Characteristics and Outcomes of Patients With History of CABG Undergoing Cardiac Catheterization Via the Radial Versus Femoral Approach.

OBJECTIVES: The aims of this study were to examine rates of radial artery access in post-coronary artery bypass grafting (CABG) patients undergoing diagnostic catherization and/or percutaneous coronary intervention (PCI), whether operators with higher procedural volumes and higher percentage radial use were more likely to perform diagnostic catherization and/or PCI via the radial approach in post-CABG patients, and clinical and procedural outcomes in post-CABG patients who undergo diagnostic catherization and/or PCI via the radial or femoral approach. BACKGROUND: There are limited data comparing outcomes of patients with prior CABG undergoing transradial or transfemoral diagnostic catheterization and/or PCI. METHODS: Using the National Cardiovascular Data Registry CathPCI Registry, all diagnostic catheterizations and PCIs performed in patients with prior CABG from July 1, 2009, to March 31, 2018 (n = 1,279,058, 1,173 sites) were evaluated. Temporal trends in transradial access were examined, and mortality, bleeding, vascular complications, and procedural metrics were compared between transradial and transfemoral access. RESULTS: The rate of transradial access increased from 1.4% to 18.7% over the study period. Transradial access was associated with decreased mortality (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.75 to 0.91), decreased bleeding (OR: 0.57; 95% CI: 0.51 to 0.63), decreased vascular complications (OR: 0.38; 95% CI: 0.30 to 0.47), increased PCI procedural success (OR: 1.11; 95% CI: 1.06 to 1.16; p < 0.0001), and significantly decreased contrast volume across all procedure types. Transradial access was associated with shorter fluoroscopy time for PCI-only procedures but longer fluoroscopy time for diagnostic procedures plus ad hoc PCI and diagnostic procedures only. Operators with a higher rate of transradial access in non-CABG patients were more likely to perform transradial access in patients with prior CABG. CONCLUSIONS: The rate of transradial artery access in patients with prior CABG undergoing diagnostic catheterization and/or PCI has increased over the past decade in the United States, and it was more often performed by operators using a transradial approach in non-CABG patients. Compared with transfemoral access, transradial access was associated with improved clinical outcomes in patients with prior CABG.

Reduced radiation exposure in the cardiac catheterization laboratory with a novel vertical radiation shield.

OBJECTIVES: Investigation of novel vertical radiation shield (VRS) in reducing operator radiation exposure. BACKGROUND: Radiation exposure to the operator remains an occupational health hazard in the cardiac catheterization laboratory (CCL). METHODS: A mannequin simulating an operator was placed near a computational phantom, simulating a patient. Measurement of dose equivalent and Air Kerma located the angle with the highest radiation, followed by a common magnification (8 in.) and comparison of horizontal radiation absorbing pads (HRAP) with or without VRS with two different: CCL, phantoms, and dosimeters. Physician exposure was subsequently measured prospectively with or without VRS during clinical procedures. RESULTS: Dose equivalent and Air Kerma to the mannequin was highest at left anterior oblique (LAO)-caudal angle (p < .005). Eight-inch magnification increased mGray by 86.5% and µSv/min by 12.2% compared to 10-in. (p < .005). Moving 40 cm from the access site lowered µSv/min by 30% (p < .005). With LAO-caudal angle and 8-in. magnification, VRS reduced µSv/min by 59%, (p < .005) in one CCL and µSv by 100% (p = .016) in second CCL in addition to HRAP. Prospective study of 177 procedures with HRAP, found VRS lowered µSv by 41.9% (µSv: 15.2 ± 13.4 vs. 26.2 ± 31.4, p = .001) with no difference in mGray. The difference was significant after multivariate adjustment for specified variables (p < .001). CONCLUSIONS: Operator radiation exposure is significantly reduced utilizing a novel VRS, HRAP, and distance from the X-ray tube, and consideration of lower magnification and avoiding LAO-caudal angles to lower radiation for both operator and patient.

SCAI expert consensus statement update on best practices for transradial angiography and intervention.

Transradial angiography and intervention continues to become increasingly common as an access site for coronary procedures. Since the first "Best Practices" paper in 2013, ongoing trials have shed further light onto the safest and most efficient methods to perform these procedures. Specifically, this document comments on the use of ultrasound to facilitate radial access, the role of ulnar artery access, the utility of non-invasive testing of collateral flow, strategies to prevent radial artery occlusion, radial access for primary PCI and topics that require further study.

Novel method for radial sheath removal using manual pressure over hemostatic pad combined with ulnar compression.

OBJECTIVES: Study a novel method using manual pressure on a hemostatic pad and hemoband for ulnar compression as a potential alternative for radial sheath removal. BACKGROUND: The standard for transradial access site (TRA) sheath removal requires an inflatable pressure band over the radial artery and recently a band over the ulnar artery to reduce complications. We present a novel technique using a SoftSeal®-STF hemostatic pad over the radial artery combined with a hemoband over the ulnar artery after sheath removal. METHODS: All patients had activated clotting time (ACT); sheath removal was performed immediately upon transfer to the recovery room. A hemoband compressed the ulnar artery, radial artery flow was measured using plethysmography and pulse oximetry while direct pressure applied using SoftSeal-STF hemostatic pad for 15 min after radial sheath removed. Radial artery patency was measured using reverse Barbeau test. If radial artery occlusion (RAO) present, patient was asked to return in one month to repeat test. RESULTS: Fifty-nine patients were enrolled in the study, one-third with diabetes mellitus, one-third with prior coronary artery bypass surgery, and one-third with history of percutaneous coronary intervention. Mean ACT 261 ± 50 sec, all patients had 4 Fr sheaths and no PCI were performed. Three (6%) patients had minor bleeding requiring use of a pressure band and one (2%) had RAO, which re-canalized at one month. CONCLUSIONS: Manual pressure of SoftSeal-STF hemostatic pad combined with ulnar compression is a potential alternative to current practice with an inflatable pressure band.

Early Access to the Cardiac Catheterization Laboratory for Patients Resuscitated From Cardiac Arrest Due to a Shockable Rhythm: The Minnesota Resuscitation Consortium Twin Cities Unified Protocol.

BACKGROUND: In 2013 the Minnesota Resuscitation Consortium developed an organized approach for the management of patients resuscitated from shockable rhythms to gain early access to the cardiac catheterization laboratory (CCL) in the metro area of Minneapolis-St. Paul. METHODS AND RESULTS: Eleven hospitals with 24/7 percutaneous coronary intervention capabilities agreed to provide early (within 6 hours of arrival at the Emergency Department) access to the CCL with the intention to perform coronary revascularization for outpatients who were successfully resuscitated from ventricular fibrillation/ventricular tachycardia arrest. Other inclusion criteria were age >18 and <76 and presumed cardiac etiology. Patients with other rhythms, known do not resuscitate/do not intubate, noncardiac etiology, significant bleeding, and terminal disease were excluded. The primary outcome was survival to hospital discharge with favorable neurological outcome. Patients (315 out of 331) who were resuscitated from VT/VF and transferred alive to the Emergency Department had complete medical records. Of those, 231 (73.3%) were taken to the CCL per the Minnesota Resuscitation Consortium protocol while 84 (26.6%) were not taken to the CCL (protocol deviations). Overall, 197 (63%) patients survived to hospital discharge with good neurological outcome (cerebral performance category of 1 or 2). Of the patients who followed the Minnesota Resuscitation Consortium protocol, 121 (52%) underwent percutaneous coronary intervention, and 15 (7%) underwent coronary artery bypass graft. In this group, 151 (65%) survived with good neurological outcome, whereas in the group that did not follow the Minnesota Resuscitation Consortium protocol, 46 (55%) survived with good neurological outcome (adjusted odds ratio: 1.99; [1.07-3.72], P=0.03). CONCLUSIONS: Early access to the CCL after cardiac arrest due to a shockable rhythm in a selected group of patients is feasible in a large metropolitan area in the United States and is associated with a 65% survival rate to hospital discharge with a good neurological outcome.

The effect of Definity on systemic and pulmonary hemodynamics in patients.

BACKGROUND: The purpose of this study was to evaluate the pulmonary and systemic hemodynamic effects of Definity in patients with normal as well as those with elevated pulmonary artery pressure at baseline. Secondary objectives of the study were to evaluate safety and determine whether any potential immunologic reactions develop after Definity administration. METHODS: Patients with normal and elevated pulmonary artery systolic pressure undergoing right-heart catheterization received Definity (10 µL/kg) as a slow bolus over 30 to 60 sec. Multiple sequential measurements of right atrial pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, mean pulmonary artery pressure, cardiac output, and pulmonary capillary wedge pressure were made before and after Definity administration. Vital signs, electrocardiograms, and blood samples were taken at multiple time points. Patients were followed for the development of adverse events. RESULTS: A total of 32 patients (16 with elevated pulmonary artery systolic pressure > 35 mm Hg) were enrolled. No significant changes in any pulmonary or systemic hemodynamic parameters, vital sign values, electrocardiographic data, or laboratory variables were found for data obtained before versus after receipt of Definity. CONCLUSIONS: The administration of Definity at the approved dosage does not change pulmonary or systemic hemodynamics in control patients or those with mild to moderate pulmonary hypertension. No significant changes were noted in a wide array of clinical and laboratory safety assessments after patients were exposed to Definity.

Percutaneous management of a long saphenous vein graft aneurysm: a case report and review of literature.

Aneurysms of saphenous vein grafts are rare but can result in complications such as myocardial infarction or death. Percutaneous treatment has included a variety of approaches, including covered stents. Long aneurysms in saphenous vein grafts pose an additional challenge due to the lack of coronary covered stents with sufficient length. We present successful treatment of a long saphenous vein graft aneurysm with use of peripheral covered stents over two coronary guidewires, a 55-centimeter 8-French sheath and no guide catheter.

Stem cells for myocardial repair with use of a transarterial catheter.

BACKGROUND: Using a swine model of postinfarction left ventricle (LV) remodeling, we investigated marrow-derived, multipotent progenitor cell (MPC) transplantation into hearts with acute myocardial infarction (AMI) via a novel transarterial catheter. METHODS AND RESULTS: The left anterior descending coronary artery was balloon-occluded after percutaneous transluminal angiography to generate AMI (60-minute no-flow ischemia). The transarterial catheter was then placed in the same coronary artery, and either 50x10(6) MPCs (cell group, n=6) or saline (control, n=6) was injected into the border zone (BZ) myocardium. LV function was assessed by magnetic resonance imaging before AMI and at 1 and 4 weeks after AMI, whereas myocardial energy metabolism was assessed by (31)P-magnetic resonance spectroscopy at week 4. One week after AMI, the ejection fraction was significantly reduced in both groups from a baseline of approximately 50% to 31.3+/-3.9% (cell group) and 33.3+/-3.1% (control). However, at week 4, the cell group had a significant recovery in ejection fraction. The functional improvements were accompanied by a significant improvement in myocardial bioenergetics. Histologic data demonstrated a 0.55% cell engraftment rate 4 weeks after MPC transplantation. Only 2% of engrafted cells were costaining positive for cardiogenic markers. Vascular density in the BZ was increased in the cell group. Conditioned medium from cultured MPCs contained high levels of vascular endothelial growth factor, which was increased in response to hypoxia. MPCs cocultured with cardiomyocytes inhibited changes in cardiomyocyte mitochondrial membrane potential and cytochrome c release induced by tumor necrosis factor-alpha. CONCLUSIONS: Thus, a paracrine effect may contribute significantly to the observed therapeutic effects of MPC transplantation.

Coronary artery disease in young women and men with long-standing insulin-dependent diabetes.

The prevalence and predictors of coronary artery disease were examined in people aged 40 years and younger with insulin-dependent diabetes mellitus. Analysis was performed on those who presented between 1999 and 2003 for kidney and/or pancreas transplant at the University of Minnesota, as all patients who have diabetes mellitus are required to have perioperative cardiology evaluation. The mean age was 33.5 +/- 4.4 years for 88 subjects, all had insulin-dependent diabetes mellitus, and 33% were dialysis dependent. Severe coronary artery disease was found in 18.2% of women and in 24.2% of men. Three-vessel coronary artery disease trended less in women (9.1%) compared with men (12.1%). Multivariate predictors for severe and 3-vessel coronary artery disease included prior coronary artery disease, hypertension duration, and ST-T wave changes on electrocardiogram. Coronary artery disease is twice as high as expected in young woman. Studies on early management for atherosclerosis are warranted in this high-risk population.

Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling.

BACKGROUND: The present study examined whether transplantation of adherent bone marrow-derived stem cells, termed pMultistem, induces neovascularization and cardiomyocyte regeneration that stabilizes bioenergetic and contractile function in the infarct zone and border zone (BZ) after coronary artery occlusion. METHODS AND RESULTS: Permanent left anterior descending artery occlusion in swine caused left ventricular remodeling with a decrease of ejection fraction from 55+/-5.6% to 30+/-5.4% (magnetic resonance imaging). Four weeks after left anterior descending artery occlusion, BZ myocardium demonstrated profound bioenergetic abnormalities, with a marked decrease in subendocardial phosphocreatine/ATP (31P magnetic resonance spectroscopy; 1.06+/-0.30 in infarcted hearts [n=9] versus 1.90+/-0.15 in normal hearts [n=8; P<0.01]). This abnormality was significantly improved by transplantation of allogeneic pMultistem cells (subendocardial phosphocreatine/ATP to 1.34+/-0.29; n=7; P<0.05). The BZ protein expression of creatine kinase-mt and creatine kinase-m isoforms was significantly reduced in infarcted hearts but recovered significantly in response to cell transplantation. MRI demonstrated that the infarct zone systolic thickening fraction improved significantly from systolic "bulging" in untreated animals with myocardial infarction to active thickening (19.7+/-9.8%, P<0.01), whereas the left ventricular ejection fraction improved to 42.0+/-6.5% (P<0.05 versus myocardial infarction). Only 0.35+/-0.05% donor cells could be detected 4 weeks after left anterior descending artery ligation, independent of cell transplantation with or without immunosuppression with cyclosporine A (with cyclosporine A, n=6; no cyclosporine A, n=7). The fraction of grafted cells that acquired an endothelial or cardiomyocyte phenotype was 3% and approximately 2%, respectively. Patchy spared myocytes in the infarct zone were found only in pMultistem transplanted hearts. Vascular density was significantly higher in both BZ and infarct zone of cell-treated hearts than in untreated myocardial infarction hearts (P<0.05). CONCLUSIONS: Thus, allogeneic pMultistem improved BZ energetics, regional contractile performance, and global left ventricular ejection fraction. These improvements may have resulted from paracrine effects that include increased vascular density in the BZ and spared myocytes in the infarct zone.

Acute coronary syndromes in patients with renal disease: what are the issues?

Patients with chronic kidney disease and acute coronary syndromes are at high risk for both bleeding and ischemic events. This risk increases with the severity of renal insufficiency. Management for acute coronary syndromes in the setting of kidney disease is a paradox; as the benefit of current treatment is high, so is the risk for complications. Patients with chronic renal disease are frequently excluded from randomized clinical trials, and therefore, the optimal treatment strategies are often speculative in this high-risk patient population. Additional research is needed to further refine the optimal management of patients with chronic kidney disease in the setting of acute coronary syndromes.

Feasibility assessment of aortic valve area in patients with aortic stenosis using a pressure wire through a 4 French system and single femoral arterial access.

OBJECTIVE: We sought to determine the safety, success and accuracy of using a pressure wire through a 4 French catheter with single arterial access to determine the aortic valve area in patients with aortic stenosis. BACKGROUND: Conventional invasive techniques to assess aortic stenosis are associated with procedural risks secondary to bilateral femoral access or the sheath size and reduced accuracy using femoral sheath pressure to replace ascending aortic pressure. METHODS: Cardiac output was measured using a pulmonary artery catheter. With a 4 French catheter through single femoral access ascending aortic pressure and, with a pressure wire, left ventricular pressure were recorded simultaneously in four patients with aortic stenosis. Likewise, both pressures were recorded using the pullback method. Pressure gradients were determined by both methods and aortic valve area calculated with the Gorlin equation prior to correlation. Of note, patients with significant arrhythmias such as atrial fibrillation or frequent premature atrial or ventricular contractions were excluded to maintain accuracy of the pullback method. RESULTS: All hemodynamic parameters were successfully obtained in all four patients. The correlation between pressure wire and pullback method was highly significant in this case series (n = 4, r = 0.983, p = 0.017). There were no complications. CONCLUSION: The results suggest that the aortic valve area can be safely and accurately evaluated with a pressure wire using a 4 French system. This novel method could be the preferred method for patients with vascular access limitations.

Iso-osmolar radio contrast iodixanol in patients with chronic kidney disease.

BACKGROUND: Although radio contrast volume has been associated with worsening post-procedural kidney function, this relationship has not been extensively studied using an iso-osmolar contrast agent in chronic kidney disease patients. METHODS: We retrospectively studied patients undergoing cardiac catheterization at the University of Minnesota from 2000 to 2004, using the iso-osmolar contrast agent, iodixanol. All patients were included who had calculated creatinine clearance (CCR) < 60 mL/min, not on dialysis, and serum creatinine measured on the same day and within 7 days after the procedure. Comparison of a subgroup with severe chronic kidney disease and diabetes mellitus was compared to a similar historical control group that used the low-osmolar contrast agent, iohexol. RESULTS: Serum creatinine and CCR were 2.9 +/- 1.5 mg/dL and 33.4 +/- 12.0 mL/min (mean +/- standard deviation), respectively, at baseline in 117 cases. Peak creatinine increased by 0.03 +/- 0.7 mg/dL after 84.3 +/- 67.3 mL of iodixanol was used. Contrast-induced nephropathy definition was fulfilled in 22 (18.8%) cases. A non-significant negative correlation was found between the volume of iodixanol and the change in creatinine (r2 = 0.0011, p = 0.7254). A subgroup with severe chronic kidney disease and diabetes mellitus with iodixanol had a significantly lower creatinine increase (n = 25, 0.09 +/- 0.5 mg/dL), compared to historical controls (n = 42, 0.7 +/- 0.8 mg/dL) with iohexol (p < 0.001). A non-significant positive correlation between volume of contrast and change in creatinine was found in this subgroup who received iodixanol (n = 25, r2 = 0.0756, p = 0.1835), but was significant in the historical controls who received iohexol (n = 42, r2 = 0.135, p = 0.017). CONCLUSIONS: The volume of iso-osmolar radio contrast does not affect the incidence of contrast-induced nephropathy in patients with chronic kidney disease. A randomized trial evaluating the incidence of contrast nephropathy would verify the safety of ad hoc versus staged angiographic procedures in this population.

Pseudoperforation during kissing balloon angioplasty.

We describe a case of apparent perforation during kissing balloon angioplasty of a bifurcation lesion. There was no evidence of perforation on follow-up angiography or via intravascular ultrasound. Possible etiologies include minimal perforation that immediately sealed postdeflation or forced contrast into the microvascular bed via a proximal side branch.

Cutting balloon angioplasty vs. conventional balloon angioplasty in patients receiving intracoronary brachytherapy for the treatment of in-stent restenosis.

The objective of this study was to evaluate the safety and efficacy of cutting balloon angioplasty (CBA) for the treatment of in-stent restenosis prior to intracoronary brachytherapy (ICB). Cutting balloon angioplasty may reduce the incidence of uncontrolled dissection requiring adjunctive stenting and may limit "melon seeding" and geographic miss in patients with in-stent restenosis who are subsequently treated with ICB. We performed a retrospective case-control analysis of 134 consecutive patients with in-stent restenosis who were treated with ICB preceded by either CBA or conventional balloon angioplasty. We identified 44 patients who underwent CBA and ICB, and 90 control patients who underwent conventional percutaneous transluminal coronary angioplasty (PTCA) and ICB for the treatment of in-stent restenosis. Adjunctive coronary stenting was performed in 13 patients (29.5%) in the CBA/ICB group and 41 patients (45.6%; P < 0.001) in the PTCA/ICB group. There was no difference in the injury length or active treatment (ICB) length. The procedural and angiographic success rates were similar in both groups. There were no statistically significant differences in the incidence of death, myocardial infarction, recurrent angina pectoris, subsequent target lumen revascularization, or the composite endpoint of all four clinical outcomes (P > 0.05). Despite sound theoretical reasons why CBA may be better than conventional balloon angioplasty for treatment of in-stent restenosis with ICB, and despite a reduction in the need for adjunctive coronary stenting, we were unable to identify differences in clinical outcome.

Incidence, correlates, management, and clinical outcome of coronary perforation: analysis of 16,298 procedures.

BACKGROUND: Coronary perforation is a serious but uncommon complication of percutaneous coronary intervention (PCI) and is associated with significant morbidity and mortality. METHODS: We performed an analysis of the Mayo Clinic PCI database. Clinical records, procedural reports, and angiographic studies were reviewed. Multiple logistic regression analysis was performed to identify clinical, procedural, anatomic, and angiographic correlates of coronary perforation. RESULTS: A total of 16,298 PCI procedures were performed between January 1990 and December 2001. We identified 95 coronary perforations (0.58%; 95% CI, 0.47-0.71). The incidence of coronary perforation varied with time. Correlates of coronary perforation included the use of an atheroablative device and female sex. Twelve patients (12.6%) sustained an acute myocardial infarction, and cardiac tamponade developed in 11 patients (11.6%). Management strategies included reversal of heparin, pericardiocentesis, placement of a covered stent, and surgical repair. Seven patients died (7.4%). CONCLUSIONS: Coronary perforation during PCI is rare, but is associated with significant morbidity and mortality. The variable frequency of perforation may be explained by temporal variations in the use of atheroablative devices.

Smooth muscle progenitor cells in human blood.

BACKGROUND: Recent animal data suggest that vascular smooth muscle cells within the neointima of the vessel wall may originate from bone marrow, providing indirect evidence for circulating smooth muscle progenitor cells (SPCs). Evidence for circulating SPCs in human subjects does not exist, and the mechanism whereby such putative SPCs may home to sites of plaque formation is presently not understood but is likely to involve expression of specific surface adhesion molecules, such as integrins. In this study, we aimed to culture smooth muscle outgrowth cells (SOCs) from SPCs in human peripheral blood and characterize surface integrin expression on these cells. METHODS AND RESULTS: Human mononuclear cells isolated from buffy coat were seeded on collagen type 1 matrix and outgrowth cells selected in endothelial growth medium (EGM-2) or EGM-2 and platelet-derived growth factor BB. Selection in platelet-derived growth factor BB-enriched medium caused rapid outgrowth and expansion of SOC to >40 population doublings in a 4-month period. These SOCs were positive for smooth muscle cell-specific alpha actin (alphaSMA), myosin heavy chain, and calponin on immunofluorescence and Western blotting and were also positive for CD34, Flt1, and Flk1 receptor but negative for Tie-2 receptor expression, suggesting a potential bone marrow angioblastic origin. In contrast, endothelial outgrowth cells (EOCs) grown in EGM-2 alone and the initial MNC population were negative for these smooth muscle-specific markers. Integrin alpha5beta1 expression by FACS and Western blotting was significantly increased in SOCs compared with EOCs, and this was confirmed by 8-fold greater adhesion of SOC to fibronectin (P<0.001), an effect that could be decreased using an alpha5beta1 antibody. Finally, SOC showed a significantly greater in vitro proliferative potential compared with EOCs of similar passage (P<0.001). CONCLUSIONS: This study demonstrates for the first time outgrowth of smooth muscle cells with a specific growth, adhesion, and integrin profile from putative SPC in human blood. These data have implications for our understanding of adult vascular smooth muscle cell differentiation, proliferation, and homing.

A tissue-engineered stent for cell-based vascular gene transfer.

Cell-based gene transfer using a stent platform would provide a significant advantage in terms of site-specific gene expression in the vasculature. The current study presents a novel stent design that allows stable in vivo transgene expression over a 4-week period in the vasculature. A mesh-stent coated with fibronectin provided an excellent platform for adherent porcine smooth muscle cells (SMC). Autologous porcine SMC were stably transduced with a plasmid encoding green fluorescence protein (GFP), seeded at high density in the mesh-stent, and deployed in the porcine coronary artery. Stable in vivo GFP expression within the mesh-stent (5.2 x 10(5) GFP-positive cells/cm(2) mesh) was demonstrated 1 month after implantation in the porcine coronary artery by fluorescence microscopy and flow cytometry. No significant change in GFP positive cell number within the stent occurred over a 1-month period in vivo when compared to preinsertion. Angiographic and histologic analysis revealed mild neointimal proliferation and no inflammatory infiltrate in the stented segment. This study has implications for treatment of cardiovascular and other diseases where long-term cell-based delivery of transgene is a desirable therapeutic option.