BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

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Sudden cardiac death remains the leading cause of death in the U.S. A left ventricular ejection fraction (LVEF)<30% to 35% identifies a population of patients at increased risk for sudden cardiac death. Once identified, an implantable cardioverter-defibrillator (ICD) is effective in reducing the occurrence of sudden cardiac death. Yet in a substantial proportion of patients who receive an ICD based on reduced LVEF, the device never delivers therapy. Furthermore, the majority of patients who die suddenly do not qualify for ICD placement under current LVEF-based criteria in the guidelines. This review considers the potential role of cardiac imaging in improving the selection of patients most likely to benefit from an ICD. The presence of myocardial scar and/or unrevascularized myocardial ischemia provides an important substrate for the occurrence of potentially fatal ventricular arrhythmias. The presence of clinical heart failure further increases the risk of ventricular arrhythmia. The sympathetic nervous system provides an important trigger for major arrhythmic events, both through global overactivity and through regional heterogeneity of sympathetic activity. A mismatch of myocardial perfusion and innervation may pose a particularly great risk. Imaging modalities provide unique opportunities to investigate the anatomic and pathophysiologic substrates, as well as the triggering effects of cardiac sympathetic innervation. Combining imaging and electrophysiologic modalities offers promise for improved accuracy in future selection of patients with heart failure for ICD placement.

SUMMARYBackground: The routine use of vascular imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in guiding percutaneous coronary interventions (PCI) is still controversial especially when using drug-eluting stents. A meta-analysis of trials using bare metal stents was previously published. Methods: We conducted a meta-analysis of available published trials that compared imaging-guided PCI and angiography-guided PCI in patients undergoing routine PCI only. Trials that enrolled patients with acute coronary syndrome were excluded to decrease heterogeneity. We aimed to study both drug-eluting stents (DES) as well as bare metal stents (BMS). We identified seven randomized controlled trials on IVUS-guided bare metal stents. We also identified three randomized controlled trials on IVUS-guided drug-eluting stents. To improve the power of the drugeluting stent data, we identified, and included, nine registries that compared IVUS-guided PCI to angiography-guided PCI in the drug-eluting stent era. Nonrandomized registries that included BMS only were excluded as there are multiple previous meta-analyses that studied these patients. Finally, we identified one registry that compared OCT-guided PCI to angiography-guided PCI using either a BMS or a DES. A total of 14,197 patients were studied overall. The meta-analysis was conducted using a random effect model. Results: Imaging guidance was associated with a significantly larger postintervention minimal luminal diameter (SMD: 0.289. 95% CI: 0.213-0.365. P < 0.01).Imaging-guided stenting was associated with a significant decrease in the major adverse cardiac events (MACE) in the DES patients (odds ratio: 0.810. 95% CI: 0.719-0.912. P < 0.01) and combined DES and BMS patients (odds ratio: 0.782. 95% CI: 0.686-0.890. P < 0.01). Imaging guidance was associated with significantly lower events of death from all causes in DES patients (odds ratio: 0.654. 95% CI: 0.468-0.916. P < 0.01) and in the combined DES and BMS patients (odds ratio: 0.727. 95% CI: 0.540-0.980. P < 0.01).The risk of myocardial infarction (MI) was significantly lower with imaging guidance in both, DES patients (odds ratio: 0.551. 95% CI: 0.363-0.837. P < 0.01) and combined DES and BMS patients (odds ratio: 0.589. 95% CI: 0.425-0.816. P < 0.01). This may, in part, be explained by the significantly lower risk of stent thrombosis in imaging-guided DES patients (odds ratio: 0.651. 95% CI: 0.499-0.850. P < 0.01) and combined DES and BMS patients (odds ratio: 0.665. 95% CI: 0.513-0.862. P < 0.01). Patients who received a DES showed no difference between imaging guidance and angiography guidance in repeated target lesion revascularization, while the analysis of BMS alone and the DES and BMS combined showed significant superiority of the imagingguided PCI group. Conclusion: Imaging-guided PCI significantly lowered the risk of death, MI, stent thrombosis, and the combined MACE in DES-implanted patients and all stented patients (DES or BMS). However, imaging guidance had no significant...

The endeavor to study desensitization in kidney transplantation has not been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization, and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive three weekly infusions of SG (320 mg/kg). The study was stopped after five subjects were enrolled, and their data were analyzed after completing a follow-up period of 90 days. Two subjects had elevated troponin I levels in setting of SG infusion, one of which was interpreted as a non-ST elevation myocardial infarction. All other adverse events were transient. SG pharmacokinetic analysis showed mean (SD) C max , T max , AUC, and half-life of 4.39 (0.69) mg/mL, 2.42 (0.91) hours, 171.86 (52.35) mg h/mL, and 40.60 (11.96) hours, respectively. None of the subjects developed new anti-HLA antibodies following SG infusion and throughout the study period. In conclusion, SG is a potential alternative to PRBCs in ESRD patients considered for kidney transplantation as it was not associated with humoral sensitization. Larger studies in highly sensitized patients are required to further evaluate for potential safety signals. K E Y W O R D S