
==== Front
Heart Rhythm O2
Heart Rhythm O2
Heart Rhythm O2
2666-5018
Elsevier

S2666-5018(24)00227-7
10.1016/j.hroo.2024.07.008
Brief Report
Incidence and predictors of cardiomyopathy after implantation of leadless pacemakers: A comparative analysis with patients with transvenous systems
Kleiman Jeremy MD
Varrias Dimitrios MD
Varkey Ashwin MD
Young Alexandra MD
Wolf Elliot BA
Gasparis Christopher BA
Leavitt Jonas BS
Coleman Kristie M. BSN Kcoleman1@northwell.edu
∗
Epstein Laurence M. MD, FHRS
Mountantonakis Stavros E. MD, MBA, FHRS
Northwell Health, New Hyde Park, New York
∗ Address reprint requests and correspondence: Ms Kristie M. Coleman, Department of Cardiology, Lenox Hill Hospital, 100 E 77th St, New York, NY 10075. Kcoleman1@northwell.edu
17 7 2024
8 2024
17 7 2024
5 8 597600
© 2024 Heart Rhythm Society. Published by Elsevier Inc.
2024
Heart Rhythm Society
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords

Pacemaker-induced cardiomyopathy
Leadless pacemaker
Permanent pacemaker
Cardiomyopathy
Pacemaker implantation
==== Body
pmc Key Findings

▪ Pacing-induced cardiomyopathy (PICM), associated with high pacing burden, is a known complication in patients with permanent pacemakers.

▪ We conducted a retrospective study examining baseline and follow-up echocardiograms, and we found that there was no significant difference in the incidence of PICM between the 2 groups, with 13% and 12% of patients developing cardiomyopathy in the leadless pacemaker (LP) and transvenous pacemaker (TVP) groups, respectively.

▪ Predictors for the development of PICM were chronic kidney disease, wide baseline QRS width, and medical history of congestive heart failure.

▪ Although there were similar overall complications in both groups, there were fewer reinterventions in the LP group.

▪ Our study further reveals the safety of LPs, which may be a better option than TVPs in patients without sinus node dysfunction and who are at high risk for periprocedural complications.

Introduction

Pacing-induced cardiomyopathy (PICM) is a known complication in patients with permanent pacemakers (PPMs), typically occurring in patients with high right ventricular pacing burden. The introduction of the leadless pacemaker (LP) has eliminated pocket- and lead-related complications, but limited data are available on the incidence of PICM in the population with LPs and how this incidence compares to that of patients with transvenous pacemakers (TVPs).1,2 With this retrospective analysis, we sought to report the differences in PICM from a cohort where all implantation procedures were performed within the same health care system in the modern era.

Methods

Population

Patients implanted with either LPs or TVPs in 1 of 8 hospitals of Northwell Health between January 2015 and December 2021 were identified. Patients with a baseline left ventricular ejection fraction (LVEF) of <50% and a history of myocardial infarction or coronary artery bypass graft were excluded.

Data gathering

Medical history, using international classification of diseases, 10th revision codes, and baseline demographic data were obtained from our electronic medical record system. The medical records of patients identified were then manually reviewed for baseline echocardiogram within 6 months before implantation, follow-up echocardiogram at least 1 year postimplantation, pacing indications, and clinical outcomes during the perioperative period and during follow-up. In addition, we manually reviewed the 12-lead electrocardiograms (ECGs) and calculated native and pacing QRS widths, as well as the postoperative chest radiograph to determine the location of the pacing bipole. The baseline QRS width was taken from an ECG within 6 months before implantation. The width was taken from an escape beat only if there were no other ECGs from this period showing a beat conducted through the atrioventricular node. Pacing percentages for LPs were pulled from the Medtronic datamart, and those for TVPs were pulled through the common health system device monitoring platform. Patients from the LP or TVP group missing the above data were excluded from the study.

Comparator study groups and outcome measures

After identifying patients with LPs meeting the inclusion and exclusion criteria, we randomly selected patients with TVPs implanted during the same period in a 3:1 ratio.

Our primary end point was the development of PICM defined as a decline in LVEF by ≥10% and with an absolute LVEF of <50%. Patients who met the primary end point were manually adjudicated to rule out alternative etiologies for cardiomyopathy. The secondary end points were device-related complications and mortality.

Statistical analysis

Baseline clinical and demographic variables were compared using the Wilcoxon T test (continuous) or Fisher exact test (categoric). Patients were grouped on the basis of the type of device into 2 groups: LP and TVP. We constructed a logistic regression model for the development of cardiomyopathy as a function of age, sex, diabetes, history of congestive heart failure (CHF), hypertension, QRS width at baseline, QRS width postimplantation, lead location, and pacing location. Finally, we constructed a Cox regression model for all-cause mortality, and a 2-sided P value of <.05 was used as a measure of statistical significance. R version 4.0.0 (2023) and STATA (Stata/IC 16.1, StataCorp LP, College Station, TX) were used to perform statistical analysis.

Results

Study population

The final study population consisted of 223 patients, 61 in the LP group and 162 in the TVP group. Of the 61 patients with LPs, 41 had Micra VR devices and 20 had Micra AV devices. In the TVP group, 143 had dual-chamber PPMs and 19 had single-lead PPMs. The only statistically significant difference in baseline characteristics between the 2 groups was sex (37% vs 51% female in the LP vs TVP group, respectively; P = .04). The percentage of patients with QRSd > 120 ms was 32.35% (P = .72). Of the patients with QRSd > 120 ms, 60% had right bundle branch block, 27.1% had left bundle branch block, and 12.9% had intraventricular conduction delay. Regarding lead location, apical bipole implantation occurred earlier in the study period. Demographic and clinical characteristics stratified by study group are displayed in Table 1.Table 1 Baseline demographic characteristics, characteristics, and medical history

Clinical characteristic	TVP (n = 162)	LP (n = 61)	
Age at implantation (y)	79 (73–85)	79 (72–85)	
Sex: female	86 (51.5%)	23 (37.7%)	
Race			
 White	125 (77%)	52 (85%)	
 African American	14 (8.6%)	2 (3.2%)	
 Asian	5 (3%)	1 (1.6%)	
 Native American	1 (0.6%)	0 (0.0%)	
 Other	15 (9%)	4 (6%)	
BMI (kg/m2)	27.4 (24.1–31.2)	28.0 (24–33)	
CAD	73 (45%)	31 (51%)	
CHF	49 (30%)	24 (39%)	
HTN	125 (77%)	56 (91%)	
DM	52 (32%)	16 (26%)	
CKD	23 (14%)	6 (10%)	
Stroke or TIA	21 (13%)	5 (9%)	
LVEF at baseline (%)	63 (57–67)	63 (57–75)	
Implant indication			
 SND	77 (47.5%)	16 (26.2%)	
 AV node dysfunction	77 (47.5%)	34 (55.7%)	
 Unspecified AV conduction disease	8 (5.0%)	11 (18.0%)	
 nQRS (ms)	102 (90–126)	103 (96–133)	
 pQRS (ms)	157.5 (143–173)	162 (146–173)	
Implant location			
 Apical	110 (67.9%)	14 (23.0%)	
 Septal	52 (32.1%)	47 (77.0%)	
Values are presented as median (interquartile range) or percentage.

AV = atrioventricular; BMI = body mass index; CAD = coronary artery disease; CHF = congestive heart failure; CKD = chronic kidney disease; DM = diabetes mellitus; HTN = hypertension; LP = leadless pacemaker; LVEF = left ventricular ejection fraction; nQRS = native QRS duration; pQRS = paced QRS duration; SND = sinus node dysfunction; TIA = transient ischemic attack; TVP = transvenous pacemaker.

Complications

Overall, the rate of acute procedural complications was 3.28% in the LP group compared with 1.23% in the TVP group (P = .50), which included 2 hematomas in both groups. There were no chronic complications recorded in the LP group as compared with 1 microperforation with pericardial effusion and 2 revisions due to malfunction or infection in the TVP group.

Clinical outcomes

In total, 12.1% of our patients developed cardiomyopathy in the span of 3 years. The percentage of cardiomyopathy in the LP group was 13% (8 of 61) vs 12% in the TVP (19 of 162) (P = .77). On average, LVEF decreased to 26% in those with LPs who developed PICM compared with 22% in those with TVPs. The change in LVEF 1 year postimplantation for both the TVP and LP groups is presented in Figure 1. Those in the LP group were pacing, on average, 50% compared with 37% in the TVP group (P = .03). In the TVP group, 64 (38%) paced, on average, over 40% compared with 34 (55%) in the LP group (P = .03).Figure 1 Development of pacing-induced cardiomyopathy from baseline to 1 year postimplantation in the (A) transvenous pacemaker group and (B) leadless pacemaker group. LVEF = left ventricular ejection fraction.

In a multivariate approach, the 2 factors that were independently associated with the development of cardiomyopathy were prolonged baseline QRS width (odds ratio [OR] 5.36; 95% confidence interval [CI] 1.39–20.70; P = .015) and a history of CHF (OR 3.53; 95% CI 1.00–12.40; P = .049) (Table 2). Cox regression analysis showed no difference in PICM between the leadless and control groups (Figure 2). There were 4 deaths from any cause (6%) in the TVP group compared with 21 (12%) in the LP group (P = .177).Table 2 Multivariate analysis assessing independent predictors of PICM in LP and TVP groups combined

Variable	OR	95% CI	P	
TVP vs LP	2.80	0.43–18.4	.282	
Age	1.03	0.96–1.10	.468	
Sex: male	0.40	0.11–1.43	.160	
Race	0.87	0.64–1.18	.366	
BMI	0.94	0.85–1.05	.267	
Baseline LVEF	1.00	0.91–1.09	.94	
CAD	0.77	0.022–2.65	.672	
HTN	0.69	0.12–3.82	.671	
DM	1.22	0.33–4.5	.766	
CKD	4.10	0.83–20.4	.084	
CHF	3.53	1.00–12.4	.049	
nQRS > 120 ms	5.36	1.39–20.7	.015	
pQRS	0.99	0.97–1.0	.981	
Pacing > 40%	0.24	0.03–1.74	.159	
BMI = body mass index; CAD = coronary artery disease; CHF = congestive heart failure; CI = confidence interval; CKD = chronic kidney disease; DM = diabetes mellitus; HTN = hypertension; LP = leadless pacemaker; LVEF = left ventricular ejection fraction; nQRS = native QRS duration; OR = odds ratio; PICM = pacing-induced cardiomyopathy; pQRS = paced QRS duration; TVP = transvenous pacemaker.

Figure 2 Kaplan-Meier curve depicting freedom from development of pacing-induced cardiomyopathy (PICM) over time (days postimplantation) in the transvenous pacemaker (TVP) and leadless pacemaker (LP) groups (P = .72).

Discussion

In a highly selective cohort consisting of patients within a large health care system with all implantation procedures performed in the current era, we report that the incidence of unexplained cardiomyopathy after pacemaker implantation was not significantly different between patients with TVPs and those with LPs after adjusting for known predictors of PICM, including lead location and percent pacing. The cardiomyopathy incidence observed in our study is likely an overestimation because of the inherent selection bias of a retrospective study. As routine echocardiographic evaluation a year after pacemaker implantation is not a standard practice in our institution, patients included in the analyses had a clinical indication to undergo echocardiography. Therefore, we cannot ascertain the true incidence of PICM in this population. However, this selection bias affects both groups equally. Although comparable incidence rates of PICM have been reported in patients with transvenous systems, 12.3%–16.1%, the most recent data from the Micra post-approval registry revealed a lower PICM incidence of 0.3% in patients with leadless systems.3, 4, 5, 6 This is lower than what we found in our study and what is reported by a similar study by Sanchez et al,4 our results offer an estimate of the real-world incidence of PICM in a diverse health system.

The only predictors in the development of cardiomyopathy were a history of CHF and a QRSd > 120 ms, which has been reported as a predictor of PICM by Khurshid et al.7 A meta-analysis by Somma et al8 found for every 1% increase in baseline LVEF, there was a reduced risk of PICM (OR 0.95; 95% CI 0.93–0.97; P < .001).8 Similarly, our analysis found that a history of CHF as a predictor of PICM. Patients with a history of heart failure likely had a preserved LVEF, though they may have had a reduced LVEF at some point that recovered before implantation. These patients may have had more frequent echocardiographic evaluation and opportunities for diagnosing PICM because of their medical history, which is a limitation of our study as mentioned above. Another limitation of our study is that we did not factor in the use of algorithms to reduce right ventricular pacing, which would be important in future analyses, given the relationship between increased pacing burden and cardiomyopathy.3,7,9

A prevalent clinical practice is the preferential selection of LPs in patients with relatively short life expectancy and high infectious risk because of the proven low infectious long-term risk and decreased incidence of acute procedural complications associated with LPs.10, 11, 12 This is reflected by our cohort and others, where LPs are chosen over TVPs, even for primary sinus node dysfunction. Such practice leads to unnecessary ventricular pacing with various degrees of fusion between conducted and paced beats that worsens ventricular dyssynchrony and increases the risk of cardiomyopathy.13, 14, 15 Management options for patients with LPs and PICM are limited, as the concerns of device-related risks of implantation of a resynchronization device are the same or even greater than during the initial implantation. This difference is evident in the high all-cause mortality observed in the LP group.

Conclusion

Our comparative analysis suggests that the development of cardiomyopathy in patients with LPs is not negligible, and therefore this risk should be weighed against the lower periprocedural and infectious risks associated with an LP, especially for patients requiring atrial pacing.

Funding Sources

This study was supported by Medtronic External Research Protocol Number 13058.

Disclosures

The authors have no conflicts of interest to disclose.

Authorship

All authors attest they meet the current ICMJE criteria for authorship.

Patient Consent

The Northwell Health Human Research Protection Program approved the study through expedited approval and a waiver of consent was obtained.

Ethics Statement

This study was approved by the Northwell Health Human Research Protection Program (21-1290).
==== Refs
References

1 Reynolds D. Duray G.Z. Omar R. A leadless intracardiac transcatheter pacing system N Engl J Med 374 2016 533 541 26551877
2 El-Chami M.F. Bockstedt L. Longacre C. Leadless vs. transvenous single-chamber ventricular pacing in the Micra CED study: 2-year follow-up Eur Heart J 43 2021 1207 1215
3 Kiehl E.L. Makki T. Kumar R. Incidence and predictors of right ventricular pacing-induced cardiomyopathy in patients with complete atrioventricular block and preserved left ventricular systolic function Heart Rhythm 13 2016 2272 2278 27855853
4 Sanchez R. Nadkarni A. Buck B. Incidence of pacing-induced cardiomyopathy in pacemaker-dependent patients is lower with leadless pacemakers compared to transvenous pacemakers J Cardiovasc Electrophysiol 32 2021 477 483 33205561
5 Kim J.H. Kang K.W. Chin J.Y. Kim T.S. Park J.H. Choi Y.J. Major determinant of the occurrence of pacing-induced cardiomyopathy in complete atrioventricular block: a multicentre, retrospective analysis over a 15-year period in South Korea BMJ Open 8 2018 e019048
6 El-Chami M.F. Garweg C. Clementy N. Leadless pacemakers at 5-year follow-up: the Micra transcatheter pacing system post-approval registry Eur Heart J 45 2024 1241 1251 38426911
7 Khurshid S. Epstein A.E. Verdino R.J. Incidence and predictors of right ventricular pacing-induced cardiomyopathy Heart Rhythm 11 2014 1619 1625 24893122
8 Somma V. Ha F.J. Palmer S. Mohamed U. Agarwal S. Pacing-induced cardiomyopathy: a systematic review and meta-analysis of definition, prevalence, risk factors, and management Heart Rhythm 20 2023 282 290 36356656
9 Bansal R. Parakh N. Gupta A. Incidence and predictors of pacemaker-induced cardiomyopathy with comparison between apical and non-apical right ventricular pacing sites J Interv Card Electrophysiol 56 2019 63 70 31363943
10 El-Chami M.F. Bonner M. Holbrook R. Leadless pacemakers reduce risk of device-related infection: review of the potential mechanisms Heart Rhythm 17 2020 1393 1397 32247833
11 Guha A. Maddox W.R. Colombo R. Cardiac implantable electronic device infection in patients with end-stage renal disease Heart Rhythm 12 2015 2395 2401 26253036
12 Johansen J.B. Jørgensen O.D. Møller M. Arnsbo P. Mortensen P.T. Nielsen J.C. Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients Eur Heart J 32 2011 991 998 21252172
13 Mizner J. Jurak P. Linkova H. Smisek R. Curila K. Ventricular dyssynchrony and pacing-induced cardiomyopathy in patients with pacemakers, the utility of ultra-high-frequency ECG and other dyssynchrony assessment tools Arrhythm Electrophysiol Rev 11 2022 e17 35990106
14 Dreger H. Maethner K. Bondke H. Baumann G. Melzer C. Pacing-induced cardiomyopathy in patients with right ventricular stimulation for >15 years Europace 14 2012 238 242 21846642
15 Walters T.E. Rahmutula D. Szilagyi J. Left ventricular dyssynchrony predicts the cardiomyopathy associated with premature ventricular contractions J Am Coll Cardiol 72 2018 2870 2882 30522650
