Chubb H, Bulic A, Mah D, Moore JP, Janousek J, Fumanelli J, Asaki SY, Pflaumer A, Hill AC, Escudero C, Kwok SY, Mangat J, Ochoa Nunez LA, Balaji S, Rosenthal E, Regan W, Horndasch M, Asakai H, Tanel R, Czosek RJ, Young ML, Bradley DJ, Paul T, Fischbach P, Malloy-Walton L, McElhinney DB, Dubin AM.J Am Coll Cardiol. 2022 Aug 30;80(9):902-914. doi: 10.1016/j.jacc.2022.05.053.PMID: 36007989
Take Home Points:
- The risk for heart transplantation or death was significantly higher in the functionally univentricular patients with a permanent ventricular pacemaker system. (HR 3.8)
- The risk of single ventricle failure was significantly higher in the functionally univentricular patients with permanent ventricular pacemaker system. (HR 4.7)
- Patients with permanent ventricular pacemaker systems had a higher rate of decline in ventricular function (HR 3.5)
- Higher amount of ventricular pacing resulted in a higher risk for death or transplantation (HR 2.0) and Fontan-failure (HR1.8)
- Type of pacing system (single chamber, dual chamber, CRT) did not impact outcomes.
- Increased ventricular pacing, higher QRS z-score, higher heart rate, and non-apical ventricular lead position were associated with heart transplantation or death.
- Potential considerations to mitigate the deleterious effects of ventricular pacing in univentricular hearts include apical pacing, minimizing ventricular pacing, and targeting lead location to provide shorter paced QRS duration z-scores.
Comment from Dr. Akash Patel (Cleveland), section editor of Congenital Electrophysiology Journal Watch.
A significant portion of patients with functionally univentricular hearts have shown over time to require pacemaker therapy for sinus node dysfunction, tachy-brady syndrome, and AV block with data ranging from 8 to 45%. Previous studies have shown that ventricular pacing in this population is associated with increased morbidity (poor functional status, depressed ventricular function) and mortality (death or transplant). The objectives of this study were to establish a clear profile of pacemaker-attributable risk and identify risk factors that may be modified to alleviate the detrimental impact of ventricular pacing.
This was retrospective multi-center matched control study of functionally univentricular patients with an epicardial pacemaker and functional ventricular pacing lead (PPMv). It included those patients after Jan 1, 2000, with an implant done before 30 years of age. Cases were matched based on ventricular morphology (left vs right), sex, most recent palliative surgical procedure (maximum 1 year discrepancy), and age. All single ventricle palliative surgical procedures were included. The primary outcome was heart transplantation or death. The secondary outcome was death alone and single ventricle failure, which was defined as identification of PLE, plastic bronchitis, listing for heart transplant, VAD, heart transplantation, or death.
Baseline characteristics at time of enrollment showed a total of 449 patients with 213 matched permanent pacemaker patients with ventricular pacing (PPMv) and 213 controls from 22 centers and 9 countries. 5% of patients with ventricular pacing were unmatched and included only in the analysis of risk factors for PPMv alone. The median year of birth was 2002 [1995-2008] and the median age at enrollment was 5.3 years [IQR: 1.5-13.2]. There was no difference between cases and controls regarding year of birth, age of enrollment, sex, systemic ventricle morphology, presence of heterotaxy, total cardiac medications, number of bypass procedures, age at Fontan, and presence of aortic stenosis or arch obstruction. The PPMv group were different than the matched controls with regards to the following: 1) higher inotropic support, antiarrhythmic medication use, total number of surgical procedures 2) less extracardiac and more fenestrated Fontan procedures and 3) worse ventricular function, atrioventricular valve regurgitation, and aortic regurgitation. Overall, the PPMv group was “sicker” than the control group. See figure below.
The specific cardiac anatomies included HLHS (24%), DILV (20%), Tricuspid Atresia (13%), DORV (11%), Unbalanced AV Canal (10%), PA/IVS (3%), Ebstein (1%), and Other (18%). The PPMv matched patients included significantly more DILV (24% vs 16%) and less PA/IVS (1% vs 6%). See figure below.
The median follow-up was 7.0 years [IQR: 3.5 – 11.6] with no difference between the cases and controls. The primary outcome of heart transplantation or death occurred in 47 (22.1%) of the 213 matched subjects with PPMv vs. 14 (6.6%) of the 213 matched controls. The risk for heart transplantation or death was significantly higher in the PPMv group (univariable: 4.6; 95% CI: 2.4-8.7; P < 0.001, multivariable HR: 3.8; 95% CI: 1.9-7.6; P < 0.001). Factors significantly associated with primary outcome based on multivariate analysis included heart failure medications (HR 1.545), toral cardiac medications (HR 1.135), qualitative function on echo (HR 1.59), and aortic arch obstruction (HR 5.675). The secondary outcome of death alone (censored at heart transplantation) and single ventricle failure occurred in 31 (14.5%) and 61 (28.6%) patients with PPMv, respectively; in control patients, the figures were 8 (3.8%) and 19 (8.9%), respectively. (HR: 6.0; 95% CI: 2.5-14.0; P < 0.001 and HR: 4.7; 95% CI: 2.6-8.4; P < 0.001, respectively). See Figure and Table Below.
Of note, the PPMv group had a higher rate of decline in ventricular function (to first-time identification of at least moderate dysfunction. (HR: 3.52; 95% CI: 2.4-5.2; P < 0.0001), but no difference in progression of systemic AVVR. In addition, PPMv patients had significant lengthening in the QRS duration from baseline intrinsic QRS by 18 ± 2 ms (z-score: 1.6 ± 0.2) following pacemaker implantation. This prolongation in QRS during remained constant at least 10 years. See Figure below.
Analysis of the 236 patients with PPMv showed heart transplantation or death occurred in 51 (21.7%) with a median follow-up 6.3 years [IQR: 3.0-11.3]. On multivariate analysis, the primary outcome was associated with increased Vp (weighted average Vp), higher heart rate (weighted average), non-apical lead position, and higher QRS z-score (weighted average). Of note, note average QRS duration was not associated with primary outcome.
Average percent ventricular pacing was noted to be 90.8% [IQR: 4.3 – 100] in this cohort. The higher amount of ventricular pacing was shown to result in a higher risk for death or transplantation. Of note, the average Vp was similar in those with single-chamber vs multi-chamber pacing systems (84% [IQR: 13 -100] vs 86% [IQR: 3-100]; p= 0.57). See below.
The impact of pacing strategy was not shown to be associated with the primary or secondary outcomes. ed. 200 (85%) had dual chamber devices, 28 (12%) had single chamber devices, and 8(3%) had multisite/CRT systems.
This study provides additional insight into our understanding of the impact of ventricular pacing in patients with univentricular hearts. As has been described, ventricular pacing is “bad” for these patients resulting in a higher risk for death, transplantation, and single ventricle failure. This study demonstrates a more rapid decline in ventricular function with ventricular pacing and the deleterious effects of non-apical pacing location, higher burden of ventricular pacing, and wider paced QRS complexes (z-score duration).
Univentricular patients requiring ventricular pacing are often more complex and sicker as demonstrated by the higher need for inotropic support, antiarrhythmic medications, fenestrated Fontan procedures, worse function and atrioventricular valve regurgitation, and more surgeries. Therefore, an individualized approach balancing risks and benefits is needed in these patients. This study provides a thoughtful framework of modifiable pacing strategies (apical pacing location, minimize ventricular pacing, and shorter paced QRS duration z-score) that can be used to potentially mitigate the deleterious effects of chronic ventricular pacing. See Figure below.