Risk Factors for Non-Benefit of ICD Therapy: The Role of Age and Comorbidities

Background: Studies have demonstrated overall prognostic benefits of ICD implantation in patients at increased risk of sudden cardiac death. However, results are inconsistent in certain subgroups, including patients with end-stage renal disease, non-ischemic cardiomyopathy, diabetes mellitus, and especially the elderly. This study aims to evaluate the prognostic implications of comorbidities on ICD outcomes and compare trends in patient selection and outcomes over a decade-long inclusion period.

Methods: This study analysed 422 patients undergoing ICD implantation between 2011 and 2020. Patient data, including medical history, medication, laboratory results, ECG, and echocardiography at the time of ICD implantation, were collected. All patients underwent routine check-ups and device interrogations at our outpatient clinic six weeks after implantation, followed by regular checks every six months either at our university outpatient clinic or at a cardiologist's practice. The study endpoint “no-benefit” was characterized by death from any cause occurring without prior appropriate ICD therapy. Benefit of ICD implantation was defined as either receiving appropriate ICD therapy before death or receiving appropriate ICD therapy and surviving until the end of the observation period.

Results: 86 of 422 patients (20%) were female and the mean left ventricular ejection fraction was 32.3 ± 10.3%. The mean age of the patients was 66.9 ± 11.3 years, ranging from 22 to 89 years. At the time of implantation, 101 patients (24%) were younger than 60 years old, 118 (28%) were aged between 60 and 69 years, 158 (37%) between 70 to 79 years, and 45 (11%) were aged 80 years or older. During a mean follow‐up of 4.2 ± 3.0 years, 106 patients (25%) died. No-benefit of ICD implantation was observed in 84 patients (20%) and benefit in 89 patients (21%). Independent risk factors for no-benefit were age ≥ 68 years (HR 4.599, p<0.001), anemia (HR 2.549, p<0.001), peripheral artery disease (HR 2.066, p=0.007), and chronic obstructive pulmonary disease (HR 1.939, p=0.014).
Subgroup analysis by age < 68 years and ≥ 68 years (an independent risk factor in multivariate analysis) demonstrated that with increasing number of independent risk factors, the no-benefit rates increased significantly in both groups (each p<0.001), however, to a greater extent in the 68 years and older group (Figure 1).
With increasing age, the prevalence rates of risk factors for no-benefit of ICD implantation also increased on average. Interestingly, there was little difference between the group aged 80 years and older compared to the groups aged 70-79 years (p=0.124) and 60-69 years (p=0.129). However, we found higher prevalence of multiple risk factors compared to the group < 60 years (p<0.001) (Figure 2).

Conclusion: Our analysis covers a trend that extends over an entire decade, providing valuable insights into the development of ICD patient collectives and selection over time. Our study emphasizes the importance of age for the potential non-benefit of ICD therapy. However, even young patients with a high burden of comorbidities have a high risk of not benefiting from ICD therapy. A careful patient selection and consideration of individual risk factors besides age is important.

Figure 1: Kaplan-Meier survival analysis for age < 68 years and age ≥ 68 years.

 

Figure 2: Prevalence of risk factors in different age groups.