Severe Pulmonary Hypertension Secondary to Concomitant Mitral Stenosis with Veno-occlusive Disease in the Context of Systemic Sclerosis: Importance of Careful and Comprehensive Assessment

Pulmonary Arterial Hypertension (PAH) is a clinical syndrome consisting of physiologic/ hemodynamic criteria that are a consequence of several etiologies. Confirmation of pulmonary hypertension is based on right heart catheterization. Pulmonary hypertension is a devastating condition that can lead to considerable morbidity and premature mortality. In the last few decades, significant advancement in the pharmacotherapy of pulmonary hypertension has resulted from better understanding of the complex pathogenesis and pathophysiology of this dreaded disease. Despite these accomplishments, pharmacotherapy of pulmonary hypertension is still far from perfect, and the mortality in this modern treatment era is still unacceptably high. We report a complex clinical presentation characterized by severe pulmonary hypertension secondary to concomitant mitral stenosis with veno-occlusive disease in the context of systemic sclerosis. Our case highlights the importance of a systematic and comprehensive diagnostic approach to avoid missing an underlying pathology.

Clinical features of POEMS syndrome initially diagnosed as pulmonary hypertension / 中华全科医师杂志

Objective:To analyze the clinical characteristics, diagnosis and treatments of patients with POEMS syndrome initially diagnosed as pulmonary hypertension (PH).Methods:Clinical data of 7 patients who were initially diagnosed as PH and finally diagnosed as POEMS syndrome in Shanghai Pulmonary Hospital from May 2013 to November 2021 were retrospectively reviewed. Clinical manifestations, laboratory tests, echocardiography, hemodynamic findings, treatment and prognosis of patients were analyzed.Results:Seven patients, including 4 males and 3 female, aged (55±9) (44-62) years were presented with elevated pulmonary artery pressure by echocardiography at admission. Chest tightness and shortness of breath (7/7), fatigue (6/7) and lower limb edema (4/7) were the most common symptoms in the first-episode. Meanwhile, patients also presented symptoms associated with POEMS syndrome, including multiple peripheral neuropathy (7/7), multiserosal cavity effusion (6/7), organomegaly (5/7), skin changes (5/7), and endocrine lesions (4/7). Serum levels of vascular endothelial growth factor (VEGF) were significantly increased in all patients. The pulmonary arterial systolic blood pressure was (66±21)mmHg (1 mmHg=0.133 kPa) estimated by echocardiography. Six patients underwent right heart catheterization and significantly increased mean pulmonary artery pressure((35±9) mmHg) was confirmed; and their pulmonary vascular resistance was (4.00±2.10) Wood U. All patients received corresponding treatment for POEMS syndrome. The excise tolerance was improved in 5 patients after successful treatment with stable or reversed WHO functional class. One patient received hemodialysis treatment for uncontrolled POEMS. One patient died during follow-up. The echocardiography was followed up in 4 patients, and 2 of whom had a complete reversal of PH, 1 had a partial reversal, and 1 had not yet reversed.Conclusions:In patients with PH who have multisystem manifestations, such as multiple peripheral neuropathy, multiserosal cavity effusion, organomegaly and skin changes, POEMS syndrome should be considered, and proper and active treatment of POEMS may reverse PH and improve the prognosis of patients.

Revisión Sistemática Exploratoria sobre Uso de Óxido Nítrico Inhalado para Evaluación de Reactividad Vascular Pulmonar en Laboratorio de Hemodinamia en Sujetos Pediátricos con Hipertensión Pulmonar / Exploratory Systematic Review on the Use of Inhaled Nitric Oxide for Evaluation of Pulmonary Vascular Reactivity in Hemodynamics Laboratory in Pediatric Subjects with Pulmonary Hypertension

Introducción. La hipertensión arterial pulmonar (HAP) es una enfermedad que presenta un elevado índice de mortalidad en la población pediátrica. Para su diagnóstico, el gold standard es la prueba de reactividad vascular pulmonar (PRVP), debido a que permite medir la respuesta vasodilatadora del lecho vascular pulmonar frente a la administración de moléculas con acción terapéutica, como el óxido nítrico inhalado (iNO). Esta prueba al ser positiva se asocia a un mejor pronóstico. En la actualidad existe incertidumbre y falta de consenso sobre la indicación y administración de iNO durante la PRVP. Objetivo. Describir el uso reportado en la literatura sobre iNO en PRVP en sujetos pediátricos con HAP. Métodos. Revisión sistemática exploratoria sensible en bases de datos PubMed, Epistemonikos, Cochrane, Scopus, Lilacs y Scielo, que describen el uso de iNO durante la PRVP en sujetos pediátricos con HAP. Resultados. se identificaron 8.906 artículos, de los cuales se seleccionaron 5 para la revisión cualitativa. La PRVP se realizó durante el cateterismo cardiaco derecho (CCD) en sujetosentre 2 semanas y 18 años de edad. Los diagnósticos fueron HAP primaria, idiopática y asociada a patología cardiaca congénita, cardiomiopatía y enfermedad pulmonar. Esta prueba fue realizada en sujetos sólo con soporte de oxígeno o con sedación profunda en ventilación mecánica invasiva, con dosis variables de oxígeno (21 y 100%) e iNO (3 y 80 ppm), o asociado a otras moléculas como iloprostol®, dilitiazem, sildenafil y/o epoprostenol. La administración de iNO disminuyó presión de arteria pulmonar y la resistencia vascular pulmonar, con mantención de presión arterial sistémica y gasto cardiaco y sin complicaciones asociadas a su uso. Conclusiones. Existen escasos estudios sobre iNO en PRVP pediátrica y con calidad metodológica limitada. El iNO se utiliza como método diagnóstico de vaso reactividad en sujetos pediátricos con HAP asociada a cardiopatía congénita, primaria o secundaria. Los protocolos para su uso son variables con dosis entre 20 y 40 ppm, con o sin uso de oxigeno adicional, con tiempos poco precisos y sin consenso en equipos de administración.

Background. Pulmonary arterial hypertension (PAH) is a disease that has a high mortality rate among the pediatric population. For its diagnosis, the pulmonary vascular reactivity test (PVRT) is considered the "Gold Standard", because it allows to measure the vasodilator response of pulmonary vascular circulation with the administration of molecules with therapeutic action, such as inhaled nitric oxide (iNO). This test, when positive, is associated with a better prognosis of the disease. Currently, there's uncertainty and lack of consensus on the indication and administration of iNO during the PVRT. Objetives. to describe use of iNO in PVRT in pediatric users with PAH reported in the literature. Methods. Scoping review of studies published between 1992 and 2021 in PubMed, Epistemonikos, Cochrane, Scopus, Lilacs and Scielo databases, which describe the use of iNO during PVRT in pediatric users with PAH, in English and Spanish. Primary and secondary studies with a sensitive search strategy were considered. Results. 8,906 articles were identified, 40 were selected by title, 8 by full text, and 5 for final qualitative review. Of the total of articles selected, 3 were primary and 2 secondary studies. PVRT was performed during right heart catheterization (RHC) in a population between 2 weeks and 18 years old. Diagnoses were primary PAH, idiopathic PAH and PAH associated with congenital heart disease, cardiomyopathy and pulmonary disease. This test was carried out in subjects on spontaneous ventilation with oxygen support or with deep sedation in invasive mechanical ventilation, with variable oxygen doses between 21 and 100%, with exclusive use of iNO between 3 and 80 ppm, being more used between 20 and 40 ppm, or associated with other molecules such as iloprostol®, dilithiazim, sildenafil and / or epoprostenol. In all selected studies, administration of iNO decreased PAP (pulmonary artery pressure) and PVR (pulmonary vascular resistance), with maintenance of SBP (systemic arterial blood pressure) and cardiac output. The primary studies were made up of pre and post-test of serial or parallel interventions. The selected studies of iNO in PVRT did not report complications associated with its use. Conclusions. studies on iNO in pediatric PVRT are scarce in number of publications and methodological quality. iNO is used as a diagnostic method of vasoreactivity in pediatric users with PAH associated with congenital, primary, or secondary heart disease. The protocols for its use are variable with recommended doses between 20 and 40 ppm, with or without the use of additional O2, with imprecise times and without consensus in administration equipment. The response to PVRT serves as a guide for the treatment and prognosis of pediatric users with PAH.

Valoración de ecuaciones derivadas del flujo pulmonar y regurgitación tricuspídea: utilidad en el test de vasoreactividad pulmonar / Valuation of equations derived from Pulmonary Flow and Tricuspid Regurgitation: usefulness in Pulmonary Vasoreactivity Testing

RESUMEN: Antecedentes: La presión media arterial pulmonar (PMAP) es una variable hemodinámica indispensable para el diagnóstico, clasificación y pronóstico de la Hipertensión Pulmonar (HP). Su cuantificación se realiza en forma invasiva por cateterismo cardíaco derecho (CCD) y no invasivamente por ecocardiografía Doppler. Masuyama propuso su medición mediante el gradiente transvalvular pulmonar diastólico derivado de la velocidad máxima inicial de la regurgitación pulmonar (∆RPi2) correspondiendo cercanamente a la medición invasiva. Objetivos: Revalidar 3 métodos ecocardiográficos que estiman la PMAP y valorar la utilidad del método de Chemla en el Test de Reactividad Vascular Pulmonar (TRVP). Métodos: Estudio prospectivo, observacional, doble ciego divido en dos etapas. A) o I) 30 pacientes se realizó ecocardiografía Doppler diagnóstica en nuestro centro. Se midieron regurgitación tricuspídea (RT) y tiempo de aceleración pulmonar (TAP) para derivar las siguientes ecuaciones: 1) 0.61xPSAP+1.95 (Chemla) 2) Gradiente presión media RT (∆PmRT) +PAD (presión-aurícula derecha) (Aduen) y 3) 79-0.45xTAP o 90-0.60xTAP, según sea el valor del TAP. B) o II) 10 pacientes enrolados para realizar el TRVP comparando la medición ecocardiográfica (Chemla) con CCD. Resultados: En la primera parte del estudio se encontró alta correlación entre las 3 ecuaciones: ChemlaAduen, R2=0.91; Chemla-Kitabatake, R2=0.87; Aduen-Kitabatake, R2=0,91. En la segunda parte comparando la PMAP-Chemla y Cateterismo derecho (CD) obtuvimos alta correlación: en tiempo 0, 30 min y recuperación:(R2=0.87, 0.99, 0.98, respectivamente). Ambas partes del estudio mostraron límites de concordancia satisfactoria con valor medio de la diferencia entre los métodos cercano a 1 en el t30 y tR del TRVP. Conclusión: los métodos dependientes de la medición de la RT son efectivos y confiables para estimar la PMAP. El método de Chemla es útil en el TRVP.

ABSTRACTS: Background: Mean Pulmonary arterial pressure (PMAP)is an indispensable hemodynamic variable for the diagnosis, classification and prognosis of Pulmonary Hypertension (PH). Its quantification is performed invasively by cardiac catheterization and non-invasively by Doppler echocardiography. Masuyama proposed its measurement by the transvalvular diastolic pulmonary gradient derived from the initial maximum velocity of pulmonary regurgitation(ΔPRi2) corresponding closely to the invasive measurement. Objectives: to compare 3 known echocardiographic methods to estimate MPAP and demonstrate the usefulness of the Chemla method in the Pulmonary Vascular Reactivity Test (PVRT). Methods: prospective, observational, double-blind study divided into two stages. A) 30 patients underwent diagnostic Doppler echocardiography. Tricuspid regurgitation (TR) and pulmonary acceleration time (PAT) were measured to derive the equations: 1) 0.61xSPAP + 1.95 (Chemla) 2) Gradient mean pressure TR (ΔPmTR) + RAP (right atrium pressure) (Aduen).3) 79-0.45xPAT o 90-0.60xPAT depending on the value of PAT. B) 10 patients enrolled to PVRT comparing the echocardiographic measurement (Chemla) with right catheterization. Results: in the first part of the study a high correlation between the 3 equations was found : ChemlaAduen, R2 = 0.91; Chemla-Kitabatake, R2=0.87; Aduen-Kitabatake, R2=0.91. In the second part comparing the MPAP-Chemla and RHC we obtained a high correlation in time 0, 30 min and recovery: (R2=0.87,0,99,0.98, respectively). Both parts of the study showed satisfactory limits concordance with mean value of the difference between the methods close to 1 in the t30 and tR of the TRVP. Conclusion: the methods dependent on the measurement of the TR are effective and reliable for estimating MPAP. The Chemla method is useful in the PVRT.

Prevalence of Pulmonary Arterial Hypertension in Korean Adult Patients with Systemic Sclerosis: Result of a Pilot Echocardiographic Screening Study

BACKGROUND: Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with systemic sclerosis (SSc). Early detection and prompt treatment of PAH associated with SSc (SSc-PAH) result in better prognosis. We conducted echocardiographic study to presume the prevalence of PAH in Korean adult SSc patients and to diagnose SSc-PAH in their early stages with right heart catheterization (RHC). METHODS: We performed free of charge echocardiographic study including 37 adult SSc patients at the Chungnam National University Hospital. The possibility of PAH is determined by the estimation of pulmonary arterial pressure by peak tricuspid regurgitation velocity of > 3.0 m/s. Patients with possible PAH were recommended to undergo RHC to confirm the diagnosis. RESULTS: In 37 patients, 8 patients were suspected with PAH. Among them, 6 patients agreed to be examined with RHC, and 4 were confirmed with PAH. The prevalence of possible PAH was 21.6% (8 of 37 patients), and that of confirmed PAH was 10.8% (4 of 37 patients). Four patients who were confirmed with SSc-PAH through RHC have been treated with specific pulmonary vasodilators and maintained stable. CONCLUSION: Eight patients (21.6%) were possible PAH and 4 (10.8%) were diagnosed as SSc-PAH by RHC after the echocardiographic screening study of 37 adult SSc patients.

Optimization of detection method of pulmonary arterial pressure / 中国药理学通报

Aim To optimize the traditional method of right catheterization in rats and establish a rapid , stable and reliable method of the right heart catheter guided intubation to measure pulmonary artery pressure. Methods Nighty male wistar rats were used to optimize the method of detection of pulmonary arte-rial pressure. Three catheter namely PE50, PU I, and PU II were used for choosing the best intubation. The new technology of right catheterization was established and used for the research of pulmonary arterial hypertension. Results The PU I catheter was obviously better than PE50 and PU II catheter in the success rate and measurement time ( P <0. 05 ) . The method of right heart catheter guided intubation was significantly superior to the traditional right heart direct intubation (P<0. 05 or P<0. 01). After improving the right catheterization, the detection of hemo-dynamic indexes in PAH-model rat was successful with regular pressure curve and reliable experimental data. Conclusions The right heart catheter guided intubation method has a high suc-cess rate and it can detect the pulmonary artery pressure quick-ly, easily, and can help other researchers to complete experi-ment as efficiently as possible.

Visão geral do diagnóstico e identificação de pacientes de risco / Overview of the diagnosis and identification of at-risk populations

A hipertensão pulmonar é um estado hemodinâmico e fisiopatológico que pode ser encontrado em diversas condições clínicas e quando presente, está associada ao aumento da morbimortalidade. Somados à etiologia diversa estão os achados clínicos inespecíficos. Esses dois aspectos contribuem para o atraso no diagnóstico e, por conseguinte, no início do tratamento. Daí a importância da sistematização da avaliação diagnóstica aliada à suspeição clínica na investigação de dispneia, sobretudo nas populações de risco, visando o diagnóstico etiológico correto e a instituição de medidas terapêuticas adequadas. O seguimento desses pacientes deverá ser feito também de forma sistemática, associado a ferramentas complementares que permitam a avaliação adequada da gravidade da doença...

Pulmonary hypertension is a hemodynamic and pathophysiological state that can be find in various clinical conditions and is associated with increased morbidity and mortality. As symptoms are nonspecific and the condition is uncommon, usually the diagnosis is delayed and, consequently, the start of treatment.Hence, the importance of systematization of diagnostic evaluation combined with clinical suspicion in dyspnea research, especially in at-risk populations, in order to achieve the correct etiologic diagnosis and institution of appropriate therapeutic measures. The follow-up of these patients also should be do systematically, together with complementary tools that allow the proper assessment of disease severity...

Changes features of middle hepatic vein flow velocity waveform in patients with pulmonary hypertension caused by congenital heart disease / 中华医学超声杂志（电子版）

were measured at the end of inspiratory.ResultsThe differences of following parameters were statistically significant between the healthy control group, mild PH group, moderate PH group and severe PH group: velocity time integral of ventricular systolic wave (SVTI), velocity time integral of ventricular diastolic wave (DVTI), AR, AR/S, ARVTI/SVTI, AR/(S+D), ARVTI/(SVTI+DVTI,F=2.940, 2.838, 3.373, 7.681, 3.478, 12.052, 4.806;P<0.05,<0.05,<0.05,<0.01,<0.05,<0.01,<0.01). Correlation analysis showed that ratio of AR/(S+D) was positively correlated with pulmonary artery mean pressure (r= 0.575,P<0.01). ConclusionsThe ratio of AR/(S+D) of MHV Doppler flow spectra was correlated with pulmonary artery mean pressure. The ratio increased along with the increasing of pulmonary pressure in CHD patient. The Doppler echocardiographic detection of MHV flow had a certain reference value for the diagnosis of PH. The ratio of AR/(S+D) could be a new non-invasive parameter for evaluating PH.

Relationship between the size of ostium secundum atrial seplal defect and the pulmonary arterial pressure in children less than 5 years of age / 介入放射学杂志

Objective to investigate the relationship between the size of ostium secondary atrial septal defect (ASD) and the pulmonary arterial pressure (PAP) in children less than 5 years of age. Methods During the period from April 2000 to January 2011, a total of 189 child patients less than 5 years of age with ostium secondary ASD were admitted to General Hospital of Shenyang Military Command. Under general anaesthesia with ketamine cardiac catheterization was performed, PAP was measured, and percutaneous occlusion of ASD was carried out in all patients. The clinical indexes, including sex, age, body height, body weight, body surface area, diameter of ASD defect, heart- to- thorax ratio, the systolic, diastolic and mean pressure of the pulmonary artery, etc. were determined. The patients were followed up for one year and postoperative cardiac ultrasonography was performed to check the results. The patients were divided into groups according to the defect size. Results The 189 patients consisted of 77 males and 112 females with a male-to-female ratio of 1 ∶ 1.5. The mean age was (4.1 ± 0.9) years old, ranging from 2 to 5 years old. The mean weight was (17.2 ± 3.6) kg, ranging from 10.0 to 30.0 kg. The mean height was (104.9 ± 9.2) cm, ranging from 77 to 135 cm. The mean body surface area (BSA) was (0.71 ± 0.10) m2, ranging from 0.46 to 1.02 m2. The mean size of ASD was (12.6 ± 4.8) mm, ranging from 5 to 29 mm. The mean size of ASD, which was modified by BSA, was (18.0 ± 7.0) mm/m2, ranging from 5.3 to 38.9 mm/m2. The mean systolic PAP was (41.1 ± 8.9) mmHg with a range of 15 - 67 mmHg. The mean diastolic PAP was (16.8 ± 6.5) mmHg with a range of 3 - 45 mmHg. The mean PAP was (24.9 ± 6.7) mmHg with a range of 12 - 48 mmHg. One hundred and fifty- nine patients (89.4%) had pulmonary arterial hypertension (PAH) which was determined by right heart catheterization, but no patient showed PAH when the pulmonary arterial pressure was measured by echocardiography before the procedure as well as 1, 3, 6, 12 months after the procedure. No definite correlation existed between the size of ASD and the pulmonary artery pressure (P > 0.05). Conclusion Pulmonary artery pressure measured by right heart catheterization has no definite correlation with the size of ASD in children less than 5 years of age. Pulmonary artery pressure obtained from right heart catheterization is higher than that determined by cardiac ultrasonography, which may be caused by the effect of ketamine when general anaesthesia is used in performing right heart catheterization.

Hipertensión pulmonar: la mirada del especialista / Pulmonary hypertension: the specialist opinion / Hipertensão pulmonar: a opinião do especialista

La hipertensión pulmonar constituye una de las enfermedades con creciente prevalencia en la actualidad, con pronóstico ominoso y deterioro en la calidad de vida de los pacientes. El fracaso de la función del ventrículo derecho, consecuencia del remodelado en el lecho vascular pulmonar, que provoca un estado hemodinámico caracterizado por elevación sostenida de la presión en el circuito arterial pulmonar, es el resultado final del aumento de la poscarga. En las últimas décadas, los avances en el conocimiento de esta enfermedad, así como las nuevas investigaciones, han logrado brindar información para llegar al diagnóstico precoz y el tratamiento más adecuado. Ambos constituyen la base para lograr un cambio en la evolución de esta enfermedad, mejorando la calidad de vida y supervivencia de los pacientes. Si bien, es importante el conocimiento por parte de los equipos de salud, la derivación a centros especializados en el manejo de estos pacientes con médicos capacitados contribuirá significativamente a cambiar el curso evolutivo natural de esta enfermedad. La presente revisión tiene como objetivo brindar información actualizada, aportando datos que permitan facilitar la detección precoz, el diagnóstico y el tratamiento de estos pacientes, permitiendo una correcta atención o, en su defecto, realizar la derivación a centros especializados de referencia.

Pulmonary hypertension is a disease with currently increasing relevance, poor prognosis and impaired quality of life of patients. The right heart failure is the end result of the remodeling in pulmonary vascular tree causing a hemodynamic state with sustained elevation of pressure in pulmonary arteries and the subsequent afterload increase. In recent decades, advances in our understanding of this disease, as well as new research has been able to provide information to make an early diagnosis and the most appropriate treatment. Both are the basis for change in the evolution of the disease, improving patient's quality of life and survival. It's also important to change the natural history of the disease, the knowledge of health team and the timely consultation with clinics and physicians with special trainee in management of these patients. This review aims to provide updated information, providing data to facilitate the early detection, diagnosis and treatment of these patients allowing a proper attention or, alternatively, make referrals to specialized referral centers.

A hipertensão pulmonar é uma das doenças com maior relevância no momento, com prognóstico desfavorável nos pacientes e deterioração da qualidade de vida. A falha do ventrículo direito, resultado da remodelação do leito vascular pulmonar causando estado hemodinâmico com elevação sustentada da pressão nas artérias pulmonares e ao aumento da pós-carga é o resultado final. Nos últimos tempos, avanços no conhecimento desta doença bem como a investigação têm fornecido informações para obter o diagnóstico precoce e o tratamento mais adequado. Ambos são a base para as alterações sobre a evolução desta doença, melhorando a qualidade de vida e sobrevida. Embora seja importante o conhecimento das equipes de saúde, ir à clínica e os médicos com estagiário especial na gerência destes pacientes é uma contribuição significativa para alterar a história natural dessa doença. Esta revisão tem como objetivo fornecer informações atualizadas, fornecendo dados para facilitar a detecção precoce, diagnóstico e tratamento destes pacientes permitindo uma atenção adequada ou, em alternativa, fazer encaminhamentos para centros de referência especializados.

Exploración de la hemodinámica en la hipertensión pulmonar mediante cateterismo cardíaco derecho / Exploration of hemodynamics in pulmonary hipertension by right heart catherization

El diagnóstico final de hipertensión pulmonar se realizamediante cateterismo cardíaco derecho. Existe hipertensiónpulmonar cuando la presión media en la arteria pulmonarsupera los 25 mmHg en situación basal. Una adecuadaexploración hemodinámica permite encuadrar la hipertensiónpulmonar en algunos de los cinco grupos de la clasificaciónclínica actual. Se dan las recomendaciones para los diferentesespecialistas de cuándo efectuar el cateterismo derecho, quéparámetros se deben de registrar y como realizar e interpretaruna prueba aguda de vasorreactividad en la hipertensiónarterial pulmonar.

The final diagnosis of pulmonary hypertension is made byright heart catheterization. Pulmonary hypertension is presentwhen the average pressure in the pulmonary artery exceeds 25mm Hg at baseline. Proper hemodynamic assessment allowsclassification of pulmonary hypertension into one of five clinicalcategories. Recommendations are provided for specialists, whento conduct right heart catheterization, which parameters mustbe recorded and how to perform and interpret a test for acutevasoreactivity in pulmonary arterial hypertensio.