Complicaciones infecciosas relacionadas con la asistencia circulatoria mecánica de corta duración en candidatos a trasplante cardiaco urgente / Infectious complications associated with short-term mechanical circulatory support in urgent heart transplant candidates

Introducción y objetivos: El uso de dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante es frecuente en España. Se desconocen la epidemiología y la repercusión de las complicaciones infecciosas en estos pacientes. Métodos: Descripción sistemática de la epidemiología y análisis de la repercusión pronóstica de las complicaciones infecciosas en un registro multicéntrico retrospectivo de pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante cardiaco urgente entre 2010 y 2015 en 16 hospitales españoles. Resultados: Se estudió a 249 pacientes; 87 (34,9%) de ellos tuvieron un total de 102 infecciones. La vía respiratoria fue la localización más frecuente (n=47; 46,1%). En 78 casos (76,5%) se obtuvo confirmación microbiológica; se aislaron en total 100 gérmenes causales, con predominio de bacterias gramnegativas (n=58, 58%). Los pacientes con complicaciones infecciosas presentaron mayor mortalidad durante el periodo de asistencia circulatoria mecánica (el 25,3 frente al 12,3%; p=0,009) y menor probabilidad de recibir un trasplante (el 73,6 frente al 85,2%; p=0,025) que los pacientes sin infección. La mortalidad posoperatoria tras el trasplante fue similar en ambos grupos (con infección, el 28,3%; sin infección, el 23,4%; p=0,471). Conclusiones: Los pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente al trasplante cardiaco están expuestos a un alto riesgo de complicaciones infecciosas, las cuales se asocian con una mayor mortalidad en espera del órgano (AU)

Introduction and objectives: Short-term mechanical circulatory support is frequently used as a bridge to heart transplant in Spain. The epidemiology and prognostic impact of infectious complications in these patients are unknown. Methods: Systematic description of the epidemiology of infectious complications and analysis of their prognostic impact in a multicenter, retrospective registry of patients treated with short-term mechanical devices as a bridge to urgent heart transplant from 2010 to 2015 in 16 Spanish hospitals. Results: We studied 249 patients, of which 87 (34.9%) had a total of 102 infections. The most frequent site was the respiratory tract (n=47; 46.1%). Microbiological confirmation was obtained in 78 (76.5%) episodes, with a total of 100 causative agents, showing a predominance of gram-negative bacteria (n=58, 58%). Compared with patients without infection, those with infectious complications showed higher mortality during the support period (25.3% vs 12.3%, P=.009) and a lower probability of receiving a transplant (73.6% vs 85.2%, P=.025). In-hospital posttransplant mortality was similar in the 2 groups (with infection: 28.3%; without infection: 23.4%; P=.471). Conclusions: Patients supported with temporary devices as a bridge to heart transplant are exposed to a high risk of infectious complications, which are associated with higher mortality during the organ waiting period (AU)

Human health risk assessment associated with the consumption of mussels (Perna perna) and oysters (Crassostrea rhizophorae) contaminated with metals and arsenic in the estuarine channel of Vitória Bay (ES), Southeast Brazil.

The estuarine channel of Vitória Bay was evaluated regarding bioaccumulation of metals (Al, Ba, Mn, Fe, Zn, Cu, Cr, Pb, Ni, Cd, Hg) and As in mollusks. Mussels from an aquaculture farm and transplanted into the estuary, whereas oysters were collected in situ in the same area. Concentrations of Al, Mn, Fe, Cr and As were higher in P. perna, whereas C. rhizophorae bioaccumulated more Ba, Zn and Cu. Arsenic concentrations in P. perna exceeded the limit of the Brazilian legislation in the outer estuary. Salinity seemed to influence metal uptake differently for each bivalve, with P. perna absorbing more metal at higher salinities and C. rhizophorae in areas of lower salinity. Hazard index (HI) >1 revealed risk for both bivalves for high level consumers. Target Cancer Risk (TCR) for As revealed threat for human health associated with the consumption of mussels and oysters from the study area.

Consenso para la mejora de la atención integral de los pacientes con insuficiencia cardíaca aguda / Consensus on improving the comprehensive care of patients with acute heart failure

El último consenso sobre insuficiencia cardíaca aguda de la Sociedad Española de Cardiología, la Sociedad Española de Medicina Interna y la Sociedad Española de Medicina de Urgencias y Emergencias se elaboró en 2015, por lo que era necesaria una actualización para revisar las diversas novedades relacionadas con la temática de insuficiencia cardíaca aguda que han ido apareciendo los últimos años. Entre ellas están la publicación de las nuevas guías europeas sobre insuficiencia cardíaca en el 2016, nuevos estudios sobre el manejo farmacológico de los pacientes durante la hospitalización y novedades sobre diversos aspectos relacionados con la insuficiencia cardíaca aguda, tales como el abordaje precoz, terapia intermitente, insuficiencia cardíaca avanzada y congestión refractaria. Por ello, este consenso se elaboró con la intención de actualizar todos los aspectos relacionados con la insuficiencia cardíaca aguda y proporcionar un documento que detallase de manera completa el diagnóstico, tratamiento y manejo de esta enfermedad (AU)

The latest acute heart failure consensus document from the Spanish Society of Cardiology, Spanish Society of Internal Medicine, and Spanish Society of Emergency Medicine was published in 2015, which made an update covering the main novelties regarding acute heart failure from the last few years necessary. These include publication of updated European guidelines on heart failure in 2016, new studies on the pharmacological treatment of patients during hospitalization, and other recent developments regarding acute heart failure such as early treatment, intermittent treatment, advanced heart failure, and refractory congestion. This consensus document was drafted with the aim of updating all aspects related to acute heart failure and to create a document that comprehensively describes the diagnosis, treatment, and management of this disease (AU)

Evaluation of bioavailability of trace metals through bioindicators in a urbanized estuarine system in southeast Brazil.

The mussel Perna perna is one of the most used bioindicators of coastal areas and the most economically exploited species in Brazil through mariculture. In the present study, P. perna was used to investigate metal pollution in the estuarine area of Vitória Bay. Four sampling sites were located along an estuarine branch of Vitória Bay and stations were sampled during three campaigns. Trace metals in the tissues of P. perna were evaluated as well as dissolved trace metals and other ancillary variables in the water column. Dissolved Cd, Pb, Cu, Ni, and Fe concentrations surpassed the tolerance limits stablished by legislation in all the sampling campaigns. P. perna exhibited concentrations in disagreement with the Brazilian legislation for Cr and As. A general trend of higher concentrations in outer stations was observed for most metals, what suggested the occurrence of flocculation process in the lower estuary, reducing the concentrations of dissolved elements and increasing their bioavailability for the biota through the particulate form. Cd was highlighted with elevated concentrations in dissolved fraction but not detected in P. perna, probably due to chlor-complex formation under influence of more saline waters. Al, Ba, Mn, Fe, Cu, Zn, Ni, Cr, Pb, and As were considered bioavailable, once they were accumulated in the mussels' tissues. Hazard index (HI) and target cancer risk (TCR) showed that the consumption of mussels from the study area offers health risk issues, being iron and arsenic the main contributors for the high indexes.

Consensus on improving the comprehensive care of patients with acute heart failure. / Consenso para la mejora de la atención integral de los pacientes con insuficiencia cardíaca aguda.

The latest acute heart failure consensus document from the Spanish Society of Cardiology, Spanish Society of Internal Medicine, and Spanish Society of Emergency Medicine was published in 2015, which made an update covering the main novelties regarding acute heart failure from the last few years necessary. These include publication of updated European guidelines on heart failure in 2016, new studies on the pharmacological treatment of patients during hospitalization, and other recent developments regarding acute heart failure such as early treatment, intermittent treatment, advanced heart failure, and refractory congestion. This consensus document was drafted with the aim of updating all aspects related to acute heart failure and to create a document that comprehensively describes the diagnosis, treatment, and management of this disease.

Prevalence and incidence of hyperkalaemia in the Spanish population with heart failure with reduced ejection fraction: a systematic review and populational relevance. / Prevalencia e incidencia de hiperpotasemia en población española con insuficiencia cardiaca con fracción de eyección deprimida: revisión sistemática y relevancia poblacional.

BACKGROUND AND OBJECTIVES: Hyperkalaemia (K+ levels≥5.5mmol/L) is a severe ion imbalance that occurs in patients who have heart failure (HF) with reduced ejection fraction (HFrEF) and increases the risk of ventricular fibrillation. Given that there are no estimates on the number of patients with this complication, the aim of this study was to estimate the prevalence and incidence of hyperkalaemia in patients with HFrEF in Spain. MATERIAL AND METHODS: Based on a systematic literature search and through a meta-analysis, we calculated an HFrEF prevalence of ≤40% in the European and U.S. POPULATION: Based on another systematic literature search, we calculated the prevalence of hyperkalaemia in patients with HF and its annual incidence rate. Considering the previous values and the Spanish population pyramid in 2016, we estimated the number of individuals with HFrEF who currently have hyperkalaemia and those who develop it each year in Spain. RESULTS: Approximately 17,100 (10,000 men and 7100 women) of the 508,000 patients with HFrEF in Spain have hyperkalaemia. Furthermore, approximately 14,900 patients with HFrEF (9500 men and 5400 women) develop hyperkalaemia each year. CONCLUSIONS: Approximately 1 of every 30 patients with HFrEF has plasma potassium values >5.5 mmol/L.

Mechanical support with venoarterial extracorporeal membrane oxygenation (ECMO-VA): Short-term and long-term prognosis after a successful weaning. / Soporte mecánico con membrana de oxigenación extracorpórea veno-arterial (ECMO-VA): evolución a corto y a largo plazo tras la retirada de la asistencia.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) affords mechanical circulatory assistance associated to high mortality. However, weaning from such mechanical support may not imply improved short- or long-term survival. This study describes the characteristics and evolution of patients with refractory cardiogenic shock (RCS) subjected to venoarterial ECMO (VA-ECMO) in a hospital with a heart transplant program. DESIGN: A single-center, retrospective cohort study was carried out. SETTING: The cardiovascular ICU of a tertiary hospital. PATIENTS: Forty-six patients consecutively subjected to VA-ECMO over 6 years. INTERVENTIONS: Hospital mortality after weaning from ECMO and overall survival (OS) were analyzed. RESULTS: Fifteen patients (33%) died with VA-ECMO and 31 (67%) were weaned after 8 days of support (IQR: 5-15). Fourteen patients under went transplantation. Hospital mortality in these patients was 32% (10/31), and was associated to age (P=.001), SAPS II score (P=.009), cannulation bleeding (P=.01) and post-acute myocardial infarction RCS (P=.001). After a median follow-up of 27 months (IQR: 11-49), 91% of the patients discharged from hospital were still alive. Overall survival after weaning from assistance was associated to the type of cardiac disease (P=.002). Patients with RCS after acute myocardial infarction had a poorer prognosis. CONCLUSIONS: In our experience, VA-ECMO can be used as mechanical assistance in the management of RCS. The technique is associated to high early mortality, though the long-term survival rate after hospital discharge is good.

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.

Health-related quality of life, social support, and caregiver burden between six and 120 months after heart transplantation: a Spanish multicenter cross-sectional study.

A multicenter cross-sectional study was conducted to determine the current heart transplant (HTx) outcomes in Spain. Clinical and functional status, health-related quality of life (HRQoL), social support, and caregiver burden were analyzed in 303 adult transplant recipients (77.9% males) living with one functioning graft. Mean age at time of HTx (SD) was 56.4 (11.4) years, and the reason for transplantation in all patients was congestive heart failure. All patients had received a first heart transplant 6 (± 1), 12 (± 2), 36 (± 6), 60 (± 10), or 120 (± 20) months previously. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D, the Duke-UNC Functional Social Support Questionnaire, and the Zarit Caregiver Burden Scale. Reasonable HRQoL, social support, and caregiver burden levels were found at all time points, although a slight decrease in HRQoL was recorded at 120 months (p ≤ 0.033). Multivariate regression analyses showed that complications, comorbidities, and hospitalizations were associated with HRQoL (EQ-5D: 48.4% of explained variance, F4,164 = 38.46, p < 0.001; KCCQ overall summary score: 45.0%, F3,198 = 54.073, p < 0.001). Patient functional capabilities and complications affected caregiver burden (p < 0.05). In conclusion, HTx patients reported reasonable levels of HRQoL with low caregiver burden. Clinical variables related to these outcomes included functional status, complications, and number of admissions.

Mycobacterium abscessus pulmonary infection complicated with vertebral osteomyelitis in a heart transplant recipient: case report and literature review.

Infections produced by Mycobacterium abscessus are emerging in immunosuppressed patients, such as solid organ transplant recipients. We report the first case, to our knowledge, of a vertebral osteomyelitis caused by M. abscessus in a heart transplant recipient, and review the risk factors, manifestations, and therapeutic approaches to this uncommon disease.

Chronic renal dysfunction in maintenance heart transplant patients: the ICEBERG study.

Chronic renal dysfunction (CRD) is a major complication after heart transplantation. We sought to describe the renal function over time, to assess the risk factors associated with CRD development, and to evaluate the clinical attitudes on diagnosis and treatment of CRD. A retrospective, cross-sectional, multicenter study was conducted in 13 outpatient clinics in Spain. A total of 244 heart recipients who survived more than 2 years after transplantation were included. Post-transplantation follow-up was 7.7 years (range: 2-22 years). CRD was diagnosed in 32.4% of patients at a mean of 3.3 years after transplantation. Serum creatinine increased 0.1 ± 0.2 mg/dL per year in CRD group compared with 0.0 ± 0.2 mg/dL per year in non-CRD group (P = .003) and glomerular filtration rate decreased -1.5 ± 4.3 mL/min/1.73 m(2) per year in CRD group versus -0.1 ± 4.8 mL/min/1.73 m(2) per year in non-CRD group (P = .027). After CRD diagnosis, major changes in immunosuppression based on calcineurin inhibitors reduction were instituted in 46.8% of patients. Multivariate model identified recipient age (P < .0001), female sex (P = .0398), and time since transplant (P < .0001) as predictors of CRD. In conclusion, the prevalence of CRD in long-term heart recipient survivors was quite high. CRD was associated with nonmodifiable factors (age, gender, and time since transplant).

Everolimus is associated with a reduced incidence of cytomegalovirus infection following de novo cardiac transplantation.

BACKGROUND: Cytomegalovirus (CMV) causes several complications following cardiac transplantation including cardiac allograft vasculopathy. Previous studies suggested that immunosuppressive treatment based on everolimus might reduce CMV infection. Aiming to better characterize the action of everolimus on CMV and its interplay with patient/recipient serology and anti-CMV prophylaxis, we analyzed data from 3 large randomized studies comparing various everolimus regimens with azathioprine (AZA)- and mycophenolate mofetil (MMF)-based regimens. METHODS: CMV data were analyzed from 1009 patients in 3 trials of de novo cardiac transplant recipients who were randomized to everolimus 1.5 mg/day, everolimus 3 mg/day, or AZA 1-3 mg/kg/day, plus standard-dose (SD) cyclosporine (CsA; study B253, n = 634); everolimus 1.5 mg/day plus SD- or reduced-dose (RD)-CsA (study A2403, n = 199); and everolimus 1.5 mg/day plus RD-CsA or MMF plus SD-CsA (study A2411, n = 176). RESULTS: In study B253, patients allocated to everolimus experienced almost a 70% reduction in odds of experiencing CMV infection compared with AZA (P < 0.001). In study A2403, CMV infection was low in both everolimus arms, irrespective of CsA dosing, and in study A2411, patients allocated to everolimus experienced an 80% reduction in odds of experiencing CMV infection, compared with MMF (P < 0.001). CMV syndrome/disease was rare and less frequent in everolimus-treated patients. Subgroup analyses showed that the benefit everolimus provides, in terms of CMV events, is retained in CMV-naïve recipients and is independent of anti-CMV prophylaxis or preemptive approaches. CONCLUSIONS: Everolimus is associated with a lower incidence of CMV infection compared with AZA and MMF, which combined with its immunosuppressive efficacy and antiproliferative effects may positively impact long-term outcomes.

Accuracy of noninvasive estimation of pulmonary wedge pressure by echocardiographic indices in heart transplant recipients.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) can be estimated from transmitral or color M-mode Doppler flow propagation velocities. However, it has been recommended to not use these indices in heart transplant recipients. Our aim was to compare the accuracy of color M-mode, Doppler, and Doppler tissue imaging (DTI)-derived indices to predict PCWP in heart transplant recipients. METHODS: We studied 50 consecutive heart transplant recipients scheduled for routine right-sided heart catheterization and endomyocardial biopsy. Their mean age was 49 ± 17 years and the mean time after heart transplantation was 29 ± 41 months. An echocardiogram was performed immediately after the invasive procedure. We analysed PCWP, transmitral flow velocity variables (peak velocity during early filling (E) and deceleration time [DT]), color M-mode Doppler flow propagation velocity (Vp), and mitral annulus peak early diastolic velocity (E') from DTI. Doppler estimated-PCWP (ePCWP) was calculated as follows: (5.27 × E/Vp) + 4.6. RESULTS: Mean ejection fraction was 66 ± 11%. The mean invasive measured PCWP was 11.14 ± 5.4 mm Hg and the mean noninvasive ePCWP was 11.13 ± 1.8 mm Hg (r = 0.66; P < .0001). A good correlation was present between invasive PCWP and mitral PW-Doppler and DTI parameters: peak E 91 ± 22 cm/s (r = 0.34; P = .02) and DT 143 ± 26 s (r = -0.436; P = .002), E/E' ratio medial mitral annulus 10 ± 4 cm/s (r = 0.353; P = .026) and E/E' ratio lateral mitral annulus 6 ± 2 cm/s (r = 0.462; P = .002). E/Vp was the most accurate index for predicting PCWP (r = 0.615; P < .0001). CONCLUSIONS: Compared with other indirect Doppler indices, E/Vp showed the best correlation to predict PCWP in heart transplant recipients. Despite previous recommendations, PCWP can be accurately estimated from color M-mode indices, giving useful information and avoiding the risks of invasive measurements.

Proliferation signal inhibitors and post-transplant malignancies in heart transplantation: practical clinical management questions.

Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.

Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF).

PURPOSE: We performed a survey on acute heart failure (AHF) in nine countries in four continents. We aimed to describe characteristics and management of AHF among various countries, to compare patients with de novo AHF versus patients with a pre-existing episode of AHF, and to describe subpopulations hospitalized in intensive care unit (ICU) versus cardiac care unit (CCU) versus ward. METHODS AND RESULTS: Data from 4,953 patients with AHF were collected via questionnaire from 666 hospitals. Clinical presentation included decompensated congestive HF (38.6%), pulmonary oedema (36.7%) and cardiogenic shock (11.7%). Patients with de novo episode of AHF (36.2%) were younger, had less comorbidities and lower blood pressure despite greater left ventricular ejection fraction (LVEF) and were more often admitted to ICU. Overall, intravenous (IV) diuretics were given in 89.7%, vasodilators in 41.1%, and inotropic agents (dobutamine, dopamine, adrenaline, noradrenaline and levosimendan) in 39% of cases. Overall hospital death rate was 12%, the majority due to cardiogenic shock (43%). More patients with de novo AHF (14.2%) than patients with a pre-existing episode of AHF (10.8%) (p = 0.0007) died. There was graded mortality in ICU, CCU and ward patients with mortality in ICU patients being the highest (17.8%) (p < 0.0001). CONCLUSIONS: Our data demonstrated the existence of different subgroups based on de novo or pre-existing episode(s) of AHF and the site of hospitalization. Recognition of these subgroups might improve management and outcome by defining specific therapeutic requirements.

Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods.

PURPOSE: To date, treatment with intravenous (IV) agents such as vasodilators, diuretics, and inotropes has shown marginal or mixed benefits in acute heart failure (AHF) trials. The aim of this study was to identify the risks and benefits of IV drugs in patients hospitalized with acute decompensated heart failure. METHODS: The AHF global survey of standard treatment (ALARM-HF) reviewed in-hospital treatments in eight countries. The present study was a post hoc analysis of ALARM-HF data in which propensity scoring was used to identify groups of patients who differed by treatment but had the same multivariate distribution of covariates. Such propensity matching allowed estimations of the effect of specific treatments on the outcome of in-hospital mortality. RESULTS: Unadjusted analysis showed a lower in-hospital mortality rate in AHF patients receiving "diuretics + vasodilators" (n = 1,805) compared to those receiving "diuretics alone" (n = 2,362) (7.6 vs. 14.2%, p < 0.0001). Propensity-based matching (n = 1,007 matched pairs) confirmed the lower mortality of AHF patients receiving diuretics + vasodilators: 7.8 versus 11.0% (p = 0.016). Unadjusted analysis showed a much greater in-hospital mortality rate in patients receiving IV inotropes (25.9%) compared to those who did not (5.2%) (p < 0.0001). Propensity-based matching (n = 954 pairs) confirmed that IV catecholamine use was associated with 1.5-fold increase for dopamine or dobutamine use and a >2.5-fold increase for norepinephrine or epinephrine use. CONCLUSIONS: In terms of in-hospital survival, a vasodilator in combination with a diuretic fared better than treatment with only a diuretic. Catecholamine inotropes should be used cautiously as it has been seen that they actually increase the risk for in-hospital mortality.

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.

Temporal trends in the use of proliferation signal inhibitors in maintenance heart transplantation: a Spanish multicenter study.

Proliferation signal inhibitors (PSI; sirolimus, everolimus) are being increasingly used in heart transplantation. We performed an observational, retrospective, multicenter study in 9 Spanish centers seeking to describe the clinical context in which a PSI was used among maintenance heart recipients and its evolution over time. We collected a cohort of 548 patients in whom a PSI was prescribed from October 2001 to March 2009. The group was divided into 3 time periods. The use of PSI steeply increased in the 2005-2006 period, remaining stable thereafter. There were no significant differences over time with regard to age, gender, or time from transplantation to the introduction of the PSI. Everolimus usage overtook sirolimus from 2005 on; currently, >90% of the subjects with PSI indications are prescribed everolimus. Compared with earlier periods, patients in the more recent period (October 2006-March 2009) showed less vascular graft disease and better basal renal function, irrespective of the primary indication for the PSI prescription. Also, skin cancer overtook solid cancer as the main type of neoplasm in patients for whom malignancy was the primary indication for the use of the PSI. The actuarial incidence of PSI withdrawal owing to adverse effects did not change significantly over time.

Incidence and risk factors for nonmelanoma skin cancer after heart transplantation.

INTRODUCTION: The incidence of skin cancer in heart transplant (HT) patients is higher than in the general population, reversing the proportion of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with a predominance of the former. The etiologic role of new immunosuppressants is not well known. We sought to ascertain the incidence of SCC and BCC in HT patients and the risk factors for its occurrence. PATIENTS AND METHODS: We report the incidence of all types of post-HT skin cancer, SCC, and BCC among adult HT patients in Spain (4089 subjects) as well as the influence of gender, age at heart transplant, immunosuppression, and sunlight exposure. RESULTS: The incidence rates of SCC and BCC, per 1000 persons/year, were 8.5 and 5.2, respectively. Males had a higher risk of SCC but not BCC. Induction therapy increased the risk of SCC and BCC. The relative risk of mycophenolate mofetil (MMF) was 0.3 (0.2-0.6; P<.0005) and azathioprine (AZA) 1.8 (1.2-2.7; P<.0032) for SCC, whereas tacrolimus and cyclosporine showed no difference. The relative risk of BCC was not affected by any immunosuppressant. CONCLUSION: Age at transplantation>45 years, induction therapy use, and high sunshine zone were risk factors for both SCC and BCC. Different immunosuppressive agents have different risks of nonmelanoma skin cancer, as AZA increases the risk of SCC and MMF is a protective factor. The relative risk of BCC was not affected by any immunosuppressor.