Nomgram model for individual prediction of coronary heart disease with pulmonary hypertension / 公共卫生与预防医学

Objective To establish an individual Nomgram model for predicting the risk of coronary heart disease complicated with pulmonary hypertension. Methods From January 2017 to December 2021 , 352 patients with coronary heart disease (CHD) complicated with pulmonary hypertension in our hospital were selected, and 352 patients with coronary heart disease but without pulmonary hypertension were selected as the control group. The clinical baseline data of the two groups were analyzed first, and then logistics multivariate analysis was performed. To explore the risk factors of coronary heart disease complicated with pulmonary hypertension, the Nomgram model was established to predict the risk, and the predictive value of the model was tested by receiver characteristic curve (ROC). Results Logistics multivariate analysis showed that alcoholism, smoking, stroke history, hypertension course, CHD course, PASP, HCT, PaCO2, D-dimer, NIHSS score and low PaO2 were all independent risk factors for CHD complicated with pulmonary hypertension. Nomgram model prediction results for patients with coronary heart disease showed that Alcohol abuse, smoking, stroke history, duration of hypertension (5.66 years), duration of coronary heart disease (2.12 years), NIHSS (12.33 points), PASP (75.22mmHg), HCT (33.22%), PaCO2 (56.11mmHg), D-dimer (255.12μg/L), PaO2 (56.22mmHg) is a risk factor for coronary heart disease complicated with pulmonary hypertension. ROC curve showed that the area under the prediction curve of Nomgram model for coronary heart disease complicated with pulmonary hypertension was 0.675. Conclusion Nomgram model can predict pulmonary hypertension in patients with coronary heart disease to a certain extent.

Análisis ecocardiográfico de la variabilidad de la presión sistólica arterial pulmonar en la hipertensión pulmonar / Echocardiographic analysis of pulmonary arterial systolic pressure in pulmonary hypertension

Resumen Introducción: La confiabilidad de la presión sistólica arterial pulmonar por ecocardiografía transtorácica se encuentra limitada por su variabilidad para definir la hipertensión pulmonar. Objetivo: Conocer la variabilidad en la presión sistólica arterial pulmonar estimada por ecocardiografía en la hipertensión pulmonar. Métodos: En el periodo 2016-2020 se captaron sujetos con hipertensión pulmonar que tuvieron estimada la presión sistólica de la arteria pulmonar por ecocardiografía transtorácica y por cateterismo cardiaco derecho. Se obtuvieron sus variables demográficas. Los datos se analizaron con el estadístico descriptivo de Bland-Altman y el coeficiente de correlación intraclase (intervalo de confianza al 95%). Resultados: Se estudiaron 152 sujetos, edad 60 ± 12 años. Índice de masa corporal 27.64 ± 4.69 kg/m2. La presión sistólica de la arteria pulmonar por ecocardiografía transtorácica 58.99 ± 18.62 vs. cateterismo cardiaco 55.43 ± 16.79. Diferencia media (sesgo) -3.6 (29.1, -36.2) y coeficiente de correlación intraclase 0.717 (0.610, 0.794). Conclusiones: La variabilidad es amplia y el acuerdo es sustancial con la presión sistólica de la arteria pulmonar. Se aconseja estimarla solo como tamizaje de la hipertensión pulmonar.

Abstract Introduction: The reliability of pulmonary arterial systolic pressure by transthoracic echocardiography is limited by its variability to define pulmonary hypertension. Objective: To know the variability of pulmonary arterial systolic pressure estimated by echocardiography in pulmonary hypertension. Their demographic variables were obtained. Methods: From 2016-2020 subjects with pulmonary hypertension were recruited, with pulmonary artery systolic pressure estimated by transthoracic echocardiography and by right heart catheterization. Data were analyzed using the Bland-Altman descriptive statistic and the intraclass correlation coefficient (95% confidence interval). Results: 152 subjects, age 60 ± 12 years, were studied. Body mass index 27.64 ± 4.69 kg/m2. The pulmonary artery systolic pressure estimated by transthoracic echocardiography 58.99 ± 18.62 vs. cardiac catheterization 55.43 ± 16.79 mmHg. Mean difference (bias) -3.6 (29.1, -36.2) and intraclass correlation coefficient 0.717 (0.610, 0.794). Conclusions: Variability is wide, and agreement is substantial for pulmonary artery systolic pressure. It is recommended to estimate only as screening for pulmonary hypertension.

Subcostal right ventricular free wall strain in patients with pulmonary hypertension / Strain subcostal de la pared libre del ventriculo derecho en pacientes con hipertensión pulmonar

Abstract Right ventricular longitudinal strain (RVLS) is frequently used as a measure of right ventricular systolic function. Abnormal RV strain is associated with poor prognosis in patients with pulmonary hyper tension (PH); however, the measure is not always easy to obtain in patients with poor apical acoustic windows. Objective: This study aims to analyze the RVLS and determine if there is a difference when measured from the apical and subcostal views. Methods: In this cross-sectional study, we analyzed 22 adult outpatients (≥ 18 years old), 81% female, mean age 49.9 ± 17.3 years, with a diagnosis of PH using right heart catheterization, followed from January 2016 to January 2020. Results: RVLS measured in the RV free wall from the apical views was -15% (-19% to -10%) and subcostal views -14.5% (-18% to -11%) were highly correlated (Person's r = 0.969, p < 0.0001). Segment by segment analysis did not show significant differences either: basal four-chamber vs. sub costal view was -16.5% (-21% to -11%) vs. -15.5% (-20% to -11%), p = 0.99, mid four-chamber view vs. subcotal view was -16.5% (-21% to -12%) vs. -16.5% (-20% to -11%), p = 0.87, apical four-chamber view vs. subcostal view was -12% (-18% to -8%) vs. -13.5% (-19% to -10%), p = 0.93. Conclusion: Subcostal RVLS free wall is a feasible and accurate alternative to conventional RVLS free wall from the apical view in patients with pulmonary hypertension and could be useful in patients with poor acoustic apical four-chamber windows.

Resumen El strain longitudinal del ventrículo derecho (SLVD) permite medir la función sistólica del ventrículo derecho (VD). La disminución del strain (deformación) del VD se asocia con mal pronóstico en pacientes con hipertensión pulmonar (HP), pero no siempre es fácil de obtener en pacientes con mala ventana acústica apical. Objetivo: Este estudio tiene como objetivo analizar el SLVD y determinar si las vistas apical y subcostal son comparables. Métodos: En este estudio transversal, se incluyeron 22 pacientes adultos ambulatorios (≥18 años), 81% mujeres, edad promedio 49.9 ± 17.3 años, con diagnóstico de HP mediante cateterismo cardíaco derecho, seguidos desde enero de 2016 hasta enero de 2020. Se midió la deformación de la pared libre del ventrículo derecho desde las vistas de cuatro cámaras apical y cuatro cámaras subcostal. Resultados: El SLVD medido en la pared libre del VD desde la vista apical fue -15% (-19% a -10%) vs. -14.5% (-18% a -11%) cuando se midió desde la vista subcostal (p = 0,99). El análisis segmento por s egmento tampoco mostró diferencias significativas: el segmento basal apical vs. subcostal fue -16.5% (-21% a -11%) vs. -15.5% (-20% a -11%), p = 0.99, el segmento medio apical vs. la vista subcotal fue -16.5% (-21% a -12%) vs. a -16.5% (-20% a -11%), p = 0.87, el segmento apical vs. la vista subcostal fue -12% (-18% a -8%) frente a -13.5% (-19% a -10%), p = 0.93. Conclusión: En pacientes con HP, el SLVD obtenido en la pared libre subcostal es una alternativa útil en los casos con ventana acústica apical subóptima.

El péptido Pro-BNP como predictor de daño cardíaco en pacientes con esclerosis sistémica / Pro-BNP Peptide as a Predictor of Cardiac Damage in Systemic Sclerosis Patients

Introducción: La esclerosis sistémica es una enfermedad crónica del tejido conectivo de carácter autoinmune, de causa desconocida, que produce exceso de colágeno provocando fibrosis en la piel, con afectación de órganos internos. Los anticuerpos frecuentes son: antitopoisomerasa 1 y anticentrómero. Las formas clínicas son la cutánea difusa y cutánea limitada. La prevalencia de la afectación cardíaca varía entre un 8-28 por ciento y en fases tardías la presencia de signos y síntomas cardiovasculares es de mal pronóstico y una de las principales causas de mortalidad. Objetivo: Determinar la asociación entre afectación cardíaca y las formas clínicas, el pro-péptido natriurético cerebral N-terminal (NT-proBNP) y los autoanticuerpos en la esclerosis sistémica. Métodos: Se realizó un estudio descriptivo transversal de un universo de 140 pacientes, la muestra fue de 54 pacientes. Se le realizó ecocardiograma, niveles de NT-proBNP, anti-scl 70, anticentrómero y determinación de formas clínicas a todos los pacientes que cumplieron criterios de inclusión y que fueron atendidos en el Hospital: Hermanos Ameijeiras Habana-Cuba, entre julio de 2016 a diciembre de 2017. Resultados: La edad media fue 51,76 ± 12,82. Sexo femenino en un 96,3 por ciento. El 72,2 por ciento era piel blanca. La afectación cardíaca de la EScd fue de 77,5 por ciento, hormona NT-proBNP tuvo niveles elevados en un 55,0 por ciento. Los anti-scl-70 estuvieron negativos en el 70 por ciento (n = 28) de los pacientes con afectación cardíaca. El anti-centrómero estuvo negativo en el 95,0 por ciento (n = 38). Conclusiones: Se determinó que la afectación cardíaca en pacientes con esclerosis sistémica, es independiente de las formas clínicas y de la presencia de autoanticuerpos. Los pacientes que tuvieron los niveles séricos de NT-proBNP elevados presentaron afectación cardíaca(AU)

Introduction: Systemic sclerosis is a chronic autoimmune connective tissue disease of unknown cause, which produces excess collagen causing fibrosis in the skin, affecting internal organs. Common antibodies are antitopoisomerase 1 and anticentromere. The clinical forms are diffuse cutaneous and limited cutaneous. The prevalence of cardiac involvement varies between 8-28percent and in late stages the presence of cardiovascular signs and symptoms have poor prognosis and one of the main causes of mortality. Objective: To determine the association between cardiac involvement and clinical forms, N-terminal pro-brain natriuretic peptide (NT-proBNP) and autoantibodies in SSc. Methods: A cross-sectional descriptive study of a universe of 140 patients was carried out. Fifty four patients made up the sample. An echocardiogram, NT-proBNP, Anti-scl 70, anticentromere levels and determination of clinical forms were performed on all patients who met the inclusion criteria and who were treated at Hermanos Ameijeiras hospital in Havana, Cuba, from July 2016 to December 2017. Results: The mean age was 51.76 ± 12.82. Female sex accounted 96.3percent. 72.2percent were white skinned. Cardiac involvement of EScd was 77.5percent, NT-proBNP hormone had high levels in 55.0percent. Anti-scl-70 were negative in 70percent (n=28) of patients with cardiac involvement. Anti-centromere (ACT) was negative in 95.0percent (n=38). Conclusions: Cardiac involvement in patients with SS is independent of the clinical forms and the presence of autoantibodies. Patients with elevated NT-proBNP serum levels had cardiac involvement(AU)

An 8-year-old boy with diffuse cystic pulmonary tuberculosis: An intriguing story

Diffuse cystic lung disease due to pulmonary tuberculosis (TB) is rare. We describe an 8-year-old boy who presented with acute onset respiratory distress while on a compliant anti-tubercular treatment for a recently diagnosed pulmonary TB. On clinical examination, hypoxemia, clubbing, and features of the right-sided heart failure were observed. High-resolution computed tomography of the chest revealed extensive cystic lung parenchymal changes with ground glassing and consolidation, and echocardiography indicated the presence of pulmonary arterial hypertension. His treatment included supplemental oxygen, sildenafil, prednisolone, and anti-tubercular drugs. At the two-year follow-up, the patient showed complete clinical recovery and resolution of cysts on the chest X-ray.

Evaluación de la función ventricular en la hipertensión pulmonar por resonancia magnética cardíaca / Evaluation of ventricular function in pulmonary hypertension by cardiac magnetic resonance

Resumen Objetivo: Evaluar la función del ventrículo derecho (VD) e izquierdo (VI) en la hipertensión pulmonar (HP) mediante resonancia magnética cardíaca (RMC). Material y métodos: En pacientes con (grupo HP; n = 9) y sin (grupo control; n = 9) HP se evaluó volumen telediastólico (VTD) y telesistólico (VTS) y fracción de eyección (FE) de ventrículo derecho (VD) e izquierdo (VI), área de aurícula derecha (AD) e izquierda y diámetro de arteria pulmonar (AP). Resultados: En HP, el VD presentó mayor VTD y VTS y menor FE (HP 52 ± 5% vs. control 64 ± 2%; p < 0,05). Solo en HP se observó movimiento anormal del tabique interventricular y realce tardío en los puntos de inserción del VD en VI. En HP aumentó el área de AD y el diámetro de AP. En VD, solo en HP, la FE se correlacionó negativamente con VTD (Pearson r: –0,8290; p < 0,01) y VTS (Pearson r: –0,7869; p < 0,05). Conclusiones: La evaluación de pacientes con HP mediante RMC demuestra alteraciones fisiológicas y anatómicas de las cavidades derechas con disminución de la FE del VD que también afecta la interrelación VD/VI. Se recalca la importancia de una evaluación temprana y secuencial del VD con RMC para valorar la mejor estrategia terapéutica para cada caso en particular.

Abstract Objective: To evaluate the function of the right ventricle (RV) and left ventricle (LV) in pulmonary hypertension (PH) through cardiac magnetic resonance imaging (CMR). Material and method: In patients with (PH group; n = 9) and without PH (control group; n = 9), end-diastolic volume (EDV) and end-systolic volume (ESV) and ejection fraction (EF) of right (RV) and left (LV) ventricle, area of the right (RA) and left (LA) atrium and diameter of the pulmonary artery (PA) were evaluated. Results: In PH, the RV increased EDV and ESV and decreased EF (PH: 52 ± 5% vs. control: 64 ± 2%; p < 0.05). Abnormal movement of the interventricular septum and late enhancement in the insertion points of the RV in the LV were only observed in HP. HP increased the area of RA and the diameter of PA. In LV, only in HP, EF was negatively correlated with EDV (Pearson r: –0.8290; p < 0.01) and ESV (Pearson r: –0.7869; p < 0.05). Conclusions: CMR evaluation of patients with PH demonstrates physiological and anatomical alterations of the right cavities with decreased EF in RV that also affects the RV/LV interrelationship. The importance of an early and sequential evaluation of the RV with CMR is emphasized to assess the best therapeutic strategy for each particular case.

Estudo Morfofuncional do Átrio Esquerdo Isolado de um Modelo Experimental de Hipertensão Pulmonar em Ratos / Isolated Left Atrium Morphofunctional Study of an Experimental Pulmonary Hypertension Model in Rats

Resumo Fundamento A alta incidência de arritmias atriais na hipertensão pulmonar (HP) pode estar associada a um prognóstico ruim, e o átrio esquerdo (AE) pode desempenhar um papel neste quadro. Um achado importante nos estudos de HP é que a remodelação do AE é subestimada. Objetivo Este estudo investigou a morfologia e a função mecânica do AE, bem como a suscetibilidade ao desenvolvimento de arritmias em um modelo de HP induzida por monocrotalina (HP-MCT). Métodos Ratos Wistar com 4 semanas de idade receberam 50 mg/kg de MCT. Foram realizadas análises eletrocardiográficas e histológicas para avaliar o estabelecimento do modelo de HP-MCT. O tecido foi montado em banho de órgão isolado para caracterizar a função mecânica do AE. Resultados Em comparação com o grupo controle, o modelo de HP-MCT apresentou hipertrofia do AE e alterações da atividade elétrica cardíaca, conforme evidenciadas pelo aumento da duração da onda P, PR e intervalo QT. Não foi observada alteração no inotropismo do AE isolado de ratos com HP-MCT; no entanto, o tempo para atingir a contração máxima foi atrasado. Finalmente, não observamos diferença na suscetibilidade à arritmia no AE dos ratos com HP-MCT após o protocolo de estimulação intermitente. Conclusão A remodelação morfofuncional do AE não levou ao aumento da suscetibilidade à arritmia ex vivo após a aplicação do protocolo de estimulação intermitente.

Abstract Background The high incidence of atrial arrhythmias in pulmonary hypertension (PH) might be associated with poor prognosis, and the left atrium (LA) may play a role in this. An important finding in PH studies is that LA remodeling is underestimated. Objective This study investigated LA morphology and mechanical function, as well as the susceptibility to develop arrhythmias in a monocrotaline-induced PH (MCT-PH) model. Methods Wistar rats aged 4 weeks received 50 mg/kg of MCT. Electrocardiography and histology analysis were performed to evaluate the establishment of the MCT-PH model. The tissue was mounted in an isolated organ bath to characterize the LA mechanical function Results Compared with the control group (CTRL), the MCT-PH model presented LA hypertrophy and changes in cardiac electrical activity, as evidenced by increased P wave duration, PR and QT interval in MCT-PH rats. In LA isolated from MCT-PH rats, no alteration in inotropism was observed; however, the time to peak contraction was delayed in the experimental MCT-PH group. Finally, there was no difference in arrhythmia susceptibility of LA from MCT-PH animals after the burst pacing protocol. Conclusion The morphofunctional remodeling of the LA did not lead to increased susceptibility to ex vivo arrhythmia after application of the burst pacing protocol.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension / Perda de resposta a bloqueadores dos canais de cálcio após acompanhamento prolongado em pacientes com hipertensão arterial pulmonar idiopática

ABSTRACT Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

RESUMO Pacientes com hipertensão arterial pulmonar (HAP) idiopática com resposta positiva ao teste de vasorreatividade aguda e resposta clínica a bloqueadores dos canais de cálcio (BCC) durante no mínimo um ano são tradicionalmente denominados "respondedores verdadeiros". No entanto, pouco se sabe sobre a manutenção da resposta a BCC durante períodos mais longos. Avaliamos a perda de resposta a BCC após tratamento prolongado em uma coorte de pacientes com HAP idiopática previamente considerados respondedores verdadeiros. Nossos dados sugerem que pacientes com HAP idiopática podem deixar de apresentar resposta clínica a BCC mesmo depois de um ano de estabilidade clínica, reforçando a necessidade de reavaliação multidimensional constante para avaliar a necessidade de terapias específicas para HAP e classificar esses pacientes corretamente.

The mechanism of bone morphogenetic protein 2 regulating pulmonary vascular remodeling in pulmonary hypertension / 中国医师进修杂志

Objective:To explore the mechanism of bone morphogenetic protein 2 (BMP-2) regulating pulmonary vascular remodeling in pulmonary hypertension (PH).Methods:Pulmonary artery smooth muscle cells (PASMC) groups: control group, PH group, PH+BMP-2 group, PH+BMP-2+ small interfering BMP receptor(si-BMPR)-Ⅰa group, PH+BMP-2+ si-BMPR-Ⅰb group, PH+BMP -2+si-BMPR-Ⅱ group. In vitro PH model was induced by hypoxia. The three BMP-2 receptors were silenced by the transfection of si-BMPR-Ⅰa, si-BMPR-Ⅰb and si-BMPR-Ⅱ plasmids, respectively. Cell proliferation and apoptosis in each group were detected, transient receptor potential ion channel C1/6 (TRPC1/6), p21 mRNA and protein levels, and intracellular Ca 2+ concentration were detected. Results:The intracellular Ca 2+ concentration in the PH group was higher than that in the control group: (785.15 ± 44.26) nmol/L vs. (224.15 ± 15.87) nmol/L, the and apoptosis rate was lower than that in the control group: (3.15 ± 0.22)% vs. (7.31 ± 0.45)%, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP-2 group was (297.64 ± 21.46) nmol/L, and was lower than that in the PH group, and apoptosis rate was (6.88 ± 0.75)%, and was higher than that in the PH group, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP-2+si-BMPR-Ⅰa group, PH+BMP-2+ si-BMPR-Ⅰb group, PH+BMP -2+si-BMPR-Ⅱ group was (412.31 ± 29.57), (384.34 ± 30.66), (695.23 ± 39.85) nmol/L, and was higher than that in the PH+BMP-2 group, and apoptosis rate was (4.10 ± 0.27)%, (4.26 ± 0.28)%, (3.33 ± 0.24)%, and was lower than that in the PH+BMP-2 group, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP -2+si-BMPR-Ⅱ group was higher than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+ si-BMPR-Ⅰb group, the apoptosis rate was lower than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+ si-BMPR-Ⅰb group, there were statistical differences ( P<0.05). Conclusions:BMP-2 mainly inhibits the expression of TRPC1/6 by interacting with the receptor BMPR-Ⅱ, inhibits the influx of Ca 2+ and promotes the expression of p21, thereby inhibiting the proliferation of PASMC and promoting apoptosis, participating in pulmonary vascular remodeling in PH.

The predictive value of CT pulmonary angiography combined with echocardiography for the degree of pulmonary hypertension / 西安交通大学学报(医学版)

【Objective】 To compare the value of CT pulmonary angiography (CTPA) and echocardiography in predicting the degree pulmonary hypertension (PH). 【Methods】 Fifty-four patients in our hospital who underwent right heart catheterization, CTPA and echocardiography for suspected or confirmed PH from November 2013 to April 2021 were retrospectively recruited. Pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (PAMP) were measured by right heart catheterization. According to PAMP, the patients were divided into non-PH group and mild, moderate, and severe PH groups. The three-dimensional model of the pulmonary artery was obtained by computer-aided segmentation, and the best fitting circle diameter (Dfit), inscribed circle diameter (Dmin), circumscribed circle diameter (Dmax), hydraulic diameter (Dh), cross-sectional area (Area), circumference (Scf), and the largest area and largest short diameter of the right ventricle were measured. Echocardiography was used to estimate PASP. The differences in the above parameters between different PH groups were compared, the correlations of the above parameters with PASP and PAMP were analyzed, and statistically significant indicators were included to establish three predictive models of PAMP (Model 1: CTPA pulmonary artery; Model 2: CTPA pulmonary artery+CTPA right ventricle; Model 3: CTPA pulmonary artery+CTPA right ventricle+echocardiography), and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance of the three models. 【Results】 Some parameters of main pulmonary artery (Dfit, Dmin, Dmax, Dh, Area, Scf), right pulmonary artery (Dmax, Dh, Area, Scf), left pulmonary artery (Dfit), and right ventricular short diameter increased with the increase of PAMP (P<0.05). Dfit, Dmin, Dh, and area of main pulmonary artery, right pulmonary artery and left pulmonary artery were positively correlated with PASP and PAMP (P<0.05). Right ventricular short diameter and right ventricular maximum area were positively correlated with PASP (P<0.05), and right ventricular short diameter was positively correlated with PAMP (P<0.05). The estimated value of pulmonary artery systolic blood pressure in echocardiography was positively correlated with PASP and PAMP (P<0.05). Model 1, Model 2 and Model 3 could all be used to identify mild PH and moderate PH, among which Model 3 had the best performance in identifying non-PH and mild PH, moderate PH and severe PH. 【Conclusion】 CTPA and echocardiography are helpful in assessing the degree of PH, and the combination of the two has better accuracy in distinguishing non-PH from mild PH, moderate and severe PH.

Chronic Thromboembolic Pulmonary Hypertension and ChronicThromboembolic Pulmonary Disease / 罕见病研究

Chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) are diseases that occur after acute pulmonary embolism resulting from residual and organized intra-pulmonary thrombus, with or without pulmonary hypertension(PH). The prognosis of these diseases has been dramatically improved with the continuous progress of treatment and the updated concept of the comprehensive treatment strategy. However, there is a lack of awareness of these diseases among medical practitioners, and a lack of epidemiological data in China, with unknown pathogenesis and non-specific clinical manifestations. Therefore, it is easy to misdiagnosis, underdiagnosis and delay diagnosis in clinical practice. To enhance the understanding of medical personnel, this paper summarizes the definition, epidemiology, pathology, pathogenesis, diagnosis and treatment of CTEPH and CTEPD.

The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-κB signaling pathway / 药学学报

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

Risk factors and prognosis of pulmonary hypertension associated with bronchopulmonary dysplasia in extremely preterm infants / 中国新生儿科杂志

Objective:To study the risk factors and prognosis of pulmonary hypertension(PH) associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants(EPIs).Methods:From January 2020 to December 2021, EPIs [gestational age (GA) <32 w] with BPD admitted to NICU of our hospital were retrospectively assigned into two groups: BPD with late-onset PH(PH group) and BPD without late-onset PH(non-PH group). Their general condition, treatment and prognosis were compared and the risk factors of late-onset PH were analyzed.Results:A total of 229 EPIs with BPD were enrolled, including 24(10.5%) in the PH group and 205(89.5%) in the non-PH group. The PH group had significantly smaller GA [(27.9±2.3) w vs. (28.7±1.8) w], longer mechanical ventilation [42.0(16.0, 84.0) d vs. 9.0(2.0, 23.0) d], longer hospital stay [100.5(86.3, 142.0) d vs. 77.0(56.5, 96.5)d],higher incidence of early-onset PH(54.2% vs. 9.3%) and higher mortality rate(33.3% vs. 9.8%) than the non-PH group ( P<0.05). Multivariate logistic regression analysis showed prolonged mechanical ventilation ( OR=1.046, 95% CI 1.011~1.064), early-onset PH ( OR=5.414, 95% CI 1.796~16.323) were independent risk factors for BPD with late-onset PH. 8(33.3%) patients in the PH group died, including 2 with grade Ⅱ BPD and 6 grade Ⅲ BPD. Conclusions:Prolonged mechanical ventilation and early-onset PH are independent risk factors for late-onset PH in BPD infants. BPD infants with late-onset PH have longer hospital stay, higher mortality and worse prognosis.

Risk factors and clinical outcomes of early-onset pulmonary hypertension in preterm infants with gestational age≤ 32 weeks / 中国新生儿科杂志

Objective:To study the risk factors and clinical outcomes of early pulmonary hypertension in preterm infants with gestational age(GA)≤32 w.Methods:From October 2017 to May 2021,preterm infants with GA≤ 32 w admitted to NICU of our hospital were retrospectively studied. According to their echocardiography 2 w after birth, the infants were assigned into early-onset pulmonary hypertension (ePH) group and non-PH group. SPSS 21.0 statistical software was used to analyze the general status, complications and clinical outcomes of the two groups. Multiple logistic regression was used to analyze the risk factors of early-onset PH.Results:A total of 183 cases were enrolled, including 24 in the ePH group and 159 in the non-PH group. The incidences of birth asphyxia, hemodynamically significant patent ductus arteriosus (hsPDA), FiO 2≥30% within 6 h after birth, late-onset PH, severe bronchopulmonary dysplasia(BPD) and intracranial hemorrhage(ICH) in the ePH group were significantly higher than the non-PH group( P<0.05). hsPDA was the independent risk factor for early-onset PH ( OR=11.781, 95% CI 4.192-33.108). Conclusions:Preterm infants with GA≤32 w and early-onset PH are at increased risks of ICH, late-onset PH and severe BPD, hsPDA is the independent risk factor for early-onset PH.

Alleviating experimental pulmonary hypertension via co-delivering FoxO1 stimulus and apoptosis activator to hyperproliferating pulmonary arteries

Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).@*METHODS@#A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue.@*RESULTS@#The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05).@*CONCLUSIONS@#Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.

Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance / 中国中药杂志

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.

Maternal and fetal/neonatal outcomes of pregnancies complicated by pulmonary hypertension: a retrospective study of 154 patients

Abstract Objectives: To determine the main clinical and demographic outcomes related to Pulmonary Hypertension (PH) and adverse obstetric and fetal/neonatal outcomes. Methods: This study retrospectively analyzed the medical record data of 154 patients with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2011 and December 2020. Results: According to the severity of elevated Pulmonary Artery Systolic Pressure (PASP), 82 women (53.2%) were included in the mild PH group, 34 (22.1%) were included in the moderate PH group, and 38 (24.7%) were included in the severe PH group. There were significant differences in the incidence of heart failure, premature delivery, Very-Low-Birth-Weight (VLBW) infants, and Small-for-Gestational-Age (SGA) infants among the three PH groups (p < 0.05). Five (3.2%) women died within 7-days after delivery, 7 (4.5%) fetuses died in utero, and 3 (1.9%) neonates died. The authors found that PASP was an independent risk factor for maternal mortality. After adjustment for age, gestational weeks, systolic blood pressure, Body Mass Index (BMI), mode of delivery, and anesthesia, the risk of maternal mortality in the severe PH group was 20.21 times higher than that in the mildmoderate PH group (OR = 21.21 [95% CI 1.7~264.17]), p < 0.05. All 131 (85.1%) patients were followed up for 12 months postpartum. Conclusions: The authors found that the risk of maternal mortality in the severe PH group was significantly higher than that in the mild-moderate group, highlighting the importance of pulmonary artery pressure screening before pregnancy, early advice on contraception, and multidisciplinary care.

The Use of Ketamine as an Induction Agent for Anesthesia in Pulmonary Thromboendarterectomy Surgery: A Case Series

Pulmonary thromboendarterectomy (PTE) surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH). The induction of anesthesia in patients with severe pulmonary hypertension (PHT) can be challenging, with a risk of cardiovascular collapse. The administration of ketamine in patients with PHT is controversial, with some recommendations contraindicating its use. However, ketamine has been used safely in children with severe PHT. We present a retrospective case series of adult patients with severe PHT presenting for PTE surgery, using intravenous ketamine as a co?induction anesthetic agent.