Does pretransplant left ventricular assist device therapy improve results after heart transplantation in patients with elevated pulmonary vascular resistance?

Objective: Pulmonary hypertension (PH), defined as a pulmonary vascular resistance (PVR) >2.5 Wood units (WU) and (or) a transpulmonary gradient (TPG) >12 mmHg, is an established risk factor for mortality in heart transplantation. Elevated PVR in heart transplant candidates can be reduced using a left ventricular assist device (LVAD), and LVAD is proposed to be the treatment of choice for candidates with PH. We analyzed the effect on PVR of pretransplant LVAD therapy in patients with PH and compared posttransplant outcome with matched controls. Long-term survival was compared between heart transplant recipients with mild, moderate or severe PH and patients with no PH. Methods: Heart transplant recipients 1988–2007 (n = 405) were reviewed and divided into two groups with respect to pretransplant PVR: <2.5 WU (n = 148) and >2.5 WU (n = 158). From the group with PH, patients subjected to pretransplant LVAD therapy (n = 11) were analyzed with respect to PVR at implant and at transplant and, with respect to outcome, compared to matched historical controls (n = 22). Patients with PH without LVAD treatment (n = 147) were stratified into three subgroups: mild, moderate and severe PH and survival according to Kaplan–Meier was analyzed and compared to patients with no PH. Results: LVAD therapy reduced PVR from 4.3 ± 1.6 to 2.0 ± 0.6 WU, p < 0.05. Three cases of perioperative heart failure required mechanical support whereas one control patient developed perioperative right heart failure requiring mechanical support. The incidence of other perioperative complications was comparable between groups. There was no difference in survival between LVAD patients and controls, 30-day survival was 82% and 91%, respectively and 4-year survival was 64% and 82%, respectively. Conclusions: Pretransplant LVAD therapy reduces an elevated PVR in heart transplant recipients, but there was no statistically significant difference in posttransplant survival in patients with PH with, or without LVAD therapy. The study revealed no differences in survival in patients regardless of the severity of the PH.     

Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

BACKGROUND: Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. METHODS: Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. RESULTS: The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. CONCLUSION: Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.     

Impact of current management practices on early and late death in more than 500 consecutive cardiac transplant recipients

OBJECTIVE: To study risk factors for early and late death after heart transplantation in the current era. SUMMARY BACKGROUND DATA: The current cardiac transplant population differs from earlier periods in that an increasing number of sicker patients, such as those with ventricular assist device (LVAD) support, prior cardiac allotransplantation, and pulmonary hypertension, are undergoing transplantation. In addition, sensitized patients constitute a greater proportion of the transplanted population. Emphasis has been placed on therapies to prevent early graft loss, such as the use of nitric oxide and improved immunosuppression, in addition to newer therapies. METHODS: Five hundred thirty-six patients undergoing heart transplantation between 1993 and 1999 at a single center were evaluated (464 adults and 72 children; 109 had received prior LVAD support and 24 underwent retransplantation). The mean patient age at transplantation was 44.9 years. Logistic regression and Cox proportional hazard models were used to evaluate the following risk factors on survival: donor and recipient demographics, ischemic time, LVAD, retransplantation, pretransplant pulmonary vascular resistance, and immunologic variables (ABO, HLA matching, and pretransplant anti-HLA antibodies). RESULTS: The rate of early death (less than 30 days) was 8.5% in adults and 8.8% in children. The actuarial survival rate of the 536 patients was 83%, 77%, and 71% at 1, 3, and 5 years, respectively, by Kaplan Meier analysis. Risk factors adversely affecting survival included the year of transplant, donor age, and donor-recipient gender mismatching. Neither early nor late death was influenced by elevated pulmonary vascular resistance, sensitization, prior LVAD support, or prior cardiac allotransplantation. CONCLUSIONS: Previously identified risk factors did not adversely affect short- or long-term survival of heart transplant recipients in the current era. The steady improvement in survival during this period argues that advances in transplantation have offset the increasing acuity of transplant recipients.     

Normalization of high pulmonary vascular resistance with LVAD support in heart transplantation candidates.

OBJECTIVE: Pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) lead to poor outcome after heart transplantation due to postoperative failure of the non-conditioned right ventricle. The role of continuous flow left ventricular assist device (LVAD) support in the reduction of elevated PVR was evaluated in a series of clinical implants. METHODS: Among 17 patients with terminal heart failure receiving a MicroMed DeBakey LVAD as bridge to transplant, there were six patients with pulmonary hypertension (mean systolic PAP 47 mmHg) and high PVR (398 dynes/cm5), previously not considered suitable for heart transplantation, who underwent serial right heart catheters during their LVAD support period. RESULTS: In these patients mean systolic pulmonary pressure dropped to 29 mmHg and PVR decreased to a mean 167 dynes/cm5 under LVAD support. Clinical improvement was significant in all patients. Four patients were successfully transplanted without major postoperative difficulties (mean duration 130 days support) and all are doing well to date. Post-transplant-PVR remained in the normal range in all transplanted patients. CONCLUSIONS: Elevated PVR and severe PH were both previously considered as contraindication for heart transplantation. A period of LVAD pumping leads to a progressive decrease of PVR and normalization of pulmonary pressures, making these patients amenable for heart transplantation. LVAD as bridge to heart transplantation is safe and highly beneficial for terminal heart failure patients with severe PH.     

How does successful bridging with ventricular assist device affect cardiac transplantation outcome?

A best evidence topic in cardiac surgery was written according to a structured protocol. The issue was to determine the impact of bridge-to-transplant ventricular assist device support on survival after cardiac transplantation. Altogether 428 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The treatment options for patients with advanced heart failure or those with deteriorating end-organ function on maximal medical therapy are limited to intravenous inotropes and mechanical assistance with intra-aortic balloon pump (IABP) or ventricular assist device (VAD). Studies exploring the effect of VADs on post-transplant mortality have yielded conflicting results. The Registry of the International Society for Heart and Lung Transplantation continues to identify mechanical support as a risk factor for decreased survival after transplantation. A limitation of this report is that the multivariable adjustment uses variables recorded not at the time of device implant but at the time of transplant. Some of the recipient characteristics thus may be altered by the device implant. Compared with the previous reports the latest data show improvement in post-transplant survival in the recent era. In addition, the excess risk appears to be limited to the early post-transplant period. Experienced centers consistently report outstanding post-transplant results with left ventricular assist device (LVAD) bridging. Of the 12 papers seven showed no difference in survival, and five showed a reduced survival. In the papers showing no difference, one year survival averaged from 85% in supported patients to 87% in non-supported patients. In papers reporting a difference in outcome, one year averaged survival was 74% in LVAD recipients compared to 90% in non-bridged patients. Decreased survival is associated with patients suffering from dilated cardiomyopathy, transplanted within two weeks of LVAD implantation and bridged to transplantation before 2003 as opposed to patients transplanted more recently. Based on the available evidence we conclude that in selected patients survival after heart transplantation in patients bridged with VAD is comparable to those who did not receive the device.     

Cardiac transplant outcome of patients supported on left ventricular assist device vs. intravenous inotropic therapy.

BACKGROUND: Although the left ventricular assist device (LVAD) has been increasingly used as a bridge to transplant, its effect on post-transplant outcome is uncertain. We, therefore, designed this study using the Cardiac Transplant Research Database to compare patients supported on an LVAD before transplant with those treated with intravenous inotropic medical therapy. METHODS AND RESULTS: Of the 5,880 patients transplanted between 1990 and 1997, a total of 502 received support from LVADs and 2,514 received intravenous inotropic medical therapy at the time of transplant. Kaplan-Meier analysis showed no significant difference in post-transplant survival between the LVAD and medical-therapy groups (p = 0.09). Results of a multivariate Cox regression analysis were consistent with that of the Kaplan-Meier analysis and did not identify LVAD as a significant risk factor for mortality. The percentage of patients who received LVADs as a function of total transplants increased from 2% in 1990 to 16% in 1997. Furthermore, although the number of extracorporeal LVADs remained relatively constant, the number of intracorporeal LVADs increased over time. Multivariate parametric analysis found that the risk factors for post-transplant death in the LVAD group were extracorporeal LVAD use (p = 0.0004), elevated serum creatinine (p = 0.05), older donor age (p = 0.03), increased donor ischemic time (p < 0.0001), and earlier year of transplant (p = 0.03). CONCLUSIONS: Given a limited donor supply, the intracorporeal LVAD helps the sickest patients survive to transplant and provides post-transplant outcome similar to that of patients supported on inotropic medical therapy. Therefore, patients supported on LVADs before transplant may receive the greatest marginal benefit when compared with other transplant candidates.     

Is the transpulmonary pressure gradient a predictor for mortality after orthotopic cardiac transplantation?

Elevated pulmonary vascular resistance (PVR) is a well-known risk factor for right ventricular failure after orthotopic cardiac transplantation. The influence of preoperative transpulmonary pressure gradient (TPG) and PVR on post-transplant 30 days mortality was evaluated. To analyze the response of PVR and TPG to cardiac transplantation, we analyzed 718 adult patients undergoing primary cardiac transplantation. Indications for operation were: 35.2% ischemic cardiomyopathy (ICM), 61.2% idiopathic dilated cardiomyopathy (DCM), and 3.3% other diagnosis (e.g. hypertrophic cardiomyopathy). The mean age (51.9) and the mean ischemic time (169.7 min) were comparable between 30 days survivors and nonsurvivors. Student's t-tests and chi-square analysis were used to compare data from 30-day survivors and nonsurvivors. Statistical significance was defined as P < 0.05. Fisher's exact test and multiple logistic regression analysis was performed to evaluate the relationship between hemodynamic parameters and outcome after transplantation. Primary end-point was 30 days mortality and secondary end-point long-term survival of patient groups with different TPG and PVR values. In survivors the mean TPG was 10.3 +/- 5.1 (mean +/- SD) vs. 13 +/- 6.6 in patients who died after transplantation (P = 0.0012). The PVR was 2.6 +/- 1.4 vs. 3.5 +/- 2.2 (P = 0.0012). In multivariate logistic regression, the parameters TPG and PVR exhibit a significant influence between survivors and nonsurvivors after cardiac transplantation within 30 days (TPG: P = 0.0012; PVR: P = 0.0012). The mortality rates in patients with TPG > 11 mmHg and PVR < 2.8 Wood units or TPG < 11 mmHg and PVR > 2.8 Wood units were comparable to those with TPG < 11 mmHg and PVR < 2.8 mmHg. The TPG is an important predictor in nonrejection-related early mortality after orthotopic cardiac transplantation. The determination of TPG in combination with PVR is a more reliable predictor of early post-transplant survival than PVR alone.     

Reversibility of fixed pulmonary hypertension in left ventricular assist device support recipients

Objective: Conflicting data still exist concerning the reversibility of secondary severe ‘fixed’ pulmonary hypertension (PH) by the use of left ventricular assist device (LVAD) support in terms of time necessary to provide a bridge to ‘transplantability’. Methods: We retrospectively reviewed 145 patients with heart failure and severe PH treated by LVAD support between 2000 and 2009. There were 133 men (91.7%) and 12 women (8.3%) with a mean age of 52.95 ± 12.01 years. Patients were divided into two groups depending on preoperative PH reversibility. Fixed PH was defined by a mean pulmonary arterial pressure (mPAP) >25 mmHg, a pulmonary vascular resistance (PVR) >2.5 Wood Unit (WU) and a transpulmonary gradient (TPG) >12 mmHg, despite pharmacological treatment. Results: Fifty-six patients had fixed PH (group A) and 89 reversible PH (group B). Only 27 patients of group A underwent right heart catheterization evaluation during LVAD support; the remaining 29 patients had other contraindications to heart transplantation (HTx). The 27 patients were divided into three subgroups on the basis of examination time during LVAD support: <6 months (11 patients), between 6 and 12 months (six patients) and >12 months (10 patients). The mPAP, PVR, and TPG decreased significantly during LVAD support (mPAP, 37.26 ± 6.35 mmHg vs 21.00 ± 7.51 mmHg, p = 0.007; PVR, 3.49 ± 1.47 WU vs 1.53 ± 0.66 WU, p = 0.000; and TPG, 15.04 ± 5.22 mmHg vs 7.78 ± 3.21 mmHg, p = 0.019). A significant reduction of all parameters was observed during the first 6 months and later on there was no further decrease. There were no significant differences between the three subgroups (mPAP, p = 0.680; PVR, p = 0.723; and TPG, p = 0.679) in terms of time of reversibility. LVAD support allowed 19 patients to be transplanted. Conclusions: Patients with fixed PH can be treated with LVAD support. Our data suggest that 6 months after LVAD implantation it is possible to observe an important reduction of PH and evaluate the potential transplantability of patients. Longer support does not add any effect of LVAD on PH.     

Left ventricular assist devices as bridge to heart transplantation: The Niguarda Experience

BACKGROUND: Congestive heart failure is the leading cause of death in Western countries. Heart transplantation currently is the only accepted therapy for patients with end-stage heart failure, but the supply of donor hearts is inadequate, and different mechanical circulatory support systems have been investigated as bridges to heart transplant. METHODS: Since April 1992, 53 patients (47 men, 6 women, aged 12 to 61 years) received left ventricle mechanical circulatory support as bridge to heart transplant. The two principal devices used were: the Novacor LVAS in 31 patients and the DeBakey VAD in 11 patients. RESULTS: All patients survived the operation. Mean duration of LVAD support was 2.8 +/- 5.6 months. Thirty-seven patients (71.1%) underwent heart transplantation. Twelve major bleeding episodes occurred in nine patients (16.9%). Globally, major and minor neurologic events occurred in 13 patients (24.5%). Ten patients (19.9%) assisted with the Novacor Wearable LVAS device were discharged at home while waiting for heart transplant (HTx). The mean follow-up of the 34 discharged transplanted patients was 45.3 +/- 37 months. Actuarial survival of transplanted patients while on LVAD was 91.0 +/- 4.9% and 83.4 +/- 8.5% at 1 and 5 years, respectively. No differences in post-transplant long-term survival and rejection and allograft vasculopathy occurred between patients transplanted with or without LVAD implanted. CONCLUSIONS: LVAD therapy proved to be effective in bridging patients with end-stage heart failure to HTx. While on LVAD support, patients assisted with implantable wearable devices could be discharged at home, ameliorating their quality of life. The excellent survival rate after HTx is concomitant with a low incidence of rejection and cardiac allograft vasculopathy.     

The Survival Benefit of Liver Transplantation

Demand for liver transplantation continues to exceed donor organ supply. Comparing recipient survival to that of comparable candidates without a transplant can improve understanding of transplant survival benefit. Waiting list and post-transplant mortality was studied among a cohort of 12 996 adult patients placed on the waiting list between 2001 and 2003. Time-dependent Cox regression models were fitted to determine relative mortality rates for candidates and recipients. Overall, deceased donor transplant recipients had a 79% lower mortality risk than candidates (HR = 0.21; p < 0.001). At Model for End-stage Liver Disease (MELD) 18-20, mortality risk was 38% lower (p < 0.01) among recipients compared to candidates. Survival benefit increased with increasing MELD score; at the maximum score of 40, recipient mortality risk was 96% lower than that for candidates (p < 0.001). In contrast, at lower MELD scores, recipient mortality risk during the first post-transplant year was much higher than for candidates (HR = 3.64 at MELD 6-11, HR = 2.35 at MELD 12-14; both p < 0.001). Liver transplant survival benefit at 1 year is concentrated among patients at higher risk of pre-transplant death. Futile transplants among severely ill patients are not identified under current practice. With 1 year post-transplant follow-up, patients at lower risk of pre-transplant death do not have a demonstrable survival benefit from liver transplant.     

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Left ventricular unloading in a patient with end-stage cardiomyopathy and medically unresponsive pulmonary hypertension

Severe, medically unresponsive pulmonary hypertension (PHT) is considered to be a contraindication for orthotopic heart transplantation (OHT). Chronic left ventricular (LV) unloading using a left ventricular assist device (LVAD) might result in reversal of the elevated pulmonary vascular resistance (PVR), allowing successful OHT in such patients. In this study, we present a patient with end-stage ischemic cardiomyopathy and fixed, elevated PVR (7.1 Wood units) who underwent implantation of a Novacor LVAD (Baxter Healthcare Corp., Deerfield, IL, U.S.A.), with a subsequent reduction in PVR to 1.2 Wood units and successful OHT eleven months post-LVAD implantation. Three years after heart transplant, the patient still leads an active life with no right heart failure. In conclusion, OHT is not contraindicated in patients with end-stage heart failure and medically unresponsive PHT in the presence of elevated left atrial pressure. Left ventricular unloading should be considered in these patients to allow reversal of the elevated PVR before OHT.     

Prognostic value of serum carcinoembryonic antigen levels in patients who undergo lung transplantation

BACKGROUND: Potential candidates for lung transplantation undergo a rigorous evaluation before transplant. Serum carcinoembryonic antigen (CEA) levels are used as a screening tool for occult malignancy in many lung transplant centers. We reviewed the pre-transplant CEA levels in lung transplant recipients in our institution to determine their prognostic significance. MATERIALS AND METHODS: We performed a retrospective database review of the first 200 patients that had undergone lung or heart-lung transplant at our institution (dates were 1/20/92-7/25/98). Data extracted included CEA levels (in ng/ml) at the time of lung transplant evaluation, demographic data, and survival. Patients had one of the following diagnoses: alpha-1-anti-trypsin deficiency, cystic fibrosis, chronic obstructive pulmonary disease, Eisenmenger's syndrome, idiopathic pulmonary fibrosis, primary pulmonary hypertension, sarcoidosis, or other. RESULTS: After excluding re-transplants, CEA results were available for 174 of 193 (90.2%) patients. CEA levels were elevated in 85 patients (48.9%) with a mean value of 3.15 +/- 2.55 (normal < 2.5). Solid organ cancers developed in 6 patients, at a median follow-up of 27.5 months after transplant. Their mean pre-transplant CEA level was similar to the rest of the group (3.52 +/- 2.05). Pre-transplant CEA levels did not predict post-transplant survival. Patients with idiopathic pulmonary fibrosis had the highest pre-transplant CEA levels, whereas patients with primary pulmonary hypertension and Eisenmenger's syndrome had the lowest (5.36 +/- 4.59, 0.83 +/- 0.56, and 1.43 +/- 0.81, respectively; p = 0.0001). CONCLUSIONS: CEA levels are high in patients with end-stage lung disease, especially IPF. Their levels appear to be a marker of the underlying disease and do not predict the post-transplant survival or development of malignancy.     

Impact of postoperative pulmonary hypertension on outcome after heart transplantation

Objectives: We wanted to investigate the effects of postoperative pulmonary hypertension (PH_postop: mean pulmonary artery pressure [MPAP]?≥?25?mmHg), diastolic pressure gradient (DPG), pulmonary vascular resistance (PVR), and repeated hemodynamic measurements on long-term survival after heart transplantation (HT).

Design: Eighty-nine patients who underwent HT at Skåne University Hospital in Lund in the period 1988–2010 and who were evaluated with right-heart-catheterization at rest, prior to HT and repeatedly during the first postoperative year, were grouped based on their MPAP, DPG, and PVR.

Results: One year after HT, survival was lower in patients with PH_postop than in those without, in patients with DPG?≥7?mmHg than in those with DPG?<7?mmHg, and in patients with PVR?>3 WU than in those with PVR?≤3 WU. Moreover, compared to patients with no PH_postop or with PH_postop at one evaluation during the first year after HT, PH_postop at repeated evaluations was associated with higher mortality (hazard ratio 3.4, 95% CI 1.4–8.0). There was no significant difference in acute cellular rejection between patients with and without PH_postop, but postoperative kidney function was worse in patients with repeated PH_postop.

Conclusions: When defined according to present guidelines, PH one year after HT may emerge as a prognostic marker for long-term outcome after HT. Moreover, PH_postop at repeated evaluations during the first year after HT had stronger prognostic value than PH_postop at a single examination, illustrating a means of identifying a high-risk population. However, confirmation in larger multi-center studies is warranted.     

Mechanical circulatory support as a bridge to transplant candidacy

Abstract Introduction: The use of mechanical circulatory support (MCS) in nontransplant eligible candidates remains controversial. Our decision to offer MCS for nontransplant candidates has led to their reevaluation after a period of left ventricular assist device (LVAD) support. Methods: From 2001 to September 2009, we had 37 patients who received an implantable LVAD, 22 (59%) were not deemed to be transplant eligible at the time of LVAD insertion (bridge to candidacy, BTC group). Results: Fifteen (41%) patients were considered transplant eligible (bridge to transplant, BTT group) at the time of device insertion and received a HeartMate XVE (n = 7), HeartMate 2 (n = 7), or a Novacor LVAS (n = 1). In the BTC group, patients received the HeartMate XVE device (n = 11), HeartMate 2 (n = 5), or the Novacor LVAS (n = 6). The primary criterion for transplant ineligibility was refractory pulmonary hypertension (PH) in 18 patients, 3 patients did not meet our body mass index criteria (>35 kg/m²), and 2 patients were dialysis‐dependent. Six (27%) BTC patients died on support. Overall, 16/22 patients (73%) were subsequently listed for transplantation, with one listed for combined heart–lung due to refractory PH. Twelve patients (75%) underwent successful heart transplantation. Three patients died during their transplant. Overall posttransplant survival at one year shows lower survival in the BTC group compared to the BTT group (67% vs. 100%, p = 0.05). At two years and three years the survival was lower, but not statistically different (BTC vs. BTT: 67% vs. 90% and 64% vs. 87%, respectively, p = NS). Conclusions: MCS can successfully convert a large proportion of transplant‐ineligible patients into acceptable candidates. (J Card Surg 2011;26:542‐547)     

Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation—a preliminary study

Objectives: Elevated pulmonary vascular resistance (PVR) unresponsive to pharmacological intervention is a major limitation in heart transplantation (HTX). The post-operative course of these patients is associated with an increased risk of life-threatening right heart failure. We evaluated the efficiency of an implantable left ventricular assist device (LVAD) to decrease PVR by unloading the left ventricle and to lower the risk of later orthotopic HTX. Methods: Six patients with end-stage heart failure (NYHA class IV) and ’fixed‘ pulmonary hypertension (PVR 5.7±0.7, range 4.4–6.5 Wood units) were analyzed. Despite maximal pharmacological intervention at initial evaluation (oxygen inhalation, nitrates, alprostadil infusion) PVR could not be reduced to under 2.5 Wood units. Four patients received a TCI Heartmate, one patient a Novacor, and one patient a Jarvik 2000. Results: All patients survived the LVAD implantation, four patients could be discharged from hospital. Cardiac index and pulmonary artery pressure values returned to normal during the early post-operative phase. After a mean support time of 191±86 days PVR had fallen to 2.0±1.2 (range 0.8–3.6) Wood units. All patients could be bridged to transplantation, one patient died 3 months after transplant, five patients are still alive after a mean follow-up of 16.2±10.5 months. Conclusions: Mechanical support using an implantable LVAD is a very efficient approach with an acceptable risk to treat severe pulmonary hypertension in end-stage heart failure patients before HTX. Adequate reduction of PVR can be expected within 3–6 months. Subsequent HTX is associated with a good outcome.     

Outcome of infants listed for lung or heart/lung transplantation

BACKGROUND: Little is known about outcome, characteristics, or organ availability for infants listed for lung or heart/lung transplantation. METHODS: Within a 45-month period at one institution, all pediatric patients who were listed for primary lung or heart/lung transplantation and who reached the end point of either transplant or death prior to transplant were identified. Outcomes for those patients listed as younger than and older than 1 year of age were compared. RESULTS: Among 48 pediatric patients, 19 were infants less than one year of age. The median age among infants at listing was 3.7 months (range 0.5 to 8.9 months). Death before transplant occurred in 10 of 19 infants (53%) compared with 14 of 29 (48%) children. When comparing those infants who died prior to transplant with those who received organs, there were no significant differences with respect to size, blood type, age at listing, presence of pulmonary hypertension, or type of transplant for which the patient was listed. There was a trend toward poorer pre-transplant survival for infants when compared with children. Waiting times were significantly shorter for infants vs children (p = 0.02). The incidence of acute cellular rejection and serious infection was similar in the 2 groups. Infants had significantly longer hospitalization post-transplant and a trend toward poorer hospital survival, although survival at 1 year was comparable between the 2 groups. CONCLUSION: The outcome for infants listed for lung or heart/lung transplantation is similar to that of children; thus, very young age should not be considered a contraindication to lung or heart/lung transplantation. Earlier diagnosis and listing may decrease pre-transplant mortality.     

Patient selection for left ventricular assist devices

The use of mechanical support as a bridge to cardiac transplant has become the standard of care in many cardiac transplant centers. This therapy has been shown to increase survival and improve morbidity in carefully selected patients waiting for heart transplantation. With approximately 30000 patients being listed worldwide for transplant every year and only 3500 transplantations performed annually, alternative strategies need to be developed to minimize morbidity and mortality in this high-risk population. Patient selection remains the primary determinant of success with left ventricular assist device (LVAD) therapy. This article will review both the cardiac and extracardiac considerations needed in the assessment of patient suitability for LVAD support as a bridge to transplantation.     

Iloprost improves hemodynamics in patients with severe chronic cardiac failure and secondary pulmonary hypertension

PURPOSE: Significant pulmonary hypertension is a predictor of postoperative right heart insufficiency and increased mortality in patients undergoing orthotopic heart transplantation. Since the use of iv vasodilators is limited by their systemic effects, we evaluated the pulmonary and systemic hemodynamic effects of inhaled aerosolized iloprost (IP) in heart transplant candidates with elevated pulmonary vascular resistance (PVR). METHODS: Twenty-nine male heart transplant candidates because of dilated or ischemic cardiomyopathy with elevated PVR were included in the study. After assessing baseline hemodynamics, 50 micro g aerosolized IP were administered by inhalation. RESULTS: Inhalation of iloprost reduced PVR index (PVRI; 416 +/- 180 vs 349 +/- 173 dyn x sec(-1) x m(-2) x cm(-5); P < 0.01) and mean pulmonary artery pressure (MPAP; 28.6 +/- 9 vs 24.2 +/- 9.1 mmHg; P < 0.01), but did not affect blood pressure or systemic vascular resistance. An additional improvement of ventricular performance with an increase of cardiac index (CI; 2.8 +/- 0.7 vs 2.6 +/- 0.7 L x min(-1) x m(-2); P < 0.05) and a decrease of pulmonary capillary wedge pressure (PCWP; 15.6 +/- 6.8 vs 12.8 +/- 7.1 mmHg; P < 0.01) was observed after inhalation of IP. CONCLUSIONS: Inhaled aerosolized iloprost effectively reduces MPAP and is accompanied by an increase in CI and stroke index. Further advantages of iloprost inhalation are the lack of adverse reactions and ease of administration. Iloprost may be a useful drug to screen for vascular reactivity in cardiac transplantation patients.     

Analysis and predictors of pulmonary vascular resistance after cardiac transplantation

Elevated pulmonary vascular resistance is a known risk factor for early death from acute right ventricular failure after orthotopic cardiac transplantation. Patients in whom the elevated pulmonary vascular resistance is due primarily to increased left atrial pressure ("reactive") frequently have normalization of resistance after transplantation, but few studies have detailed the time course and magnitude of these changes. To analyze the response of pulmonary vascular resistance to cardiac transplantation, we analyzed data from 4353 right heart catheterizations on all 182 patients undergoing cardiac transplantation between 1981 and Jan. 1, 1990. Before transplantation 18% of patients had a pulmonary vascular resistance greater than 4 WU, 16% had a pulmonary artery systolic pressure greater than 60 mm Hg, and 16% had a transpulmonary gradient greater than 14 mm Hg. In the overall group of patients, pulmonary vascular resistance (mean value 2.63 WU), transpulmonary gradient (mean value 9.9 mm Hg), and pulmonary artery systolic pressure (mean value 48.0 mm Hg) were normalized within 1 week of cardiac transplantation. In patients with a high preoperative pulmonary vascular resistance (greater than or equal to 4 WU), the resistance fell promptly within 1 week of transplantation but continued to be slightly elevated throughout the period of follow-up. By multiple regression analysis, pulmonary vascular resistance at 1 week and 1 year after transplantation was significantly correlated with the pretransplantation resistance. Pulmonary vascular resistance anytime after transplantation was related to preoperative resistance, body surface area, and pulmonary artery diastolic pressure. Inferences: (1) As a group, cardiac transplant recipients have a normal pulmonary vascular resistance, transpulmonary gradient, and pulmonary artery systolic pressure within 1 week after transplantation with little change thereafter for at least several years. (2) Patients with reversible elevation of pulmonary vascular resistance before cardiac transplantation typically have a reactive and a fixed component. Cardiac transplantation relieves the reactive but not the fixed component. As a result, pulmonary vascular resistance early (within 1 week) and late after transplantation will have fallen but not completely normalized.