Larry Diaz-Sandoval

Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial)

NAC reduces the risk of postcardiac catheterization nephropathy in patients with chronic renal insufficiency and decreased ejection fraction. Thus, it should be considered as routine prophylaxis in patients with chronic renal insufficiency undergoing cardiac catheterization.

Local Gene Transfer of phVEGF-2 Plasmid by Gene-Eluting Stents An Alternative Strategy for Inhibition of Restenosis

Background—Drug-eluting stents represent a useful strategy for the prevention of restenosis using various antiproliferative drugs. These strategies share the liability of impairing endothelial recovery, thereby altering the natural biology of the vessel wall and increasing the associated risk of stent thrombosis. Accordingly, we tested the hypothesis that local delivery via gene-eluting stent of naked plasmid DNA encoding for human vascular endothelial growth factor (VEGF)-2 could achieve similar reductions in neointima formation while accelerating, rather than inhibiting, reendothelialization. Methods and Results—phVEGF 2-plasmid (100 or 200 μg per stent)–coated BiodivYsio phosphorylcholine polymer stents versus uncoated stents were deployed in a randomized, blinded fashion in iliac arteries of 40 normocholesterolemic and 16 hypercholesterolemic rabbits. Reendothelialization was nearly complete in the VEGF stent group after 10 days and was significantly greater than in control stents (98.7±1% versus 79.0±6%, P <0.01). At 3 months, intravascular ultrasound analysis revealed that lumen cross-sectional area (4.2±0.4 versus 2.27±0.3 mm2, P <0.001) was significantly greater and percent cross-sectional narrowing was significantly lower (23.4±6 versus 51.2±10, P <0.001) in VEGF stents compared with control stents implanted in hypercholesterolemic rabbits. Transgene expression was detectable in the vessel wall along with improved functional recovery of stented segments, resulting in a 2.4-fold increase in NO production. Conclusions—Acceleration of reendothelialization via VEGF-2 gene–eluting stents provides an alternative treatment strategy for the prevention of restenosis. VEGF-2 gene–eluting stents may be considered as a stand-alone or combination therapy.

Endothelial recovery: The next target in restenosis prevention

By most accounts, the field of interventional cardiology appears to have achieved one of its most elusive milestones, the virtual eradication of restenosis. In the present issue of Circulation, however, Hedman and colleagues 1 report the results of a pilot study of gene therapy with vascular endothelial growth factor (VEGF) for restenosis prevention. Are these authors attempting to develop a treatment for a disease that no longer exists? Or is it possible that the mounting exuberance anticipating the release of drug-eluting stents is ignoring a major liability of these otherwise promising therapies? See p 2677

Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association

Non–vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.

Gene therapy for cardiovascular angiogenesis

Atherosclerosis and endothelial dysfunction are responsible for the pathophysiologic basis of the spectrum of cardiovascular disorders including ischaemic heart disease (IHD), the leading cause of morbidity and mortality in the US. There have been major advances, including the use of pharmacotherapy, coronary and peripheral percutaneous transluminal interventions (PTI), coronary and peripheral bypass surgery and primary/secondary prevention measures. There are, however, multiple unmet needs: IHD refractory to medical therapy and unsuitable for revascularisation; critical limb ischaemia unsuitable for PTI or surgery; restenosis; ischaemic/diabetic neuropathy and heart failure. Cardiovascular gene therapy (GT) with vascular endothelial growth factor (VEGF) has yielded improved perfusion and reduced ischaemia in preclinical models of IHD. Several preclinical studies and Phase I and II clinical trials have shown the safety and therapeutic potential of GT in the treatment of IHD, peripheral arterial disease (PAD), restenosis, and ischaemic and diabetic neuropathy, pointing to the need for Phase III clinical trials.

META-ANALYSIS OF DRUG-COATED BALLOON VERSUS STANDARD BALLOON ANGIOPLASTY FOR TREATMENT OF INFRAPOPLITEAL LESIONS IN CRITICAL LIMB ISCHEMIA

Drug-Coated Balloon (DCB) angioplasty has emerged as a feasible and effective option for the treatment of infrapopliteal (IP) arterial lesions in patients with CLI. The purpose was to conduct a meta-analysis of the best available evidence comparing the safety and efficacy of DCB versus standard PTA

SAFETY AND EFFICACY OF USING RECOIL STENTS FOR TREATMENT OF ISCHEMIC STROKE: A META-ANALYSIS OF RCTS

Thrombectomy with the use of a stent retriever (SR), in addition to IV rt-PA, improve reperfusion rates and long-term functional outcome. We planned to evaluate the safety and feasibility of SR compared to IV rtPA for treatment of ischemic stroke. We searched Pub Med and Cochrane until October 2015

Gene Therapy for Angiogenesis

Atherosclerosis and endothelial dysfunction are responsible for the pathophysiologic basis of the spectrum of cardiovascular disorders including ischemic heart disease (IHD), the leading cause of morbidity and mortality in the United States. There have been major advances including the use of pharmacotherapy, coronary and peripheral percutaneous transluminal interventions (PTI), coronary and peripheral bypass surgery, and primary/secondary prevention measures. There are, however, multiple unmet needs: IHD refractory to medical therapy and unsuitable for revascularization; critical limb ischemia (CLI) unsuitable for PTI or surgery; restenosis; ischemic/diabetic neuropathy; and heart failure. Cardiovascular gene therapy (GT) with vascular endothelial growth factor (VEGF) and other angiogenic factors such as fibroblast growth factor (FGF) has yielded improved perfusion and reduced ischemia in preclinical models of IHD. Several preclinical studies, phase I and II clinical trials, have shown the safety and therapeutic potential of GT in the treatment of IHD, peripheral arterial disease (PAD), restenosis, and ischemic and diabetic neuropathy, pointing to the need for carefully designed phase III clinical trials, which would have to address the advantages and disadvantages of the diverse delivery strategies, candidate genes, and methods of functional assessment of angiogenesis, while selecting relevant primary and secondary