Apixaban versus enoxaparin in the prevention of venous thromboembolism following total knee arthroplasty: a single-centre, single-surgeon, retrospective analysis.

BACKGROUND: There is a high risk of developing venous thromboembolism (VTE) following total knee arthroplasty (TKA). Conventional thromboprophylactic agents have limitations, such as route of administration, the need for monitoring, narrow therapeutic windows and interactions. Apixaban is a new oral anticoagulant with the potential to overcome these limitations. AIMS: To report the efficacy and safety of apixaban and low-molecular-weight heparin, enoxaparin, in VTE prophylaxis following TKA. METHODS: This single-centre, single-surgeon, retrospective analysis included 506 consecutive patients who underwent TKA between 2009 and 2015 and received enoxaparin or apixaban as thromboprophylaxis. Baseline characteristics of patients, in-hospital rates of VTE, total DVT, proximal or distal DVT, pulmonary embolism, bleeding outcomes and mortality were compared between the two groups. RESULTS: In-hospital VTE occurred in 22 (8.9%) patients in the enoxaparin group and 11 (4.5%) patients in the apixaban group (P = 0.049). Nine (3.6%) patients in the enoxaparin group and one (0.4%) in the apixaban group experienced a postoperative drop in haemoglobin ≥20 g/L that either necessitated transfusion of ≥2 units blood, caused haemodynamic instability or both (P = 0.020). Thirty-five patients experienced other bleeding events, with 25 (9.9%) in the enoxaparin group and 10 (4.0%) in the apixaban group (P = 0.009). There were no statistically significant differences in rates of total DVT, proximal or distal DVT, pulmonary embolism or mortality between the groups. CONCLUSIONS: Compared with enoxaparin, thromboprophylaxis with apixaban resulted in a lower VTE incidence and fewer haemorrhagic complications.

Thromboprophylaxis in patients undergoing total hip and knee arthroplasty: a review of current practices in an Australian teaching hospital.

BACKGROUND: Venous thromboembolism (VTE) remains a cause of significant morbidity and mortality following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Prophylaxis significantly reduces the rate of VTE following these procedures. Previous studies report suboptimal uptake of guideline recommended thromboprophylaxis. AIMS: To describe VTE prophylaxis prescribing practices in a major hospital for joint replacement surgery. To determine the proportion of patients receiving guideline recommended thromboprophylaxis. To define the incidence of in-hospital VTE following THA and TKA. METHODS: A retrospective chart review of 402 consecutive patients undergoing THA or TKA from June to October 2013. Patient characteristics, operative and anaesthetic factors, details of thromboprophylaxis and the incidence of in-hospital VTE are reported. Comparison is made with recent guidelines. RESULTS: Four hundred and two patients underwent THA (n = 202) or TKA (n = 200). Ninety-nine per cent of patients received mechanical prophylaxis. One hundred percent of patients received chemoprophylaxis in hospital. Enoxaparin was most commonly prescribed followed by aspirin. Patients undergoing TKA were more likely to receive an anticoagulant (89.9% vs 47.8% for THA, P < 0.05). 74.5% received chemoprophylaxis on discharge (mean duration 22.1 days). The incidence of in-hospital VTE was 4.7%. CONCLUSIONS: The proportion of study patients receiving thromboprophylaxis compares favourably with prior research. The overall incidence of VTE is higher than that demonstrated in major orthopaedic trials. Inadequate duration of chemoprophylaxis remains a potential area of improvement. Extended prophylaxis should be prescribed as per current guidelines. Comparison between efficacy and safety of various agents is the subject of future research.

[Growth factors for therapeutic angiogenesis in cardiovascular diseases]. / Factores de crecimiento para la angiogénesis terapéutica en las enfermedades cardiovasculares.

Therapeutic angiogenesis based on the administration of growth factors with angiogenic activity allows enhancement of collateral vessels able to palliate insufficient tissue perfusion secondary to obstruction of native arteries. At present, this type of therapy is addressed to patients that fail to respond to conventional treatment (surgical or percutaneous revascularization). The most extensively investigated angiogenic growth factors are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). These cytokines can be administered either as recombinant proteins or as the genes encoding for these proteins. Both approaches have pros and cons that are under investigation in animal models and in clinical studies. Although clinical trials consist so far of small, often non-randomized series, preliminary results are promising. For example, administration of VEGF or FGF has been associated to objective evidence of increased tissue perfusion in patients with myocardial ischemia, and to a significant improvement of pain and ischemia in patients with peripheral arterial disease. Contrarily to expected, these interventions have been associated to scant adverse side effects, although larger clinical trials will be necessary in order to prove the safety and effectiveness of these interventions. Nevertheless, it seems clear that it is feasible to induce effective therapeutic angiogenesis in selected patients without significant associated toxicity.

Assessment of risks associated with cardiovascular gene therapy in human subjects.

Clinical trials of cardiovascular gene therapy, whether using viral (53%) or nonviral (47%) vectors, have thus far disclosed no evidence indicative of inflammatory or other complications, including death, directly attributable to the vector used. Indeed, despite the fact that initial trials of cardiovascular gene therapy targeted patients with end-stage vascular disease, including critical limb ischemia and refractory myocardial ischemia, the mortality for patients enrolled in clinical trials of cardiovascular gene therapy reported to date compares favorably with mortality for similar groups of patients in contemporary controlled studies of medical or interventional therapies. The most common morbidity reported after cardiovascular gene transfer is lower extremity edema; in contrast to data involving genetically engineered mice, however, evidence of life- or limb-threatening edema has not been described in any patients, including patients after gene transfer for myocardial ischemia. Concerns regarding the potential for angiogenic cytokines to promote the progression of atherosclerosis are not supported by angiographic follow-up of patients with coronary or peripheral vascular disease. The levels and duration of gene expression investigated for therapeutic angiogenesis transfer have been unassociated with hemangioma formation. Likewise, there is little evidence from either preclinical or clinical studies to support the notion that the administration of angiogenic growth factors, per se, is sufficient to stimulate the growth of neoplasms. Patients enrolled in clinical studies of angiogenic cytokines, including patients with diabetes and a previous history of retinopathy, have disclosed no evidence to suggest that ocular pathology is a risk of angiogenic growth factor gene transfer.

Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia.

BACKGROUND: Catheter-based myocardial gene transfer (GTx) has not been previously tested in human subjects. Accordingly, we performed a pilot study to investigate the feasibility and safety of catheter-based myocardial GTx of naked plasmid DNA encoding vascular endothelial growth factor-2 (phVEGF-2) in patients with chronic myocardial ischemia. METHODS AND RESULTS: A steerable, deflectable 8F catheter incorporating a 27-guage needle was advanced percutaneously to the left ventricular myocardium of 6 patients with chronic myocardial ischemia. Patients were randomized (1:1) to receive phVEGF-2 (total dose, 200 microgram), which was administered as 6 injections into ischemic myocardium (total, 6.0 mL), or placebo (mock procedure). Injections were guided by NOGA left ventricular electromechanical mapping. Patients initially randomized to placebo became eligible for phVEGF-2 GTx if they had no clinical improvement 90 days after their initial procedure. Catheter injections (n=36) caused no changes in heart rate or blood pressure. No sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforations were observed. phVEGF-2-transfected patients experienced reduced angina (before versus after GTx, 36.2+/-2.3 versus 3.5+/-1.2 episodes/week) and reduced nitroglycerin consumption (33.8+/-2.3 versus 4.1+/-1.5 tablets/week) for up to 360 days after GTx; reduced ischemia by electromechanical mapping (mean area of ischemia, 10.2+/-3.5 versus 2.8+/-1.6 cm(2), P=0.04); and improved myocardial perfusion by SPECT-sestamibi scanning for up to 90 days after GTx when compared with images obtained after control procedure. Conclusions-This randomized trial of catheter-based phVEGF-2 myocardial GTx provides preliminary indications regarding the feasibility, safety, and potential efficacy of percutaneous myocardial GTx to human left ventricular myocardium.

Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease: anesthetic management and results.

UNLABELLED: Gene transfer for therapeutic angiogenesis represents a novel treatment for medically intractable angina in patients judged not amenable to further conventional revascularization. We describe the anesthetic management of 30 patients with class 3 or 4 angina, enrolled in a Phase 1 clinical trial to assess the safety and bioactivity of direct myocardial gene transfer of naked DNA-encoding vascular endothelial growth factor (phVEGF(165)), as sole therapy for refractory angina. The phVEGF(165) was injected directly into the myocardium through a mini-thoracotomy. All patients had major clinical predictors for adverse perioperative cardiac complications. Fast-track anesthetic management with remifentanil and desflurane, multimodal analgesia, and aggressive hemodynamic control with nitroglycerin and esmolol were used. All patients tolerated anesthesia and surgery without problems. No perioperative myocardial infarction, hemodynamic instability, or ventricular failure occurred. VEGF injections caused no clinically significant changes in cardiovascular function. Mean hospital stay was 3.8 days. There was one late death (5 months postoperative). Twenty-nine of 30 patients experienced reduced angina (56.2 +/- 4.1 episodes/week preoperatively versus 3.8 +/- 1.6 postoperatively, P < 0.0001) and reduced sublingual nitroglycerin consumption (60.1 +/- 4.4 tablets/week preoperatively versus 2.9 +/- 1.1 postoperatively, P < 0.0001). IMPLICATIONS: Previously revascularized patients now judged "inoperable," continue to present with chronic, recurrent angina. Our study describes the anesthetic considerations and management of such patients treated with a novel approach by using gene therapy to stimulate angiogenesis and improve perfusion to ischemic myocardium.

Therapeutic angiogenesis in critical limb and myocardial ischemia.

Research in animal models of ischemia has shown that administration of angiogenic growth factors, either as a recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization to promote the development of supplemental collateral blood vessels that will constitute endogenous bypass conduits around occluded native arteries; a strategy termed "therapeutic angiogenesis." In animal models and clinical trials, the best studied cytokines with angiogenic activity are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with critical limb ischemia demonstrated resolution of rest pain and/or improved limb integrity, increased pain-free walking time and ankle-brachial index, newly visible collateral vessels by digital subtraction angiography, and qualitative evidence of improved distal flow by magnetic resonance imaging. Initial clinical trials in patients with end-stage coronary artery disease using direct myocardial injection via thoracotomy resulted in large increases in exercise time and marked reductions in anginal symptoms, as well as objective evidence of improved perfusion and left ventricular function. Larger scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein, and have not shown significant improvement in exercise time or angina compared to placebo. Larger scale placebo-controlled studies of gene transfer using catheter-based endocardial delivery are in progress. Future clinical studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors, as well as the requirement for endothelial progenitor cell or stem cell supplementation, to provide effective and safe therapeutic angiogenesis for patients with critical limb ischemia and chronic myocardial ischemia who are not candidates for conventional revascularization procedures.

Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb?

This article is based on an Experimental Biology symposium held in April 2001 and presents the current status of gene therapy for cardiovascular diseases in experimental studies and clinical trials. Evidence for the use of gene therapy to limit neointimal hyperplasia and confer myocardial protection was presented, and it was found that augmenting local nitric oxide (NO) production using gene transfer (GT) of NO synthase or interruption of cell cycle progression through a genetic transfer of cell cycle regulatory genes limited vascular smooth muscle hyperplasia in animal models and infra-inguinal bypass patients. The results of application of vascular endothelial growth factor (VEGF) GT strategies for therapeutic angiogenesis in critical limb and myocardial ischemia in pilot clinical trials was reviewed. In addition, experimental evidence was presented that genetic manipulation of peptide systems (i.e., the renin-angiotensin II system and the kallikrein-kinin system) was effective in the treatment of systemic cardiovascular diseases such as hypertension, heart failure, and renal failure. Although, as of yet, there are no well controlled human trials proving the clinical benefits of gene therapy for cardiovascular diseases, the data presented here in animal models and in human subjects show that genetic targeting is a promising and encouraging modality, not only for the treatment and long-term control of cardiovascular diseases, but for their prevention as well.

VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease.

BACKGROUND: Direct transfection of ischemic myocardium with naked plasmid DNA encoding for vascular endothelial growth factor-165 (VEGF165) has been shown to mobilize endothelial progenitor cells (EPCs). This study examined the kinetics of circulating EPCs isolated from peripheral blood mononuclear cells after gene transfer, and their role in neovascularization of ischemic myocardium. METHODS: The mononuclear cell population was isolated from peripheral venous blood samples of patients with functional class III or IV angina receiving intramyocardial VEGF165 gene transfer. Peripheral blood mononuclear cells were examined by an in vitro EPC culture assay and fluorescent-activated cell sorting. The data were compared with a control group consisting of patients who had undergone off-pump coronary artery bypass grafting without receiving gene transfer. RESULTS: Coinciding with a rise in VEGF levels, mobilization of EPCs increased significantly over base line for 9 weeks after the treatment (121+/-14 cells/mm2 versus 36.8+/-8 cells/mm2, p < 0.0005), followed by a subsequent decrease. Fluorescent-activated cell sorting analysis confirmed culture assay data, with a statistically significant rise in cells expressing vascular endothelial-cadherin, CD51/61 [alphavbeta3], CD62E [E-selectin], CD34, and KDR. The control group failed to show significant mobilization of EPCs. CONCLUSIONS: Mobilization of EPCs with resultant postnatal vasculogenesis, may play a role in revascularizing ischemic myocardium following human gene transfer with VEGF165.

Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia.

BACKGROUND: NOGA left ventricular (LV) electromechanical mapping (EMM) can be used to distinguish among infarcted, ischemic, and normal myocardium. We investigated the use of percutaneous LV EMM to assess the efficacy of myocardial gene transfer (GTx) of naked plasmid DNA encoding for vascular endothelial growth factor (phVEGF(165)), administered during surgery by direct myocardial injection in patients with chronic myocardial ischemia. METHODS AND RESULTS: A total of 13 consecutive patients (8 men, mean age 60.1+/-2. 3 years) with chronic stable angina due to angiographically documented coronary artery disease, all of whom had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with direct myocardial injection of phVEGF(165) via a minithoracotomy. Foci of ischemic myocardium were identified on LV EMM by preserved viability associated with an impairment in linear local shortening. Myocardial viability, defined by mean unipolar and bipolar voltage recordings >/=5 and >/=2 mV, respectively, did not change significantly after GTx. Analysis of linear local shortening in areas of myocardial ischemia, however, disclosed significant improvement after (15.26+/-0.98%) versus before (9.94+/-1.53%, P:=0. 004) phVEGF(165) GTx. The area of ischemic myocardium was consequently reduced from 6.45+/-1.37 cm(2) before GTx to 0.95+/-0. 41 cm(2) after GTx (P:=0.001). These findings corresponded to improved perfusion scores calculated from single-photon emission CT-sestamibi myocardial perfusion scans recorded at rest (7.4+/-2.1 before GTx versus 4.5+/-1.4 after GTx, P:=0.009) and after pharmacological stress (12.8+/-2.7 before GTx versus 8.5+/-1.7 after GTx, P:=0.047). CONCLUSIONS: The results of EMM constitute objective evidence that phVEGF(165) GTx augments perfusion of ischemic myocardium. These findings, together with reduction in the size of the defects documented at rest by serial single-photon emission CT-sestamibi imaging, suggest that phVEGF(165) GTx may successfully rescue foci of hibernating myocardium.

Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease.

BACKGROUND: Patients presenting with medically intractable angina who have undergone previous coronary bypass (CABG) and/or percutaneous revascularization procedures are frequently deemed "inoperable" based on angiographic findings of diffuse distal disease or a lack of available conduits. We initiated a phase I clinical trial to assess the safety and bioactivity of intramyocardial transfection of plasmid DNA encoding for the angiogenic mitogen vascular endothelial growth factor (ph-VEGF165) in such patients. METHODS: phVEGF165 (125 microg, n = 10; 250 microg, n = 10) was injected directly into the myocardium through a mini left anterior thoracotomy as sole therapy in 20 patients (15 male, 5 female, age 48 to 74 years) with class III or IV angina, reversible ischemia on stress sestamibi scans, and "inoperable" coronary artery disease. RESULTS: All patients tolerated surgery uneventfully and were extubated on the table. No perioperative myocardial infarction, hemodynamic instability, or change in ventricular function occurred. Mean hospital stay was 3.9 days. There was one late death (4 months). Plasma VEGF protein level increased from 30.6+/-4.1 pg/mL pretreatment to 73.7+/-10.1 pg/mL 14 days posttreatment (p = 0.0002) and returned to baseline by day 90. All 16 patients followed to day 90 reported a reduction in angina (nitroglycerin use/week = 60.2+/-4.9 preop vs 3.5+/-1.6 at 90 days; p<0.0001). Seventy percent (7 of 10) patients were completely angina free at 6 months. A reduction in ischemic defects on single photon emission computerized tomography sestamibi scans was observed in 13 of 17 patients at 60 days (7 of 8 in the 250-microg group). Stress perfusion score decreased from 19.4+/-3.7 at baseline to 15.9+/-3.4 at 60 days (p = 0.025). Angiographic evidence of improved collateral filling of at least one occluded vessel was observed in all patients evaluated at day 60. CONCLUSIONS: Direct myocardial gene transfer with phVEGF165 via a mini-thoracotomy can be performed safely and may result in significant symptomatic improvement in patients with "inoperable" coronary artery disease.

Intraoperative multiplane transesophageal echocardiography for guiding direct myocardial gene transfer of vascular endothelial growth factor in patients with refractory angina pectoris.

Gene transfer for therapeutic angiogenesis represents a novel treatment for patients with chronic angina refractory to standard medical therapy and not amenable to conventional revascularization. We sought to assess the role of intraoperative multiplane transesophageal echocardiography (MPTEE) in guiding injection of naked DNA encoding vascular endothelial growth factor (VEGF) into the left ventricular (LV) myocardium of patients with refractory angina. After exposing the LV myocardium via a limited lateral thoracotomy, each of 17 patients in this series received 4 separate injections of VEGF DNA into different myocardial sites. Initial injections in the first patient produced intracavitary microbubbles, indicating injection of DNA into the LV chamber. Subsequently, each injection was preceded by a test injection of agitated saline. The absence of microbubbles while visualizing the LV cavity during the test injection verified that the ensuing injection of DNA would not be inadvertently squandered in the LV chamber itself. Intracavitary LV microbubbles were observed by MPTEE in 13 of 64 (20.3%) saline test injections and in 8 of 16 (50.0%) patients in which saline test injection was used, leading to adjustments in needle position. MPTEE imaging detected a previously unknown large, apical left ventricular thrombus in one patient, thereby preventing inadvertent injection of VEGF DNA through the myocardium into the thrombus. Imaging during and after injection verified no deleterious impact on LV function. We conclude that MPTEE is a useful tool for ensuring that myocardial gene therapy performed by direct needle injection results in gene transfer to the LV myocardium.

Gene therapy for myocardial angiogenesis.

In patients in whom antianginal medications fail to provide sufficient symptomatic relief, additional interventions such as angioplasty or bypass surgery may be required. Although both types of intervention have been shown to be effective for various types of patients, a certain group of patients may not be candidates for either intervention because of the diffuse nature of their coronary artery disease. Moreover, there are many patients in whom recurrent narrowing and/or occlusion of bypass conduits after initially successful surgery has left the patient again symptomatic with no further angioplasty or surgical option. Ischemic muscle represents a promising target for gene therapy with naked plasmid DNA. Intramuscular transfection of genes encoding angiogenic cytokines, particularly those naturally secreted by intact cells, may constitute an alternative treatment strategy for patients with extensive tissue ischemia in whom contemporary therapies (antianginal medications, angioplasty, bypass surgery) have previously failed or are not feasible. This strategy is designed to promote the development of supplemental collateral blood vessels that will constitute endogenous bypass conduits around occluded native arteries, a strategy termed "therapeutic angiogenesis." Preclinical animal studies from our laboratory have established that intramuscular gene transfer may be used to successfully accomplish therapeutic angiogenesis. More recently, phase 1 clinical studies from our institution have established that intramuscular gene transfer may be used to safely and successfully accomplish therapeutic angiogenesis in patients with critical limb ischemia. The notion that this concept could be extrapolated to the treatment of chronic myocardial ischemia was demonstrated in our laboratory by administering recombinant human vascular endothelial growth factor (VEGF) to a porcine model of chronic myocardial ischemia. Recent experiments performed in this same porcine model of myocardial ischemia have shown that direct intramyocardial gene transfer of naked plasmid DNA encoding VEGF (phVEGF(165), the identical plasmid used in our previous animal and human clinical trials) can be safely and successfully achieved through a minimally invasive chest wall incision. Finally, initial results have supported the concept that intramyocardial injection of naked plasmid DNA encoding VEGF can achieve therapeutic angiogenesis, as demonstrated by clinical improvement in patient symptoms and improved myocardial perfusion shown by single-photon emission computed tomography-sestamibi imaging.

Catheter-based myocardial gene transfer utilizing nonfluoroscopic electromechanical left ventricular mapping.

OBJECTIVES: This study investigated the feasibility and safety of percutaneous, catheter-based myocardial gene transfer. BACKGROUND: Direct myocardial gene transfer has, to date, required direct injection via an open thoracotomy. METHODS: Electroanatomical mapping was performed to establish the site of left ventricular (LV) gene transfer. A steerable, deformable 7F catheter with a 27G needle, which can be advanced 3 to 5 mm beyond its distal tip, was then directed to previously acquired map sites, the needle was advanced, and injections were made into the LV myocardium. RESULTS: In two pigs in which methylene blue dye was injected, discretely stained LV sites were observed at necropsy in each pig, corresponding to the injection sites indicated prospectively by the endocardial map. In six pigs in which the injection catheter was used to deliver plasmid using cytomegalovirus promoter/enhancer, encoding nuclear-specific LacZ gene (pCMV-nlsLacZ) (50 microg/ml) to a single LV myocardial region, peak beta-galactosidase activity after five days (relative light units [RLU], mean 135,333+/-28,239, range = 31,508 to 192,748) was documented in the target area of myocardial injection in each pig. Percutaneous gene transfer of pCMV-nlsLacZ (50 microg/ml) was also performed in two pigs with an ameroid constrictor applied to the left circumflex coronary artery, in each pig, peak beta-galactosidase activity after five days (214,851 and 23,140 RLU) was documented at the injection site. All pigs survived until sacrifice, and no complications were observed with either the mapping or the injection procedures. CONCLUSIONS: Percutaneous myocardial gene transfer can be successfully achieved in normal and ischemic myocardium without significant morbidity or mortality. These findings establish the potential for minimally invasive cardiovascular gene transfer.

Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia.

BACKGROUND: We initiated a phase 1 clinical study to determine the safety and bioactivity of direct myocardial gene transfer of vascular endothelial growth factor (VEGF) as sole therapy for patients with symptomatic myocardial ischemia. METHODS AND RESULTS: VEGF gene transfer (GTx) was performed in 5 patients (all male, ages 53 to 71) who had failed conventional therapy; these men had angina (determined by angiographically documented coronary artery disease). Naked plasmid DNA encoding VEGF (phVEGF165) was injected directly into the ischemic myocardium via a mini left anterior thoracotomy. Injections caused no changes in heart rate (pre-GTx=75+/-15/min versus post-GTx=80+/-16/min, P=NS), systolic BP (114+/-7 versus 118+/-7 mm Hg, P=NS), or diastolic BP (57+/-2 versus 59+/-2 mm Hg, P=NS). Ventricular arrhythmias were limited to single unifocal premature beats at the moment of injection. Serial ECGs showed no evidence of new myocardial infarction in any patient. Intraoperative blood loss was 0 to 50 cm3, and total chest tube drainage was 110 to 395 cm3. Postoperative cardiac output fell transiently but increased within 24 hours (preanesthesia=4.8+/-0.4 versus postanesthesia=4.1+/-0.3 versus 24 hours postoperative=6. 3+/-0.8, P=0.02). Time to extubation after closure was 18.4+/-1.4 minutes; average postoperative hospital stay was 3.8 days. All patients had significant reduction in angina (nitroglycerin [NTG] use=53.9+/-10.0/wk pre-GTx versus 9.8+/-6.9/wk post-GTx, P<0.03). Postoperative left ventricular ejection fraction (LVEF) was either unchanged (n=3) or improved (n=2, mean increase in LVEF=5%). Objective evidence of reduced ischemia was documented using dobutamine single photon emission computed tomography (SPECT)-sestamibi imaging in all patients. Coronary angiography showed improved Rentrop score in 5 of 5 patients. CONCLUSIONS: This initial experience with naked gene transfer as sole therapy for myocardial ischemia suggests that direct myocardial injection of naked plasmid DNA, via a minimally invasive chest wall incision, is safe and may lead to reduced symptoms and improved myocardial perfusion in selected patients with chronic myocardial ischemia.

Coronary artery stenting for spontaneous coronary artery dissection: a case report and review of the literature.

Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndromes. It occurs in three major groups: in young women in the peripartum period, in patients with atherosclerotic disease, and in an idiopathic group. There are a number of associated conditions, but the pathogenesis remains unclear. Diagnosis can only be made at angiography. Treatments include medical therapy, coronary artery bypass grafts, and newer interventional procedures. We report on a case of spontaneous coronary artery dissection involving the left circumflex artery in a young adult male presenting with a myocardial infarction after exercise. There were no risk factors for coronary artery disease and no evidence of atherosclerosis on angiography. The dissection was treated with primary coronary artery stenting without predilation, achieving an excellent result. To our knowledge, this is the third known case of successful coronary artery stenting for this condition and the first case of primary stenting without prior angioplasty.