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Left ventricular assist devices (LVADs) are associated with the development of antihuman leukocyte antigen (HLA) antibodies, which can create a challenge for future transplantation in these patients. The differential effects of Heartmate 3 (HM3) versus Heartmate II (HMII) on de novo HLA allosensitization remain unknown. Patients who underwent HMII or HM3 implantation and had no prior HLA antibodies by solid-phase assay (Luminex) testing were included in this study. Complement-dependent cytotoxicity (CDC) panel reactive antibody (PRA) levels and Luminex antibody profiles were followed until cardiac transplantation, device explantation, or death. Electronic medical records were reviewed to examine posttransplant outcomes. Thirty-eight HM3 and 34 HMII patients with complete data were followed for 1.5 ± 1.1 years on device support. HM3 and HMII groups had similar age at implant, female gender, ischemic heart failure etiology, bridge strategy at implant, as well as intraoperative and postoperative transfusion requirements. 39.5% of HM3 and 47.1% of HMII patients developed detectable HLA antibodies by Luminex testing (p = 0.516). Development of high-level (mean fluorescence intensity >10,000) antibodies was significantly lower in HM3 than HMII patients (5.3 vs. 20.6%, p = 0.049). CDC PRA testing showed fewer HM3 patients with a positive result (PRA > 0%) than HMII patients (39.4 vs. 70.0%, p = 0.015). Among transplanted patients, those who had developed de novo sensitization on LVAD support showed a trend toward incidence of moderate to severe grade rejection compared with unsensitized patients (23.8 vs. 4.8%, p = 0.078). HM3 is associated with lower risk of de novo HLA sensitization compared with HMII., (Copyright © ASAIO 2021.)

A 77-year-old man who underwent a heart transplant 7 years ago presented with multiple bloody bowel movements. Endoscopic and histologic evaluation revealed chronic active ileitis, granulomatous inflammation, multinucleated giant cells, and a rare, equivocal acid-fast bacterium in the terminal ileum. Positive sputum cultures for Mycobacterium tuberculosis and acid-fast bacilli established a diagnosis of intestinal tuberculosis, and RIPE (rifabutin, isoniazid, pyrazinamide, ethambutol) therapy was initiated. Elevated IgG levels on quantitative immunoglobulin testing and a bone marrow biopsy specimen of ≥60% plasma cells confirmed the diagnosis of multiple myeloma that later transformed into its aggressive form, plasma cell leukemia. Induction chemotherapy was initiated; however, the patient experienced retroperitoneal bleeding and pancytopenias, limiting the continuation of chemotherapy, and as a result, the patient was transitioned to palliative care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Bridge to transplantation (BTT) with left ventricular assist devices (LVADs) is a mainstay of therapy for heart failure in patients awaiting heart transplantation (HT). Criteria for HT listing do not differ between patients medically managed and those mechanically bridged to HT. The objectives of the present study were to evaluate the impact of BTT with LVAD on posttransplantation survival, to describe differences in causes of 1-year mortality in medically and mechanically bridged patients, and to evaluate differences in risk factors for 1-year mortality between those with and those without LVAD at the time of HT., Methods: Using the United Network of Organ Sharing database, we identified 5486 adult, single-organ HT recipients transplanted between 2008 and 2015. Patients were propensity matched for likelihood of LVAD at the time of HT. Kaplan-Meier survival estimates were used to assess the impact of BTT on 1- and 5-year mortality. Logistic regression analysis was used to evaluate the odds ratio of 1-year mortality for patients BTT with LVAD compared with those with medical management across clinically significant variables at various thresholds., Results: Early mortality was higher in mechanically bridged patients: 9.5% versus 7.2% mortality at 1 year (P<0.001). BTT patients incurred an increased risk of 1-year mortality with an estimated glomerular filtration rate of 40 to 60 mL·min -1 ·1.73 m -2 (odds ratio, 1.69; P=0.003) and <40 mL·min -1 ·1.73 m -2 (odds ratio, 2.16; P=0.005). A similar trend was seen in patients with a body mass index of 25 to 30 kg/m 2 (odds ratio, 1.88; P=0.024) and >30 kg/m 2 (odds ratio, 2.11; P<0.001). When patients were stratified by BTT status and the presence of risk factors, including age >60 years, estimated glomerular filtration rate <40 mL·min -1 ·1.73 m -2 , and body mass index >30 kg/m 2 , there were significant differences in 1-year mortality between medium- and high-risk medically and mechanically bridged patients, with 1-year mortality in high-risk BTT patients at 17.6% compared with 10.4% in high-risk medically managed patients., Conclusions: Bridge to HT with LVAD, although necessary because of organ scarcity and capable of improving wait list survival, confers a significantly higher risk of early posttransplantation mortality. Patients bridged with mechanical support may require more careful consideration for transplant eligibility after LVAD placement.

Background: Allospecific anti-HLA antibodies (Abs) are associated with rejection of solid organ grafts. The 2 main kits to detect anti-HLA Ab in patient serum are commercialized by Immucor and One Lambda/ThermoFisher. We sought to compare the performance of both platforms., Methods: Background-adjusted mean fluorescence intensity (MFI) values were used from both platforms to compare sera collected from 125 pretransplant and posttransplant heart and lung transplant recipients., Results: Most HLA class I (94.5%) and HLA class II (89%) Abs with moderate to high MFI titer (≥4000) were detected by both assays. A modest correlation was observed between MFI values obtained from the 2 assays for both class I ( r = 0.3, r 2 = 0.09, P < 0.0001) and class II Ab ( r = 0.707, r 2 = 0.5, P < 0.0001). Both assays detected anti-class I and II Ab that the other did not; however, no specific HLA allele was detected preferentially by either of the 2 assays. For a limited number of discrepant sera, dilution resulted in comparable reactivity profiles between the 2 platforms., Conclusions: Immucor and One Lambda/ThermoFisher assays have a similar, albeit nonidentical, ability to detect anti-HLA Ab. Although the correlation between the assays was present, significant variances exist, some of which can be explained by a dilution-sensitive "prozone" effect.

Background: Pre-transplant sensitization is a limiting factor in solid-organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed generation of Nabs after VAD implantation in pre-transplant sera and examined their contribution to cardiac allograft outcome., Methods: IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant recipients, including 128 patients with VAD (VAD patients) and 78 patients without VAD (no-VAD patients). Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by enzyme-linked immunosorbent assay., Results: No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared with no-VAD patients. This increase was likely due to the presence of the VAD, as revealed by lower serum IgG Nabs levels before implantation. Elevated pre-transplant IgG Nabs level was associated with development of primary graft dysfunction (PGD)., Conclusions: Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with development of PGD suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication., (Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Donor-specific anti-HLA antibodies (DSA) are common after heart transplantation and are associated with rejection, cardiac allograft vasculopathy, and mortality. A noninvasive diagnostic test for pathologic antibody-mediated rejection (pAMR) does not exist., Methods: From January 1, 2010, through August 31, 2013, 221 consecutive adult patients underwent heart transplantation and were followed through October 1, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included association of DSA (stratified by major histocompatibility complex class and de novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of cardiac allograft vasculopathy., Results: During the study period, 69 patients (31.2%) had DSA (24% had de novo DSA), and there were 74 episodes of pAMR in 38 patients. Sensitivity of DSA at any mean fluorescence intensity to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (odds ratio = 5.37; 95% confidence interval [CI], 1.34-21.47; p = 0.018), adjusting for age, sex, and timing of AMR. Circulating class II DSA after transplantation increased risk of future pAMR (hazard ratio = 2.97; 95% CI, 1.31-6.73; p = 0.009). Patients who developed de novo class II DSA had 151% increased risk of graft loss (contingent on 30-day survival) compared with patients who did not have DSA (95% CI, 1.11-5.69; p = 0.027)., Conclusions: DSA were inadequate to diagnose pAMR. Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Mechanical circulatory support (MCS) is increasingly used as a bridge to heart transplantation. It is not known whether patients who receive MCS as bridge to transplantation (BTT) have more frequent and severe infectious complications in the first transplant year., Methods: Using a retrospective cohort in a single large transplant center from 2009 to 2014, we compared rates of post-transplant infections among patients bridged to transplantation with medical therapy (n = 134) or MCS (n = 178) over the first post-transplant year. Serious infections necessitated >14 days of continuous intravenous antibiotic therapy., Results: Pre-transplant device infections were common in the MCS group (32.6%). The proportion of patients with any infection (74.2% vs 60.5%; p = 0.01, relative risk 1.23 [1.04 to 1.44]) or serious infections (45.5% vs 31.3%; p = 0.01, relative risk 1.45 [1.08 to 1.96]) in the first post-transplant year was significantly higher in the MCS group than in the medical therapy group, respectively. MCS patients but not medical therapy patients had significantly higher 1-year all-cause mortality in the presence of post-operative infections (16.7% vs 4.3%, p = 0.04). Device-related infections occurred in 67 (37.6%) MCS patients up to 337 days post-transplant, including 26 (14.6%) patients without a known or active pre-operative device infection. In multivariable analyses, age, intensive care unit length of stay, presence of pre-transplant device infection and use of an anti-thymocyte agent were associated with increased rates of infection., Conclusion: More infectious complications are experienced by patients who receive MCS as BTT, with a significant occurrence of device-related infections. MCS patients with post-transplant infections have higher mortality at 1 year compared with uninfected MCS patients., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Antibody-mediated rejection (AMR) has been associated with increased death and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction, whereas recent reports have demonstrated an association with increased mortality. We investigated the timing of AMR and its association with graft dysfunction, death, and CAV., Methods: This retrospective cohort study identified all adult orthotopic heart transplant (OHT) recipients (N = 689) at Columbia University Medical Center from 2004 to 2013. There were 68 primary cases of AMR, which were stratified by early (< 1 year post-OHT) or late (> 1 year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression., Results: From January 1, 2004, through October 1, 2015, early AMR (median 23 days post-OHT) occurred in 43 patients and late AMR (median 1,084 days post-OHT) occurred in 25. Graft dysfunction was less common with early compared with late AMR (25.6% vs 56%, p = 0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1 year: 80% vs 93%, 5 years: 51% vs 73%, p < 0.05). When stratified by graft dysfunction, only those with late AMR and graft dysfunction had worse survival (30 days: 79%, 1 year: 64%, 5 years: 36%; p < 0.006). The association remained irrespective of age, sex, donor-specific antibodies, left ventricular assist device use, reason for OHT, and recovery of graft function. Similarly, those with late AMR and graft dysfunction had accelerated development of de novo CAV (50% at 1 year; hazard ratio, 5.42; p = 0.009), whereas all other groups were all similar to the general transplant population., Conclusions: Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR, there is an early and sustained increased risk of death and rapid development of de novo CAV despite aggressive treatment., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac retransplantation is increasing in frequency. Recent data have shown that retransplantation outcomes are now comparable with primary transplantation. The use of mechanical circulatory support (MCS) as a bridge to retransplantation has similar post-retransplant outcomes to those without MCS, but the success of bridging patients to retransplant with MCS has not been well studied., Methods: From January 2000 to February 2014 at Columbia University Medical Center, 84 patients were listed for retransplantation. Of this cohort, 48 patients underwent retransplantation, 15 were bridged with MCS, 24 died, and 6 clinically improved. A retrospective analysis was performed examining waiting list time, survival to retransplantation, and survival after retransplant. The effect of the United Network of Organ Sharing (UNOS) allocation policy change in 2006 on waiting list time and MCS use was also investigated., Results: Of 48 patients who underwent retransplantation, 11 were bridged with MCS. Overall 1-year survival to retransplantation was 81.3%. There was no significant difference in waiting list survival (p = 0.71) in those with and without MCS. Death from cardiac arrest or multiorgan failure with infection was more frequent in the medically managed group (p = 0.002). After the UNOS 2006 allocation policy change, waiting list time (599 ± 936 days in Era 1 vs 526 ± 498 days in Era 2, p = 0.65) and waiting list survival (p = 0.22) between eras were comparable, but there was a trend toward greater use of MCS (p = 0.13). Survival after retransplant was acceptable., Conclusion: The use of MCS as a bridge to cardiac retransplantation is a reasonable strategy., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Human immunodeficiency virus (HIV) infection has evolved from a highly stigmatized disease with certain progression to acquired immunodeficiency syndrome (AIDS) to a chronic disease affecting over 1 million Americans. With the success of current anti-retroviral therapies, cardiovascular disease, including advanced heart failure (HF), will be a major cause of morbidity and mortality in this population., Methods: A survey concerning heart transplantation (HT) and left ventricular assist device (LVAD) implantation attitudes and outcomes in HIV-infected patients was distributed to 103 American and 9 Canadian HT centers via fax, e-mail or telephone., Results: Eighty-nine centers (79%) responded. Eighteen HTs were performed in HIV(+) patients with 1-, 2- and 5-year survival of 100%, 100% and 63%, respectively. Eighty-two centers (92%) have never performed HT in HIV(+) patients and 51 centers (57%) marked HIV(+) status as a contraindication. Rationales for contraindication included: (1) high-risk patients should be avoided given the scarcity of organ supply (59%); (2) immunosuppression required for HT may induce progression to AIDS (51%); and (3) drug interactions may worsen patients' clinical outcomes (49%). Thirty-five left ventricular assist device (LVAD) implantations in HIV(+) patients were reported. Sixty-eight centers (76%) have never implanted an LVAD in an HIV(+) patient and 21 centers (20%) marked HIV(+) status as a contraindication, of which 61% indicated concern for device-related infection., Conclusions: Most centers either explicitly consider HIV(+) status as a contraindication for or have never treated HIV(+) patients with advanced HF therapy. Our findings suggest unequal access to care and underscore the need to educate cardiovascular health-care providers on progress made with HIV therapies., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: On April 4, 2012, the U.S. Food and Drug Administration issued a Class 1R recall of the HeartMate II (Thoratec Corporation, Pleasanton, CA) left ventricular assist device (LVAD) due to spontaneous detachment of the bend relief from its intended position in patients implanted with the most recent version of the HM II. This study examined the incidence and timing of outflow graft bend relief disconnection in patients implanted with the HM II LVAD., Methods: All patients supported with the modified version of the HM II LVAD were asked to report for dedicated abdominal X-ray imaging to assess the position of the bend relief. Also performed was a retrospective review of X-ray images of all patients who had previously been supported with this version but had since received a transplant, undergone LVAD explant, or died., Results: Between March 9, 2011, and April 9, 2012, 59 patients underwent primary implant with the modified version HM II. Follow up X-ray images were available for 56 patients (95%). The bend relief was found fully disconnected in 6 of 56 (11%) and partially disconnected in 13 (23%). Two of 6 patients (33%) with full bend relief disconnection and 1 of 13 of the initially partially disconnected patients (7.7%) required urgent surgical intervention due to symptoms of hemolysis and/or heart failure., Conclusions: Bend relief disconnection is common and may be observed immediately after implant but may also develop over time. Full bend relief disconnect may present with hemolysis and/or heart failure symptoms and often requires surgical revision. Surveillance abdominal X-ray imaging should be performed routinely on all patients who were implanted with the modified version HM II., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to develop a novel approach to optimizing continuous-flow left ventricular assist device (CF-LVAD) function and diagnosing device malfunctions., Background: In CF-LVAD patients, the dynamic interaction of device speed, left and right ventricular decompression, and valve function can be assessed during an echocardiography-monitored speed ramp test., Methods: We devised a unique ramp test protocol to be routinely used at the time of discharge for speed optimization and/or if device malfunction was suspected. The patient's left ventricular end-diastolic dimension, frequency of aortic valve opening, valvular insufficiency, blood pressure, and CF-LVAD parameters were recorded in increments of 400 rpm from 8,000 rpm to 12,000 rpm. The results of the speed designations were plotted, and linear function slopes for left ventricular end-diastolic dimension, pulsatility index, and power were calculated., Results: Fifty-two ramp tests for 39 patients were prospectively collected and analyzed. Twenty-eight ramp tests were performed for speed optimization, and speed was changed in 17 (61%) with a mean absolute value adjustment of 424 ± 211 rpm. Seventeen patients had ramp tests performed for suspected device thrombosis, and 10 tests were suspicious for device thrombosis; these patients were then treated with intensified anticoagulation and/or device exchange/emergent transplantation. Device thrombosis was confirmed in 8 of 10 cases at the time of emergent device exchange or transplantation. All patients with device thrombosis, but none of the remaining patients had a left ventricular end-diastolic dimension slope >-0.16., Conclusions: Ramp tests facilitate optimal speed changes and device malfunction detection and may be used to monitor the effects of therapeutic interventions and need for surgical intervention in CF-LVAD patients., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Historically, advanced heart failure therapies were considered inappropriate for patients infected with human immunodeficiency virus (HIV). As HIV has become a chronic illness with the advent of highly active anti-retroviral therapy (HAART), cardiac transplantation has been used for selected HIV patients with end-stage heart failure. We present a case series describing the clinical outcomes with left ventricular assist device (LVAD) use in 4 patients with HIV. Three of the patients are alive: 1 after a successful bridge to transplant and the other 2 on continued device support at 18 and 13 months after implantation. No infectious complications occurred in 3 patients, and no opportunistic infections occurred in the fourth patient. De novo allosensitization did not occur in our patients after LVAD implantation. With the ongoing donor shortage, implantation of an LVAD in advanced heart failure patients with HIV with controlled viremia on HAART represents a viable option., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Graft dysfunction (GD) after heart transplantation (HTx) is a major cause of morbidity and mortality. The impact of different pathophysiologic mechanisms on outcome is unknown. In this large, single-center study we aimed to assess the incidence of GD and compare the outcomes with different histopathologic mechanisms of rejection., Methods: We analyzed a data set of 1,099 consecutive patients after their HTx at Columbia University Medical Center between January 1994 and March 2008, and identified all patients hospitalized with new-onset GD. Based on the histopathologic data, patients were divided into GD-unexplained (Group-GD-U), GD-antibody-mediated rejection (Group-GD-AMR), GD-cardiac allograft vasculopathy (Group-GD-CAV) and GD-acute cellular rejection (Group-GD-ACR) groups. We compared the in-hospital and 3-, 6- and 12-month mortality across these groups using the chi-square test. We also compared the 3-, 6- and 12-month survival curves across groups using the log-rank test., Results: Of 126 patients (12%) identified with GD, complete histology data were available for 100 patients. There were 21, 20, 27 and 32 patients identified in Group-GD-U, Group-GD-AMR, Group-GD-CAV and Group-GD-ACR, respectively. The in-hospital mortality rates were 52%, 20%, 15% and 6%, respectively. The in-hospital mortality rate was significantly higher in Group-GD-U compared with all other groups (p = 0.0006). The 3-, 6- and 12-month survival rate was also significantly lower in Group-GD-U compared with all other groups., Conclusion: A significant proportion of patients presenting with new-onset GD have unexplained histopathology. Unexplained GD is associated with a significantly higher mortality rate. New diagnostic tools are necessary to better understand and detect/predict this malignant phenotype., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Building on our institution's commercial electronic health record and custom personal health record Web portal, we developed a tablet computer application to provide interactive information to hospital patients. Using Apple iPad devices, the prototype application was provided to five patients in a cardiology step-down unit. We conducted detailed interviews to assess patients' knowledge of their inpatient care, as well as their perceptions of the usefulness of the application. While patients exhibited varying levels of comfort with using the tablet computer, they were highly enthusiastic about the application's ability to supply health information such as their inpatient medication histories and photographs of their care providers. Additional research is warranted to assess the benefit such applications may have for addressing inpatient information needs, enhancing patient-provider communication and improving patient satisfaction.

Background: Human immunodeficiency virus (HIV) infection is widely considered a contraindication for cardiac transplantation. However, with the newer anti-retroviral drugs, the estimated 10-year survival after seroconversion is exceeds 90%. This case series describes the intermediate range outcome of HIV-positive cardiac transplant recipients., Methods: A retrospective analysis of 1679 cardiac transplant patients was undertaken to identify HIV-positive recipients., Results: Seven patients were identified. Five (4 men) were diagnosed with HIV before transplantation and 2 patients seroconverted after transplantation. Dilated cardiomyopathy was the indication for transplant in all patients. The 5 HIV recipients were aged 42 +/- 8 years, and time after HIV seroconversion averaged 9.5 years. All underwent cardiac transplantation as high-risk candidates. The CD4 count was 554 +/- 169 cells/microl, and viral load was undetectable in all patients at the time of transplantation. Two patients seroconverted to HIV-positive status at 1 and 7 years after transplant. No AIDS-defining illness was observed in any patient before or after transplant. Six patients received highly active anti-retroviral therapy. Viral load remained low in the presence of immunosuppression. All patients are alive with a follow-up from transplant of 57 +/- 78.9 months., Conclusion: Excellent intermediate term outcome is noted in carefully selected HIV-positive patients. No significant AIDS-related infections or complications occurred.