The signal-averaged electrocardiogram in cardiac transplantation. A noninvasive marker of acute allograft rejection.

Cardiac allograft rejection represents a major cause of morbidity and mortality in transplanted patients. Noninvasive markers of rejection have been sought, though transvenous endomyocardial biopsy remains the "gold standard" for the diagnosis of rejection. Sixty-one signal-averaged electrocardiograms (five in patients with rejection and 56 in patients without rejection) were obtained on 41 patients and prospectively analyzed in frequency domain via fast Fourier transform (FFT). Patients with acute allograft rejection demonstrate a significant increase in the high-frequency components of the QRS complex upon FFT analysis (QRS area ratio 203 +/- 57 vs. 66 +/- 10, P = 0.0007) compared with patients without rejection. Thus, frequency domain analysis may be a useful noninvasive marker of acute cardiac allograft rejection.

Myoblast transplantation in the porcine model: a potential technique for myocardial repair.

The use of transgenic cells transplanted in syngeneic rodents has shown modest success, but allogeneic and xenogeneic transplants have not been uniformly successful. To assess the feasibility of xenogeneic and allogeneic myoblast transplantation, we subjected seven adult swine to transplantation of murine atrial tumor cells (xenogeneic), neonatal porcine myocytes (allogeneic), and human fetal cardiomyocytes into the left ventricular wall. After general anesthesia, isolated cells were injected along the anterior and posterior walls of the porcine left ventricle. All the animals were immuno-suppressed and observed for 1 month after injection, at which time they were killed and analyzed. This report will present results primarily concerned with the success of human cell transfers. In all injected sites examined, the transplanted cells thrived within the host myocardium with no significant rejection. Transplant cells formed close associations with host myocytes that resembled nascent intercalated disks on electron microscopy. These cells also contained myofibrils and other cell architecture resembling the transplanted cell lines. Additionally, these cells appeared to produce an angiogenic influence resulting in the proliferation of the surrounding microvasculature. We believe that these findings indicate successful xenogeneic and allogeneic myoblast cell transplantation in a large animal model. These experiments set the stage for future studies to assess the ability of these cells to form a syncytium, contract, and potentially repair failed myocardium.

Atrioventricular valve competence after takedown to improve exposure during ventricular septal defect repair.

Although the atrioventricular valve and its attachments can sometimes obscure the superior margin of a ventricular septal defect, concern for valvular competence has made surgeons hesitant to take down the atrioventricular valve. Over a 10-year period, the right atrioventricular valve was taken down to improve exposure for ventricular septal defect repair in 40 patients at our institution, and follow-up echocardiographic studies to determine the degree of valvular regurgitation were available in 32. On the basis of the area of the color flow jet, valvular regurgitation was graded as none in 22 and trivial in 10. Heart block did not develop in any patient, and there were no deaths. Takedown and resuspension of the atrioventricular valve is a safe and effective technique that improves exposure for ventricular septal defect repair and does not adversely affect valve competence.

Long-term outcome of cardiac allograft vasculopathy treated by transmyocardial laser revascularization: early rewards, late losses.

Transmyocardial laser revascularization (TLR) was initially touted as a promising therapeutic alternative for tackling the growing problem of cardiac allograft vasculopathy in late heart transplant survivors. We first described 4- and 8-week observations of application of this surgical technique, in which we professed enthusiasm for TLR in providing symptomatic relief and in reducing ischemic burden. In this report, we present the long-term (24-month) impact of TLR on clinical outcome, channel patency, and recrudescence of ischemic burden. In the long term, surgical TLR provides neither consistent symptomatic improvement nor an ameliorative effect on the natural history of cardiac allograft vasculopathy.

Cardiomyocyte transplantation in a porcine myocardial infarction model.

Transplantation of cardiomyocytes into the heart is a potential treatment for replacing damaged cardiac muscle. To investigate the feasibility and efficiency of this technique, either a cardiac-derived cell line (HL-1 cells), or normal fetal or neonatal pig cardiomyocytes were grafted into a porcine model of myocardial infarction. The myocardial infarction was created by the placement of an embolization coil in the distal portion of the left anterior descending artery in Yorkshire pigs (n = 9). Four to 5 wk after creation of an infarct, the three preparations of cardiomyocytes were grafted, at 1 x 10(6) cells/20 microL into normal and into the middle of the infarcted myocardium. The hearts were harvested and processed for histologic examinations 4 to 5 wk after the cell grafts. Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal pig cardiomyocytes formed stable grafts within the normal myocardium without any detrimental effect including arrhythmia. In addition, a marked increase in angiogenesis was observed both within the grafts and adjacent host myocardium. Electron microscopy studies demonstrated that fetal pig cardiomyocytes and the host myocardial cells were coupled with adherens-type junctions and gap junctions. Histologic examination of graft sites from infarct tissue failed to show the presence of grafted HL-1 cells, fetal, or neonatal pig cardiomyocytes. Cardiomyocyte transplantation may provide the potential means for cell-mediated gene therapy for introduction of therapeutic molecules into the heart.

Right heart failure: best treated by avoidance.

Right heart failure continues to affect our clinical success with left ventricular assist device support. The inability to consistently predict the probability of the onset of right heart dysfunction contributes to this problem. We have developed an aggressive approach to the management of these patients in an attempt to decrease the incidence of this condition, which continues to carry a very high operative mortality.

Technique of right heart protection and deairing during heartmate vented electric LVAD implantation.

Continued experience with the TCI Heartmate Ventricular Assist System has led to improvements in our ability to avoid and manage right heart dysfunction during weaning from cardiopulmonary bypass. The advent of the electric device has intensified the need for these techniques because of its elevated minimal heart rate (50 beats/min) at start-up and the demands this places on the native right heart. We have developed and here describe a technique we have used successfully in our last 8 patients to assist in deairing and filling of the ventricular assist device, to partially support the right heart during the initial wean from cardiopulmonary bypass, and to avoid occasional overdistention of the right heart during early high left ventricular assist device flow.

Ventricular assist device programs: design and function.

Ventricular assist device programs can be structured in a variety of models and can make use of personnel derived from a broad spectrum of clinical and hospital-based practice. When aggressively and proactively negotiated with payers, these programs can be cost-effective and thoroughly self-sustaining.

Ventriculocoronary artery bypass results using a mesh-tipped device in a porcine model.

BACKGROUND: In this report we describe the in vivo evaluation of a device and ventriculocoronary artery bypass procedure that creates a permanent transmyocardial channel between the left ventricle and a coronary artery. METHODS: The transmyocardial device, an L-shaped titanium tube with a meshed distal tip and an exterior polyester cuff, was implanted from the base of the left ventricle to the proximal left anterior descending coronary artery in 11 healthy juvenile domestic pigs using a beating-heart approach. Flow rates were measured at implant. Patency was assessed at explant for surviving animals at 2 (n = 3) and 4 weeks (n = 4). RESULTS: Flow through the transmyocardial device after implantation was 74% of base line. Forward flow occurred during systole. Luminal patency was 100% at 2 weeks and 75% at 4 weeks. Histologic analysis showed little to no intimal proliferation at the coronary interface. CONCLUSIONS: This short-duration study shows promise for perfusing ischemic myocardium with systolic flow. The transmyocardial titanium conduit and treated coronary artery patency was good at 2 and 4 weeks and warrants further studies.

Cardiac transplantation: clinical aspects of recipient selection.

The improved outcome following cardiac transplantation has produced changes in the traditional criteria for potential candidates. We have analyzed these changes and the clinical aspects involved in the selection process, which are of critical importance to assure an excellent result of cardiac transplantation in patients with advanced heart failure.

Tracheoplasty for congenital long-segment intrathoracic tracheal stenosis.

Congenital long-segment intrathoracic tracheal stenosis (CTS) is a rare life-threatening obstruction in infancy and childhood. From July 1983 to March 1988 six infants aged 14 days to 14 months with CTS were identified. Symptoms ranged from recurrent stridor and wheezing to severe respiratory compromise and hypercarbia. Routine chest x-rays were not diagnostic. Definitive diagnosis was made by bronchoscopy, which showed complete tracheal rings in all patients with severely compromised tracheobronchial lumens. In three patients, pericardium was successfully used for anterior tracheoplasty with one early death due to fulminant sepsis in an infant with undiagnosed sickle cell disease. The other two died late, at 3 and 9 months from problems unrelated to the repair. In three patients a rib graft was used for repair; in one, tracheoplasty was required after earlier repair of tetralogy of Fallot. All are late survivors with no postoperative symptoms. After recognition of CTS, prompt surgery is warranted to avoid the late complications of tracheostomy for long-term ventilatory support. Rigid repair with rib cartilage is preferable to use of pericardium. Proper rib harvesting with intact perichondrium, intraoperative bronchoscopy, oxygenation by cardiopulmonary bypass, and meticulous graft alignment are necessary for successful postoperative outcome.

High-risk surgery as an alternative to transplantation.

Between April 1992 and April 1994, 185 patients were waiting for a cardiac transplant at our institution. Transplantation was performed in 118 of these patients. Twenty-six patients (14%) died while awaiting a donor heart: 13 of these were in the intensive care unit on multiple inotropic medications, mechanical support, or both; another 13 were either in the hospital on a single inotropic medication or at home with or without inotropic support. The remaining 41 patients were still awaiting transplantation at the end of the study period. During the same interval, 20 comparably ill patients who were referred to our institution for transplantation were considered for high-risk conventional surgical procedures. These patients underwent clinical evaluation to determine whether they had viable muscle that was salvageable and electrophysiologic status that was alterable. On this basis, these 20 patients underwent a variety of combined high-risk procedures. Two patients died; the operative mortality was 5% and the cumulative mortality was 10%. We conclude that these initial results support our original impression that mortality rates are higher in patients waiting for cardiac donation than in patients undergoing high-risk surgical procedures. Therefore, we will continue to investigate high-risk conventional surgery as an alternative to cardiac transplantation.

Surgical management of ventricular tachyarrhythmias.

Advances in the surgical management of ventricular tachyarrhythmias have been dramatic in recent years. Seriously ill patients, with or without ventricular aneurysms, who have medically refractory ventricular tachyarrhythmias may be candidates for intraoperative electrophysiologic mapping with surgical excision and/or cryoblation of the foci of their arrhythmias. In properly selected patients current techniques may offer success rates in excess of 90%. We report two cases of patients who have undergone such a procedure with excellent results. Indications for and results of surgical management are discussed.

Cardiac assist devices: bridging and beyond.

Due to the high incidence of death while awaiting cardiac transplantation today, most major transplant centers have adopted the use of left ventricular assist devices in order to stave off the complications of end-stage heart failure and allow patients to maintain a good physiologic state going into heart transplantation. These devices are safe and may one day prove to be a substitute for the short supply of donor organs.

Lung transplantation in Louisiana: report of the first twenty lung transplants performed in the state.

Lung transplantation is a successful alternative treatment for a variety of end-stage lung diseases. The first 20 lung transplants performed in Louisiana between November 1990 and July 1994 are reported from Ochsner Foundation Hospital. Transplant procedures included 1 heart-lung, 11 bilateral sequential lung, and 8 single-lung transplants in 8 males and 11 females (1 retransplantation). The average age was 38 years (range 7-60), and the median waiting time was 34.5 days (range 1-329). Indications for transplant included emphysema, pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. Overall 1-year and 3-year survival were 65.0% and 58.5%, respectively. Infection was the major cause of morbidity and mortality. Rejection episodes were observed but treated successfully in all 20 patients. Lung transplantation has proved to be a successful treatment for a variety of severely limiting and terminal pulmonary conditions for patients in our state.

Minimally invasive coronary artery bypass surgery.

In the hope of decreasing patient trauma and morbidity, cardiothoracic surgeons at the Ochsner Clinic are currently investigating techniques of performing coronary bypass surgery without the use of the cardiopulmonary bypass machine, which can cause complications following surgery in patients with certain coexisting conditions (such as renovascular, cerebrovascular, or pulmonary disease), particularly elderly patients. The initial 15 at-risk patients who underwent off-pump coronary artery bypass have demonstrated extremely encouraging results in reducing previously expected complication rates. Operative and intermediate survival was 100%. Eighty percent (80%) of procedures were accomplished without red blood cell transfusion, 100% were extubated within 24 hours of surgery, and (with the exception of two out-layers who had prolonged stays due to non-cardiac causes) the average length of stay was 5 days with only 18% demonstrating postoperative atrial arrhythmia. We are evaluating our technique to conform to multicenter protocols in the hope of identifying precisely which groups of patients will receive the maximal benefit from this procedure.

The organ allocation controversy: how did we arrive here?

The Department of Health and Human Services (HHS) recently issued a final regulation governing the Organ Procurement and Transplantation Network (OPTN) that directs the allocation of organs to the sickest patients first without regard to a host of medical, geographic, and social factors that members of the transplant community view as an essential part of a sound organ allocation policy.Current organ allocation mechanisms are based on policies that reflect a broad consensus of medical experts and provide equal consideration for both the needs of the sickest patients and the efficient use of organs. This system also reduces potential waste of organs by minimizing cold ischemic time, increases access to transplantation for patients in local communities, provides positive incentives for local citizens and medical professionals to support organ donation initiatives, and decreases the cost of organ transplantation.Representatives of the American Society of Transplant Surgeons have testified before Congress that "giving priority to the sickest patients first over broad geographic areas would be wasteful and dangerous, resulting in fewer patients transplanted, increased death rates, increased retransplantation due to poor organ function, and increased overall cost of transplantation." In response, Congress enacted a 1-year moratorium on the implementation of the HHS rule and provided for a study of the current organ allocation policy and HHS regulation by The Institute of Medicine.

Factors affecting immediate and long-term survival after emergent and elective splanchnic-systemic shunts.

The course of 121 shunted cirrhotic patients, managed according to a prospective protocol over a period of 10 years, was analyzed to determine predictors of 30-day and long-term survival. Forty-five per cent of the patients underwent emergent decompression within 12 hours of active bleeding, and 34% of the shunts were selective. Logistic regression linked early mortality to bilirubin and blood-urea nitrogen (BUN) (p = 0.001), and long-term survival to the presence of preoperative ascites and higher levels of alkaline phosphatase (p = 0.027), but neither variable set was a more accurate predictor than Child Class. Emergency shunt patients had greater risk of early death, 44% vs. 17% for patients shunted electively (p = 0.001), but beyond 30 days, their Kaplan-Meier survival curves were identical. Independently, angiographic prograde portal flow was favorably associated with short-term (p = 0.003) but not prolonged survival. The presence of Mallory bodies, fatty metamorphosis, and acute periportal inflammation, alone or in combination, had no prognostic value. Continued post-operative alcohol ingestion jeopardized long-term survival (p = 0.017). Survival of nonalcoholics was enhanced by selective as opposed to total splanchnic decompression (p = 0.009).