Three year post heart transplant outcomes of desensitized durable mechanical circulatory support patients.

BACKGROUND: The risks and benefits of desensitization therapy (DST) in highly sensitized mechanical circulatory support (MCS) patients are not well known. We investigated 3 year post-transplant outcomes of desensitized durable MCS patients. METHODS: Among 689 consecutively enrolled heart transplantation recipients between 2010 and 2016, we categorized them into Group A (desensitized MCS patients, n = 21), Group B (desensitized non-MCS patients, n = 28) and Group C (all nondesensitized patients, n = 640). Post-transplant outcomes included the incidence of primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, antibody mediated rejection (AMR) and infectious complications. RESULTS: The types of DST in Groups A and B were similar and included combinations of rituximab/intravenous immunoglobulin and plasmapheresis/bortezomib. Group A, compared with Group B, showed significantly higher pre-DST panel reactive antibody (PRA) (92.2 ± 9.8 vs. 83.3 ± 15.6, P = 0.007) and higher PRA reduction after DST (-22.2 ± 26.9 vs. -6.3 ± 7.5, P = 0.015). Groups A and C showed comparable primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, and AMR. Although statistically not significant, Group A showed numerically higher 3-year freedom from AMR than Group B. Infectious complications were similar in both Groups A and B. CONCLUSIONS: DST for MCS patients showed significant PRA reduction, resulting in an expansion of the donor pool. The post-transplant outcome of desensitized MCS patients showed comparable clinical outcomes to non-desensitized control patients in the same study period, revealing the safety and efficacy of DST.

Temporary Mechanical Circulatory Support in Patients with Cardiogenic Shock: Clinical Characteristics and Outcomes.

Patients with cardiogenic shock may require stabilization with temporary mechanical circulatory support (tMCS) to assess candidacy for definitive therapy, including heart transplantation (HTx) or durable MCS, and/or maintain stability while on the HTx waiting list. We describe the clinical characteristics and outcomes of patients with cardiogenic shock who underwent intra-aortic balloon pump (IABP) vs. Impella [Abiomed, Danvers, MA, USA] placement at a high-volume advanced heart failure center. We assessed patients ≥ 18 years who received IABP or Impella support for cardiogenic shock from 1 January 2020 to 31 December 2021. Ninety patients were included, 59 (65.6%) with IABP and 31 (34.4%) with Impella. Impella was used more frequently in less stable patients, as evidenced by higher inotrope scores, greater ventilator support, and worse renal function. While patients on Impella support had higher in-hospital mortality, despite the worse cardiogenic shock in patients for whom clinicians chose Impella support, over 75% were successfully stabilized to recovery or transplantation. Clinicians elect Impella support over IABP for less stable patients, though a high proportion are successfully stabilized. These findings demonstrate the heterogeneity of the cardiogenic shock patient population and may inform future trials to assess the role of different tMCS devices.

Post-transplantation outcomes of sensitized patients receiving durable mechanical circulatory support.

BACKGROUND: Sensitization, defined as the presence of circulating antibodies, presents challenges, particularly in patients undergoing heart transplantation (HTx) bridged with durable mechanical circulatory support (MCS). We aimed to investigate the post-transplantation outcomes of sensitized MCS patients. METHODS: Among 889 consecutively enrolled heart transplant (HTx) recipients between 2010 and 2018, 86 (9.7%) sensitized MCS patients (Group A) were compared with sensitized non-MCS patients (Group B, n = 189), non-sensitized MCS patients (Group C, n = 162), and non-sensitized non-MCS patients (Group D, n = 452) regarding post-HTx outcomes, including the incidence of primary graft dysfunction (PGD), 1-year survival, and 1-year freedom from antibody-mediated rejection (AMR). RESULTS: Sensitized MCS patients (Group A) showed comparable rates of PGD, 1-year survival, and 1-year freedom from AMR with Groups C and D. However, Group A showed significantly higher rates of 1-year freedom from AMR (95.3% vs 85.7%, p = 0.02) and an earlier decline in panel-reactive antibody (PRA) levels (p < 0.01) than sensitized non-MCS patients (Group B). Desensitization therapy effectively reduced the levels of PRA in both Groups A and B. When Group A was further divided according to the presence of preformed donor-specific antibodies (DSA), patients with preformed DSA showed significantly lower rates of 1-year freedom from AMR than those without (84.2% vs 98.5%, p = 0.01). CONCLUSIONS: Sensitized MCS patients showed significantly lower rates of AMR and an earlier decline in PRA levels following HTx than sensitized non-MCS patients. Removal of MCS at the time of transplantation might underlie these observations.

Total Artificial Heart as Bridge to Cardiac Retransplantation.

Mechanical circulatory support has been performed as a bridge to cardiac retransplantation in selected patients with graft failure. However, there is limited published experience on the use and potential benefit of the total artificial heart (TAH) as a bridge to cardiac retransplantation. We report on our institutional experience with 3 patients that received TAH as a bridge to retransplant, with 1 patient surviving post-retransplantation. This case series demonstrates the high-risk nature of this undertaking in cardiac retransplant candidates and highlights the issue of sensitization portending greater risk for poor outcomes after TAH as bridge to retransplantation.

The Impact of a High-risk Psychosocial Assessment on Outcomes After Durable Mechanical Circulatory Support.

Patient adherence is vital to the success of durable mechanical circulatory support (MCS), and the pre-MCS assessment of adherence by the multidisciplinary advanced heart failure team is a critical component of the evaluation. We assessed the impact of a high-risk psychosocial assessment before durable MCS implantations on post-MCS outcomes. Between January 2010 and April 2018, 319 patients underwent durable MCS at our center. We excluded those who died or were transplanted before discharge. The remaining 203 patients were grouped by pre-MCS psychosocial assessment: high-risk (26; 12.8%) versus acceptable risk (177; 87.2%). We compared clinical characteristics, nonadherence, and outcomes between groups. High-risk patients were younger (48 vs. 56; p = 0.006) and more often on extracorporeal membrane oxygenation at durable MCS placement (26.9% vs. 9.0%; p = 0.007). These patients had a higher incidence of post-MCS nonadherence including missed clinic appointments, incorrect medication administration, and use of alcohol and illicit drugs. After a mean follow-up of 15.3 months, 100% of high-risk patients had unplanned hospitalizations compared with 76.8% of acceptable-risk patients. Per year, high-risk patients had a median of 2.9 hospitalizations per year vs. 1.2 hospitalizations per year in acceptable-risk patients. While not significant, there were more driveline infections over the follow-up period in high-risk patients (27% vs. 14.7%), deaths (27% vs. 18%), and fewer heart transplants (53.8% vs. 63.8%).The pre-MCS psychosocial assessment is associated with post-MCS evidence of nonadherence and unplanned hospitalizations. Attention to pre-MCS assessment of psychosocial risk factors is essential to optimize durable MCS outcomes.

A New Paradigm in Mechanical Circulatory Support: 100-Patient Experience.

BACKGROUND: Acutely decompensated heart failure presents a complicated challenge. Established temporary support measures have significant adverse effects. A minimally invasive temporary left ventricular assist device (LVAD), the Impella 5.0 (Abiomed, Danvers, MA), has been developed to support these patients. METHODS: Patients with acutely decompensated heart failure in whom medical management had failed and who required additional support using an Impella 5.0 device were evaluated from January 2014 to September 2018 at a single center in a retrospective manner using a prospectively maintained database. Patients were treated with the device as a bridge to recovery (BTR; n = 30), bridge to durable device (BTDD; n = 23), or bridge to transplantation (BTT; n = 47). All devices were placed using an axillary artery approach. Demographic features and outcomes were evaluated for each group and compared. RESULTS: A total of 100 patients underwent insertion of an axillary Impella 5.0 LVAD. Patients had an average age of 56.7 ± 13.2 years, were predominantly male (84%), and had a severely depressed left ventricular ejection fraction (average 16%), and most had an Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 (57%) or 2 (33%) score. When divided into groups, there was no difference in age or INTERMACS score, but a statistical difference was noted in baseline left ventricular ejection fraction (20%, 14%, 15%) and creatinine level (1.0, 2.0, 1.6), in the BTR, BTDD, or BTT group, respectively (all P < .05). Survival was 64% overall, and it was 50%, 48%, and 81% for BTR, BTDD, and BTT, respectively (P = .007). Survival improved during this experience and was 90% overall in the most recent 30 patients. CONCLUSIONS: Use of this minimally invasive LVAD system is an attractive strategy to support patients with acute decompensated heart failure to recovery, durable LVAD, or heart transplantation.

Mechanical circulatory support for cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, typically from abnormal deposition of AL or ATTR amyloid protein, can result in heart failure requiring transplantation (HTx). The role of mechanical circulatory support (MCS) is not well-established. The purpose of this study was to present our experience with MCS in patients with cardiac amyloidosis. METHODS: Consecutive patients with cardiac amyloidosis who received MCS at Cedars-Sinai Medical Center between 2010 and 2018 were reviewed. Clinical characteristics and outcomes were compared to a control group of MCS patients without amyloid matched 2:1 for age and INTERMACS Profile. RESULTS: 11 amyloid patients underwent durable MCS, two with paracorporeal biventricular assist devices and 9 with total artificial hearts. No patients received isolated left ventricular assist device support. By 1 year, 9 (82%) of patients in the MCS-Amyloid group had been transplanted and 2 (18%) had died. In the MCS-No Amyloid group, by 1 year, 8 (36%) of patients had been transplanted, 10 (46%) had died, and 4 (18%) were still living with MCS. CONCLUSIONS: Over a 9-year period, patients with amyloid cardiomyopathy who required MCS at our institution all received durable biventricular MCS. For carefully selected patients, this approach is feasible with acceptable outcomes as bridge to transplantation.

Evaluation of 30 Day Readmissions After Index Ventricular Assist Device Implantation in the United States.

Ventricular assist device (VAD) implantation has improved quality of life and short-term survival for advanced heart failure patients. There are limited data from single-center studies addressing the characteristics and etiologies of 30 day readmissions after VAD implant. We used the Nationwide Readmissions Database (NRD) 2014 to identify insertion of implantable heart assist system during index admission. Primary and secondary outcomes were 30 day readmissions and leading etiologies, respectively. We analyzed 1,481 patients who received VAD during the primary admission of whom 1,315 patients survived to hospital discharge (mortality rate 11.2%), and 60.6% were discharged to a nursing facility. One hundred and thirty-one (10.0%) patients were readmitted within 30 days of primary hospitalization. Leading etiologies of 30 day readmission were bleeding (24%), heart failure (18%), and device complications (14%). Mean length of stay during readmission was 13.8 days with a mortality rate of 2.1%. Fifty percent of 30 day readmissions were readmitted from day 22 to 30. Variables for predictors of 30 day readmissions were not statistically significant. By identifying gastrointestinal bleeding, heart failure, and device complications as leading etiologies of 30 day readmission post-VAD implantation, providers can potentially modify practices to prevent hospital readmissions, decreasing cost of care, and improving the quality of life of patients.

Desensitization Strategies Pre- and Post-Cardiac Transplantation.

OPINION STATEMENT: Panel reactive antibody (PRA) testing has become standard in the evaluation of patients prior to cardiac transplant. Sensitizing events such as blood transfusions, which result in the accumulation of pre-transplant antibodies, should be avoided as clinically feasible. Desensitization therapy might be considered in sensitized patients with cPRA > 50 % although distinct cutoff PRA values for initiating therapy pre-transplant are patient and transplant program dependent. Post-cardiac transplant, quantitative antibodies should also be periodically analyzed, at intervals individualized to the patient. Donor-specific antibodies (DSA) after cardiac transplantation have been shown to be associated with worsened survival. It appears that complement fixing DSA confer the greatest risk for antibody-mediated rejection post-transplant. Desensitization strategies aim to reduce the number of clinically important antibodies prior to and after transplant, both by removal of antibodies and cessation of further production. Current desensitization regimens include pharmacologic, procedural, and surgical modalities, and must be individualized to the patient. Currently, most cardiac transplant programs tailor the post-transplant immunosuppressive regimen based on clinical factors and immunologic assays and may include the use of cytolytic induction and/or intravenous immune gammaglobulin in higher risk patients.

Bone formation during distraction osteogenesis is dependent on both VEGFR1 and VEGFR2 signaling.

INTRODUCTION: Distraction osteogenesis (DO) is characterized by the induction of highly vascularized new bone formation through an intramembranous process largely devoid of the formation of cartilage. MATERIALS AND METHODS: To test the hypothesis that DO is strictly dependent on vascualrization, we inhibited vascular endothelial growth factor (VEGF) activity by antibody blockade of both receptors VEGFR1 (Flt-1) and VEGFR2 (Flk-1) or only VEGFR2 (Flk-1) in a previously developed murine tibia DO model. During normal DO, VEGFR1 (Flt-1), VEGFR2 (Flk-1), VEGFR3 (Flt4) and all four VEGF ligand (A, B, C, and D) mRNAs are induced. RESULTS: The expression of mRNA for the receptors generally paralleled those of the ligands during the period of active distraction. Bone formation, as assessed by muCT, showed a significant decrease with the double antibody treatment and a smaller decrease with single antibody treatment. Vessel volume, number, and connectivity showed progressive and significant inhibition in all of these of parameters between the single and double antibody blockade. Molecular analysis showed significant inhibition in skeletal cell development with the single and double antibody blockade of both VEGFR1 and 2. Interestingly, the single antibody treatment led to selective early development of chondrogenesis, whereas the double antibody treatment led to a failure of both osteogenesis and chondrogenesis. CONCLUSIONS: Both VEGFR1 and VEGFR2 are functionally essential in blood vessel and bone formation during DO and are needed to promote osteogenic over chondrogenic lineage progression.