Tricuspid insufficiency after cardiac-implantable electronic device placement.

OBJECTIVE: Device-related estimates of incidence and significance of tricuspid regurgitation (TR) is mainly based on case reports and small observational studies. We sought to determine whether right-heart device implantation increased the risk of TR in this interventional study.
METHODS: All patients who underwent permanent pacemaker (PPM) or other device implantation were assessed for degree of TR at one year. The data collected was analyzed on IBM SPSS version 26. Descriptive statistics were applied for qualitative variables. Mean and standard deviation were applied for quantitative variables. Regression analysis and paired t-tests were applied for the degree of change and predictors of TR.
RESULTS: Out of 165 participants, 73.94% were male. The mean age of the participants was 59.86 ± 12.03 years. Dual-chamber pacemaker (DDDR) was the most common device implanted (78.18%) causing significant TR and drop in left ventricular ejection fraction as compared to other devices (p-value < 0.05). The paired t-test for changes in ejection fraction (LVEF) and TR were also significant (p-value < 0.05). A regression model predicted significant TR to depend on baseline LVEF (p-value < 0.05).
CONCLUSION: Device-related worsening of TR is related to mechanical mechanisms. It is significantly associated with DDDR pacemakers after a 1-year follow-up.

Introduction

The technology of endocardial transvenous lead for permanent cardiac pacing has advanced since the advent of this procedure [1]. These pacing leads have become thin, highly flexible due to multi-helical alloy with long-lasting covering sheaths being used [2]. However, despite its size and easy maneuverability, the anatomy mandates that the lead be placed across the tricuspid valve [3]. This is associated with the risk of tricuspid valve dysfunction [2,4].

Tricuspid regurgitation (TR) is a frequently seen valvular lesion on echocardiography with about 1.6 million people in the USA being affected. The incidence is less than 0.1% worldwide [5]. Several isolated presentations of pulvonic valve vegetation are also seen with right heart device placement [6]. Significant TR is associated with increased risk for developing a variety of complications, which include congestive cardiac failure, elevated mortality, decreased functional class, and peripheral edema [7].

The mechanisms include interference of valve coaptation, perforation of the valve by lead entrapment, and asynchrony of the right and left ventricular activation by the permanent pacemaker (PPM) [8]. Asynchrony is specifically true for patients with single-chamber devices in situ as it causes pseudo-regurgitation as a result of atrial contraction against a closed tricuspid valve [1,9]. Despite, correction by upgrading the single chamber device in place, significant TR requires emergent lead retraction [10-12].

Therefore, the objective of this study was to determine whether right-heart device implantation increased the risk of TR. The study also aimed at determining predictors for the possible change.

Methods

This prospective, interventional study was conducted at Abbas Institute of Medical Sciences between November 2019 to November 2020. All patients provided informed written consent, and Institutional Ethical Board approval was granted before data collection (Study ID#AIMS/08/19). The sample size was calculated using a software. A preliminary report from the registered patients for pacemaker placement revealed about 286 patients who had received implantation devices. Using this expected number, the sample size was about 165 patients when assuming an anticipated frequency of 0.5 and confidence intervals of 95%. The exclusion criteria, apart from patients’ age less than 18 years and inability to give consent, for the study were as follows:

Previous known regurgitation valve disease

Known structural heart disease, such as Hypertrophic Obstructive Cardiomyopathy (HOCM), Ebstein’s anomaly, flail leaflet, rupture of valve or prolapse

Prior coronary artery by-pass

Prior device in place including permanent pacemaker, implantable cardioverter defibrillator, and cardiac resynchronization device

Multiple leads in place from previous devices,

Previous device explantation and reimplantation

History of infected wound from device implantation

History of lead associated endocarditis or native valve endocarditis

History of rheumatic fever

Suboptimal visualization of the heart, such as suboptimal window of acoustic artifacts due to leads or otherwise.

All the devices were put in the hospital electrophysiology lab. In dual-chamber, rate-modulated pacemaker (DDDR) and implantable cardioverter defibrillator (ICD), one lead was placed in right ventricular (RV) apex and other lead in right atrial appendage (RAA). In single chamber pacemaker (VVIR), a single lead was placed in RV apex. As for cardiac resynchronization device (CRT), a third lead was placed in the coronary sinus. The devices were inserted according to the broad categories of heart block and failure with DDDR and VVIR used for heart blocks and CRT used for heart failure.

The baseline variables were recorded in the in-house data entry system (HMIS). This included age, gender, comorbid, cause of device insertion, and the type of device to be implanted. The number of leads inserted were also assessed as demonstrated by chest X-ray in the hospital image viewer (PACS) or by implantation report. All participants underwent standard two-dimensional echocardiography with the same echocardiography machine (Vivid 7, General Electric Ultrasound) and 2.5 to 3 MHz transducer was used to assess the pertinent cardiac structures and measurements. Images included parasternal, apical, and subcostal views. Tricuspid valve regurgitation was estimated visually, by a qualitative method of eyeballing the jet of tricuspid regurgitation and calculating the jet area, using color flow Doppler. The regurgitation was also approximated quantitatively using vena contracta width. There were different categories for width used to assess grade of tricuspid regurgitation; vena contracta <0.50 cm was grade 1+, ≥0.50 but <0.69 cm was grade 2+ and ≥0.69 cm was grade 3+ [13]. In addition to TR, echocardiographic characteristics included left ventricular ejection fraction (LVEF) by visual estimation and modified Simpson’s method. Other parameters such as left atrial volume index (LAVI) and right atrial volume index (RAVI) were also measured. Patients with acoustic shadows and artifacts due to leads were eliminated by taking measurements in right ventricular outflow tract (RVOT) view, parasternal short axis (PSAX), substernal and four chamber view. The prevalence of significant TR was assessed by comparing the echocardiograms before device implantation and following device implantation. Significant TR was defined as an increase of more than one degree from baseline, that is, an increase ≥2. Echocardiogram was followed up after 1 year to see the degree of TR change overtime.

Descriptive statistics were used for qualitative variables. Mean and standard deviation were used for variables such as age. The proportion of participants with significant TR using both quantitative and qualitative techniques were compared using chi-square test. Student’s t-test was used to determine the significance of changes in TR and ejection fraction before and after intervention for all devices. Regression analysis was done to determine the association of predictors with the risk of significant TR. The data were analyzed using IBM Statistical Software for Social Sciences (SPSS) version 26. A p-value of <0.05 was considered significant.

Results

There were 165 participants in the study. Out of 165 participants, 122 participants (73.94%) were male and 43 participants were female (26.06%). The mean age of the participants was 59.86 ± 12.03 years. The characteristics of the patients are shown in Table 1.

Table 1.

Baseline and follow-up characteristics

Characteristics (Chronic)
Age; mean ± SD	59.86 ± 12.03
Females; n (%)	43 (26.06%)
Co-morbid conditions n (%)
Hypertension	77 (46.67)
Ischemic Heart Disease	73 (44.20)
Chronic Kidney Disease	15 (9.13)
Smokers	54 (32.70)
Characteristics (Clinical)	Baseline	1-year follow-up
Severity of TR; n (%)
None (0)	140 (84.80)	50 (30.30)
Mild (1+)	25 (15.20)	46 (27.90)
Moderate (2+)	0 (0.00)	40 (24.20)
Severe (3+)	0 (0.00)	29 (17.60)
LA volume (Mean±S.D)	27.16 ± 7.57	30.81 ± 15.91
RA volume (Mean±S.D)	25.86 ± 3.15	31.07 ± 6.30
Annular tricuspid diameter (Mean±S.D; cm)	25.71 ± 2.98	27.32 ± 4.11
LVEF (Mean±S.D; %)	37.24 ± 14.55	33.09 ± 14.21
Vena contracta width (Mean±S.D; cm)	0.07 ± 0.01	0.45 ± 0.20

TR-tricuspid regurgitation, LA-left atrium, RA-right atrium, LVEF-left ventricular ejection fraction, SD-standard deviation, n-frequency.

There were no patients with significant TR at the start of the study. There were 11 participants (6.67%) with atrial fibrillation at the start of the study. After the intervention, 5 additional participants (9.69%) had developed atrial fibrillation. This increase in the number of participants was not significant (p > 0.05). 41.20% of the participants had developed significant TR at the 1-year follow-up (p < 0.05).

The indications and proportions of different devices used in the study are shown in Table 2.

Table 2.

Devices used and their indications

Indications	Devices
	DDDR (n, %)	VVIR (n, %)	ICD (n, %)	CRT (n, %)
AV block	128 (77.58)	14 (8.48)	0 (0.00)	0 (0.00)
Scar VT	1 (0.61)	0 (0.00)	5 (3.03)	0 (0.00)
Heart Failure	0 (0.00)	0 (0.00)	0 (0.00)	5 (3.03)
Ischemic VT	0 (0.00)	0 (0.00)	12 (7.27)	0 (0.00)

DDDR- dual-chamber, rate-modulated pacemaker, VVIR- single chamber pacemaker, ICD- implantable cardioverter defibrillator, CRT- cardiac resynchronization device, n-frequency.

The differences in grades of TR did not vary when both the vena contracta technique and qualitative technique were compared (p > 0.05). The change in mean LVEF at 1-year follow-up was significant (p < 0.05). The paired t-test for the mean vena contracta width, at baseline and at follow-up, was significant (p < 0.05). The independent samples test for changes in TR and TR before intervention revealed that there were significant differences in the distribution of participants (p < 0.05). The changes in LVEF and TR were not significantly determined by gender, type of device, cause of device insertion, and comorbid conditions (p > 0.05). The changes in regurgitation and LVEF for the devices are shown in Table 3.

Table 3.

Left ventricular ejection fraction and tricuspid regurgitation across devices

Device	LVEF			TR
	Baseline LVEF (Mean±S.D)	1-year follow-up LVEF (Mean±S.D)	p-value	Baseline vena contracta(Mean±S.D)	1-year follow-up vena contracta(Mean±S.D)	p-value
DDDR	37.87 ± 15.04	33.91 ± 14.37	0.03	0.08 ± 0.03	0.45 ± 0.20	<0.05
VVIR	35.36 ± 12.48	27.86 ± 14.10	0.15	0.00 ± 0.00	0.51 ± 0.17	<0.05
ICD	36.47 ± 12.47	32.35 ± 13.00	0.35	0.09 ± 0.02	0.48 ± 0.21	<0.05
CRT	29.00 ± 14.32	27.50 ± 13.52	0.87	0.20 ± 0.10	0.30 ± 0.17	0.29

DDDR- dual-chamber, rate-modulated pacemaker, VVIR- single chamber pacemaker, ICD- implantable cardioverter defibrillator, CRT- cardiac resynchronization device, LVEF-left ventricular ejection fraction, TR- tricuspid regurgitation, S.D.-standard deviation.

The paired t-tests for mean RAVI, LAVI and annular tricuspid diameter, at baseline and at 1-year follow-up, were all significant (p < 0.05). The difference in changes in left atrium volume index at 1-year follow-up was significant for patients who had either ischemic heart disease or smoked (p < 0.05). The changes in echocardiographic parameters across all devices are shown in Table 4.

Table 4.

LAVI, RAVI and tricuspid annular diameter across devices

Parameter	Device	Baseline(Mean±S.D)	1-year followup(Mean±S.D)	p-value
LAVI	DDDR	25.26 ± 4.29	29.24 ± 16.76	<0.05
	VVIR	47.57 ± 3.23	48.50 ± 2.77	0.40
	ICD	24.47 ± 4.80	27.41 ± 5.28	0.09
	CRT	28.20 ± 5.54	33.40 ± 4.56	0.14
RAVI	DDDR	26.04 ± 3.04	31.14 ± 6.23	<0.05
	VVIR	24.71 ± 2.40	32.14 ± 6.89	<0.05
	ICD	25.06 ± 3.05	30.47 ± 7.05	<0.05
	CRT	27.20 ± 3.56	28.40 ± 4.39	0.65
Tricuspid annular diameter (cm)	DDDR	25.46 ± 2.92	26.95 ± 4.17	<0.05
	VVIR	26.57 ± 3.18	27.86 ± 3.94	0.33
	ICD	26.82 ± 3.45	29.63 ± 3.74	<0.05
	CRT	27.00 ± 2.12	27.80 ± 1.64	0.52

LA-left atrial volume index, RA-right atrial volume index, DDDR- dual-chamber, rate-modulated pacemaker, VVIR- single chamber pacemaker, ICD- implantable cardioverter defibrillator, CRT- cardiac resynchronization device, S.D.-standard deviation.

A logistic regression model was used to determine predictors of significant TR. The model predicted significant TR from many independent variables. After adjustments, the independent predictor for the outcome was baseline LVEF. However, not all the variables significantly added to the results as shown in Table 5. No statistical difference was observed in level of TR between devices.

Table 5.

Regression analysis

Variables	Adjusted Estimates			Unadjusted estimates
	Risk	95% CI	p-value	Risk	95% CI	p-value
Age	0.99	0.97–1.02	0.68	1.00	0.97–1.03	0.94
Gender	1.37	0.65–2.88	0.41	1.04	0.45–2.42	0.93
Type 2 Diabetes Mellitus	1.58	0.80–3.15	0.18	2.11	0.99–4.51	0.54
Hypertension	1.70	0.79–3.62	0.17	2.15	0.91–5.10	0.08
Chronic Kidney Disease	0.48	0.17–1.33	0.16	0.33	0.10–1.09	0.06
Ischemic heart disease	1.21	0.62–2.37	0.58	1.18	0.56–2.48	0.67
Smoking	0.89	0.44–1.08	0.75	1.01	0.44–2.29	0.99
Baseline AF	0.43	0.13–1.51	0.19	0.72	0.11–4.99	0.74
Baseline LVEF	1.06	1.03–1.09	0.00	1.05	1.03–1.09	0.00
Baseline TR	7.37	2.59–20.95	0.00	3.26	0.95–10.99	0.06
Baseline LAVI	0.98	0.94–1.02	0.27	0.99	0.93–1.06	0.73
Baseline tricuspid annular diameter	0.96	0.86–1.07	0.47	0.97	0.85–1.09	0.58

AF-atrial fibrillation, LVEF-left ventricular ejection fraction, TR-tricuspid regurgitation, LA-left atrial volume index.

The patients were managed conservatively except for cases which had either grade 3 tricuspid regurgitation or symptoms of right heart failure in which cardiac surgery consultation was requested for tricuspid repair or lead extraction. However, the management of tricuspid regurgitation was beyond the focus of the study.

Discussion

In our study, we found that there was about a 70:30 ratio of male to female participants. The female participants (26.06%) were similar to the percentage of participants (22.00%) in another study focusing on electrical failure secondary to pacing leads [14]. The mean age of our participants was 59.86 ± 12.03 years. In contrast, a 2015 study reported higher mean age of 74.00 ± 14.00 years [15]. The ejection fraction in our study decreased after the placement of leads from 37% to about 33%. A similar result was noted in another study that determined left ventricular ejection fraction less than 40% and mid-range ejection fraction as predictors for deterioration of cardiac function [16].

In our study, the grade of tricuspid regurgitation had increased at a 1-year follow-up and 41.20% of the participants had developed a significant tricuspid regurgitation at 1-year follow-up. This was in contrast to another study which concluded that 10% of the participants had developed significant tricuspid regurgitation and had an increase of two grades in the phenomenon [17]. This was surprising considering the age of the participants as less than 60 years. The possible reasons for the findings include the presence of multiple comorbid conditions amongst the patients. There is a significant risk of tricuspid regurgitation (26.50%) with left heart ischemic disease [18].

The most common device used was DDDR. This device had decreased ejection fraction significantly by about 4% in our study. This finding is comparable to a study that investigated cardiomyopathy due to pacemaker leads and DDDR was associated with a high incidence of cardiomyopathy characterized by a fall in ejection fraction by 10% [19]. In contrast to our study findings of a non-significant decrease in ejection fraction in patients with CRT, a recent study had shown a significant improvement in LVEF [20]. In our study, except for CRT, all devices were associated with an increase in tricuspid regurgitation which is in contrast to a previous study suggesting VVIR as the least acceptable device due to the risk of significant TR (p < 0.05) [21].

Our study showed that DDDR insertion was associated with significantly increased LAVI, RAVI and tricuspid annular diameter, VVIR insertion was associated with significantly increased RAVI and ICD was associated with significantly increased RAVI and tricuspid diameter. These findings were in contrast to a 2019 study which mentioned that device implantation did not significantly impact the dimensional volumes of the chambers [20]. The possible reason for the finding in our study is related to LV dysfunction as seen by reduced LVEF ejection fractions. Owing to LV dysfunction and positive remodeling, there is gradual dilation of cardiac chambers leading to both mitral and tricuspid regurgitation.

Our study did not determine age to be a significant predictor of worsening TR after lead placement as compared to another study [17]. The number of leads did not predict TR and the position of leads was more important [22]. The leads impinging on the anterior leaflet, the anteroposterior or anteroseptal commissure, and interfering with leaflet mobility were associated with a higher risk [23]. Baseline LVEF was an important predictor as explained by previous findings. This is attributable to some mechanisms including technical difficulties experienced during the pacing technique, pacing burden load, lead location, and even, number [24]. However, in contrast to a recent study, atrial fibrillation status was not an important predictor for significant TR [20]. The possible explanation for this is that in case of atrial fibrillation, the central pacemaker is implanted and in that case, the device implantation, not atrial fibrillation, would be a significant predictor for TR.

Although not extensively explored in our study, surgery, including lead extraction or valve repair, has been considered an efficacious procedure in patients with class IV heart failure secondary to tricuspid regurgitation, and therefore, these specific cases were sent for a surgery review [25].

In contemporary electrophysiology, introduction of leadless pacemakers has demonstrated safety and efficacy in short and intermediate follow-up as an alternative to transvenous pacing. This technology shows promise for cardiac pacing devices in the future. The LEADLESS trial was the first human trial for leadless pacing using a Nanostim device. The trial enrolled 33 patients with successful implantation achieved in 97% patients. The complication free rate was 94% at three months. Several other clinical trials have been conducted till now and show benefit of this technology for select patients [26].

Study limitations

The limitations of the study include a small sample size and center-specific study. Additionally, the time for lead insertion and its subsequent position were not investigated. The results of the study were based on techniques which yielded similar results for significant TR. Another limitation of the study was that right ventricular systolic pressures were not measured because the centre does not include the parameter under normal circumstances, considering that the values for these pressures have not been well-defined. The management for device-related TR was beyond the scope of this study and therefore, the data as well as analysis were not extended to that stage.

Conclusion

Worsening of TR is a common finding from baseline to 1-year with a device in the right ventricle, especially after PPM implantation. This is due to either mechanical or physiological mechanisms. Clinical consideration includes the extraction of the offending leads. Large, well-controlled prospective studies are need to assess the incidence and timing of TR along with associated prognosis and mortality.