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This study sought to assess the utility of the Destination Therapy Risk Score (DTRS) in patients with continuous flow left ventricular assist devices (LVAD).The DTRS was developed to predict the risk of 90-day in-hospital mortality with pulsatile flow LVAD as destination therapy (DT). Despite ongoing use in patients with continuous flow devices, its utility has not been studied in such populations.The DTRS was determined in 1,124 patients with the continuous flow HeartMate II (Thoratec Corporation, Pleasanton, California) LVAD as a bridge to transplant (BTT, n = 486) and DT (n = 638) and 114 DT patients with the pulsatile flow HeartMate XVE (Thoratec Corporation). Patients were divided into risk groups based on DTRS: low (0-8), medium (9-16), and high (16).The 90-day in-hospital mortality for low-, medium-, and high-risk groups was 8%, 7%, and 16%, respectively, for BTT patients; 9%, 12%, and 19%, respectively, for DT patients; and 11%, 18%, and 25%, respectively, for XVE DT patients. The high-risk groups had more than a 2-fold increased risk of mortality compared with the low-risk groups. However, the area under the receiver-operating characteristic curve for 90-day in-hospital mortality yielded modest values ranging from 0.54 to 0.58 for the HeartMate II BTT and DT groups, respectively. Survival rates over 2 years were statistically significantly different as stratified by the 3 DTRS groups for patients implanted for DT but not for BTT.DTRS provides poor discrimination of mortality for BTT patients and only modest discrimination for DT patients receiving continuous flow LVAD.

Background The Model for End-stage Liver Disease (MELD) score is a marker of multisystem organ dysfunction. It has been used to predict outcomes in patients undergoing hepatic and nonhepatic interventions. End-stage heart disease exhibits a varying degree of multiorgan dysfunction, which impacts the adverse events related to ventricular assist device (VAD) therapy. Our aim for the present study was to investigate the value of MELD score in predicting adverse events related with VAD therapy. Methods Data were collected on demographics, clinical characteristics, MELD score; Interagency Registry for Mechanically Assisted Circulatory Support-defined VAD adverse events within the first 6 months, and survival from VAD recipients (n = 286; from 1996 to 2009). Univariable, multivariable, and Cox regression analyses were performed using SAS software (SAS Institute, Cary, NC). Results The mean MELD score was 14.4 ± 5.9. Actuarial incidence of infections, bleeding events, and cardiovascular dysfunction at 6 months was 65.4%, 52.1%, and 45.6%, respectively. Multivariable Cox proportional hazards model (controlling for gender, type of device, diagnosis, intention to treat, urgency, and inotropic use) confirmed that MELD score predicted mortality, respiratory, and renal dysfunction at 6 months ( p Conclusions Preoperative MELD score is predictive of mortality, respiratory, and renal dysfunction at 6 months after controlling for gender, type of device, diagnosis, intention to treat, urgency, and inotropic use. The MELD score may be used as a quantitative tool to assess the adverse events associated with VAD therapy.

Calcineurin inhibitor (CNI)-associated renal insufficiency is common after cardiac transplantation (CTX); however, the addition of sirolimus allows for CNI dose reduction and this strategy may limit CNI renal toxicity. This study examines the long-term effects of such a strategy.Patients from a single center who had CTX from 1990 to 2007 and who were converted to sirolimus and a dose-reduced CNI were compared to group-matched controls maintained on CNI and an antiproliferative agent.One hundred and fifty-five patients (79 sirolimus and 76 controls) were included and had similar baseline characteristics. Sirolimus was started a mean of 1429 d post-CTX and maintained for a mean of 823 d. Reason for conversion to sirolimus was renal insufficiency (34%), vasculopathy (29%), recurrent rejection (19%), and other (18%). The eGFR was not different between groups at baseline (44.7 mL/min/1.73 m(2) vs. 46.0, p = 0.64) or at any point during follow-up: 90 d, 180 d, 1 yr, 2 yr, and 3 yr. conclusion: Patients converted to a regimen of sirolimus and a dosed-reduced CNI have stable renal function over the following three yr, but do not have an improvement in renal outcomes compared to patients maintained on full dose CNI.

Right ventricular (RV) failure following implantation of a left ventricular assist device (LVAD) is a significant complication that is often difficult to predict. To address this problem, we developed a cost-sensitive decision tree to evaluate the risk of RV failure, hence the need for a right ventricular assist device (RVAD). The model was developed based on retrospective analysis of 183 patients who received an LVAD at the University of Pittsburgh Medical Center. It exhibited a specificity of 87% (identifying 136 out of 156 patients who did not receive an RVAD). With respect to the need for RVAD support, the model however identified 20 patients (13%) as RVAD-dependent which in fact did not receive an RVAD. These patients however exhibited significantly lower 90-day survival as those on which the model and expert agreed as RVAD independent. Future development of this model is intended to provide decision support to both aid and translate the judgment of clinical experts.

The Centers for Medicare and Medicaid Services announced that all hospitals implanting ventricular assist devices are required to have certification from the The Joint Commission for disease-specific care destination therapy with a ventricular assist device effective March 27, 2009, in order to receive Medicare reimbursement for services rendered to patients who have devices implanted for destination therapy. On February 23, 2007, The Joint Commission released the certification requirements for ventricular assist devices implanted for destination therapy in an 8-page document so that hospitals could prepare to meet the 2009 certification deadline. The Artificial Heart Program of the University of Pittsburgh Medical Center undertook a multidisciplinary project, under the guidance of the nurse coordinator, to prepare the hospital and program for a precertification survey by The Joint Commission for disease-specific destination therapy ventricular assist device certification. The Presbyterian Hospital Artificial Heart Program was awarded The Joint Commission's device-specific certification for destination therapy with ventricular assist devices in June 2008.

Risk stratification for mechanical circulatory support (MCS) has emerged as an important tool in patient selection and outcomes assessment. Most studies examining risk stratification have been limited to pulsatile devices. We use the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) to stratify patients with continuous-flow devices and assess outcomes in less severe, but functionally impaired, heart failure patients.This study included 101 bridge-to-transplant and destination-therapy patients at 3 centers. Three groups were studied: Group 1, cardiogenic shock (INTERMACS Profile 1); Group 2, inotrope-dependent (INTERMACS Profile 2 or 3); and Group 3, ambulatory advanced heart failure (INTERMACS Profiles 4 to 7). The outcomes of interest were actuarial survival, survival to discharge and length of stay.Survival at 36 months was better in Group 3 than in Group 1 (95.8% vs 51.1%, p = 0.011), but not between Groups 2 and 3 (68.8 vs 95.8%, p = 0.065). Lengths of stay for Groups 1 to 3 were 44, 41 and 17 days: Groups 1 vs 3, p0.001; Groups 2 vs 3, p0.001; and Groups 1 vs 2, p = 0.62. Lengths of stay for survivors were 49, 39 and 14 for the 3 groups: Groups 1 vs 3, p0.001; Groups 2 vs 3, p0.001; and Groups 1 vs 2, p = 0.28.INTERMACS classification is a useful metric for risk-stratifying candidates for MCS. Less acutely ill but functionally impaired heart failure patients receiving continuous-flow LVADs had longer short- and long-term survival and shorter lengths of stay compared with patients who were more acutely ill.

ObjectiveThe aim of this study was to evaluate the incidence, risk factors, and effect on outcomes of right ventricular failure in a large population of patients implanted with continuous-flow left ventricular assist devices.MethodsPatients (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec, Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the occurrence of right ventricular failure. Right ventricular failure was defined as requiring a right ventricular assist device, 14 or more days of inotropic support after implantation, and/or inotropic support starting more than 14 days after implantation. Demographics, along with clinical, laboratory, and hemodynamic data, were compared between patients with and without right ventricular failure, and risk factors were identified.ResultsOverall, 30 (6%) patients receiving left ventricular assist devices required a right ventricular assist device, 35 (7%) required extended inotropes, and 33 (7%) required late inotropes. A significantly greater percentage of patients without right ventricular failure survived to transplantation, recovery, or ongoing device support at 180 days compared with patients with right ventricular failure (89% vs 71%, P < .001). Multivariate analysis revealed that a central venous pressure/pulmonary capillary wedge pressure ratio of greater than 0.63 (odds ratio, 2.3; 95% confidence interval, 1.2–4.3; P = .009), need for preoperative ventilator support (odds ratio, 5.5; 95% confidence interval, 2.3–13.2; P < .001), and blood urea nitrogen level of greater than 39 mg/dL (odds ratio, 2.1; 95% confidence interval, 1.1–4.1; P = .02) were independent predictors of right ventricular failure after left ventricular assist device implantation.ConclusionsThe incidence of right ventricular failure in patients with a HeartMate II ventricular assist device is comparable or less than that of patients with pulsatile-flow devices. Its occurrence is associated with worse outcomes than seen in patients without right ventricular failure. Patients at risk for right ventricular failure might benefit from preoperative optimization of right heart function or planned biventricular support.

Background Severe pulmonary hypertension (PH) in heart failure (HF) is a risk factor for adverse outcomes after heart transplantation (HTx). Left ventricular assist devices (LVADs) improve pulmonary hemodynamics, but our understanding of the degree of improvement and the effect on outcomes is still evolving. Methods We reviewed invasive pulmonary hemodynamics from 58 consecutive patients receiving LVAD support as a bridge to HTx from 1996 to 2003. The primary outcome was change in baseline transpulmonary gradient (TPG) during LVAD support and after HTx/recovery. The secondary outcome was post-HTx survival. Results All patients (age, 49 ± 14 years, 79% male, 40% ischemic) received a pulsatile LVAD (median support, 97 days; interquartile range [IQR], 31–222). Hemodynamic measurements were obtained at baseline (median, 1 day; IQR, 1–3), during early (median, 1 day; IQR, 0–4) and late (median, 75 days; IQR, 24–186) LVAD support, and after HTx/recovery (median, 28 days; IQR, 17–40). Improvement in TPG occurred throughout LVAD support and was sustained after HTx/recovery. Levels of TPG reductions in patients with a baseline TPG in the highest quartile (14.1–26.0 mm Hg) were 8.6 ± 3.5 vs 6.5 ± 3.1 mm Hg in the lowest quartile (2.0–7.7 mm Hg) during LVAD support ( p = 0.102), with 90% vs 100% 30-day post-HTx survival ( P = 0.113). Conclusion Pulmonary hemodynamics and post-HTx survival were similar after pulsatile LVAD support in patients with and without pre-implant PH. LVAD support may be a useful strategy to reverse PH in carefully selected patients, thus improving candidacy for HTx.

Background: Myocardial recovery after ventricular assist devices (VAD) is rare but appears more common in nonischemic cardiomyopathies (NICM). We sought to evaluate left ventricular (LV) end diastolic diameter (LVEDD) for predicting recovery after VAD. Methods and Results: NICM patients receiving long-term mechanical support between 1996 and 2008 were reviewed. Subjects were divided into 3 groups: mild, moderate, and severe dilation (Group A: LVEDD !6.0 cm [n 5 22]; Group B: 6.0-7.0 cm [n 5 32]; Group C: O7.0 cm [n 5 48], respectively). Overall, recovery (successful explant without transplantation) occurred in 14 of 102 subjects (14%). Of these, 2 died and 2 required transplantation within 1 year. Recovery was more common in patients without LV dilation (Groups A/B/C 5 32%/22%/0%, P ! .001), as was sustained recovery (alive and transplant free 1 year after explant; A/B/C 5 27%/10%/0%, P 5 .001). Of the recovery patients in Group A, 6/7 (86%) had sustained recovery versus 3/6 (50%) in Group B. Conclusions: Recovery occurred in 32% of NICM patients without significant LV dilation at time of VAD, the majority of whom experienced significant sustained recovery. Recovery was not evident in those with severe LV dilation. Routine echocardiography at the time of implant may assist in targeting patients for recovery after VAD. (J Cardiac Fail 2010;16:99e105)

Although ventricular assist devices (VADs) provide effective treatment for end-stage heart failure, VAD support remains associated with significant risk for adverse events (AEs). To date there has been no detailed assessment of the incidence of a full range of AEs using standardized event definitions. We sought to characterize the frequency and timing of AE onset during the first 60 days of VAD support, a period during which clinical observation suggests the risk of incident AEs is high.A retrospective analysis was performed utilizing prospectively collected data from a single-site clinical database including 195 patients aged 18 or greater receiving VADs between 1996 and 2006. Adverse events were coded using standardized criteria. Cumulative incidence rates were determined, controlling for competing risks (death, transplantation, recovery-wean).During the first 60 days after implantation, the most common AEs were bleeding, infection, and arrhythmias (cumulative incidence rates, 36% to 48%), followed by tamponade, respiratory events, reoperations, and neurologic events (24% to 31%). Other events (eg, hemolysis, renal, hepatic events) were less common (rates15%). Some events (eg, bleeding, arrhythmias) showed steep onset rates early after implantation. Others (eg, infections, neurologic events) had gradual onsets during the 60-day period. Incidence of most events did not vary by implant era (1996 to 2000 vs 2001 to 2006) or by left ventricular versus biventricular support.Understanding differential temporal patterns of AE onset will allow preventive strategies to be targeted to the time periods when specific AE risks are greatest. The AE incidence rates provide benchmarks against which future studies of VAD-related risks may be compared.

Background: Internal cardioversion of atrial fibrillation with direct current energy has become an increasingly employed technique for patients who fail external cardioversion. Hypothesis: The purpose of this study was to determine whether internal cardioversion could be avoided by careful attention to cardioversion technique in a group of patients referred specifically for internal cardioversion after failed external cardioversion by community cardiologists. Methods: We performed external cardioversion utilizing two operators applying significant pressure to the thorax with up to 360 J prior to the planned internal cardioversion in 20 patients referred for internal cardioversion after failed attempts at external cardioversion. Results: Sixteen patients (80%) were successfully cardioverted and avoided the risk, inconvenience, and cost of internal cardioversion. Conclusion: External cardioversion with significant anterior paddle pressure by two operators can decrease the need for internal cardioversion in a significant portion of patients referred to electrophysiologists for internal cardioversion and should be considered prior to an invasive procedure.

Short-term mechanical circulatory support may be lifesaving in patients with right ventricular (RV) failure related to post-cardiotomy cardiogenic shock (PCCS), cardiac transplantation (CTx), and long-term therapy with a left ventricular assist device (LVAD). This study evaluates our clinical experience using the CentriMag (Levitronix LLC, Waltham, Mass) system for temporary mechanical RV support.A retrospective review was performed of 29 patients (mean age, 57 +/- 14 years) in whom the CentriMag system was used for RV support from September 2005 to March 2008.The indication for RV support was PCCS in 7 (24%), CTx in 10 (35%), and LVAD placement in 12 (41%). The mean support time was 8 +/- 8 days. The device was successfully weaned in 3 PCCS patients (43%), 7 CTx patients (70%), and 7 LVAD patients (58%). Complications included major infection (pneumonia, sepsis, or LVAD pocket infection) in 13 (45%), arrhythmia in 13 (45%), reoperation for bleeding in 10 (35%), stroke/encephalopathy in 3 (10%), and air embolism in 1 (3%). Early mortality (30 days or before discharge) occurred in 14 patients (48%) of which 9 (31%) died with the device in place. Late death occurred in 2 of 15 patients (13%) who survived to discharge. There were no device failures.The CentriMag system provides effective temporary mechanical circulatory support for RV failure. Ease of implantation and a high rate of successful device weaning justify the use of the CentriMag system for temporary RV support.

Objectives Cardiac allograft vasculopathy remains a major cause of mortality after cardiac transplantation. Percutaneous revascularization has become the mainstay of therapy given the poor historical outcomes with surgery. Outcomes following surgical revascularization are evaluated to determine whether surgery remains a viable therapeutic option. Methods A retrospective analysis was performed of 13 heart transplant recipients who had cardiac allograft vasculopathy requiring coronary artery bypass grafting with or without adjunctive percutaneous coronary intervention for revascularization from 1999 to 2008. Results Thirteen patients had 14 coronary artery bypass grafting procedures at 141 ± 66 months after transplantation. The average number of grafts was 2.3. Eight were performed without cardiopulmonary bypass, of which 5 were approached via left thoracotomy and the remainder via repeat sternotomy. One patient had renal failure and a cerebrovascular accident. Percutaneous coronary intervention before or after coronary artery bypass grafting was required in 3 patients. There were no perioperative mortalities. At mean follow-up of 39 ± 36 months, 3 patients have died, 2 from progressive cardiac allograft vasculopathy and 1 from lung cancer. Kaplan-Meier survival for this group of patients was 92%, 83%, and 83% at 1, 5, and 7 years, respectively. Conclusions Surgical revascularization for cardiac allograft vasculopathy remains a viable treatment option for appropriate patients and may be performed safely with good medium-term outcomes. However, patients remain at risk for disease progression and may require percutaneous or surgical reintervention.

Chronic steroid use after cardiac transplantation (CTX) is accompanied by co-morbidities that are dependent on length of exposure.A retrospective review of all CTX without induction therapy from 1999-2004. After 2001, an aggressive strategy of steroid weaning was introduced.A total of 165 patients underwent CTX, 82 from 1999-2001 (group 1) and 83 from 2002-2004 (group 2). There were no significant differences in recipient or donor characteristics between group 1 and group 2. The baseline calcineurin was cyclosporine in 41% and 5% (p0.0001) and tacrolimus in 59% and 95% (p0.0001), respectively. The mean duration of steroid use was 1023 d in group 1 and 383 d in group 2 (p0.0001). The overall incidence of anyor =ISHLT grade 3A rejection per year after CTX for group 1 vs. group 2 was as follows: year 1: 40% vs. 49% (p = NS) and year 2: 7.4% vs. 9.2% (p = NS).Steroid withdrawal by one yr after CTX using a contemporary immunosuppressive regimen is possible in most patients. In comparison with a slower steroid wean, a faster wean is not associated with an excess of significant rejection in the first two yr post CTX.

Introduction: The HM continuous flow LVAD has been shown to have good reliability and an excellent safety profile when used as a bridge to transplantation (BTT). Initially, there were concerns that the continuous flow and design of the HM might pre-dispose patients to thromboembolic events or pump thrombosis and therefore oral anticoagulation with coumadin was recommended. Our study evaluates the risk of thromboembolism and pump thrombosis related to the degree of anticoagulation as reflected by the International Normalized Ratio (INR). Methods: We evaluated all patients enrolled in the HM BTT pivotal trial from 1 to 6 months post-implant in order to eliminate perioperative events unrelated to anticoagulation. All patients were on aspirin and some also on persantine. An INR was measured monthly per protocol. Each individual INR sample from each time interval was assigned to ranges of INR values. Adverse events analyzed were ischemic (I) and hemorrhagic (H) stroke, pump thrombosis (T), and GI bleeding (G). Patients with adverse events were associated with the most recent INR at the start of the time interval. Results: The median duration of support for 189 patients was 132 days (range: 1–672 days) (cumulative: 96.9 patient years). There were 7 (3.7 %) patients with thrombotic events and 11 (5.8 %) patients with hemorrhagic events. The only pump thrombosis occurred with an INR > 2.5 (0.5 %). Conclusions: The rates of thromboembolism, including stroke and pump thrombosis appear to be low with the HM as BTT. The thrombotic events appear to be offset by an equivalent number of hemorrhagic events. There appears to be no correlation between the degree of anticoagulation with warfarin, as reflected by the INR, and the frequency of thrombotic or hemorrhagic events. Therefore, particularly in patients having recurrent episodes of bleeding, the risk of lowering the target INR appears to be small.

Background The survival after lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension has been reportedly the lowest among the major diagnostic categories of lung transplant recipients. Methods Retrospective analysis was performed for lung and heart-lung transplant recipients for idiopathic pulmonary arterial hypertension from 1982 to 2006. The patients were divided into 2 groups, based on the era; group 1: 1982 to 1993, and group 2: 1994 to 2006. Since 1994, we have introduced our current protocols including prostaglandin E 1 and nitroglycerin for donor lung preservation, and lung protection with cold and terminal warm blood pneumoplegia as well as immunosuppression with alemtuzumab induction. These modifications were introduced in different years over a wide span of time (1994 to 2003). Results Group 1 had 59 patients (35 ± 1 years old, ranging 15 to 53, 20 male and 39 female) with 7 single lung, 11 double lung, and 41 heart-lung, whereas group 2 had 30 (43 ± 2 years old, ranging 17 to 65, 9 male and 21 female) with 2 single, 20 double, and 8 heart-lung transplantations. The recipient age was significantly ( p = 0.004) higher in group 2, and group 2 had significantly older (35 ± 3 vs 26 ± 1, p = 0.002) and more female donors (73% vs 41%, p = 0.007) compared with group 1. The actuarial survival was significantly ( p = 0.004) better in group 2 with 86% at 1 year, 75% at 5 years, and 66% at 10 years compared with group 1 with 58% at 1 year, 39% at 5 years, and 27% at 10 years. Conclusions With our current pulmonary protection and immunosuppression, the long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension is excellent.

Background Acute rejection continues to occur beyond the first year after cardiac transplantation, but the optimal strategy for detecting rejection during this late period is still controversial. Gene expression profiling (GEP), with its high negative predictive value for acute cellular rejection (ACR), appears to be well suited to identify low-risk patients who can be safely managed without routine invasive endomyocardial biopsy (EMB). Methods The Invasive Monitoring Attenuation Through Gene Expression (IMAGE) study is a prospective, multicenter, non-blinded, randomized clinical trial designed to test the hypothesis that a primarily non-invasive rejection surveillance strategy utilizing GEP testing is not inferior to an invasive EMB-based strategy with respect to cardiac allograft dysfunction, rejection with hemodynamic compromise (HDC) and all-cause mortality. Results A total of 199 heart transplant recipients in their second through fifth post-transplant years have been enrolled in the IMAGE study since January 13, 2005. The study is expected to continue through 2008. Conclusions The IMAGE study is the first randomized, controlled comparison of two rejection surveillance strategies measuring outcomes in heart transplant recipients who are beyond their first year post-transplant. The move away from routine histologic evaluation for allograft rejection represents an important paradigm shift in cardiac transplantation, and the results of this study have important implications for the future management of heart transplant patients.

Background: Renal dysfunction is common among patients with either Diabetes Mellitus or end-stage heart failure. It has been established that renal function improves after continuous-flow left ventricular assist device (CF-LVAD) implantation. However, it is unknown if this improvement is also observed in diabetic patients who are at risk of renal disease at baseline. Thus, the aim of this study was to examine if patients with diabetes experienced the same improvement in renal function after CF-LVAD as non-diabetics. Method: A retrospective chart review of pts implanted with a CF-LVAD at Columbia University Medical Center from Jan 2007-December 2014 was completed. Calculated glomerular filtration rate (GFR) was used to assess renal function, and was measured on admission 1, 3 and 6 months after CF-LVAD implantation. Renal dysfunction at baseline was defined as a GFR ! 60 ml/min/ m. Diabetic status was assessed at the time of CF-LVAD evaluation. Results: During the study period, 178 patients were implanted with a CF-LVAD (148 Heartmate II, 30 Heartware). Fifteen patients were on dialysis at the time of implant and were excluded from the analysis. Of the remaining 163 patients, 81(49.7%) were diabetic and 83 (51.4%) were non-diabetic. Patients with diabetes were more likely to be older and have a history of hypertension, but were otherwise comparable at baseline. The median GFR at the time of CF-LVAD implant was not significantly different in diabetics and non-diabetics, at 46.8 ml/min/ m2 (IQR 5 39.1-70.3) and 53.9

Therapies for heart failure (HF) with a low ejection fraction (EF) have delayed disease progression and prolonged survival, but the implications of these therapies on the end stages of HF have not been examined.Patients seen by the Brigham and Women's cardiomyopathy service with an EFor =35%, at least 1 outpatient visit or at least 30 days of follow-up who died between January 1, 2000, and October 20, 2003, were evaluated retrospectively. Of the 160 patients who died since 2000, 80 (50%) were outpatients. In the 6 months before death, 93% of patients had New York Heart Association (NYHA) class III or IV symptoms. The NYHA class, clinical characteristics, medications, and comorbidities differed little between inpatient and outpatient deaths. Renal insufficiency and hyponatremia were worse in the months preceding death than at the time of death (creatinine: 3.2 versus 2.3 mg/dL, P.0001; sodium: 128 versus 135 mmol/L, P.0001, respectively). Death was considered sudden in only 21% of patients.Deaths in the current era of HF management occur in patients with long-standing HF characterized by biventricular dysfunction and advanced symptoms. Most deaths are heralded by hyponatremia, acute on chronic renal insufficiency, and frequent hospitalizations.

More than 5 million Americans have congestive heart failure, and 550,000 new cases are diagnosed each year. This condition results in almost 1 million hospital discharges and more than 50,000 deaths a year at a cost of $28.8 billion (1). Coronary artery disease (CAD) remains a leading cause of heart failure. Since the early trials of surgical vs medical management of coronary artery disease in the late 1970s, there have been substantial changes in the surgical techniques and the medical management of chronic CAD, acute coronary syndromes, and heart failure.

Aim Antibody mediated rejection (AMR) remains problematic in solid organ transplantation. New treatment modalities are continually being considered, especially those interfering with the complement cascade. However, assays predicting the efficacy of AMR treatments are poor at best, despite the sensitivity of single antigen bead (SAB) testing and new SAB functional assays. Recently, the therapeutic use of C1 esterase inhibitor (C1-INH) has been proposed to prevent/minimize complement-mediated allograft damage by donor specific HLA antibodies by blocking initial complement activation. Here, we test a novel modification of the Luminex C1q Screen® SAB assay using C1-INH, in vitro, to predict the susceptibility of HLA antibodies to C1-INH inhibition. Methods Highly sensitized heart (n=6) and small bowel (n=3) patient sera were tested for HLA antibody by complement dependent cytotoxicity (CDC) T and B cell crossmatch(XM), T cell cytotoxic PRA and by Luminex C1q Screen®. C1-INH (Berinert®, CSLBehring) was added to assays (0.025U/μl–0.4U/μl) and inhibition of cell death or MFI was measured. As a control, human α1-proteinase inhibitor (Zemaira®) was substituted for C1-INH to demonstrate specificity. Results C1-INH added to sera inhibited CDC-XM positivity in a dose-dependent manner (0.4U/μl to 0.025U/μl). Similarly, the MFI of C1qScreen positive HLA antibodies was reduced >80% when 0.4U/μl C1-INH was added to the assay. High-titer (>1:16) C1q positive HLA specificities were less affected by C1-INH compared to lower-titer ( Conclusions The in vitro efficacy of C1-INH to inhibit complement activating HLA antibodies in both CDC and C1q Screen® was dependent on the titer of C1q reactive IgG antibodies. These assays may potentially define HLA antibodies susceptible to C1-INH therapy. Lunz: CSL Behring: Grant Research. Vensak: CSL Behring: Employee. Berger: CSL Behring: Employee. Zeevi: CSL Behring: Grant Research.

BACKGROUND—Severe pulmonary hypertension (PH) in heart failure (HF) is a risk factor for adverse outcomes after heart transplantation (HTx). Left ventricular assist devices (LVADs) improve pulmonary hemodynamics, but our understanding of the degree of improvement and the effect on outcomes is still evolving. METHODS—We reviewed invasive pulmonary hemodynamics from 58 consecutive patients receiving LVAD support as a bridge to HTx from 1996 to 2003. The primary outcome was change in baseline transpulmonary gradient (TPG) during LVAD support and after HTx/recovery. The secondary outcome was post-HTx survival. RESULTS—All patients (age, 49 ± 14 years, 79% male, 40% ischemic) received a pulsatile LVAD (median support, 97 days; interquartile range [IQR], 31–222). Hemodynamic measurements were obtained at baseline (median, 1 day; IQR, 1–3), during early (median, 1 day; IQR, 0–4) and late (median, 75 days; IQR, 24–186) LVAD support, and after HTx/recovery (median, 28 days; IQR,17–40). Improvement in TPG occurred throughout LVAD support and was sustained after HTx/recovery. Levels of TPG reductions in patients with a baseline TPG in the highest quartile (14.1–26.0 mm Hg) were 8.6 ± 3.5 vs 6.5 ± 3.1 mm Hg in the lowest quartile (2.0 –7.7 mm Hg) during LVAD support (p = 0.102), with 90% vs 100% 30-day post-HTx survival (P = 0.113). CONCLUSION—Pulmonary hemodynamics and post-HTx survival were similar after pulsatile LVAD support in patients with and without pre-implant PH. LVAD support may be a useful strategy to reverse PH in carefully selected patients, thus improving candidacy for HTx. © 2010 International Society for Heart and Lung Transplantation. All rights reserved. Reprint requests: Marc A. Simon, MD, FACC, Assistant Professor of Medicine, Cardiovascular Institute, University of Pittsburgh, Scaife Hall S554, 200 Lothrop St, Pittsburgh, PA 15213. Telephone: 412-647-1174. Fax: 412-647-3913. simonma@upmc.edu. Disclosure statement None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose. NIH Public Access Author Manuscript J Heart Lung Transplant. Author manuscript; available in PMC 2011 March 29. Published in final edited form as: J Heart Lung Transplant. 2010 February ; 29(2): 201–208. doi:10.1016/j.healun.2009.09.013. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript

Microchimerism, or the existence of fetal cells in the maternal circulation, may pesists many years post-partum, and has been postulated as one mechanism for autoimmune illness in women. An auto-immune pathogenesis has been postulated for primary dilated cardiomyopathy in general and peripartum disease in particular. The prevalence of microchimerism in women with dilated cardiomyopathy (DCM) and peripartum disease (PPCM) has not been previously evaluated. Method: We screened for the presence of microchimerism in the peripheral circulation of 121 women with heart failure enrolled in the GRACE Study (Genetic Risk Assessment of Cardiac Events) at the University of Pittsburgh Medical Center. DNA was obtained from peripheral blood by the method of leukocyte centrifugation and cell lysis. The presence of microchimerism was evaluated by PCR amplification using primers which amplified a segment common to both the X and Y chromosome. This would therefore result in a single band in women, with second smaller band (Y band) of equal intensity in male subjects. Persistent microchimerism (of male but not of female orgin) would also be evident by a faint Y band. Eighty-three female subjects with DCM, 11 with PPCM, and 27 with cardiomyopathy due to ischemic heart disease (IschCM) were screened for the presence of microchimersim. Results: Microchimerism was seen in 6 of 83 (8%) subjects with primary dilated cardiomyopathy (Mean age 49 6 17, median age 52, range 29 to 81; LVEF 0.25 6 0.13). Of note, microchimerism was not evident in any of the 11 subjects with a primary diagnosis of PPCM. Microchimerism was also not evident in any of the 27 subjects with an ischemic cardiomyopathy (LVEF 0.25 6 0.07), though the ischemic cohort was older (Mean age 58 6 12, median 60, range 32 to 77). Conclusions: Microchimerism of was evident in women with primary dilated cardiomyopathy but not in a similar cohort with an ischemic etiology of heart failure. Microchimerism was no more prevalent with peripartum disease than in the subjects with primary idiopathic cardiomyopathy. Though the differences in women with ischemic and non-ischemic etiologies potentially are of interest, whether microchimerism is causative or just a reflection of a disturbance in autoimmunity requires further study.

AND CIRCULATORY SUPPORT? -FROM CLINICAL EXPERIENCES OF HEARTMATE II WITH SEVERE CONGESTIVE HEART FAILURE PATIENTSHiroyuki Tsukui, Steve Winowich, Eileen Stanford, Jeffrey J Teuteberg, Robert L Kormos. Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA; Cardiology, University of Pittsburgh, Pittsburgh, PA. Purpose: Rotary pumps such as the Heartmate II left ventricular assist device (LVAD) (Thoratec Corporation, Pleasanton, CA) are small, nonpulsatile pumps designed for long-term use. However, its capability for providing full cardiac decompression and circulatory support has been questioned and indeed some have felt that the only safe way rotary pumps can be used is in an assistive mode. Methods: Three patients (Ischemic cardiomyopathy: 2, Post-partum cardiomyopathy: 1, ejection fraction: 10–20%) implanted the HeartMate II LVAD were followed using regular transthoracic echocardiography (TTE). Pump rpm, aortic valve opening (AVO), and left ventricular end-diastolic diameter (LVDd) were measured while changing pump rpm. Results: Full cardiac decompression and circulatory support were observed in all three patients. With the increasing of pump rpm, LVDd and the frequency of AVO decreased in inverse proportion. At an appropriate pump rpm setting, the aortic valve closed completely and LVDd decreased to 60–70% of preoperative LVDd without causing suction by the apical cannula. Longterm renal and circulatory function was normal without heart failure symptoms. Considerations: The Heartmate II provides sufficient circulatory support at an appropriate pump rpm setting in patients with severe congestive heart failure. Long-term full circulatory support can be achieved which is a requirement for destination therapy. INITIAL RESULTS WITH THE PEDIATRIC JARVIK 2000 HEART Robert Jarvik, Bartley Griffith, Greg Burgreen, Michael Morrow, Andrew Lewis. Research, Jarvik Heart, Inc., New York, NY; U of Maryland, Baltimore, MD; Mississippi State U, Starkville, MS. Under the NIH program to develop pediatric mechanical circulatory support systems, we have completed design, fabrication, and initial bench testing of the child model pump, an intraventricular axial flow pump connected from apex to aorta like the adult model Jarvik 2000. The device is one third the size and weight of the adult pump. Parameters include: Adult Jarvik 2000: 26 mm diameter x 7.5 cm long, 30cc, 90g, 16 mm diameter aortic graft, 8–12,000 RPM, 1–6 L/min. Pediatric Jarvik 2000: 17.8 mm diameter x 5.5 cm long, 10cc, 35g, 10mm diameter aortic graft, 10–14,000 RPM, 0.5–5 L/min. Computational fluid dynamics run on the initial prototype blade design predicted excellent flow pressure performance and very good pressure recovery by the stators which has been confirmed In Vitro, as shown below. Negligible losses were predicted by CFD at the pump outflow and graft. Modification of the leading edge of the impeller based on the CFD results was made to avoid local cavitation. Other blade design iterations are planned based on the In Vivo findings. Implants in small sheep will begin in February 2005. The system initially utilizes the same controller as the adult model while a smaller controller and battery system are developed.

Pump thrombosis requiring device exchange is a dreaded complication after implantation of a left ventricular assist device (LVAD). Sub-optimal inflow cannula (IC) positioning at the time of implant or changes in IC position due to weight gain or ventricular remodeling may lead to non-laminar flow.