Mending a Broken Heart: Treatment of Stress-Induced Heart Failure after Solid Organ Transplantation

Stress-induced heart failure, also known as Broken Heart Syndrome or Takotsubo Syndrome, is a phenomenon characterized as rare but well described in the literature, with increasing incidence. While more commonly associated with postmenopausal women with psychiatric disorders, this entity is found in the postoperative patient. The nonischemic cardiogenic shock manifests as biventricular failure with significant decreases in ejection fraction and cardiac function. In a review of over 3000 kidney and liver transplantations over the course of 17 years within two transplant centers, we describe a series of 7 patients with Takotsubo Syndrome after solid organ transplantation. Furthermore, we describe a novel approach of successfully treating the transient, though potentially fatal, cardiogenic shock with a percutaneous ventricular assistance device in two liver transplant patients, while treating one kidney transplant patient medically and the remaining four liver transplant patients with an intra-aortic balloon pump. We describe our experience with Takotsubo’s Syndrome and compare the three modalities of treatment and cardiac augmentation. Our series is novel in introducing the percutaneous ventricular assist device as a more minimally invasive intervention in treating nonischemic heart failure in the solid organ transplant patient, while serving as a comprehensive overview of treatment modalities for stress-induced heart failure

Hepatitis C status and infectious complications in the surgical intensive care unit: a retrospective analysis of 1,941 consecutive patients

BACKGROUND: Hepatitis C virus (HCV) infection is thought to be associated with immune dysfunction. We hypothesized that HCV status would be associated with increased infectious complications in the surgical intensive care unit (SICU). METHODS: All patients admitted to our SICU between 2008 and 2012 were included. We evaluated 90-day mortality and infectious complications in the SICU. Multivariate logistic regression was performed to identify predictors of infectious complications and 90-day mortality. RESULTS: A total of 1,941 patients were included. The HCV-positive group had a higher overall incidence of infectious complications (25% vs 18%), particularly ventilator-associated pneumonia (VAP) and bacteremia. The increased incidences of VAP and bacteremia persisted when cirrhotic patients were excluded. Prolonged intubation (Odds Ratio [OR] = 2.1), abdominal surgery (OR = 1.6), and model for end-stage liver disease ≥ 15 (OR = 1.4) were independent predictors of SICU infectious complications. CONCLUSIONS: The HCV-positive group had an increased incidence of infectious complications in the SICU, particularly VAP and bacteremia. This effect persisted when cirrhotic patients were excluded

The Current State of Donor-Derived Cell-Free DNA Use in Allograft Monitoring in Kidney Transplantation

Renal transplantation is the definitive therapy for patients suffering from end-stage renal disease. Though there have been significant advances in immunosuppression in these patients, there is still up to 30% acute and subclinical rejection. Current standards employ lab markers of renal function and biopsy results for accurate diagnosis. However, donor derived cell-free DNA has been identified as a measurable lab test that may be able to adequately diagnose rejection at early stages, precluding the need for invasive procedures like biopsy. We obtained published data directly from companies that offer ddcfDNA assay tests and additionally conducted a literature review using databases like PUBMED and NIH U.S. National Library of Medicine. We comprehensively compare the most used ddcfDNA assays, delineate their respective limitations, and further explore future directions in the utility of ddcfDNA in renal transplant patients

Antibody Therapeutics as Interfering Agents in Flow Cytometry Crossmatch for Organ Transplantation

Donor–recipient matching is a highly individualized and complex component of solid organ transplantation. Flowcytometry crossmatching (FC-XM) is an integral step in the matching process that is used to detect pre-formed deleterious anti-donor immunoglobulin. Despite high sensitivity in detecting cell-bound immunoglobulin, FC-XM is not able to determine the source or function of immunoglobulins detected. Monoclonal antibody therapeutic agents used in a clinic can interfere with the interpretation of FC-XM. We combined data from the prospectively maintained Antibody Society database and Human Protein Atlas with a comprehensive literature review of PubMed to summarize known FC-XM-interfering antibody therapeutics and identify potential interferers. We identified eight unique FC-XM-interfering antibody therapeutics. Rituximab (anti-CD20) was the most-cited agent. Daratumuab (anti-CD38) was the newest reported agent. We identified 43 unreported antibody therapeutics that may interfere with FC-XM. As antibody therapeutic agents become more common, identifying and mitigating FC-XM interference will likely become an increased focus for transplant centers

No Child Left Behind: Liver Transplantation in Critically Ill Children

Advances in critical care prolong survival in children with liver failure, allowing more critically ill children to undergo orthotopic liver transplantation (OLT). In order to justify the use of a scarce donor resource and avoid futile transplants, we sought to determine survival in children who undergo OLT while receiving pre-OLT critical care. We analyzed 13,723 pediatric OLTs using the United Network for Organ Sharing (UNOS) database from 1987 to 2015, including 6,746 recipients in the Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) era (2002 to 2015). There were 1,816 recipients (26.9%) admitted to the ICU at the time of transplantation. We also analyzed 354 pediatric OLT recipients at our center from 2002 to 2015, one of the largest institutional experiences. Sixty-five recipients (18.3%) were admitted to the ICU at the time of transplantation. Kaplan-Meier, volume threshold, and multivariable analyses were performed. Patient survival improved steadily over the study period, (66% 1-year survival in 1987 vs 92% in 2015; p < 0.001). Our institutional experience of ICU recipients in the MELD/PELD era had acceptable outcomes (87% 1-year survival), even among our sickest recipients with vasoactive medications, mechanical ventilation, dialysis, and molecular adsorbent recirculating system requirements. Volume analysis revealed inferior outcomes (hazard ratio [HR] 1.68; 95% CI 1.11 to 2.51) in low-volume centers (<5 annual cases). Identifiable risk factors (previous transplantation, elevated serum sodium, hemodialysis, mechanical ventilation, body weight < 6 kg, and low center volume) increased risk of mortality. This analysis demonstrates that the use of advanced critical care in children and infants with liver failure is justified because OLT can be performed on the sickest children and acceptable outcomes achieved. It is an appropriate use of a scarce donor allograft in a child who would otherwise succumb to a terminal liver disease

Donor hepatitis C status is not associated with an increased risk of acute rejection in kidney transplantation

Introduction: In renal transplantation, donor hepatitis C virus (HCV) status is crucial to consider when selecting a recipient given the high likelihood of transmission. We analyzed the effect of donor HCV status on post-renal transplant rejection and virologic infectious outcomes using electronic health record data from multiple US health care organizations. Methods: Using real world data from electronic health records of renal transplant recipients, a propensity score-matched case-control study of one-year renal transplant outcomes was conducted on cohorts of HCV-negative recipients who received an organ from an HCV-positive donor (HCV D+/R-) versus from an HCV-negative donor (HCV D-/R-). Donor HCV positivity was defined as new recipient HCV positivity within 30 days post-transplant. Cohorts were matched by major risk factors for rejection including age, gender, race, etiologies of end-stage renal disease, dialysis dependence, donor type, induction immunosuppression, and virologic lab studies. The primary outcome was one-year incidence of rejection. Secondary outcomes included longitudinal measures of liver and kidney function, incidence of non-HCV viremia, and DAA treatment pathways and responses. Results: Data from 900 renal transplant recipients were analyzed, 450 subjects per group (D+/R-, D-/R-). Mean age at transplant was 57.1 ± 11.9 years, 60 % were male, and 38 % were African American. Kaplan-Meier analysis showed a significantly increased incidence of one-year rejection for HCV D-/R- compared to HCV D+/R- (16.6% vs 22.8 %, p = 0.02). This difference did not persist on a sub-analysis excluding subjects with delayed graft function (DGF) (16.3% vs 19.2 %, p = 0.25). Although mean eGFR was initially higher in HCV D+/R-, there were no significant differences in liver or kidney allograft function at 12 months. There was no significant difference for composite viremia (CMV/EBV/BK; 37.66% vs 31.60 %, p = 0.07). The most common DAA regimen was glecaprevir/pibrentasvir (52.8 %). DAA treatment responses were excellent, with most subjects having a negative viral load by 90 days (mean: 1.7 ± 1.9 log units/mL). Conclusion: Donor HCV positivity did not negatively impact one-year rejection outcomes post-renal transplantation. Importantly, this effect was not biased by age. Anti-HCV treatment was effective and liver and kidney function were excellent at one-year post-transplant. These data support the continued expansion of the donor pool by utilizing organs from HCV-positive donors in the era of anti-HCV direct-acting antiviral therapies

Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older

Introduction and Objectives: Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies(OT-0401, REVERSE, CONFIRM). Patients and Methods: The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal—defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 μmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death—and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events. Results: Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data. Conclusions: Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome. Clinical trial numbers: OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT0277071

Do Patients with Autoimmune Conditions Have Less Access to Liver Transplantation despite Superior Outcomes?

Orthotopic liver transplantation (OLT) is a lifesaving therapy for patients with irreversible liver damage caused by autoimmune liver diseases (AutoD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, it is unclear how access to transplantation differs among patients with various etiologies of liver disease. Our aim is to evaluate the likelihood of transplant and the long-term patient and graft survival after OLT for each etiology for transplantation from 2000 to 2021. We conducted a large retrospective study of United Network for Organ Sharing (UNOS) liver transplant patients in five 4-year eras with five cohorts: AutoD (PBC, PSC, AIH cirrhosis), alcohol-related liver disease (ALD), hepatocellular carcinoma (HCC), viral hepatitis, and nonalcoholic steatohepatitis (NASH). We conducted a multivariate analysis for probability of transplant. Intent-to-treat (ITT) analysis was performed to assess the 10-year survival differences for each listing diagnosis while accounting for both waitlist and post-transplant survival. Across all eras, autoimmune conditions had a lower adjusted probability of transplant of 0.92 (0.92, 0.93) compared to ALD 0.97 (0.97, 0.97), HCC 1.08 (1.07, 1.08), viral hepatitis 0.99 (0.99, 0.99), and NASH 0.99 (0.99, 1.00). Patients with AutoD had significantly better post-transplant patient and graft survival than ALD, HCC, viral hepatitis, and NASH in each and across all eras (p-values all &lt; 0.001). Patients with AutoD had superior ITT survival (p-value &lt; 0.001, log rank test). In addition, the waitlist survival for patients with AutoD compared to other listing diagnoses was improved with the exception of ALD, which showed no significant difference (p-value = 0.1056, log rank test). Despite a superior 10-year graft and patient survival in patients transplanted for AutoD, patients with AutoD have a significantly lower probability of receiving a liver transplant compared to those transplanted for HCC, ALD, viral hepatitis, and NASH. Patients with AutoD may benefit from improved liver allocation while maintaining superior waitlist and post-transplant survival. Decreased access in spite of appropriate outcomes for patients poses a significant risk for increased morbidity for patients with AutoD