Risk factors for first and recurrent ICD therapy in primary and secondary prevention patients with an implantable cardioverter defibrillator

Abstract Introduction Implantable cardioverter-defibrillators (ICD) are used to prevent sudden cardiac death in patients with elevated risk of life-threatening arrhythmia. Medical treatment of heart disease and the population of ICD carriers have changed since the pivotal studies 20 years ago, sparking a need for improved ICD candidate selection and identification of risk factors for ICD therapy. Purpose This study aimed to examine risk factors associated with incident and recurrent ICD shock. Methods This single-center, prospective registry-based study examined patients with ICD for primary or secondary prevention (PP, SP) implanted between January 2010 and January 2020. Outcomes were appropriate (ADC) and inappropriate (IADC) ICD shock. Supplementary analyses for the risks of recurrent shock were conducted if incident therapy occurred. Results Overall, 2997 patients were analyzed (median follow-up 6.5 years, mean age 63.8 years±12.7, 20% female, 27% CRT-D carriers and 47.8 % SP). A total of 386(13%) and 85(2.8%) experienced ADC and IADC, respectively and 143(37%) and 17(20%) recurrent therapies, respectively. Event rates were 2.6(2.4-2.9) [PP 1.7 (1.4-2.0); SP 3.7(3.3-4.2)] and 0.5 (0.4-0.7) [PP 0.4(0.2-0.5); SP 0.7(0.5-0.9)] per 100 person-years for incident ADC and IADC, respectively. For recurrent ADC and IADC, event rates were 14.6(12.3-17.2) [PP 14.1(10.1-19.2); SP 14.7(11.9-17.8)] and 2.9(1.3-5.4) [PP 2.6(0.5-7.7); SP 3.0(1.1-6.6)], respectively. Figure 1 shows cumulative incidences for PP and SP. Females had a lower risk of incident ADC (HR 0.68 [95% CI 0.50;0.92] p=0.01) overall and when SP (HR 0.66 [95% CI 0.45;0.97] p=0.04), as did CRT-D overall (HR 0.60 [95% CI 0.45;0.82] p=0.001) and in SP (HR 0.42 [95% CI 0.24;0.74] p=0.003). Previous revascularization was associated with a lower risk of incident IADC (HR 0.58 [95% CI 0.36;0.94] p=0.03) overall and in SP (HR 0.51 [95% CI 0.28;0.93] p=0.03). Left ventricular ejection fraction (LVEF) <35 and BMI >30 in SP patients were associated with increased risk of incident ADC and IADC respectively (HR 1.38 [95% CI 1.04;1.84] p=0.03) and HR 2.48 [95% CI 1.16;5.32] p=0.02). Association with higher risk of recurrent ADC was only seen in BMI <18.5 for SP patients (HR 87.37 [95% CI 8.43;905.72] p<0.001), no associations for recurrent IADC were observed. No interactions between SP/PP and risk factors, except for BMI>30 on IADC (p for interaction=0.01) occurred. PP (HR 0.38 [95% CI 0.16;0.89] p=0.02) and SP (HR 1.77 [95% CI 1.04;3.03] p=0.03). Conclusion This large single-center study found higher rates of incident and recurrent ICD shock in SP versus PP. Female sex and CRT-D were associated with lower risk of ADC, previous revascularization with increased risk of IADC. BMI>30 and reduced LVEF were associated with increased risk of incident ADC and IADC respectively. Further contemporary studies are needed to cast light on the clinical implications of risk factors.