Retrasplante pulmonar con cross-match positivo en trasplante pulmonar primario complicado con rechazo mediado por anticuerpos / Lung Retransplantation with Positive Crossmatch in Primary Lung Transplantation Complicated by Antibody-Mediated Rejection

La hipertensión arterial pulmonar (HAP) representa el 2,6% de los trasplantes pulmonares (TP), con una mediana de supervivencia condi cional (desde los 30 días del TP) de 9,8 años. Son frecuentes, el rechazo celular agudo (ACR) y la disfunción crónica del injerto (CLAD), mientras que es infrecuente el rechazo mediado por anticuerpos (AMR). El retrasplante pulmonar (RTP) constituye el 4% del TP mundial, debido a complicaciones en la vía aérea, disfunción primaria del injerto, ACR y CLAD. Mujer de 22 años, portadora de HAP idiopática (HAPI) desde el año 2013, trasplantada bipulmonar (TBP) en enero de 2018. A los 16 meses presentó neumonía adquirida en la comuni dad. En una internación posterior, presentó ACR y a pesar de pulsos de metilprednisolona, progresó a requerimientos de cánula de alto flujo y ventilación mecánica no invasiva hospitalaria, caída del VEF1, y tomografía de tórax con vidrio esmerilado difuso y engrosamiento irregular reticular del intersticio subpleural; interpretándose como CLAD a predominio de síndrome de bronquiolitis obliterante (BOS), con presencia de anticuerpos específicos contra el donante (DSA). En enero de 2020 se realizó nuevo TP y ante cross-match positivo, se realizó plasmaféresis y reposición de IgG. Al mes del egreso, no se observaron signos de rechazo en control de biopsias transbronquiales. Entre 2 y 10% de los pacientes con indicación primaria de TP por HAPI son sometidos a retrasplante pulmonar (RTP). La presencia de DSA y el miss-match de HLA, no son contraindicaciones para el RTP.

Pulmonary arterial hypertension (PAH) represents 2.6% of lung transplantations (LT), with a conditional median survival (from 30 days after LT) of 9.8 years. Acute cellular rejection (ACR) and chronic lung allograft dysfunction (CLAD) are common; whereas the antibody-mediated rejection (AMR) is not. Lung retransplantation (LR) accounts for 4% of global LTs for complications in the airways, primary allograft dys function, ACR and CLAD. 22-year-old woman with idiopathic PAH (IPAH) since 2013, who underwent a double-lung transplantation (DLT) in January 2018. 16 months after transplantation she presented community-acquired pneumonia. During a subsequent hospitalization, she presented ACR. Despite the fact that she received pulse methylprednisolone, she required high-flow cannula therapy and hospital non-invasive mechanical ventilation; the FEV1 was reduced and she underwent a chest tomography with diffuse ground glass opacities and irregular reticular thickening of the subpleural interstitium; interpreting the predominance of BOS (bronchiolitis obliterans syndrome) as CLAD, with presence of donor-specific antibodies (DSA). In January 2020, she received a new DLT and due to a positive crossmatch, she was treated with plasmapheresis and IgG replacement. One month after hospital discharge, no signs of rejection were observed at the BTB (bone-patellar tendon-bone) control. Between 2 to 10% of patients with primary indication of LT for IPAH are subjected to lung retransplantation (LR). The presence of DSA and HLA (human leucocyte antigen) mismatch aren't contraindications to LR.

Conducción anestésica perioperatoria en gestante a término con hipertensión pulmonar idiopática / Perioperative anesthetic management in term pregnant women with idiopathic pulmonary hypertension

Introducción: La hipertensión arterial pulmonar es una enfermedad con una baja incidencia en la gestante, aunque trae consigo una alta mortalidad una vez presentada. Un diagnóstico oportuno y un manejo perioperatorio adecuado minimizan el riesgo de desenlace fatal tanto para la madre como el feto. Objetivo: Describir el comportamiento de la hipertensión arterial pulmonar en la gestante a término y su conducción anestésica. Presentación del caso: Paciente de 23 años, antecedentes de salud, edad gestacional de 35.2 semanas. Luego de presentar dolor de espalda y ardor en el pecho relacionado con el esfuerzo, palpitaciones, disnea y bloqueo de rama derecha en electrocardiograma, se ingresa en UTI con sospecha de tromboembolismo pulmonar, el cual queda descartado tras diagnóstico confirmatorio de hipertensión pulmonar después de realizar angio TAC y ecocardiografía. Se decide realizar cesárea programada bajo técnica regional peridural, sin complicaciones tanto para la madre como el niño. Después de 2 días bajo vigilancia intensiva se traslada a su centro hospitalario de cabecera. Conclusiones: La vía del parto, así como una elección adecuada de la técnica anestésica, puede ser la diferencia entre el éxito y la fatalidad. Las técnicas regionales suelen recomendarse por encima de la técnica de anestesia general siempre que no se presenten contraindicaciones(AU)

Introduction: Pulmonary arterial hypertension is a disease with low incidence in the pregnant woman, although it brings about high mortality once presented. Timely diagnosis and adequate perioeprative management minimize the risk of fatal outcome for both mother and fetus. Objective: To describe pulmonary arterial hypertension and its anesthetic management in the term pregnant woman. Case presentation: 23-year-old female patient, with health history and gestational age of 35.2 weeks. After presenting back pain and chest burning associated with exertion, palpitations, dyspnea and right bundle branch block in the electrocardiogram, the patient was admitted to the intensive care unit with suspected pulmonary thromboembolism, which was ruled out due to the confirmatory diagnosis of pulmonary hypertension after performing computerized tomography angiography and echocardiography. Scheduled cesarean section was decided to be perform using the regional peridural technique, without complications for both the mother and the child. After two days under intensive surveillance, she was transferred to her primary hospital. Conclusions: The route of delivery, as well as an adequate choice of the anesthetic technique, can be the difference between success and fatality. Regional techniques are usually recommended over the general anesthesia technique, as long as there are no contraindications(AU)

Pulmonary Arterial Capacitance Index Is a Strong Predictor for Adverse Outcome in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension.

OBJECTIVES: To evaluate the clinical utility of pulmonary artery capacitance index (PACi) in the assessment of disease severity and prognostic value in children with idiopathic and heritable pulmonary arterial hypertension (PAH). STUDY DESIGN: PACi is defined as the ratio of stroke volume index over pulmonary pulse pressure. A retrospective study was performed to compare PACi, brain natriuretic peptide (BNP), 6-minute walk distance, New York Heart association (NYHA) functional class, and adverse outcomes (hospitalization due to heart failure, lung transplantation, and cardiac mortality) in 72 Japanese children (10 ± 3.6 years) with idiopathic and heritable PAH. RESULTS: PACi had significant correlations with pulmonary vascular resistance index (r =-0.73, P < .0001), BNP levels (r = -0.40, P = .0008), and 6-minute walk distance (r = 0.57, P < .05). Statistically significant differences in PACi were observed between NYHA functional class II vs combined III and IV (median; 1.1 vs 0.6 mL/mm Hg/m2, respectively, P < .05). There were 25 of 72 (35%) children who had an adverse event including initiation of hospitalization due to heart failure, lung transplantation, and death. Cumulative event-free survival rate was significantly lower when PACi was <0.85 mL/mm Hg/m2 (log-rank test, P < .0001). CONCLUSIONS: PACi correlated with BNP and NYHA functional class and may serve as a strong prognostic marker in children with idiopathic and heritable PAH.

Mortalidad por hipertensión arterial pulmonar idiopática en la Argentina / Mortality due to idiopathic pulmonary hypertension in Argentina / Mortalidade por hipertensão arterial pulmonar idiopática na Argentina

Objetivo. Describir la tasa de mortalidad anual por hipertensión arterial pulmonar idiopática (HAPI) en la República Argentina durante un lapso de diez años (2000-2009). Materiales y métodos. Se incluyeron todos los fallecimientos identificados con el número de registro I27.0 (CIE10) de la base de datos de la Dirección de Estadística e Información de Salud del Ministerio de Salud, Presidencia de la Nación, República Argentina. Los datos poblacionales fueron obtenidos del Instituto Nacional de Estadísticas y Censos de la República Argentina. Resultados. Entre los años 2000 y 2009 la tasa anual de mortalidad por HAPI en Argentina fue relativamente constante y osciló entre 1,39 y 2,39 muertes/1.000.000 habitantes. Fue más alta en las mujeres (1,76 a 3,16/1.000.000) que en los varones (0,9 a 2,11/1.000.000). El número más elevado de muertos por HAPI en los adultos se registró en el grupo de los mayores de 70 años. Las tasas de mortalidad más altas se encontraron en las provincias de Tierra del Fuego (31,42/1.000.000) y San Juan (17,61/1.000.000). Sin embargo, la superposición de los IC 95% de las tasas de mortalidad específica, ajustadas por edad y sexo, en el año 2009, sugiere que no hay diferencias significativas de mortalidad por HAPI entre las provincias. Conclusiones. En nuestro conocimiento éste es el primer estudio de las tasas de mortalidad por HAPI en la Argentina durante una década. La información obtenida puede servir de base para realizar, oportunamente, estudios más detallados de mortalidad específica. Parece necesario implementar un registro nacional de esta enfermedad para disponer de una información más confiable y poder promover la estandarización de las conductas diagnósticas y terapéuticas en todo el país, optimizando los recursos disponibles.

Objetive. To describe the annual mortality rate due to idiopathic pulmonary arterial hypertension (IPAH) in Argentina for a period of ten years (2000-2009). Materials and methods. The study included all I27.0 (ICD-10) coded deaths on the database of the Statistics and Health Information Board (Dirección de Estadística e Información de Salud: DEIS) of the Ministry of Health, National Presidency, Argentina. Population data were obtained from the National Institute of Statistics and Census (Instituto Nacional de Estadísticas y Censos: INDEC), Argentina. Results. Between 2000 and 2009 the IPAH annual mortality rate in Argentina was relatively constant and ranged between 1.39 and 2.39 deaths/1,000,000 inhabitants. It was higher in women (1.76 to 3.16/1,000,000) than in men (0.9 to 2.11/1,000,000). In adults, the highest number of IPAH deaths was recorded in the age group over 70 years. The highest mortality rates were recorded in the provinces of Tierra del Fuego (31.42/1,000,000) and San Juan (17.61/1,000,000). However, the overlap of the 95% of the specific mortality rates, adjusted for age and sex, in 2009, suggesting no significant difference in IPAH mortality between provinces. Conclusions. To our knowledge this is the first study of mortality rates from IPAH in Argentina for a period of 10 years. The information obtained can eventually become a basis for more detailed studies of specific mortality. It seems necessary to implement a national registry of this disease to provide more reliable information and to promote the standardization of diagnostic and therapeutic procedures nationwide, optimizing available resources.

Objetivo. Descrever a taxa de mortalidade anual devido à hipertensão arterial pulmonar idiopática (HAPI) na Argentina por um período de dez anos (2000-2009). Materiais e métodos. O estudo incluiu todos os óbitos identificados com o número de registro I27.0 (CID-10) da base de dados da Direção de Estatística e Informação em Saúde, Ministério da Saúde, Presidência da Nação, Argentina. Os dados populacionais foram obtidos do Instituto Nacional de Estatística e Censos (Instituto Nacional de Estadísticas y Censos: INDEC), Argentina. Resultados. Entre 2000 e 2009, a taxa anual de mortalidade por HAPI na Argentina foi relativamente constante e variou entre 1,39 e 2,39 mortes/1.000.000 de habitantes. Ela foi maior em mulheres (1,76-3,16/1.000.000) do que nos homens (0,9-2,11/1.000.000). Em adultos, o maior número de mortes por HAPI foi registrada na faixa etária acima de 70 anos. As maiores taxas de mortalidade foram registradas nas províncias de Tierra del Fuego (31,42/1.000.000) e San Juan (17,61/1.000.000). No entanto, a sobreposição de 95% das taxas de mortalidade específicas, ajustadas por idade e sexo, em 2009, sugerindo que não houve diferença significativa na mortalidade por HAPI entre as províncias. Conclusões. Para nosso conhecimento, este é o primeiro estudo de taxas de mortalidade por HAPI na Argentina por um período de 10 anos. A informação obtida pode eventualmente tornar-se uma base para estudos mais detalhados de mortalidade específica. Afigura-se necessário para implementar um registro nacional desta doença para fornecer informações mais seguras e para promover a padronização de procedimentos diagnósticos e terapêuticos em todo o país, otimizando os recursos disponíveis.

Hipertensão arterial pulmonar idiopática / Idiopathic pulmonar arterial hypertension

A hipertensão arterial pulmonar idiopática (HAPI) constitui o protótipo da hipertensão arterial pulmonar, fazendo parte da classificação clínica internacional de hipertensão pulmonar. O termo idiopático é reservado para a classificação da forma esporádica de hipertensão arterial pulmonar (HAP), desde que nenhuma causa aparente ou identificável esteja presente. A confirmação de caso de HAPI deve ser feito após extensa investigação diagnóstica. As outras condições que compõem o Grupo 1 compartilham com ela características histopatológicas e hemodinâmicas e constituem, como classe, o grupo mais avaliado quanto à eficácia e segurança dos medicamentos atualmente disponíveis para o seu tratamento...

Idiopathic pulmonary arterial hypertension (IPAH) is the prototype of pulmonary arterial hypertension syndrome, part of the international clinical classification of pulmonary hypertension. The term idiophatic is reserved for classification of the sporadic form of pulmonary arterial hypertension (PAH), provided that no apparent or identifiable cause is present. Confirmation of case HAPI should be done after extensive diagnostic investigation. The other conditions that make up the Group 1 share it with histopathologic and hemodynamic characteristics and are, as a class, the most evaluated group regarding the efficacy and safety of drugs currently available for its treatment...

Immunopathological aspects of schistosomiasis-associated pulmonary arterial hypertension.

OBJECTIVES: Pulmonary hypertension is a lethal complication of chronic hepatosplenic schistosomiasis. Little is known of the underlying (immuno-)histopathological characteristics of lung vasculopathy. METHODS: We characterized vasculopathy and inflammation in lung tissue of 10 patients with Schistosomiasis-associated PH (SCH-PH) in comparison to 22 idiopathic pulmonary arterial hypertension (IPAH) patients and 10 normal controls. SCH-PH cases were younger than controls. RESULTS: Plexiform lesions and/or angiomatoid lesions were found in 10/10 SCH-PH, and 19/22 IPAH patients (χ² p = 0.22). Lung granulomas with Schistosoma eggs were found in 2/10 of SCH-PH cases. PAH cases had increased peri-arterial density of CD3+ T cells, chymase+ and tryptase+ mast cells when compared to controls (p ≤ 0.047). SCH-PH showed increased density of CD4+ cells when compared to controls (p = 0.025), paralleled by an increased density of dendritic CD83+ cells when compared to both controls and IPAH patients (p ≤ 0.022). CONCLUSION: Both SCH-PH and IPAH feature plexogenic arteriopathy and increased periarterial T cell and mast cell density. SCH-PH and IPAH differ only with respect to the density of dendritic CD83+ cells. These findings imply ongoing antigenic stimulation in SCH-PH, yet a pattern of pulmonary vasculopathy similar to IPAH, suggestive of a final common pathway in their pathogenesis of PAH.

Interpretación de la relación presión-flujo en la hipertensión arterial pulmonar idiopática / Pressure-flow relationships interpretation in idiopathic pulmonary arterial hypertension

Objetivo: Conocer más de la relación presión arterial pulmonar media/índice cardiaco y sus perfiles en enfermos con hipertensión arterial pulmonar idiopática. Métodos: La presión arterial pulmonar media/índice cardiaco y la presión extrapolada al eje de cero flujo se obtuvo en 40 enfermos respirando aire ambiente, oxígeno 99.5% e hidralazina. Se obtuvieron dos grupos de acuerdo a criterios de "respuesta vasodilatadora aguda", respondedores (n = 20) y no respondedores (n = 20). Se analizó este criterio versus el propuesto por la Task Force de la Sociedad Europea de Cardiología en la población respondedora. Resultados: La presión arterial pulmonar media/Índice cardiaco se ubicó de forma anormal en el diagrama de presión-flujo de la cohorte total, (p < 0.01). Sin alteraciones en el intercambio gaseoso o mecánica pulmonar. Para los enfermos respondedores versus no respondedores, la pendiente fue anormal 2.2 (95%IC:1.1-3.3) vs. 5.89 (95%IC:4.69-7.11) mm Hg/L min/m² e incremento de la presión extrapolada al eje de cero flujo (38.2 ± 7.5 a 66.3 ± 7.5 mm Hg, p < 0.01). Sin diferencias con oxígeno al 99.5%. Con vasodilatador, la presión arterial pulmonar media disminuyó (52.1 ± 9.5 a 40 ± 5.5 mm Hg, p < 0.01) vs. no se modificó (96.2 ± 8.5 vs. 90 ± 7.5 mmHg, p = 0.3), pendiente 1.15 (95%IC:0.68-1.62) vs. 1.28 (95%IC:0.78-1.78) mmHg/Lmin/m², la presión extrapolada al eje de cero flujo no cambió vs. incrementó (69.4 ± 7.8 a 85.1 ± 8.5 mm Hg, p < 0.01), en relación al control. En no respondedores con vasodilatador, la presión arterial pulmonar media/índice cardiaco (90 ± 7.5 mmHg, pendiente:1.28; 95%IC: 0.78 - 1.78 mm Hg/L min/m²) fue diferente al comparar respondedores con menor o mayor de 40 mm Hg de presión arterial pulmonar media. Presiones 34 ± 3 vs. 45 ± 4 mm Hg y pendientes 1.14 (95%IC: 0.67 -1.61 vs. 2.22 (95%IC: 1.35 - 3.09 mm Hg/L min/m²), respectivamente p < 0.01. Conclusiones: Las anormalidades de la relación presión arterial pulmonar media/Índice cardiaco reflejan el incremento de las resistencias vasculares pulmonares reales a nivel arteriolar pulmonar en enfermos con hipertensión arterial pulmonar idiopática. Ambos criterios de respuesta vasodilatadora aguda son de utilidad para identificar respondedores y no, en esta población de enfermos.

Objectives: We analyze exercise-derived mean pulmonary artery pressure/cardiac index relationship to expand the concepts regarding its nature and to better identify "responders" in idiopathic pulmonary arterial hypertension patients. Methods: Mean pulmonary artery pressure/cardiac index relationship and extrapolated pressure to zero flow were obtained in 40 patients' breathing room air, oxygen 99.5% and hydralazine. The hemodynamic characteristics were analyzed for the cohort and separate for responders (n = 20) and non responders (n = 20) according to the acute response to vasodilator. We tested this previous criteria versus the Task Force on diagnosis and treatment prescribed by the European Society of Cardiology. Results: The mean pulmonary arterial pressure/cardiac index was located abnormally in the pressure-flow diagram of the total cohort (p < 0.01). No alterations in gas exchange or lung mechanics. For patients responders versus non-responders, the slope was abnormal 2.2 (95% CI:1.1-3.3) vs. 5.89 (95% CI: 4.69 - 7.11), mm Hg/L min/m² and increased extrapolated pressure to zero flow (38.2 ± 7.5 to 66.3 ± 7.5 mm Hg, p <0.01). Without difference with oxygen 99.5%. With vasodilator effect, mean pulmonary arterial pressure decreased (52.1 ± 9.5 to 40 ± 5.5 mm Hg, p <0.01) versus it did not change (96.2 ± 8.5 versus 90 ± 7.5 mm Hg, p=0.3), slope 1.15 (95% CI: 0.68 - 1.62) vs. 1.28 (95% CI: 0.78-1.78) mmHg/L min/m², the extrapolated pressure to zero flow did not change (69.4 ± 7.8 to 85.1 ± 8.5 mm Hg), p <0.01, compared to control. In non-responders with vasodilator, mean pulmonary arterial pressure/cardiac index (90 ± 7.5 mmHg, slope: 1.28, 95% CI :0.78 - 1.78 mm Hg/L min/m²) was different between responders < or > 40 mmHg mean pulmonary arterial pressure. Pressures were 34 ± 3 vs. 45 ± 4 mm Hg and slopes 1.14 (95% CI: 0.67 - 1.61) vs. 2.22(95% CI: 1.35 - 3.09) mm Hg/L min/m², p <0.01, respectively.. Conclusions: Abnormalities of the mean pulmonary arterial pressure/cardiac index relationship exercise-derived seems to reflect "mainly arteriolar" increased lineal pulmonary vascular resistance in idiopathic pulmonary arterial hypertension patients. Both acute vasodilator response criteria are useful to identify responders and not responders in this patient population.

Hipertensão arterial pulmonar idiopática manifestada durante a gestação: correlação anátomo-clínica com necropsia. Relato de caso / Idiopathic pulmonary arterial hypertension manifested during pregnancy: anatomical-clinical correlation with necropsy. Case report

JUSTIFICATIVA E OBJETIVOS: A hipertensão arterial pulmonar idiopática (HAPI) é uma entidade rara, com prevalência estimada em 1-2 casos por milhão de pessoas. Sua relação com a gestação é relatada na literatura com freqüência de 4,5% em pacientes com HAPI. O objetivo deste estudo foi demonstrar um caso de HAPI relacionado com a gravidez, de evolução prolongada, a discordância entre o grau de lesão das artérias de pequeno calibre na anatomia patológica e a medida da pressão da artéria pulmonar no ecocardiograma. RELATO DO CASO: Paciente com 33 anos, branca, em sua segunda gestação, iniciou com quadro de dispnéia e edema nos membros inferiores, intensificados ao final do segundo trimestre, sendo realizada cesariana eletiva. Manteve os sintomas por dois meses. Referiu também dor precordial no hipocôndrio direito em sua segunda internação. Ao exame físico, observou-se estase jugular e hepatomegalia dolorosa, à ausculta cardíaca observou-se ritmo de galope protodiastólico, hiperfonese de segunda bulha em focos da base e sopro holossistólico em foco tricúspide. A investigação complementar confirmou a origem idiopática da doença. O óbito ocorreu por choque cardiogênico. CONCLUSÕES: A observação clínica indicou o diagnóstico de HAPI, afastando outras causas de hipertensão pulmonar. À necropsia, o diagnóstico pôde ser reforçado e foram afastadas outras causas específicas de hipertensão pulmonar na gestação. Apesar de não ter sido realizado estudo hemodinâmico, a pressão média da artéria pulmonar estimada pelo exame ultra-sonográfico foi discordante com a magnitude das lesões nas artérias de pequeno calibre detectadas no exame histopatológico. A HAPI durante a gestação possui elevada mortalidade e trata-se de uma doença ainda sem cura e com muitos aspectos fisiopatológicos a serem esclarecidos. As medidas de maior impacto continuam sendo a prevenção na gestação; e, se esta ocorrer, recomenda-se a sua interrupção precoce.(AU)

BACKGROUND AND OBJECTIVES: Idiopathic pulmonary arterial hypertension (IPAH) is a rare entity, with prevalence estimated in 1-2 cases/1.000.000. Its relationship with pregnancy, in the literature, is reported a 4.5% rate of patients with IPAH. The objective of this study was to demonstrate a case of IPAH related to pregnancy with extended evolution and the discord between the injury degree of the small bore arteries in the pathological anatomy and the measure of pulmonary artery pressure in echocardiography. CASE REPORT: Patient, 33 years-old, white, in her second pregnancy, initiated with symptoms of dyspnea and peripheral edema, intensified in the end of the second trimester, been realized cesarean section. She kept the symptoms for two months and related precordial and right hypochondriac pain in her second hospitalization. On physical examination, there were elevated jugular venous pressure and painful enlarged liver. On auscultation, there were gallop rhythm, prominent aortic and pulmonary second heart sounds and tricuspid pansystolic murmur. The complementary investigation confirmed the idiopathic origin of the disease. The death occurred due cardiogenic shock. CONCLUSION: The clinical observation indicates the diagnosis of IPAH, excluding other causes of pulmonary hypertension. In the necropsy, the diagnosis could have been confirmed and other specific causes of pulmonary hypertension in pregnancy could have been excluded. Although right heart catheterization haven’t been realized, the pulmonary artery pressure determined by echocardiography is discordant of the magnitude of the injuries in the small bore arteries detected in the microscopic examination. IPAH during pregnancy has great mortality and is an illness still without cure and with many physiopathological aspects to be revealed. The pregnancy prevention is recommended, if the pregnancy occurs, precocious interruption of the same one must be realized.(AU)