Reduction in mortality associated with secondary cytomegalovirus prophylaxis after solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) is the most important viral pathogen in solid organ transplant (SOT) recipients. The role of secondary CMV prophylaxis in this population remains unclear. METHODS: Retrospective cohort study in a single center. SOT recipients treated for CMV infection from 2007 to 2014 were studied to determine the efficacy and safety of secondary prophylaxis and its impact on graft loss and mortality. The outcome variable was CMV replication in the first 3 months after the end of therapy. Secondary variables were crude mortality and graft lost censored at 5 years after transplantation. Propensity score for the use of secondary prophylaxis was used to control selection bias. RESULTS: Of the 126 treated patients, 103 (83.1%) received CMV secondary prophylaxis. CMV relapse occurred in 44 (35.5%) patients. The use of secondary prophylaxis was not associated with fewer relapses (34.0% in patients with prophylaxis vs 42.9% in those without prophylaxis, P = .29). After a mean follow-up of 32.1 months, graft loss was not different between both groups but patient mortality was significantly lower in patients who received secondary prophylaxis (5.8% vs 28.6%, P = .003). CONCLUSION: Secondary prophylaxis did not prevent CMV infection relapse but it was associated with improved patient survival.

Cancer Incidence in Heart Transplant Recipients With Previous Neoplasia History.

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.

The falling incidence of hematologic cancer after heart transplantation.

BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.

Postoperative management and nursing care after implantation of a total artificial heart: Scoping review.

INTRODUCTION: End-stage heart failure (HF) is a condition whose only successful long-term treatment, with a survival of more than 10 years, is heart transplantation. However, limited organ availability and the progressive increase in the number of patients with advanced HF have served as an impetus for the development of implantable mechanical assistive devices. AIM: To provide an overview of postoperative management and nursing care after the implementation of a Total Artificial Heart (TAH). METHODS: A scoping review was carried out by consulting the PUBMED, CINAHL, and COCHRANE databases. From all the documents located, information was extracted on the date of publication, country of publication, type of study, and results of interest to answer the research question. In addition, the degree of recommendation was identified. RESULTS: Twenty-three documents were included in the scoping review. Results were classified in relation to: 1) description of the CAT SynCardia®; 2) nursing care in the immediate postoperative period (management of the device and management of hematological, infectious, nephrological, nutritional complications, related to immobilization, sleep-rest disturbances, psychological disorders, and patient and family education); and 3) follow-up at home. CONCLUSIONS: The complexity of implantation of the TAH, the multiple related complications that can arise during this process, both in the immediate post-operative and late, require a standardised and multidisciplinary management. The absence of standardised protocols raises the need for future studies to measure the effectiveness of care in patients with TAH. A multidisciplinary approach is crucial. Nurses must acquire autonomy and involvement in decision-making and develop competencies to address the patient's and family's physiological and psychosocial needs.

Accuracy of different reconstruction intervals to quantify left ventricular function and mass in cardiac computed tomography examinations.

PURPOSE: To compare the accuracy of cardiac dual-source CT (DSCT) reconstructions obtained at 5% and 10% of the cardiac cycle and MRI for quantifying global left ventricular (LV) function and mass in heart transplant recipients. MATERIAL AND METHODS: We prospectively included 23 heart transplant recipients (21 male, mean age 60±11.7 years) who underwent cardiac DSCT and MRI examinations. We compared LV parameters on cardiac DSCT reconstructions obtained at 5% (0%-95%) and 10% (0%-90%) intervals of the cardiac cycle and on double-oblique short-axis MR images. We determined ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and myocardial mass using commercially available semiautomated segmentation analysis software for DSCT datasets and conventional manual contour tracing for MR studies. RESULTS: Using different reconstruction intervals to quantify LV parameters at DSCT resulted in non-significant differences (P>.05). Compared to MRI, DSCT slightly overestimated LV-EDV, ESV, and mass when both 5% (11.5±25.1ml, 6.8±10.9ml, and 28.3±21.6g, respectively) and 10% (mean difference 15.3±26.3ml, 7.4±11.5ml, and 29.3±18.7g, respectively) reconstruction intervals were used. DSCT and MRI estimates of EF and SV were not significantly different. CONCLUSION: In heart transplant recipients, DSCT allows reliable quantification of LV function and mass compared with MRI, even using 10% interval reconstructions.

Lung cancer after heart transplantation: results from a large multicenter registry.

In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan-Meier 2-year survival to 70% versus 16% among inoperable patients.

Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study.

BACKGROUND: The objectives of this epidemiological, prospective study were to describe the characteristics of cytomegalovirus (CMV) infection in heart transplant (HT) recipients and to identify the variables that may influence the development of CMV viremia and CMV disease in these patients. METHODS: HT recipients ≥18 years of age (n=199) were included in the study. Variables studied included CMV serostatus, immunosuppressive treatment, and administration of anti-CMV prophylaxis. RESULTS: The mean age of the population was 52 years, and 84% were males. Immunosuppressive regimens were administered as induction therapy to 92.5% of patients; 88.5% of patients received calcineurin inhibitors as maintenance therapy. Anti-CMV treatment was given to 59% of 199 patients as prophylaxis (70%), preemptive therapy (10%), or to treat CMV infection (20%). Overall, 43% of patients had at least 1 positive viremia test. No patient with a high-risk serostatus (donor+/recipient-) receiving prophylaxis developed CMV syndrome, and only 2.5% of 199 patients developed CMV invasive disease. Multivariate analysis showed that having a positive donor CMV serostatus was associated with an increased risk of developing CMV viremia (P<0.012), while use of mammalian target of rapamycin (mTOR) inhibitors was associated with a decreased risk (P=0.005). CONCLUSIONS: In a population of HT recipients, the CMV infection rate was similar to that seen in previous studies, but the progression to overt CMV disease was very low. Having a CMV-positive donor was identified as an independent risk factor for developing CMV viremia, while the use of mTOR inhibitors was protective against viremia.

Cardiac magnetic resonance imaging myocardial perfusion reserve index in heart transplant patients. / Valoración del índice de reserva de perfusión miocárdica por resonancia magnética en pacientes con trasplante cardíaco.

OBJECTIVE: To compare the myocardial perfusion reserve index (MPRI) measured during stress cardiac magnetic resonance imaging (MRI) with regadenoson in patients with heart transplants versus in patients without heart transplants. MATERIAL AND METHODS: We retrospectively compared 20 consecutive asymptomatic heart transplant patients without suspicion of microvascular disease who underwent stress cardiac MRI with regadenoson and coronary computed tomography angiography (CTA) to rule out cardiac allograft vasculopathy versus 16 patients without transplants who underwent clinically indicated stress cardiac MRI who were negative for ischemia and had no signs of structural heart disease. We estimated MPRI semiquantitatively after calculating the up-slope of the first-pass enhancement curve and dividing the value obtained during stress by the value obtained at rest. We compared MPRI in the two groups. Patients with positive findings for ischemia on stress cardiac MRI or significant coronary stenosis on coronary CTA were referred for conventional coronary angiography. RESULTS: More than half the patients remained asymptomatic during the stress test. Stress cardiac MRI was positive for ischemia in two heart transplant patients; these findings were confirmed at coronary CTA and at conventional coronary angiography. Patients with transplants had lower end-diastolic volume index (59.3±15.2 ml/m2 vs. 71.4±15.9 ml/m2 in those without transplants, p=0.03), lower MPRI (1.35±0.19 vs. 1.6±0.28 in those without transplants, p=0.003), and a less pronounced hemodynamic response to regadenoson (mean increase in heart rate 13.1±5.4 bpm vs. 28.5±8.9 bpm in those without transplants, p <0.001). CONCLUSION: Stress cardiac MRI with regadenoson is safe. In the absence of epicardial coronary artery disease, patients with heart transplants have lower MPRI than patients without transplants, suggesting microvascular disease. The hemodynamic response to regadenoson is less pronounced in patients with heart transplants than in patients without heart transplants.

Outcomes of heart transplantation for cardiac amyloidosis: subanalysis of the spanish registry for heart transplantation.

Amyloidosis (Am), a systemic disease, has poor prognosis because of organ damage produced by protein deposition in the extracellular space. Although heart transplantation (HTx) is possible, donor availability concerns and high mortality make this approach controversial. The Spanish Registry for Heart Transplantation includes 25 Am patients (54 +/- 9 years): 13 with AL type, 2 with AA and 10 with TTR mutation. Fifteen patients (60%) died during follow-up (4.9 +/- 1.3 years): 9 AL-Am patients, both AA-Am patients and 4 with TTR-Am. HTx survival for Am patients was similar to patients without Am at 1 month but significantly worse at 5 years: 46% versus 78% (p < 0.02). Of 10 AL-Am patients undergoing successful HTx, 4 died of systemic Am. Stem cell transplantation was performed in 3 (1 died of acute rejection). Five of 10 patients with TTR-Am underwent liver transplant; 4 remained alive at the last follow-up. Findings include poor outcome for AL-Am patients despite HTx and better survival for TTR-Am patients if HTx is associated with liver transplantation. Given the shortage of donors and poor outcome for Am patients, we would recommend that HTx be reserved for patients without or with mild systemic Am and be supplemented by additional therapies as indicated.

[Global evaluation of the heart in heart transplant recipients using dual-source computed tomography]. / Valoración global del corazón en el paciente con transplante cardiaco mediante tomografía computarizada de doble fuente.

In routine clinical practice surveillance of heart transplant recipients is usually performed using echocardiography and conventional coronary angiography. The latter permits diagnosis and follow-up of coronary allograft vasculopathy. However, this procedure is invasive and is not free of complications. Conventional multislice computed tomography (MSCT) has been shown to be a useful non-invasive tool for ruling out coronary artery disease and evaluating cardiac function. However, due to its limited temporal resolution betablocker administration is required, and its usefulness in certain patient populations with restricted response to this medication, such as heart transplant recipients, may therefore be limited. Dual-source CT (DSCT) allows evaluation of the coronary arteries in all individuals independent of their heart rate. In the case presented here, we demonstrate that DSCT may be useful for evaluating cardiac function and ruling out coronary allograft vasculopathy in heart transplant recipients.

Malignancy after heart transplantation: incidence, prognosis and risk factors.

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.

[Extracorporeal circulation and hypothermy surgery in tumors with vena cava extension: 20 years experience at the University Clinic of Navarra]. / Cirugía con circulación extracorpórea e hipotermia en tumores con extensión a vena cava: 20 años de experiencia de la clínica Universitaria de Navarra.

OBJECTIVE: We present our 20 years experience treating patients with vena cava extension in whom an extracorporeal circulation, hypothermia, cardio circulatory arrest (ECC-H-CCA) in order to perform, together with a tumoral resection, a thrombus resection. MATERIAL AND METHODS: From 1985 to 2005 a total of 28 retroperitoneal tumor were treated: 25 renal cancers, a Wilms tumor, a paratesticular rabdomiosarcoma, and a pheocromocitoma. All of them had an extension by means of thrombus above the suprahepatics veins. All of them were treated by means of ECC-H-CCA for thrombus extraction. A descriptive study of the serie is performed as well as a Kaplan Meyer survival study. RESULTS: Surgical complications were present within 10 patients (35%), with a surgical mortality of two patients (7%): one intra-operatively because a massive embolism of the lungs and the other because of a lung embolism on the 4th post-operative day. Global actuarial survival was 29.1+/-10% at three years and 17.5+/-8% at five years. Analyzing only who do not have metastatic lesions, nor lymph nodes at diagnosis their three year survival was 50.9+/-16.3% and 32.2+/-16% at five years. Mean while those who have any metastatic lesion at diagnosis their three and five years survival was 20.8+/-12% and 10.4+/-9% respectively. CONCLUSIONS: The employ of surgical techniques with ECC-H-CCA with in oncological pathology associated with vena cava thrombus is justified and its employment does not worsen the survival; it is indicated because its results, allowing a complete tumoral resection in a safe and reproducible fashion.

Two-dose daclizumab, tacrolimus, mycophenolate mofetil, and steroid-free regimen in de novo cardiac transplant recipients: early experience.

BACKGROUND: Tacrolimus (TAC) with mycophenolate mofetil (MMF) and a steroid-free regimen seems to have good efficacy in preventing acute rejection in cardiac transplant recipients, although concern exists about nephrotoxicity. Induction therapy with Daclizumab seems to give protection without side effects. Data are lacking about the outcome of 2-dose Daclizumab+TAC+MMF and a steroid-free regimen. MATERIALS AND METHODS: We retrospectively reviewed 28 consecutive de novo heart transplantations performed at a single center between January 2001 and June 2006. Patients received induction therapy with 2-dose Daclizumab. Maintenance immunosuppression included TAC, MMF, and prednisone during the first 6 months. The endpoints were the incidence of acute rejection, patient and graft survival, and clinical tolerability. RESULTS: Among 28 patients of mean age 57 +/- 9 years, 2 subjects (7%) died in the perioperative period due to infections. The mean follow-up was 2.8 +/- 1.5 years. There were no late deaths. Six patients experienced acute rejection (International Society of Heart and Lung Transplantation [ISHLT] >or=3A) that required treatment during the first 3 months. At follow-up, only 3 patients (>or=3A) required treatment. Mean creatinine level increased from 1.08 +/- 0.37 at baseline to 1.08 +/- 0.41 at 1 year (n = 23; P = not significant [NS]) to 1.39 +/- 0.68 (n = 13; P < .05) at 4 years, 1.65 +/- 0.51 (n = 8; P < .05) at 5 years. No patient required replacement therapy. CONCLUSIONS: A steroid-free protocol with 2-dose Daclizumab induction therapy and maintenance with TAC and MMF seemed to be safe to prevent acute rejection. Creatinine levels were slightly but significantly increased.

Impact on renal function of the use of sirolimus in cardiac transplantation.

INTRODUCTION: During the last few years sirolimus has been introduced as an alternative to preserve renal function in transplant recipients receiving calcineurin inhibitors. MATERIALS AND METHODS: We reviewed our results on the use of sirolimus in cardiac transplant recipients. RESULTS: Twenty-seven patients with an average age of 63 years received sirolimus. The average time after transplantation was 73.4 +/- 58.9 months and the average follow-up was 31.7 +/- 18.01 months. Sirolimus was prescribed in 37% of cases due to chronic renal failure (CRF), 14.8% because of cardiac allograft vasculopathy (CAV), 11.1% for tumors, 22.2% de novo, 7.4% for CRF and tumor, and 7.4% for CRF and CAV. Among the patients with CRF (n = 14), there were 5 (35%) on dialysis at the moment of starting the treatment and 1 was retired from dialysis. The other 4 (28.5%) patients had to be treated with dialysis after starting the treatment. In all, 42.8% of the patients with nephropathy maintained stable renal function or improved. Among the 17 (63%) patients who did not require dialysis, there was no significant change in renal function after 6 months or 1, 2, and 3 years follow-up. CONCLUSIONS: The use of sirolimus in cardiac transplantation maintains stable renal function in the majority of patients in the medium term.

[Cardiac and vascular homograft valves transplant]. / Trasplante de homoinjertos valvulares cardiacos y vasculares.

The advances in the manipulation of human tissues, the development of cryobiology, paediatric cardiac surgery, the impossibility of obtaining an ideal prosthetic cardiac valve and the surgical treatment of cardiovascular infections have revived interest in the use of homografts. The donors of these homografts can be: a) Live donors: aortic and pulmonary valve of the recipient of a heart transplant; b) Multiorgan donors with a diagnosis of death according to neurological criteria, whose heart is rejected for heart transplant; c) Cadaver donors with asystolia of less than 8 hours. Homograft cardiac valves are the substitute of choice in aortic valve endocarditis, patients with counter-indications for anticoagulation, reconstruction of the outflow tract of the right ventricle, aortic valve replacement in children and young adults through the Ross operation, and an optional indication is the aortic valve and/or rising aorta replacement in patients over 60 years of age. Although there are not sufficiently broad series of homogratfs with arterial substitutes, with respect to the number of patients and time of evolution, the results suggest that this can benefit patients with vascular infection, immunodepressed patients or complex patients whose technique during the operation might require a homograft.

[Heart transplant]. / Trasplante cardíaco.

A heart transplant is at present considered the treatment of choice in cases of terminal cardiac insufficiency refractory to medical or surgical treatment. Due to factors such as the greater life expectancy of the population and the more efficient management of acute coronary syndromes, there is an increasing number of people who suffer from heart failure. It is estimated that the prevalence of the disease in developed countries is around 1%; of this figure, some 10% are in an advanced stage and are thus potential receptors of a heart transplant. The problem is that it is still not possible to offer this therapeutic form to all of the patients that require it. Consequently, it is necessary to optimise the results of the heart transplant through the selection of patients, selection and management of donors, perioperative management and control of the disease due to graft rejection. Since the first transplant carried out in 1967, numerous advances and changes have taken place, which has made it possible to increase survival and quality of life of those who have received a new heart. In this article we review the most relevant aspects of the heart transplant and the challenges that are currently faced.

[Cell transplant and regenerative therapy with stem cells]. / Trasplante celular y terapia regenerativa con células madre.

One of the fields of medicine that has raised the most expectations in recent years is cell therapy with stem cells. The isolation of human embryo cells, the apparent and unexpected potentiality of adult stem cells and the development of gene therapy lead us to imagine a hopeful future for a significant number of diseases that are at present incurable. In this article we will sketch out the panorama of stem cell research, describing the main achievements in this field as well as some of the questions that await an answer. In spite of the great expectations, it is essential that we maintain a critical and realistic spirit when it comes to analysing the scientific advances in this area.

Prosthetic valve endocarditis caused by Brucella melitensis. A report of four cases successfully treated with tetracycline, streptomycin, and sulfamethoxazole and trimethoprim plus valve replacement.

Optimal treatment of prosthetic valve endocarditis due to Brucella melitensis is unknown. The presence of ring abscess makes extensive surgical débridement and valve replacement essential steps of management. Antimicrobial therapy with tetracycline hydrochloride plus streptomycin sulfate or sulfamethoxazole and trimethoprim can achieve the sterilization of infected cardiac tissue. Late bland periprosthetic leaks occur frequently. Reoperation can be safely performed after a period of antimicrobial therapy. Prolonged treatment with doxycycline hyclate seems advisable.