Neurohormonal status is associated with long-term appropriate implantable cardioverter defibrillator therapy for life-threatening ventricular arrhythmia

Abstract Background Neurohormonal status is associated with the risk of life-threatening ventricular arrhythmia. Purpose We aimed to assess whether neurohormonal status in patients with an implantable cardioverter defibrillator (ICD) is correlated with the risk of long-term appropriate shock or overdrive delivered by the ICD for life-threatening arrhythmia. Methods A total of 331 clinically stable patients with ICD without any past history of shock or overdrive for life-threatening ventricular arrhythmia were enrolled in a two-center prospective cohort and followed up for a median time of 7.9 years. At enrolment, patients’ medical history, treatment, clinical and imaging data were recorded and, blood and, blood samples were drawn for the assessment of standard biological parameters as well as 3 neurohormones (aldosterone, A type NT-pro-Atrial natriuretic peptide (ANP) and MR-pro-Adrenomedullin (ADM). The primary endpoint of the study was the occurrence of appropriate shock or overdrive delivered by the ICD (ICD therapy). A multivariable cox model adjusted on age, gender, primary or secondary prevention ICD as well as all baseline variables unequally distributed between groups with or without ICD therapy was used for the assessment of the relationship between the 3 neurohormones and the primary endpoint. Results The population consisted of patients with a mean age of 60±15 years, among which 59(18%) women and 160(48%) with a secondary prevention indication for ICD. At baseline all data were similar between patients with or without ICD therapy with the exception of weight, systolic blood pressure, left ventricular ejection fraction (LVEF) and serum potassium and creatinine levels. No other variable, including MADIT and SHOCKED score were significantly associated with the risk of ICD therapy. Death was recorded in 114(34%) patients and a total of 78(24%), 76(23%) and 106(33%) patients had appropriate shock, overdrive and ICD therapy respectively during the follow-up. On multivariable analysis, highest levels of ANP and lowest levels of ADM but not aldosterone were independently associated with life-threatening ventricular arrhythmia requiring ICD therapy (table). Other correlates of ICD therapy were lower LVEF and, higher weight, serum potassium and creatinine concentrations. ANP and ADM had a stepwise additive impact on the risk of ICD therapy. (Figure 1) Conclusions In a stable all comer population with ICD and no history of ICD therapy, blood levels of neurohormones ANP and ADM are associated with the risk of life-threatening ventricular arrhythmia requiring ICD-delivered shock or overdrive independent of other correlates. ANP and ADM concentrations may be useful in identifying patients at high risk of such arrhythmia and who may most benefit from ICD implantation.