We screened a compendium of gene profiles from 19 paired human heart samples harvested at the time of implant and explant of a left ventricular assist device (LVAD) for novel genes regulating the Ras/MEK/ERK cascade. From this analysis we identified Sprouty1, an evolutionally conserved gene that acts as an intrinsic inhibitor of the Ras/MEK/ERK pathway. Sprouty1 mRNA and protein were significantly upregulated in the heart in response to mechanical unloading with a LVAD. The upregulation of Sprouty1 in the heart following mechanical unloading was accompanied by a significant decrease in phosphorylated ERK1/2. Gain of function experiments demonstrated that upregulation of Sprouty1 in isolated cardiac myocytes led to a significant decrease and altered kinetics of ERK1/2 phosphorylation. Immunohistochemistry of human hearts revealed that Sprouty1 was also expressed in the microvasculature. Upregulation of Sprouty1 in endothelial cells led to a significant decrease in VEGF-induced endothelial cell proliferation. To our knowledge, these findings are the first to define Sprouty expression in the heart and suggest that Sprouty1 may serve as an intrinsic mediator governing ventricular remodeling through a coordinated coupling of both myocyte and vascular alterations in response to mechanical load.

Mechanical unloading of the heart with a left ventricular assist device (LVAD) significantly decreases mortality in patients with heart failure. Moreover, it provides a human model to define the critical regulatory genes governing myocardial remodeling in response to significant reductions in wall stress. Statistical analysis of a gene expression library of 19 paired human heart samples harvested at the time of LVAD implant and again at explant revealed a set of 22 genes that were downregulated and 85 genes that were upregulated in response to mechanical unloading with a false discovery rate of less than 1%. The analysis revealed a high percentage of genes involved in the regulation of vascular networks including neuropilin-1 ( a VEGF receptor), FGF9, Sprouty1, stromal-derived factor 1, and endomucin. Taken together these findings suggest that mechanical unloading alters the regulation of vascular organization and migration in the heart. In addition to vascular signaling networks, GATA-4 binding protein, a critical mediator of myocyte hypertrophy, was significantly downregulated following mechanical unloading. In summary, these findings may have important implications for defining the role of mechanical stretch and load on autocrine/paracrine signals directing vascular organization in the failing human heart and the role of GATA-4 in orchestrating reverse myocardial remodeling. This unbiased gene discovery approach in paired human heart samples has the potential to provide critical clues to the next generation of therapeutic treatments aimed at heart failure.

With the advent of implanting ventricular assist devices (VAD) as destination therapy, maximum limits of device durability will be identified as clinical results succeed in providing long term survival. This is one center's experience with long term Thoratec Heartmate VAD usage and the necessity for device change-out(DCO). Between January 1, 2000 and December 31, 2002, 58 patients underwent implantation of the Heartmate LVAD. 8 implants were a part of the REMATCH trial and 50 were bridge to transplantation. 9 patients required DCO for device failure. 4 patients required a second DCO. Inflow valve dysfunction was the etiology in 7 devices, motor malfunction in 4 devices, and infection in 2. The 30 day mortality was 8.6% (5/58) after first implant, 22.2% (2/9) after first DCO, and 0% (0/4) after second DCO. The mean implant to failure time was 332 days (range: 15–632 days). Mean time to failure of the inflow valve was 408 days (range: 240–632). Mean time to failure of motor malfunction was 285 days (range: 15–439). One patient that had change-out for infection died within 30 days and the second survived to successful transplantation. Of 50 bridge to transplant patients, the longest implant free of device failure was 681days. 6 of the 8 REMATCH patients were > 30-day survivors and all 6 had DCOs. Three had a second DCO. All 6 were long-term survivors. Based on clinical input, the manufacturer made technological changes, which greatly enhanced the durability. All 7 inflow valve failures were in the original VE series, with no such failures with the newer XVE series.

Introduction: Pulmonary hypertension (PHTN) is often a complicating feature of heart disease and when fixed, can exclude patients from transplant. As pulmonary vascular resistance (PVR) increases, there is a linear increase in operative risk. Traditionally, nitroprusside is used to assess reversibility of pulmonary pressures, however response and tolerance to nitroprusside are variable. We report the use of nesiritide to assess reversibility of pulmonary pressures in patients being evaluated for cardiac transplant. Methods: A retrospective analysis of transplant candidates with PHTN was undertaken at our institution. Between 2002–2004, six patients received nesiritide to assess reversibility of PHTN. The etiology of heart failure was ischemic heart disease in 4 patients, dilated cardiomyopathy in 1, and valvular in 1 patient. The mean pulmonary artery systolic pressure (PASP) was 62.7 mm Hg ( range 52–74 mm Hg), pulmonary artery diastolic pressure (PADP) 28.2 mm Hg (range 19–40 mm Hg), and PA mean 40.4 mm Hg (range 28–52 mm Hg). Mean transpulmonary gradient (TPG) was 15.6 mm Hg (10–20 mm Hg) and mean PVR was 3.72 units (1.73–7.41 units). Results: Nesiritide was infused at a mean dose of 0.018 mcg/kg/min for an average of 13.3 days (5–38 days). The mean PASP decreased by 50.2% to 31.2 mm Hg (range 24–45 mm Hg), PADP by 54% (mean 13 mm Hg, 5–20 mm Hg), PA mean by 49% (20.55 mm Hg,14–28.3 mm Hg), TPG by 49% (8 mm Hg, 0–17 mm Hg), and PVR by 55% (1.67 units, 1.3–2.3 units). Four patients have undergone successful heart transplantation, one directly and 3 following LVAD as bridge therapy. Two patients presently have an LVAD as bridge to transplant. Of the patients who underwent LVAD implantation, one had recurrent pulmonary hypertension following LVAD implant which resolved following continued nesiritide infusion. Transplant was performed successfully in this patient. No patient had RV failure perioperatively following LVAD or transplant, and none required RVAD. Conclusion: In our experience, nesiritide is effective in reversing PHTN in patients being evaluated for transplant. Reversibility of PHTN with nesiritide is associated with successful transplantation with absence oF RV failure and need for RVAD perioperatively.

Purpose: The overall survival rate of patients who present with acute myocardial infarction (AMI) has improved over the years. Yet some of patients face exceedingly high mortality, in excess of 50%, when AMI is associated with cardiogenic shock. We hypothesize that left ventricular assist device (LVAD) implantation in this high risk population could improve their survival.

Background: Ventricular assist devices (VAD) are widely used as bridge to transplant and have recently been approved as destination therapy in patients who are not transplant candidates. There is substantial data to suggest that support with a VAD may lead to recovery of myocyte function, however there is limited data on recovery of left ventricular (LV) function sufficient to allow successful device removal. We report 7 patients who, following LVAD support, recovered LV function and were able to undergo successful explant of the device.

HeartMate XVE LVAD was developed based on the modifications from the previous VE type. It was aimed to prolong the lifespan of the device especially the inflow valve. However the clinical data to compare the performance of these two types of LVAD is limited. In this study we compared the device related complications between the two devices. Methods: Between 1998 and 2003, thirty-two HeartMate VE and 47 XVE LVADs were implanted in 32 and 41 patients respectively as a “bridge” to transplantation. In order to evaluate the true impact of the devices we excluded those who developed early postoperative neurological complication and/or died of multi-organ failure within the first 2 weeks after implantation and those who received the 2nd or 3rd device. A total of 30 VE and 33 XVE patients met the criteria of study. The length of device implantation and device related complications were compared. RESULTS: it-test and Fisher test were used)TableConclusions: Though not statistically significant due to relatively small numbers, the expected advantages from XVE such as prolonged motor and valve performance have not been shown when compared with VE. There seems to have increased risk of device related complications, mostly infection in the XVE LVAD.

BackgroundThe HeartMate vented electric left ventricular assist device has been approved for use as destination therapy. Thus, the study of quality-of-life outcomes, as well as morbidity and mortality, is imperative. The purpose of our study was to describe change with time (from 1 month to 1 year) in patients who received a HeartMate vented electric left ventricular assist device as a bridge to heart transplantation and to identify quality-of-life predictors of survival after left ventricular assist device implantation.MethodsA nonrandom sample of 78 patients who received a HeartMate vented electric left ventricular assist device (primarily middle-aged, white married males) who had quality-of-life data at 1, 2, 3, 6, 9, or 12 months after implant was the subject of this report. The sample size decreased with time primarily because of heart transplantation. Patients completed the following booklets of questionnaires: Quality of Life Index, Rating Question Form, Heart Failure Symptom Checklist, and Sickness Impact Profile. Analyses included both descriptive analyses and modeling procedures (mixed-effects models and Cox proportional hazards models).ResultsQuality-of-life outcomes were fairly good and stable from 1 month to 1 year after HeartMate vented electric left ventricular assist device implantation. Both positive and negative changes were detected in all quality-of-life domains (physical and occupational function, social interaction, somatic sensation, and psychological state) after left ventricular assist device insertion. Items from the physical domain of quality of life, specifically walking and dressing oneself, were significantly associated with the risk of dying after left ventricular assist device implantation.ConclusionsIdentifying poor quality-of-life outcomes within 1 year after left ventricular assist device implantation provides direction to develop strategies to improve outcomes. Physical and occupational rehabilitation, psychosocial intervention, and monitoring symptom distress and physical disability may contribute to improved quality-of-life outcomes and survival after left ventricular assist device implantation.

This report describes 2 patients with an aortic bioprosthesis. Both patients developed total thrombotic occlusion of the sub-aortic left ventricular outflow tract consequent to insertion of a left ventricular assist device (LVAD). Replacing a mechanical valve with a bioprosthesis in patients receiving a left ventricular assist device offers no additional protection against thrombosis of the aortic prosthesis. Pericardial patching below the aortic prosthesis at the time of LVAD implantation may be performed, but will significantly impede or prohibit the native ventricle from ejecting blood and demonstrating any degree of recovery.

Purpose: Patients with profound heart failure unresponsive to medical therapy may require ventricular assist devices as a bridge therapy to heart transplantation, and survival benefit of such device therapy has been well established. However, RV failure requiring RVAD or prolonged inotropic support (>14 days) following LVAD implant compromised patient outcome. We have reviewed our incidence of RV failure and preventive therapeutic options.

Left ventricular assist devices unload the left ventricle and decrease left atrial pressure. This hemodynamic change may cause a right to left atrial shunt and hypoxemia in patients with patent foramen ovale. We prospectively studied the best time for performing diagnostic transesophageal echocardiography in left ventricular assist device patients. Intraoperative transesophageal echocardiography was performed in 14 patients before cardiopulmonary bypass was initiated and after left ventricular assist device was implanted. No patent foramen ovale was detected when transesophageal echocardiography was done before bypass, but a patent foramen ovale was found in 3 patients when transesophageal echocardiography was performed after left ventricular assist device was activated. Patent foramen ovale was confirmed by inspection in all three patients and surgically closed during the same procedure. There were no patent foramen ovale closure-related complications.

OBJECTIVESTo describe quality-of-life outcomes; determine relationships between quality of life and demographic, physical, psychosocial, and clinical variables; and identify predictors of quality of life at 1 month after implantation of a left ventricular assist device.METHODSPatients who received either an implantable pneumatic (n = 38) or a vented electric (n = 54) left ventricular assist device as a bridge to heart transplantation between August 1, 1994, and August 31, 1999, completed 6 instruments used to measure quality of life andfactors related to quality of life. Data were analyzed by using descriptive statistics, Pearson correlations, Mann-Whitney U tests, and forward, stepwise multiple regression.RESULTSOverall satisfaction with quality of life was quite high as determined from the total score on the Quality of Life Index (mean = 0.69). Patients were very satisfied with the implantation and thought that they would do well after future heart transplant surgery. Patients had a moderate level of stress. Significant predictors of overall quality of life were psychological symptoms, stress, and race; these accounted for 46% of variance in quality of life.CONCLUSIONSPatients were satisfied with their quality of life at 1 month after implantation of a left ventricular assist device. However, they were least satisfied with their health and functioning and yet were optimistic about how well they thought they would do after heart transplantation. Psychological factors were the strongest predictors of satisfaction with overall quality of life.

Background: Cardiogenic shock is the leading cause of death in patients hospitalized for acute myocardial infarction (AMI). Recent SHOCK trial demonstrated exceedingly high 30 days mortality for this group. Current treatment modalities remain suboptimal. We examined the role of ventricular assist device (VAD) in this high-risk population.

During the past decade, patients with implanted left ventricular assist devices (VADs) began to leave the hospital environment under Food and Drug Administration (FDA) sponsored Investigational Device Exemption trials. These trials culminated in the approval of two VADs (HeartMate VE [Thoratec Laboratories, Inc., Pleasanton, CA] and Novacor [World Heart Corporation, Ottawa, Ontario, Canada) for use in out-patients as a bridge to cardiac transplantation. A variety of other new assist devices, including axial flow VADs and total artificial hearts, are now entering out-patient trials as a bridge to cardiac transplantation or as a permanent implant. 1–3 Out-patient programs have been designed according to the needs and requirements of each participating center. In general they follow examples provided by the FDA sponsored out-patient trial designs and the information published from individual programs. 4–13 However, there has not yet been a national symposium to present the details of administering an out-patient VAD program. The purpose of this symposium was to present information on various aspects of out-patient VAD management, followed by a question and discussion period. Symposium participants were from centers with active out-patient VAD programs (the University of Iowa [Dr. Richenbacher and Ms. Seemuth], the University of Minnesota [Ms. Ormaza], Pennsylvania State University [Dr. Boehmer], and the University of Alabama at Birmingham [Dr. Holman]). A review of out-patient VAD programs indicates that roughly 40% to 60% of patients with implanted left VADs pending cardiac transplantation are discharged. However, at the University of Iowa 12/14 bridge to transplant patients were discharged during the past two years. 14 An 86% discharge rate may too high to set as a benchmark for all bridge to transplant programs, but it does serve as an example of what can be achieved with appropriate patient selection and an education program that is highly focused on returning patients to their homes. The importance of the Iowa experience is that similar rates of discharge will be necessary, together with a low re-admission rate, to justify the use of VADs as permanent implants. Training of the patient and their care givers was the subject of a presentation from the University of Minnesota. Their approach incorporates early initiation of education (preimplant or immediate postimplant) to minimize the duration of postimplant hospitalization. The goals of their program are to provide the information necessary for successful out-patient existence together with counseling that reduces apprehension of the patient and his or her support group. An interesting aspect of the Minnesota program is its attention to the patient’s neuropsychiatric status, including stress management and assessment of postimplant cognitive function. A program for patient and care giver education was outlined that can be completed in 7 days and includes 1:1 instruction reinforced with computer-based self-examination. The computer-based module was developed by Thoratec [Thoratec Laboratories, Inc; Pleasanton, California; USA] as a CD-ROM explaining use of the HeartMate VE system. Other details of educating the community health care and utility providers for the in-patient to out-patient transition were discussed. 15 At the University of Iowa, letters are sent to the power and phone providers to notify them of the patient’s need for these services, and to request high priority for service in the event of an outage. It was noted in the discussion that power and phone providers (depending on location) may be under no legal obligation to provide this coverage. Thus, alternative plans for managing outages must be formulated if the providers are unwilling to give the VAD patient living at home top priority for restoring service in the event of an outage. Other providers included in the educational effort include: local physicians and dentists, emergency medical service (EMS) personnel, physical therapists, emergency room (ER) staff and transport personnel, friends and relatives, visiting nurses, employers, and educational facility personnel (e.g., school nurses). This level of education requires a large commitment from university based personnel. At the University of Iowa this is largely the responsibility of the VAD coordinator, Kate Seemuth, R.N., M.S.N. 15 The discussion brought up several problems facing out-patient VAD programs and questions regarding the details of designing these programs. The training of local EMS and ER personnel is problematic because incomplete attendance at training sessions and staff turnover make it possible for a patient with an urgent problem to encounter EMS or ER personnel who are unfamiliar with VADs. The approach to this problem at other centers has been to supply these providers with videotaped presentations that can be used repeatedly (University of Alabama at Birmingham) or computer-based distance learning courses (University of Iowa) that can be taken at any time of the day or night. Training the patient and their family to direct the actions of EMS and ER personnel in collaboration with personnel at the implant center is another approach that was advocated by several centers. An informal survey of attendees at the meeting indicated that restrictions on out-patient activity are easing as experience with out-patient VAD therapy increases. This includes, most notably, allowing patients to live at increasing distances from the implant center, and allowing the patient to spend periods of time without a trained care giver within sight or earshot. The patient is provided with a cell phone or other communication device, and plans are made for immediate response in the event of an emergency. The experience of automatic cardioverter-defibrillator patients provides a useful precedent for developing strategies to give progressively greater freedom to VAD patients. There was general agreement that VAD patients should begin out-patient life with weekly visits to clinic. If this goes well, most centers lengthen the time between clinic visits to 1 month. Procuring funds to supply out-patients with disposable items (e.g., vent filters and dressing supplies) remains an unresolved problem for many programs. The use of day trips and overnight visits as a prelude to full discharge is embraced by many centers, but this is not universal. Several VAD-related problems, including infection of percutaneous drive line sites and inflow valve disruption in the HeartMate VE left VAD have been successfully managed, at least for periods of time, in patients at great distances from the implant center. The safe limits to such out-patient therapy have not yet been clearly defined. Out-patient therapy has progressed from investigational status to an accepted component of VAD support for patients bridged to transplantation. The details of running such a program vary from center to center, partly in response to local conditions and partly because of incomplete information regarding the optimal approach. The major challenge facing out-patient VAD therapy at the present time is managing patients with permanently implanted devices.

Background No studies have analyzed quality of life (QOL) from before to after heart transplantation in patients with a left ventricular assist device (LVAD). Therefore, the purpose of this longitudinal, multi-site study was to compare QOL outcomes of patients listed for heart transplantation who required a left ventricular assist device (LVAD) at 3 months after implantation of an LVAD vs 3 months after heart transplantation. Methods A non-random sample of 40 patients (predominantly middle-aged, married, white men), who had paired data at both 3 months after LVAD implantation and 3 months after heart transplantation, were investigated. Patients completed self-report questionnaires (with acceptable reliability and validity) at both time periods, including the Quality of Life Index, Rating Question Form, Heart Failure Symptom Checklist, Sickness Impact Profile, LVAD Stressor Scale (completed only after LVAD implant), Heart Transplant Stressor Scale (completed only after heart transplant) and Jalowiec Coping Scale. Descriptive analyses and comparative analyses using paired t-tests were performed with statistical significance set at 0.01. Results Patients were significantly more satisfied with their lives overall and with their health and functioning at 3 months after heart transplantation as compared with 3 months after LVAD implantation. Mobility, self-care ability, physical ability and overall functional ability improved from 3 months after LVAD implant to 3 months after heart transplant. There was significantly less symptom distress after LVAD implant as compared with after heart transplant for the neurologic, dermatologic and physical sub-scales. Work/school/financial stress was significantly lower after heart transplant vs after LVAD implant. In contrast, 2 other areas of stress were significantly lower after LVAD implant vs after heart transplant: self-care stress and hospital/clinic-related stress. Conclusions Differences were found in QOL outcomes at 3 months after LVAD implant as compared with 3 months after heart transplant. Our findings point out specific areas of concern with respect to QOL after LVAD implant and post-transplant, some of which are amenable to health-care provider interventions.

BACKGROUND. Severe pulmonary hypertension (PHT) from end-stage left ventricular (LV) failure that is unresponsive to medical therapy is an absolute contraindication for orthotopic heart transplantation. Pulmonary venous congestion has been shown to be an important determinant of systolic PHT. We hypothesized that left ventricular assist device (LVAD) bridge therapy to heart transplant may reverse pulmonary venous congestion, and thus allows these patients to become suitable transplant candidates.

BACKGROUND:The successful use of left ventricular assist devices (LVADs) as a bridge to heart transplantation has prompted our examination of quality of life (QOL) outcomes. The purposes of this study are to describe QOL in patients 1 to 2 weeks after LVAD implantation and to compare QOL in a smaller cohort of patients from before to 1 to 2 weeks after surgery.METHODS:Data were collected from a convenience sample of 81 patients who completed booklets of questionnaires that measure domains of QOL 1 to 2 weeks after LVAD insertion and from 30 of 81 patients who completed booklets at both the pre-implantation and post-implantation periods. Patients completed booklets of 6 to 8 self-reporting instruments, with acceptable reliability and validity. Data were analyzed using descriptive and comparative statistics (chi-square, Mann-Whitney U and Wilcoxon signed ranks tests) with p = 0.01 considered statistically significant.RESULTS:One to 2 weeks after LVAD implantation, patients were quite satisfied with their lives, experienced moderately low amounts of stress, coped well, and perceived themselves as having good health and QOL, low symptom distress, and moderately low functional disability. Patients reported significantly better QOL, more satisfaction with health and functioning, and were significantly less distressed by symptoms from immediately pre-operatively to post-operatively. However, patients reported significantly more self-care disability and more dissatisfaction with socioeconomic areas of life from before to immediately after surgery. Psychological distress was low and did not change with time.CONCLUSION:Given that QOL improved from before to after LVAD implantation, our findings provide a springboard for investigation of the impact of LVADs on long-term QOL outcomes.