Manejo y tratamiento actual de la insuficiencia cardiaca en unidades acreditadas de cardiología y medicina interna en España / Current heart failure disease management and treatment in accredited units from cardiology and internal medicine in Spain

Antecedentes y objetivos La insuficiencia cardiaca (IC) es una patología compleja con una alta prevalencia, incidencia y mortalidad que conlleva un importante coste sanitario. En España existen unidades de IC (UIC) multidisciplinares, lideradas por cardiología y medicina interna. Nuestro objetivo era conocer su organización actual y adherencia a las últimas recomendaciones científicas. Materiales y métodos Un comité científico formado por cardiólogos e internistas elaboró una encuesta a finales de 2021, que fue enviada a 110 UIC. Setenta y tres de cardiología, acreditadas por SEC-Excelente, y 37 de medicina interna, integradas en el programa UMIPIC. Resultados Se recibieron 83 encuestas cumplimentadas (75,5%); 49 de cardiología y 34 de medicina interna. Los resultados mostraron que las UIC están integradas mayoritariamente por un cardiólogo, internista y enfermería especializada (34,9%). El perfil de paciente atendido en las UIC cardiológicas es muy diferente al paciente de las UMIPIC, siendo estos últimos mayores, con fracción de eyección ventricular izquierda conservada y más carga de comorbilidad. La mayoría de UIC actualmente realizan seguimiento mixto, presencial y telemático (73,5%). Los péptidos natriuréticos son los biomarcadores más utilizados (90%). Se titulan los cuatro grupos farmacológicos fundamentales de tratamiento de la IC a la vez mayoritariamente (85%). Solo 24% de las unidades mantienen una comunicación fluida con atención primaria. Conclusiones Los dos modelos de UIC liderados por cardiología y medicina interna son complementarios, disponen de enfermería especializada, y siguen al paciente de forma mixta, con una adherencia farmacológica muy alta a las últimas recomendaciones científicas. El principal punto de mejora es la coordinación con atención primaria (AU)

Background and objectives Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective was to describe its current organizational model and their adherence to the latest scientific recommendations. Materials and methods In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units [73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine (integrated in UMIPIC program)]. Results We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. Conclusions Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area (AU)

Current heart failure disease management and treatment in accredited units from cardiology and internal medicine in Spain.

BACKGROUND AND OBJECTIVES: Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective is to describe its current organizational model and their adherence to the latest scientific recommendations. MATERIALS AND METHODS: In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units. 73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine, (integrated in UMIPIC program). RESULTS: We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. CONCLUSIONS: Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area.

Impact of mobilization in patients with short-term mechanical circulatory support such as Levitronix® CentriMag as a bridge to heart transplantation.

INTRODUCTION: Despite the benefits of mobilisation in the critical patient, the evidence in patients with Levitronix® CentriMag as a bridge to heart transplantation (HT) is scarce. The objective of this study is to analyze the impact of mobility on these patients. METHODS: Retrospective observational study of patients who received a HT with Levitronix® CentriMag admitted between 2010 and 2019 to a tertiary hospital. Degree of mobility and nutritional status were assessed at the time of HT. Outcomes including infections, length of hospital admission and mortality were evaluated. RESULTS: 27 patients were included and divided in two groups according to degree of mobility (22 with low mobility and 5 with high mobility). 90-day survival after HT was 63.6% in patients with low mobility and 80% in high mobility group; no statistically significant differences were observed. No differences were observed regarding ICU discharge after HT at 30 days. Nevertheless, lower albumin levels were observed in low mobility group (24,5 g/L (IQR: 23-30) vs 33 g/L (IQR: 26-36); p = .029). Invasive mechanical ventilation (IMV) post HT was longer in patients with low mobility (p = .014). There were no significant differences in appearance of pressure ulcers, or post HT infections among mobility groups. CONCLUSIONS: Patients with high mobility had a shorter time of IMV and a better nutritional status. No complications were observed associated to mobility. No differences were observed between the degree of mobility and 90-day mortality, ICU stay or post HT adverse events.

Diferencias de género en la titulación de fármacos de pacientes con insuficiencia cardiaca y fracción de eyección reducida del ensayo ETIFIC / Gender differences in drug titration among heart failure patients with reduced ejection fraction in the ETIFIC trial

Introducción y objetivos El tratamiento óptimo disminuye la mortalidad y hospitalizaciones por insuficiencia cardiaca (IC) en pacientes con IC y fracción de eyección reducida. En los ensayos clínicos las mujeres estuvieron infrarrepresentadas y no fueron evaluadas específicamente. Este estudio buscó comparar la seguridad y efectividad de titulación (ajuste de dosis) de fármacos en mujeres y varones. Métodos Estudio post hoc de género del ensayo aleatorizado multicéntrico ETIFIC. Se incluyeron pacientes hospitalizados con IC de novo y fracción de eyección reducida. Proceso estructurado de titulación en unidades de IC. Objetivo principal: la dosis relativa media de bloqueadores beta (% de la dosis objetivo) alcanzada por mujeres frente a varones. Objetivos secundarios: dosis relativas medias de otros fármacos de IC, eventos adversos y resultados clínicos a 6 meses. Resultados Se incluyeron 320 pacientes, 83 (25,93%) mujeres y 237 (74,06%) varones. (76 frente a 213 analizados). Media±desviación estándar de dosis relativa de bloqueadores beta mujeres frente a varones: 62,08±30,72% frente a 64,4±32,77%; diferencia −2,32%; IC95%, −10,58-5,94; p=0,580, antagonistas del receptor de mineralocorticoides 79,85±27,72% comparado con 67,29±31,43%; p=0,003, sin diferencias significativas en dosificación de otros fármacos. El análisis multivariante no encontró diferencias significativas. Mortalidad cardiovascular 1 (1,20%) frente a 3 (1,26%), p=1 y 0 hospitalizaciones por IC (0,00%) frente a 10 (4,22%), p=0,125. Conclusiones En un análisis post hoc del ensayo ETIFIC de titulación en IC no encontramos diferencias de género significativas en dosificación, mortalidad cardiovascular y hospitalizaciones por IC (AU)

Introduction and objectives Optimal medical therapy decreases mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. Women have been underrepresented in clinical trials and not specifically evaluated. This study aimed to compare the safety and effectiveness of drug titration in women vs men. Methods This post hoc gender study of the ETIFIC multicenter randomized trial included hospitalized patients with new-onset HF with reduced ejection fraction and New York Heart Association II-III and no contraindications to beta-blockers. A structured 4-month titration process was implemented in HF clinics. The primary endpoint was the mean relative dose (% of target dose) of beta-blockers achieved by women vs men. Secondary endpoints included the mean relative doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists, adverse events, and other clinical outcomes at 6 months. Results A total of 320 patients were included, 83 (25.93%) women and 237 (74.06%) men (76 vs 213 analyzed). The mean±standard deviation of the relative doses achieved by women vs men were as follows: beta-blockers 62.08%±30.72% vs 64.4%±32.77%, with a difference of−2.32% (95%CI,−10.58-5.94), P = .580; and mineralocorticoid receptor antagonists 79.85%±27.72% vs 67.29%±31.43%, P =.003. No other differences in drug dosage were found. Multivariate analysis showed nonsignificant differences. CV mortality was 1 (1.20%) vs 3 (1.26%), P=1, and HF hospitalizations 0 (0.00%) vs 10 (4.22%), P=.125. Conclusions In a post hoc analysis from the HF-titration ETIFIC trial, we found nonsignificant gender differences in drug dosage, cardiovascular mortality, and HF hospitalizations (AU)

Caracterización de la amiloidosis cardiaca hereditaria por transtirretina en España / Characterization of hereditary transthyretin cardiac amyloidosis in Spain

Introducción y objetivos: La amiloidosis hereditaria por transtirretina (ATTRv) es una enfermedad causada por mutaciones en el gen de la transtirretina que frecuentemente presenta afección cardiaca debido al depósito de amiloide en el miocardio. Nuestro objetivo es describir esta afección en una cohorte española. Métodos: Estudio retrospectivo multicéntrico de pacientes con ATTRv y afección cardiaca provenientes de centros españoles. Se recogieron datos demográficos, clínicos y genéticos.Resultados: En 26 centros se incluyó a 181 pacientes, el 65,2% varones, con una mediana de edad al diagnóstico de 62 años. Las mutaciones más frecuentes fueron Val50Met (67,7%) y Val142Ile (12,4%). El principal motivo de consulta fue extracardiaco (69%), principalmente neurológico. La media de la fracción aminoterminal del propéptido natriurético cerebral (NT-proBNP) fue 2.145±3.586 pg/ml. Lo más característico del electrocardiograma fueron el patrón de seudoinfarto (25,9%) y el bloqueo auriculoventricular (25,3%). El grosor ventricular medio fue 15,4±4,1mm. El strain longitudinal estaba reducido en segmentos basales en el 29,4%. Se observó realce tardío subendocárdico difuso en el 58,8%. En la gammagrafía había captación de grados 2-3 en un 75%. En el seguimiento, el 24,9% ingresó por insuficiencia cardiaca, el 34,3% precisó marcapasos y el 31,6%, trasplante hepático. El 32,5% falleció, principalmente por insuficiencia cardiaca (28,8%). Las mutaciones diferentes de Val50Met se asociaron en general con un peor pronóstico. Conclusiones: La ATTRv cardiaca en España tiene un espectro genético y de afección heterogéneo. El pronóstico es malo principalmente por las complicaciones cardiacas, por lo que son esenciales un diagnóstico y un tratamiento precoces (AU)

Introduction and objectives: Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. Methods: Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. Result: A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis.Conclusions: HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital (AU)

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)

Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells.

BACKGROUND: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. METHODS: HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. RESULTS: Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. CONCLUSIONS: HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

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.

Curva de aprendizaje y pronóstico en pacientes con shock cardiogénico refractario tratados con soporte ventricular tipo ECMO / Learning curve and prognosis in patients with refractory cardiogenic shock receiving ECMO ventricular support

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Factors influencing mortality in solid organ transplant recipients with bloodstream infection.

Although bloodstream infection (BSI) is a major cause of mortality after solid organ transplantation, information regarding its prognostic factors is scarce. To identify risk factors for 30-day mortality in solid organ transplant (SOT) recipients with BSI, we prospectively recorded all episodes of BSI occurring in adult SOT recipients from January 2007 to October 2014 at a university hospital. We identified 361 consecutive episodes of BSI involving 246 patients. The 30-day case-fatality rate from the onset of BSI was 11.4%. Factors independently associated with 30-day mortality in a logistic regression analysis were shock at presentation (OR 13.658; 95% CI 5.985-31.168), acute graft rejection in the previous 6 months (OR 3.681; 95% CI 1.059-12.795), and a platelet count of <50,000 × 10(9)/L (OR 3.070; 95% CI 1.173-8.038). Kidney recipients were the patients with the best prognosis (OR 0.375; 95% CI 0.156-0.900). Our findings may help to identify SOT recipients with BSI who are at the highest risk of death.

Donor-transmitted malaria after heart transplant managed successfully with artesunate.

Donor-transmitted malaria is a rare complication in solid organ transplantation, which causes high mortality. Data concerning the use of artesunate in solid organ transplant recipients are lacking. We report a heart transplant patient who developed donor-derived severe Plasmodium falciparum malaria, successfully treated with artesunate. Transmission of malaria to 2 of the other transplant recipients from the same donor was also documented.

Renal function improvement after conversion to proliferation signal inhibitors during long-term follow-up in heart transplant recipients.

INTRODUCTION: The use of proliferation signal inhibitors (PSIs) for calcineurin-inhibitor (CNI) minimization or conversion protocols has been promoted for heart transplantation (HT) in the contexts of renal insufficiency, cardiac allograft vasculopathy (CAV), or malignancy. We evaluated our experience with conversion of patients from a CNI-based to a PSI-based immunosuppressive regimen. We focused on improvement in renal function. METHODS: This prospective follow-up included 96 HT patients converted to a PSI-based regimen from 2001 to 2010. We evaluated changes in creatinine clearance (CrCl) prior to at 1 year and at the end of follow-up after conversion. RESULTS: Ninety-six patients including 86% men showed a mean age of 62 ± 8 years. They were converted to a PSI-based regimen at 6.3 ± 4 years post-HT due to the following causes: CNI toxicity (45%), CAV (16%), cancer (16%), CNI toxicity + CAV (17%), or CNI toxicity + cancer (6%). CNI withdrawal was achieved in 77 cases (80%) and minimization in 19 (20%). Everolimus was used in 54 (56%) and sirolimus in 42 (44%) cases. Median follow-up time was 3.8 years. PSI discontinuation due to side effects was common (38%). There were 43 deaths mainly due to cancer and CAV. CrCl improved albeit not significantly in the withdrawal group from a median of 51 mL/min preconversion to 59 mL/min at the last follow-up (P = .12). In the minimization group, median CrCl worsened from a median of 61 mL/min preconversion to 51 mL/min at the last follow-up (P = .001). In the 58 cases (61%) of CNI nephrotoxicity, median CrCl improved from a median of 41 mL/min preconversion to 49 mL/min at the last follow-up (P = .04). CONCLUSION: Despite high rates of discontinuation of PSIs during long-term follow-up, the conversion regimen seemed to be useful to diminish CNI-related renal insufficiency especially with CNI withdrawal.

Clinical features and outcomes of tuberculosis in solid organ transplant recipients.

BACKGROUND: Tuberculosis (TB) remains a significant opportunistic infection in solid organ transplant (SOT) recipients. Moreover, its optimal treatment in SOT recipients is challenging due to the toxicity and potential drug-drug interactions of antituberculus drugs. We sought to assess the frequency, clinical characteristics, treatments, and outcomes of TB among SOT recipients. METHODS: We reviewed retrospectively the medical charts of all TB cases occurring among SOT recipients from January 2000 to December 2011, retrieving data regarding baseline and clinical features, as well as treatment and outcomes. RESULTS: Eighteen of 2005 SOT recipients developed TB (0.9%). The frequency according to the type of allograft was 0.9% (10 of 1120) for kidney, 1% (7 of 701) for liver, and 0.5% (1 of 184) for heart recipients. Six patients (33%) had prior exposure to TB: a positive tuberculin test (n = 3), a positive quantiferon-TB (n = 1) for a prior history of TB (n = 3). None of them received antituberculus prophylaxis. The mean time after transplantation to TB diagnosis was 64 months (range 2-169). Five patients (28%) developed TB within the first year posttransplantation. The mean duration of symptoms before diagnosis was 30 days (range 1-180). Nine patients (50%) displayed pulmonary TB; 7 (39%) had disseminated infections, and 2 (11%) had lymph node involvement. None of the Mycobacterium tuberculosis isolates were resistant to first-line antituberculus drugs. All patients were given isoniazide. Most of them received a 3-drug regimen. Rifampin was prescribed in 11 cases. Seven patients (5 liver and 2 kidney recipients) developed hepatotoxicity. One patient developed rejection without allograft loss. Mortality during antituberculus treatment was 17% (3/18). CONCLUSIONS: In this study, 0.9% of SOT recipients developed TB, which frequently presented with extrapulmonary involvement, causing considerable mortality. Hepatotoxicity mainly among liver transplant recipients was a significant therapeutic drawback.

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors.

Ganciclovir-resistant (GanR) cytomegalovirus (CMV) infection after organ transplantation is emerging as a significant therapeutic challenge. We report two cases of GanR CMV infection successfully managed by switching immunosuppression from calcineurin inhibitors to an mTOR inhibitor-based regimen. This salvage therapy should be considered when other options are not available.