Emergency pacemaker implantation in nonagenarians with CHB: single- versus dual-chamber pacing

In ambulatory patients with complete heart block (CHB), dual-chamber (DDD) pacing confers physiological benefits versus single-chamber (VVI) pacing, however, the impact on mortality is disputed. Nonagenarians constitute an expanding proportion of pacemaker recipients, yet data on device selection and outcomes are limited, especially in emergency situations.

In nonagenarians with emergent CHB, we compared the clinical characteristics and outcomes of patients receiving VVI versus DDD pacemakers. Cox proportional-hazards analysis examined all-cause mortality and death from congestive cardiac failure (CCF).

There were 168 consecutive patients followed-up for 30.6 ± 15.5 months. Of these, 22 patients (13.1%) received VVI pacemakers; when compared with DDD recipients, these patients had similar median age (93 vs. 91 years, p=0.15) and left ventricular (LV) systolic function (LV ejection fraction [EF] 49.2% ± 9.7 vs. 50.7% ± 10.1, p=0.71), but were more frail (Rockwood scale 5.2 ± 1.8 vs. 4.3 ± 1.1, p=0.004) and more likely to have dementia (27.3% vs. 8.9%, p=0.011). Post-implant, device interrogation demonstrated that VVI recipients had higher respiratory rates (21.3 ± 2.4 vs. 17.5 ± 2.6 breaths per minute, p=0.002), lower mean heart rates (65.5 ± 10.1 vs. 71.9 ± 8.6 bpm, p=0.002), and lower daily activity levels (0.57 ± 0.3 vs. 1.5 ± 1.1 hours of activity, p=0.016) than DDD recipients. Adjusting for age, frailty and dementia, VVI pacing was associated with an increased risk of all-cause mortality (adjusted hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.08 to 4.1, p=0.03) and death from CCF (adjusted HR 7.1, 95%CI 2.5 to 20.6, p<0.001).

In conclusion, in nonagenarians with emergent CHB, dual-chamber pacing was associated with improved symptomatic and prognostic outcomes versus single-chamber pacing.

Introduction

In ambulatory individuals with high-grade atrioventricular (AV) block, it is well-established that restoration of AV synchrony with dual-chamber pacing confers important physiological benefits over single-chamber pacing, including improvements in exercise capacity, reduction in incident atrial fibrillation (AF), and avoidance of pacemaker (PPM) syndrome.^1,2 The impact of dual-chamber pacing on mortality remains disputed and, in older people, it has been proposed that the expected advantages of physiological pacing strategies may be mitigated by the higher prevalence of comorbidities and non-arrhythmic death.^1,3 Accordingly, the PASE (Pacemaker Selection in the Elderly, 1998), UKPACE (United Kingdom Pacing and Cardiovascular Events, 2005), and CTOPP (Canadian Trial of Physiological Pacing, 2004) randomised-controlled trials did not report survival differences between single- or dual-chamber pacing strategies in patients over the age of 65, 70, or 75 years of age, respectively.^4–6

Despite this, more recently, Krzemień-Wolska et al. (2018) and Pérez-Díaz et al. (2019) reported an association between dual-chamber pacing and improved survival in patients over 80 years of age with a mixture of symptomatic AV block and sinus node disease.^7,8 Likewise, Loirat et al. (2015) found that single-chamber pacing in sinus rhythm (i.e. non-physiological pacing) was independently associated with all-cause mortality in nonagenarians.^7,9 While these contemporary observational studies appear to support dual-chamber devices in older patients, the decision to add complexity to a pacemaker procedure by implanting a second (i.e. atrial) lead is particularly consequential in this population. In nonagenarians undergoing pacemaker implant, Dang et al. (2018) reported that procedural complications conferred a four-fold risk of mortality.¹⁰

Although nonagenarians comprise only 1% of the UK population, at our institution, since 2016, over 10% of patients who underwent cardiac implantable electronic device (CIED) procedures were aged over 90 years (figure 1).¹¹ As such, we suggest that more data are necessary to help guide device selection in this expanding population, particularly in emergency situations where clinical review and physician decision-making are time critical. We, therefore, investigated the presentation, demographics, symptomatic and prognostic outcomes for nonagenarians undergoing emergency pacemaker implant for complete heart block (CHB), examining the impact of single- (VVI) versus dual-chamber (DDD) pacing.

Method

Data were extracted from a secure internal registry comprising 7,383 consecutive transvenous CIED procedures performed at a single UK tertiary cardiac centre from 2016 to 2019. Clinical records were screened to identify emergency transvenous pacemaker implants for patients with CHB over 90 years of age (figure 1). Patients with atrial arrhythmias or sinus arrest were excluded.

Admission pathway

All included patients were admitted to our centre in an emergency via the London Ambulance Service. Patients were either diagnosed with CHB in the community and conveyed directly to our centre from their place of residence, or transferred following redirection from one of 11 regional emergency departments. On arrival, clinical assessment and bedside tests included 12-lead electrocardiogram (ECG), focused echocardiogram, and venous blood gas sampling. Frailty was estimated according to the Rockwood clinical frailty scale.¹² Unstable patients underwent treatment with positive chronotropic drugs (atropine boluses or an isoprenaline infusion) and external transcutaneous pacing, as required. A consultant electrophysiologist reviewed the clinical data to determine the urgency of pacemaker implantation. Clinical sessions were defined as ‘in hours’ between 0800 and 1700 on Monday to Friday; all other sessions were defined as ‘out of hours’.

Implant technique

All procedures were performed in a catheter laboratory under local anaesthetic and sedation, or under general anaesthetic. All patients received a bolus of two intravenous antibiotics within two hours of the procedure: gentamicin 5 mg/kg (maximum dose 450 mg) plus either flucloxacillin 1 g or, in patients with penicillin allergy or a positive or unknown methicillin-resistant Staphylococcus aureus (MRSA) status, teicoplanin 6 mg/kg rounded to the nearest 100 mg. Patients with both penicillin and teicoplanin allergy received either a cephalosporin or vancomycin, depending on the nature of the allergic reaction. Chlorhexidine scrub was used prior to skin draping. Local anaesthetic was administered in the form of 1% lignocaine. Following infraclavicular incision, a pre-pectoral pocket was fashioned, unless precluded by lack of subcutaneous tissue, in which case a sub-pectoral pocket was used. Venous access was obtained via direct cephalic cannulation, or by extrathoracic axillary puncture guided by fluoroscopy or ultrasound. Active or passive leads were deployed according to operator preference. All lead collars were secured with Ethibond, and wounds were closed with layers of Polydioxanone (PDS), Vicryl, Monocryl, or a combination of these sutures. 3M Steri-Strips and a Softpore^TM adhesive dressing were affixed to the skin surface, and a pressure dressing applied according to operator preference. No post-procedural oral antibiotics were prescribed in this study. Patients were advised to keep their wounds covered and dry for seven days; this was extended to 10 days in those with a history of diabetes. In the absence of complications, ambulatory patients were discharged 24 hours following their implant. Those patients requiring further rehabilitation were transferred back to their local hospital for ongoing management.

Follow-up

Patients were reviewed in a specialist CIED clinic at one, six and 12 months post-implant, and annually thereafter, unless an expedited review was requested by the patient or patient’s physician. In the event of death, cause of death was retrieved from the patient’s general practitioner.

Ethics

The study was registered with the local clinical effectiveness unit; as this was a retrospective analysis of registry data for the purposes of quality assurance, the need for formal ethical approval was waived by our institution.

Statistical methods

Statistical analysis was performed using R. The Shapiro-Wilk test discerned whether or not data were normally distributed. Categorical group variables were compared using a Z-test for differences of proportion. Continuous variables were analysed using two-tailed unpaired t-tests for normally distributed data or the Mann–Whitney U test for non-normally distributed data. Group outcomes were compared using Fisher’s exact test. Univariate Cox-proportional hazards analysis for the prediction of all-cause mortality and death from congestive cardiac failure (CCF) was performed for patients’ baseline characteristics, risk factors and procedural variables. The proportional hazards assumption was tested according to the relationship between scaled Schoenfeld residuals with time. Stepdown multi-variate analysis (R package: My.stepwise) was performed subsequently including all uni-variate factors with p<0.25; a variance inflating factor (VIF) was generated to assess for multi-collinearity with a cut-off of 2.5 set for categorical variables and 10 for continuous variables. Normally distributed data are presented as mean ± standard deviation (SD) and non-normally distributed data as median (interquartile range [IQR]). Hazard ratios (HR) are provided with 95% confidence intervals (CI); the level of significance for all tests was set at p<0.05.

Results

There were 168 patients included and they were followed-up for 30.6 ± 15.5 months. Patients’ baseline characteristics, admission physiological data and outcomes – stratified by type of device received – are shown in table 1. There were 62 patients (36.9%) admitted directly from their place of residence. There were 106 patients (63.1%) admitted during an out-of-hours clinical session, and 90 patients (53.6%) underwent PPM implant during the same clinical session in which they arrived. There were 26 patients (15.6%) who required an isoprenaline infusion, eight (4.8%) necessitated a period of transcutaneous pacing, and 12 (7.1%) underwent temporary wire insertion at the start of the implant procedure. There were four complications; one pneumothorax in a patient receiving a single-chamber pacemaker, one cardiac perforation requiring pericardiocentesis in a patient receiving a dual-chamber pacemaker, and two atrial lead displacements in patients receiving dual-chamber pacemakers, which required revision procedures. Four patients died prior to hospital discharge; two of cardiogenic shock and two of community-acquired bronchopneumonia.

Patients who received VVI pacemakers were more frail (Rockwood scale 5.2 ± 1.8 vs. 4.3 ± 1.1, p=0.004), more likely to have cognitive impairment (prevalence of dementia 27.3% vs. 8.9%, p=0.011), and more likely to live in a residential home (27.3% vs. 10.3%, p=0.024) than those who received DDD pacemakers.

With regards to physiological data from device interrogations, VVI recipients had higher respiratory rates (21.3 ± 2.4 vs. 17.5 ± 2.6 breaths per minute, p=0.002), lower mean heart rates (65.5 ± 10.1 vs. 71.9 ± 8.6 bpm, p=0.002), and lower daily activity levels (0.57 ± 0.3 vs. 1.5 ± 1.1 hours of activity, p=0.016) than DDD recipients.

In keeping with their increased frailty, death at 90 days post-implant (31.8% vs. 6.2%, p<0.001) and long term (59.1% vs. 35.6%, p<0.001) was more common in the VVI group. VVI patients were also more likely to die from congestive cardiac failure than DDD recipients (40.9% vs. 6.2%, p<0.001) despite similar baseline left ventricular (LV) ejection fraction. These findings were corroborated by temporal survival estimates: all-cause mortality log-rank p=0.0002 (figure 2); death from CCF log-rank p<0.0001 (figure 3).

Uni-variate and subsequent stepdown multi-variate analysis is shown in table 2. After adjusting for significant covariates, VVI pacemakers were independently associated with all-cause mortality (adjusted HR 2.1, 95%CI 1.08 to 4.1, p=0.03) and death from CCF (adjusted HR 7.1, 95%CI 2.5 to 20.6, p<0.001).

Discussion

In nonagenarians undergoing emergency pacemaker implantation for CHB, we found an association between dual-chamber pacing and improved symptomatic and prognostic outcomes versus single-chamber pacing. Implanting physicians had a tendency to select frailer patients for single-chamber pacing, and while the observed differences in post-implant activity levels and all-cause mortality might be expected given this divergence in patients’ functional baseline, adjusted analysis suggested that the decision to institute non-physiological pacing was independently associated with adverse outcomes.

As expected in a cohort with CHB, the ventricular pacing percentage was high, but, importantly, did not differ between groups. As such, the differences in mortality – and especially death from CCF – are less likely to be explained by pacing-induced ventricular dysfunction, and may instead relate to asynchronous ventricular pacing from single-chamber devices. By preserving chronotropic response and avoiding retrograde atrial activation, dual-chamber devices with atrial tracking have been shown to increase cardiac output by an average of 800 ml per minute.² Accordingly, in the present study, patients implanted with dual-chamber pacemakers maintained significantly higher mean heart rates, and had lower mean respiratory rates, than their single-chamber counterparts. Furthermore, the burden of atrial pacing seen in dual-chamber pacemaker recipients was relatively low (22%), suggesting that the majority of our nonagenarian patients retain good sinus node function – this further supports the benefits of atrial tracking for delivering not only synchronous AV pacing, but also physiological heart rate variability, even in very old patients.

Notably, our findings contrast with those of the PASE, CTOPP and UKPACE randomised-controlled trials. As a retrospective analysis, the authors acknowledge that the present study results are prone to bias and random chance, however, there are also important distinctions in study design and population, which could account for the disparate results. To begin with, temporal changes in life-expectancy – and, hence, the degree of benefit conferred from physiological pacing – may account for differences in the distribution of adverse events between trials. Furthermore, while the present study exclusively recruited participants with CHB, the PASE and CTOPP trials randomised patients with both AV block and sinus node disease, and the UKPACE trial included 26% of patients with second-degree AV block; this may have resulted in significant differences in both pacing burden and mode between studies. Importantly, the CTOPP and PASE trials did not record the percentage of ventricular pacing during the follow-up period, and these data were also missing in one-third of patients in the UKPACE trial. We suggest that, when examining clinical outcomes, percentage pacing burden is an imperative metric given the association between right ventricular pacing and subsequent systolic dysfunction, and we propose that the possibility of lower than expected ventricular pacing burden in the single-chamber device arms may have reduced the incidence of adverse events in these trials.¹³ Finally, given the requirements for informed consent and reasonable prognosis (i.e. life-expectancy of >1 year) to participate in these randomised trials, it is likely that the examined participants were less frail than the present study’s real-world population, and perhaps, therefore, less susceptible to the deleterious effects of asynchronous pacing from single-chamber pacemakers.

Observational studies have previously reported single-chamber pacemaker implant rates as high as 80% in nonagenarians.¹⁰ While our physicians preferentially selected frailer patients for single-chamber devices, this only comprised 13% of our cohort. This reflects data from Greenspon et al. (2012) who, in a large US registry study, reported a trend towards the use of dual-chamber pacemakers; by 2009, only 14% of implanted pacemaker devices were single-chamber, down from 36% in 1993.¹⁴

Although large studies have examined the feasibility and safety of pacemaker implant in patients over 90 years of age,¹⁵ to our knowledge, we present the highest volume examination of a nonagenarian cohort with exclusively CHB, and also the first study to include solely emergency procedures. While these procedures represent only 2.3% of our CIED case load, this is an expanding patient group with a paucity of data regarding device selection. Procedural complications in this cohort can prove particularly grave, hence, it is critical that the decision to proceed to dual-chamber implant be evidence-based.

Limitations

As a single-centre analysis, our results may not be generalisable to the wider population, however, our population was drawn from a catchment area of four million individuals via 11 different referring hospitals, so we suggest that the final cohort is heterogeneous. The relatively high event rate was sufficient to facilitate multi-variate analysis adjusting for important confounders, however, unequal group sizes precluded certain subanalyses. While the Rockwood clinical frailty scale is a quantitative metric, bedside assessment of frailty is subjective, and the published data may not truly reflect patients’ functional status in all cases. There was a particularly high incidence of death from CCF in patients with single-chamber pacemakers; although this was recorded from participants’ death certificates, autopsy data was not available for adjudication. It is possible that patients’ community doctors were biased by the recent cardiac history of pacemaker insertion, and, therefore, recorded ‘CCF’ as the most likely cause of death in the absence of a more plausible explanation, giving rise to a falsely elevated event rate. The rate of complications in patients receiving dual-chamber pacemakers was low (2.1%) and may not be representative of the wider population; importantly, higher complication rates might influence operator decision-making regarding single- versus dual-chamber pacing. Finally, as a retrospective analysis, this study was not designed to assess causation and can only be hypothesis generating; it is possible that not all significant confounders have been accounted for in the multi-variate modelling.

Conclusion

In nonagenarians presenting in an emergency with CHB, dual-chamber pacing was independently associated with favourable long-term symptomatic and prognostic outcomes versus single-chamber pacing, with a similar incidence of procedural complications between groups. Our data add further support to the routine use of dual-chamber devices in this expanding cohort, however, a randomised-controlled trial would be required to demonstrate a causal relationship.

Key messages

• Data on device selection and outcomes for nonagenarians with complete heart block (CHB) are limited
• Dual-chamber pacing was associated with improved symptomatic outcomes compared with single-chamber pacing in nonagenarians with CHB
• Single-chamber pacing was associated with increased risk of all-cause mortality and death from congestive cardiac failure compared with dual-chamber pacing in nonagenarians with CHB

Conflicts of interest

None declared.

Funding

None.

Study approval

The study was registered with the local clinical effectiveness unit; as this was a retrospective analysis of registry data for the purposes of quality assurance, the need for formal ethical approval was waived by our institution.

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