Current practice in patient selecting for long-term mechanical circulatory support.

With the advances of mechanical circulatory support, the selection of patients has undergone many changes over the last decade. Determining who is suitable for left ventricular assist device (LVAD) implantation is important to understanding the overall risk and outcomes. As devices improve, it is expected that changes will continue in this field. This review describes current state of patient selection, evaluation, and optimization prior to implantation of a long-term circulatory support device.

Clinical course and predictors of pericardial effusion following cardiac transplantation.

OBJECTIVE: Pericardial effusions occur frequently after orthotopic heart transplantation. There have been conflicting reports describing etiology, prognosis, and outcomes associated with these early postoperative effusions. METHODS: A retrospective review of 91 patients transplanted between January 2001 and September 2004 was performed. Pericardial effusion was defined by serial echocardiography and graded as none, small, moderate, or large. A total of 1088 echocardiograms were evaluated during the first posttransplant year. Perioperative variables were evaluated by logistic regression analysis to define predictors for occurrence of effusions. RESULTS: Echocardiographic data were available for 88 patients. Thirty-one patients (35%) developed moderate to large effusion in the immediate postoperative period. Three patients developed hemodynamic compromise that required immediate intervention. All other effusions resolved within 3 months of heart transplantation without any specific intervention. Only prolonged donor ischemic time was associated with higher risk of occurrence of moderate to large pericardial effusions (odds ratio 1.012, 95% confidence interval 1.001 to 1.019, P = .033). There was no difference in morbidity or early mortality between patients with and without pericardial effusions. CONCLUSION: Moderate to large pericardial effusions occur frequently after heart transplantation. In a vast majority, these effusions are not associated with any adverse clinical outcomes and resolve within 3 months postoperatively. Early postoperative close monitoring is still required to evaluate for tamponade.

Potential renal protective benefits of intra-operative BNP infusion during cardiac transplantation.

BACKGROUND: Recombinant BNP (nesiritide) is known to reduce endothelin levels, cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We hypothesized that intraoperative infusion of BNP may benefit renal function in cardiac transplant patients. METHODS: From June 2003 to September 2005, 22 consecutive heart transplant patients received BNP at a dose of 0.01 microg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion was continued for a mean of 3.3 +/- 1.9 days. Hemodynamics, urine output, and serum creatinine levels were prospectively collected and compared with 22 consecutive patients who underwent heart transplantation between May 2002 and June 2003 following the identical transplant protocol, but without BNP infusion (group B). RESULTS: At 24 hours postoperatively, mean blood pressure was comparable between groups (87 +/- 11 mm Hg vs 89 +/- 17 mm Hg, P = .7), but pulmonary artery pressure (18 +/- 5 mm Hg vs 24 +/- 5 mm Hg, P = .001) and central venous pressure (12 +/- 5 mm Hg vs 16 +/- 4 mm Hg, P = .01) were lower with BNP infusion, whereas cardiac index was augmented (2.8 +/- 0.5 vs 2.4 +/- 0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was equally distributed between groups (P > or = .72). Postoperative urine output for the initial 24 hours was higher in group A (84 +/- 15 vs 55 +/- 36 mL/h, P = .01). None of the patients with BNP infusion required additional diuretics or renal replacement therapy during the first week after transplantation. Mean postoperative serum creatinine levels as compared with preoperative values remained unchanged within group A (P = .12), but increased significantly in group B (P < .001). CONCLUSIONS: Intraoperative BNP infusion in heart transplant recipients was associated with favorable postoperative hemodynamics, significantly improved urine output, and stable serum creatinine levels. A prospective, randomized, multicenter trial is warranted to evaluate the potential renal protective benefits of intraoperative BNP infusion in this patient population.

Right ventricular dysfunction in patients with acute inferior MI: role of RV mechanical support.

Right ventricular dysfunction after myocardial infarction is associated with high morbidity and mortality. If optimal medical management is ineffective, early consideration should be given to right-sided temporary mechanical assistance.

Clinical experience with 202 adults receiving extracorporeal membrane oxygenation for cardiac failure: survival at five years.

OBJECTIVES: We sought to determine 5-year survival after extracorporeal membrane oxygenation for cardiac failure and its predictors, to assess survival and its predictors after bridging to transplantation or weaning from extracorporeal membrane oxygenation, and to identify factors influencing the likelihood of these outcomes. METHODS: Two hundred two adults (mean age, 55 +/- 14 years) were supported with extracorporeal membrane oxygenation between 1992 and July 1999 after cardiac failure. Follow-up extended to 7.5 years (mean, 3.8 +/- 2 years). Multivariable hazard function analysis identified predictors of survival, and logistic regression identified the determinants of bridging or weaning. RESULTS: Survival at 3 days, 30 days, and 5 years was 76%, 38%, and 24%, respectively. Patients surviving 30 days had a 63% 5-year survival. Risk factors (P <.1) included older age, reoperation, and thoracic aorta repair. Forty-eight patients were bridged to transplantation, and 71 were weaned with intent for survival. Survival was similar after either outcome (44% vs 40% 5-year survival, respectively). Failure to bridge or wean included (P <.03) renal and hepatic failure on extracorporeal membrane oxygenator support, occurrence of a neurologic event, and absence of infection. The dominant modes of death were cardiac failure and multisystem organ failure. CONCLUSIONS: Extracorporeal membrane oxygenation is versatile and salvages some patients who would otherwise die. Improvement in intermediate-term outcome will require a multidisciplinary approach to protect organ function and limit organ injury before and during this support.

Safety and efficacy of intraarterial thrombolysis for perioperative stroke after cardiac operation.

BACKGROUND: Acute ischemic stroke after cardiac operations is a devastating complication with limited therapeutic options. As clinical trials of thrombolysis for acute ischemic stroke exclude patients with recent major surgery, the safety of intraarterial thrombolysis in this setting is unknown. METHODS: Thirteen patients with acute ischemic stroke within 12 days of cardiac operation underwent intraarterial thrombolysis within 6 hours of stroke symptom onset. The National Institutes of Health Stroke Scale was used to assess neurologic recovery. RESULTS: The mean age was 69 years (standard deviation +/-5 years) and 62% were men. Cardiac procedures included valve operations in 6 patients, coronary artery bypass grafting in 4, valve and coronary artery bypass grafting in 2, and left ventricular assist device in 1 patient. Atrial fibrillation occurred in 5 patients (38%). The mean time from operation to stroke was 4.3 days (standard deviation +/- 3 days). Thrombolysis was initiated within 3.6 hours (standard deviation +/-1.6 hours) of stroke symptom onset. Recanalization was complete in 1 patient, partial in 5, and 7 patients had low flow. Neurologic improvement occurred in 5 patients (38%). One patient needed a chest tube for hemothorax, 2 others were transfused for low hemoglobin. No operative intervention for bleeding was necessary. CONCLUSIONS: In select patients with acute ischemic stroke after recent cardiac operation, intraarterial thrombolysis appears to be reasonably safe and may lead to neurologic recovery.

Platelet transfusions are associated with the development of anti-major histocompatibility complex class I antibodies in patients with left ventricular assist support.

BACKGROUND: Preformed anti-human leukocyte antigen (HLA) antibodies delay heart transplantation in patients with left ventricular assist devices (LVAD) because of difficulty in finding crossmatch-negative donors. These antibodies may also be associated with adverse outcome after transplantation. METHODS: In a retrospective analysis of 40 patients with LVAD at Columbia-Presbyterian Medical Center between 1990 to 1996, age, sex, diagnosis, race, duration of support, transfusions, and infections were studied by univariate and multivariate analysis as predictors for development of either anti-HLA class I (anti-I) or anti-HLA class II (anti-II) immunoglobulin G (IgG) or M (IgM) antibodies. RESULTS: Eighteen (45%) patients had development of anti-I and 20 (50%) had development of anti-II antibodies over the study period. Median time for LVAD support was 142 days (range 35 to 439). Only total number of perioperative platelet transfusions predicted the development of anti-I IgG antibodies (p = .04). No other associations were found for development of anti-I IgM or anti-II antibodies of either IgG or IgM specificity. Patients who had development of anti-I IgG received a mean of 13.9 (SE +/- 2.6) units of platelets compared with a mean of 7.7 (SE +/- 2.3) units in those who did not (p = .01). By Kaplan-Meier analysis, at the median duration of follow-up, 8% of patients receiving < 6 units were predicted to have development of anti-I antibodies compared with 63% receiving > 6 units (p = .002). In the last 7 patients, leukocyte filters were used to decrease the antigenic load during platelet and red blood cell transfusions. Only 1 of 7 (14%) patients had development of anti-HLA antibodies compared with 31 of 33 (94%) in whom filters were not used (p < .005). CONCLUSIONS: These results indicate that platelet transfusion during LVAD implantation is a risk factor associated with development of HLA class I IgG antibodies. Use of leukocyte filters during platelet transfusion may decrease the risk of development of anti-HLA antibodies.

Preformed IgG antibodies against major histocompatibility complex class II antigens are major risk factors for high-grade cellular rejection in recipients of heart transplantation.

BACKGROUND: Preformed anti-HLA antibodies reacting specifically with donor lymphocytes have been associated with acute vascular rejection and early cardiac allograft failure. However, the effect of preformed anti-HLA antibodies directed against allogeneic major histocompatibility complex (MHC) class I or II antigens of a donor panel on heart transplantation outcome has not been extensively studied. METHODS AND RESULTS: The study group consisted of 68 patients who received cardiac transplants between 1989 and 1996 and who were at high risk for developing anti-HLA antibodies before transplantation. The effect of preformed antibodies against allogeneic MHC class I or class II antigens on the development of early high-grade cellular rejection and on cumulative annual rejection frequency was determined. Both patients with left ventricular assist devices and retransplantation candidates had a similar increase in the frequency of IgG anti-MHC class II antibodies (IgG anti-II) compared with control subjects (P<0.0001), whereas the frequency of IgG anti-MHC class I antibodies (IgG anti-I) was elevated only in patients with left ventricular assist devices. Pretransplantation IgG anti-II predicted early development of high-grade cellular rejection (P=0.006) and higher cumulative annual rejection frequency (P<0.001) in both of these sensitized patient groups. Among retransplantation recipients, a match between donors 1 and 2 at HLA-A additionally predicted an earlier time to a high-grade cellular rejection. CONCLUSIONS: These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.

Short-term outcome of chronic immunosuppression on the development of breast lesions in premenopausal heart and lung transplant patients.

The risk of development of breast lesions in patients on chronic immunosuppression is unknown. In order to assess this risk, a retrospective review was performed of the records of 87 women between the ages of 12 and 47 years who received thoracic organ transplant from 1987 to 1996 at our institution. Inclusion criteria consisted of patients who were premenopausal, had no previous history of breast disease, and survived for at least 1 year posttransplantation. All patients were on a triple immunosuppressive regimen consisting of cyclosporine, steroids, and azathioprine. Mean follow-up was 4 +/- 1.2 years with a range of 1-6 years. During this period, 21 patients (24%) with a mean age of 38 +/- 10 years had screening or diagnostic mammography. The remainder of patients with a mean age of 24 +/- 9 years were followed clinically. Overall, 10 patients (11%) developed a total of 17 palpable, solid lesions at 33 to 72 months posttransplantation. Fifteen of these lesions were surgically excised. Five of the patients had multiple lesions. Pathological examination of the specimens revealed fibroadenoma in nine, fibrocystic disease in four, low grade phylloides tumor in one, and T-cell lymphoma in one case. None of the patients have developed primary breast cancer during follow-up. In conclusion, short-term immunosuppression does not increase the risk of the development of benign breast lesions in young women after thoracic organ transplantation, but rather the distribution of benign lesions is similar in an age-matched population. There were several cases of multiple fibroadenomas in the transplant population, but mammography revealed no malignant disease in this age group and does not need to be utilized in this population beyond what is considered standard for immunocompetent patients. The long-term effect ofimmunosuppressive therapy on the developmentof breast cancer in this group remains to be defined.

Bouveret's syndrome: diagnosis by helical CT scan.

Calculous cholecystitis severe enough to result in pyloric outlet obstruction is a rare occurrence. Impaction of a large calculus in the duodenum or stomach as a consequence of fistula formation is usually diagnosed on upper gastrointestinal series. Computed tomography is uncommonly used to diagnose this condition and was diagnostic in our patient.

Inflow valve regurgitation during left ventricular assist device support may interfere with reverse ventricular remodeling.

BACKGROUND: Left ventricular assist devices have been reported previously to reverse ventricular remodeling in patients with dilated cardiomyopathy. In patients with prolonged mechanical support, structural failure of the left ventricular assist device inflow valve can cause regurgitation into the left ventricle, which may affect adversely this process. METHODS: Left ventricular end-diastolic pressure-volume relation of hearts explanted from 8 patients with left ventricular assist device and 8 control subjects with idiopathic cardiomyopathy was determined ex vivo at the time of transplantation. RESULTS: Duration of mechanical support ranged from 210 to 276 days (mean +/- standard deviation = 283 +/- 76 days) in 3 patients with inflow valve regurgitation versus 100 to 155 days (132 +/- 22 days) in 5 patients without (p = 0.005). The end-diastolic pressure-volume relation of all hearts supported mechanically was shifted to the left toward normal controls. This effect was markedly attenuated in patients with inflow valve regurgitation. CONCLUSIONS: Mechanical assistance can cause reverse remodeling in patients with dilated cardiomyopathy as evidenced by the shift in the end-diastolic pressure-volume relation curve to the left. Inflow valve failure, associated with prolonged support, can attenuate changes in left ventricular structure and dimension. Ineffective pressure and volume unloading may explain these observations.

Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure.

BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.

Randomized, double-blind trial of inhaled nitric oxide in LVAD recipients with pulmonary hypertension.

BACKGROUND: Pulmonary vascular resistance is often elevated in patients with congestive heart failure, and in those undergoing left ventricular assist device (LVAD) insertion, it may precipitate right ventricular failure and hemodynamic collapse. Because the effectiveness of inotropic and vasodilatory agents is limited by systemic effects, right ventricular assist devices are often required. Inhaled nitric oxide (NO) is an effective, specific pulmonary vasodilator that has been used successfully in the management of pulmonary hypertension. METHODS: Eleven of 23 patients undergoing LVAD insertion met criteria for elevated pulmonary vascular resistance on weaning from cardiopulmonary bypass (mean pulmonary artery pressure > 25 mm Hg and LVAD flow rate < 2.5 L x min[-1] x m[-2]) and were randomized to receive either inhaled NO at 20 ppm (n = 6) or nitrogen (n = 5). Patients not manifesting a clinical response after 15 minutes were given the alternative agent. RESULTS: Hemodynamics for the group at randomization were as follows: mean arterial pressure, 72 +/- 6 mm Hg; mean pulmonary artery pressure, 32 +/- 4 mm Hg; and LVAD flow, 2.0 +/- 0.3 L x min(-1) x m(-2). Patients receiving inhaled NO exhibited significant reductions in mean pulmonary artery pressure and increases in LVAD flow, whereas none of the patients receiving nitrogen showed hemodynamic improvement. Further, when the nitrogen group was subsequently given inhaled NO, significant hemodynamic improvements ensued. There were no significant changes in mean arterial pressure in either group. CONCLUSIONS: Inhaled NO induces significant reductions in mean pulmonary artery pressure and increases in LVAD flow in LVAD recipients with elevated pulmonary vascular resistance. We conclude that inhaled NO is a useful intraoperative adjunct in patients undergoing LVAD insertion in whom pulmonary hypertension limits device filling and output.

Photo-oxidized bovine arterial grafts: short-term results.

Biologic grafts are the conduit of choice for vascular reconstructive procedures. The short-term thrombogenicity, patency, and stability of bovine arterial grafts, altered by a dye-mediated photo-oxidation process, was evaluated in the canine common femoral vein (CFV) and artery (CFA) model. Modified bovine interposition grafts were implanted in the CFV of 12 dogs and in the CFA of 11 dogs, respectively. Polytetrafluoroethylene (PTFE) implants on the contralateral side served as controls. Patency and histology were assessed at 1, 2, 4, and 6 weeks. In the CFV, patency of photo-oxidized grafts was 83% at 1 week and 71% at 2 weeks, compared to 17% and 0% for PTFE, respectively (p = 0.0033). In CFA, patency was 82% for the photo-oxidized graft and 63% for PTFE at 6 weeks (p = NS). Photo-oxidized grafts were nonreactive, without evidence of degenerative changes or cellular infiltration at all time periods. Compared to commercially available PTFE, photo-oxidized arterial grafts have superior patency in the CFV, and comparable patency in the CFA. Preliminary results demonstrate that these xenografts are stable and without degenerative changes. If corroborated by long-term data, these grafts may be a suitable alternative to currently available prosthetics for peripheral vascular reconstructive procedures.

The influence of infection on survival and successful transplantation in patients with left ventricular assist devices.

BACKGROUND: Mechanical cardiac assistance has recently emerged as a tenable option in the treatment of end-stage heart failure. In spite of recent technical improvements that have reduced the incidence of life-threatening complications, the reported frequency of infections in these patients has remained high. METHODS: Over a 5-year period, 60 patients underwent insertion of a left ventricular assist device (LVAD) at our institution. Detailed medical records were kept prospectively for all patients, and a variety of endpoints were analyzed, including the incidence, nature, and sequelae of infections before and after LVAD implantation and after transplantation. RESULTS: Twenty-nine of 60 patients (48%) undergoing LVAD insertion subsequently had development of infections. The most frequent sites of infection were blood, LVAD drivelines, and central venous catheters, representing 61% of all infections. At the time of LVAD implantation, 13 of 60 patients (22%) had culture-proven infections. In spite of an increased incidence of subsequent infection (77% vs 40%), there were no differences in rates of mortality (31% vs 26%), LVAD endocarditis, (23% vs 11%) and eventual transplantation (62% vs 57%) between these patients and those without periimplantation infections. Although the overall mortality rate was not influenced by infections during LVAD support (28% vs 26%), the development of LVAD endocarditis was associated with a high mortality rate. Finally, although patients with infections during LVAD support had significantly longer median support times than those who remained infection free (101 vs 49 days, respectively), there was no difference in the rate of successful transplantation (59% vs 58%) or in the rate of infection after transplantation (35% vs 28%). CONCLUSIONS: Infections are common in patients undergoing LVAD support, but they do not adversely affect survival, the rate of successful transplantation, or the incidence of posttransplantation infection. Periimplantation infections may increase the risk of subsequent infections, but they also do not influence survival or transplantability. Patients with development of LVAD endocarditis are at increased risk for morbidity and death and require early and aggressive therapy, potentially including device explantation.

Asymptomatic microembolism in patients with long-term ventricular assist support.

The incidence of clinically significant thromboembolic events is reported to be as high as 25% in patients with left ventricular assist devices (LVAD). Clinically detectable neurologic deficits resulting from thromboembolic events are reported to occur at a frequency of 0.0056% per patient-month with the Thermo Cardiosystems Heartmate 1000 (Woburn, MA) intraperitoneal LVAD (TCI). To date, the occurrence of asymptomatic cerebral microemboli in patients with this device has not been characterized. Transcranial doppler (TCD) monitorings were used for evaluation of the incidence of cerebral microembolism in 14 patients with the TCI LVAD. Studies were performed after LVAD support ranging from 7 to 305 days. Overall, 35 studies were obtained from the left middle cerebral artery for a duration of 30 minutes per study and the number of high intensity transient signals (HITS) were recorded. In one patient with a fatal stroke, an average of 0.86 HITS per study period (0.03/min) was observed. In 13 patients without any symptoms, an average of 0.46 HITS per study (0.016/min) was observed. Overall, no HITS were determined in 74% of the studies. Although the clinical significance or the nature of these microemboli is unknown, the data support that microembolism with the TCI LVAD is a rare event despite absence of anticoagulation. Long-term detailed neurocognitive testing and hematologic assessment is needed to establish the clinical relevance of these microemboli in patients with detected signals.

Circulatory resuscitation with left ventricular assist device support reduces interleukins 6 and 8 levels.

BACKGROUND: Elevated tumor necrosis factor serum levels have been reported in patients with severe congestive heart failure. This study was designed to characterize the cytokine profile in patients with acute circulatory collapse. METHODS: Blood drawn from 14 consecutive patients within 24 hours before undergoing left ventricular assist device placement and after at least 30 days of mechanical assistance or before transplantation was assayed for levels of interleukin 6, interleukin 8, and tumor necrosis factor-alpha. RESULTS: Interleukin 6 level was elevated in 11 (79%), interleukin 8 in 10 (71%), and tumor necrosis factor in 2 (14%) of the 14 patients. After hemodynamic recovery, interleukin 6 levels decreased from 33.6 +/- 9 pg/mL to 11.3 +/- 4 pg/mL (p = 0.05) and interleukin 8 levels decreased from 122 +/- 34 pg/mL to 19.7 +/- 8 pg/mL (p = 0.005). Tumor necrosis factor-alpha levels did not vary significantly; they were associated with infection in 2 left ventricular assist device recipients and normalized after left ventricular assist device support. All patients had resolution of circulatory shock after mechanical support and had improvement in parameters of end-organ function. CONCLUSIONS: Circulatory shock treated with left ventricular assist device placement is associated with a proinflammatory response similar to that seen in septic shock. The decrease in cytokine serum levels that follows hemodynamic recovery suggests that these cytokines may be markers of tissue damage and may modulate cardiac dysfunction.

Extended indications for lung volume reduction surgery in advanced emphysema.

BACKGROUND: Lung volume reduction surgery has shown early promise as a palliative therapy in severe emphysema. Selection of potential candidates has been based on certain functional and anatomic criteria, and a variety of operative contraindications have been proposed. METHODS: Over 15 months, we performed lung volume reduction surgery in 85 patients selected on the basis of severe hyperinflation with air trapping, diaphragmatic dysfunction, and disease heterogeneity. Patients were not excluded on the basis of severe hypercapnia, steroid dependence, profound pulmonary dysfunction, or inability to complete preoperative rehabilitation. RESULTS: We observed significant improvements in pulmonary function, exercise capacity, and dyspnea, with an acceptable 30-day perioperative mortality of 7% and actuarial survival of 90% and 83% at 6 and 12 months, respectively. In each "high-risk" group, perioperative mortality, actuarial survival to 1 year, and functional results were equivalent, and in some cases superior, to those in the corresponding "low-risk" patients. CONCLUSIONS: Severe hypercapnia, steroid dependence, profound pulmonary dysfunction, and inability to complete preoperative rehabilitation do not preclude successful lung volume reduction surgery and should not be regarded as absolute exclusionary criteria.