Gender differences in the long-term outcomes after valve replacement surgery.

OBJECTIVE: To compare the long-term outcomes in women and men after valve replacement surgery. DESIGN: Observational study. SETTING: Postoperative aortic valve replacement (AVR) or mitral valve replacement (MVR). PATIENTS: 3118 patients (1261 women, 1857 men) who underwent AVR or MVR between 1976 and 2006 (2255 AVR, 863 MVR), with mean follow-up of 5.6 (4.5) years. MAIN OUTCOME MEASURES: The independent effect of gender on the risk of long-term complications (reoperation, stroke and death) after valve replacement surgery using multivariate actuarial methods. RESULTS: After implantation of an aortic valve bioprosthesis, women had a significantly lower rate of reoperation compared to men (comorbidity-adjusted hazard ratio (HR) 0.4; 95% confidence intervals (CI) 0.2 to 0.9). In contrast, if an aortic mechanical prosthesis had been implanted, women were more at risk for late stroke compared to men (HR 1.7; CI 1.1 to 2.7). After adjustment for age and co-morbidities, women had significantly better long-term survival compared to men after bioprosthetic AVR (HR 0.5; CI 0.3 to 0.6), but there was no survival difference between genders after mechanical AVR. Trends existed towards better survival for women after bioprosthetic MVR (HR 0.6; CI 0.4 to 1.0) and mechanical MVR (HR 0.8; CI 0.5 to 1.1). CONCLUSION: The long-term outcomes after valve replacement surgery differ between women and men. Although women have more late strokes after valve replacement, they undergo fewer reoperations and have better overall long-term survival compared to men.

Assessment of cyclosporine pharmacokinetic parameters to facilitate conversion from C0 to C2 monitoring in heart transplant recipients.

BACKGROUND: Cyclosporine (CsA) 2-hour postdose (C2) monitoring is recommended to assess CsA exposure and predict clinical outcomes among heart transplant recipients. We correlated pharmacokinetic parameters and clinical outcomes in stable long-term heart transplant recipients monitored with C0 to develop an algorithm to convert patients from C0 to C2 monitoring. METHODS: Paired CsA C0-C2 measurements and serum creatinine levels were obtained from 35 heart transplant recipients more than 2 years posttransplantation (mean 8.8+/-4.7 years). RESULTS: The mean CsA dose and C0, C2, and C0/C2 ratio were 85+/-23 mg/12 hours, 123+/-41 ng/mL, 572+/-274 ng/mL and 4.8+/-2.1, respectively. C0 correlated weakly with C2 (r=.42, P=.011). The CsA dose correlated better with C2 (r=.58; P<.001) than with C0 (r=.37; P=.026). A good correlation was noted between C2 and the C2/C0 ratio (r=.73; P<.001), but none between C0 and the C2/C0 ratio. A borderline significant inverse correlation was noted between C0 and the worst endomyocardial biopsy score (r=-.34; P=.045), whereas none was noted with C2. Serum creatinine level did not correlate with either C2 or C0. Among patients with C0 within our target of 100 to 150 ug/L, six had C2 above 300 to 600 ug/L as suggested by the literature. CONCLUSIONS: In long-term heart transplant recipients, we could not identify a single pharmacokinetic parameter that could be used to develop an algorithm to convert from C0 to C2 monitoring; however, C2 may be better than C0 for identifying patients at risk of overexposure to CsA.

A multicenter, randomized, controlled trial of Celsior for flush and hypothermic storage of cardiac allografts.

BACKGROUND: A multicenter, randomized, controlled, open-label trial was conducted to evaluate the safety and efficacy of Celsior when used for flush and hypothermic storage of donor hearts before transplantation. METHODS: Heart transplant recipients were randomized to one of two treatment groups in which donor hearts were flushed and stored in either Celsior or conventional preservation solution(s) (control). Study subjects were followed for 30 days after transplantation. RESULTS: A total of 131 heart transplant recipients were enrolled (Celsior, n = 64; control, n = 67). The treatment groups were evenly distributed in donor and recipient base line characteristics. Graft loss rate was lower in the Celsior group on day 7 (3% versus 9%) and on day 30 (6% versus 13%), but the difference was not statistically significant based on 95% confidence interval analysis. No significant difference was measured between the Celsior and control groups in 7-day patient survival (97% versus 94%) and the proportion of patients with one or more adverse events (Celsior, 88%; control 87%) or serious adverse events (Celsior, 38%; control, 46%). Significantly fewer patients in the Celsior group developed at least one cardiac-related serious adverse event (13% versus 25%). CONCLUSIONS: Celsior was demonstrated to be as safe and effective as conventional solutions for flush and cold storage of cardiac allografts before transplantation.

The HeartSaver left ventricular assist device: an update.

BACKGROUND: Ventricular assist devices have been shown to be effective as bridges to transplantation and recovery for patients with end-stage heart failure. Current technology has been limited because of the need for percutaneous connections with controllers. The HeartSaver ventricular assist device (VAD) (World Heart Corporation, Ottawa, Ontario, Canada) was developed with the intention of having a completely implantable, portable VAD system. The system consists of an electrohydraulic blood pump, internal and external battery power, and a transcutaneous energy transfer and telemetry unit that allows for power transmission through the skin. Control of the device may be achieved locally or remotely through a variety of communication systems. METHODS: The device has been modified with the Series II preclinical version being available for in vitro (mock loop) and in vivo (bovine model) testing. RESULTS: Seventeen Series II devices have been functional on mock loops or other testing trials for an accumulated 900 days of operation. There have been eight acute experiments using a bovine model to test various components as they have become available from manufacturing. Mean pump output was 10.4 +/- 1.1 L/min in full-fill/full-eject mode. Changes in the last 24 months include (1) cannula redesign for better port alignment and integration of tissue valves; (2) battery redesign to convert to new lithium-ion cells; (3) optimized infrared information and electromagnetic inductance energy transmission through various skin thicknesses and pigmentation; and (4) improved reliability of internal and external controller hardware and software. CONCLUSIONS: Modifications have been required to optimize the HeartSaver VAD's performance. The final HeartSaver VAD design will be produced in the near future to allow for formal in vitro and in vivo testing before clinical implantation.

Circulatory support for cardiogenic shock due to acute myocardial infarction: a Canadian experience.

BACKGROUND: Cardiogenic shock due to acute myocardial infarction (AMI) is associated with high mortality. Circulatory support devices may be used to assist these patients while they await cardiac transplantation. METHODS AND RESULTS: From 1986 to 1997, 25 patients in cardiogenic shock complicating AMI within 3.6+/-0.7 days of the event were supported with artificial hearts. Of the 25 patients, 21 were men with a mean age of 48.4 +/- 1.8 years. The age range was 26 to 62 years. Patients were considered for a device when the following criteria were met: cardiac index less than 1.8 L/min/m2, wedge pressure greater than 20 mmHg despite one or two inotropes and/or intra-aortic balloon support. They received either a CardioWest total artificial heart (n=13), a Thoratec biventricular assist device (n=6) or left ventricular assist device (LVAD) (n=6). Three patients were not considered transplant candidates and died while on the devices (two with multiorgan failure and one found to have a bronchogenic carcinoma after implant), with 22 undergoing cardiac transplantation within 8.6+/-2.2 days of device implant. Six patients died in hospital after the transplants (27.3% mortality). Complications included bleeding or tamponade in seven (28%), pneumonia in six (24%) and right ventricular failure in three LVAD patients (12%). Post-transplant actuarial one-, two- and five-year survival rates were 71.4%, 71.4% and 51%, respectively. CONCLUSIONS: Circulatory support devices offer a means to maintain organ perfusion in patients who develop cardiogenic shock due to AMI. Patients can then undergo transplantation with a reasonable expectation for survival when the alternative is death. Eventually the availability of permanent support devices may obviate the need for transplant in these patients.

Progress with the HeartSaver Ventricular Assist Device.

BACKGROUND: Ventricular assist devices (VADs) have been shown to be effective for short- or long-term circulatory support. Devices are either being adapted or newly designed for longer term or permanent support, with the goal to provide patients with improved quality of life. Since 1990, a program has been in place to develop a totally implantable, permanent VAD. METHODS: A multidisciplinary team is developing this VAD with specific goals in mind: (1) that it have an intrathoracic position, (2) that it be a totally implantable device without any percutaneous connections, and (3) that it be possible to communicate with the device from remote locations. These goals would allow for complete patient mobility and flexibility for follow-up. RESULTS: The electrohydraulically actuated VAD combines the blood pump, volume displacement chamber, energy converter, and internal electronic module into a single compact unit. The device called the HeartSaver VAD is powered by a transcutaneous energy transfer system and can be remotely monitored and controlled. Prototypes of different versions of the device have been tested in vitro and in vivo with satisfactory performance. CONCLUSIONS: The prototypes of the HeartSaver VAD have functioned well under test conditions and fulfilled the outlined goals. Further development and testing of the design are being conducted before clinical availability.

Discoordinate modulation of natriuretic peptides during acute cardiac allograft rejection in humans.

BACKGROUND: Increased circulating levels of the cardiac polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) may be observed after orthotopic cardiac transplantation. Both the hypertrophic and inflammatory processes in the allograft may contribute to this increase, but no mechanistic explanation has been suggested for this observation. METHODS AND RESULTS: Plasma immunoreactive ANF and BNP determinations were performed in 10 consecutive transplant patients. These were correlated with degree of rejection as reflected by histopathological findings at serial endomyocardial biopsies. Three patients had associated hemodynamic measurements and blood samples 24 hours before and after transplantation. All rejection episodes that received treatment were accompanied by a marked increase in BNP plasma levels to > approximately 400 pg/mL. Steadily increasing BNP levels preceded overt rejection as assessed by histopathological criteria. The increase in plasma BNP was not always accompanied by an increase in ANF, which suggests the specific upregulation of BNP gene expression during acute rejection episodes. Treatment of the acute rejection episodes led to a substantial decrease of BNP plasma levels. CONCLUSIONS: The significant selective increase in plasma BNP levels found in the present study has not been previously described. This finding provides a new insight into the mechanism of allograft rejection and the modulation of natriuretic peptide synthesis and release. Furthermore, although preliminary, the data suggest that BNP plasma levels could form the basis for a new, noninvasive screening test to predict acute cardiac allograft rejection. Because treatment with the antilymphocyte monoclonal antibody OKT3 (murine monoclonal antibody to the CD3 antigen of the human T-cell) decreased BNP plasma levels, cytokine production by T-cells may mediate the selective increase in circulating BNP.

Economic analysis of outreach assessment clinics in breast screening programmes.

A model is developed for the economic evaluation of outreach assessment clinics following screening and used to identify the cost-minimizing strategy for assessing women from three island communities in the Scottish Breast Screening Programme (SBSP). There are four options of interest depending on: whether the women are assessed on the mainland or at outreach assessment clinics; and whether all women have two view screening rather than only those being screened for the first time. The benefits of outreach assessment are assumed to be solely in terms of convenience to women and reductions in the time and travel costs of women recalled for assessment. The costs are modelled in order to compare outreach and no outreach options. The results show that for the numbers of women currently screened outreach assessment is the cost-minimizing strategy. The model provides useful guidance with respect to screening policy and is readily applied to the case of outreach assessment in mainland communities outwith major population centres and to breast and other screening programmes in other countries.

Development of a ventricular assist device for out-of-hospital use.

BACKGROUND: Success with temporary ventricular assist devices, has prompted interest in devices developed for long term use outside of the hospital setting. METHODS: A totally implantable intrathoracic electro-hydraulic ventricular assist device has been developed. Design focused on providing the recipient with a near normal quality of life. To meet this goal the system utilizes transcutaneous energy transfer and biotelemetry to eliminate percutaneous drive-lines/cables as well as a displacement chamber capable of pressure equalization to atmospheric pressures, so as to eliminate the need for percutaneous venting. An implanted battery provides backup power to allow the recipient the ability to bathe, shower, or swim without connection to an external power source. An integrated telemedicine capability allows the device to be monitored/controlled remotely, using telephone lines. RESULTS: The system has been tested in vitro with early prototypes running for up to 5 1/2 years. The system was studied in calves (n = 25) with durations of support of up to 30 days, demonstrating the ability of the device to function as a totally implantable device without percutaneous connections. CONCLUSIONS: The various in vitro and in vivo studies have demonstrated the feasibility of the totally implantable device. Chronic in vivo experiments will follow in preparation for regulatory submissions for human use.

Delay in revascularization is associated with increased mortality rate in patients with severe left ventricular dysfunction and viable myocardium on fluorine 18-fluorodeoxyglucose positron emission tomography imaging.

BACKGROUND: The identification of high-risk patients who require early revascularization has become increasingly important with the present emphasis on reducing health care resources. This is particularly relevant to health care systems with prolonged waiting times for interventions. Myocardial viability imaging with the use of fluorine 18-fluorodeoxyglucose (FDG) PET may help to identify high-risk patients with severe left ventricular dysfunction. The aim of this study was to evaluate the consequences of prolonged waiting time on cardiac outcomes in patients with left ventricular dysfunction directed to revascularization based on FDG PET imaging. METHODS AND RESULTS: Forty-six patients with coronary disease and an ejection fraction of < or = 35% were considered candidates for revascularization based on FDG PET viability imaging. Thirty-five of 46 patients were subsequently accepted for revascularization. Patients were divided into 2 groups based on the median waiting time after PET: an early group (< 35 days; n = 18) and a late group (> or = 35 days; n = 17). Preoperative mortality rates were significantly increased in the late group (4 of 17 [24%] versus 0 of 18 in the early group; P < 0.05). In postoperative follow-up (17 +/- 7 months), cardiac events occurred in 2 of 18 (11%) and 1 of 13 (7.8%) patients in the early and late groups, respectively. Left ventricular ejection fraction increased after early revascularization (24 +/- 7% to 29 +/- 8%, P < 0.001, baseline versus 3 months) but not in the late group (27 +/- 5% to 28 +/- 6%, P = NS). CONCLUSIONS: Preoperative FDG PET can be used to identify a high-risk group of patients who may benefit from early revascularization. A long waiting time for revascularization is associated with a high mortality rate and suggests that early revascularization is desirable after the identification of hibernating viable myocardium.

Evaluation of porcine valves prepared by dye-mediated photooxidation.

BACKGROUND: Previous studies demonstrated that dye-mediated photooxidation can stabilize bovine pericardium. Here, photooxidized porcine valve cusp and root tissue were assessed in comparison to fresh and glutaraldehyde-treated samples. METHODS AND RESULTS: In an in vitro tissue solubility test, both photooxidized and glutaraldehyde-treated tissues were resistant to protein extraction compared to fresh tissue. A rat subcutaneous model was used to test in vivo stability and calcification potential. In this study, four of the six fresh leaflets were not visible because of resorption while both photooxidized and glutaraldehyde-treated tissues were biostable. Mineral contents of the rat explants were much lower for both fresh and photooxidized leaflets when compared with glutaraldehyde-treated leaflets. Also, the aortic root calcified whether treated or not with the most mineral being associated with glutaraldehyde-treated root. Analysis of photooxidized porcine valves explanted from the mitral position in sheep indicated a material that was biostable and contained only minor calcification, perhaps due to deformed stents. CONCLUSIONS: Porcine valve tissue treated by dye-mediated photooxidation is biostable and resistant to calcification, and has potential for use in heart valve bioprostheses.

Multi-purpose mechanical circulatory device.

A mechanical circulatory assist device for long term use outside the hospital setting has been developed. The device can be used for left, right or bi-ventricular support, and several of the developed technologies are applicable for total artificial hearts and non-pulsatile flow systems. The totally implantable device is principally designed for left ventricular support with implantation in the left hemithorax. The system utilizes transcutaneous energy and information transfer sub-systems, and has no percutaneous connections. In vitro durability testing has been conducted for periods from 1-4 years. Bovine experiments have been conducted with sustained circulation for periods form 1.5 to 96 hours. The in vitro and in vivo evaluation to date has demonstrated that the system can function effectively as a totally implantable ventricular assist device. The transcutaneous energy and information transfer sub-systems provided the ability to power, monitor and control the device, without the need for percutaneous connections. Design optimization and chronic in vivo evaluation is planned.

Preoperative and postoperative comparison of patients with univentricular and biventricular support with the thoratec ventricular assist device as a bridge to cardiac transplantation.

OBJECTIVES: The goal of this study was to determine whether there are differences in populations of patients with heart failure who require univentricular or biventricular circulatory support. METHODS: Two hundred thirteen patients who were in imminent risk of dying before donor heart procurement and who received Thoratec left (LVAD) and right (RVAD) ventricular assist devices at 35 hospitals were divided into three groups: group 1 (n = 74), patients adequately supported with isolated LVADs; group 2 (n = 37), patients initially receiving an LVAD and later requiring an RVAD; and group 3 (n = 102), patients who received biventricular assistance (BiVAD) from the beginning. RESULTS: There were no significant differences in any preoperative factors between the two BiVAD groups. In the combined BiVAD groups, pre-VAD cardiac index (BiVAD, 1.4 +/- 0.6 L/min per square meter, vs LVAD, 1.6 +/- 0.6 L/min per square meter) and pulmonary capillary wedge pressure (BiVAD, 27 +/- 8 mm Hg, vs LVAD, 30 +/- 8 mm Hg) were significantly lower than those in the LVAD group, and pre-VAD creatinine levels were significantly higher (BiVAD, 1.9 +/- 1.1 mg/dl, vs LVAD, 1.4 +/- 0.6 mg/dl). In addition, greater proportions of patients in the BiVAD groups required mechanical ventilation before VAD placement (60% vs 35%) and were implanted under emergency conditions than in the LVAD group (22% vs 9%). The survival of patients through heart transplantation was significantly better in patients who had an LVAD (74%) than in those who had BiVADs (58%). However, there were no significant differences in posttransplantation survival through hospital discharge (LVAD, 89%; BiVAD, 81%). CONCLUSION: Patients who received LVADs were less severely ill before the operation and consequently were more likely to survive after the operation. As the severity of illness increases, patients are more likely to require biventricular support.

A remotely controlled and powered artificial heart pump.

An intrathoracic pulsatile artificial heart pump has been developed. Transcutaneous energy transfer and biotelemetry systems provide continuous power and remote monitoring and control, with no percutaneous connections required. The electrohydraulic system can be used either as a ventricular assist device or with modifications as a total artificial heart. The device uses a unidirectional axial flow pump coupled with a pressure activated one-way valve to allow hydraulic fluid to passively return to the volume displacement chamber during diastole. The transcutaneous energy transfer system provides power to the device and recharges the implantable battery pack. A wearable external controller and external battery pack provide the patient enhanced mobility and thus an improved quality of life. The biotelemetry system allows control and monitoring of the device after implantation, as well as an added capability to monitor and control the device remotely over public communication lines. Early prototypes have functioned failure free for up to 3 years in vitro. The device has sustained circulation in vivo for up to 4 days. Design optimization is continuing, and chronic in vivo evaluation is planned.

Evolution of an electrohydraulic ventricular assist device through in vivo testing. The EVAD Team.

A totally implantable intrathoracic electrohydraulic ventricular assist device has been developed at the University of Ottawa Heart Institute. In vivo testing has been instrumental in its progressive development. A total of 15 experiments (4 acute, 11 performance) have been performed using male calves (62-117 kg). Data from the acute experiments, human fit trials, fluid dynamic studies, and hydraulic/energy efficiency analyses formed the basis for the development of a compact, single piece ventricular assist device called the Unified System in which the volume displacement chamber, motor, and blood chamber are housed within a compact 600 cc, 740 g unit. The performance experiments indicated that the unified system could support calves for periods up to 96 hr. The mean postoperative cardiac output was 7.1 +/- 0.7 L/ min (range = 4.9-11), mean blood pressure was 99.7 +/- 5.8 mmHg, and mean pulmonary artery pressure was 32.1 +/- 1.2 mmHg. The operative technique for intrathoracic implantation has been developed. The major problems encountered were of respiratory failure, improved by device repositioning in the calf; decreased blood inflow to the device that was improved by cannula redesign; circuit board fracture corrected by design modification; and a power supply problem that was limited to a single unit. The preliminary experiments have helped in the design modifications of the Unified System. The improved version of the system will undergo formal performance, reliability, and chronic in vivo testing before human implantation.

Chronic hypoxia induces adaptive metabolic changes in neonatal myocardium.

The effect of chronic hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic ischemia to determine high-energy phosphate levels, glycogen stores, and lactate accumulation. Time to peak ischemic myocardial contracture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/gm dry wt, p = 0.001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group. Initial energy charge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia. Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14.7 micromol/gm dry weight, p = 0.02) when compared with the control group. Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of ischemia. Time to peak ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic ischemia. These beneficial effects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis during ischemia.

Cardiac transplantation after mechanical circulatory support: a Canadian perspective.

BACKGROUND: To assess the relative efficacy of cardiac transplantation after mechanical circulatory support with a variety of support systems, we analyzed our consecutive series of patients who had and did not have mechanical support before transplantation. METHODS: A review of 209 patients undergoing cardiac transplantation from 1984 to May 1995 was performed. Group 1 consisted of 110 patients who were maintained on oral medications while awaiting transplantation, and group 2 consisted of 60 patients who required intravenous inotropic support. Group 3 included 39 patients who had transplantation after mechanical circulatory support for cardiogenic shock. The indication for device implantation was acute onset of cardiogenic shock in 38 patients and deterioration while awaiting transplantation in 1 patient. The support systems were an intraaortic balloon pump in 13 (subgroup 3A), a ventricular assist device in 7 (subgroup 3B), and a total artificial heart in 19 patients (subgroup 3C). RESULTS: After transplantation, infection was more common in group 3 (56%) than in group 1 (28%) or group 2 (32%) (p = 0.005). Survival to discharge was lower for group 3 (71.7%) than for group 1 (90.9%) or 2 (88.3%) (p = 0.009). For mechanically supported patients, survival to discharge was 84.6% in subgroup 3A, 71.4% in subgroup 3B, and 63.1% in subgroup 3C (p = not significant). CONCLUSIONS: Transplantation after mechanical support offers acceptable results in this group of patients for whom the only alternative is certain death. Patient selection and perioperative management remain the challenge to improving these results.

Right ventricular blood flow during left ventricular support in an experimental porcine model.

BACKGROUND: Right ventricular blood flow may be adversely affected during left ventricular assist device (LVAD) use leading to right ventricular (RV) ischemia and RV dysfunction. This study characterized normal RV blood flow responses to LVAD operation. METHODS: Seven Yorkshire pigs weighing 74.4 +/- 3.4 kg underwent right coronary artery blood flow measurements with an ultrasonic flow probe and injection of radiolabeled microspheres. A Thoratec LVAD was used in either synchronous or asynchronous modes and RV loading was increased using a pulmonary artery snare. RESULTS: The RV blood flow was compared between three regions that differed in proximity to the right coronary artery: proximal segment, mid-RV, and distal. The right ventricular distal flow was 0.93 +/- 0.07 mL x min-1 x g-1 compared with 0.74 +/- 0.06 mL x min-1 x g-1 at right ventricular proximal flow during control measurements (p = 0.0001). This difference was maintained during LVAD operation in either synchronous or asynchronous modes and also during pulmonary artery constriction. CONCLUSIONS: Global RV flow is not adversely affected by LVAD use. A flow gradient occurs along the right coronary artery with the distal vascular bed having relatively less reserve, which may be more susceptible to ischemia in patients with preexisting coronary disease or RV distention during LVAD use.