Septal flash (SF), a marker of left ventricular (LV) dyssynchrony in the presence of a left bundle branch block (LBBB), has been shown to predict improved ventricular function and outcome when corrected with cardiac resynchronization therapy. We hypothesized that a SF is present in patients receiving right ventricular (RV) pacing and its presence and extent could predict the development of LV dysfunction and remodelling.
Seventy-four consecutive patients receiving conventional RV pacing (>6 months, >85% paced) were studied with two-dimensional (2D) echocardiography. Indications for pacing were sinus-node dysfunction and atrioventricular conduction disorders. The presence of a SF was determined on stepwise advanced 2D echocardiographic views and confirmed using greyscale M-mode. Septal flash excursion was quantified by the amplitude of the early inward motion, measured from QRS onset to maximal inward motion. Fifty-seven (of 74; 77%) patients receiving RV pacing had a detectable SF. Patients with a SF had lower LV ejection fraction (EF) (52 ± 10 vs. 60 ± 4%, P < 0.001) and greater indexed end-systolic volume (33 ± 16 vs. 23 ± 5 mL/m2, P < 0.001). Receiver operating characteristic analysis demonstrated that a SF of 3.5 mm was the optimal cut-off value (area under the curve = 0.95) to identify reduced LV function (EF < 50%) with a sensitivity of 91% and a specificity of 90%.
A SF was present in a majority of patients receiving conventional RV pacing and its magnitude was related to LV dysfunction and adverse remodelling. Given the similarities observed in LBBB and pacemaker-induced dyssynchrony, SF magnitude might be a predictor for the development of LV dysfunction and adverse remodelling in patients receiving conventional RV pacing.
Septal flash (SF), a marker of left ventricular (LV) dyssynchrony in the presence of a left bundle branch block, has been shown to predict improved ventricular function and outcome when corrected with cardiac resynchronization therapy.
Increasing amount of data has shown that conventional right ventricular (RV) apical pacing may have unfavourable effects on cardiac structure and LV function, and may lead to heart failure and increased mortality.
We demonstrated a SF in a majority of patients receiving conventional RV apical pacing and its magnitude was related to worse LV function and adverse remodelling.
Given the similarities observed in left bundle branch block and pacemaker-induced dyssynchrony, SF magnitude might be a predictor for the development of LV dysfunction and adverse remodelling in patients receiving conventional RV pacing.
Introduction
For patients with sinus-node dysfunction and advanced atrioventricular (AV) conduction disorders, cardiac pacing is the only effective treatment. In cardiac pacing, the right ventricular (RV) apex is typically the place where the endocardial pacing lead is positioned due to the ease of site accessibility and lead stability. Generally, RV apical pacing is effective and well tolerated. However, increasing amount of data has shown that conventional RV apical pacing may have unfavourable effects on cardiac structure and left ventricular (LV) function, and may lead to heart failure and increased mortality.1,2 Upgrade to cardiac resynchronization therapy (CRT) may to some extent reverse the unfavourable effects of RV apical pacing. Furthermore, it has even been proposed that selected patients with indication for conventional pacemaker treatment should receive CRT as primary treatment to prevent the unfavourable effects of RV pacing.2–5 However, CRT implantation is expensive and it is difficult to predict which patients will develop dyssynchrony and heart failure due to RV pacing and which patients will respond to CRT. It has been shown in earlier studies that a septal flash (SF),6 defined as early fast inward/outward motion of the interventricular septum during isovolumic contraction and within the QRS complex, is a hallmark of the mechanical consequences of a left bundle branch block (LBBB) and serves as a correctable mechanism that could predict response to CRT as well as outcome.7–10 However, it has not been investigated whether a SF is present in patients with RV pacing, whether it can be used as a marker of LV mechanical dyssynchrony, and whether it is a mechanistic event that relates to LV dysfunction.
We hypothesized that a SF, a hallmark of LV intra-ventricular dyssynchrony, is induced by conventional RV pacing and its extent is associated with LV dysfunction in permanently paced patients.
Methods
Seventy-four consecutive patients coming to our outpatient pacemaker clinic for follow-up, who had conventional RV pacing, during at least 6 months and with at least 85% pacing, were included in the study and were clinically and echocardiographically evaluated at inclusion. Left ventricular ejection fraction (EF) before pacemaker implantation was not known. Electrocardiogram was performed at the time of inclusion, and paced QRS duration was assessed. The pacemakers had been implanted via a standard percutaneous transvenous approach. In all patients, the RV bipolar leads were systematically positioned at the RV apex. The indications for RV pacing were sinus-node dysfunction, bradycardia due to advanced AV-block, and AV-node ablation. Exclusion criteria were pregnancy, congenital heart disease, severe valvular dysfunction, open chest surgery, and percutaneous coronary intervention within the previous 3 months.
The study fulfilled the Declaration of Helsinki and was approved by the ethics committee of our institution and informed consent was obtained from all individuals.
Echocardiography
Each individual underwent a comprehensive two-dimensional (2D) echocardiographic study using a commercially available ultrasound scanner (Vivid Q, GE Healthcare) with a 2.5 MHz phased array transducer. Standard echocardiographic views were obtained, including parasternal long- and short-axis and apical four-, two-chamber, and apical long-axis views. Two-dimensional images were acquired with a frame rate of >50 Hz. Images were analysed offline with commercially available software (EchoPAC, GE Vingmed) by an experienced observer unaware of the clinical or functional outcome of the patients. Left ventricular dimensions were measured according to the recommendations of the European Association of Cardiovascular Imaging. Left ventricular EF was measured using the biplane Simpson method.
Two-dimensional speckle-tracking echocardiography
The endocardial borders were traced in the end-systolic frame of the 2D images from the apical four-, two-chamber, and apical long-axis views for the assessment of longitudinal strain. Frame rate was 56 ± 12 Hz for greyscale imaging. Strain was evaluated on a frame-by-frame basis by automatic tracking of acoustic markers throughout the cardiac cycle. The operator manually adjusted segments that failed to track properly. Any segment that subsequently failed to track was excluded. Peak systolic LV longitudinal myocardial strain by 2D speckle-tracking echocardiography was assessed in 18 LV segments and averaged to LV global longitudinal strain (GLS).
Intra-ventricular dyssynchrony assessment
Assessment of the magnitude of the SF, systolic excursion and PSS at the septum in different cardiac views in patients with RV pacing. The left upper panel shows parasternal long-axis view of the heart in a patient with RV pacing and normal LV function. The left lower panel shows an M-mode image of the septum demonstrating a minimal SF (thick white arrow), normal systolic excursion (thick yellow arrow), and no PSS. The middle upper panel shows parasternal short-axis view of the heart in a patient with RV pacing and mildly reduced LV function (EF 46%). The middle lower panel shows an M-mode image of the septum demonstrating a slightly greater SF, reduced systolic excursion, and PSS (thin white arrow). The right upper panel shows apical four-chamber view of the heart in a patient with RV pacing and severly reduced LV function (EF 35%). A pacemaker lead can be appreciated in the RV (red arrow). The right lower panel shows an M-mode image of the septum demonstrating a large SF, PSS, and no systolic excursion. PM, pacemaker; PSS, post-systolic shortening; SE, systolic excursion; SF, septal flash.
Statistical analyses
Analyses were carried out using a standard statistical software program (SPSS version 21, SPSS Inc., Chicago, IL, USA). Data were presented as mean ± SD, and numbers and percentages, respectively. The χ2 test (categorical variables) and Student's t-test (continuous variables) were used to determine differences between two groups. Correlation of two continuous variables were analysed by means of the linear regression and expressed by the Pearson's r coefficient. Logistic regression analysis was performed to determine the independent prognostic value of SF excursion for predicting LV dysfunction in patients with RV pacing. Age, number of years with pacemaker, extent of RV pacing, paced QRS duration, presence of atrial fibrillation, and SF excursion were selected for inclusion in a multivariate logistic regression analysis. The selection of variables was based on statistical significance of P < 0.05 in the univariate logistic regression analysis in addition to parameters that could influence LV function over time. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated for SF excursion and paced QRS duration. The value closest to the upper left corner of the ROC curve determined optimal sensitivity and specificity for the ability of SF excursion and paced QRS duration to discriminate between those with and without LV dysfunction. Reproducibility was expressed as intra-class correlation coefficient. P-values were two-tailed, and values of <0.05 were considered significant.
Results
We have included 74 consecutive patients receiving conventional RV pacing in 99 ± 1% of the time. The pacemakers were implanted 8.4 ± 5.3 years earlier. Of all patients, we found SF to be present in 57/74 (77%). Table 1 depicts the characteristics of the study population.
Clinical characteristics
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| Age, years | 77 ± 12 | 80 ± 13 | 76 ± 12 | 0.2 |
| Male, % | 44 (60) | 10 (59) | 34 (60) | 1.0 |
| Heart rate, bpm | 63 ± 6 | 65 ± 8 | 62 ± 5 | 0.3 |
| Paced QRS duration, ms | 152 ± 22 | 145 ± 15 | 154 ± 23 | 0.1 |
| Body surface area, m2 | 1.8 ± 0.2 | 1.8 ± 0.2 | 1.9 ± 0.2 | 0.7 |
| Hypertension, % | 50 (68) | 13 (77) | 37 (65) | 0.4 |
| Diabetes mellitus, % | 16 (22) | 1 (6) | 15 (26) | 0.07 |
| Hyperlipidaemia, % | 25 (34) | 5 (29) | 20 (35) | 0.7 |
| Coronary artery disease, % | 9 (12) | 2 (12) | 7 (12) | 1.0 |
| Earlier myocardial infarction, % | 2 (3) | 1 (6) | 1 (2) | 0.4 |
| Dilated cardiomyopathy, % | 2 (3) | 0 (0) | 2 (4) | 0.4 |
| Hypertrophic cardiomyopathy, % | 2 (3) | 2 (12) | 0 (0) | <0.01 |
| Earlier cardiotoxic treatment, % | 1 (1) | 0 (0) | 1 (2) | 0.6 |
| Atrial fibrillation, % | 15 (20) | 3 (18) | 12 (21) | 0.8 |
| ACE/ARB treatment, % | 40 (54) | 8 (47) | 32 (56) | 0.5 |
| β-Blocker treatment, % | 13 (18) | 3 (18) | 10 (18) | 1.0 |
| Other antihypertensive treatment, % | 20 (27) | 8 (47) | 12 (21) | 0.03 |
| PM indication | ||||
| Sinus-node dysfunction, % | 8 (11) | 1 (6) | 7 (12) | 0.5 |
| AV-node ablation, % | 5 (7) | 1 (6) | 4 (7) | 0.9 |
| AV conduction disorders, % | 61 (82) | 15 (88) | 46 (81) | 0.5 |
| PM mode | ||||
| VVI, % | 31 (42) | 8 (47) | 23 (40) | 0.6 |
| DDD, % | 43 (58) | 9 (53) | 34 (60) | 0.6 |
| Years with PM, years | 9 ± 6 | 10 ± 4 | 8 ± 6 | 0.3 |
| Extent of RV pacing, % | 98 ± 2 | 98 ± 2 | 98 ± 2 | 0.4 |
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| Age, years | 77 ± 12 | 80 ± 13 | 76 ± 12 | 0.2 |
| Male, % | 44 (60) | 10 (59) | 34 (60) | 1.0 |
| Heart rate, bpm | 63 ± 6 | 65 ± 8 | 62 ± 5 | 0.3 |
| Paced QRS duration, ms | 152 ± 22 | 145 ± 15 | 154 ± 23 | 0.1 |
| Body surface area, m2 | 1.8 ± 0.2 | 1.8 ± 0.2 | 1.9 ± 0.2 | 0.7 |
| Hypertension, % | 50 (68) | 13 (77) | 37 (65) | 0.4 |
| Diabetes mellitus, % | 16 (22) | 1 (6) | 15 (26) | 0.07 |
| Hyperlipidaemia, % | 25 (34) | 5 (29) | 20 (35) | 0.7 |
| Coronary artery disease, % | 9 (12) | 2 (12) | 7 (12) | 1.0 |
| Earlier myocardial infarction, % | 2 (3) | 1 (6) | 1 (2) | 0.4 |
| Dilated cardiomyopathy, % | 2 (3) | 0 (0) | 2 (4) | 0.4 |
| Hypertrophic cardiomyopathy, % | 2 (3) | 2 (12) | 0 (0) | <0.01 |
| Earlier cardiotoxic treatment, % | 1 (1) | 0 (0) | 1 (2) | 0.6 |
| Atrial fibrillation, % | 15 (20) | 3 (18) | 12 (21) | 0.8 |
| ACE/ARB treatment, % | 40 (54) | 8 (47) | 32 (56) | 0.5 |
| β-Blocker treatment, % | 13 (18) | 3 (18) | 10 (18) | 1.0 |
| Other antihypertensive treatment, % | 20 (27) | 8 (47) | 12 (21) | 0.03 |
| PM indication | ||||
| Sinus-node dysfunction, % | 8 (11) | 1 (6) | 7 (12) | 0.5 |
| AV-node ablation, % | 5 (7) | 1 (6) | 4 (7) | 0.9 |
| AV conduction disorders, % | 61 (82) | 15 (88) | 46 (81) | 0.5 |
| PM mode | ||||
| VVI, % | 31 (42) | 8 (47) | 23 (40) | 0.6 |
| DDD, % | 43 (58) | 9 (53) | 34 (60) | 0.6 |
| Years with PM, years | 9 ± 6 | 10 ± 4 | 8 ± 6 | 0.3 |
| Extent of RV pacing, % | 98 ± 2 | 98 ± 2 | 98 ± 2 | 0.4 |
Data expressed as mean ± SD, n (%). Right column shows P-values for Student's t-test and χ2 tests.
ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blockers; AV, atrioventricular; PM, pacemaker; RV, right ventricular; SF, septal flash.
Clinical characteristics
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| Age, years | 77 ± 12 | 80 ± 13 | 76 ± 12 | 0.2 |
| Male, % | 44 (60) | 10 (59) | 34 (60) | 1.0 |
| Heart rate, bpm | 63 ± 6 | 65 ± 8 | 62 ± 5 | 0.3 |
| Paced QRS duration, ms | 152 ± 22 | 145 ± 15 | 154 ± 23 | 0.1 |
| Body surface area, m2 | 1.8 ± 0.2 | 1.8 ± 0.2 | 1.9 ± 0.2 | 0.7 |
| Hypertension, % | 50 (68) | 13 (77) | 37 (65) | 0.4 |
| Diabetes mellitus, % | 16 (22) | 1 (6) | 15 (26) | 0.07 |
| Hyperlipidaemia, % | 25 (34) | 5 (29) | 20 (35) | 0.7 |
| Coronary artery disease, % | 9 (12) | 2 (12) | 7 (12) | 1.0 |
| Earlier myocardial infarction, % | 2 (3) | 1 (6) | 1 (2) | 0.4 |
| Dilated cardiomyopathy, % | 2 (3) | 0 (0) | 2 (4) | 0.4 |
| Hypertrophic cardiomyopathy, % | 2 (3) | 2 (12) | 0 (0) | <0.01 |
| Earlier cardiotoxic treatment, % | 1 (1) | 0 (0) | 1 (2) | 0.6 |
| Atrial fibrillation, % | 15 (20) | 3 (18) | 12 (21) | 0.8 |
| ACE/ARB treatment, % | 40 (54) | 8 (47) | 32 (56) | 0.5 |
| β-Blocker treatment, % | 13 (18) | 3 (18) | 10 (18) | 1.0 |
| Other antihypertensive treatment, % | 20 (27) | 8 (47) | 12 (21) | 0.03 |
| PM indication | ||||
| Sinus-node dysfunction, % | 8 (11) | 1 (6) | 7 (12) | 0.5 |
| AV-node ablation, % | 5 (7) | 1 (6) | 4 (7) | 0.9 |
| AV conduction disorders, % | 61 (82) | 15 (88) | 46 (81) | 0.5 |
| PM mode | ||||
| VVI, % | 31 (42) | 8 (47) | 23 (40) | 0.6 |
| DDD, % | 43 (58) | 9 (53) | 34 (60) | 0.6 |
| Years with PM, years | 9 ± 6 | 10 ± 4 | 8 ± 6 | 0.3 |
| Extent of RV pacing, % | 98 ± 2 | 98 ± 2 | 98 ± 2 | 0.4 |
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| Age, years | 77 ± 12 | 80 ± 13 | 76 ± 12 | 0.2 |
| Male, % | 44 (60) | 10 (59) | 34 (60) | 1.0 |
| Heart rate, bpm | 63 ± 6 | 65 ± 8 | 62 ± 5 | 0.3 |
| Paced QRS duration, ms | 152 ± 22 | 145 ± 15 | 154 ± 23 | 0.1 |
| Body surface area, m2 | 1.8 ± 0.2 | 1.8 ± 0.2 | 1.9 ± 0.2 | 0.7 |
| Hypertension, % | 50 (68) | 13 (77) | 37 (65) | 0.4 |
| Diabetes mellitus, % | 16 (22) | 1 (6) | 15 (26) | 0.07 |
| Hyperlipidaemia, % | 25 (34) | 5 (29) | 20 (35) | 0.7 |
| Coronary artery disease, % | 9 (12) | 2 (12) | 7 (12) | 1.0 |
| Earlier myocardial infarction, % | 2 (3) | 1 (6) | 1 (2) | 0.4 |
| Dilated cardiomyopathy, % | 2 (3) | 0 (0) | 2 (4) | 0.4 |
| Hypertrophic cardiomyopathy, % | 2 (3) | 2 (12) | 0 (0) | <0.01 |
| Earlier cardiotoxic treatment, % | 1 (1) | 0 (0) | 1 (2) | 0.6 |
| Atrial fibrillation, % | 15 (20) | 3 (18) | 12 (21) | 0.8 |
| ACE/ARB treatment, % | 40 (54) | 8 (47) | 32 (56) | 0.5 |
| β-Blocker treatment, % | 13 (18) | 3 (18) | 10 (18) | 1.0 |
| Other antihypertensive treatment, % | 20 (27) | 8 (47) | 12 (21) | 0.03 |
| PM indication | ||||
| Sinus-node dysfunction, % | 8 (11) | 1 (6) | 7 (12) | 0.5 |
| AV-node ablation, % | 5 (7) | 1 (6) | 4 (7) | 0.9 |
| AV conduction disorders, % | 61 (82) | 15 (88) | 46 (81) | 0.5 |
| PM mode | ||||
| VVI, % | 31 (42) | 8 (47) | 23 (40) | 0.6 |
| DDD, % | 43 (58) | 9 (53) | 34 (60) | 0.6 |
| Years with PM, years | 9 ± 6 | 10 ± 4 | 8 ± 6 | 0.3 |
| Extent of RV pacing, % | 98 ± 2 | 98 ± 2 | 98 ± 2 | 0.4 |
Data expressed as mean ± SD, n (%). Right column shows P-values for Student's t-test and χ2 tests.
ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blockers; AV, atrioventricular; PM, pacemaker; RV, right ventricular; SF, septal flash.
No differences in age, sex, heart rate, body surface area, co-morbidity, use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and β-blockers, and paced QRS duration were observed between those with and without a SF (Table 1). There was no difference in pacemaker indication and pacing mode, extent of RV pacing, and number of years with pacemaker treatment between the two groups (Table 1).
Echocardiographic findings
Table 2 shows the echocardiographic findings in patients with and without a SF. Of all patients, 21 (28%) had reduced LV function (EF < 50%) and 53 (72%) had normal LV function (EF ≥ 50%). Patients with a SF had significantly lower EF than patients without a SF (52 ± 10 vs. 60 ± 4%, P < 0.001). Furthermore, patients with a SF had larger LV end-systolic volume, lower cardiac output, cardiac index, mitral and tricuspid A velocities, tricuspid annular plane systolic excursion, and longer isovolumetric relaxation time (all P < 0.05).
Echocardiographic data
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| LVEF, % | 54 ± 10 | 60 ± 4 | 52 ± 10 | <0.001 |
| LVGLS, % | −18 ± 3 | −20 ± 2 | −17 ± 4 | <0.001 |
| Apical LV strain, % | −20 ± 5 | −22 ± 6 | −17 ± 7 | <0.05 |
| Basal LV strain, % | −16 ± 3 | −16 ± 5 | −15 ± 5 | 0.3 |
| Apico-basal difference in LV strain, % | 3 ± 5 | 6 ± 4 | 2 ± 4 | <0.01 |
| LVEDV, mL | 119 ± 37 | 106 ± 25 | 122 ± 40 | 0.1 |
| LVEDV/BSA, mL/m2 | 64 ± 19 | 57 ± 11 | 66 ± 20 | 0.9 |
| LVESV, mL | 56 ± 29 | 42 ± 11 | 61 ± 32 | <0.001 |
| LVESV/BSA, mL/m2 | 30 ± 15 | 23 ± 5 | 33 ± 16 | <0.001 |
| SV, mL | 73 ± 15 | 76 ± 12 | 72 ± 15 | 0.2 |
| SI, mL/m2 | 40 ± 8 | 43 ± 8 | 39 ± 8 | 0.1 |
| CO, L/min | 4.6 ± 1.0 | 5.2 ± 0.7 | 4.4 ± 1.0 | <0.01 |
| CI, L/min/m2 | 2.6 ± 0.5 | 2.9 ± 0.4 | 2.4 ± 0.5 | <0.01 |
| IVSd, mm | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.8 |
| LVIDd, mm | 50 ± 7 | 49 ± 7 | 50 ± 7 | 0.8 |
| LVIDd/BSA, mm/m2 | 27 ± 4 | 27 ± 3 | 27 ± 5 | 0.6 |
| LVPWd, mm | 10 ± 1 | 10 ± 1 | 10 ± 1 | 0.4 |
| Mitral E velocity, cm/s | 0.8 ± 0.2 | 0.9 ± 0.2 | 0.8 ± 0.3 | 0.4 |
| Mitral DT, ms | 225 ± 66 | 202 ± 46 | 219 ± 70 | 0.4 |
| Mitral A velocity, cm/s | 0.8 ± 0.3 | 1.1 ± 0.4 | 0.8 ± 0.2 | <0.001 |
| Mitral E/A ratio | 1.0 ± 0.6 | 0.7 ± 0.4 | 0.9 ± 0.8 | 0.3 |
| IVRT, ms | 86 ± 29 | 75 ± 22 | 90 ± 30 | <0.05 |
| RVFAC, % | 42 ± 8 | 41 ± 13 | 36 ± 15 | 0.3 |
| RVD area, cm2 | 21 ± 3 | 21 ± 4 | 20 ± 3 | 0.4 |
| RVD area/BSA, cm2/m2 | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.7 |
| RVS area, cm2 | 12 ± 2 | 12 ± 3 | 12 ± 2 | 0.7 |
| RVS area/BSA, cm2/m2 | 6 ± 1 | 6 ± 1 | 6 ± 1 | 0.5 |
| TAPSE, mm | 19 ± 3 | 21 ± 4 | 18 ± 3 | <0.05 |
| Tricuspid E velocity, cm/s | 0.6 ± 0.1 | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.8 |
| Tricuspid DT, ms | 245 ± 62 | 248 ± 60 | 238 ± 62 | 0.7 |
| Tricuspid A velocity, cm/s | 0.5 ± 0.2 | 0.6 ± 0.3 | 0.5 ± 0.1 | <0.05 |
| Tricuspid E/A ratio | 1.3 ± 0.4 | 0.9 ± 0.5 | 0.9 ± 0.7 | 0.9 |
| LA diameter, mm | 41 ± 7 | 40 ± 7 | 41 ± 6 | 1.0 |
| LA area, cm2 | 21 ± 7 | 19 ± 5 | 21 ± 7 | 0.4 |
| RA area, cm2 | 17 ± 4 | 17 ± 5 | 17 ± 4 | 0.9 |
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| LVEF, % | 54 ± 10 | 60 ± 4 | 52 ± 10 | <0.001 |
| LVGLS, % | −18 ± 3 | −20 ± 2 | −17 ± 4 | <0.001 |
| Apical LV strain, % | −20 ± 5 | −22 ± 6 | −17 ± 7 | <0.05 |
| Basal LV strain, % | −16 ± 3 | −16 ± 5 | −15 ± 5 | 0.3 |
| Apico-basal difference in LV strain, % | 3 ± 5 | 6 ± 4 | 2 ± 4 | <0.01 |
| LVEDV, mL | 119 ± 37 | 106 ± 25 | 122 ± 40 | 0.1 |
| LVEDV/BSA, mL/m2 | 64 ± 19 | 57 ± 11 | 66 ± 20 | 0.9 |
| LVESV, mL | 56 ± 29 | 42 ± 11 | 61 ± 32 | <0.001 |
| LVESV/BSA, mL/m2 | 30 ± 15 | 23 ± 5 | 33 ± 16 | <0.001 |
| SV, mL | 73 ± 15 | 76 ± 12 | 72 ± 15 | 0.2 |
| SI, mL/m2 | 40 ± 8 | 43 ± 8 | 39 ± 8 | 0.1 |
| CO, L/min | 4.6 ± 1.0 | 5.2 ± 0.7 | 4.4 ± 1.0 | <0.01 |
| CI, L/min/m2 | 2.6 ± 0.5 | 2.9 ± 0.4 | 2.4 ± 0.5 | <0.01 |
| IVSd, mm | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.8 |
| LVIDd, mm | 50 ± 7 | 49 ± 7 | 50 ± 7 | 0.8 |
| LVIDd/BSA, mm/m2 | 27 ± 4 | 27 ± 3 | 27 ± 5 | 0.6 |
| LVPWd, mm | 10 ± 1 | 10 ± 1 | 10 ± 1 | 0.4 |
| Mitral E velocity, cm/s | 0.8 ± 0.2 | 0.9 ± 0.2 | 0.8 ± 0.3 | 0.4 |
| Mitral DT, ms | 225 ± 66 | 202 ± 46 | 219 ± 70 | 0.4 |
| Mitral A velocity, cm/s | 0.8 ± 0.3 | 1.1 ± 0.4 | 0.8 ± 0.2 | <0.001 |
| Mitral E/A ratio | 1.0 ± 0.6 | 0.7 ± 0.4 | 0.9 ± 0.8 | 0.3 |
| IVRT, ms | 86 ± 29 | 75 ± 22 | 90 ± 30 | <0.05 |
| RVFAC, % | 42 ± 8 | 41 ± 13 | 36 ± 15 | 0.3 |
| RVD area, cm2 | 21 ± 3 | 21 ± 4 | 20 ± 3 | 0.4 |
| RVD area/BSA, cm2/m2 | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.7 |
| RVS area, cm2 | 12 ± 2 | 12 ± 3 | 12 ± 2 | 0.7 |
| RVS area/BSA, cm2/m2 | 6 ± 1 | 6 ± 1 | 6 ± 1 | 0.5 |
| TAPSE, mm | 19 ± 3 | 21 ± 4 | 18 ± 3 | <0.05 |
| Tricuspid E velocity, cm/s | 0.6 ± 0.1 | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.8 |
| Tricuspid DT, ms | 245 ± 62 | 248 ± 60 | 238 ± 62 | 0.7 |
| Tricuspid A velocity, cm/s | 0.5 ± 0.2 | 0.6 ± 0.3 | 0.5 ± 0.1 | <0.05 |
| Tricuspid E/A ratio | 1.3 ± 0.4 | 0.9 ± 0.5 | 0.9 ± 0.7 | 0.9 |
| LA diameter, mm | 41 ± 7 | 40 ± 7 | 41 ± 6 | 1.0 |
| LA area, cm2 | 21 ± 7 | 19 ± 5 | 21 ± 7 | 0.4 |
| RA area, cm2 | 17 ± 4 | 17 ± 5 | 17 ± 4 | 0.9 |
Data expressed as mean ± SD, n (%). Right column shows P-values for Student's t-test and χ2 tests.
BSA, body surface area; CI, cardiac index; CO, cardiac output; DT, deceleration time; EDV, end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; FAC, fractional area change; GLS, global longitudinal strain; IVRT, isovolumic relaxation time; IVSd, interventricular septum diastole; LA, left atria; LV, left ventricular; LVIDd, left ventricular internal diameter diastole; LVPWd, left ventricular posterior wall diastole; RA, right atria; RV, right ventricle; RVD, right ventricular diastolic; RVS, right ventricular systolic; SF, septal flash; SI, stroke index; SV, stroke volume; TAPSE, tricuspid annular plane systolic excursion.
Echocardiographic data
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| LVEF, % | 54 ± 10 | 60 ± 4 | 52 ± 10 | <0.001 |
| LVGLS, % | −18 ± 3 | −20 ± 2 | −17 ± 4 | <0.001 |
| Apical LV strain, % | −20 ± 5 | −22 ± 6 | −17 ± 7 | <0.05 |
| Basal LV strain, % | −16 ± 3 | −16 ± 5 | −15 ± 5 | 0.3 |
| Apico-basal difference in LV strain, % | 3 ± 5 | 6 ± 4 | 2 ± 4 | <0.01 |
| LVEDV, mL | 119 ± 37 | 106 ± 25 | 122 ± 40 | 0.1 |
| LVEDV/BSA, mL/m2 | 64 ± 19 | 57 ± 11 | 66 ± 20 | 0.9 |
| LVESV, mL | 56 ± 29 | 42 ± 11 | 61 ± 32 | <0.001 |
| LVESV/BSA, mL/m2 | 30 ± 15 | 23 ± 5 | 33 ± 16 | <0.001 |
| SV, mL | 73 ± 15 | 76 ± 12 | 72 ± 15 | 0.2 |
| SI, mL/m2 | 40 ± 8 | 43 ± 8 | 39 ± 8 | 0.1 |
| CO, L/min | 4.6 ± 1.0 | 5.2 ± 0.7 | 4.4 ± 1.0 | <0.01 |
| CI, L/min/m2 | 2.6 ± 0.5 | 2.9 ± 0.4 | 2.4 ± 0.5 | <0.01 |
| IVSd, mm | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.8 |
| LVIDd, mm | 50 ± 7 | 49 ± 7 | 50 ± 7 | 0.8 |
| LVIDd/BSA, mm/m2 | 27 ± 4 | 27 ± 3 | 27 ± 5 | 0.6 |
| LVPWd, mm | 10 ± 1 | 10 ± 1 | 10 ± 1 | 0.4 |
| Mitral E velocity, cm/s | 0.8 ± 0.2 | 0.9 ± 0.2 | 0.8 ± 0.3 | 0.4 |
| Mitral DT, ms | 225 ± 66 | 202 ± 46 | 219 ± 70 | 0.4 |
| Mitral A velocity, cm/s | 0.8 ± 0.3 | 1.1 ± 0.4 | 0.8 ± 0.2 | <0.001 |
| Mitral E/A ratio | 1.0 ± 0.6 | 0.7 ± 0.4 | 0.9 ± 0.8 | 0.3 |
| IVRT, ms | 86 ± 29 | 75 ± 22 | 90 ± 30 | <0.05 |
| RVFAC, % | 42 ± 8 | 41 ± 13 | 36 ± 15 | 0.3 |
| RVD area, cm2 | 21 ± 3 | 21 ± 4 | 20 ± 3 | 0.4 |
| RVD area/BSA, cm2/m2 | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.7 |
| RVS area, cm2 | 12 ± 2 | 12 ± 3 | 12 ± 2 | 0.7 |
| RVS area/BSA, cm2/m2 | 6 ± 1 | 6 ± 1 | 6 ± 1 | 0.5 |
| TAPSE, mm | 19 ± 3 | 21 ± 4 | 18 ± 3 | <0.05 |
| Tricuspid E velocity, cm/s | 0.6 ± 0.1 | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.8 |
| Tricuspid DT, ms | 245 ± 62 | 248 ± 60 | 238 ± 62 | 0.7 |
| Tricuspid A velocity, cm/s | 0.5 ± 0.2 | 0.6 ± 0.3 | 0.5 ± 0.1 | <0.05 |
| Tricuspid E/A ratio | 1.3 ± 0.4 | 0.9 ± 0.5 | 0.9 ± 0.7 | 0.9 |
| LA diameter, mm | 41 ± 7 | 40 ± 7 | 41 ± 6 | 1.0 |
| LA area, cm2 | 21 ± 7 | 19 ± 5 | 21 ± 7 | 0.4 |
| RA area, cm2 | 17 ± 4 | 17 ± 5 | 17 ± 4 | 0.9 |
| Total study population (n = 74) | Patients without SF (n = 17) | Patients with SF (n = 57) | P-value | |
|---|---|---|---|---|
| LVEF, % | 54 ± 10 | 60 ± 4 | 52 ± 10 | <0.001 |
| LVGLS, % | −18 ± 3 | −20 ± 2 | −17 ± 4 | <0.001 |
| Apical LV strain, % | −20 ± 5 | −22 ± 6 | −17 ± 7 | <0.05 |
| Basal LV strain, % | −16 ± 3 | −16 ± 5 | −15 ± 5 | 0.3 |
| Apico-basal difference in LV strain, % | 3 ± 5 | 6 ± 4 | 2 ± 4 | <0.01 |
| LVEDV, mL | 119 ± 37 | 106 ± 25 | 122 ± 40 | 0.1 |
| LVEDV/BSA, mL/m2 | 64 ± 19 | 57 ± 11 | 66 ± 20 | 0.9 |
| LVESV, mL | 56 ± 29 | 42 ± 11 | 61 ± 32 | <0.001 |
| LVESV/BSA, mL/m2 | 30 ± 15 | 23 ± 5 | 33 ± 16 | <0.001 |
| SV, mL | 73 ± 15 | 76 ± 12 | 72 ± 15 | 0.2 |
| SI, mL/m2 | 40 ± 8 | 43 ± 8 | 39 ± 8 | 0.1 |
| CO, L/min | 4.6 ± 1.0 | 5.2 ± 0.7 | 4.4 ± 1.0 | <0.01 |
| CI, L/min/m2 | 2.6 ± 0.5 | 2.9 ± 0.4 | 2.4 ± 0.5 | <0.01 |
| IVSd, mm | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.8 |
| LVIDd, mm | 50 ± 7 | 49 ± 7 | 50 ± 7 | 0.8 |
| LVIDd/BSA, mm/m2 | 27 ± 4 | 27 ± 3 | 27 ± 5 | 0.6 |
| LVPWd, mm | 10 ± 1 | 10 ± 1 | 10 ± 1 | 0.4 |
| Mitral E velocity, cm/s | 0.8 ± 0.2 | 0.9 ± 0.2 | 0.8 ± 0.3 | 0.4 |
| Mitral DT, ms | 225 ± 66 | 202 ± 46 | 219 ± 70 | 0.4 |
| Mitral A velocity, cm/s | 0.8 ± 0.3 | 1.1 ± 0.4 | 0.8 ± 0.2 | <0.001 |
| Mitral E/A ratio | 1.0 ± 0.6 | 0.7 ± 0.4 | 0.9 ± 0.8 | 0.3 |
| IVRT, ms | 86 ± 29 | 75 ± 22 | 90 ± 30 | <0.05 |
| RVFAC, % | 42 ± 8 | 41 ± 13 | 36 ± 15 | 0.3 |
| RVD area, cm2 | 21 ± 3 | 21 ± 4 | 20 ± 3 | 0.4 |
| RVD area/BSA, cm2/m2 | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.7 |
| RVS area, cm2 | 12 ± 2 | 12 ± 3 | 12 ± 2 | 0.7 |
| RVS area/BSA, cm2/m2 | 6 ± 1 | 6 ± 1 | 6 ± 1 | 0.5 |
| TAPSE, mm | 19 ± 3 | 21 ± 4 | 18 ± 3 | <0.05 |
| Tricuspid E velocity, cm/s | 0.6 ± 0.1 | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.8 |
| Tricuspid DT, ms | 245 ± 62 | 248 ± 60 | 238 ± 62 | 0.7 |
| Tricuspid A velocity, cm/s | 0.5 ± 0.2 | 0.6 ± 0.3 | 0.5 ± 0.1 | <0.05 |
| Tricuspid E/A ratio | 1.3 ± 0.4 | 0.9 ± 0.5 | 0.9 ± 0.7 | 0.9 |
| LA diameter, mm | 41 ± 7 | 40 ± 7 | 41 ± 6 | 1.0 |
| LA area, cm2 | 21 ± 7 | 19 ± 5 | 21 ± 7 | 0.4 |
| RA area, cm2 | 17 ± 4 | 17 ± 5 | 17 ± 4 | 0.9 |
Data expressed as mean ± SD, n (%). Right column shows P-values for Student's t-test and χ2 tests.
BSA, body surface area; CI, cardiac index; CO, cardiac output; DT, deceleration time; EDV, end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; FAC, fractional area change; GLS, global longitudinal strain; IVRT, isovolumic relaxation time; IVSd, interventricular septum diastole; LA, left atria; LV, left ventricular; LVIDd, left ventricular internal diameter diastole; LVPWd, left ventricular posterior wall diastole; RA, right atria; RV, right ventricle; RVD, right ventricular diastolic; RVS, right ventricular systolic; SF, septal flash; SI, stroke index; SV, stroke volume; TAPSE, tricuspid annular plane systolic excursion.
All 17 patients without a SF had normal LV function, while a SF was demonstrated in all 21 patients with reduced LV function. Importantly, the magnitude of SF was greater (5 ± 1 vs. 2 ± 1 mm) and systolic septal excursion was smaller (4 ± 1 vs. 8 ± 2 mm) in patients with reduced LV function compared with patients with normal LV function (both P < 0.001).
Left ventricular ejection fraction vs. SF excursion in 74 patients with RV pacing (R = −0.76, P < 0.001). LVEF, left ventricular ejection fraction; SF, septal flash.
Left ventricular systolic septal excursion vs. SF excursion in 74 patients with RV pacing (R = −0.81, P < 0.001). LV, left ventricular; SF, septal flash.
Paced QRS duration vs. SF excursion in 74 patients with RV pacing (R = 0.32, P < 0.01). SF, septal flash.
Receiver operating characteristic curve analyses for the ability of SF excursion and paced QRS duration to identify RV-paced patients with reduced LV function (EF < 50%, n = 74). AUC, area under the curve; SF, septal flash.
Septal flash excursion was independent predictor of LV dysfunction in a multivariate logistic regression analysis (P = 0.001; Table 3).
Predictors of left ventricular function in patients with right ventricular pacing
| Univariate logistic regression | Multivariate logistic regression | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Age, years | 0.97 | 0.93–1.02 | 0.3 | 0.95 | 0.86–1.05 | 0.3 |
| Years with PM, years | 1.05 | 0.96–1.15 | 0.3 | 0.90 | 0.76–1.08 | 0.3 |
| Extent of RV pacing, % | 0.88 | 0.68–1.15 | 0.4 | 0.70 | 0.39–1.25 | 0.2 |
| Paced QRS duration, ms | 0.97 | 0.95–1.00 | 0.05 | 1.02 | 0.97–1.07 | 0.5 |
| Atrial fibrillation, n | 0.57 | 0.14–2.27 | 0.4 | 2.01 | 0.17–25.9 | 0.6 |
| SF excursion, mm | 0.15 | 0.06–0.38 | <0.001 | 0.10 | 0.03–0.37 | 0.001 |
| Univariate logistic regression | Multivariate logistic regression | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Age, years | 0.97 | 0.93–1.02 | 0.3 | 0.95 | 0.86–1.05 | 0.3 |
| Years with PM, years | 1.05 | 0.96–1.15 | 0.3 | 0.90 | 0.76–1.08 | 0.3 |
| Extent of RV pacing, % | 0.88 | 0.68–1.15 | 0.4 | 0.70 | 0.39–1.25 | 0.2 |
| Paced QRS duration, ms | 0.97 | 0.95–1.00 | 0.05 | 1.02 | 0.97–1.07 | 0.5 |
| Atrial fibrillation, n | 0.57 | 0.14–2.27 | 0.4 | 2.01 | 0.17–25.9 | 0.6 |
| SF excursion, mm | 0.15 | 0.06–0.38 | <0.001 | 0.10 | 0.03–0.37 | 0.001 |
CI, confidence interval; OR, odds ratio; SF, septal flash; RV, right ventricular; PM, pacemaker.
Predictors of left ventricular function in patients with right ventricular pacing
| Univariate logistic regression | Multivariate logistic regression | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Age, years | 0.97 | 0.93–1.02 | 0.3 | 0.95 | 0.86–1.05 | 0.3 |
| Years with PM, years | 1.05 | 0.96–1.15 | 0.3 | 0.90 | 0.76–1.08 | 0.3 |
| Extent of RV pacing, % | 0.88 | 0.68–1.15 | 0.4 | 0.70 | 0.39–1.25 | 0.2 |
| Paced QRS duration, ms | 0.97 | 0.95–1.00 | 0.05 | 1.02 | 0.97–1.07 | 0.5 |
| Atrial fibrillation, n | 0.57 | 0.14–2.27 | 0.4 | 2.01 | 0.17–25.9 | 0.6 |
| SF excursion, mm | 0.15 | 0.06–0.38 | <0.001 | 0.10 | 0.03–0.37 | 0.001 |
| Univariate logistic regression | Multivariate logistic regression | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Age, years | 0.97 | 0.93–1.02 | 0.3 | 0.95 | 0.86–1.05 | 0.3 |
| Years with PM, years | 1.05 | 0.96–1.15 | 0.3 | 0.90 | 0.76–1.08 | 0.3 |
| Extent of RV pacing, % | 0.88 | 0.68–1.15 | 0.4 | 0.70 | 0.39–1.25 | 0.2 |
| Paced QRS duration, ms | 0.97 | 0.95–1.00 | 0.05 | 1.02 | 0.97–1.07 | 0.5 |
| Atrial fibrillation, n | 0.57 | 0.14–2.27 | 0.4 | 2.01 | 0.17–25.9 | 0.6 |
| SF excursion, mm | 0.15 | 0.06–0.38 | <0.001 | 0.10 | 0.03–0.37 | 0.001 |
CI, confidence interval; OR, odds ratio; SF, septal flash; RV, right ventricular; PM, pacemaker.
Left ventricular function by GLS and apical strain were decreased (both P < 0.05), while there was no difference in basal strain (P = 0.3) between patients with a SF compared with patients without a SF. Consequently, the difference between apical and basal strain was smaller in patients with a SF compared with those without (P < 0.01) (Table 2). Left ventricular GLS, apical and basal LV longitudinal strain correlated to SF excursion (R = 0.75, 0.67, and 0.46, P < 0.001, respectively).
Interestingly, 50 (65%) patients had PSS. Systolic septal excursion in patients with and without PSS were 8 ± 2 and 6 ± 2 mm (P < 0.001).
According to a ROC curve analysis, paced QRS duration, a marker of electrical dyssynchrony, of 150 ms was a poor predictor (AUC = 0.59) of reduced LV function with a sensitivity of 67% and a specificity of 43% (Figure 5).
Intra-observer and inter-observer intra-class correlation was performed in 10 patients and were 0.89 and 0.82 for SF excursion.
Discussion
In this study, we examined a SF, a distinct hallmark of intra-ventricular dyssynchrony, and its association with decreased LV function and adverse remodelling in patients with RV apical pacing. A SF was present in the majority of patients receiving conventional RV pacing and its magnitude was inversely related to LV function and directly related to end-systolic volume.
Even though RV pacing has been utilized for half a century, its association with heart failure and adverse LV remodelling has only been acknowledged in the last decade with publications of various large-scale pacemaker and implantable cardioverter–defibrillator trials.5,11
Pacing from the RV apex can cause an abnormal electrical activation pattern of the ventricles, which is manifested on an electrocardiogram as a widening of the QRS with a pattern of LBBB. This abnormal electrical activation pattern may consequently induce distinct mechanical changes, i.e. mechanical dyssynchrony. It has been demonstrated in experimental models that acute induction of LBBB results in an immediate reduction of LV systolic function.12 Similarly, in RV-paced patients, an abnormal contraction pattern might be the primary cause of LV dysfunction. During RV pacing, the electrical wave front does not propagate through the His–Purkinje conduction system at first, but rather through the myocardium. As a consequence, similarly but not identically to LBBB, the electrical wave front propagates slower and provokes heterogeneity in electrical activation of the myocardium. This is characterized by early activation of the interventricular septum and late activation of the lateral wall of the LV.13,14 The paced region contracts early at a time of low load, and then it is stretched later in systole as the lateral wall ultimately contracts. As a consequence, this abnormal sequence leads to an electromechanical delay in contraction (dyssynchrony) and subsequently, to redistribution of work and blood flow to late activated regions,13 which in turn induce histological alterations, and structural changes such as asymmetric hypertrophy,14 atrial remodelling,15 and decreased LV function. The main reason for the LV dysfunction in these patients seems to be the reduced contribution of the septal segments in global myocardial deformation secondary to RV pacing.13 In addition to systolic dysfunction, early- and late-contracting regions cause a drop in LV filling time, leading to diastolic dysfunction.13,16
In accordance with these predictable mechanisms, we found reduced LV function as assessed by EF, and increased end-systolic volumes as a sign of adverse LV remodelling in patients with a SF. Furthermore, mitral and tricuspid A velocities were reduced, which might be explained by atrial remodelling and reduced atrial function secondary to LV and RV dysfunction.15 Whereas the prolonged isovolumetric relaxation time was probably a consequence of the mechanical interaction of early- and late-contracting segments during relaxation.16 Moreover, PSS was frequent, and its presence and magnitude correlated with the presence and extent of SF in the study population. The reason for the development of PSS may have been the occurrence of regional variations in the magnitude and duration of the contraction forces within the LV at the beginning of systole, as demonstrated in an earlier study.17 Therefore, PSS was likely a consequence of SF in these patients.
The occurrence of intra-ventricular dyssynchrony in patients with RV pacing has been demonstrated earlier by different echocardiographic techniques18,19 and has been reported to be present in up to 45–50% of patients with normal EF, and to increase parallel with decreasing LV function.18,19 According to these findings, patients with normal baseline systolic function were more resilient to develop dyssynchrony than those with impaired baseline EF. Nevertheless, a drop in LV function even in patients with normal baseline LV function has been reported.3,4 A recent study demonstrated a significant reduction in both EF and GLS over 2 years of permanent pacing, in patients with normal baseline LV function.20 Importantly, apical strain and longitudinal dyssynchrony parameters were also impaired. Similarly, we found impaired LV function by GLS in patients with a SF. Furthermore, apical function by strain was worse in patients with a SF, while basal function was similar when compared with patients without a SF, resulting in a reduced or in some cases even reversed apico-basal gradient in patients with a SF.
Our study included patients with both normal and severely reduced LV function (EF range 24–70%), with a mean EF of 54 ± 10%. We found dyssynchrony assessed by SF excursion of >3.5 mm to be present in 79% of the patients with reduced EF. The considerably higher percentage of patients with dyssynchrony in our population compared with the previous studies could be explained by the high percentage (99 ± 1%) and long duration of RV pacing (8 ± 5 years). A high cumulative percentage of RV pacing has been shown earlier to be associated with increased dyssynchrony and adverse clinical events.11,18
Interestingly, although a large number of patients (36/63%) with normal LV function exhibited a SF, its magnitude was generally low (2 ± 1 mm), suggesting that the mere presence of a SF may not necessarily be sufficient to induce LV dysfunction. For these reasons, we imply that not only the presence of a SF but also its magnitude holds significance regarding LV function and remodelling and therefore should be assessed.
The PACE study3,4 was designed to examine whether biventricular pacing is superior to RV pacing in preserving LV function and preventing adverse remodelling in patients with a normal EF and standard indications for pacing. Yu et al.3 found that in patients with normal baseline systolic function, conventional RV pacing resulted in a reduction in LV function and adverse remodelling with an increase in end-systolic volume. Importantly, biventricular pacing prevented these adverse effects. The fact that biventricular pacing prevents fall in LV function in patients with RV pacing suggests that the mechanism behind the development of LV dysfunction is intra-ventricular dyssynchrony. Left ventricular dyssynchrony as a cause of impaired LV function in patients with RV pacing is further supported by our finding of a SF, a distinct marker of intra-ventricular dyssynchrony, in our study population. Previous studies have demonstrated that a SF is a predictor of intra-ventricular dyssynchrony, heart failure, and a mechanism that, when corrected, is associated CRT response in patients with LBBB.7–10 According to our findings, the magnitude of a SF in patients with RV pacing was associated with LV dysfunction and adverse remodelling, suggesting dyssynchrony as the aetiology, similar to earlier studies.4,7,8
Even though, the application of biventricular pacing in patients with indication for pacemaker treatment is appealing in light of the results of the PACE study, the high cost and complications associated with biventricular pacemakers are potential concerns. Furthermore, in most patients, RV pacing is effective and well tolerated. Therefore, a simple, bedside, non-invasive method that could predict the development of heart failure and adverse remodelling in patients with RV pacing would be of great clinical interest. Additionally, since there was a wide range of the magnitude of the SF, this might suggest that it will vary depending on the exact place of the lead in the septal wall and that its acute assessment during lead implantation could be an alternative approach to find the best lead position minimizing future LV deterioration.
Clinical implications
Identification of a non-invasive and mechanistic marker of LV dyssynchrony that has prognostic implications for patients with RV pacing could have major clinical implications with regards to the intensity of existing and future, medical and invasive treatment of these patients.
By early identification of patients at risk for developing heart failure and adverse remodelling due to RV pacing, larger clinical trials might clarify whether earlier and more aggressive medical treatment, alternative lead positioning, or implantation of a biventricular pacemaker system might prevent or slow down the development and progression of LV dysfunction and remodelling.
Study limitations
This was a cross-sectional observational study and consequently, we have no reliable information about LV function and QRS duration of the study population before pacemaker implantation. Therefore, it is uncertain if the reduction in myocardial function was secondary to RV pacing or to other causes. Nevertheless, there were no differences in co-morbidities influencing cardiac function.
Eight patients with sinus-node disease were paced in the RV, even though AAI or DDD mode might have preserved the spontaneous ventricular activation. Right ventricular pacing was chosen in these patients due to a combination of easier pacemaker implant, high age (82 ± 11 years), low level of activity, numerous co-morbidities, poor quality of life (e.g. dementia), and low life expectancy.
The sample size was relatively small, and there was no follow-up in order to detect differences in clinical events. However, the study was designed with adequate power to test for the expected differences between patients with and without a SF with respect to LV systolic function and LV volume. Prospective, randomized trials with long-time follow-up, large sample size, and sufficient power to evaluate clinical outcomes between patients with and without a SF are warranted.
Conclusions
A SF was present in a majority of patients receiving conventional RV pacing, and its magnitude was related to LV dysfunction and adverse remodelling. Given the similarities observed in LBBB and pacemaker-induced dyssynchrony, SF magnitude might be a predictor for the development of LV dysfunction and adverse remodelling in patients receiving conventional RV pacing.
Funding
This work was supported by the South-Eastern Norway Regional Health Authority and by the Bergesen Foundation and has received funding from the EU FP7 for research, technological development, and demonstration under grant agreement VP2HF (No. 611823).
Conflict of interest: none declared.
