|
LVEF
|
53.93 ± 11.45
|
53.11 ± 11.67
|
0.536
|
Ejection fraction
|
0.558
|
Preserved EF
|
26 (74.3%)
|
21 (67.7%)
|
|
Reduced EF
|
9 (25.7%)
|
10 (32.3%)
|
Mitral regurgitation
|
0.472
|
No
|
27 (77.1%)
|
21 (67.7%)
|
|
Mild
|
7 (20.0%)
|
7 (22.6%)
|
Moderate
|
0 (0.0%)
|
2 (6.5%)
|
Severe
|
1 (2.9%)
|
1 (3.2%)
|
Tricuspid regurgitation
|
0.406
|
No
|
28 (80.0%)
|
21 (67.7%)
|
|
Mild
|
5 (14.3%)
|
9 (29.0%)
|
Moderate
|
1 (2.9%)
|
1 (3.2%)
|
Severe
|
1 (2.9%)
|
0 (0%)
|
Probability of pulmonary hypertension
|
0.248
|
Low
|
30 (85.7%)
|
29 (93.5%)
|
|
Intermediate
|
3 (8.6%)
|
0 (0%)
|
High
|
2 (5.7%)
|
2 (6.5%)
|
EF = ejection fraction; LAVI = left atrial volume index; LA = left atrium; LV = left ventricle; LVEDd = left ventricular end diastolic dimension; LVEF = left ventricular ejection fraction
Compared with baseline, the mean LVEF was increased in LBBAP group (45.58 ± 11.08% to 53.11% ± 11.67%, p = 0.536), while in the HBP group the mean LVEF was remain preserved (51.17 ± 13.87% to 53.93 ± 11.45%) (Figure 3).
Patients with left ventricular dysfunction
Subgroup analysis was performed for patient with LV dysfunction. Majority of patients receiving HBP had no history of previous pacemaker implantation (69.2%), while only 25% patients in LBBAP group had neither history of temporary nor permanent pacemaker implantation, respectively. There was a reduction in QRS duration in the HBP group, while in the LBBAP group the QRS duration was relatively similar. At the end of follow up, 38.5% of patients in HBP group and 50% in LBBAP group had LVEF improvement (p=0.515).
Table 4. Subgroup Analysis on Patient with Left Ventricular Dysfunction
|
Pre PPM
|
p Value
|
Post PPM
|
p Value
|
HBP
n = 13
|
LBBAP
n = 20
|
HBP
n = 13
|
LBBAP
n = 20
|
Mean follow up (months)
|
|
5.00 ± 4.45
|
6.50 ± 4.16
|
0.332
|
Age
|
64.08 ± 8.98
|
63.35 ± 11.90
|
0.852
|
|
Chambers pacing
|
|
|
0.963
|
|
Single
Dual
|
4 (30.8%)
9 (69.2%)
|
6 (30.0%)
14 (70.0%)
|
|
|
Pacing selectivity
Selective
Nonselective
|
7 (53.8%)
6 (46.2%)
|
16 (80.0%)
4 (20.0%)
|
0.110
|
|
Previous pacemaker
|
No
|
9 (69.2%)
|
5 (25.0%)
|
0.053
|
|
TPM
|
4 (30.8%)
|
11 (55.0%)
|
PPM
|
0 (0%)
|
4 (20.0%)
|
QRS duration
|
128.15 ± 41.04
|
129.05 ± 33.84
|
0.946
|
113.23 ± 19.50
|
123.35 ± 11.68
|
0.071
|
LVEF
|
35.31 ± 7.86
|
38.75 ± 6.95
|
0.197
|
44.54 ± 11.28
|
51.35 ± 13.14
|
0.135
|
LA dilatation
|
No
|
10 (76.9%)
|
9 (45.0%)
|
0.070
|
12 (92.3%)
|
8 (40.0%)
|
0.003*
|
Yes
|
3 (23.1%)
|
11 (55.0%)
|
1 (7.7%)
|
12 (60.0%)
|
LV dilatation
|
No
|
3 (23.1%)
|
9 (45.0%)
|
0.201
|
8 (61.5%)
|
14 (70.0%)
|
0.614
|
Yes
|
10 (76.9%)
|
11 (55.0%)
|
5 (38.5%)
|
6 (30.0%)
|
LVEDD
|
52.46 ± 7.63
|
52.45 ± 7.61
|
0.997
|
49.92 ± 9.55
|
48.65 ± 7.94
|
0.681
|
Mitral regurgitation
|
No
|
6 (46.2%)
|
16 (80.0%)
|
0.130
|
8 (61.5%)
|
14 (70.0%)
|
0.547
|
Mild
|
5 (38.5%)
|
3 (15.0%)
|
5 (38.5%)
|
5 (25.0%)
|
Moderate
|
2 (15.4%)
|
1 (5%)
|
0 (0%)
|
1 (5.0%)
|
Severe
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
Tricuspid regurgitation
|
No
|
5 (38.5%)
|
16 (80.0%)
|
0.081
|
9 (69.2%)
|
13 (65.0%)
|
0.503
|
Mild
|
4 (30.8%)
|
3 (15.0%)
|
2 (15.4%)
|
6 (30.0%)
|
Moderate
|
3 (23.1%)
|
1 (5.0%)
|
1 (7.7%)
|
1 (5.0%)
|
Severe
|
1 (7.7%)
|
0 (0%)
|
1 (7.7%)
|
0 (0%)
|
Probability of PH
|
Low
|
4 (30.8%)
|
14 (70.0%)
|
0.046*
|
10 (76.9%)
|
18 (90.0%)
|
0.194
|
Intermediate
|
5 (38.5%)
|
5 (25.0%)
|
2 (15.4%)
|
0 (0%)
|
High
|
4 (30.8%)
|
1 (5.0%)
|
1 (7.7%)
|
2 (10.0%)
|
Reduced EF
|
Yes
|
|
8 (61.5%)
|
10 (50.0%)
|
0.515
|
Improved LVEF
|
Yes
|
|
5 (38.5%)
|
10 (50.0%)
|
0.515
|
EF = ejection fraction; LAVI = left atrial volume index; LA = left atrium; LV = left ventricle; LVEDd = left ventricular end diastolic dimension; LVEF = left ventricular ejection fraction; PH = pulmonary hypertension PPM = permanent pacemaker; TPM = temporary pacemaker;
*P value <0.05
Majority of patients in the HBP group receive no or less than 50% of recommended dose of the guideline medical therapies, while in the LBBAP group, more patients received adequate dose of renin-angiotensin-aldosterone system (RAAS) blockers (ACE-I, ARB, or ARNI) and MRA.
Table 5. Guideline Medical Therapy in Patients with Left Ventricular Dysfunction
Medication
|
HBP
n = 13
|
LBBAP
n = 20
|
p Value
|
No ACE-I/ARB
|
7 (53.8%)
|
7 (35.0%)
|
0.035*
|
ACE-I/ARB <50% target dose
|
5 (38.5%)
|
3 (15.0%)
|
ACE-I/ARB ≥50% target dose
|
1 (7.7%)
|
10 (50.0%)
|
No ARNI
|
11 (84.6%)
|
18 (90.0%)
|
0.898
|
ARNI <50% target dose
|
1 (7.7%)
|
1 (5.0%)
|
ARNI ≥50% target dose
|
1 (7.7%)
|
1 (5.0%)
|
No beta blocker
|
7 (53.8%)
|
7 (35.0%)
|
0.412
|
Beta blocker <50% target dose
|
2 (15.4%)
|
7 (35.0%)
|
Beta blocker ≥50% target dose
|
4 (30.8%)
|
6 (30.0%)
|
No MRA
|
8 (61.5%)
|
7 (35.0%)
|
0.275
|
MRA <50% target dose
|
0 (0%)
|
1 (5%)
|
MRA ≥50% target dose
|
5 (38.5%)
|
12 (60.0%)
|
SGLT2 inhibitor (no)
|
11 (84.6%)
|
19 (95.0%)
|
0.311
|
SGLT2 inhibitor (yes)
|
2 (15.4%)
|
1 (5.0%)
|
ACE-I = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor neprilysin inhibitor; MRA = mineralocorticoid receptor antagonist