Objective Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD). Methods 785 patients aged: 63±12 undergoing coronary angiography were independently enrolled into discovery (N=186) and replication (N=599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6 yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI. Results The incidence of cardiovascular death/MI was 13% (N=99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR=4.81, p=1 × 10−6) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67 to 0.73, p=0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts. Conclusion Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification.

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Background Abiraterone, an androgen deprivation therapy (ADT), has been used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). It has been associated with increased risks of hypokalemia and cardiac disorders. We report a case of torsades de pointes (TdP) associated with abiraterone use and refractory hypokalemia in a man with mCRPC. Case summary A 78-year-old man with mCRPC presented to the emergency room for generalized weakness. Laboratory results revealed a potassium level of 2.2 mmol/L (3.5-5.0), magnesium level of 2.4 mg/dl (1.6-2.5), and normal kidney and hepatic functions. Initial EKG showed atrial fibrillation with rapid ventricular rate of 106 b.p.m., frequent premature ventricular contractions (PVCs), and a QTc of 634 ms. The patient had multiple episodes of TdP, became pulseless and underwent advanced cardiac life support, including defibrillation. Despite a total of 220 mEq of intravenous potassium chloride, his potassium level only improved to 2.8 mmol/L. He received spironolactone and amiloride to promote urinary potassium reabsorption in addition to hydrocortisone, in an effort to reduce abiraterone’s effect on increasing mineralocorticoid synthesis. Discussion Abiraterone has been widely used in mCRPC since its approval by the FDA in 2011. Regulatory guidelines and standardized close QTc and electrolyte monitoring in patients may help prevent fatal arrhythmias associated with abiraterone.