Cardiac resynchronization therapy
Comparison of the effects of left vs. right ventricular pacing on left ventricular remodelling
lçDepartment of Cardiology, Kocaeli University Medical Faculty, 41380 Kocaeli, Turkey
Manuscript submitted 4 June 2008. Accepted after revision 17 October 2008.
* Corresponding author. Tel: +90 262 303 8484, Email: ihubildir{at}gmail.com
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Abstract |
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Aims: Patients having conduction disease and indications for a standard pacemaker implantation are treated with right ventricular (RV)-based pacemaker therapy. The aim of this study was to investigate echocardiographic and clinical effects of RV and left ventricular (LV)-based pacing in patients with standard pacemaker indication and LV dysfunction.
Methods and results: Thirty-nine patients with symptomatic bradycardia due to sinus or atrioventricular nodal dysfunction and having absolute standard pacemaker indication, low LV ejection fraction (EF) (35–50%) and QRS duration <120 ms were included in the study. Pacemaker properties, echocardiographic, and clinical results were evaluated in both patient groups after a long-term follow-up period. A significant increase in LVEF (left ventricular ejection fraction) was observed in left pacing group (from 37 ± 10 to 41 ± 9%, P < 0.01) and a statistically significant decrease in right pacing group (from 40 ± 7 to 37 ± 10%, P < 0.05). Intraventricular asynchrony was not developed in left pacing group, whereas significant asynchrony occurred in 73% of patients in right pacing group. New-onset interventricular asynchrony was detected in three and 10 patients in LV pacing group and RV pacing groups, respectively. Intraventricular and interventricular asynchrony was found together in seven of RV lead implanted patients. Although statistically insignificant, LV end-diastolic diameter was increased (from 56 ± 6 to 60 ± 6 mm) and EF was decreased (from 39 ± 7 to 33 ± 9%) in these patients (P = 0.07). During follow-up, 40% of patients in RV pacing group were admitted to the hospital due to heart failure in contrast to LV pacing group.
Conclusion: LV-based pacemaker implantation is more suitable for patients having standard pacemaker indications and LV dysfunction even in the absence of ventricular asynchrony.
Key Words: Left ventricular pacing, Right ventricular pacing, Left ventricular remodelling, Asynchrony, Heart failure
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Introduction |
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Right ventricular (RV) pacing is a standard pacemaker treatment modality implanted in all bradycardic patients without heart failure. However, RV pacing results in decreased left ventricular (LV) ejection fraction (EF), while changing the ventricular activation pattern and contraction.1
–4 For this reason, many pacing procedures were tried from different areas of the right ventricle to find an optimal pacing focus.5–7 Among them His bundle pacing, septal pacing, and especially RV outflow tract pacing are the most widely examined modalities. Studies about the acute effect of RV outflow tract pacing on haemodynamics showed only the non-inferiority of this pacing site and that long-term data on chronic pacing are limited.8
In recent years, biventricular pacemakers (BVP) are used in the treatment of patients with symptomatic heart failure, LV systolic dysfunction, and intraventricular conduction delay.9–11 LV pacing improves systolic function in contrast to RV pacing and leads to reverse remodelling in left heart chambers.12,13 Effects of LV pacing on clinical and echocardiographic parameters in patients with standard pacemaker indications has not been studied widely. In this study, we aimed to investigate the long-term clinical and echocardiographic effects of RV and LV pacing in patients with standard pacemaker indications and low LVEF (left ventricular ejection fraction).
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Methods |
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Patients group
Between January 2002 and December 2004 the rate responsive ventricular demand pacemaker (VVIR) pacemaker was implanted in 108 patients, rate adaptive dual chamber pacemaker (DDDR) pacemaker in 183 patients and atrial synchronous ventricular pacemaker (VDD) pacemaker in 120 patients according to traditional selection criteria. A total of 39 patients with symptomatic bradycardia due to sinus or atrioventricular (AV) node dysfunction and having absolute standard pacemaker indications, decreased LVEF (35–50%), and QRS duration <120 ms were included in this study. Five patients had atrial fibrillation and severe bradycardia, six patients had AV node conduction disease and severe bradycardia and 28 patients had sinus node dysfunction. The pacing site was selected according to the clinical conditions of the patients. Main reason for the non-randomization was the concern about safety of LV pacing in patients with certain cardiac conditions. Therefore RV pacemakers were implanted to the patients with syncope history and to patients with AV node dysfunction. RV pacing was implanted in dependent patients because of risk of LV lead movement.
Exclusion criteria were normal LV systolic function, QRS duration >120 ms, intraventricular asynchrony in echocardiographic evaluation, indications for internal cardioverter-defibrillator (ICD) and BVP (Note: we obtained the informed consent of all subjects and approved it in an ethical committee.).
Pacemaker implantation
All pacemaker implantations were performed using transvenous approach through the left infraclavicular route. RV leads were placed in the RV apex in 15 patients and LV leads were implanted in posterior, posterolateral or lateral cardiac veins in 15, four and five patients, respectively. LV leads were implanted according to the best measurement of the suggested lead localizations. VVIR pacemakers were implanted in patients with atrial fibrillation using LV leads. VDD pacemakers were implanted in patients with bradycardia due to AV node dysfunction. DDDR pacemakers were implanted in patients with sick sinus syndrome (Figure 1). Seven patients had syncope history and they received RV pacing.
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The patients with RV leads were followed up for 38 ± 12 months and those with LV leads for 35 ± 11 months. At the end of the follow-up period, clinical conditions of the patients, pacemaker dysfunction and safety of the LV and RV leads, changes in LV dimensions and LV function, and presence of intraventricular asynchrony were compared with baseline values.
Echocardiography
Echocardiographic examination was performed before pacemaker implantation and at the end of the follow-up period with a digital ultrasound machine (GE Vivid 7, Horten, Norway) using a combined tissue imaging and Doppler transducer. LV wall thickness, left atrial and LV dimensions were measured from parasternal long axis M-mode tracings according to standard criteria. LVEF was estimated from apical four-chamber and two-chamber views using Simpson’s method.
Interventricular asynchrony is evaluated by assessing the extent of interventricular mechanical delay, defined as the time difference between LV and RV pre-ejection intervals. An interventricular mechanical delay 
40 ms is considered indicative of interventricular asynchrony.14
Colour Doppler tissue velocity data were recorded in the apical four-chamber view at the end of the follow-up period. The frame rate ranged from 80 to 115 frame/s, pulse repetition frequencies ranged from 0.5 to 1 kHz, resulting in aliasing velocities ranging from 16 to 32 cm/s. Tissue Doppler imaging parameters were measured from colour-coded images of three consecutive heart beats by offline analysis. To assess LV asynchrony, the sample volume was placed in the basal portions of the septum and lateral wall, the time to peak systolic velocity was obtained in the septum and lateral wall and the septal-to-lateral delay in peak velocity was calculated as an indicator of LV asynchrony.15 Intraventricular asynchrony was defined as a contraction delay between the septum and lateral wall >65 ms.16
Statistical analysis
Data are given as mean ± standard deviation. Echocardiographic findings before and after implantation were compared with each other using Wilcoxon signed-rank test. In comparison of echocardiographic and clinical results between the patients with RV- and LV-based pacemakers, continuous variables that were normally distributed were analysed with two-tailed t-test and unequally distributed variables were analysed with Mann–Whitney U test. Categorical data and proportions were analysed using Chi-square (
2) or Fisher’s exact test when required. A P-value <0.05 is accepted as statistically significant.
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Results |
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Baseline clinical characteristics of all patients are summarized in Table 1.
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Pacemaker
The mean pacing ratio was 92.3 ± 9.5 and 81.7 ± 13.2% in RV and LV lead implanted patients, respectively (P > 0.05). Pacing threshold and lead impedance values were detected in normal ranges during and after implantation. Baseline lead impedances of the RV and LV were similar. Baseline pacing threshold values of the right lead were significantly lower than the left lead. Although there were no significant changes in the impedance and threshold values of the right lead after implantation, both impedance and threshold values compared with baseline were decreased significantly in the left lead (Table 2). In the VDD group, there was >80% ventricular pacing. LV systolic function was significantly improved in patients with atrial fibrillation and single chamber VVIR pacemaker in the LV pacing group.
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A significant reduction of New York Heart Association (NYHA) class was observed in patients with LV pacing (from 2.1 ± 0.5 to 1.3 ± 0.6, P < 0.05). Functional class decreased at least by one stage in 15 patients, remained unchanged in seven patients and increased in two patients. However, NYHA functional class increased significantly in patients with RV pacing (from 1.4 ± 0.5 to 2.2 ± 0.7, P < 0.05). NYHA class increased in nine patients and remained unchanged in six patients.
Forty per cent of the patients with RV pacing were admitted to the hospital due to heart failure. There was no hospital admission or new onset of heart failure in the LV pacing group.
Echocardiography
Baseline LVEF, LV end-diastolic and end-systolic diameters were similar in both groups. At the end of the follow-up period, EF decreased in eight patients with RV apical pacing and remained unchanged in other seven patients. Mean EF of the group with RV pacemaker decreased significantly compared with baseline values. In the LV pacing group, the EF did not change in five patients, decreased in five patients and increased in 14 patients after implantation. Mean LVEF of the patients with LV-based pacemakers increased significantly compared with baseline values. Although LV end-diastolic diameters did not change significantly in the LV-based pacemaker group, it increased in the RV-based pacemaker group. Echocardiographic parameters are summarized in Table 3.
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Intraventricular asynchrony
Intraventricular asynchrony was not detected in LV lead implanted patients, whereas 11 patients (73%) in the RV lead group had marked new-onset asynchrony (P < 0.001). Mean contraction delay between septum and lateral wall in LV and RV pacing patient groups were 28 ± 6 and 84 ± 21 ms, respectively (P = 0.002)(Figure 2A). There was a negative correlation between the degree of intraventricular asynchrony and the relative change in the LVEF (in right pacing group r = –0.78, P = 0.01; in left pacing group r = –0.66, P = 0.003). We assessed the relationship between the intraventicular conduction time and LVEF. Figure 3 shows the relationship between the intraventricular conduction time and change in the LV systolic function.
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Interventricular asynchrony
New-onset interventricular asynchrony was detected in three and 10 patients in LV and RV lead groups, respectively. The time difference between LV and RV pre-ejection intervals was 30 ± 9 and 54 ± 19 ms, respectively (P = 0.001) (Figure 2B). There was a significant relationship between the degree of interventricular asynchrony and the relative change in the LVEF in the RV pacing group (r = –0.83, P = 0.003).
Intraventricular and interventricular asynchrony was found together in seven of RV lead implanted patients. Although statistically insignificant, the LVEF decreased and end-diastolic diameter increased in these patients (P = 0.07). Although LV end-diastolic diameter was 56 ± 6 mm and EF was 39 ± 7% before implantation, LV end-diastolic diameter increased to 60 ± 6 mm and EF decreased to 33 ± 9% after follow-up period.
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Discussion |
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In the present study, LV pacing resulted in favourable effects on clinical condition and echocardiographic parameters of the patients with permanent pacemaker indication and mild to moderate LV systolic dysfunction. In the LV pacing group new-onset intraventricular asynchrony did not develop, LV systolic function improved and there was a significant LV reverse remodelling in contrast to the RV pacing group.
Although RV pacing affects the diastolic filling pattern positively, standard DDDR pacemaker implantation has been abandoned because of adverse effects on LV systolic function in heart failure patients.17 Multicenter Automatic Defibrillator Implantation Trial II3 study showed that RV pacing was found to be associated with increased incidence of heart failure in the ICD group. Similar results were obtained from the Dual Chamber and VVI Implantable Defibrillator Study.4
Consistent with previous studies, RV pacing was found to decrease LV systolic function significantly during a long-term follow-up period in this study. Atrioventricular synchrony was maintained in patients with RV pacing. In the VDD group, there was >80% ventricular pacing. In contrast to the RV pacing, LV systolic function was significantly improved in patients with atrial fibrillation and single chamber VVIR pacemaker despite the absence of the atrial contraction in the LV pacing group. Although the baseline echocardiographic parameters before pacemaker implantation were similar in both groups, the reason for the significantly decreased LV systolic function and increased incidence of heart failure in the RV pacing patient group was thought to result from different localization of ventricular pacing electrode. The LV paced from posterior or lateral localization via coronary sinus, contracts more effectively and improves systolic functions in contrast to RV apical pacing. In a study evaluating pacing localization, the optimal LV function resulted most accurately only by left and biventricular pacing.9
In this study, the effects of the LV and RV pacing on ventricular synchrony were also evaluated. None of the patients had any asynchrony before pacemaker implantation. After implantation, new-onset inter- and intraventricular asynchrony developed in the RV pacing group and it was the main physiopathological mechanism for the worsening of the LV dysfunction. The significant relationship between the degree of developed intraventricular asynchrony and the decrease in EF was supporting this hypothesis. In none of the patients with LV pacing significant intraventricular asynchrony developed and interventricular asynchrony was developed in three patients. LV systolic functions and clinical conditions of the patients in this group were much better and probably related to the absence of ventricular asynchrony. LV activation does not use Purkinje system after RV activation with RV pacing. Activation occurs via conduction from myocardium to myocardium. Activation of the LV free wall delays and delayed contraction results in interventricular asynchrony. In the LV pacing, the activation of the RV occurs over the right bundle branch at the longest AV intervals. This results in the fusion of LV pacing and intrinsic conduction of RV, so biventricular activation was obtained.18 For this reason interventricular asynchrony does not develop in LV pacing.
In studies evaluating dilated cardiomyopathy patients, the positive effect of the LV pacing on the LV systolic function was equal or even superior to biventricular pacing.9,10,19,20 Various clinical studies showed improvements in the cardiac functions and clinical conditions after upgrading of the RV pacing to biventricular pacing.21 Several studies also showed regression in the LV diameters after biventricular pacing.12 Some studies have shown benefit in LV pacing alone, but those were performed in populations similar to those of cardiac resynchronization therapy, not in patients with a narrow QRS and no dysynchrony.
Although our patient group was different, similar to other studies there were no adverse effects of LV pacing on the remodelling. LV end-diastolic diameters after left pacing were similar to baseline values, but end-systolic diameters improved significantly. The main reasons for the better LVEF and clinical conditions of the patients in the left pacing group were the synchronized contraction, improvements in systolic diameters and the absence of the development of remodelling.
Limitations of the study
This is a non-randomized study and the pacing site was selected according to the clinical condition of the patients. Main reason for the non-randomized methodology was the concern about safety of LV pacing in patients with certain cardiac conditions. Nevertheless, LV pacing caused no safety problems as mentioned earlier.
LV pacing was not compared with other pacing modalities, such as biventricular pacing or RV outflow tract pacing. Previous studies have shown that, despite a different effect on LV electrical dispersion, left univentricular pacing can achieve the same mechanical synchronization as biventricular pacing. However, comparison of LV pacing with other pacing modalities in patients with standard pacemaker indications and mild–moderate LV dysfunction may reveal important findings in the management of these patients.
In conclusion, LV-based pacemaker system can be used safely as RV-based pacemakers. In contrast to right apical pacing, left epicardial pacing does not lead to ventricular asynchrony, and affects the LV systolic function and the clinical condition of patients positively. We conclude that in patients with permanent pacemaker indications and mild to moderate LV systolic dysfunction, LV pacing—even in the absence of ventricular asynchrony—is more suitable than RV apical pacemakers.
Conflict of interest: there is not any actual or potential conflict of interest of the authors.
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