Induction and aggravation of atrioventricular valve regurgitation in the course of chronic right ventricular apical pacing

Abstract

Aims

Valvular regurgitation, especially on the right side of the heart, is a common finding even in patients without endocardial pacing leads. The severity of valvular regurgitation can change after permanent pacemaker (PPM) implantation. Ventricular pacing has been shown to cause ventricular dysfunction. The purpose of this study was to evaluate the mid-term effects of right ventricular (RV) apical pacing on atrioventricular (AV) valvular regurgitation in patients with a normal left ventricular function before PPM implantation.

Methods and results

Patients who required dual-chamber pacemakers due to a high-degree AV block were enrolled in the study. Initial echocardiography was performed before PPM implantation and re-evaluation by echocardiography was performed every 24 months thereafter. A total of 125 patients (61 male; mean age: 66.57 ± 6.45 years) were included in the study, and 115 pacemaker-dependent patients were followed up (mean ± SD; 4.08 ± 0.8 years). Echocardiography demonstrated mild tricuspid regurgitation (TR) and mitral regurgitation (MR) in 70 (60.1%) and 34 (29.6%) patients before PPM implantation, respectively. Moderate TR and MR were detected in 10 (8.7%) and 1 (0.9%) patients, respectively. Thirty-six (31.6%) patients showed moderate-to-severe TR at long-term follow-up, compared with the 10 (8.7%) patients, who had the same degree of TR before RV apical pacing (P< 0.001). Mild and moderate MR were detected in 54 (47%) and 8 (7%) patients after PPM implantation on the last echocardiography(P< 0.001). Baseline systolic pulmonary artery pressure (PAP) was 29.24 ± 8.45 mmHg, which increased to 36 ± 11 mmHg on the last echocardiography (P< 0.001).

Conclusion

Considering the haemodynamic effects at mid-term follow-up, left ventricular dysfunction is rare in patients with RV apical pacing and normal baseline left ventricular function. Right ventricular apical pacing is associated with a significant increase in the prevalence and severity of TR and MR.

Permanent pacemaker, RV apical pacing, Tricuspid regurgitation, Mitral regurgitation

Introduction

Right ventricular (RV) apical pacing induces an iatrogenic left bundle branch block pattern of electrical conduction abnormalities that causes interventricular and intraventricular desynchronization.^1,2 In addition to the undesirable effects of RV apical pacing on ventricular function, progression of mitral (MR) and tricuspid regurgitation (TR) has been described.³ The immediate effects of RV apical pacing on valvular regurgitation have been studied in small patient cohorts,^4,5 but the mid-term and long-term effects are yet to be fully explored in larger patient groups. The purpose of this study was to evaluate the mid-term effects of RV apical pacing on atrioventricular (AV) valvular regurgitation in patients with a normal left ventricular function before pacemaker implantation.

Methods

Patient selection

Patients with intermittent high-degree atrioventricular block (AVB), including second- and third- degree AVB were enrolled. The exclusion criteria were: (i) persistent complete heart block; (ii) sinus node dysfunction with a normal AV nodal function; (iii) left ventricular dysfunction; and (iv) documented coronary artery disease. The RV pacing lead was implanted in the RV apex. The study was approved by the Ethics committee of our centre. The mean follow-up duration was 4.08 ± 0.8 years.

Echocardiography

A comprehensive evaluation of the AV valves was conducted before permanent pacemaker (PPM) implantation. It included the measurement of the left ventricular function, and the evaluation of AV valves. The intensity of MR was assessed using the Doppler vena contracta width [mild if vena contracta width (cm) <3 mm and severe if>7 mm] and colour jet area (mild if the colour jet area <20%, moderate if 20–40%, or severe if >40%), regurgitant volume (mild if regurgitant volume <30 mL, moderate if 30–60 mL, or severe if >60 mL) and regurgitant fraction (mild if regurgitant fraction <30%, moderate if 30–50%, or severe if >50 mL). Quantification of TR was done using Doppler vena contracta width [moderate if vena contracta width (cm) <0.7 and sever if ≥0.7] and colour jet area (mild if the colour jet area was <5 cm²; moderate if 5–10 cm²; or severe if >10 cm²). The RV systolic pressure or pulmonary artery systolic pressure was measured using the TR jet. The most important factor in determining the systolic pressure is the method of right atrial (RA) pressure measurement. The RA pressure was measured considering the RA size, severity of TR, and the inferior vena cava size. Right atrial pressure was considered 5 mm if the RA size was normal, TR was mild, and the inferior vena cava was normal sized. For moderate degrees of TR with mild or no atrial enlargement, an assumed constant of 10 mm was employed. For severe TR in the presence of a dilated RA, and a dilated inferior vena cava without respiratory variation, an assumed constant of 15 mm was used.

The 12-lead electrocardiography

Transient complete heart block and/or advanced AVB were detected in 63(55%) patients. Second-degree AVB (Mobitz Type I AVB, Type II AVB, and 2:1 AVB) was seen in 52(45%) patients. In the last group, 28 patients had a P to R wave interval longer than 200 ms. QRS complex had right bundle branch block (RBBB) or left bundle branch block (LBBB) pattern in 90 (78%) patients.

Pacemaker analysis

Pacemaker analysis was performed twice a year. Patients with a ventricular pacing rate of more than 90% were considered to be pacemaker dependent. Some of the patients were pacemaker dependent due to the nominal programmed paced AV and sensed AV intervals. Seventy per cent of the patients were pacemaker dependent with programmed AV interval >200 ms.

Statistical analysis

Continuous variables were presented as the mean ± standard deviation (SD), and the categorical variables were presented as percentages. All the above analyses were considered significant at P < 0.05 (two tailed). SPSS 15.0 (SPSS inc., Chicago, IL, USA) was utilized for data storage and analysis. The baseline characteristics of the patients and their relationships were analysed using the χ² , Wilcoxon signed-rank test, pair t-tests, and logistic regression.

Results

Baseline characteristics

A total of 125 patients, 61 male and 64 female, were enrolled in this prospective study. Ten patients were not pacemaker dependent at the end of the first year; the remaining 115 patients were followed up. Demographic and echocardiographic characteristics of the studied patients are depicted in Table 1. The mean age of the patients was 66.57 ± 6.45 years, and the follow-up duration (mean ± SD) was 4.08 ± 0.8 years. All the patients had RV apical pacing. The mean left ventricular ejection fraction (mean ± SD, %) was 55.41 ± 2.63 before, and 51.03 ± 2.87 after pacemaker implantation (P value<0.001). One of the patients died due to cardiogenic shock 1 year after anteroseptal myocardial infarction.

Table 1

Baseline demographic and echocardiographic data

Baseline characteristics	All patients (n= 115)
Age (years)	66.57 ± 6.45
Sex (male/female)	56/59
Follow-up period (years)	4.08 ± 0.8
Sinus rhythm	115 (100%)
12-lead ECG
Transient CHB and/or advanced AVB (%)	63(55%)
Others (%)	52(45%)
QRS pattern
RBBB or LBBB (%)	90(78%)
Normal	25(22%)
Echocardiographic parameters before pacemaker implantation
LVEF	55.41 ± 2.63%
PAP	29.24 ± 8.45 (mmHg)
MR
Mild	29.6%
Moderate	0.9%
Severe	0 %
TR
Mild	60.1
Moderate	8.7%
Severe	0 %

LVEF, left ventricular ejection fraction;PAP, pulmonary artery pressure; TR, tricuspid regurgitation; MR, mitral regurgitation.

Tricuspid and mitral valve regurgitation

The results of the different echocardiographic parameters are demonstrated in Table 2. Mild TR and MR were detected in 70 (60.1%) and 34 (29.6%) patients before PPM implantation, respectively. Sixty per cent (60.1%) of the patients did not have MR the number of the patients with mild MR increased after RVA pacing (P= 0.001). Moderate TR and MR (Figure 1) were demonstrated in 10 (8.7%) and 1 (0.9 %) patients, respectively (Table 3). Thirty-six (31.6%) patients showed moderate-to-severe TR at long-term follow-up, compared with the 10 (8.7 %) patients who had the same degree of TR before RV apical pacing (Table 3, P< 0.001), which was independent of the systolic pulmonary artery pressure (PAP; P value = 0.1).

Figure 1

Presence of moderate tricuspid regurgitation after pacemaker implantation in a patient with normal tricuspid valve.

Table 2

Different echocardiographic parameters before and after permanent pacemaker implantation

	Before PPM implantation	After PPM implantation	P value
MR
Jet area (%)	15 ± 3.9	19.8 ± 7.3	<0.001
Vena contracta width (cm)	0.2 ± 0.09	0.27 ± 0.13	0.001
Regurgitant fraction (%)	21.8 ± 4.9	27.1 ± 7.9	0.001
Regurgitant volume (mL)	22.3 ± 9	26.4 ± 11.3	0.001
TR
Colour jet area (cm2)	3.1 ± 1.7	5.6 ± 2.8	0.001
Vena contracta width (cm)	0.3 ± 0.15	0.54 ± 0.17	0.003

TR, tricuspid regurgitation; MR, mitral regurgitation.

Table 3

Frequency of different degrees of mitral regurgitation and tricuspid regurgitation before and after permanent pacemaker implantation

	Before		After
	number	%	number	%
MR
—No MR and/or trivial MR	80	68.8	52	46
—Mild MR	34	29.6	54	47
—Moderate MR	1	0.9	8	7
—Severe MR	–	–	–
TR
—No TR and/or trivial TR	35	30.3	4	3.5
—Mild TR	70	60.1	74	65
—Moderate TR	10	8.7	30	26.3
—Severe TR	–	–	6	5.3

TR, tricuspid regurgitation; MR, mitral regurgitation.

Age and sex were not associated with valvular regurgitation after RV apical pacing. The systolic PAP was 29.24 ± 8.45 mmHg. Forty-five patients had a systolic PAP of more than 30 mmHg. The systolic PAP rose to 36 ± 11 mmHg on the last echocardiography (P< 0.001).

Discussion

In concert with the data regarding the adverse haemodynamic and clinical effects of the spontaneous LBBB, newer data are emerging, which convincingly indicate that the iatrogenic variety of LBBB, produced by conventional RV apical pacing, may be equally harmful. More data on the adverse effect of RV apical pacing have just become available via studies assessing the prevalence of left ventricular dysfunction in patients with moderately left ventricular dysfunction.^6–9 In the present study, we assessed the adverse impacts of RV apical pacing on the left ventricular function during the years after pacemaker implantation in patients with preserved left ventricular function. Despite the fact that RV apical pacing can lead to haemodynamic deterioration and clinical worsening in patients with left ventricular dysfunction, in most of our patients receiving pacemakers with ventricular apical pacing, the ventricular function was preserved in normal limits during a follow-up period of 4.08 ± 0.8 years. None of the patients developed symptomatic left ventricular dysfunction except for one. Severe LV dysfunction occurred in the last patient due to acute anteroseptal myocardial infarction, and the patient died due to cardiogenic shock. We concluded that in the absence of an underlying left ventricular dysfunction, RV apical pacing can be safe at mid-term follow-up.

Right ventricular apical pacing and valvular regurgitation

Some researchers have reported TR after endocardial pacing lead implantation.^10–12 In contrast, several studies have reported no significant change in valvular regurgitation after implantation.^13–15 The diagnosis of TR can be difficult by echocardiography even in experienced centres. The detection of TR may be missed because of acoustic shadowing from the PPM leads and suboptimal visualization of the regurgitant jet. There are some data demonstrating more severe degrees of TR after pacing, especially in those with RV apical pacing.¹⁶ This may be due to the damage of the tricuspid valve by the implantation procedure,¹⁷ mechanical interference of the pacing leads with the tricuspid valve function, and RV mechanical dyssynchrony as a consequence of RV apical pacing.¹⁶ The present study is the largest study to date to have documented intensification of TR after RV apical pacing at mid-term follow-up. None of the patients developed symptoms related to the pacing effect on the tricuspid and mitral valves. Mitral regurgitation was not evaluated systematically after PPM implantation. It has been shown in dog models that RV pacing can increase mitral and tricuspid valve incompetence.¹⁸ While the incidence of MR appeared to be low at baseline, this study shows that MR can increase in the course of time due to permanent RV apical pacing. This holds true, especially in patients with pre-existing MR. Left ventricular dyssynchrony can be considered as a cause of MR after long-term RV apical pacing. There are a few reported cases of acute severe MR as an immediate perioperative complication of PPM insertion, leading to acute haemodynamic deterioration.

Rita et al.¹⁹ demonstrate that RVA pacing might immediately induce severe MR and acute cardiac failure, even in patients with preserved left ventricular contraction. This case shows the clinical and echocardiographic improvement in acute MR induced by RVA pacing via the RV outflow tract pacing, probably by improving ventricular dyssynchrony.¹⁹

In this study, we evaluated the role of the pre-pacemaker systolic PAP in predicting ventricular dysfunction or valvular regurgitation after PPM implantation which had not been addressed previously. We found that the pre-pacemaker systolic PAP per se was not a risk factor for TR after PPM implantation. None of our patients had moderate or sever pulmonary hypertension. Therefore, the effects of RV apical pacing in the last group are unknown.

Study limitation

This was a single-centre experience, and we were unable to assess a relationship between the physical characteristics of PPM leads and the likelihood of tricuspid valve damage. Figure 1.

Conclusion

Considering the haemodynamic effects at mid-term follow-up, left ventricular dysfunction is rare in patients with RV apical pacing and normal baseline left ventricular function. Right ventricular apical pacing is associated with a significant increase in the prevalence and severity of TR and MR.

Conflict of interest: none declared.