Extracorporeal Membrane Oxygenation (ECMO): An Option for Cardiac Reccovery from Advanced Cardiogenic Shock.

Mechanical circulatory support can prevent multi-organ failure and death in patients with advanced cardiogenic shock. Here we describe our experience using extracorporeal membrane oxygenation (ECMO) for treatment of advanced cardiogenic shock which has been used by our team for daily routine care in more than 200 patients during the last five years at the Penn State Medical Center. Venoarterial (VA) ECMO has been used as a viable therapeutic option for advanced cardiogenic shock as a bridge to recovery (BTR) or bridge to next decision (BTD). Our group performed a retrospective review of data from 155 patients from our single center cohort treated with VA ECMO for advanced cardiogenic shock. After successful ECMO treatment, the one year survival rate of patients with ischemic heart disease was 73.7 %, and the one year survival for patients with non-ischemic heart disease was 75%.

Pump Thrombosis following HeartMate II Left Ventricular Assist Device Implantation in a Patient with Aspirin and Plavix Resistance.

Despite advances in pump technology, thromboembolic events and pump thrombosis are potentially life-threatening complications in patients with continuous flow ventricular assist devices. Here we describe a patient with pump thrombosis following LVAD HeartMate II implantation presenting with Aspirin and Plavix resistance and signs of acute hemolysis as manifested by high LDH, changing pump power, pulse index and reduced pump flows.

Cardiac hypertrophy after transplantation is associated with persistent expression of tumor necrosis factor-alpha.

BACKGROUND: The mechanisms that contribute to cardiac allograft hypertrophy are not known; however, the rapid progression and severity of hypertrophy suggest that nonhemodynamic factors may play a contributory role. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine produced in cardiac allografts and capable of producing hypertrophy and fibrosis; therefore, we suggest that TNF-alpha may play a contributory role. Accordingly, the aims of our study were to define the role of systemic hypertension in the development of hypertrophy, characterize the histological determinants of hypertrophy, and characterize the expression of myocardial TNF-alpha after heart transplantation. METHODS AND RESULTS: To separate the effect of hypertension from immune injury in the development of cardiac allograft hypertrophy, we measured the gain in left ventricular mass by 2D echocardiography in heart transplant recipients and lung transplant recipients who developed similar rates of systemic hypertension. The gain in left ventricular mass was 73% in heart transplant recipients and 7% in lung transplant recipients (P<0.0001). By comparing myocardial samples obtained during the first week after transplant and at 1 year, we found that there was a significant increase in total collagen content (P<0.0001), collagen I (P<0.0001), collagen III (P<0.0001), and myocyte size (P<0.0001). These changes were associated with persistent myocardial TNF-alpha expression. CONCLUSIONS: We suggest that the contribution of hypertension to cardiac allograft hypertrophy is minimal and that persistent intracardiac expression of TNF-alpha may contribute to the development of cardiac allograft hypertrophy.

Hemodynamic follow-up of cardiac allografts from poisoned donors.

BACKGROUND: The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents. METHODS: Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/ thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients. RESULTS: Early mortality in this group was 11%; cumulative survival after 5 years was 74%. CONCLUSIONS: Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.

Extended donor criteria: hemodynamic follow-up of heart transplant recipients receiving a cardiac allograft from donors > or = 60 years of age.

BACKGROUND: Heart transplantation (HT) has become a therapeutic option for patients suffering from endstage heart failure. The increasing demand for cardiac allografts has led to a shift toward extended donor criteria. In a retrospective analysis of 859 HT recipients, we report on the hemodynamic outcome of 19 HT patients who received cardiac allografts from donors > or =60 years of age. METHODS: From March 1989 to December 1997, we performed 883 orthotopic HT in 74 children and 809 adults at our transplant center. Within this period, 19 patients (17 women and 2 men) received cardiac allografts from donors > or =60 years of age. Recipient age ranged from 57 to 78 years (mean, 65+/-5 years). RESULTS: HT could be performed successfully in 19 cases. The early mortality rate was 16% (n=3). The late mortality rate was 37% (n=7). All long-term survivors are stable at New York Heart Association classification II (New York Heart Association Class II = resting hemodynamics: cardiac output normal; left ventricular end diastolic filling pressure elevated; clinically not compromised during mild to moderate workout). Although only 19 patients were retrospectively evaluated, there was a statistically significant (P<0.05) difference in survival among patients who received organs from male (11 vs. 8*) compared with female (8 vs. 2*) (*=death) donors. CONCLUSION: In our experience, it is possible to increase the cardiac donor pool by accepting allografts from donors, preferably female, > or =60 years of age in selected cases without a coronary angiogram, if hemodynamic parameters are in a normal range on mild-to-moderate inotropic support. We do not recommend cardiac allografts from donors > or =60 if there are signs of coronary insufficiency in the electrocardiogram, if left ventricle filling pressures are above normal on mild-to-moderate inotropic support and optimum hemodynamic management, or if there are signs of segmental dysfunction or mitral insufficiency >I in the echocardiogram.

Extended donor criteria: use of cardiac allografts after carbon monoxide poisoning.

BACKGROUND: An increasing demand for cardiac allografts for the treatment of end-stage cardiac failure has led to a shift in the traditional views about donor criteria. The use of allografts exposed to high concentrations of carbon monoxide is still under discussion. The current literature on this topic is contradictory. We describe our experience with orthotopic cardiac transplantation, using cardiac allografts after carbon monoxide poisoning. METHODS: Between March 13, 1989 and August 1, 1996, 770 orthotopic heart transplantations were performed in our center. Within this period, we accepted five cardiac allografts from brain-dead, carbon monoxide-poisoned donors. Donor history showed carbon monoxide intoxication in all cases. At the time of organ explantation, donor hemodynamic parameters were feeble in all patients. RESULTS: The postoperative course was uneventful in three of the five recipients. The overall 3-year survival rate in this small group is 40%. Induction therapy or rescue therapy with mono/polyclonal antibodies was not necessary. Myocardial right-ventricular biopsies did not show any specific signs of carbon monoxide poisoning. CONCLUSIONS: In our opinion, cardiac allografts from donors exposed to carbon monoxide can be transplanted successfully in infants and adults, if there are no signs of severe hemodynamic dysfunction in the presence of a normal central venous pressure and low-dose support with catecholamines and there are no electrocardiographic changes in combination with elevated transaminase. With extended donor criteria, the hearts of carbon monoxide-poisoned victims could increase the number of suitable organs and lower the death rate of patients on the United Network for Organ Sharing and Eurotransplant International Foundation waiting lists.

Results of heart transplantation in patients with preexisting malignancies.

Twenty patients with end-stage heart failure and preexisting malignancies underwent heart transplantation at a single center, with a neoplasm-free interval before the procedure of 0 to 240 months. Twelve patients were long-term survivors (2 to 72 months); there were 2 early and 6 late deaths, thus justifying heart transplantation in patients with preexisting malignancies in individual cases.

Outcome of heart transplantation in patients previously infected with hepatitis C virus.

The lack of knowledge about the course of hepatitis C virus infection (HCV) before heart transplantation (HTx) prompted us to describe our experience with 4 such patients who presented with positive HCV serology before surgery. Two experienced non-liver related deaths at 3.5 and 5 years after HTx, and none of the patients developed signs of hepatic insufficiency during the follow-up (mean 3.8 years). Tests for HCV antibodies were frequently negative, whereas viral RNA was detected in 81% of the measurements, showing that virus detection techniques seem to be more sensitive than serology techniques in detecting HCV infection in this group of patients. Although immunosuppression promotes active HCV replication, it does not seem to change the chronic features of HCV infection during the first years in patients with good liver function.

Regression of fibrosis and hypertrophy in failing myocardium following mechanical circulatory support.

BACKGROUND: The cellular and structural changes that occur during long-term ventricular unloading leading to cardiac recovery are poorly understood. However, we have previously demonstrated that left ventricular assist device (LVAD) support leads to a significant decrease in intracardiac tumor necrosis factor-alpha (TNF-alpha), a protein capable of producing hypertrophy and fibrosis. METHODS: To further define the beneficial effects of long-term ventricular unloading on cardiac function, we determined the effect of mechanical circulatory support on fibrosis and hypertrophy in paired myocardial samples of 18 patients with end-stage cardiomyopathy obtained at the time of LVAD implantation and removal. RESULTS: We determined total collagen as well as collagen I and III by a semiquantitative analysis of positive immune-stained areas in pre- and post-LVAD myocardial samples. We found that total collagen content was reduced by 72% (p < 0.001), whereas collagen I content decreased by 66% (p < 0.001) and collagen III content was reduced by 62% (p < 0.001). Next, we determined myocyte size by direct analysis of cellular dimensions utilizing a computerized edge detection system in pre- and post-LVAD myocardial samples. We found that myocyte size decreased in all patients studied for an average reduction of 26% (33.1 +/- 1.32 to 24.4 +/- 1.64 microm, p < 0.001). CONCLUSION: These data demonstrate that long-term mechanical circulatory support significantly reduces collagen content and decreases myocyte size. We suggest that the reduction of fibrosis and hypertrophy observed may in part contribute to the recovery of cardiac function associated with long-term mechanical circulatory support.

Managing heart failure with immunomodulatory agents.

The evidence in favor of immune activation as an operative mechanism that contributes to the progression of heart failure continues to accumulate. Indeed, a number of clinical trials have demonstrated the clinical interest of interventions in this area for many years, but none have proven useful. The only trial ever conducted to define the effect of immunotherapy in mortality, however, is the one currently ongoing using Etanercept in patients with symptomatic heart failure. Irrespective of the final outcome of the study, the growing interest in inflammation as a contributory pathway in disease progression has now opened the field to develop new strategies for intervention. Whether specific or non-specific therapies may prove useful will be defined only by the results of randomized clinical trials.

Pre-existing elevated pulmonary vascular resistance: long-term hemodynamic follow-up and outcome of recipients after orthotopic heart transplantation.

BACKGROUND: Elevation of pulmonary vascular resistance (PVR) has been considered to predict a bad outcome after orthotopic heart transplantation (HTx). A transpulmonary gradient (TG) > or =15 mmHg and PVR > or =5 wood (w) are correlated with a three-fold increase in 2-days as well as 30-days and 6-, 12-month mortality. METHODS: We performed a retrospective analysis of 400 consecutive transplanted patients (pts) on hemodynamic data over a time period of 3.5 years. In 83 pts (23%) preoperative PVR was > or =5 w and TG >15 mmHg. Vasodilator studies were performed in this group of pts in order to evaluate pulmonary vasoreactivity or hemodynamic improvement. RESULTS: Hemodynamic follow-up post-transplantation showed a significant (p<0.001) decrease in mean TG to 8.8 mmHg within the first, 7.7 after the fifth year as well as decrease in PVR from 5.5 to 1.6, within the first and fifth year post-transplantation. Compared to the control group (n=286) (re-transplants n=6 and pediatric pts n=25 excluded) pts with TG <15 mmHg and/or PVR <5 w, transplanted within the same period, 30-day mortality and cumulative survival after 1 and 5 years do not show any significant difference with a mortality of 3%, 22% and 33% (p<0.05). Subgroup analysis for pts with endstage of ischemic versus dilatative cardiomyopathy has not shown any significant difference in mortality. CONCLUSIONS: In a retrospective analysis of 400 pts elevated PVR does not predict a bad outcome after orthotopic heart transplantation in early and late mortality.

Influence of different assist devices on survival after orthotopic heart transplantation.

BACKGROUND: In 1995, a risk factor of 1.88 was indicated for one-year mortality in connection with bridging to heart transplantation. Both one-year and three-year survival rates in patients bridged to transplantation were less than 80%. METHODS: From 3/89 to 12/98, 903 orthotopic heart transplantations were performed at our center in 888 recipients. Bridging was necessary in 142 patients. RESULTS: The one-year survival rate was 76% in pts without VAD, 86% in pts bridged with VAD and 66% in pts with VAD due to postcardiotomy syndrome. The three-year survival rates were 73%, 80% and 55% respectively. CONCLUSIONS: Early and late results in patients bridged to transplantation remarkably improved over 1995. One-year and long-term survival rates are significantly lower when assist devices are used in patients with postcardiotomy syndrome. Despite a high incidence of assist-related complications, electively bridged patients showed significantly better early and long-term results than the control group.

Mechanical circulatory support after orthotopic heart transplantation.

Frequently the only therapy for primary graft- and right heart failure, as well as low output syndrome from acute of chronic rejection, is implantation of a mechanical circulatory support system, until recompensation or retransplantation. At our institution, mechanical assist devices were implanted in 25 heart recipients for a cute rejection (n=9), primary graft failure (n=7), acute right heart failure (n=7), and chronic rejection with low output syndrome (n=2). Patients (pts) with primary graft failure (n=3) received an intraaortic balloon pump (IABP), one pt an IABP plus Abiomed-System for left ventricular support, one pt the Thoratec-System for biventricular support. Patients with right heart failure (RHF) received the Biomedicus centrifugal pump for right ventricular support. Nine pts suffered from acute rejection. Six pts received an IABP, one the Biomedicus as femoro-femoral bypass, one the Abiomed-System for biventricular support, two the Thoratec-System for biventricular support and two within this group switched from the Biomedicus pump to the Thoratec-System for biventricular support. Patients with chronic graft failure (n=2) received the Novacor-System (LVAD) for left ventricular support, one received a Tojobo-System and an oxygenator for biventricular support post coronary artery bypass surgery. Support time ranged from 0.5-h to 73 days. Five pts were weaned. Two (8%) of 25 pts were retransplanted, 18 (72%) died in spite of mechanical support from multiple organ failure. The use of a mechanical assist device after heart transplantation is encouraging only in the case of early right heart failure, as well as primary and chronic graft failure. In view of the poor results, the use of mechanical assist devices should not be recommended in the case of heart failure caused by acute rejection.

Heart transplantation for end-stage heart failure caused by iron overload.

Few reports exist concerning heart transplantation in recipients with end-stage myocardiopathy-associated heart failure caused by iron overload occurring with beta-thalassaemia, Diamond-Blackfan syndrome or haemochromatosis. Seven potential transplant candidates (six male, one female, mean age 26 years) with such heart failure, following desferrioxamine application subcutaneously over a number of years, and intravenously during their hospitalization before transplantation, were retrospectively analysed. Five were New York Heart Association (NYHA) class IV, three experienced one or more resuscitations immediately before transplantation could be performed. Continuous, high-volume, veno-venous haemofiltration was necessary in two patients. One of these two candidates additionally had to be bridged, first with a right ventricular, then with a biventricular assist device. Five of the seven patients survived, two with haemochromatosis, one with beta-thalassaemia major and one with Diamond-Blackfan syndrome following transplantation. One non-transplanted candidate with beta-thalassaemia major has been recompensated for 5 years. Survival was 14-74 months. Our results demonstrate the feasibility and indication of transplantation in patients with such heart failure and the satisfying outcome of immunosuppression is described.

Influence of cytoimmunological state on the development of tuberculosis in heart transplant recipients.

We examined the relationship between the development of tuberculosis and the cytoimmunological state of orthotopic heart transplant (HTx) recipients, which is affected by immunosuppressive therapy. Tuberculosis developed in 7 (1%) of 716 HTx recipients (four men and three women, aged 33-71 years) during a 7-year period, the standardized annualizing rate being about 1370/100000 per year, which is greater than the 17.5/100000 per year in the general population of Germany. Tuberculosis developed in the early posttransplant period in four patients when they were experiencing episodes of ongoing rejection, after 2.5, 3.5, 4.0, and 9.0 months, respectively, the standardized annualizing rate being 780/100000 per year. In three of those four patients, cytoimmunological monitoring was carried out until the development of tuberculosis. The repeated administration of pulsed corticosteroid therapy followed by oral steroids reduced T-cell and CD4+ T-cell counts, which could have increased the risk of tuberculosis developing if they were exposed. The cytoimmunological state of the remaining three patients in whom tuberculosis developed late after HTx, when episodes of ongoing rejection did not exist, was similar to the preoperative state, the standardized annualizing rate being 590/100000 per year. These findings indicate that the relatively high incidence of tuberculosis in post-HTx patients could be attributable to the immunosuppressive therapy given, including steroids.