Showing papers in "Journal of Heart and Lung Transplantation in 2009"

INTERMACS Profiles of Advanced Heart Failure: The Current Picture

Abstract: Background The current classification of patients with New York Heart Association Class IV symptoms does not offer adequate description to allow optimal selection of patients for the current options of medical and pacing therapies, cardiac transplantation and mechanical circulatory support. Methods Seven clinical profiles and an arrhythmia modifier were developed and implemented into the first year of data collection for the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). The INTERMACS Coordinators' Council provided ongoing feedback regarding the characterization of patients receiving implantable devices. Results The definition of 7 clinical profiles revealed that 80% of current devices are being used in the 2 profiles with the highest levels of clinical compromise. The INTERMACS Coordinators' Council helped to identify gaps in the characterization of hospitalized patients on temporary assist devices and of homebound patients with resting symptoms, which has led to revised definitions of Profile 3 and 4 and the addition of 2 new modifiers, for temporary circulatory support devices in the hospital, and for frequent rehospitalization of patients at home. Conclusions Patients considered for mechanical circulatory support can now be classified using the 7 profiles plus 3 modifiers developed through INTERMACS. Further understanding these profiles and their impact on outcome should help to better select patients and therapies in the advanced stages of disease.

Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device: analysis of outpatient anti-coagulation.

Abstract: Background The HeartMate II (Thoratec, Pleasanton, CA) is an effective bridge to transplantation (BTT) but requires anti-coagulation with warfarin and aspirin. We evaluated the risk of thromboembolism and hemorrhage related to the degree of anti-coagulation as reflected by the international normalized ratio (INR). Methods INRs were measured monthly for 6 months in all discharged HeartMate II BTT patients and at an event. Each INR was assigned to ranges of INRs. Adverse events analyzed were ischemic and hemorrhagic stroke, pump thrombosis, and bleeding requiring surgery or transfusion. Events were correlated to the INR during the event and at the start of the month. Results In 331 patients discharged on support, 10 had thrombotic events (9 ischemic strokes, 3 pump thromboses), and 58 had hemorrhagic events (7 strokes, 4 hemorrhages requiring surgery, and 102 requiring transfusions). The median INR was 2.1 at discharge and 1.90 at 6 months. Although the incidence of stroke was low, 40% of ischemic strokes occurred in patients with INRs 3.0. The highest incidence of bleeding was at INRs > 2.5. Conclusions The rate of thromboembolism during long-term outpatient support with the HeartMate II is low. The low number of thrombotic events appears to be offset by a greater number of hemorrhagic events. An appropriate target INR is 1.5 to 2.5 in addition to aspirin therapy. In patients having recurrent episodes of bleeding, the risk of lowering the target INR appears to be small.

Asymptomatic Antibody-mediated Rejection After Heart Transplantation Predicts Poor Outcomes

Abstract: Background Antibody-mediated rejection (AMR) has been associated with poor outcome after heart transplantation. The diagnosis of AMR usually includes endomyocardial biopsy findings of endothelial cell swelling, intravascular macrophages, C4d+ staining, and associated left ventricular dysfunction. The significance of AMR findings in biopsy specimens of asymptomatic heart transplant patients (normal cardiac function and no symptoms of heart failure) is unclear. Methods Between July 1997 and September 2001, AMR was found in the biopsy specimens of 43 patients. Patients were divided into 2 groups: asymptomatic AMR (AsAMR, n = 21) and treated AMR (TxAMR with associated left ventricular dysfunction, n = 22). For comparison, a control group of 86 contemporaneous patients, without AMR, was matched for age, gender, and time from transplant. Outcomes included 5-year actuarial survival and development of cardiac allograft vasculopathy (CAV). Patients were considered to have AMR if they had ≥ 1 endomyocardial biopsy specimen positive for AMR. Results The 5-year actuarial survival for the AsAMR (86%), TxAMR (68%), and control groups (79%) was not significantly different ( p = 0.41). Five-year freedom from CAV (≥ 30% stenosis in any vessel) was AsAMR, 52%; TxAMR, 68%; and control, 79%. Individually, freedom from CAV was significantly lower in the AsAMR group compared with the control group ( p = 0.02). There was no significant difference between AsAMR vs TxAMR and TxAMR vs control for CAV. Conclusions Despite comparable 5-year survival with controls after heart transplantation, AsAMR rejection is associated with a greater risk of CAV. Trials to treat AsAMR to alter outcome are warranted.

RADIAL: a novel primary graft failure risk score in heart transplantation.

Abstract: Background Primary graft failure (PGF) is the leading cause of early mortality after heart transplantation (HT). Our aim is to propose a working definition of PGF and to develop a predictive risk score. Methods PGF was defined by four criteria reflecting significant myocardial dysfunction, severe hemodynamic impairment, early onset after HT, and absence of secondary causes of graft dysfunction. We identified independent risk factors for PGF in a derivation series of 621 HTs and constructed a predictive model. After proving its internal consistency we tested the model in a prospective validation series. Results The incidence and lethality of PGF in our series were 9% and 80%, respectively. We identified 6 multivariate risk factors for PGF ( R ight atrial pressure ≥10 mm Hg, recipient A ge ≥60 years, D iabetes mellitus, I notrope dependence, donor A ge ≥30 years, L ength of ischemic time ≥240 minutes—i.e., RADIAL). Analysis of isolated right ventricular failure showed similar predictors. The RADIAL score was obtained by adding 1 point for each of these factors present in a given HT. PGF incidence increased significantly as the RADIAL score increased ( p Conclusions PGF as defined by these criteria showed a high impact on early post-HT mortality in our series. The RADIAL score showed good ability to predict the development of PGF, and could be useful in the prevention and early treatment of this complication.

Acute antibody-mediated rejection after lung transplantation.

Abstract: The role of humoral immunity after lung transplantation remains unclear. In this report, we describe the pathologic findings and clinical course of a case of acute antibody-mediated rejection (AMR) after lung transplantation. After an uncomplicated early course, a 31-year-old man with cystic fibrosis developed acute graft dysfunction 1 month after bilateral lung transplantation. Lung biopsies showed acute pneumonitis with capillary injury, neutrophilic infiltration and nuclear dust. Immunostaining for C4d demonstrated endothelial cell deposition, and circulating donor-specific human leukocyte antigen (HLA) antibodies were identified. Despite severe hypoxemic respiratory failure, he responded well to a regimen consisting of methylprednisolone, plasma exchange, intravenous immunoglobulin and rituximab therapy. He completely recovered clinically although donor-specific HLA antibodies have remained detectable. The incidence of acute AMR after lung transplantation is unknown, but this case fulfills all of the consensus diagnostic criteria, and we suggest that AMR could be an under-recognized cause of acute graft dysfunction.

Incidence of ventricular arrhythmias in patients on long-term support with a continuous-flow assist device (HeartMate II).

Abstract: The incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients supported with a continuous-flow left ventricular assist device (LVAD) has not been investigated in detail. In 23 consecutive recipients of a HeartMate II, we analyzed the incidence of VT/VF during a total of 266 months of follow-up. Sustained VT or VF occurred in 52% of the patients, with the majority of arrhythmias occurring in the first 4 weeks after LVAD implantation. VT/VF requiring implantable cardioverter-defibrillator (ICD) shock or external defibrillation occurred in 8 patients and significant hemodynamic instability ensued in 3 patients. There were no clear predictors of VT/VF, and it is argued that prophylactic ICD implantation should be considered in patients supported with a continuous-flow LVAD.

Usefulness of the INTERMACS scale to predict outcomes after mechanical assist device implantation.

Abstract: Background The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale classifies advanced heart failure patients according to hemodynamic status This study assessed the usefulness of the INTERMACS scale to predict outcomes in advanced heart failure patients undergoing mechanical circulatory support (MCS) Methods Fifty-four patients underwent MCS implantation from 2001 to 2007 Group A included 27 patients at INTERMACS level 1 and 2 Group B included 27 at INTERMACS level 3 and 4 Patient characteristics pre-MCS implant, incidence of complications during support, and survival between groups were compared Results Before MCS implantation, Group A had significantly lower cardiac index, mean arterial blood pressure, systolic pulmonary pressure, higher central venous pressure, and lower urine output ( p p Conclusion INTERMACS levels identified patients at risk for developing complications after MCS support INTERMACS is a valid score system that should be considered as a tool to assess patient profile and predict complications and mortality after MCS implantation

Report from a consensus conference on the sensitized patient awaiting heart transplantation.

Abstract: A consensus conference took place on April 8, 2008 to assess the current status of sensitization in the pre–heart transplant patient, the use and efficacy of desensitization therapies, and the outcome of desensitized patients after heart transplantation. The conference had 71 participants (transplant cardiologists, surgeons, immunologists and pathologists; see Appendix) representing 51 heart transplant centers from North America, Europe, Asia and Australia. Prior to the conference, survey data (regarding the sensitized patient) were submitted by 23 of the 51 centers participating in the conference (Table 1).

Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation

Abstract: Background Cardiac allograft vasculopathy (CAV) is primarily immune-mediated. We investigated the role of cellular rejection in CAV development. Methods The study comprised 252 cardiac transplant recipients (mean age, 49.02 ± 17.05 years; mean follow-up, 7.61 ± 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R=1, 2R=2, 3R=3) and any rejection score (ARS; calculated as 0R=0, 1R=1, 2R=1; 3R=1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. CAV was defined as coronary stenosis of 40% or more and/or distal pruning of secondary side branches. Thirty-two patients had undergone 3-dimensional intravascular ultrasound (IVUS) at baseline and with virtual histology (VH) IVUS at 24 months. Results In univariate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 0.99–3.90, p = 0.05) and ARS (HR, 2.22; 95% CI, 1.01–4.95; p = 0.047) were associated with increased risk of CAV. In multivariate analysis, 6-month TRS (HR, 2.84; 95% CI, 1.44–6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset ( p = 0.018). There was direct correlation ( r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core demonstrated by VH-IVUS at 24 months. Conclusion Recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.

Impact of U.S. Lung Allocation Score on Survival After Lung Transplantation

Abstract: Background The Lung Allocation Score (LAS) dramatically changed organ allocation in lung transplantation. The impact of this change on patient outcomes is unknown. The purpose of the study was to examine early mortality after lung transplantation under the LAS system. Methods All patients undergoing first-time lung transplantation during the period from May 1, 2005 through April 30, 2008 were included in the study. The cohort was divided into quintiles by LAS. A high-risk group (LAS >46) was comprised of the highest quintile, Quintile 5, and a low-risk group (LAS ≤46) included the lower quintiles, Quintiles 1 through 4. A time-to-event analysis was performed for risk of death after transplantation using Kaplan–Meier survival and Cox proportional hazards models. Results There were 4,346 patients who underwent lung transplantation during the study period. Patients in the high-risk group (LAS >46) were more likely to have idiopathic pulmonary fibrosis (IPF; 52.9% vs 23.8%, p p p p Conclusions Overall 1-year survival under the new LAS system appears to be similar to that in historic reports. However, risk of death was significantly increased among patients with LAS >46.

Cardiovascular mortality among heart transplant recipients with asymptomatic antibody-mediated or stable mixed cellular and antibody-mediated rejection.

Abstract: Background Little has been reported on the clinical significance of asymptomatic antibody-mediated rejection (AMR) alone or mixed rejection (MR), defined as concurrent cellular rejection (CR) and AMR in heart transplantation. In this study, we examined whether a differential impact on cardiovascular mortality (CVM) existed when comparing asymptomatic AMR, to stable MR or CR. Methods The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program pathology database of all heart transplant recipients between 1985 and 2004 was queried. Patients were classified as cellular, antibody-mediated, or mixed rejectors based on their predominant pattern of rejection type in the first three months post-transplant. Kaplan-Meier survival curves were fit to each of the three groups and analyses were adjusted for age at the time of transplant, gender, and underlying primary cardiac disease. Results Eight hundred and sixty nine heart transplant recipients qualified for analysis. Over the study period, patients with asymptomatic AMR or stable MR patterns had significantly worse CVM when compared to patients with stable CR pattern (AMR, 21.2%; MR, 18.0%; CR, 12.6%; AMR vs. CR, p = 0.009; MR vs. CR, p = 0.001). In contrast, CVM was comparable in patients with asymptomatic AMR or stable MR patterns ( p = 0.9). Conclusions Asymptomatic or subclinical AMR and MR are clinically relevant, should be recognized, and deserve consideration for therapeutic intervention in hopes of avoiding adverse outcomes.

Assessment of arterial blood pressure during support with an axial flow left ventricular assist device.

Abstract: Background Axial-flow left ventricular assist devices (LVADs) have a number of advantages over pulsatile LVADs, including their small size and better durability. Although the design of axial-flow pumps should result in fewer serious complications during support, some adverse events persist. Thus, optimizing patient treatment may minimize complications, allowing broader acceptance of these devices. In this study, we analyzed standard blood pressure measurements obtained by cuff and arterial lines and used these values to help establish guidelines for the safe operation of axial-flow LVADs. Methods The study included 35 heart failure patients who had received a Jarvik 2000 (Jarvik Heart Inc, New York, NY) axial-flow LVAD as a bridge to cardiac transplantation. Blood pressure and echocardiographic data were collected during speed-change studies. Results Systolic blood pressure did not change, but diastolic, mean, and pulse pressure values changed significantly with changes in pump speed ( p p p = 0.33). A pulse pressure calculation of 15 mm Hg was predictive of aortic valve opening 65% of the time. Conclusions Because aortic valve opening minimizes the risk of complications, a safe zone for most patients is a pulse pressure > 15 mm Hg. Arterial blood pressure changes during axial-flow LVAD support can be predicted and may be used as a guide for the proper management of pump speed settings. A calculated pulse pressure from an arterial line or automated cuff may be used to determine a safe zone of Jarvik 2000 operation, leading to fewer complications.

Increased CD62e+ Endothelial Microparticle Levels Predict Poor Outcome in Pulmonary Hypertension Patients

Abstract: Background: Endothelial and leukocytes-derived microparticles (EMPs and LMPs, respectively) are increased in patients with pulmonary hypertension (PH). We hypothesized that the levels of circulating EMPs and LMPs could predict outcome in these patients. Methods: Patients undergoing right heart catheterization for untreated pre-capillary PH were eligible for the study. Baseline hemodynamics and biologic and clinical parameters were measured at the time of enrollment. Measurements of CD62e, CD144 and CD31/CD41 EMPs and CD45 LMPs were performed using flow cytometry in venous platelet-free plasma samples. After inclusion, patients were treated at the discretion of the physician and prospectively followed for 12 months. The primary end-point was the combined occurrence of death and re-admission for right heart failure (RHF) or worsening of RHF symptoms. Results: Seven of 21 patients (mean age 54.1 3.5 years, 62% female) experienced the primary end-point during the study period. These patients had higher baseline levels of CD62e EMPs, LMPs and hsCRP (high sensitivity C-reactive protein) compared to patients without events (p 0.05), whereas no difference was observed for other microparticles and functional and hemodynamics parameters. Receiver operating curve analysis showed that baseline CD62e EMPs levels of 353 events/l predicted clinical complications. Kaplan‐Meier analysis revealed that patients with baseline CD62e EMPs above this cut-off value had a significantly worse prognosis compared with those subjects who had levels below this cut-off (p 0.02, log-rank statistics). Conclusions: Elevated levels of circulating CD62e EMPs but not LMPs in PH patients prior to treatment are associated with adverse clinical events. Assessment of CD62e EMPs levels may represent a new tool for stratification of PH patients. J Heart Lung Transplant 2009;28:1081‐6. Copyright © 2009 by the International Society for Heart and Lung Transplantation.

Efficacy of Oral Ribavirin in Lung Transplant Patients With Respiratory Syncytial Virus Lower Respiratory Tract Infection

Abstract: Background Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRI) and is a risk factor for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Currently, the most widely used therapy for RSV is inhaled ribavirin. However, this therapy is costly and cumbersome. We investigated the utility of using oral ribavirin for the treatment of RSV infection after LTx. Methods RSV was identified in nasopharyngeal swabs (NPS) or bronchoalveolar lavage (BAL) using direct fluorescent antibody (DFA) in 5 symptomatic LTx patients diagnosed with LRI. Data were collected from December 2005 and August 2007 and included: age; gender; type of LTx; underlying disease; date of RSV; pulmonary function prior to, during and up to 565 days post-RSV infection; need for mechanical ventilation; concurrent infections; and radiographic features. Patients received oral ribavirin for 10 days with solumedrol (10 to 15 mg/kg/day intravenously) for 3 days, until repeat NPS were negative. Results Five patients had their RSV–LRI diagnosis made at a median of 300 days post-LTx. Mean forced expiratory volume in 1 second (FEV 1 ) fell 21% ( p 1 returned to baseline and was maintained at follow-up of 565 days. There were no complications and no deaths with oral therapy. A 10-day course of oral ribavirin cost $700 compared with $14,000 for nebulized ribavirin at 6 g/day. Conclusions Treatment of RSV after LTx with oral ribavirin and corticosteroids is well tolerated, effective and less costly than inhaled ribavirin. Further studies are needed to directly compare the long-term efficacy of oral vs nebulized therapy for RSV.

Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1.

Abstract: Background Post-transplant baseline forced expiratory volume in 1 second (FEV 1 ) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV 1 . Methods A multivariate survival and competing risk analysis of a large consecutive series of patients ( n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation ( n = 39) and no available lung function measurements ( n = 4). Results The first maximum FEV 1 occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an increased cause-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV 1 was a significant confounder in all survival and competing risk analyses of BOS ( p Conclusion Despite early diagnosis and prompt treatment, acute cellular rejection remains an independent risk factor for the development of BOS after adjusting for the confounding of post-transplant baseline FEV 1 .

Gastroesophageal reflux in bronchiolitis obliterans syndrome: a new perspective.

Abstract: Background Long-term survival after lung transplantation (LTx) is limited largely by bronchiolitis obliterans syndrome (BOS). Gastroesophageal reflux disease (GERD) is proposed as a risk factor for BOS development. This study investigates the relationship between BOS and GERD measured by esophageal impedance. Methods After the initiation of routine screening for GERD, 59 LTx recipients underwent ambulatory esophageal impedance monitoring. Exposure to acid reflux and non-acid liquid reflux was recorded. Clinical outcomes were reviewed to analyze any effect of reflux on the time to development of BOS. Results Thirty-seven (65%) had abnormal acid reflux and 16 (27%) had abnormal non-acid reflux. There was no relationship between acid reflux and BOS. The hazard ratio (HR) for development of BOS in the presence of abnormal non-acid reflux was 2.8 ( p = 0.043). The HR for development of BOS increased to 3.6 ( p = 0.022) when the number of acute rejection episodes was also taken into account. Conclusions GERD is prevalent in LTx recipients and may represent a modifiable risk factor for BOS. This study found non-acid reflux, measured by esophageal impedance to be associated with the development of BOS. Prospective studies are now required to investigate a causal association between GERD and the development of BOS and to establish the role of surgery for GERD in preventing progression to BOS. The methods used to identify GERD in future studies may be important.

Incidence and risk factors for mortality in infants awaiting heart transplantation in the USA.

Abstract: Background Infants awaiting heart transplantation (HT) face the highest wait-list mortality among all children and adults listed for HT in the USA. We sought to determine the risk of death for infants Methods We analyzed outcomes for all infants listed for HT in the USA from January 1999 to July 2006, using data reported to the U.S. Scientific Registry of Transplant Recipients. Results Of the 1,133 listed infants, 61% were Conclusions One in four infants listed for HT in the USA die before a donor heart can be identified. Wait-list mortality is associated with weight

Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety.

Abstract: Background The main problem with using nebulized liposomal amphotericin (n-LAB) as prophylaxis for Aspergillus infection after lung transplantation is the lack of knowledge of its pharmacokinetics and its possible adverse effects. The aim of this study was to measure post-inhalation amphotericin B concentration in the respiratory tract and serum of lung transplant patients and assess the effects of n-LAB on respiratory function. Methods Thirty-two consecutive bronchoscopies were performed on 27 lung transplant patients at two hospitals. Amphotericin B concentration in the first and third aliquot of bronchoalveolar lavage material was measured in steady state. The first aliquot approximates most closely the true amphotericin B concentrations in the proximal airway, whereas the third aliquot provides an optimum sample from the distal airway. Results At 2 days, mean amphotericin B concentrations were 11.1 μg/ml (95% confidence interval [CI]: 16.5 to 5.7 μg/ml) and 9.0 μg/ml (95% CI: 14.3 to 3.8 μg/ml) in the first and third aliquot, respectively. Thereafter, concentrations declined progressively. At 14 days, concentrations were 3.0 μg/ml (95% CI: 4.4 to 1.5 μg/ml) in the first aliquot and 4.1 μg/ml (95% CI: 6.1 to 2.1 μg/ml) in the third aliquot ( p = not statistically significant). Traces of amphotericin B (0.1 μg/ml) were found in serum samples from only 1 of 27 patients. Mean value of forced expiratory volume in the first second (FEV 1 ) was similar before and after n-LAB. Conclusions Amphotericin B concentrations after n-LAB remained high for 14 days, at adequate concentrations for prophylaxis of Aspergillus infection. No significant systemic absorption of amphotericin B was detected and no effect was observed on respiratory function. This promising prophylactic regimen warrants assessment in future clinical studies.

Can the Seattle Heart Failure Model Be Used to Risk-stratify Heart Failure Patients for Potential Left Ventricular Assist Device Therapy?

Abstract: Background According to results of the REMATCH trial, left ventricular assist device therapy in patients with severe heart failure has resulted in a 48% reduction in mortality. A decision tool will be necessary to aid in the selection of patients for destination left ventricular assist devices (LVADs) as the technology progresses for implantation in ambulatory Stage D heart failure patients. The purpose of this analysis was to determine whether the Seattle Heart Failure Model (SHFM) can be used to risk-stratify heart failure patients for potential LVAD therapy. Methods The SHFM was applied to REMATCH patients with the prospective addition of inotropic agents and intra-aortic balloon pump (IABP) ± ventilator. Results The SHFM was highly predictive of survival ( p = 0.0004). One-year SHFM-predicted survival was similar to actual survival for both the REMATCH medical (30% vs 28%) and LVAD (49% vs 52%) groups. The estimated 1-year survival with medical therapy for patients in REMATCH was 30 ± 21%, but with a range of 0% to 74%. The 1- and 2-year estimated survival was ≤50% for 81% and 98% of patients, respectively. There was no evidence that the benefit of the LVAD varied in the lower vs higher risk patients. Conclusions The SHFM can be used to risk-stratify end-stage heart failure patients, provided known markers of increased risk are included such inotrope use and IABP ± ventilator support. The SHFM may facilitate identification of high-risk patients to evaluate for potential LVAD implantation by providing an estimate of 1-year survival with medical therapy.

Physical activity in daily life 1 year after lung transplantation.

Abstract: Background Reduced physical fitness has been reported to occur after lung transplantation. Pre- and post-transplant factors, including an inactive lifestyle, have been proposed as possible causes. However, daily physical activity has not been objectively assessed so far in lung recipients. The purpose of this study was to objectively measure daily physical activity in lung recipients. Methods Twenty-two clinically stable patients with single ( n = 7) and bilateral lung grafts ( n = 15) underwent measurements of physical activity with activity monitors at least 12 months after surgery. Results were compared with findings from 22 healthy, age- and gender-matched control subjects. Results Substantial and statistically significant differences in daily activity were observed. Steps, standing time and moderate-intensity activity of lung recipients were reduced by 42%, 29% and 66%, respectively, relative to controls. Daily sedentary time was increased by 30%. Daily steps correlated with self-reported physical functioning ( r = 0.81), 6-minute walk distance ( r = 0.68), quadriceps force ( r = 0.66) and maximum workload ( r = 0.63). Conclusions This study has shown for the first time that daily activity is substantially reduced after lung transplantation and related to measures of physical fitness and health-related quality of life. Future studies need to examine whether physical activity can be modified to improve functional recovery after lung transplantation.

Mechanical circulatory support in patients with heart failure secondary to transposition of the great arteries

Abstract: Advances in palliation of congenital heart disease have resulted in improved survival to adulthood. Many of these patients ultimately develop end-stage heart failure requiring left ventricular assist device implantation (LVAD). However, morphologic differences in the systemic ventricle of these patients require careful attention to cannula placement. We report on the evolution of our surgical technique for implanting LVADs in 3 patients with transposition of the great arteries and congenitally corrected transposition of the great arteries. Applying standard LV cannulation techniques to the systemic ventricle led us too anteriorly in our first patient, creating obstruction by the moderator band. Subsequent use of epicardial and transesophageal echocardiography allowed for intraoperative localization of the intracardiac muscular structures to identify the optimal cannulation site. The acute angle of the inflow cannula on the DeBakey LVAD (MicroMed Technology, Houston, TX) required flipping the device 180°. The HeartMate II device (Thoratec, Pleasanton, CA) could be shifted towards the midline. One patient underwent successful transplant and 2 are home waiting for a donor organ. We conclude from our experience that LVAD surgery can be safely performed in patients with congenital heart disease when implanted under echocardiographic guidance.

Prophylaxis versus preemptive anti-cytomegalovirus approach for prevention of allograft vasculopathy in heart transplant recipients.

Abstract: Background Cytomegalovirus (CMV) infection may influence the development of cardiac allograft vasculopathy (CAV). Prophylactic or preemptive administration of anti-CMV agents effectively prevents acute CMV manifestations. However, studies comparing allograft-related outcomes between these anti-CMV approaches are lacking. Herein we report a longitudinal observational study comparing CAV development between prophylactic and preemptive approaches. Methods The 1-year change in maximal intimal thickening (MIT) assessed by intravascular ultrasound at 1 and 12 months after heart transplantation (the major surrogate for late survival) was compared in groups of patients routinely assigned to a preemptive strategy (from November 2004 to October 2005; n = 21) or receiving valganciclovir prophylaxis (from November 2005 to October 2006; n = 19). CMV infection was monitored with pp65 antigenemia. Results The 1-year increase in MIT was significantly lower in patients receiving prophylaxis compared with those managed preemptively (0.15 ± 0.17 vs 0.31 ± 0.20 mm; p = 0.01). Prophylaxed recipients presented less frequently with MIT change ≥0.3 mm ( p = 0.03) and ≥0.5 mm ( p = 0.10) than those managed preemptively. Prophylaxis was also associated with later onset of CMV infection ( p = 0.01), lower peak CMV detection ( p p = 0.04). After adjusting for metabolic risk factors and other possible confounders, prophylaxis remained independently associated with lower risk for MIT change ≥0.3 mm (odds ratio=0.09, 95% confidence interval 0.01 to 0.93; p = 0.04). Conclusions Universal prophylaxis was associated with delayed onset of CMV infection, lower viral burden, reduced CMV disease/syndrome and less intimal thickening, as compared with a preemptive anti-CMV approach. Randomized studies are required to confirm the potential benefits of prophylaxis vs a preemptive approach in heart transplant recipients.

Initial Experience With Lung Donation After Cardiocirculatory Death in Canada

Abstract: Background Organ donation after cardiac death (DCD) has the potential to alleviate some of the shortage of suitable lungs for transplantation. Only limited data describe outcomes after DCD lung transplantation. This study describes the early and intermediate outcomes after DCD lung transplantation in Canada. Methods Data were collected from donors and recipients involved in DCD lung transplantations between June 2006 and December 2008. Described are the lung DCD protocol, donor characteristics, and the occurrence of post-transplant events including primary graft dysfunction (PGD), bronchial complications, acute rejection (AR), bronchiolitis obliterans syndrome (BOS), and survival. Results Successful multiorgan controlled DCD increased from 4 donors in 2006 to 26 in 2008. Utilization rates of lungs among DCD donors were 0% in 2006, 11% in 2007, and 27% in 2008. The lung transplant team evaluated 13 DCD donors on site, and lungs from 9 donors were ultimately used for 10 recipients. The 30-day mortality was 0%. Severe PGD requiring extracorporeal membrane oxygenation occurred in 1 patient. Median intensive care unit stay was 3.5 days (range, 2–21 days). Hospital stay was 25 days (range, 9–47 days). AR occurred in 2 patients. No early BOS has developed. Nine (90%) patients are alive at a median of 270 days (range, 47–798 days) with good performance status and lung function. One patient died of sepsis 17 months after transplantation. Conclusion DCD has steadily increased in Canada since 2006. The use of controlled DCD lungs for transplantation is associated with very acceptable early and intermediate clinical outcomes.

Lung Transplantation for Lymphangioleiomyomatosis: The European Experience

Abstract: Background: Lung transplantation has been accepted widely as therapy for end-stage pulmonary lymphangioleiomyomatosis (LAM); however, single-center and national experience is limited due to the rarity of LAM. Methods: We report the recent European experience of lung transplantation for LAM. A self-administered questionnaire was distributed to 30 European lung transplant centers to evaluate patients who underwent primary lung transplantation for LAM (1997 to 2007). Results: Seventy percent of centers responded to the questionnaire. A total of 61 lung transplants were undertaken in women only, with mean age at transplant 41.3 years (SD 5.1). Centers performed a median of 2 (0 to 9) transplant operations. Severe pleural adhesions were the most common intra-operative complication. Early deaths (N = 6) were due to primary graft or multiple-organ failure or sepsis. Twelve recipients were diagnosed with bronchiolitis obliterans syndrome at a median of 20 months (range 10 to 86 months) post-transplant. LAM-related complications included renal angiomyolipoma and pneumothorax in the native lung. Recurrence of LAM occurred in 4 recipients. As of December 2007, actuarial Kaplan–Meier survival was 79% at 1 year and 73% at 3 years post-transplant. Conclusions: Post-transplant outcome for pulmonary LAM in the recent era appears to have improved compared with the previous era. LAM-related complications remain common, but recurrence of LAM in the allograft is rare.

Effect of etiology and timing of respiratory tract infections on development of bronchiolitis obliterans syndrome.

Abstract: Background Among the many potential risk factors influencing the development of bronchiolitis obliterans syndrome (BOS), acute cellular rejection is the most frequently identified. Despite the unique susceptibility of the lung allograft to pathogens, the association with respiratory tract infections remains unclear. In this study we analyze the role respiratory tract infections have on the development of BOS after lung transplantation. Methods Data from a single center were analyzed from 161 lung recipients transplanted from November 1990 to November 2005, and who survived >180 days. Univariate and multivariate Cox regression analyses were performed using BOS development and the time-scale was reported with hazard ratios (HRs) and confidence intervals (CIs). Results Significant findings by univariate analysis per 100 patient-days prior to BOS onset included acute rejection, cytomegalovirus (CMV) pneumonitis, Gram-negative respiratory tract infections, Gram-positive respiratory tract infections and fungal pneumonias. Multivariate analysis indicated acute rejection, Gram-negative, Gram-positive and fungal pneumonias with HRs (CI) of 84 (23 to 309), 6.6 (1.2 to 37), 6,371 (84 to 485,000) and 314 (53 to 1,856) to be associated with BOS, respectively. Acute rejection, CMV pneumonitis, Gram-positive pneumonia and fungal pneumonitis in the first 100 days had HRs (CI) of 1.8 (1.1 to 3.2), 3.1 (1.3 to 6.9), 3.8 (1.5 to 9.4) and 2.1 (1.1 to 4.0), respectively, and acute rejection and fungal pneumonitis in the late post-operative period with HRs (CI) of 2.3 (1.2 to 4.4) and 1.5 (1.1 to 1.9), respectively. Conclusions In addition to acute rejection, pneumonias with GP, GN and fungal pathogens occurring prior to BOS are independent determinants of chronic allograft dysfunction. Early recognition and treatment of these pathogens in lung transplant recipients may improve long-term outcomes after transplantation.

Utility of virtual crossmatch in sensitized patients awaiting heart transplantation.

Abstract: Background Organ transplant candidates with serum antibodies directed against human leukocyte antigens (HLA) face longer waiting times and higher mortality while awaiting transplantation. This study examined the accuracy of virtual crossmatch, in which recipient HLA-specific antibodies, identified by solid-phase assays, are compared to the prospective donor HLA-type in heart transplantation. Methods We examined the accuracy of virtual crossmatch in predicting immune compatibility of donors and recipients in heart transplantation and clinical outcomes in immunologically sensitized heart transplant recipients in whom virtual crossmatch was used in allograft allocation. Results Based on analysis of 257 T-cell antihuman immunoglobulin complement-dependent cytotoxic (AHG-CDC) crossmatch tests, the positive predictive value of virtual crossmatch (the likelihood of an incompatible virtual crossmatch resulting in an incompatible T-cell CDC-AHG crossmatch) was 79%, and the negative predictive value of virtual crossmatch (the likelihood of a compatible virtual crossmatch resulting in a compatible T-cell CDC-AHG crossmatch) was 92%. When used in a cohort of 28 sensitized patients awaiting heart transplantation, 14 received allografts based on a compatible virtual crossmatch alone from donors in geographically distant locations. Compared with the other 14 sensitized patients who underwent transplant after a compatible prospective serologic crossmatch, the rejection rates and survival were similar. Conclusion Our findings are evidence of the accuracy of virtual crossmatch and its utility in augmenting the opportunities for transplantation of sensitized patients.

Impact of recipient body mass index on organ allocation and mortality in orthotopic heart transplantation.

Abstract: Background It is unknown whether obesity affects organ allocation in orthotopic heart transplantation (OHT). The United Network for Organ Sharing (UNOS) database provides an opportunity to examine this issue. Methods We reviewed UNOS data to identify 27,002 OHT candidates placed on the heart transplantation wait list (1998 to 2007). Patients were stratified by body mass index (BMI) at listing. Multivariate Cox proportional hazards model estimated the chance of receiving OHT, adjusting for factors that might affect allocation. Mortality on the wait list and post-OHT mortality were estimated using the Kaplan–Meier method. Results Of 27,002 patients listed, the distribution of BMI was as follows: BMI 18.5 to 24.9, n = 9,734 (36.0%); BMI 25 to 29.9, n = 10,063 (37.2%); BMI 30 to 34.9, 5,500 (20.4%); and BMI ≥35, 1,705 (6.3%). BMI was strongly associated with a decrease in the likelihood of receiving OHT once on the wait list (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.95 to 0.96, p p Conclusions Obese individuals wait longer and have a lower likelihood of receiving a donor heart after listing, despite similar short-term survival. The results of this study point to a potential provider bias for obese individuals in OHT.

Prognostic Value of Bronchoalveolar Lavage Neutrophilia in Stable Lung Transplant Recipients

Abstract: Background Bronchoalveolar lavage (BAL) neutrophilia may identify patients prone to develop bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). This study assessed the predictive value of BAL neutrophilia in stable recipients. Methods Evaluated were 63 consecutive recipients 3 to 12 months after LTx demonstrating no acute rejection (AR) and lymphocytic bronchitis (LB; B ≤ 1 without infection; BOS, 0). Recipients were subdivided into never-BOS (follow-up ≥ 12 months) and ever-BOS groups (i.e., BOS development ≥ 1 after bronchoscopy). Results The groups were statistically indistinguishable for demographic data and preceding AR and LB episodes. Onset of BOS was at a median of 232 days (range, 87–962) after bronchoscopy. The ever-BOS group (16 patients) demonstrated a significantly higher percentage of neutrophils compared with the never-BOS group (47 patients) at the time of bronchoscopy (33.6% ± 2.1% vs 9.9% ± 1.1%, p p p Conclusion BAL neutrophilia in stable recipients is of predictive value to identify recipients at risk for BOS. These data warrant prospective confirmation and further studies to evaluate the benefit of preemptive therapy for potential BOS patients.