Abnormalities in the coronary circulation that occur as a consequence of cardiac hypertrophy.

Myocardial ischemia is frequently observed in patients with cardiac hypertrophy even when the conduit coronary arteries are normal. Recent studies indicate that impaired coronary reserve in hypertrophied hearts probably occurs because growth of the coronary bed does not keep pace with increases in cardiac mass. The imbalance between vascular proliferation and muscle growth is probably most severe when cardiac hypertrophy is produced by pressure overload. Experimental studies also suggest that abnormalities intrinsic to pressure-hypertrophied heart muscle (decreased capillary density; decreased coronary reserve; electrophysiologic abnormalities) adversely affect the response of the enlarged heart to sudden coronary occlusion. When animals with hypertension and left ventricular hypertrophy are subjected to sudden coronary occlusion, the incidence of sudden cardiac death is increased severalfold and infarct size is substantially augmented. These observations suggest that abnormalities in the coronary microcirculation that accompany cardiac hypertrophy play a significant role in the pathogenesis of the complications associated with cardiac hypertrophy.

Age-associated decline in cardiac allograft rejection.

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.

Efficacy of OKT3 retreatment for refractory cardiac allograft rejection.

Although OKT3 monoclonal antibody is a useful therapy for refractory cardiac allograft rejection, the use of OKT3 for prophylaxis may be limited by the potential of sensitization and subsequent loss of efficacy on retreatment. OKT3 was required for refractory rejection in 21 of 165 recipients transplanted between March 1985 and August 1988. Twelve of these patients had previously been exposed to OKT3, and the retreatment efficacy was evaluated. The study population averaged 42.1 +/- 15.3 years of age (mean +/- SEM) and had experienced 2 +/- 1 previous episodes of rejection. The prior episodes of rejection had been treated with pulse methylprednisolone and antithymocyte globulin, and in addition 3 patients (25%) also required a course of antilymphoblast globulin. Retreatment OKT3 for refractory rejection was required 120 +/- 94 days following transplantation. CD3+ lymphocytes were eliminated from the circulation within 24-48 hr in 11 of 12 patients, all of whom showed histologic improvement within the first week. Total resolution on the initial follow-up biopsy was noted in 9 (75%) during the course of therapy. Subsequent rejection episodes occurred in 9 (82%) of the survivors at 71 +/- 64 days. One-year survival was 83% in this vigorously rejecting patient population. Serious infections occurred within 3 months of therapy in 4 (36%). The side effects of OKT3 retreatment were similar to those seen with first exposure and did not require OKT3 discontinuation. Thus OKT3 may be administered with success in most patients who have previously been exposed to it.

A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3.

To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.

Demonstration of improved myocardial perfusion following aortic implantation of anomalous left coronary artery.

An adult with anomalous origin of the left coronary artery (originating from the pulmonary artery) had implantation of the anomalous vessel into the aorta. Exercise myocardial perfusion imaging with thallium-201, performed before and after the operation, disclosed a marked improvement in anterior-wall Tl-201 uptake. Postoperative isotope ventriculogram showed improved regional contraction in the revascularized anterolateral wall of the left ventricle. Thus, it has been demonstrated that implantation of an anomalous left coronary into the aorta improves regional myocardial perfusion and regional left-ventricular motion.

Coronary reserve in volume-induced right ventricular hypertrophy from atrial septal defect.

To assess coronary reserve in patients with right ventricular (RV) hypertrophy secondary to volume overload, the quantitative characteristics of coronary reactive hyperemia were examined in 20 patients with a large atrial septal defect (ASD). The control group consisted of 13 patients who had undergone elective cardiac surgery for abnormalities that did not involve the right ventricle or its blood supply. Coronary blood flow velocity was measured in RV branches of the right coronary artery at cardiac surgery. Echocardiographic measurements of RV diameter in ASD and in control patients (2.3 +/- 0.2 and 1.1 +/- 0.2 cm, respectively, p less than 0.05) documented the presence of substantial RV enlargement in patients with ASD. In patients with ASD and in control subjects, a 20-second coronary occlusion produced maximal coronary dilation. After release of a 20 second coronary occlusion, the peak-to-resting velocity ratio in ASD and in control patients was 3.1 +/- 0.2 and 5.5 +/- 0.1, respectively (p less than 0.05). The 50% decrease in the ratio of peak-to-resting coronary blood flow velocity, a measure of relative coronary reserve, in patients with ASD suggests that coronary reserve is compromised in volume-induced RV hypertrophy. These studies support the concept that in humans, volume-induced RV hypertrophy substantially decreases coronary reserve.

Correction of Taussig-Bing malformation by intraventricular conduit.

Repair of double-outlet right ventricle with subpulmonary ventricular septal defect (Taussig-Bing malformation) was accomplished with an intraventricular conduit. The ventricular septal defect was brought into continuity with the aorta via a tubular Dacron prosthesis, which was situated anterior to the subpulmonary conus and ran transversely from the ventricular septal defect to the subaortic conus. The transverse right ventriculotomy was not closed directly, but was sutured to the external surface of the conduit.

Bypass of superior vena cava: Six years' experience with spiral vein graft for obstruction of superior vena cava due to benign and malignant disease.

Ten patients had operations for obstruction of the superior vena cava (SVC) with SVC syndrome. Four patients had fibrosing mediastinitis and six and had bronchogenic carcinoma. A composite spiral vein graft was placed between the left jugular--subclavian vein and the right atrium to bypass the completely occluded SVC. The graft was constructed from the patient's own saphenous vein, which was split longitudinally and wrapped around a stent in spiral fashion. The edges of the vein were sutured together to form a large autogenous conduit. All patients were immediately relieved of SVC obstructive symptoms and signs. All grafts were patient at 7 days to 18 months, as determined by conventional or radionuclide venography or contrast-enhanced computerized axial tomography. The fact that SVC syndrome has not returned in any patient implies long-term patency. All patients with benign disease continue asymptomatic 3 months to 6 years after operation and have returned to gainful employment. All patients with SVC obstruction resulting from cancer died 1 to 21 months (mean 10.7 months) postoperatively. Spiral vein bypass graft provides effective treatment for SVC obstruction with immediate and long-term relief of SVC syndrome.

Experimental bypass of the left ventricle.

Bypass of the left ventricle was accomplished in dogs and the entire circulation was supported temporarily by only the right ventricle. The atrial septum was excised, and the atrium was repartitioned so that the pulmonary veins were in continuity with the right ventricle and the venae cavae were connected through the atrium. Anastomosis of the superior vena cava to the right pulmonary artery brought systemic venous return directly to the lungs. The main pulmonary artery was ligated proximal to the bifurcation, preserving distal confluence of right and left pulmonary arteries. A tubular prosthesis between the proximal pulmonary artery and the aorta connected the right ventricle to the systemic circuit. This procedure, or some modification of the principle, may have clinical feasibility in the treatment of patients with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome. Experience with an operation to establish functionally normal circulation.

A new operation to establish functionally normal circulation was performed in five neonates with hypoplastic left heart syndrome. With a limited period of cardiopulmonary bypass, deep hypothermia, and circulatory arrest, the patent ductus arteriosus was ligated. The atrial septum was excised and the atrium was repartitioned with a pericardial baffle so that pulmonary veins were in continuity with the tricuspid valve and right ventricle. The pulmonary artery was divided above the sinuses of Valsalva, and the proximal end was connected to the aortic arch with a tubular Dacron prosthesis. The distal end of the pulmonary artery was brought in continuity with the right atrium by way of a second Dacron conduit. The right ventricle thereby became the systemic ventricle and blood passed through the lungs vis a tergo. Circulation was supported temporarily, but all of the patients died from inadequate right ventricular performance or compromised coronary blood flow. This experience is presented to stimulate thought and some hope for babies with a uniformly fatal cardiac anomaly.

A turnover operation for pectus excavatum at the time of correction of intracardiac defects.

Two patients are presented who had open intracardiac procedures with simultaneous repair of pectus excavatum by sternal eversion or turnover. This method offered excellent exposure, relieved cardiac compression, maintained chest wall stability, and improved the appearance of the chest wall.

Correction of anomalous origin of the left coronary artery.

Successful surgical treatment for anomalous origin of the left coronary artery from the pulmonary artery was performed in one patient by left coronary artery-subclavian anastomosis and in two patients by direct implantation of the left coronary artery into the aorta. The excellent early and late results obtained with these methods and the suboptimal results reported with saphenous vein grafting for this lesion make these other alternatives more attractive. Direct implantation of the left coronary artery into the aorta utilizing cardiopulmonary bypass and hypothermic (4 degrees C.) potassium-induced (20 mEq. per liter) cardioplegia is now our preferred approach for most patients with this lesion.

Aortic atresia: morphologic characteristics affecting survival and operative palliation.

A quantitative anatomic study of 54 cardiac specimens with aortic atresia is related to surgical treatment of patients with aortic atresia and hypoplastic left heart syndrome. Coarctation of the aorta was present in 80% of patients with aortic atresia and should influence the extent of aortic arch reconstruction when present. Other associated cardiac defects were uncommon but, when present, may be contraindications to operative palliation because of added complexity of the operation. Anatomic abnormalities of the tricuspid or pulmonary valve were present in 7% of cases and could be important in the outcome of palliative procedures. Natural survival was related to thickness of the right ventricular wall so that selection of those infants with thicker and better functioning right ventricles may improve short-term and long-term operative results in aortic atresia.

Transient cerebral ischemic attacks associated with worn porcine heterograft prosthesis. Case report.

Details are reviewed of a case of transient cerebral ischemic attacks which probably resulted from thromboembolism from a Hancock porcine heterograft prosthesis. Cause of the embolism probably was thrombus formation on the worn cloth covering of the supporting valve stent. Technical and antomic factors which assure precise seating of the prosthesis in the mitral anulus without contacting the ventricular wall appear to be important in preventing this complication.

Septation of the univentricular heart. Transatrial approach.

The technique of septation of the univentricular heart via a transatrial approach is described in detail. Clinical details of four patients having Type A-III univentricular heart document the feasibility of working through the right-sided atrioventricular valve to place a cloth prosthesis into the ventricle to divide it into approximately equal chambers. Improved hemodynamics were observed in the postoperative period, which probably were related to retaining the integrity of the ventricular wall. This approach seems best suited to the ventricular chamber estimated to be large by echocardiography without severe pulmonary outflow tract obstruction. Techniques for enlargement of the pulmonary outflow tract are also described.

Congenital aortic stenosis with hypoplasia of the left sinus of Valsalva. Anatomic reconstruction of the aortic root.

Evaluation of the aortic root in 13 patients with congenital aortic stenosis aged 2.5 to 24 years (mean 8.3 years) has revealed morphologic characteristics of asymmetry of the aortic root caused by a small (hypoplastic) left sinus of Valsalva associated with a supravalvular ridge above the left coronary ostium and dysplasia of the aortic valve. The asymmetry resulted in folding and buckling of the left aortic cusp. The aortic valve was classified as bicuspid in 11 of the 13 patients. Preoperative aortography was characteristic and revealed the diagnosis in all patients. The average left ventricle-aorta systolic pressure gradient was 81 mm Hg. Operative repair consisted of an oblique aortotomy extended in a spiral fashion to the right and posteriorly into the left sinus of Valsalva. Seven patients had further mobilization of the posterior commissure with a second incision to the right of the commissure into the noncoronary sinus. Slightly fused valve commissures were opened in 12 patients. Aortic root reconstruction was accomplished with a spiral Dacron patch and posterior commissural repositioning. Follow-up catheterization at 9 to 35 months (mean 24 months) in five patients demonstrated an average outflow tract systolic gradient of 28 mm Hg and a more symmetrical appearance of the aortic root.

Bypass of superior vena cava. Fifteen years' experience with spiral vein graft for obstruction of superior vena cava caused by benign disease.

Nine patients had operations for obstruction of the superior vena cava with superior vena caval syndrome caused by benign disease. Three patients had fibrosing mediastinitis, four had fibrosing mediastinitis with caseous necrosis, one had thrombosis of the superior vena cava around a pacemaker electrode, and one had spontaneous thrombosis of the superior vena cava. Patients ranged in age from 25 to 68 years. All bypass operations were performed with a composite spiral vein graft constructed from the patient's own saphenous vein, split longitudinally and wrapped around a stent in spiral fashion. The edges of the vein were sutured together to form a large conduit ranging in diameter from 9.5 to 15.0 mm. Six grafts were from the left innominate vein and three grafts were from the internal jugular vein. The grafts were placed into the right atrial appendage in all except one case, in which the graft was to the distal superior vena cava. Follow-up extends from 1 to 15 years. One patient required reoperation at 4 days for thrombosis at the innominate vein-graft anastomosis. Resection of the anastomosis and reconstruction of the graft rendered the patient symptom free. Two grafts closed during the first year after operation. One patient had advancing fibrosing mediastinitis, and a second bypass graft from the external jugular veins remain patent. Another patient had recurrence of spontaneous venous thrombosis. Thus seven of nine grafts remain patent for up to nearly 15 years and all but one patient is free of superior vena caval syndrome. These data show that bypass of the obstructed superior vena cava with a spiral vein graft relieves superior vena caval syndrome and demonstrate long-term patency of the graft.

Supravalvular aortic stenosis. Repair by extended aortoplasty.

Enlargement of the aorta with a diamond-shaped patch of the noncoronary sinus of Valsalva may not be sufficient in severe cases of supravalvular aortic stenosis. This traditional reconstruction is asymmetric, and, if the fibrous supravalvular ring is thick and rigid, the aorta may not open wide with patch angioplasty, so that aortic obstruction may remain. Also, because aortic valve function may not be perfect after asymmetric reconstruction, there may be aortic valve incompetence or obstruction of coronary ostia by the valve cusps. A new reconstructive operation was designed and used in eight patients. All survived and are asymptomatic. The aortoplasty was extended so that the supravalvular ring was incised at two points in the noncoronary and in the right coronary sinuses of Valsalva. The area of stenosis was opened wide, and the cusps of the aortic valve were lengthened, which provided better approximation and function. A tubular Dacron prosthesis, tailored to reconstruct the aorta, provided a wide aortic cross-sectional area. This technique of extended aortoplasty for symmetric reconstruction of the aorta should provide more predictable relief of aortic obstruction and improved function of the aortic valve.

Vasomotor dynamics associated with cardiac operations. I. Venous tone and the effects of vasodilators.

Vasomotor dynamics were studied in 52 patients undergoing direct coronary revascularization or mitral valve replacement utilizing cardiopulmonary bypass. Emphasis was placed on the study of venous tone. Operation resulted in a general vasoconstrictive response with increased arterial resistance and reduced venous capacitance. These changes were magnified in patients who underwent mitral valve replacement for mitral valve stenosis related or partially related to reduced cardiac performance before and after operation. Nine patients became hypertensive following coronary artery bypass and were treated with nitroprusside; eight patients were given nitroglycerin to reduce venous tone and prevent hypertension. A comparison of these two vasodilators, with their somewhat different actions on the vascular bed, reveals that afterload reduction and increase of cardiac output were equivalent with both. However, nitroglycerin had the effect of increasing venous capacitance, while nitroprusside had little effect on the venous circulation. In addition, nitroglycerin was especially effective in reducing venous tone and left ventricular preload following mitral valve replacement. Relative merits of pharmacologic reduction of venous tone as a part of overall relief of increased vascular resistance following cardiac operation should be considered when attempting to obtain an optimal hemodynamic state.

Thrombosis of the Björk-Shiley prosthesis: illustrative cases and review of the literature.

Thrombosis of the Björk-Shiley prosthetic cardiac valve may occur in any valve position and regardless of anticoagulant status. Four illustrative cases are presented to demonstrate management problems. Review of cases reported in the literature suggests the minimal incidence of thrombosis of Björk-Shiley prostheses is about 2% in the aortic position and about 4% in the mitral position. Prevention of this complication appears to require continuous systemic anticoagulation with warfarin; even temporary interruption or alteration of anticoagulant regimen may be detrimental. Although changes in anticoagulation may rarely precipitate sudden thrombosis, in most cases a period averaging 10 months is required for pannus of organized thrombus to build up enough to cause acute thrombosis and malfunction of the valve. Operation to remove thrombus or replace the prosthesis is usually required for left-sided cardiac prostheses, but thrombosed valves in the tricuspid position may be successfully treated with fibrinolytic medical therapy.