Search

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long-term follow-up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32-44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18-26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow-up of 4.5 years, 91 deaths accounted for 4.21 higher-than-expected mortality in the age-matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance-either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six-month changes in the composite clinical score and in the 6-minute walk test distance were related to survival. Conclusions Persistent valvular heart disease-pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.

Background: Infection is a major cause of morbidity and mortality after heart transplantation (HT). Little information about its importance in the immediate post-operative period is available. The aim of this study was to analyze the characteristics, incidence, and outcomes of in-hospital post-operative infections after HT. Methods: We conducted an observational, single-center study based on 677 adults who underwent HT from 1991 to 2015 and who survived the surgical intervention. In-hospital post-operative infections were identified retrospectively according to the medical finding in the clinical records. Results: Over a mean hospital stay of 24.5 days, 239 patients (35.3%) developed 348 episodes of infection (2 episodes per 100 patient-days). The most common sources of infection were those related to invasive procedures (respiratory infections, 115 [33%]; urinary tract infections, 47 [13.5%]; bacteremia, 42 [12.1%]; surgical site infections, 25 [7.2%]), in addition to abdominal focus (33, 9.5%). Enterobacteriaceae (76, 21.8%) and gram-positive cocci (58, 16.7%) were the predominant germs, although opportunistic infections were not infrequent (69, 19.8%). Ninety-five septic episodes were detected with a mean Sequential Organ Failure Assessment Score of 9.5 ± 5.3 points, with hemodynamic failure being the most severe organ dysfunction and renal dysfunction the most frequent one. Management included broad-spectrum antibiotics in 48.8% of episodes and surgical management in 13.8%. The overall antimicrobial success rate was 96.3%. Higher in-hospital mortality was observed among infected patients (15.1% vs. 10.3%), but this difference was not statistically significant (p = 0.067). The one-year survival and events were not different between patients suffering from a post-operative infection and those who did not. Conclusions: In-hospital infections were frequent in the post-operative period after HT and were associated with a poor short-term outcome. Patients who survived sepsis had a similar one-year morbidity and mortality compared with patients who did not develop an infection.

Introduction: Infection is one of the most significant complications following heart transplantation (HT). The aim of this study was to identify specific risk factors for early postoperative infections in HT recipients, and to develop a multivariable predictive model to identify HT recipients at high risk., Methods: A single-center, observational, and retrospective study was conducted. The dependent variable was in-hospital postoperative infection. We examined demographic and epidemiological data from donors and recipients, surgical features, and adverse postoperative events as independent variables. Backwards, stepwise multivariable logistic regression with a P-value < 0.05 was used to identify clinical factors independently associated with the risk of in-hospital postoperative infections following HT., Results: Six hundred seventy-seven patients were included in this study. During the in-hospital postoperative period, 348 episodes of infection were diagnosed in 239 (35.9%) patients. Seven variables were identified as independent clinical predictors of early postoperative infection after HT: history of diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and use of itraconazole. Based on the results of multivariable models, we constructed a 7-variable (8-point) score to predict the risk of in-hospital postoperative infection in HT recipients, which showed a reasonable ability to predict the risk of in-hospital postoperative infection in this population. Prospective external validation of this new score is warranted to confirm its clinical applicability., Conclusions: In-hospital postoperative infection is a common complication after HT, affecting 35% of patients who underwent this procedure at our institution. Diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and itraconazole were all independent clinical predictors of early postoperative infection after HT., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite the successes from refined peri-operative management techniques and immunosuppressive therapies, antibodies remain a serious cause of morbidity and mortality for patients both before and after heart transplantation. Patients awaiting transplant who possess antibodies against human leukocyte antigen are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. The number of pre-sensitized patients has been increasing, a trend that is likely due to the increased use of mechanical circulatory support devices. Even patients who are not pre-sensitized can go on to produce donor-specific antibodies after transplant, which are associated with worse outcomes. The difficulty in managing antibodies is uncertainty over which antibodies are of clinical relevance, which patients to treat, and which treatments are most effective and safe. There is a distinct lack of data from prospective trials. An international consensus conference was organized and attended by 103 participants from 75 centers to debate contentious issues, determine the best practices, and formulate ideas for future research on antibodies. Prominent experts presented state-of-the-art talks on antibodies, which were followed by group discussions, and then, finally, a reconvened session to establish consensus where possible. Herein we address the discussion, consensus points, and research ideas., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections., Methods: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection., Results: During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection., Conclusion: Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: A high frequency of venous thromboembolism (VTE) has been observed after lung, kidney, and liver transplantation. However, data about the incidence of this complication among heart transplant (HT) recipients are lacking., Methods: We analyzed the incidence, recurrence, and predisposing factors of VTE in a single-center cohort of 635 patients who underwent HT from April 1991 to April 2013. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE episodes., Results: During a median post-transplant follow-up of 8.4 years, 62 VTE episodes occurred in 54 patients (8.5%). Incidence rates of VTE, DVT, and PE were, respectively, 12.7 (95% confidence interval [CI], 9.7-16.3), 8.4 (95% CI, 6.0-11.4), and 7.0 (95% CI 4.8-9.7) episodes per 1,000 patient-years. Incidence rates of VTE during the first post-transplant year and beyond were, respectively, 45.1 (95% CI, 28.9-67.1) and 8.7 (95% CI 6.2-11.2) episodes per 1,000 patient-years. The incidence rate of VTE recurrence after a first VTE episode was 30.5 (95% CI, 13.2-60.2) episodes per 1,000 patient-years. By means of multivariable Cox regression, chronic renal dysfunction, older age, obesity, and the use of mammalian target of rapamycin inhibitors were identified as independent risk factors for VTE among HT recipients., Conclusions: VTE is a frequent complication after HT, mainly during the first post-operative year. In view of a high recurrence rate, long-term anti-coagulation should be considered in HT recipients who experience a first VTE episode., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Solid-organ transplant recipients are at increased risk of developing cancer compared with the general population. Tumours can arise de novo, as a recurrence of a preexisting malignancy, or from the donated organ. The ATOS (Aula sobre Trasplantes de Órganos Sólidos; the Solid-Organ Transplantation Working Group) group, integrated by Spanish transplant experts, meets annually to discuss current advances in the field. In 2011, the 11th edition covered a range of new topics on cancer and transplantation. In this review we have highlighted the new concepts and best practices for managing cancer in the pre-transplant and post-transplant settings that were presented at the ATOS meeting. Immunosuppression plays a major role in oncogenesis in the transplant recipient, both through impaired immunosurveillance and through direct oncogenic activity. It is possible to transplant organs obtained from donors with a history of cancer as long as an effective minimization of malignancy transmission strategy is followed. Tumour-specific wait-periods have been proposed for the increased number of transplantation candidates with a history of malignancy; however, the patient's individual risk of death from organ failure must be taken into consideration. It is important to actively prevent tumour recurrence, especially the recurrence of hepatocellular carcinoma in liver transplant recipients. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients, with long-term intensive screening programs showing a reduced incidence of cancer post-transplantation. Proposed management strategies for post-transplantation malignancies include viral monitoring and prophylaxis to decrease infection-related cancer, immunosuppression modulation with lower doses of calcineurin inhibitors, and addition of or conversion to inhibitors of the mammalian target of rapamycin., (Copyright © 2012. Published by Elsevier Inc.)

Cytomegalovirus (CMV) is a common complication after heart transplantation, affecting almost half of all recipients. The clinical spectrum of this infection includes, in order of greater to lesser severity, latent infection, asymptomatic viremia, CMV syndrome and CMV disease. CMV is associated with rejection and vascular graft disease and is a major cause of morbidity and mortality. The factors most frequently involved in susceptibility to this infection and its severity are donor and recipient CMV serological status, the intensity of immunosuppression and the type of immunosuppressive agents used. The management strategies of this infection include universal or targeted prophylaxis, preemptive therapy and treatment of established disease. The use of preventive measures significantly reduces the incidence of symtomatic infection or CMV disease, which has been reported to be less than 3% in some recent series., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

Fulminant hepatic failure is a rare complication of infection by varicella zoster virus that is favored by immunosuppression. Within 1 week, a 43-year-old male heart transplant recipient who was admitted with epigastric pain successively developed a generalized vesicular rash, hepatitis, and secondary multiorganic failure involving encephalopathy, despite treatment with acyclovir (since Day 2) and varicella zoster virus immunoglobulin (since Day 6). Emergency liver transplantation was performed on Day 9, and 36 months later, his heart and liver function are normal.

Cardiac allograft vasculopathy (CAV) currently represents one of the most important causes of long-term morbidity and mortality in the heart transplant population. In well-designed studies with de novo patients, the use of proliferation signal inhibitors (PSIs; everolimus and sirolimus) has been shown to significantly prevent the intimal growth of graft coronary arteries in comparison to other immunosuppressive regimens, reducing the incidence of vasculopathy at 12 and 24 months. In addition, conversion to PSIs in maintenance patients with established CAV has also shown promising results in the reduction of the progression of the disease and its clinical consequences. For these reasons the interest shown by various transplantation units in the potential role of PSIs in this field is growing. The aim of the present article is to review the information obtained to date on the use of PSIs in heart transplant recipients, both in the prevention and the treatment of CAV. The principal published recommendations on the introduction and appropriate management of these drugs in clinical practice are also collected, as well as certain recommendations given by the authors based on their experience.

Introduction: Statins, although the treatment of choice for dyslipidemia after heart transplantation (HT), are not always well tolerated or effective. In such cases, administration of ezetimibe may be useful., Aim: The aim of this study was to assess the efficacy and safety of ezetimibe, with or without statins, after HT., Method: Thirty-six HT patients, 97% of whom were males of overall mean age of 57 +/- 13 years, were all unable to reach target lipid levels with statins alone and/or were intolerant of statins. They were prescribed ezetimibe, with or without a statin. Efficacy and safety were evaluated after 1, 3, 6, and 12 months., Results: Thirty-four patients were evaluated at 1 month and 12 months. Ezetimibe was prescribed to 27 patients (75%) because of statin inefficacy, and to 9 patients (25%) because of statin intolerance, manifested by myalgia in 4 cases (11%), hepatotoxicity in 2 cases (6%), and rhabdomyolysis in 3 cases (8%). Lipid levels (mg/dL; baseline vs 1 year) were as follows: cholesterol, 235 +/- 49 versus 167 +/- 32 (P = .013); LDL cholesterol, 137 +/- 47 versus 89 +/- 29 (P = .001); HDL cholesterol, 54 +/- 13 versus 51 +/- 10 (P = .235); and triglycerides, 243 +/- 187 versus 143 +/- 72 (P = .022). There were no cases of liver toxicity, renal dysfunction, or significant alteration of immunosuppressive pharmacokinetics. Ezetimibe was withdrawn from 2 patients because of hand edema or asymptomatic recurrence of rhabdomyolysis first caused by statins., Conclusions: With or without a statin, ezetimibe was generally well tolerated, reducing total cholesterol, LDL cholesterol, and triglyceride levels with no long-term alteration of HDL cholesterol levels. CPK surveillance is recommended because of a slight continued risk of adverse effects. Further studies should evaluate the benefit for survival.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

Background: Whether being older than 65 years should be considered an absolute counterindication to heart transplant (HT), as it is in some centers, is controversial. In our centre, patients older than 65 years are accepted for HT if they satisfy stringent conditions. The aim of this study was to examine whether heart recipients older than 65 years have a greater risk of rejection, neoplasia, or mortality than younger ones., Methods: We studied 445 patients who underwent HT between April 1991 and December 2003, 42 of whom were older than 65 years and 403 who were 65 years or younger. The parameters evaluated were the cumulative incidences of neoplasias and rejections (ISHLT grade > or = 3A), and the survival rates 1 month, 1 year, and 5 years post-HT., Results: The two groups had similar percentages of patients with at least one rejection episode (< or =65 years 56.9%, >65 years 51.3%; P > .05), and although there were proportionally almost twice as many tumors in the older group (14.2%) as in the younger (7.9%), this difference was not statistically significant either. Nor were there any significant differences in survival, the 1-month, 1-year, and 5-year rates being 87.8%, 82.1%, and 68.8%, respectively, in the younger group and 85.7%, 78.6%, and 73.4%, respectively, in the older., Conclusions: Among carefully selected patients aged more than 65 years, HT can be performed without incurring greater risk of rejection, malignancy, or death than is found among recipients younger than 65 years.

Background: HAV syndrome, the combination of hypotension, acidosis and vasodilation (HAV), is a serious postoperative complication after heart transplantation (HT). Its etiology and prognosis are poorly understood., Aim: To determine the incidence and prognosis of post-HT HAV syndrome and examine possible risk factors., Methods: Retrospective examination of the records of 85 consecutive patients who underwent HT between December 1999 and June 2002 sought the HAV criteria: systolic BP <85 mm Hg plus HCO3 <19 mEq/l whole excluding cardiogenic, hypovolemic and septic shock. Donor variables included sex, age, weight, height, cause of death, time in ICU, and ischemic time; while recipient variables, sex, age, weight, height, etiology of cardiopathy, previous cardiopulmonary bypass surgery, preoperative amiodarone, beta-blockers, catecholamines, mechanical ventilation or intra aortic balloon pump (IABP), RVP, time on waiting list, pump time, reoperations, polytransfusion, preoperative creatinine, GOT, GPT and GGT, induction with OKT3 or anti-CD25, bypass-to-HAV time, duration of catecholamine treatment, and 1 month survival after HT., Results: The 11 HAV cases (13%) appeared between 1 and 72 h after HT (75% in the first hour). Catecholamines were used for 1 to 6 days; control was achieved within 48 h in 58% of cases. Two HAV patients (18%) died within the first month versus six non-HAV patients (8.1%) (P=.275). Only polytransfusion showed more than a borderline value to predict HAV syndrome., Conclusions: HAV syndrome has an incidence of 13% and a mortality of 18% within 1 month post-HT. The only likely risk factor is polytransfusion.

Background: This study was conducted to analyze the type, incidence, predisposing factors and prognosis of cutaneous complications (CC) occurring in heart transplant recipients (HTR)., Patients and Methods: A retrospective study was carried out among 192 HTR with a survival > 1 month. The following variables were recorded: age, sex, place of residence, post-transplant diabetes, glucocorticoid dose, prophylaxis with acyclovir/itraconazole and CC., Results: One hundred sixty three CC were diagnosed in 93 patients. The major types were infectious complications (n = 115; 70.5%) and tumors (n = 20; 12.3%). The most common infections were viral (herpes zoster; n = 22) and fungal (pityriasis versicolor; n = 53). Out the 20 tumors, 3 were malignant: 2 squamous cell carcinomas (SCC) and 1 Kaposi sarcoma. None of the CC caused mortality or prolonged hospital stay. No relationship was found between CC and the variables studied., Conclusions: Skin infections were the most common CC in this cohort of HTR. The incidence of SCC was very low and its prognosis was good due to early diagnosis and surgical excision.

We report a case of chylous ascites in a 52-year-old woman after an orthotopic heart transplantation. The patient was successfully managed with conservative treatment including dietetic measures and repeated paracentesis. The potential aetiopathological factors involved and other implications for cardiac transplant patients are discussed.