Hospital discharge for the ventricular assist device patient: historical perspective and description of a successful program.

Patients who are supported with an implantable ventricular assist device (VAD) as a bridge to cardiac transplantation are potential candidates for hospital discharge. Hospital discharge rates in reported clinical series vary from 27% to 60%. Many of the patients included in these series, however, were subjects of premarket approval clinical trials and as such, are bound by rigid eligibility criteria for discharge. According to a voluntary registry maintained by Thermo Cardiosystems, Inc., the postmarket discharge rate in patients supported with the HeartMate VE LVAS is approximately 25%, a number that is artificially low due to incomplete reporting. The postmarket discharge rate at the busiest Thermo Cardiosystems HeartMate VE LVAS centers is 53%. Clearly, discharge rates need to increase if the VAD is ever to be considered a viable destination therapy for end-stage heart failure. The discharge program instituted at The University of Iowa incorporates patient and family training as well as community services education. Between January 1999 and April 2001, fourteen patients received VAD support as a bridge to transplantation with the HeartMate VE LVAS. Thirteen patients (93%) were discharged from the hospital. Eight of the 13 patients have been transplanted after having spent 65.8% +/- 31.4% of their period of blood pump support as an outpatient. Eight of 13 patients (62%) required a total of 20 unplanned repeat hospitalizations. A well defined, aggressively implemented discharge program can adequately prepare the VAD patient for the transition from hospital to home.

Education of the ventricular assist device patient's community services.

Two implantable, electric left ventricular assist systems have received approval from the Food and Drug Administration (FDA) for use outside a hospital environment. As patients supported with these systems are discharged from the hospital, it is important that various community services and agencies be involved in the care of this unique patient population. Between January 1999 and May 2001, The University of Iowa Hospitals and Clinics (UIHC) implanted 14 HeartMate VE LVAS (Thoratec Corporation, Pleasanton, CA) in patients as a bridge to cardiac transplantation. Of these 14 patients, 13 were discharged home from the hospital. On the basis of our 3 year experience, a discharge program has been developed to educate the ventricular assist device (VAD) patient's community services. Ten community services most critical to a safe home discharge program are identified. Timing of service contact, mechanism of contact, community education method, education content, education materials, and outpatient community service usage are described.

Clinical trial: a clinician's perspective.

As a result of my participation in several clinical trials at The University of Iowa, I have now redrawn what I perceive to be the algorithm for conduct of a clinical trial. Of note, I have excluded the development of the new device, in vitro device testing, in vivo animal experimentation, clinical protocol development, granting of an Investigational Device Exemption, and the process by which clinical sites are selected. Following my algorithm I have made no mention of the commercialization of an experimental device, including the Pre-Market Approval process and FDA panel meetings. In summary, I believe there are a variety of reasons why a principal investigator would choose to participate in a clinical trial. With tongue in cheek, I would offer fame and fortune as two possible motivating factors. Obviously, both are double-edged swords. Should a trial not turn out as hoped, celebrity can instantly turn to notoriety. With respect to fortune, administrative and clinical activity performed by the principal investigator on behalf of the clinical trial does not generate income, and, in fact, can place a considerable financial drain on the investigator's department. I believe that investigators are strongly driven by intellectual curiosity, but it is important to maintain perspective when participating in a clinical trial. The real reason we seek clinical trial site designation is to allow us to offer new, innovative therapeutic modalities to our patients. By so doing, it is imperative that we conduct the clinical trial in as thoughtful and as safe a manner as possible, with our patients' well being always foremost in our minds.

In vivo demonstration of cavitation potential of a mechanical heart valve.

Cavitation is implicated as the cause of pitting and erosion of explanted mechanical heart valves that failed. Previous in vitro studies demonstrated transient negative pressure spikes upstream of mechanical heart valves at the instant of leaflet closure. When the magnitude of the transient negative pressure spike is below the vapor pressure of the fluid flowing across the mechanical valve, cavitation bubbles have been documented near the valve housing or occluder disc. To test for the presence of transient negative pressure spikes that are conducive to cavitation in vivo, we measured left atrial pressure at the valve orifice after mitral valve replacement. Mitral valves were replaced with 27 mm prostheses in 10 goats (50-60 kg). Control animals (Group 1, n = 5) received pericardial valves. Study animals (Group 2, n = 5) received bileaflet pyrolytic carbon valves. Pressure was recorded from a high frequency atrial transducer at hyperdynamic and hypodynamic states. Transient negative pressure spikes did not occur in any Group 1 animal. Transient negative pressure spikes below the vapor pressure of blood (-713 mm Hg) were recorded in four of five Group 2 animals at the hyperdynamic state: -900, -950, -800, -400, and -1,400 mm Hg (p = 0.048 Group 1 versus Group 2, Fisher's exact test). No cavitation potential exists in vivo after bioprosthetic valve implantation. Transient negative pressure spikes below the vapor pressure of blood occur in vivo at hyperdynamic physiologic states when this bileaflet pyrolytic carbon valve is implanted in the mitral position. These studies demonstrate the potential for cavitation with implanted mechanical valves in vivo.

Time course of cytokine release and complement activation after implantation of the HeartMate left ventricular assist device.

Pro-inflammatory mediators, including interleukin-6 (IL-6), IL-8, and complement C3a, are released after cardiac surgery as part of the inflammatory response related to blood-biomaterial interaction in the cardiopulmonary bypass circuit. Post operative time course data for these mediators are not fully defined in patients receiving left ventricular assist device (LVAD) support. The authors performed enzyme linked immunosorbent assays for concentrations of IL-6, IL-8, and C3a in plasma in six HeartMate LVAD recipients at the following times: pre operatively; 4, 8, 16, 24, 36, and 48 hr post operatively; daily through the first week; and weekly thereafter for 6 weeks. All patients survived without major complications during the study. Pre operative concentrations of IL-6 and C3a in plasma were significantly increased compared with age matched controls. Post operatively, the concentrations of IL-6 and IL-8 in plasma took longer to return to baseline values after insertion of the LVAD than the trends reported in the literature after routine cardiopulmonary bypass alone. Concentrations of IL-6 and complement C3a continued to decrease to lower than baseline post operatively, reaching statistical significance after 6 weeks of LVAD support. The authors conclude that the presence of the HeartMate LVAD delays the return of pro-inflammatory mediator concentrations back to baseline values compared with routine cardiopulmonary bypass alone, but the device does not appear to be an ongoing source of cytokine release or complement activation.

Negative pressure transients with mechanical heart-valve closure: correlation between in vitro and in vivo results.

Negative pressure transients (NPT) recorded in a single closing event of mechanical valves in the mitral position in an in vitro setup are compared with data recorded in the left atrium in vivo with the valves implanted in the mitral position in an animal model. The loading at valve closure (dP/dtCL) computed from the in vivo ventricular pressure recording (ranging from 700 to 2300 mm Hg/s) agreed with the magnitudes predicted in our earlier in vitro experiments (750-3000 mm Hg/s). The NPT signals and the corresponding power spectral density plots from the in vivo data were in qualitative agreement with those recorded in vitro. The NPT magnitudes were found to be below the vapor pressure for blood in mechanical valves with rigid occluders suggesting a potential for the valve to cavitate in vivo. Our in vivo results also suggest that the valves with flexible occluders are less likely to cavitate. The correlation of the in vitro and in vivo data also suggests that the flexibility of valve housing used in the in vitro studies is not an important factor in the dynamics of mechanical valve closure in vivo.

Reversal of renal failure and paraplegia after thoracoabdominal aneurysm repair.

Repair of ruptured thoracoabdominal aortic aneurysms is complicated by high rates of perioperative paraplegia, renal insufficiency, and mortality. This report describes a patient with a ruptured thoracoabdominal aortic aneurysm in whom preoperative acute renal failure was reversed with hemodialysis, aortic replacement, and renal revascularization. Prompt cerebrospinal fluid drainage reversed delayed-onset postoperative paraplegia and led to immediate, complete neurologic recovery.

Clinical evaluation of a new in-line continuous blood gas monitor.

Two methodologies for obtaining accurate blood gas and electrolyte values during cardiopulmonary bypass (CPB) are traditional laboratory analyzers, which use an electrochemical technology, and continuous in-line monitoring systems, which use a fluorometric and/or spectrophotometric technology. The purpose of the present study was to evaluate the accuracy of a new continuous in-line monitor, the 3M CDI Blood Parameter Monitoring System 500, which provides continuous in-line measurements of pH, PCO2, PO2, potassium (K+), oxygen saturation, hematocrit, hemoglobin, and temperature, during partial or complete CPB. Study parameters included arterial pH, PCO2, PO2, and K+ values. Overall performance was analyzed by calculating the mean difference (expressed as the bias) between the CDI system 500 and the laboratory analyzer for each parameter. The accuracy of the arterial pH, PCO2, and K+ values provided by the CDI system 500 was then evaluated using target values established in the acceptable performance standards for laboratory analyzers from the Clinical Laboratory Improvement Act of 1988 (CLIA '88). The accuracy of the PO2 value provided by the CDI system 500 was evaluated using a target value of +/- 10% of the reference, or laboratory analyzer, value. A prospective multi-center trial was conducted following Institutional Review Board approval. A total of 75 cases was included in the analyses, with over 200 data points from 4 clinical locations. Results for pH, PCO2, and K+ were within the target values established by CLIA '88. pH bias was 0.00 +/- 0.02 pH units. PCO2 bias was -0.3 +/- 3.3 mm Hg. K+ bias was approximately +0.12 +/- 0.31 mmole/l. Results for PO2 were within 10% of the reference value. PO2 bias was 7.5 +/- 13.8 mm Hg. The results of this clinical trial show that the CDI System 500 continuous in-line monitoring system provides values that meet the accuracy standards for laboratory analyzers for arterial pH, PCO2, PO2, and K+.

The clamshell incision provides adequate exposure for aortic valve replacement and coronary revascularization.

The standard median sternotomy provides ready access to all surfaces of the heart and the ascending aorta. When cosmetic considerations, associated medical conditions, such as an esophageal stoma, or tracheostomy preclude use of the median sternotomy, a bilateral transverse sternotomy will provide excellent exposure of the entire ascending aorta and the lateral and inferior walls of the heart.

Lobar pulmonary edema due to mitral regurgitation: diagnosis by echocardiography.

One etiology of unilateral lobar pulmonary edema is mitral regurgitation. Echocardiography is able to demonstrate the retrograde flow of blood into the pulmonary veins and allows timely diagnosis and treatment planning. Correction of mitral regurgitation is followed by resolution of the radiographic abnormality.

Cannula selection and cannulation techniques for nonpulsatile mechanical ventricular assistance.

The successful use of mechanical ventricular assistance is, in large part, dependent upon easy insertion of well designed inflow and outflow cannulas. This manuscript describes a family of cannulas specifically designed for use in a nonpulsatile ventricular assist device (VAD) circuit. Although a variety of commercially available cannulas can be employed in a nonpulsatile VAD circuit, the cannulas described in this manuscript possess a number of unique design features. The reinforced thin-walled design and end hole construction optimize fluid flow characteristics in both the inflow and outflow cannula. The extended length allows the cannulas to transverse the skin at a point far distant from the mediastinum, reducing the potential for ascending cannula site infection. The purpose of this manuscript is not to review all cannulas available for nonpulsatile VAD circuits, but rather to describe in detail a family of cannulas that are ideal VAD cannulas based on their design characteristics. In addition individual cardiac surgeons implant very few of these devices annually. Thus the advantages and disadvantages of common cannulation sites and a proven technique for cannula insertion will also be presented.

Mediastinitis in heart transplantation.

Between March 1985 and December 1991, mediastinitis developed in 12 of 420 cardiac transplantation patients (2.8%). The mortality rate in this group of patients was 8.3% (1/12). Actuarial survival (1 year, 75%; and 5 years, 65%) was not significantly different from that of the group without mediastinitis (1 year, 88%; and 5 years, 75%). A higher percentage of the patients in the group with mediastinitis were listed as UNOS status 1 (50% versus 35%) and had a history of previous sternotomies (58% versus 44%). The presentation of mediastinitis was typical. Computed tomographic scanning with or without aspiration was a valuable adjunct in the diagnosis of mediastinitis. Induction immunotherapy with minimal steroids in the perioperative period was used in all patients. This may contribute to the patients' ability to mount an appropriate and effective response to infection, permitting earlier diagnosis. The debridement irrigation technique used in 8 of 12 patients had a low success rate of 33%, whereas the debridement muscle flap technique used in 4 of 12 was 100% successful in eliminating infection.

Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation.

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.

Outcome of cardiac transplant recipients with a positive donor-specific crossmatch--preliminary results with plasmapheresis.

To assess the influence of a positive T or B cell IgG crossmatch on the development of rejection and mortality following cardiac transplantation, we reviewed all cardiac transplants performed in Utah between March 1985 and October 1990. Of the 328 cardiac allograft recipients, 11 (3.4%) had an IgG positive crossmatch. Actuarial survival at 24 months in the positive crossmatch group was 57.3% +/- 0.02 while that of the controls was 86.1% +/- 2.1 (P < 0.05). Allograft rejection occurred earlier in recipients with a positive crossmatch (10.0 +/- 5.8 days versus 34.0 +/- 2.3 days, P < 0.001). The first allograft rejection episode in patients with a positive crossmatch was characterized by immunoglobulin and complement deposition in small blood vessels and interstitial edema and endothelial cell activation in the absence of a lymphocytic infiltrate. Furthermore, the allograft rejection in the positive crossmatch group was accompanied by hemodynamic compromise in a large proportion of the patients (73%). In addition to augmentation of immunosuppression, plasma exchange therapy was performed within the first week following transplantation in 8 of the 11 positive crossmatch patients. Survival in the patients treated with plasma exchange (75%) appears to be better than in those not receiving plasma exchange (33%) within one week of transplantation. While immunosuppressive therapy aimed at the humoral arm of the immune system and plasma exchange therapy may improve survival in recipients with a positive donor-specific crossmatch, survival is worse in patients with a positive crossmatch than in patients with a negative crossmatch. Thus, it would appear prudent to prospectively crossmatch cardiac transplant candidates with a greater risk of developing a positive crossmatch, such as those potential recipients with an elevated level of panel-reactive antibodies.

Perioperative mechanical circulatory support for transplantation.

Mechanical circulatory assistance has become a necessary supplement to more conventional means of hemodynamic support as a shortage of donor organs and associated increase in waiting time have contributed to an increased incidence of hemodynamic deterioration in potential transplant recipients. This review summarizes the experience with circulatory support before and after transplantation of the Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program and draws conclusions on the efficacy of one program's use of mechanical circulatory support. Between March 1985 and October 1990, 401 patients were accepted for first-time heart transplantation by the UTAH program. One hundred and eighty patients (46%) were supported before transplantation with conventional hemodynamic therapies, 72 patients (18%) with oral enoximone, 96 patients (25%) with intravenous inotropes, and 34 patients (9%) with an intraaortic balloon; nine patients (2%) required centrifugal blood pump circulatory support. Not included in these statistics are 10 patients awaiting transplantation as of October 10, 1990. Thirty-eight candidates (10%) died awaiting transplantation, 329 (84%) received transplantation, and 24 (6%) were removed from the transplantation list for other reasons. Ten patients (3%) required mechanical circulatory support after transplantation with 38% of this group surviving 1 year after after transplantation. No single factor, including either hemodynamic support before transplantation or donor heart ischemic time, was found to be predictive of the need for mechanical circulatory support after transplantation. One-year survival rates after transplantation of patients requiring mechanical circulatory support before transplantation (86%) were not significantly different than for all transplant patients (88%). The experience of the UTAH Cardiac Transplant Program shows that with the judicious use of mechanical circulatory support transplant patients with advanced forms of hemodynamic support can have as equal a probability of survival as patients who undergo elective transplantation.

Cardiac transplantation in a patient with a single ventricle and transposition of the great vessels.

The technical details of orthotopic cardiac transplantation in a 17-year-old man with a single ventricle and transposition of the great vessels are described. Special considerations in the evaluation and management of patients with complex congenital heart disease who are to undergo cardiac transplantation are delineated.