Faculty Bibliography

Right ventricular dysfunction after myocardial infarction is associated with high morbidity and mortality. If optimal medical management is ineffective, early consideration should be given to right-sided temporary mechanical assistance.

Recombinant human B-type natriuretic peptide (BNP) is a promising new agent in the management of heart failure. The pharmacologic properties of BNP make it desirable to use in a subset of patients after cardiac surgical operations. Among these therapeutic potentials is the effect on markedly reducing pulmonary vascular resistance and central venous pressure with mild systemic vasodilatation. In addition, BNP directly effects the kidneys to promote natriuresis. We believe this agent to be useful in the treatment of the postcardiac surgery patients with left ventricular dysfunction and mild to moderate renal insufficiency. This report summarizes our experience in 2 patients.

OBJECTIVES: This study was undertaken to identify management strategies that maximize survival of patients with stage III non-small cell lung cancer and metachronous brain metastases and to determine whether any apparent improved survival was due to treatment or simply to patient selection. METHODS: Treatment evaluations of both primary non-small cell lung cancer and brain metastases were performed in 91 patients. Optimal treatment was identified by multivariable analysis. Propensity scoring and multivariable analysis were used to separate treatment benefit from patient selection. RESULTS: Risk-unadjusted median, 12-, and 24-month survivals were 5.2 months, 22%, and 10%, respectively. Younger age (P =.006), good performance status (P =.003), stage IIIA (P =.001), lung resection (P =.02), no other systemic metastases at time of diagnosis of brain metastases (P =.02), and either metastasectomy (P <.001) or stereotactic radiosurgery (P <.001) predicted best survival. However, metastasectomy or stereotactic radiosurgery was more common after lung resection (P =.02) and in patients with good performance status (P =.006), no other systemic metastases at time of diagnosis of brain metastases (P =.01), and fewer brain metastases (P <.001), suggesting that the patients with the best risk profile were selected for aggressive therapy of both lung primary and brain metastases. Despite this selection, analysis of propensity-matched patients demonstrated the benefit of lung resection and metastasectomy or stereotactic radiosurgery (P <.001). CONCLUSIONS: Younger patients with resected stage IIIA non-small cell lung cancer who have isolated metachronous brain metastases and good performance status do best when treated with metastasectomy or stereotactic radiosurgery. This survival benefit is a brain treatment effect, not the result of selecting the best patients for aggressive therapy.

BACKGROUND: Acute ischemic stroke after cardiac operations is a devastating complication with limited therapeutic options. As clinical trials of thrombolysis for acute ischemic stroke exclude patients with recent major surgery, the safety of intraarterial thrombolysis in this setting is unknown. METHODS: Thirteen patients with acute ischemic stroke within 12 days of cardiac operation underwent intraarterial thrombolysis within 6 hours of stroke symptom onset. The National Institutes of Health Stroke Scale was used to assess neurologic recovery. RESULTS: The mean age was 69 years (standard deviation +/-5 years) and 62% were men. Cardiac procedures included valve operations in 6 patients, coronary artery bypass grafting in 4, valve and coronary artery bypass grafting in 2, and left ventricular assist device in 1 patient. Atrial fibrillation occurred in 5 patients (38%). The mean time from operation to stroke was 4.3 days (standard deviation +/- 3 days). Thrombolysis was initiated within 3.6 hours (standard deviation +/-1.6 hours) of stroke symptom onset. Recanalization was complete in 1 patient, partial in 5, and 7 patients had low flow. Neurologic improvement occurred in 5 patients (38%). One patient needed a chest tube for hemothorax, 2 others were transfused for low hemoglobin. No operative intervention for bleeding was necessary. CONCLUSIONS: In select patients with acute ischemic stroke after recent cardiac operation, intraarterial thrombolysis appears to be reasonably safe and may lead to neurologic recovery.

OBJECTIVES: We sought to determine 5-year survival after extracorporeal membrane oxygenation for cardiac failure and its predictors, to assess survival and its predictors after bridging to transplantation or weaning from extracorporeal membrane oxygenation, and to identify factors influencing the likelihood of these outcomes. METHODS: Two hundred two adults (mean age, 55 +/- 14 years) were supported with extracorporeal membrane oxygenation between 1992 and July 1999 after cardiac failure. Follow-up extended to 7.5 years (mean, 3.8 +/- 2 years). Multivariable hazard function analysis identified predictors of survival, and logistic regression identified the determinants of bridging or weaning. RESULTS: Survival at 3 days, 30 days, and 5 years was 76%, 38%, and 24%, respectively. Patients surviving 30 days had a 63% 5-year survival. Risk factors (P <.1) included older age, reoperation, and thoracic aorta repair. Forty-eight patients were bridged to transplantation, and 71 were weaned with intent for survival. Survival was similar after either outcome (44% vs 40% 5-year survival, respectively). Failure to bridge or wean included (P <.03) renal and hepatic failure on extracorporeal membrane oxygenator support, occurrence of a neurologic event, and absence of infection. The dominant modes of death were cardiac failure and multisystem organ failure. CONCLUSIONS: Extracorporeal membrane oxygenation is versatile and salvages some patients who would otherwise die. Improvement in intermediate-term outcome will require a multidisciplinary approach to protect organ function and limit organ injury before and during this support.

BACKGROUND: Preformed anti-human leukocyte antigen (HLA) antibodies delay heart transplantation in patients with left ventricular assist devices (LVAD) because of difficulty in finding crossmatch-negative donors. These antibodies may also be associated with adverse outcome after transplantation. METHODS: In a retrospective analysis of 40 patients with LVAD at Columbia-Presbyterian Medical Center between 1990 to 1996, age, sex, diagnosis, race, duration of support, transfusions, and infections were studied by univariate and multivariate analysis as predictors for development of either anti-HLA class I (anti-I) or anti-HLA class II (anti-II) immunoglobulin G (IgG) or M (IgM) antibodies. RESULTS: Eighteen (45%) patients had development of anti-I and 20 (50%) had development of anti-II antibodies over the study period. Median time for LVAD support was 142 days (range 35 to 439). Only total number of perioperative platelet transfusions predicted the development of anti-I IgG antibodies (p = .04). No other associations were found for development of anti-I IgM or anti-II antibodies of either IgG or IgM specificity. Patients who had development of anti-I IgG received a mean of 13.9 (SE +/- 2.6) units of platelets compared with a mean of 7.7 (SE +/- 2.3) units in those who did not (p = .01). By Kaplan-Meier analysis, at the median duration of follow-up, 8% of patients receiving < 6 units were predicted to have development of anti-I antibodies compared with 63% receiving > 6 units (p = .002). In the last 7 patients, leukocyte filters were used to decrease the antigenic load during platelet and red blood cell transfusions. Only 1 of 7 (14%) patients had development of anti-HLA antibodies compared with 31 of 33 (94%) in whom filters were not used (p < .005). CONCLUSIONS: These results indicate that platelet transfusion during LVAD implantation is a risk factor associated with development of HLA class I IgG antibodies. Use of leukocyte filters during platelet transfusion may decrease the risk of development of anti-HLA antibodies.

BACKGROUND: Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied. METHODS AND RESULTS: The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti-MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P=0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection. CONCLUSIONS: These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.