Clifford H. Van Meter

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.

Left Ventricular Assist Devices as Permanent Heart Failure Therapy The Price of Progress

Summary Background Data: The REMATCH trial evaluated the efficacy and safety of long-term left ventricular assist device (LVAD) support in stage D chronic end-stage heart failure patients. Compared with optimal medical management, LVAD implantation significantly improved the survival and quality of life of these terminally ill patients. To date, however, there have been no analyses of the cost related to the LVAD survival benefit. This paper addresses the cost of hospital resource use, and its predictors, for long-term LVAD patients. Methods: Detailed cost data were available for 52 of 68 REMATCH patients randomized to LVAD therapy. We combined the clinical dataset with Medicare data, standard billing forms (UB-92), and line item bills provided directly by clinical centers. Charges were converted to costs by using the Ratio-of-Cost-to-Charges for each major resource category. Results: The mean cost for the initial implant-related hospitalization was

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

210,187 ± 193,295. When implantation hospitalization costs are compared between hospital survivors and nonsurvivors, the mean costs increase from

Right heart failure: best treated by avoidance

159,271 ± 106,423 to

Intravenous thyroid hormone supplementation in heart failure with cardiogenic shock

315,015 ± 278,713. Sepsis, pump housing infection, and perioperative bleeding are the major drivers of implantation cost, established by regression modeling. In the patients who survived the procedure (n = 35), bypass time, perioperative bleeding, and late bleeding were the drivers of cost. The average annual readmission cost per patient for the overall cohort was

The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation

105,326. Conclusions: The cost of long-term LVAD implantation is commensurate with other life-saving organ transplantation procedures like liver transplantation. As an evolving technology, there are a number of opportunities for improvement that will likely reduce costs in the future.

Revascularization in severe ventricular dysfunction (15% ≤ LVEF ≤ 30%): a comparison of bypass grafting and percutaneous intervention

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.

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

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.

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

BACKGROUND Thyroid hormone level abnormalities commonly exist in severe heart failure and may be of prognostic value. The therapeutic potential of using thyroid hormone for cardiogenic shock resulting from progressive heart failure has not been previously delineated. We sought to evaluate the role of an intravenous infusion of thyroxine as an adjunct to conventional inotropic agents and intra-aortic balloon counterpulsation in patients with severe heart failure with cardiogenic shock. METHODS AND RESULTS We studied 10 consecutive patients with severe systolic heart failure that progressed to a cardiogenic shock state unresponsive to conventional pharmacological inotropic measures. Intravenous thyroxine (20 micrograms/h) was used as an adjunctive salvage measure after the failure of conventional pharmacological and mechanical support by intra-aortic balloon pump. The invasive hemodynamic profile (right atrial pressure, pulmonary capillary wedge pressure, cardiac index, mean arterial pressure), overall clinical status, core temperature, renal function, and tachyarrhythmias were compared before and sequentially at 6, 24, and 36 hours after the initiation of thyroxine administration. Long-term outcome was also defined. All patients had statistically significant improvements in cardiac index, pulmonary capillary wedge pressure, and mean arterial pressure at 24 and 36 hours post-initiation of thyroxine. No sustained tachyarrhythmias were seen during the thyroxine infusion. In 9 of 10 patients who underwent left ventricular assist device placement and/or heart transplantation, the use of thyroxine served as an effective adjunctive measure to allow transitioning to definitive surgical therapy. The 6-month and 1-year cohort survival rates, achieved by the transition to surgical therapy, were 90% and 80%, respectively. CONCLUSION The beneficial hemodynamic properties of intravenous thyroid hormone can be effectively used in otherwise terminal situations of cardiogenic shock, and in such situations, the use of thyroid hormone can serve as a pharmacological adjunct to a definite surgical intervention. Further studies in larger numbers of patients might be warranted to confirm these findings.

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

OBJECTIVE The authors present their experience with patients having undergone orthotopic heart transplantation (OHT) in whom surgical conditions subsequently developed that required operative intervention. The incidence, morbidity, and mortality of these procedures are reported. SUMMARY BACKGROUND DATA Several studies have evaluated the management options of biliary tract disease after OHT. Multiple reports of patients having undergone OHT who subsequently underwent peripheral vascular reconstructions, plastic reconstructive, and thoracic procedures also have been published. METHODS A chart review of 349 patients who underwent OHT between 1985 and 1996 was conducted to identify surgical procedures that were required in the post-transplant period. Their outcomes are reported. RESULTS Of 349 patients who underwent OHT, conditions requiring 94 surgical procedures developed in 54 patients (15%). Biliary tract disease developed in 17 patients (5%) who required cholecystectomy, 2 of the 5 patients with acute cholecystitis died. Eight patients (2%) underwent orthopedic procedures with no operative mortality. Flap advancements for sternal wound infections were performed in five patients and four deaths occurred. Seventeen thoracic procedures were performed in 11 patients with an overall mortality of 45%. Twenty-one vascular procedures were performed on 17 patients with 1 delayed death due to a malignancy. Seven patients underwent procedures of the colon and rectum with no mortality. Seven patients underwent repair of inguinal or incisional hernias with no mortality. Various infections occurred with one resultant death after operative intervention. Six procedures were performed for diseases of the small intestine with no resultant mortalities. CONCLUSIONS Patients having undergone OHT and chronic immunosuppression are at increased risk of having complications develop from infection. Acute cholecystitis and sternal wound infection caused an inordinate risk of complications and death. Malignancies developed in four patients who required surgical intervention. A heightened awareness of coexisting peripheral vascular disease in patients transplanted for ischemic cardiomyopathy should exist. Close screening before surgery and surveillance after surgery to identify risk factors for infection and vascular disease and to screen for malignancies are essential.