Thrombolytics in VAD management - A single-center experience.

BACKGROUND: With continued increase in the use of mechanical circulatory support, the incidence of device thrombus remains a challenge. This study is a retrospective analysis of data at a single center to assess the safety and efficacy of thrombolytic use in durable mechanical assist devices. METHODS: Data was analyzed retrospectively from 154 patients who underwent left ventricular assist device (LVAD) implantation from 1/1/2005 to 6/30/2014. The HMII device was implanted in 131 patients while 23 received the HVAD. LVAD thrombus was diagnosed when lactate dehydrogenase levels exceeded 1000 units/l accompanied by clinical signs of hemolysis and heart failure, echocardiographic data and surges in pump power. TPA (tissue plasminogen activator) protocol consisted of a 5 mg intravenous bolus followed by 3 mg/h infusion in normal saline for 10 h. If symptoms persisted another cycle of TPA at 1 mg/h was continued up to 48 h. RESULTS: The TPA group had a 70% success rate. Success was defined as complete resolution of hemolysis and clinical symptoms with no requirement for LVAD exchange at 30 days. 95% survival was noted at 30 days and 90% were free of a hemorrhagic stroke in the TPA group. The rates of hemorrhagic strokes in the TPA group and the control group were not different (OR = 0.92). CONCLUSION: The TPA protocol described here was successful consistently. Though this study is limited by its size and retrospective nature it leads the way for larger studies to generate more robust comparisons between different types of mechanical assist devices as well as the tailored use of thrombolytics in this patient population.

HeartMate VE LVAS design enhancements and its impact on device reliability.

OBJECTIVE: The HeartMate VE left ventricular assist system (LVAS) has supported more than 2300 patients and has been shown to be effective for bridge to cardiac transplantation and has demonstrated improved outcomes in survival as a destination therapy. Improvements in device durability are needed as bridge to transplant times increase and as we move into the era of LVAD as destination therapy. The purpose of this study is to determine if design enhancements to the HeartMate LVAS have improved device reliability and durability. METHODS: A retrospective analysis of serious mechanical failures was performed in 1865 devices (1458 VE, 407 XVE). The analysis of data included devices used to support patients from September 1998 for bridge to transplantation and destination therapy. Serious mechanical failures were defined as inflow valve dysfunction, percutaneous lead breaks, diaphragm fractures or punctures, bearing failures, outflow graft erosion and pump disconnects. RESULTS: Median device duration for the VE was 97 days (max 1206 days), and 85 days (max 517 days) for the XVE. A total of 134 serious mechanical failures occurred and included inflow valve dysfunction (5.3% VE, 2.4% XVE) (P = 0.853) percutaneous lead breaks (1.9% VE, 0% XVE) (P < 0.001) diaphragm fractures (0.1% VE, 0% XVE) (P = 0.134) outflow graft erosion (0.2% VE, 0% XVE) (P = 0.1096), pump disconnects (0.1% VE, 0% XVE) (P = 0.1336) and bearing failures (0.6% VE, 0.2% XVE) (P = 0.5538). Of the XVEs 97% were free of serious mechanical failures at 6 months and 82% at 1 year compared to 92 and 73% for the VE, respectively. The 6-month difference between the devices was statistically significant (P = 0.0063) and there was no statistically significant difference at 1 year (P = 0.1492). CONCLUSIONS: Preliminary experience with the HeartMate XVE LVAS demonstrated a significant reduction in percutaneous lead breaks. Early trends indicate positive impact of recent design modifications on XVE performance. These design modifications may improve device durability and reliability, which is crucial as we enter the era of LVADs as an alternative to medical therapy.

Optical coherence microscopy for the evaluation of a tissue-engineered artificial cornea.

A transparent artificial cornea derived from biological material is the ultimate goal of corneal research. Attempts at artificial corneal constructs produced from synthetic polymers have proved unsuccessful due to lack of biocompatibility and ability to integrate into the tissue. We have designed a corneal model derived from collagenous biological materials that has several advantages: it has low antigenicity and therefore small chance of eliciting an immune reaction, it can be broken down by the body's own cells and gradually replaced over time by natural materials, and it may contain signaling information for native cells, thereby inducing normal phenotype and behavior. In addition, a transparent corneal model has the potential to be used for testing of novel ophthalmic drugs or gene therapy approaches, eliminating the need for animal testing. We have used an optical coherence microscope (OCM) to evaluate both the structure of our tissue constructs over time in culture and the optical properties of the tissue itself. This imaging technique promises to be an important diagnostic tool in our efforts to understand the influence of mechanical forces, cell phenotype, and soluble factors on the transparency of corneal tissue.

Novel lamin A/C mutations in two families with dilated cardiomyopathy and conduction system disease.

BACKGROUND: The LMNA gene, one of 6 autosomal disease genes implicated in familial dilated cardiomyopathy, encodes lamins A and C, alternatively spliced nuclear envelope proteins. Mutations in lamin A/C cause 4 diseases: Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy type 1B, Dunnigan-type familial partial lipodystrophy, and dilated cardiomyopathy. METHODS AND RESULTS: Two 4-generation white families with autosomal dominant familial dilated cardiomyopathy and conduction system disease were found to have novel mutations in the rod segment of lamin A/C. In family A a missense mutation (nucleotide G607A, amino acid E203K) was identified in 14 adult subjects; disease was manifest as progressive conduction disease in the fourth and fifth decades. Death was caused by heart failure. In family B a nonsense mutation (nucleotide C673T, amino acid R225X) was identified in 10 adult subjects; disease was also manifest as progressive conduction disease but with earlier onset (third and fourth decades), ventricular dysrhythmias, left ventricular enlargement, and systolic dysfunction. Death was caused by heart failure and sudden cardiac death. Skeletal muscle disease was not observed in either family. CONCLUSIONS: Novel rod segment mutations in lamin A/C cause variable conduction system disease and dilated cardiomyopathy without skeletal myopathy.

Comparison of functional capacity in patients with end-stage heart failure following implantation of a left ventricular assist device versus heart transplantation: results of the experience with left ventricular assist device with exercise trial.

BACKGROUND: Use of a permanent left ventricular assist device (LVAD) has been proposed as an alternate treatment of patients with end-stage heart failure. The purpose of this study was to compare the functional capacity of patients following implantation of a LVAD vs heart transplant (HTx). METHODS: Eighteen patients from 6 centers who received an intracorporeal LVAD as a bridge to HTx underwent treadmill testing 1 to 3 months post-LVAD and again post-HTx. Baseline and peak measurements, including oxygen consumption, blood pressures, and respiratory rate were made during each treadmill test. RESULTS: Peak oxygen consumption was 14.5+/-3.9 ml/kg/minute post-LVAD and 17.5+/-5.0 ml/kg/minute post-HTx (p < .005). The percentage of the predicted peak oxygen consumption based on gender, weight, and age was 39.5%+/-5.5% post-LVAD and 47.7%+/-10.9% post-HTx (p < .005). Exercise duration was lower post-LVAD than post-HTx (10.3+/-4.2 minute vs 12.5+/-5.4 minute, p < .05). After LVAD implantation, peak total oxygen consumption correlated with peak LVAD rate and output. Eight patients reached an LVAD rate of 120 beats per minute (bpm) before the conclusion of exercise, the maximum rate for the outpatient electric device. The peak respiratory exchange ratio post-LVAD was 1.15+/-0.22 and post-HTx was 1.15+/-0.18, consistent with a good effort in both groups. CONCLUSIONS: Patients demonstrated a lower functional capacity post-LVAD than post-HTx. For some patients functional capacity post-LVAD may be improved by a higher maximum LVAD rate and output.

A technique to simplify and improve exposure in heart-lung transplantation.

Heart-lung transplantation is associated with high perioperative mortality rates. A modified operative technique was used by one surgeon operating on 17 patients at the University of Arizona, Tucson, and the Inland Northwest Thoracic Organ Transplant Program, Spokane, Washington. This technique gives greater exposure to the area of dissection behind the heart-lung block after implantation and makes maintaining hemostasis easier. No deaths from bleeding complications occurred and no reoperations for bleeding were required with this technique. The Kaplan-Meier survival was 82% at 1 year. This technique simplifies a difficult technical procedure and may reduce mortality rate.

The effects of pentoxifylline on the prevention of cyclosporine-induced nephrotoxicity in cardiac transplant patients.

The objective of this trial was to determine if oral pentoxifylline (PTX) reduced cyclosporine (CSA)-induced renal dysfunction in cardiac transplant patients in the 8 months following transplantation. The study was a prospective, open-label, crossover trial evaluating the renal effects of PTX in nine postcardiac transplant patients. Patients received PTX 2 weeks posttransplant and continued therapy for 4 months. Patients were evaluated for an additional 4 months thereafter. During the trial, various renal function tests were performed and CSA concentrations were measured at set intervals. Baseline measurements were compared with all subsequent measurements. In addition, "on-PTX" data were compared with "off-PTX" data. Significant alterations in results of renal function tests were not seen during the trial when compared with baseline values. Although no significant changes in renal function were observed during the study, no patient developed CSA-induced acute renal failure during the 4 months posttransplant. This finding suggests that PTX may offer a nephroprotective effect against CSA-induced toxicity.

Pneumocystis carinii pneumonia after heart transplantation.

Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation.

Results of heart transplantation for active lymphocytic myocarditis.

To determine whether the heart-specific immunoreactivity associated with active myocarditis affects outcome after heart transplantation, we retrospectively analyzed the outcome of 12 patients with active lymphocytic myocarditis in their explanted native hearts identified by the Registry of the International Society for Heart Transplantation. The patients were 38 +/- 10 years of age and predominantly female (75%). In nine patients (75%), endomyocardial biopsy showed active myocarditis before transplant; eight of these patients also received immunosuppression before transplant. Recipient hemodynamic study before transplantation demonstrated an ejection fraction of 0.18 +/- 0.06, cardiac index of 1.7 +/- 0.4 L/min/m2, pulmonary artery pressure of 41 +/- 6/23 +/- 6 mm Hg, and mean pulmonary capillary wedge pressure of 30 +/- 5 mm Hg. Left ventricular end-diastolic dimension by echocardiography was 6.0 +/- 1.4 cm. Four of the patients were dependent on intravenous inotropes, and six required mechanical assistance. Over a 36-month follow-up period, 2.9 +/- 2.4 episodes of rejection occurred per patient. Sixty percent of the first episodes occurred within 2 weeks of transplantation. These patients experienced a 2.2 +/- 1.1-fold increase in rejection compared with institutional average rejection rates. Survival was significantly shorter than that of age-matched or female control subjects. This study is limited by its retrospective nature and the unusual pretransplant characteristics of the subjects. It indicates that active myocarditis may predispose patients to early severe rejection and a high mortality rate after heart transplantation.

Rabbit antithymocyte globulin. A 10-year experience in cardiac transplantation.

Rabbit antithymocyte globulin, a "custom-made" pan-anti-T-cell antibody produced in rabbits, is currently being evaluated in the United States and may, within several years, become approved by the Food and Drug Administration. Because we have used this agent for induction of immunosuppression for 10 years in cardiac recipients and because the results appear to be more favorable than those obtained with other agents (horse antithymocyte globulin, antilymphocyte globulin, OKT3), we have reviewed our experience. For the purpose of analysis, all non-bridge-to-transplant cardiac recipients have been divided into three groups on the basis of immunosuppression protocol: group I (March 1979 to January 1983), 28 patients treated with rabbit antithymocyte globulin, steroids, and azathioprine; group II (January 1983 to March 1985), 29 patients treated with rabbit antithymocyte globulin, cyclosporine, and steroids; and group III (March 1985 to January 1989), 98 patients treated with rabbit antithymocyte globulin, cyclosporine, steroids, and azathioprine. Actuarial data showed advantage for group III in survival rate (1 year 94%, 2 years 91%, 3 years 88%), freedom from rejection (30% free at 1 year), freedom from infection (50% free at 1 year), freedom from death from rejection (99% free at 1 year), and freedom from death from infection (97% freedom at 1 year). Actuarial survival rates and freedom from death from rejection and infection are comparable for any of our groups with contemporary published data. In the past 3 years, we have had no death from acute rejection or from posttransplant infection. Time-related rates of infection by etiologic agents have shown a significant reduction in early bacterial, viral, and nocardial infections between groups I and III. With rabbit antithymocyte globulin 200 mg intramuscularly every day for 3 days, our current protocol, T-cells are significantly reduced and local and systemic toxicity is almost unnoticeable. A progressively increasing cyclosporine dose along with rapid tapering steroid and maintenance azathioprine immunosuppressive induction appears to be the therapy of choice in cardiac transplantation.

Thromboembolic complications of the Symbion AVAD System.

The Symbion Acute Ventricular Assist Device (AVAD) System is an experimental paracorporeal pulsatile ventricular assist device (VAD) for single or biventricular assist. Eleven patients were implanted but 2 died within 24 h and were excluded from the study. Nine patients, four with left ventricular assist devices (LVADs) and five with biventricular assist devices (BIVADs), with a mean implant time of 24 days, were studied to determine the incidence and site of thrombus formation within the device and the incidence of thromboembolic complications. Anticoagulation consisted of heparin titrated to keep the partial thromboplastin time (PTT) twice control and dipyridamole 50 to 200 mg q6h p.o. Seven of nine patients (78%) developed thrombus; five had thrombus visible within the clear housing of the device during the implant period, and two patients had thrombus discovered only after VAD explantation. Common sites of formation were the diaphragm-housing junction, the housing near the outflow orifice, and the de-airing port. Three patients with thrombus developed thromboembolic complications; two suffered strokes and one had multiorgan emboli. The Symbion AVAD System has significant thrombogenic properties that may limit its clinical application.

Heart-lung transplantation: the initial Arizona experience.

Since November 1985, cardiopulmonary transplantation has been performed at the University of Arizona heart transplant program. Seven patients, five women and two men, have undergone heart-lung transplantation. Five patients had primary pulmonary hypertension, and two patients had Eisenmenger's complex. The mean age was 31 years (range, 17 to 43 years). Average follow-up was 15 months (range, 3 to 34 months), with a total of 115 patient-months. There have been no operative or late deaths. Immunosuppression consisted of rabbit antithymocyte globulin, cyclosporine (Cyclosporin A), azathioprine, methylprednisolone, and prednisone. Our first five patients were aggressively diagnosed and treated for rejection by endomyocardial biopsy, with each patient having one or several treatments for acute rejection. These five patients had one or several episodes of severe infection, particularly cytomegalovirus. In our last two patients we omitted routine heart biopsies. Only those rejection episodes diagnosed by chest x-ray films are considered significant. Our last two patients have not been treated for acute rejection and have had no infections. Presently our immunologic surveillance consists only of careful clinical examination and frequent chest x-ray films. Any changes in the patient's condition are aggressively investigated, searching for infection or rejection. Two patients have been used as domino donors of their native heart.

Gastrointestinal cytomegalovirus infection in heart and heart-lung transplant recipients.

Cytomegalovirus (CMV) causes major morbidity in organ transplant recipients. Gastrointestinal disease was the most prominent manifestation of CMV infection in a population of heart and heart-lung transplant patients, with an incidence of 9.9%, compared with pneumonitis (4.0%) and retinitis (0%), and occurred most frequently in CMV-seronegative recipients of organs from CMV-seropositive donors. Clinical manifestations included gastritis (nine patients), gastric ulceration (four patients), duodenitis (three patients), esophagitis (one patient), pyloric perforation (one patient), and colonic hemorrhage (one patient). Patients with gastrointestinal CMV infection were treated with intravenous ganciclovir sodium therapy, 5 mg/kg twice daily, for 2 to 8 weeks, with positive clinical, endoscopic, histologic, and virologic responses. Relapses occurred in four of nine patients who were followed up for a median period of 18 months. Retreatment resulted in healing of endoscopic lesions and in viral clearing. We conclude that early endoscopic evaluation for CMV is indicated in heart and heart-lung transplant patients with gastrointestinal symptoms. This study further suggests that intravenous ganciclovir therapy is effective for the treatment of gastrointestinal CMV in these patients.

Platelet and fibrin metabolism in recipients of the Jarvik 7 total artificial heart.

Recipients of the total artificial heart are at risk for device-related thrombus formation and thromboembolism. Platelet and fibrin metabolism was studied in four patients who received the Jarvik 7 total artificial heart as a bridge to transplantation and in eight patients after orthotopic heart transplantation. Platelet activation was assessed by measurement of plasma levels of beta-thromboglobulin, fibrin formation by fibrinopeptide A, and fibrinolysis by cross-linked fibrin degradation products. These markers were increased after surgery with only minimal differences between the two patient groups for the first 3 days. In comparison to heart transplant patients, these markers remained elevated in artificial heart recipients despite anticoagulation therapy. beta-Thromboglobulin levels did not decrease in two artificial heart recipients who received aspirin. Markers of platelet and fibrin activity were greatly increased in one artificial heart recipient who had impaired inflow into the device, was not anticoagulated because of bleeding, and had extensive device-related thrombus on explantation. Plasma markers of platelet and fibrin metabolism provide biochemical assessment of in vivo thrombus activity in artificial heart recipients. Monitoring these markers may provide an additional means of guiding anticoagulation therapy in patients with artificial hearts and assessing interventions designed to reduce device-related thrombus formation.

The use of intravenous ribavirin to treat influenza virus-associated acute myocarditis.

We studied three patients with influenza virus-associated fulminant myocarditis; one was infected by type B and the others by type A influenza virus. In one patient, dissemination of type A (H1N1) virus to the myocardium was demonstrated, and viremia complicated the clinical course despite the use of oral amantadine HCl and ribavirin aerosol. All patients were treated with iv ribavirin, two initially and the third after viremia was detected during hyperacute rejection of a cardiac transplant. No significant adverse effects could be directly attributed to therapy, and viral shedding abruptly terminated coincident with its use; however, both patients treated shortly after onset of myocarditis died. The third required support by an artificial heart, and died 8 mo later. Immunotyping of myocardial tissues in two cases revealed an initial predominance of T helper cells. Serial endomyocardial biopsies available from one of these demonstrated a subsequent marked decrease in the T helper cell population as inflammation and necrosis subsided during and following therapy.

Extracorporeal pulsatile biventricular support after cardiac transplantation.

A donor heart failed to adequately sustain hemodynamic function after cardiac transplantation. The cause of the donor heart dysfunction was unknown, and there were no definite risk factors identified to suggest the heart would not recover. A Symbion Acute Ventricular Assist Device System was used to support both ventricles. The heart gradually recovered and the system was explanted after 1 week of support. The patient recuperated and has been discharged from the hospital.

Orthotopic total artificial heart bridge to transplantation: preliminary results.

A detailed summary of seven patients who received eight total artificial heart implants, including one Phoenix heart, two Jarvik 7-100 ml hearts, and five Jarvik 7-70 ml hearts, and nine heart transplants, reveals that bleeding, hemolysis, and thromboembolic and infectious problems are not the limiting factors. Size of the patient and the requirement for adequate space to permit adequate systemic and pulmonary venous filling seem to be the major limitations. Patients with a reasonable expectation of receiving a transplantation within 3 weeks are the best candidates for a bridge to transplantation. After this adhesions were found to cause severe technical problems at reoperation.

Transtracheal aspiration and fine needle aspiration biopsy for the diagnosis of pulmonary infection in heart transplant patients.

A total of 129 transtracheal aspirations or fine needle aspirations, or both, were performed in 65 heart and heart-lung transplant patients to identify the causative pathogen in suspected pulmonary infection. Transtracheal aspiration was performed in 82 instances, fine needle aspiration in 47, and both procedures in 23. Both transtracheal and fine needle aspiration were highly specific, 96% and 100%, respectively. Sensitivity for transtracheal aspiration was lower than for fine needle aspiration, 70% and 89%, respectively. The lower sensitivity of transtracheal aspiration is attributed to its performance in all patients with suspected infection regardless of chest radiographic findings. Fine needle aspiration was performed when identifiable lesions could be used as a "target." Overall accuracy of transtracheal aspiration was 78% compared to 91% for fine needle aspiration both alone and combined with transtracheal aspiration. More invasive procedures such as bronchoalveolar lavage and open lung biopsy were required in only three patients (2%). Transtracheal aspiration resulted in one minor complication (1%). The commonest complication of fine needle aspiration was pneumothorax (21%). There were no deaths associated with either procedure. We conclude that in heart and heart-lung transplant patients with suspected pulmonary infection, transtracheal aspiration and fine needle aspiration are safe and accurate methods to identify the causative organism. More invasive techniques may be required in a small minority of patients.