TY - JOUR
T1 - Common genetic variants in selected Ca2+ signaling genes and the risk of appropriate ICD interventions in patients with heart failure
AU - Francia, Pietro
AU - Adduci, Carmen
AU - Ricotta, Agnese
AU - Stanzione, Rosita
AU - Sensini, Isabella
AU - Uccellini, Arianna
AU - Frattari, Alessandra
AU - Balla, Cristina
AU - Cotugno, Maria
AU - Cappato, Riccardo
AU - Rubattu, Speranza
AU - Volpe, Massimo
PY - 2013/12
Y1 - 2013/12
N2 - Purpose: Defective Ca2+ handling in failing cardiomyocites predisposes patients with heart failure (HF) to ventricular arrhythmia. We investigated whether gene variants of Ca2+ handling proteins are associated with the occurrence of ventricular tachycardia/fibrillation (VT/VF) in HF patients implanted with a primary prevention implantable cardioverter-defibrillator (ICD). Methods: One hundred thirty-six patients with HF were followed from ICD implantation to the time of first appropriate ICD intervention for VT > 170 bpm. The following polymorphisms were genotyped: ATP2A2 rs1860561 and rs56243033; RYR2 rs4142933; CASQ2 rs4074536; SLC8A1 g.-23449C > A; PLN rs12198461; FKBP1B rs7568163. Hazard ratios (HR) were derived from Cox proportional-hazards regression analysis. Results: After a mean follow-up of 879 days (IQ range, 327 to 1,459), 34 patients (25 %) had appropriate ICD intervention. Non-sustained VT (HR, 2.12; 95 %CI, 0.87-5.19; p = 0.09) and atrial fibrillation (AF) at ICD implantation (HR, 2.33; 95 %CI, 0.89-6.10; p = 0.08) predicted appropriate ICD interventions with borderline statistical significance. Prevalence of ATP2A2 rs1860561 variant was 17 % in patients without VT/VF and 4 % in those with ventricular arrhythmia (p = 0.009). After adjustment for AF and NSVT, the rs1860561 A mutant allele independently predicted lower incidence of VT/VF (HR, 0.29; 95 %CI, 0.09-0.98; p = 0.04). Conclusions: The observation that ATP2A2 rs1860561 gene variant associated with lower risk of life-threatening arrhythmia in HF patients suggests that selected calcium gene variants may modify the risk of SD even within the complex and polygenic pathological condition of HF. Combining traditional risk factors and genetic profiling could reveal helpful to identify HF patients who will benefit most from ICD implantation.
AB - Purpose: Defective Ca2+ handling in failing cardiomyocites predisposes patients with heart failure (HF) to ventricular arrhythmia. We investigated whether gene variants of Ca2+ handling proteins are associated with the occurrence of ventricular tachycardia/fibrillation (VT/VF) in HF patients implanted with a primary prevention implantable cardioverter-defibrillator (ICD). Methods: One hundred thirty-six patients with HF were followed from ICD implantation to the time of first appropriate ICD intervention for VT > 170 bpm. The following polymorphisms were genotyped: ATP2A2 rs1860561 and rs56243033; RYR2 rs4142933; CASQ2 rs4074536; SLC8A1 g.-23449C > A; PLN rs12198461; FKBP1B rs7568163. Hazard ratios (HR) were derived from Cox proportional-hazards regression analysis. Results: After a mean follow-up of 879 days (IQ range, 327 to 1,459), 34 patients (25 %) had appropriate ICD intervention. Non-sustained VT (HR, 2.12; 95 %CI, 0.87-5.19; p = 0.09) and atrial fibrillation (AF) at ICD implantation (HR, 2.33; 95 %CI, 0.89-6.10; p = 0.08) predicted appropriate ICD interventions with borderline statistical significance. Prevalence of ATP2A2 rs1860561 variant was 17 % in patients without VT/VF and 4 % in those with ventricular arrhythmia (p = 0.009). After adjustment for AF and NSVT, the rs1860561 A mutant allele independently predicted lower incidence of VT/VF (HR, 0.29; 95 %CI, 0.09-0.98; p = 0.04). Conclusions: The observation that ATP2A2 rs1860561 gene variant associated with lower risk of life-threatening arrhythmia in HF patients suggests that selected calcium gene variants may modify the risk of SD even within the complex and polygenic pathological condition of HF. Combining traditional risk factors and genetic profiling could reveal helpful to identify HF patients who will benefit most from ICD implantation.
KW - Calcium handling proteins
KW - Gene variants
KW - Heart failure
KW - ICD
KW - Sudden death
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U2 - 10.1007/s10840-013-9827-1
DO - 10.1007/s10840-013-9827-1
M3 - Article
C2 - 24048583
AN - SCOPUS:84889085121
VL - 38
SP - 169
EP - 177
JO - Journal of Interventional Cardiac Electrophysiology
JF - Journal of Interventional Cardiac Electrophysiology
SN - 1383-875X
IS - 3
ER -