Does Age Play a Role in Patients with Heart Failure Receiving Cardiac Implantable Electronic Devices? Open Access

There has been a great increase in the global use of cardiac implantable electronic devices (CIEDs) due to growing aging population with accumulating co-morbidities. This has led to the development and progression of devices and expanding indications for the use of these devices. When CIEDs are implanted appropriately, they improve mortality and/or quality of life [1]. However, the prognosis after CIED implantation might be different according to the indication for its use, type of CIED, age, and underlying comorbidities. Chronic right ventricular pacing (RVP) may have a deleterious effect on left ventricular (LV) function in patients with preserved LV ejection fraction (LVEF), as well as in patients with reduced LVEF [2, 3]. RVP leads to an altered ventricular activation pattern resulting in intraventricular dyssynchrony and thus a prolonged QRS duration. This leads to inefficient contractile function, elevated filling pressures, and ultimately maladaptive cardiac remodeling with the development of clinical heart failure and atrial fibrillation (AF) [4]. One of the risk factors for the development of pacing-induced cardiomyopathy is the burden of RVP and pre-implantation-impaired LVEF [5, 6]. Therefore, selection for the type of CIED and follow-up after its implantation are important issues to be addressed in patients with underlying heart failure to promote survival and reduce the risk of heart failure-caused hospitalization.

In this sense, a large nationwide cohort-based study by Rorsman et al. was published in this issue of Cardiology [7]. This study aimed to investigate age-adjusted survival and risk of heart failure hospitalization in a nationwide cohort of patients with prior heart failure, who had an indication to receive a de novo CIED with an RV lead. They evaluated all-cause mortality within 5 years of post-implant, stratified for age intervals as a primary endpoint. In secondary time-dependent analyses, the risk of hospitalization for heart failure was evaluated, as was the mode of death, with particular focus on cardiac mortality (acute myocardial infarction, heart failure, or sudden cardiac death). The incidence of upgrades from pacemaker to cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillator (ICD) was also investigated. The authors used the nationwide Swedish Pacemaker Registry and identified all patients with prior heart failure diagnosis who had received a primary implant of a CIED during the period of 2005–2018. A total of 37,745 patients were included in the study and all had an RV lead each. Patients were split into groups depending on the type of device that they had received.

There were differences in comorbidities among the CIED type. Patients receiving single-chamber pacemaker were older and had a lesser incidence of ischemic heart disease, and almost all had a history of AF (93%). Comparably, prior AF was more common (44%) than in the other device groups among patients receiving single-chamber ICD (p < 0.001). Both single-chamber pacemaker and single-chamber ICD recipients had a higher prevalence of AF. Overall mortality was reported in 40% of the patients, ranging from 17% for patients with dual-chamber ICD to 61% for patients with single-chamber pacemaker within 5 years. Patients with single-chamber pacemakers had significantly higher mortality compared to all other devices (p < 0.001). Atrioventricular block (AV) as a device indication was also independently associated with higher mortality (hazard ratio 1.17 [1.09–1.25], p < 0.001).

Risk of heart failure hospitalization at any time during the 5 years of post-implant ranged from 28% (DDD pacemaker) to 39% (CRT-P), and the mean number of hospitalizations showed slightly higher values in the CRT-treated groups. In this large nationwide cohort of patients with prior heart failure diagnosis that received pacemaker or defibrillator implants, adjusted mortality was highest for patients treated with single-chamber pacemakers in all age-groups (p < 0.001). Adjusted risk of heart failure hospitalization within 5 years was highest for CRT recipients, patients with single-chamber pacemaker or ICD had a medium risk, and those with dual-chamber pacemaker or ICD had the lowest risk. They also performed age-stratified sub-analysis in patients with an indication for “AV block” who were likely to receive a high percentage of ventricular pacing, and the results were similar; patients with single-chamber pacemakers had the highest mortality.

It might be questionable that CRT treatment was associated with lower all-cause mortality despite higher risk of heart failure hospitalization. The findings can be explained as follows. While overall mortality was higher in the conventional pacemaker group, cardiovascular mortality was relatively higher in the CRT and ICD groups, mainly driven by an increase in heart failure mortality. These findings suggest the issue of selective CRT devices for patients with more prominent heart failure symptoms, compared to the patients who received conventional pacing. In the present cohort, 87% of the patients with a single-chamber device had an indication of an AV block (mostly in combination with AF), suggesting a high need for ventricular pacing and, thus, poor prognosis. Overall high mortality for the patients receiving conventional pacemaker can be explained as the presence of comorbidities and the perceived longevity of the patient.

The most common approach to managing patients with pacing-induced cardiomyopathy is to upgrade the single- or dual-lead pacemaker to a CRT device, and CRT upgrade has been shown to be a highly effective treatment for this condition [8]. Unfortunately, upgrades from pacemaker therapy in this registry were rare, ranging from 2.9% (single-chamber pacemaker to CRT) to 9.1% (dual-chamber ICD to CRT). The authors explained the reason as the trend of underuse of ICD and CRT in Sweden. There has been concern that the upgrade procedures lead to a higher morbidity and mortality than the initial implantation. Previously, in-hospital mortality for patients undergoing a CRT upgrade was 1.8%, compared with 0.8% for de novo CRT implantation [9]. Both physicians and patients might be reluctant to open the pocket and perform the upgrade procedure because the CIED upgrade procedure is usually more complex than the de novo procedure and has a high chance of infection. Therefore, it is important to properly select the CIED type during de novo procedure, particularly for indication of CRT as the initial device.

To reduce the burden of RVP, device-based algorithms designed to minimize ventricular pacing can be utilized [8]. Before applying this technology, physicians should thoroughly understand the algorithm and patients’ native AV conduction property. Implantation of the conduction system pacing has risen dramatically. Recently, left bundle branch pacing (LBBP), a major physiological conduction system pacing, has been reported to achieve better electrical and mechanical synchrony in the LV than the conventional RVP and thus can theoretically reduce the incidence of heart failure. LBBP offers a wider range of pacing targets than the His bundle, overcoming several technically challenging issues regarding His bundle pacing such as high pacing thresholds, lead fixation, and early battery depletion. LBBP resulted in improved clinical outcomes including death from any cause, first episode of heart failure hospitalization, or the need for upgrading to bi-ventricular pacing, compared to RVP [10].

Besides the burden of RVP, worsening functional tricuspid valve regurgitation was independently associated with the severity of acute decompensated heart failure presentation, lower cardiac index, and worse long-term mortality in patients with heart failure [11]. In a recent meta-analysis, CIED-associated tricuspid valve regurgitation occurred in nearly one-fourth of patients after device implantation and was associated with an increased risk of all-cause mortality and heart failure hospitalizations [12].

An important concern regarding this study is that it did not have data on several variables that possibly influenced the prognosis in heart failure, such as heart failure symptom class, medication status, LVEF, and diastolic function. Further, information regarding the degree of tricuspid valve regurgitation was not available. Despite this inherent study design, it is meaningful that this study was derived from a large real-world cohort. The registry includes all implanting centers in Sweden and covers >97% of all implants. The current study offers data regarding age-stratified clinical outcomes in patients with known heart failure according to the CIED type. Further randomized studies are warranted.