Advanced heart failure and heart transplantation in adult congenital heart disease in the current era.

BACKGROUND: Adults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short-term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical characteristics and outcomes of patients with ACHD in the current era referred for HTx at a single high-volume transplant center. METHODS: From 2010 to 2020, 37 ACHD patients were evaluated for HTx. ACHD HTx recipients were compared to non-ACHD HTx recipients matched for age, sex, listing status, and prior cardiac surgery. RESULTS: Of the 37 patients with ACHD, eight (21.6%) were declined for HTx. Of 29 ACHD patients listed, 19 (65.5%) underwent HTx. Compared with non-ACHD HTx controls, the ACHD HTx recipients had more treated cellular (21.1% vs. 15.8%, P = .010) and antibody-mediated (15.8% vs. 10.5%, P = .033) rejection. There was no difference in hospital readmission or allograft vasculopathy at 1 year. There was a nonsignificant higher 1-year mortality in ACHD HTx recipients (21.1% vs. 7.9%, P = .21). CONCLUSION: At a high-volume transplant center, ACHD patients undergoing HTx appear to have a marginally higher risk of rejection, but no significant increase in 1-year mortality. With careful selection and management, HTx for patients with ACHD may be feasible in the current era.

Soft Tissue Infection with Diaporthe phaseolorum in Heart Transplant Recipient with End-Stage Renal Failure.

Diaporthe phaseolorum is a fungal plant parasite that has rarely been described as causing invasive human disease. We report a case of human soft tissue infection with Diaporthe phaseolorum in a heart transplant patient with end-stage renal failure in New Zealand.

Ecthyma gangrenosum in a 3-year-old boy post-heart transplantation.

Ecthyma gangrenosum (EG) is a serious bacterial infection in immunocompromised patients. EG in transplant recipients is rarely reported and may go unrecognized, which may delay initiation of appropriate treatment. We report a case of EG in a pediatric heart transplant recipient who was treated successfully with antibiotics and surgical debridement.

Outcomes of Patients With Familial Transthyretin Amyloidosis After Liver Transplantation.

BACKGROUND: Familial transthyretin amyloidosis is a disease caused by misfolded transthyretin aggregates that can impair multiple organ systems. Liver transplantation is the first-line treatment for familial transthyretin amyloidosis. RESEARCH QUESTION: Our objective is to study outcomes and survival among patients with familial transthyretin amyloidosis after transplantation. DESIGN: All patients undergoing orthotopic liver transplant for familial transthyretin amyloidosis at Mayo Clinic between 1997 and 2012 were reviewed. Baseline clinical characteristics, organs transplanted, and posttransplant clinical course were assessed. RESULTS: Of the 40 patients, 7 patients had the V30M mutation and 33 had other mutations. Nineteen patients received liver only, 19 liver and heart, and 2 combined liver, heart, and kidney transplants. The 5-year overall survival was 85% for those receiving multiple organ transplant and 52% for those receiving liver transplant only ( P = .057). There was no difference in overall survival based on mutation (V30M vs other mutations), but survival was confounded by varied disease involvement and organs transplanted. Those who had early death (≤24 months from liver transplant) had a higher incidence of baseline peripheral neuropathy, autonomic neuropathy, lower modified BMI, and higher alkaline phosphatase. DISCUSSION: Outcomes of orthotopic liver transplant in familial transthyretin amyloidosis are variable due to heterogeneity in mutations and patient status at the time of transplant. Familial transthyretin amyloidosis can progress, despite liver transplantation. Patients receiving combined liver, heart/kidney transplant demonstrated improved survival compared to liver transplant alone.

Recovery From Acute Kidney Injury and CKD Following Heart Transplantation in Children, Adolescents, and Young Adults: A Retrospective Cohort Study.

BACKGROUND: Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013. PREDICTOR: The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine ≥ 1.5 times baseline within 7 days). OUTCOMES: Recovery from AKI at 3 months, ascertained as serum creatinine level < 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate < 60mL/min/1.73m(2) for more than 3 months. RESULTS: 63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively). LIMITATIONS: Retrospective design, small sample size, and single-center nature of the study. CONCLUSIONS: AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.

BK Virus Nephropathy in Heart Transplant Recipients.

Polyomavirus-associated nephropathy (PVAN) has become an important cause of kidney failure in kidney transplant recipients. PVAN is reported to affect 1% to 7% of kidney transplant recipients, leading to premature transplant loss in approximately 30% to 50% of diagnosed cases. PVAN occurring in the native kidneys of solid-organ transplant recipients other than kidney only recently has been noted. We report 2 cases of PVAN in heart transplant recipients, which brings the total of reported cases to 7. We briefly review the literature on the hypothesized causes of PVAN in kidney transplant recipients and comment on whether these same mechanisms also may cause PVAN in other solid-organ transplant recipients. PVAN should be considered in the differential diagnosis when evaluating worsening kidney function. BK viremia surveillance studies of nonkidney solid-organ recipients should be conducted to provide data to assist the transplantation community in deciding whether regular monitoring of nonkidney transplant recipients for BK viremia is indicated.

Echocardiography detects elevated left ventricular filling pressures in heart transplant recipients.

Diastolic dysfunction is a recognized complication in heart transplant (HTx) recipients that limits exercise capacity and is a risk factor for mortality. We investigated the ability of echocardiography to detect elevated pulmonary capillary wedge pressure (mean PCWP>15 mmHg) in HTx recipients. This retrospective study comprised HTx recipients with echocardiography and right heart catheterization within 24 hours (n = 100, 113 investigations). Echocardiographic assessment was performed using mitral inflow (E/A ratio, deceleration time [DT], isovolumic relaxation time [IVRT]), tissue Doppler (E/E' lateral) parameters, and the Doppler-estimated pulmonary artery systolic pressure (Doppler PASP). The right atrial pressure (RAP) was estimated based on size and the effect of respiration or sniffing on the inferior vena cava diameter. Cutoff values were determined from a derivation group (n = 57, receiver operator characteristic curve analysis) and evaluated in a test group (n = 56). Elevated PCWP were found in 38%. The RAP and PCWP were both normal in 58 investigations and elevated in 39 investigations (concordance rate of 86.6%). The presence of signs of increased RAP by echocardiography or with three of five parameters (E/A, DT, IVRT, E/E' lateral, and Doppler PASP) reaching the cutoff values ruled in elevated PCWP with positive likelihood ratios ranging from 15.3 to 9. With normal RAP by echocardiography or none of the other parameters reaching cutoff values elevated PCWP can be ruled out with negative likelihood ratios ranging from 0.07 to 0.19. In conclusion, elevated PCWP in HTx recipients can be assessed using echocardiography.

The association between body mass index, exercise capacity, and health-related quality of life in heart transplant recipients.

Introduction: Pre-transplant obesity and weight gain after heart transplantation are both associated with increased risk of poor clinical outcomes. We aimed to assess the association between overweight or obesity, exercise capacity, and health-related quality of life in heart transplant recipients. Methods: This study is based on baseline data from the IronIC trial, in which we randomized 102 heart transplant recipients with iron deficiency to ferric derisomaltose or placebo. We performed cardio pulmonary exercise testing in all participants. To assess quality of life, we used the SF-36v2 questionnaire, using two sum scores: the physical component summary and the mental component summary. A minimal clinically important difference was defined as ≥2 and ≥3 for the physical and the mental component summary, respectively. Results: 24/102 heart transplant recipients (24%) had a body mass index (BMI) ≥30 kg/m2. Peak oxygen consumption was 17.3 ± 4.6 ml/kg/min in the obese group vs. 24.7 ± 6.4 ml/kg/min in the group with a BMI <30 for a between-group difference of 7.4 (95% confidence interval 4.7-10.2) ml/kg/min: p < 0.001. The physical component summary score was on average 5.2 points lower in the patients with a body mass index ≥30 than in the lower weight group (p = 0.04). Conclusion: Almost a quarter of our heart transplant recipients in long-term follow-up had a BMI ≥30 kg/m2. These patients had substantially lower exercise capacity and lower quality of life in the physical domain.

Humoral and cellular immune response after severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccination in heart transplant recipients: An observational study in France.

Introduction: Heart transplant (HT) recipients have a high risk of developing severe COVID-19. Immunoglobulin G antibodies are considered to provide protective immunity and T-cell activity is thought to confer protection from severe disease. However, data on T-cell response to mRNA vaccination in a context of HT remains limited. Methods: In 96 HT patients, a IFN-γ release assay and an anti-Spike antibody test were used to evaluate the ability of SARS-CoV-2 mRNA vaccines to generate cellular and humoral immune response. Blood samples were collected few weeks to 7 months after vaccination. Multiple fractional polynomial and LASSO regression models were used to define predictors of T-cell response. Results: Three to five months after vaccination, three doses of vaccine induced a positive SARS-CoV-2 T-cell response in 47% of recipients and a positive humoral response in 83% of recipients, 11.1% of patients remained negative for both T and B cell responses. Three doses were necessary to reach high IgG response levels (>590 BAU/mL), which were obtained in a third of patients. Immunity was greatly amplified in the group who had three vaccine doses plus COVID-19 infection. Conclusion: Our study revealed that T and B immunity decreases over time, leading us to suggest the interest of a booster vaccination at 5 months after the third dose. Moreover, a close follow-up of immune response following vaccination is needed to ensure ongoing immune protection. We also found that significant predictors of higher cellular response were infection and active smoking, regardless of immunosuppressive treatment with mycophenolate mofetil (MMF).

Differentiating Depression From Demoralization in Organ Transplantation Recipients.

Living with end stage organ failure and transplantation has implications for physiological, psychological, and social well-being. The development of anxiety or depressive disorders are common with demoralization, another psychological syndrome, a topic of interest in psychiatry. To feel demoralized is to lose hope, courage, or confidence, which upsets normal functioning. While depression may co-exist with demoralization, they are 2 distinct entities, with the former characterized by an inability to experience pleasure and the latter characterized by helplessness and avoidance coping. In an effort to more adequately address the psychological stress in organ transplant patients, it is important to distinguish between demoralization and depression. Demoralization has prognostic implications such as negative disease outcomes such as treatment nonadherence and an increase risk of suicide. Medication for depression is not effective for demoralization syndrome. Therapeutic interventions include cognitive behavioral techniques that focus on exploration of attitudes toward hope and meaning in life.

Aspergillus endophthalmitis: Potential role for vitreous galactomannan testing?

Eye damage during invasive aspergillosis is rarely described and biological diagnosis remains challenging. Here we report the case of a heart transplant recipient with ocular aspergillosis complicating disseminated aspergillosis. Although voriconazole was rapidly given, a decrease in visual acuity of the right eye was consistent with endophthalmitis, resulting in an emergency vitrectomy. The diagnosis was rapidly confirmed: laboratory results showed the presence of Aspergillus fumigatus in a vitreous sample. A series of systemic antifungal medications (liposomal amphotericin B, caspofungin, and voriconazole), several liposomal amphotericin B ocular injections, and pars plana vitrectomy resulted in a limited positive clinical outcome. Interestingly although standard mycological follow-up procedures were negative, Aspergillus antigen testing gave an index of 5.92 on vitreous humour, thus a new intraocular injection of liposomal amphotericin B was performed and voriconazole reinitiated. Ten other vitreous samples from patients without fungal infections were also tested, all showing indexes below 0.25. Although larger studies are needed, this case illustrates that galactomannan testing of vitreous humour could be useful for the diagnosis of fungal endophthalmitis if these data are confirmed in other patients, in particular, if standard mycology is negative and PCR is not available.

Gastrointestinal presentation of COVID-19 in a pediatric heart transplant recipient.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) most commonly causes a mild respiratory illness; however, there are wide ranges of presenting symptoms and disease severity. It has a mortality rate around 7%. Case presentation: We present a case of a 9-year-old female patient with hypoplastic left heart syndrome status post heart transplantation at age of 7 days. She presented to our emergency room complaining of intermittent fever, chills, fatigue, poor appetite, and diarrhea.A throat swab nucleic acid test was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intravenous fluids therapy was used for correction of hydration status. To the best of our knowledge this is the first reported case of non-pulmonary presentation of coronavirus disease-2019 (COVID-19) in a pediatric heart transplant recipient, which was successfully managed conservatively. Conclusions: Gastrointestinal manifestations can be the only presenting symptom in pediatric heart transplant recipients with COVID-19. Conservative treatment could be used successfully. Immunomodulatory medications that are used in heart transplant recipients may have protective value in SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) in the heart transplant population: a single-centre experience.

OBJECTIVES: Few anecdotal cases have been reported in the literature regarding heart transplant recipients and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report our experience with 6 patients hospitalized in Northern Italy during the outbreak. METHODS: Of the 396 living heart transplant recipients from 1985 to 2020 included in the study, 6 patients developed the novel 2019 coronavirus disease. Risk factors, last follow-up characteristics, onset presentation, in-hospital course of disease and blood examinations data were collected for these patients. RESULTS: All patients were symptomatic and had positive results from a nasopharyngeal swab test for SARS-CoV-2. Of the 6 patients, 5 were hospitalized and 1 remained self-quarantined at home. Two patients died and 3 were discharged home. Two patients were admittted to the intensive care unit . Immunosuppressive therapy was modified with a median reduction comprising doses that were 50% cyclosporine and 50% mycophenolate. All patients received a medium-dose of corticosteroids as a bolus medication in addition to their therapy. All hospitalized patients received hydroxychloroquine; 2 patients received ritonavir/lopinavir. Broad-spectrum antibiotics for prophylaxis were administered to all. One patient had an ischaemic stroke and died of sepsis. CONCLUSIONS: In the absence of any strong evidence regarding the treatment of heart transplant recipients infected with SARS-CoV-2, we faced a new challenge in managing viral infection in an immunosuppressed population. Because immunomodulation interaction with the infection seems to be crucial for developing severe forms of the disease, we managed to reduce immunosuppressive therapy by adding medium doses of corticosteroids. Despite the limited number of affected patients, this report suggests that special considerations should be given to treating coronavirus disease in the heart transplant recipient population.

Evaluating Prognostic Factors for Liver Transplantation Among United States Patients With Hereditary Transthyretin-Mediated (hATTR) Amyloidosis Using National Registry Data.

INTRODUCTION: Orthotopic liver transplantation has been used as a treatment for hereditary transthyretin-mediated (hATTR) amyloidosis, a rare, progressive, and multisystem disease. RESEARCH QUESTION: The objective is to evaluate survival outcomes post-liver transplantation in patients with hATTR amyloidosis in the United States and assess whether previously published prognostic factors of patient survival in hATTR amyloidosis are generalizable to the US population. DESIGN: This cohort study examined patients with hATTR amyloidosis undergoing liver transplant in the United States (N = 168) between March 2002 and March 2016 using data reported to the Organ Procurement and Transplantation Network (UNOS)/United Network for Organ Sharing (OPTN). RESULTS: A multivariable Cox hazards regression model showed among all factors tested, only modified body mass index (kg/m2 × g/L) at the time of transplant was significantly associated with survival. Higher modified BMI was associated with lower risk of death relative to a reference population (<600) with historically poor post-transplant outcomes. Patients with modified BMI 1000 to <1200 (hazard ratio [HR] = 0.27; 95% confidence interval [CI] = 0.10-0.73), 1200 to <1400 (HR = 0.20; 95% CI = 0.06-0.75), and ≥1400 (HR = 0.15; 95% CI = 0.04-0.61) exhibited improved adjusted 5-year post-transplant survival of 74%, 80%, and 85%, respectively, versus 33% in the reference population. DISCUSSION: The association between a higher modified BMI threshold at the time of transplant and improved post-transplant survival suggests that the previously published patient selection criterion for modified BMI may not be applicable to the US population.

Long-Term Results of Bilateral Lung Transplantation in Patients With End-Stage Pulmonary Lymphangioleiomyomatosis.

INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare disease in women, leading to progressive deterioration of lung function and respiratory failure. We describe the outcome of patients with end-stage LAM who underwent lung transplantation at our center. MATERIALS AND METHODS: The records of patients with LAM transplanted at our institution between February 1997 and May 2015 were reviewed retrospectively. Morbidity and mortality were analyzed, and actuarial survival was calculated using Kaplan-Meier methods. The cumulative survival of transplant patients with LAM at our center was compared with survival after transplantation due to different diseases at our center and the results of the International Society for Heart and Lung Transplantation. Quality of life was assessed by a patient self-report at the end of the first postoperative year. RESULTS: During the study period, 25 patients underwent lung transplantation for LAM. All patients were women with a mean age of 50 (9) years. Thirteen patients (52%) had undergone previous thoracotomy. All patients (100%) received bilateral lung transplantation. One (4%) case of in-hospital mortality occurred and 9 (36%) late deaths. Two (8%) cases of late death were due to chronic lung allograft dysfunction. The 1-, 3-, and 5-year survival rates were 92%, 84%, and 76%, respectively. Quality-of-life ratings were above the normal in all eight 36-Item Short Form Health Survey subscales 1 year after transplantation. CONCLUSIONS: Lung transplantation offers a valuable therapy for patients with end-stage pulmonary LAM.

A case of late-onset cytomegalovirus myocarditis in an orthotopic heart transplant recipient; case report and review of the literature.

We describe a male patient who presents 2 years posttransplant with cough and dyspnea. A negative pulmonary workup led to an endomyocardial biopsy and the diagnosis of cytomegalovirus (CMV) myocarditis. The patient was treated with ganciclovir and intravenous immunoglobulin. This illustrates a very late presentation of posttransplant CMV myocarditis and the usefulness of myocardial biopsy in diagnosis of CMV carditis.

A rare fungal infection: Phaehyphomycosis due to Veronaea botryosa and review of literature.

We report a rare case of phaehyphomycosis in a 71-year-old heart transplant recipient Togo native patient. Four months after the transplant, he presented painless nodules on the right heel with superficial ulceration. The polyphasic identification uncovered a rare cause of phaehyphomycose: V. botryosa. The treatment combined surgical excision of the lesions and anti-fungal therapy with posaconazole. We discussed eleven reported cases in literature since 1990.

Post-cardiac transplant recipient: Implications for anaesthesia.

The annual heart transplant rate is gradually increasing worldwide. A proportion of this patient population present for an elective or emergency surgery which may or may not be related to the transplanted heart. A MEDLINE search for heart transplant, anaesthesia, adult, paediatric and surgery was conducted to review anaesthetic management for heart transplant recipients. Anaesthesia and perioperative management are different in these cases. A thorough understanding of the physiology of denervated heart, post-transplant morbidities and pharmacology of immunosuppressants is essential for best perioperative management and improved post-operative outcome.

Rhinocerebral mucormycosis in a 5-month heart transplant recipient.

Mucormycosis is an opportunistic acute fungal infection with a high mortality rate seen in immunocompromised patients. It is extremely rare in heart transplant recipients. Rhinocerebral mucormycosis (RM) is the most frequently observed presentation. We report a case of RM in a heart transplant recipient 5-month after the procedure, with a fatal outcome.