B. A. Reitz

The results of operative treatment in 83 patients with idiopathic hypertrophic subaortic stenosis (IHSS) are described. Most patients with the disease are asymptomatic, or derive satisfactory symptomatic improvement from nonoperative therapy: administration of propranolol, exerice limitation, control of arrhythmia, etc. Operation is required, however, in 10-15% of patients, those who remain severely symptomatic after nonoperative treatment or who become refractory to it. Operation relieves symptoms in IHSS by relieving obstruction to left ventricular outflow, and for a patient to be considered an operative candidate severe obstruction must be documented at left heart catheterization either under resting conditions or after provocative interventions. All 83 patients were severely incapacitated--58 in Class III and 24 in Class IV. Seventy had obstruction at rest (average gradient 96 mm Hg), and 13 had only provocable obstruction. At operation the hypertrophic interventricular septum was exposed via an aortotomy, and a vertical bar of muscle was resected between parallel myotomy incisions. There were six operative deaths (7%); no patient has died since 1970. Seven patients have died late after operation, five of them from causes unrelated to their heart disease or the operation. All surviving patients describe symptomatic improvement. Fifty-two patients with obstruction at rest preoperatively (average gradient 95 mm Hg) have been studied postoperatively: no resting gradient was evident in 47, while in the remaining five the gradient was less than 25 mm Hg. Recurrence of obstruction has never been observed at late catheterization (21 pts) or late echocardiographic examination (37 pts). Obstruction could not be provoked postoperatively in ten of the 11 patients who had large gradients only with the Valsalva maneuver or isoproterenol administration preoperatively. Obstructed and provocable obstructed patients had similar symptomatic improvement after operation. A variety of rhythm and conduction abnormalities were observed both pre and postoperatively, and these are described in detail. The results of operation in these 83 patients with IHSS demonstrate that gratifying symptomatic and hemodynamic improvement uniformly follows left ventriculomyotomy and myectomy. Relief of obstruction and amelioration of symptoms have proved to be long-lasting during postoperative observation periods extending to 14 years. Continued application of the operative procedure in properly selected patients appears to be indicated.

BACKGROUND: Acute rejection has emerged as an important risk factor for obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables. METHODS: Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and underwent transplantation more than 15 months before data analysis were included in this study. Several variables were entered into a Cox regression analysis to determine their association with the development of bronchiolitis obliterans syndrome. RESULTS: Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of pathologic grades of each separate acute rejection episode (p = 0.0004, likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bacterial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomegalovirus infection score, reflecting the frequency and severity of infection, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant increase in the likelihood ratio test value. Significant risk factors for moderate to severe stages of airflow limitation were at least one episode of acute rejection of grade > or = 2, younger recipient age, and any acute rejection episode 180 days or longer after transplantation. CONCLUSIONS: Increasing frequency and severity of acute rejection episodes are strongly associated with the development of bronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared to be significant by univariate analysis, but in a two-risk factor model, it did not augment the influence of acute rejection. Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and frequency of cytomegalovirus infections potentiate the effect of acute rejection. Late episodes of acute rejection and younger recipient age increase the risk for development of advanced disease.

In a prospective study of 1,009 adult patients undergoing elective cardiac surgery at The Johns Hopkins Hospital, we determined the association between a variety of preoperative and operative parameters and the risk of postoperative sternal- or mediastinal-wound infection. Of the parameters reflecting nutritional state, only one, reduced level of albumin in serum, was significantly associated with sternal- or mediastinal-wound infection by univariate analysis. The final multiple logistic regression analysis indicated that four variables were significant (P less than .05) independent predictors of sternal- or mediastinal-wound infection: obesity (relative odds = 3.8; 95% confidence limits = 1.9-7.5), diabetes mellitus (relative odds = 2.6; 95% confidence limits = 1.4-4.8), length of hospital stay before surgery greater than five days (relative odds = 2.0; 95% confidence limits = 1.2-3.5), and current cigarette smoking (relative odds = 1.8; 95% confidence limits = 1.1-3.1). Of these variables, perhaps only smoking will lend itself routinely to attempts at intervention.

Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.

Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis.