Marco A. Zenati

Abciximab and Excessive Bleeding in Patients Undergoing Emergency Cardiac Operations

BACKGROUND Abciximab (ReoPro; Eli Lilly and Co, Indianapolis, IN) is a monoclonal antibody that binds to the platelet glycoprotein IIb/IIIa receptor and produces powerful inhibition of platelet function. Clinical trials of abciximab in patients undergoing coronary angioplasty have demonstrated a reduction in thrombotic complications and have encouraged the widespread use of this agent. We have observed a substantial incidence of excessive bleeding among patients who receive abciximab and subsequently require emergency cardiac operations. METHODS The records of 11 consecutive patients who required emergency cardiac operations after administration of abciximab and failed angioplasty or stent placement were reviewed. RESULTS The interval from the cessation of abciximab administration to operation was critical in determining the degree of coagulopathy after cardiopulmonary bypass. The median values for postoperative chest drainage (1,300 versus 400 mL; p < 0.01), packed red blood cells transfused (6 versus 0 U; p = 0.02), platelets transfused (20 versus 0 packs; p = 0.02), and maximum activated clotting time (800 versus 528 seconds; p = 0.01) all were significantly greater in the early group (cardiac operation < 12 hours after abciximab administration; n = 6) compared with the late (cardiac operation >12 hours after abciximab administration; n = 5) group. CONCLUSIONS This report suggests that the antiplatelet agent abciximab is associated with substantial bleeding when it is administered within 12 hours of operation.

Outcomes of the RESTOR-MV Trial (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve)

OBJECTIVES we sought to determine whether patients with functional mitral regurgitation (FMR) would benefit from ventricular reshaping by the Coapsys device (Myocor, Inc., Maple Grove, Minnesota). BACKGROUND FMR occurs when ventricular remodeling impairs valve function. Coapsys is a ventricular shape change device placed without cardiopulmonary bypass to reduce FMR. It compresses the mitral annulus and reshapes the ventricle. We hypothesized that Coapsys for FMR would improve clinical outcomes compared with standard therapies. METHODS RESTOR-MV (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) was a randomized, prospective, multicenter study of patients with FMR and coronary disease with core laboratory analysis. After enrollment, patients were stratified to the standard indicated surgery: either coronary artery bypass graft alone or coronary artery bypass graft with mitral valve repair. In each stratum, randomization was to either control (indicated surgery) or treatment (coronary artery bypass graft with Coapsys ventricular reshaping). RESULTS the study was terminated when the sponsor failed to secure ongoing funding; 165 patients were randomized. Control and Coapsys both produced decreases in left ventricular (LV) end-diastolic dimension and MR at 2 years (p < 0.001); Coapsys provided a greater decrease in LV end-diastolic dimension (p = 0.021). Control had lower MR grades during follow-up (p = 0.01). Coapsys showed a survival advantage compared with control at 2 years (87% vs. 77%) (hazard ratio: 0.421; 95% confidence interval: 0.200 to 0.886; stratified log-rank test; p = 0.038). Complication-free survival (including death, stroke, myocardial infarction, and valve reoperation) was significantly greater with Coapsys at 2 years (85% vs. 71%) (hazard ratio: 0.372; 95% confidence interval: 0.185 to 0.749; adjusted log-rank test; p = 0.019). CONCLUSIONS analysis of RESTOR-MV indicates that patients with FMR requiring revascularization treated with ventricular reshaping rather than standard surgery had improved survival and a significant decrease in major adverse outcomes. This trial validates the concept of the ventricular reshaping strategy in this subset of patients with heart failure. (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve [RESTOR-MV]; NCT00120276).

Impact of endoscopic versus open saphenous vein harvest technique on late coronary artery bypass grafting patient outcomes in the ROOBY (Randomized On/Off Bypass) Trial

OBJECTIVE In the Randomized On/Off Bypass (ROOBY) Trial, the efficacy of on-pump versus off-pump coronary artery bypass grafting was evaluated. This ROOBY Trial planned subanalysis compared the effects on postbypass patient clinical outcomes and graft patency of endoscopic vein harvesting and open vein harvesting. METHODS From April 2003 to April 2007, the technique used for saphenous vein graft harvesting was recorded in 1471 cases. Of these, 894 patients (341 endoscopic harvest and 553 open harvest) also underwent coronary angiography 1 year after coronary artery bypass grafting. Univariate and multivariable analyses were used to compare patient outcomes in the endoscopic and open groups. RESULTS Preoperative patient characteristics were statistically similar between the endoscopic and open groups. Endoscopic vein harvest was used in 38% of the cases. There were no significant differences in both short-term and 1-year composite outcomes between the endoscopic and open groups. For patients with 1-year catheterization follow-up (n=894), the saphenous vein graft patency rate for the endoscopic group was lower than that in the open harvest group (74.5% vs 85.2%, P<.0001), and the repeat revascularization rate was significantly higher (6.7% vs 3.4%, P<.05). Multivariable regression documented no interaction effect between endoscopic approach and off-pump treatment. CONCLUSIONS In the ROOBY Trial, endoscopic vein harvest was associated with lower 1-year saphenous vein graft patency and higher 1-year revascularization rates, independent of the use of off-pump or on-pump cardiac surgical approach.

Feasibility of Combined Percutaneous Transluminal Angioplasty and Minimally Invasive Direct Coronary Artery Bypass in Patients With Multivessel Coronary Artery Disease

BACKGROUND Angioplasty has become an accepted treatment of patients with coronary artery disease and is now commonly used to treat patients with multivessel disease. The major disadvantage of angioplasty has been restenosis requiring repeat interventions with resultant loss of initial cost savings. Compared with the right and the circumflex coronary arteries, the left anterior descending artery (LAD) has been more adversely affected by restenosis. Recently, minimally invasive direct coronary artery bypass (MIDCAB) to the LAD through a small left anterior thoracotomy using the left internal mammary artery has been performed in some centers with excellent early results and with reduced costs compared with standard bypass surgery. METHODS AND RESULTS We retrospectively reviewed the first 31 consecutive patients treated in our institution with integrated coronary revascularization (ICR): MIDCAB to the LAD combined with PTCA of the other diseased vessels in patients with multivessel disease. Postoperative angiography in 84% of patients revealed a patent anastomosis and normal flow in the graft and bypassed vessel. Thirty-eight (97%) of 39 vessels were successfully treated percutaneously. At a mean follow-up of 7 months, all patients are currently asymptomatic. There have been 2 adverse clinical events, both related to angioplasty and not to MIDCAB. The average length of stay at the hospital after MIDCAB was 2.79+/-1.05 days. CONCLUSIONS These preliminary results with ICR are encouraging and suggest that a randomized, prospective clinical trial comparing ICR with standard coronary artery bypass surgery for the revascularization of symptomatic patients with multivessel disease involving the LAD is warranted.

Preliminary evaluation of a mobile robotic device for navigation and intervention on the beating heart.

This article describes the development and preliminary testing of a mobile robotic device to facilitate minimally invasive beating-heart intrapericardial intervention. The HeartLander robot will be introduced beneath the pericardium via subxiphoid incision, adhere to the epicardium, navigate to any location, and administer therapy under the control of the physician. As compared to current robotic cardiac surgical techniques, this novel paradigm obviates immobilization of the heart and eliminates access limitations. Furthermore, it does not require lung deflation and differential ventilation and thus could enable outpatient cardiac surgery. The current HeartLander prototypes use suction to maintain prehension of the epicardium and wire actuation to perform locomotion. A fiber optic videoscope displays visual feedback to the physician, who controls the device through a joystick interface. The initial prototype demonstrated successful prehension, turning, and locomotion on open-chest, beating-heart porcine models where the pericardium was removed (N = 3). A smaller second-generation prototype with an injection system demonstrated locomotion and myocardial injection of dye, both performed with the pericardium intact (N = 3). These trials illustrate the feasibility of using a miniature mobile robot to navigate upon the beating heart and perform intrapericardial therapy.

A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix

OBJECTIVE We sought to promote myocardial repair using urinary bladder matrix incorporated with a fusion protein that combined hepatocyte growth factor and fibronectin collagen-binding domain in a porcine model. Collagen-binding domain acted as an intermediary to promote hepatocyte growth factor binding and enhance hepatocyte growth factor stability within urinary bladder matrix. METHODS Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor was implanted into the porcine right ventricular wall (F group) to repair a surgically created defect. Untreated urinary bladder matrix patches (U group) and Dacron patches (D group) served as controls (N = 5/group). Electromechanical mapping was performed 60 days after surgery. Linear local shortening was used to assess regional contractility, and electrical activity was recorded. RESULTS Linear local shortening was significantly improved in the F group compared with controls (F: 0.51% +/- 1.57% [P < .05], U: -1.06% +/- 1.84%, D: -2.72% +/- 2.59%), whereas it was inferior to the normal myocardium (13.7% +/- 4.3%; P < .05). Mean electrical activity was 1.49 +/- 0.82 mV in the F group, which was statistically greater than in the control groups (U: 0.93 +/- 0.71 mV; D: 0.30 +/- 0.22 mV; P < .05) and less than the normal myocardium (8.24 +/- 2.49 mV; P < .05). Histologic examination showed predominant alpha-smooth muscle actin positive cells with the F group showing the thickest layer and the D group showing the thinnest layer, with an endocardial endothelial monolayer. Scattered isolated islands of alpha-actinin positive cells were observed only in the F group, but not in the controls, suggesting the presence of cardiomyocytes. CONCLUSION The collagen-binding domain/hepatocyte growth factor/urinary bladder matrix patch demonstrated increased contractility and electrical activity compared with urinary bladder matrix alone or Dacron and facilitated a homogeneous repopulation of host cells. Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor may contribute to constructive myocardial remodeling.

Long-Term Outcome of Lung and Heart-Lung Transplantation for Idiopathic Pulmonary Arterial Hypertension

BACKGROUND The survival after lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension has been reportedly the lowest among the major diagnostic categories of lung transplant recipients. METHODS Retrospective analysis was performed for lung and heart-lung transplant recipients for idiopathic pulmonary arterial hypertension from 1982 to 2006. The patients were divided into 2 groups, based on the era; group 1: 1982 to 1993, and group 2: 1994 to 2006. Since 1994, we have introduced our current protocols including prostaglandin E1 and nitroglycerin for donor lung preservation, and lung protection with cold and terminal warm blood pneumoplegia as well as immunosuppression with alemtuzumab induction. These modifications were introduced in different years over a wide span of time (1994 to 2003). RESULTS Group 1 had 59 patients (35 +/- 1 years old, ranging 15 to 53, 20 male and 39 female) with 7 single lung, 11 double lung, and 41 heart-lung, whereas group 2 had 30 (43 +/- 2 years old, ranging 17 to 65, 9 male and 21 female) with 2 single, 20 double, and 8 heart-lung transplantations. The recipient age was significantly (p = 0.004) higher in group 2, and group 2 had significantly older (35 +/- 3 vs 26 +/- 1, p = 0.002) and more female donors (73% vs 41%, p = 0.007) compared with group 1. The actuarial survival was significantly (p = 0.004) better in group 2 with 86% at 1 year, 75% at 5 years, and 66% at 10 years compared with group 1 with 58% at 1 year, 39% at 5 years, and 27% at 10 years. CONCLUSIONS With our current pulmonary protection and immunosuppression, the long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension is excellent.

Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation

Rejection remains a major obstacle to long-term success of pulmonary transplantation. Direct delivery of cyclosporine to lung allografts may produce better control of rejection by generating high intragraft concentrations of drug with decreased systemic delivery and toxicity. The efficacy of inhaled cyclosporine in preventing allograft rejection was compared with systemic delivery by intramuscular injections in a rat model of lung transplantation (Brown-Norway to Lewis). Group 1 animals were given no immunosuppression. Group 2 received a single i.m. injection of 25 mg/kg CsA on the day of operation while group 3 received daily doses on postoperative days 0–3. Groups 4–7 received aerosolized CsA daily for seven days. The aerosol generator produced an airborne concentration of CsA of 180 mg/ m3 with a mean particle size of 0.7 μ and estimated pulmonary depositions of CsA of 0.98–3.6 mg/kg/day. Animals were killed on POD 7, and the transplanted lungs graded histologically in a blinded fashion. All control animals showed destructive grade 4 changes by POD 7. Animals receiving high-dose aerosolized CsA (groups 6 and 7) showed minimal changes with a mean rejection grade of 1.3. A single i.m. dose of CsA (group 2) failed to prevent rejection; the mean grade was 2.2. Animals given four i.m. doses of CsA had a mean grade of 1.8. Aerosolized CsA provided significantly better control of rejection than did systemic CsA (groups 6 and 7 vs. groups 2 and 3; P<0.0002 and <0.0054, respectively). Local delivery of CsA by aerosol inhalation is effective in limiting acute rejection of the rat lung allograft.

Resource utilization for minimally invasive direct and standard coronary artery bypass grafting

BACKGROUND Minimally invasive direct coronary artery bypass grafting (MIDCABG) has been recently reintroduced into the cardiac surgical armamentarium for selected patients with suitable coronary anatomy. We hypothesized that MIDCABG had the potential for similar immediate results with decreased perioperative morbidity and decreased resource utilization compared with standard coronary artery bypass grafting (CABG). METHODS From January 1996 to August 1996, 17 MIDCABG patients were compared with 33 patients with left ventricular ejection fraction greater than 0.50 who underwent CABG with standard technique. No significant differences were observed between the two groups for preoperative variables that are known to affect cost and resource utilization. Length of stay in the hospital was 2.5 +/- 0.8 days for MIDCABG and 5.9 +/- 2 days for CABG (p < 0.0001); length of stay in the intensive care unit was 12.3 +/- 3.3 hours for MIDCABG compared to 32.3 +/- 12.6 hours for the CABG group (p < 0.0001). RESULTS Forty-one percent of MIDCABG patients were extubated in the operating room and 59% were discharged home on the first or second postoperative day versus none in the CABG group (p < 0.0001). Significantly less morbidity was observed in the MIDCABG group compared with CABG. Total ratio of cost-to-charge was

Lung reduction as bridge to lung transplantation in pulmonary emphysema

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