Aamir S. Shah

Improved Survival With Radial Artery Versus Vein Conduits in Coronary Bypass Surgery With Left Internal Thoracic Artery to Left Anterior Descending Artery Grafting

Background—Given its proven survival benefit, left internal thoracic artery to left anterior descending (LITA-LAD) grafting has become a fundamental part of CABG. This grafting also led to increased use of other arterial conduits, of which the radial artery is most popular. Whether radial grafting improves survival beyond that achieved by LITA-LAD alone is not known. Methods and Results—We compared 6-year outcomes in propensity-matched CABG-LITA-LAD patients (925 each) divided into those with ≥1 radial grafts and those with vein-only grafting. Matched patients had essentially identical demographics, comorbidities, coronary disease, and operative data. Perioperative outcomes, including death (radial, 11 [1.2%]; vein, 10 [1.1%]), were similar for the 2 groups. Cumulative 0- to 6-year survival was better for radial patients (risk ratio, 0.675), particularly after 3 years (P <0.03). Six-year survival in vein (86.8%) and radial (92.1%) patients indicated 67% greater overall vein mortality. Incidence rates of radial and vein repeated catheterization (190 of 925 [20.5%] versus 199 of 925 [21.5%]) and revascularization (8.8% versus 8.5%) were similar. Angiography data in restudied symptomatic patients showed a trend for greater radial patency. Vein failure (66 of 161 [41%]) was significantly worse than radial failure (46 of 157 [29.3%]) in patients receiving both types of grafts (P =0.039). Conclusions—Using radial as a second arterial conduit in CABG-LITA-LAD as opposed to vein grafting improves long-term outcomes as a result of decreased late deaths, especially after the third postoperative year.

Obesity and risk of new-onset atrial fibrillation after cardiac surgery.

Background— New-onset postoperative atrial fibrillation (AF) is a common complication of cardiac surgery that has substantial effects on outcomes. In the general (nonsurgical) adult population, AF has been linked to increasing obesity, which correlates with left atrial enlargement. It is not known whether postoperative AF is similarly linked to obesity. Methods and Results— This was a retrospective analysis of the incidence of AF in terms of body mass index (BMI). A total of 8051 consecutive cardiac surgery patients (1994 to 2004; mean age 64 [SD 11] years; 5372 men [67%]) who were free of any history of preoperative AF or flutter were included in the analysis. This series included 3164 obese patients (39%; median age 62 years) and 4887 nonobese patients (61%; median age 66 years), who were further divided on the basis of BMI (kg/m2) into 6 groups: BMI <22 kg/m2, 22≤BMI≤25 kg/m2 (normal), 2540 kg/m2 (obese III). Unadjusted AF incidence was similar in obese and nonobese patients (n=742 [23.5%] versus n=1068 [21.9%], respectively; P=0.099). Covariate-adjusted ORs for AF were systematically greater for larger patients than for patients in the normal group (adjusted OR [95% CI]=1.18 [1.00 to 1.40], 1.36 [1.14 to 1.63], 1.69 [1.35 to 2.11], and 2.39 [1.81 to 3.17] for overweight, obese I, obese II, and obese III, respectively). Other AF predictors included age (adjusted OR=1.52 [95% CI 1.46 to 1.58] per 10 years), mitral valve surgery (adjusted OR=2.42 [95% CI 1.92 to 3.06]), aortic valve surgery (adjusted OR=1.79 [95% CI 1.45 to 2.22]), chronic obstructive pulmonary disease (adjusted OR=1.28 [95% CI 1.12 to 1.46]), male gender (adjusted OR=1.24 [95% CI 1.10 to 1.40]), preoperative &bgr;-blocker use (adjusted OR=1.17 [95% CI 1.05 to 1.32]), vascular disease (adjusted OR=1.18 [95% CI 1.05 to 1.32]), white race (adjusted OR=1.33 [95% CI 1.07 to 1.66]), history of arrhythmia other than AF/flutter (adjusted OR=0.80 [95% CI 0.68 to 0.96]), ejection fraction <40% (adjusted OR=1.16 [95% CI 1.03 to 1.31]), left main disease (adjusted OR=1.15 [95% CI 1.00 to 1.32]), and off-pump surgery (adjusted OR=0.61 [95% CI 0.44 to 0.83]). The obesity-AF association was confirmed in 4 1-to-1 propensity-matched obese versus nonobese comparisons and in 2 separate derivation/validation subcohort analyses. Conclusions— Obesity is an important determinant of new-onset AF after cardiac surgery. Future postoperative AF risk models should incorporate BMI or obesity levels. Studies examining the efficacy of AF-minimizing prophylactic interventions in high-BMI patients, particularly in the elderly, may be warranted.

Absence of hyperacute rejection in pig-to-primate orthotopic pulmonary xenografts

The shortage of organ donors for transplantation is more pronounced for the lung than for any other solid organ. To address this problem, we evaluated the feasibility of pulmonary xenotransplantation. Preliminary investigations demonstrated that orthotopically placed pig lungs in cynomologous monkey recipients could be engrafted up to 9 hr after reperfusion without evidence of hyperacute rejection. In this study, the rejection reaction of pig lungs transplanted orthotopically into baboons (n=6) was further investigated by ELISA and immunohistochemistry. Four baboon recipients were killed at 24 hr and 2 recipients were killed at 72 hr after transplantation. Pulmonary arterial flow measurements demonstrated flow to the grafts, and systemic arterial and xenograft pulmonary venous blood gas analysis suggested function of the donor lungs during the course of engraftment. Serum levels of baboon anti-pig endothelial cell xenoanti-body were normal and decreased minimally over time. Immunohistochemical staining of biopsies demonstrated trace IgG and IgM along graft endothelium 2 hr after reperfusion. At 8 hr, biopsy samples showed no immunoglobulin bound to endothelial cells. Staining for complement was negative. Fibrin and platelets were detected along xenograft endothelium. Despite these findings, the lung xenografts appeared injured and clinically rejected. During the first 8 hr after reperfusion, the grafts were hyperemic and subsequently became focally ecchymotic. Chest x-rays showed progressive pulmonary congestion. These findings suggest that the lung may be relatively resistant to antibody-mediated hyperacute rejection and efforts are being directed toward identifying the mechanism of the observed xenograft lung injury.

Miniature axial flow pump for ventricular assistance in children and small adults.

We investigated the efficacy of the Jarvik 2000 intraventricular assist device (Jarvik Research, Inc., New York, N.Y.) in an ovine model. The device is an axial flow pump measuring 1.8 cm in diameter by 5 cm long, has a displacement volume of 12 ml, and can deliver flow from 2 to 7 L/min. Seven devices were implanted through a left thoracotomy into the left ventricle with an outflow graft to the descending aorta. Animals were treated with warfarin sodium and aspirin to maintain prothrombin times approximately 1.5 times control. Animals were followed up for 3 to 123 days. Two animals died of operative complications at days 3 and 5. One device failed at 58 days because of thrombus formation at the inflow side of the impeller. The remaining four animals were killed at days 19, 42, 42, and 123, respectively, because of broken electric power cables. Hematocrit values rose significantly higher than preoperative levels (22.8% +/- 3.8% to 30.5% +/- 3.4%); premortem elevations of values higher than baseline values of plasma free hemoglobin (10.4 +/- 7.8 mg/dl to 17.1 +/- 7.4 mg/dl) and lactate dehydrogenase (391.5 +/- 113.7 units/L to 771.2 +/- 370.8 units/L) were statistically insignificant. Serum creatinine and bilirubin levels were normal. No end-organ dysfunction arising from long-term support was evident clinically or at postmortem examination, nor was there any evidence of embolism or damage to intracardiac structures. We found the Jarvik 2000 intraventricular assist device to be easily implantable, safe, nonhemolytic, and able to provide physiologic flow with power requirements under 10 watts.

Discriminating Between Preservation and Reperfusion Injury in Human Cardiac Allografts Using Heart Weight and Left Ventricular Mass

BACKGROUND Myocardial edema caused by injury during preservation or reperfusion can affect cardiac function after heart transplantation. This study was designed to distinguish these forms of injury in human allografts. METHODS AND RESULTS In 15 donor hearts preserved in University of Wisconsin solution, heart weight (HW) was obtained immediately after explantation and after transport before implantation. Left ventricular mass (LVM) was calculated separately in 18 patients with the use of epicardial two-dimensional echocardiograms obtained both before explantation from the donor and after transplantation and weaning from cardiopulmonary bypass. While changes in LVM could be due to preservation or reperfusion injury, changes in HW can only be due to edema occurring during transport. HW averaged 339 +/- 24 g (mean +/- SE) before and 340 +/- 24 g after transport (P = NS); however, LVM increased 14 g, from 164 +/- 8 to 178 +/- 11 g (P < .05, paired t test). LVM increased in 10 of 18 patients (56%). No correlation was demonstrated between duration of ischemia (mean, 172 +/- 13 minutes) and changes in HW or LVM. Two patients died as a result of primary graft failure. In the first, HW increased 54 g, 2 SD above the mean. In the second, LVM increased 66 g, 2 SD above the mean, but HW changed minimally. CONCLUSIONS While current preservation methods result in minimal change in HW during transport, reperfusion injury frequently increases LVM. LVM determination by two-dimensional echocardiography may prove valuable in detecting allograft injury.

The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates☆☆☆★★★♢

The humoral and cell-mediated immune responses to subsequent allografts were determined in primate recipients after concordant xenotransplantation as a bridge to allotransplantation. Heterotopic heart transplants (n = 4) were performed from cynomolgus monkeys into ABH type-matched olive baboons followed 2 weeks later by allotransplantation from ABH type-matched baboon donors. Allografts were explanted at 8 weeks. All recipients underwent splenectomy at the time of xenotransplantation and received immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Concordant xenotransplantation in these primates did not induce humoral or cell-mediated immune responses that jeopardized subsequent allografts. The degree of xenospecific immune reactivity, as determined by specific cytotoxicity of recipient T-cell lines derived from the xenograft and extent of histologic xenograft rejection, did not predict the severity of subsequent allograft rejection. In two of the four recipients, xenotransplantation induced an alloreactive humoral response against antigens expressed by the B cells of more than 50% of members from a panel of 12 unrelated baboons. In all recipients, priming with xenogeneic splenocytes in vitro induced an accelerated proliferative T-cell response to allogeneic lymphocytes from 16% of this panel. This study affirms the role of concordant xenografts as appropriate biologic bridges to human allotransplantation. However, our results suggest that xenoreactive baboon memory CD4 T cells may recognize major histocompatibility complex class II--like structures shared between the xenogeneic and allogeneic targets. The potential allorecognition induced by a xenograft may affect the process of subsequent allograft donor selection.

Nitric oxide treatment for pulmonary hypertension after neonatal cardiac operation

This report describes a newborn with transposition of the great arteries who underwent a Blalock-Taussig shunt with transient improvement in oxygenation, but required emergent insertion of a central shunt later the same day due to progressive hypoxia and cardiac arrest. Two hours after central shunt insertion, sudden episodes of hypoxia and hypotension developed that were resistant to all pharmacologic therapy. Inhaled nitric oxide (25 ppm) was then administered with dramatic improvement in oxygenation and hemodynamics within minutes. The patients condition stabilized after these measures, and nitric oxide therapy was discontinued after 2 days.

Successful heart transplantation with acquired pulmonary artery atresia

Orthotopic cardiac transplantation was performed successfully in a patient with acquired atresia of the left pulmonary artery 19 years after repair of tetralogy of Fallot. Only the right lung could be incorporated into the cardiopulmonary circulation at transplantation, resulting in transient right ventricular dysfunction, which resolved with vasodilator therapy. Perfusion of a single pulmonary vascular bed does not preclude successful heart transplantation, provided there is a low pulmonary vascular resistance and pulmonary artery architecture free of stenoses.

Newborn baboon immunity: Lessons in cross-species transplantation

BACKGROUND The critical shortage of organ donors has greatly limited the number of heart transplantations performed each year. This is particularly true of the newborn patient, for whom xenotransplantation may provide an alternative therapeutic option to allotransplantation. The role of newborn immunity in xenotransplantation is not clearly understood. METHODS We examined the humoral immune responses of 9 nonimmunosuppressed newborn baboons (900 to 1200 g) aged 28 to 44 days undergoing heterotopic pig heart transplantation. Grafts were explanted between 1 and 87 hours after transplantation. RESULTS Despite the degree of species, disparity, hyperacute rejection was not observed in any of the nine transplanted grafts. Whole-cell enzyme-linked immunosorbent assay demonstrated newborn baboon serum to contain very low binding levels of anti-pig natural immunoglobulin M xenoantibody when compared with adult baboon serum. Newborn serum, like adult serum, contained anti-pig natural immunoglobulin G xenoantibody. However, newborn baboon serum was not cytotoxic to pig endothelial cells, suggesting that immunoglobulin M and not immunoglobulin G is the primary xenoreactive antibody. CONCLUSIONS The low binding levels of anti-pig immunoglobulin M xenoantibody, the absence of cytotoxicity to pig endothelial cells, and the avoidance of hyperacute rejection after heart transplantation suggest that newborn primates may have an immunologic advantage as the recipients of hearts transplanted across species barriers. Whether this advantage can be extended to the human condition is currently being explored in our laboratory.

Immunobiology of Pig-to-Baboon Lung Xenotransplantation

Pulmonary allotransplantation is now recognized as the best therapeutic option for patients with end-stage pulmonary disease. One-year survival for persons receiving pulmonary allografts for emphysematous lung disease currently exceeds 80% and rivals survival for heart allotransplantation [1]. However, despite these impressive figures, expansive growth within the field has been limited by a scarcity of donor organs adequate for transplantation. The donor organ shortage for lungs is more pronounced than for any other solid organ, with only 5%–10% of donors of heart, liver, kidneys, and pancreas of acceptable quality having lungs of similar suitability [2,3].