Shreekanth V. Karwande

Coronary artery bypass grafting with cardiopulmonary bypass versus off-pump cardiopulmonary bypass grafting: does eliminating the pump reduce morbidity and cost?

BACKGROUND Cardiopulmonary bypass (CPB) may contribute to the complications and cost of coronary artery bypass grafting (CABG). Off-pump CABG (OPCAB) allows coronary revascularization without CPB. We hypothesized that OPCAB provides satisfactory graft patency while reducing complications and cost compared with CABG with CPB. METHODS We prospectively followed 80 patients undergoing CABG: 40 patients undergoing OPCAB and 40 patients undergoing CABG with CPB. OPCAB patients underwent angiography within 48 hours of surgery to determine early graft patency. Incidence of complications, length of stay, and costs were recorded for each patient. The influence of the number of vessels bypassed was analyzed. RESULTS OPCAB patients (n = 40) underwent grafting of 2.7 +/- 0.7 vessels per patient compared with 3.6 +/- 0.8 vessels per patient in the CABG with CPB group (n = 40) (p < 0.0001). Angiography demonstrated 105 of 108 (97%) of grafts were patent in the OPCAB group. Incidence of complications, length of stay, and costs did not differ between the OPCAB and CABG with CPB groups. Number of vessels grafted showed a positive correlation to total costs in both groups. CONCLUSIONS While OPCAB provided satisfactory early graft patency, there was no significant difference between OPCAB and CABG with CPB with regard to cost, length of stay, or incidence of complications. In this study, eliminating CPB did not reduce morbidity or cost after CABG.

Early experience with sirolimus in lung transplant recipients with chronic allograft rejection

BACKGROUND Chronic lung allograft rejection, commonly manifest as obliterative bronchiolitis (OB/BOS), hinders long-term survival after lung transplantation (LT). OB/BOS is traditionally treated with augmented immunosuppression and results in short-term stabilization in pulmonary function for most patients. However, peribronchiolar fibroproliferation and airway obstruction usually recur despite initial improvements seen with increases in immunosuppression. In this observational, uncontrolled study, the effect of sirolimus, a novel immunosuppressant with anti-proliferative activity, was assessed in LT patients with OB/BOS. METHODS Between June 1999 to November 2000, LT recipients with newly diagnosed or progressive OB/BOS received sirolimus in combination with a calcineurin inhibitor (CI) and prednisone. Pulmonary function, laboratory data and adverse effects were monitored for the first 24 weeks of therapy. RESULTS Sirolimus was utilized in 12 LT recipients with OB/BOS. After drug initiation, 58% of patients required a reduction in CI dose to maintain appropriate CI trough concentrations. Despite CI dose reduction, serum creatinine rose in 75% of patients. Unexpected adverse effects included anemia of chronic disease (100%), edema (50%) and malignancy (17%). For the group, the rate of change in FEV(1) and FEF(25%-75%) was unchanged with sirolimus, but individual responses varied. CONCLUSIONS For the group, the decline in pulmonary function was not affected by the addition of sirolimus. However, among individuals with rapidly declining pulmonary mechanics, sirolimus resulted in stabilization or improvement in pulmonary function. Significant adverse effects resulted from combination sirolimus plus CI therapy. Until optimal dosing strategies and a more complete adverse effect profile are established, combination therapy should be utilized cautiously in these patients.

Avoidance of cellular blood product transfusions in LVAD recipients does not prevent HLA allosensitization

BACKGROUND Transfusion of cellular blood products during left ventricular assist device (LVAD) implantation has been associated with HLA allosensitization, resulting in the need for a negative prospective cross-match and prolonged transplant waiting times. In order to prevent this risk, we developed a protocol to avoid transfusion of cellular blood products. METHODS The protocol included preoperative patient stabilization, perioperative recombinant erythropoietin and blood conservation strategies, and postoperative monitoring of mixed venous oxygen saturation (SVO2) to assure adequate peripheral oxygen delivery. Panel reactive antibody (PRA) was measured in all patients pre and post LVAD placement to assess HLA sensitization. RESULTS Seven consecutive patients underwent LVAD implantation without transfusion of blood or platelets, one of whom expired perioperatively. Mean hematocrit was 35.2% preoperatively, and 21.8% postoperatively, reaching a nadir of 20.2%. Postoperative SVO2 was >60% in all patients. In the six survivors, mean hematocrit reach 24.3%, 27.3%, and 33.0% by postoperative day seven, fourteen, and thirty, respectively. PRA in three patients was 0% preoperatively and remained 0% until transplantation after 33, 34, and 50 days of support. In two patients, preoperative PRA was 7% and 17%, dropped to 3% and 0% after thirty days, then progressively rose to 96% and 100% after 60 and 90 days, respectively. In one other patient, preoperative PRA was 0%, remained at 0% after thirty days, then rose to 96% by 60 days. CONCLUSIONS Avoiding transfusion of cellular blood products in LVAD recipients is safe and well tolerated, but does not universally protect from HLA allosensitization. Other factors may also produce sensitization, such as immunogenic components of the LVAD, soluble antigen in fresh frozen plasma, or latent sensitization which is not initially evident in critically ill and possibly anergic patients.

Long-term results of cardiac transplantation in patients older than sixty years

Abstract Advanced age has traditionally been a contraindication to cardiac transplantation. We have, however, offered cardiac transplantation to patients older than 60 years with end-stage heart failure if they were otherwise acceptable candidates. From 1985 to 1994, 527 patients underwent cardiac transplantation. Among these patients, 101 were older than 60 years at transplantation. The mean follow-up of this group is 6 years. Patients older than 60 years had significantly fewer rejection episodes per patient than those who were younger than 60 years at transplantation (1.9 ± 1.3 vs 2.6 ± 1.8, p = 0.009). No difference in the number of infectious complications per patient was detected between the two groups. Both short-term and long-term survival after transplantation were significantly lower for patients who were older than 60 years at transplantation than for younger patients ( p p p

Cardiac retransplantation: A viable option?

To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (< 6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infection was similar in first and second transplant recipients. Second transplant recipients had a higher level of sensitization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repetition in the second donor of mismatched HLA antigens present in the first donor did not adversely affect survival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant.

Effect of a resident self-study and presentation program on performance on the thoracic surgery in-training examination.

BACKGROUND In this study we examine whether conversion from a didactic lecture format to a resident self-study and presentation program can improve performance on the Thoracic Surgery In-Training Examination (TSITE). METHODS During the first 5 years, educational conferences were didactic lectures delivered by the attending thoracic surgery staff (group 1, n = 9 residents). During the second 5 years, residents prepared and delivered reviews from major textbook sources (group 2, n = 9 residents). Scores on the American Board of Surgery In-Training Examination (ABSITE) as a chief resident in general surgery were analyzed using one-way analysis of variance to assess fund of knowledge and test-taking skills prior to thoracic surgery training for the two groups. Scores on the TSITE during the first and second years of thoracic surgery training were recorded for each resident and analyzed using a paired t test. The data are expressed as the mean +/- standard deviation. RESULTS Eighteen thoracic surgery residents over a 10-year period were involved in the study. ABSITE scores as a chief resident in general surgery did not differ between the two groups. Residents in group 1 improved their percentile rank from the first to the second year by a mean of 11%+/-12%, whereas those in group 2 improved their scores by a mean of 31%+/-21% (P < 0.05). CONCLUSIONS When compared with a didactic lecture format, a resident self study and presentation program improves performance on the Thoracic Surgery In-Training Examination. This improvement in performance typically manifests during the second year of thoracic surgery training.

Prevention of bone loss and fracture after lung transplantation: A pilot study

Background. Osteoporotic fracture is a significant source of morbidity after lung transplantation. Therapies to prevent posttransplant fracture are largely untested among lung transplant recipients. Methods. In this prospective uncontrolled study, lung transplant referrals were assessed for bone health with metabolic, radiographic, and bone mineral density measurements. Transplant recipients were treated with an antiresorptive regimen that included a bisphosphonate starting before or after transplantation. One year after transplantation, the fracture rate and bone density of patients in each group were reassessed and compared to historical controls. Between January 1996 and August 1999, 45/50 (90%) lung transplant referrals underwent bone health assessment. Transplant candidates received calcium, vitamin D, and hormone replacement therapy as indicated for hypogonadism. After July 1998, bisphosphonate therapy was added for candidates with osteopenia or osteoporosis (T score <1). After transplantation, all patients received 90 mg of pamidronate i.v. every 12 weeks, regardless of pretransplant bone density. Radiologic evaluation was performed for clinical suspicion of fracture. Bone density was remeasured 1 year after transplantation. Results. Most transplant referrals suffered from osteopenia or osteoporosis, and 29% of transplant referrals had prevalent vertebral compression fractures. Hypogonadism was untreated in 50% of men and 20% of women, and 15% of patients had hypovitaminosis D. Of the 21 patients assessed 1 year after transplantation, new fractures occurred in 4% of these patients. Lateral lumbar spine and hip bone density remained stable or improved in 65% and 86% of patients, respectively. Most of those who lost bone density had started bisphosphonate therapy after transplantation. Conclusions. Antiresorptive therapy with a bisphosphonate decreases the fracture rate and preserves bone mass 1 year after lung transplantation. In end-stage lung disease patients with osteopenia or osteoporosis, bisphosphonate therapy should be initiated before transplant surgery is contemplated.

Interleukin-18 Production Following Murine Cardiac Transplantation: Correlation with Histologic Rejection and the Induction of IFN-γ

Interleukin-18 (IL-18) and IL-12 have been shown to play an important role in the induction of interferon-gamma (IFN-gamma). IFN-gamma induces the proliferation of T cells and natural killer (NK) cells and augments the Th1 immune cascade. The role of IL-18 and IL-12 in the induction of IFN-gamma following allogeneic heart transplantation has not been described. We sought to characterize the IL-12 and IL-18 response to murine allogeneic heart transplantation, particularly with respect to IFN-gamma production and histologic transplant rejection. Forty-eight heterotopic heart transplants were performed in two groups of mice: syngeneic C3H/HeN to C3H/HeN mice and allogeneic BALB/C to C3H/HeN mice. Transplants were followed out to 2, 6, 10, and 14 days. Six transplants were performed in each group. Serum and splenic samples were used to evaluate the cytokine response by ELISA. Explanted heart tissue was processed for evidence of histologic rejection, and RT-PCR was performed to evaluate the IL-12, IL-18, and IFN-gamma signal qualitatively. Analysis of variance (ANOVA), Fishers projected least significant difference (PLSD) was used for statistical analysis. Transplant rejection occurred in the allogeneic group histologically by day 6 and clinically by day 10. Serum IFN-gamma levels rose significantly by day 6 in the allogeneic group and then continued to rise in the splenocyte cultures. Serum IL-18 also rose significantly in the allogeneic group at day 6 compared with syngeneic group. RT-PCR revealed that the allogeneic tissue contained an increased signal for IL-12, IL-18, and IFN-gamma beginning at day 6 and peaking at day 10 after transplant. Beginning 6 days after transplantation, IL-12 and IL-18 appear to play a significant role in the induction of IFN-gamma in allogeneic heart transplants.

Tricuspid valve dysfunction in the transplanted heart

Mild degrees of tricuspid regurgitation are common in the orthotopically transplanted heart, probably secondary to the geometry of the right atrial anastomosis. At the University of Utah, 5 (0.95%) of 526 patients with transplantations performed from March 1985 to December 1993 have presented with severe tricuspid regurgitation requiring operative intervention. Echocardiographic findings confirmed at the time of operation consisted of ruptured chordae to the tricuspid valve. Standard tricuspid valve repair and replacement techniques were used with good results. We postulate the chordal disruption found in these patients is secondary to injuries incurred at the time of endomyocardial biopsy.

Management of refractory empyema with early decortication.

One hundred consecutive patients underwent surgical procedures for empyema. Sixty-six patient acquired empyema from pneumonia, 16 from trauma, 11 from abdominal sepsis, and 7 from other causes. If tube thoracostomy failed, computerized tomography and ultrasonography were used to demonstrate a loculated empyema. After a median observation period of 11 days, 91 patients underwent thoracotomy and decortication and 9 patients underwent either rib resection, an Eloesser flap procedure, or both. The mortality rate was 6 percent 30 days postoperatively, the in-hospital mortality rate was 9 percent, and the overall morbidity rate was 17 percent. An excellent result was achieved in 85 percent of the patients with a recurrence rate of 4 percent. Gram-positive aerobes were the most common organisms cultured, but several opportunistic infections were encountered. We have concluded that early thoracotomy and decortication of empyema results in eradication of difficult pleural infections with hospital stays of an acceptable length and reasonably low morbidity and mortality rates.