RESUMEN
OBJECTIVE: The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. METHODS: STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. RESULTS: A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2 ± 9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr < 33.45% had more adverse long-term outcomes (log rank p < .0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p = .010). CONCLUSION: Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.
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Ecocardiografía , Atrios Cardíacos , Lupus Eritematoso Sistémico , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Pronóstico , Ecocardiografía/métodos , Persona de Mediana Edad , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/sangre , Función del Atrio Derecho/fisiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/etiología , Estudios de SeguimientoRESUMEN
Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described. Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung. In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.
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Arritmias Cardíacas , Modelos Animales de Enfermedad , Arteria Pulmonar , Animales , Ratas , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Remodelación Ventricular/fisiología , Masculino , Hipertensión Pulmonar/fisiopatologíaRESUMEN
Hyperuricemia is a known predictor of World Health Organization (WHO) Group 1 pulmonary hypertension (PH) (pulmonary arterial hypertension), but its role in excluding PH secondary to chronic lung diseases (WHO Group 3) remains unclear. We retrospectively analyzed data from 323 patients with severe chronic pulmonary diseases who underwent evaluation for lung transplantation at a tertiary medical center between June 2017 and February 2023. We examined the association between hyperuricemia (serum uric acid > 6 mg/dL or > 0.357 mmol/L) and PH [mean pulmonary arterial pressure (MPAP) > 20 mmHg]. Compared to the normouricemia group (n = 211), hyperuricemic patients (n = 112) were more likely to be younger (P = 0.02), male (P < 0.001), and present with PH (P = 0.001) and severe PH (MPAP > 35 mmHg; P < 0.001). These patients also had a higher body mass index (P = 0.004), plasma N-terminal pro-B-type natriuretic peptide (P < 0.001), serum creatinine (P < 0.001), and C-reactive protein levels (P = 0.03). Significant associations with PH included higher body mass index (P = 0.005), uric acid levels (P < 0.001), total lung capacity (P = 0.02), and residual volume (P = 0.01); shorter 6-min walk test distance (P = 0.005); and lower forced expiratory volume in one second (P = 0.006) and diffusing capacity for carbon monoxide (P < 0.001). Multivariate analysis showed elevated uric acid levels remained significantly associated with PH (OR 1.29, 95% CI 1.05-1.58, P = 0.01). In conclusion, normal serum uric acid levels serve as a significant predictor for excluding pulmonary hypertension in patients with severe chronic lung diseases.
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Hipertensión Pulmonar , Hiperuricemia , Centros de Atención Terciaria , Ácido Úrico , Humanos , Masculino , Persona de Mediana Edad , Ácido Úrico/sangre , Femenino , Estudios Retrospectivos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/fisiopatología , Anciano , Hiperuricemia/sangre , Hiperuricemia/complicaciones , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/complicaciones , Adulto , Enfermedad CrónicaRESUMEN
OBJECTIVE: This study aims to assess the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a potential indicator for predicting the probability of developing pulmonary arterial hypertension (PAH) in hyperthyroidism patients. A nomogram model will be developed based on our findings, as well as the receiver operating characteristic (ROC) curve. METHODS: The study involved 166 hyperthyroid patients treated at Yijishan Hospital, and the period covered August 2021 to August 2022. Patients were divided into two groups according to pulmonary artery systolic pressure ≥35 mmHg. Univariate and multivariate logistic analyses were performed on the two groups' demographic and laboratory data to identify potential diagnostic markers. These parameters were evaluated using ROC curves to determine their precision in forecasting PAH. The findings were validated by plotting a calibration curve based on a line chart model. RESULTS: In the study, eventually, 80 patients were enrolled: 30 in the PAH group and 50 in the No PAH group. Multipleistic regression analysis predicted the occurrence risk of developing PAH. When paired with other conventional echocardiographic parameters (such as TAPSE, MPI, and SV) and serological markers (such as FT3 and FT4), the developed model demonstrated outstanding predictive performance with an area under the ROC curve of 0.985, a Youden index of 0.971, a sensitivity of 100%, and a specificity of 97.1%. CONCLUSIONS: The nomogram model constructed by combining the TAPSE/PASP ratio with FT3 and FT4 serum markers, as well as conventional ultrasound parameters SV and MPI in hyperthyroidism patients, demonstrates robust discriminatory ability and consistency.
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Hipertiroidismo , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Ecocardiografía/métodos , Adulto , Nomogramas , Valor Predictivo de las Pruebas , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Curva ROC , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/fisiopatología , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Medición de Riesgo/métodosRESUMEN
BACKGROUND: Pulmonary hypertension is a condition that involves the remodeling of the right ventricle. Ongoing remodeling is also associated with disease prognosis. During the restructuring process, complex changes such as hypertrophy and dilatation may also be reflected in electrocardiographic parameters. OBJECTIVES: Our study aimed to investigate the relationship between prognosis and electrocardiographic parameters in patients with pulmonary arterial hypertension. METHODS: The study was designed retrospectively and included patients diagnosed with pulmonary arterial hypertension between 2010 and 2022. The patients were divided into two groups based on their survival outcome. Various parameters, including electrocardiographic, demographic, echocardiographic, catheter, and blood parameters, were compared between the two groups. A p-value of <0.05 was considered statistically significant. RESULTS: In the multivariate Cox analyses, the parameters that were found to be independently associated with survival were the 6-minute walk test, mean pulmonary artery pressure, presence of pericardial effusion, and time between the beginning of the QRS and the peak of the S wave (RS time) (p<0.05 for each). Of all the parameters, RS time demonstrated the best diagnostic performance (AUC:0.832). In the survival analysis, a significant correlation was found between RS time and survival when using a cut-off value of 59.5 ms (HR: 0.06 [0.02-0.17], p < 0.001). CONCLUSIONS: According to the results of our study, a longer RS time is associated with poor prognosis in patients with pulmonary arterial hypertension. We can obtain information about the course of the disease with a simple, non-invasive parameter.
FUNDAMENTO: A hipertensão pulmonar é uma condição que envolve a remodelação do ventrículo direito. A remodelação contínua também está associada ao prognóstico da doença. Durante o processo de reestruturação, alterações complexas como hipertrofia e dilatação também podem se refletir nos parâmetros eletrocardiográficos. OBJETIVOS: Nosso estudo teve como objetivo investigar a relação entre prognóstico e parâmetros eletrocardiográficos em pacientes com hipertensão arterial pulmonar. MÉTODOS: O estudo foi desenhado retrospectivamente e incluiu pacientes com diagnóstico de hipertensão arterial pulmonar entre 2010 e 2022. Os pacientes foram divididos em dois grupos com base no resultado de sobrevida. Vários parâmetros, incluindo parâmetros eletrocardiográficos, demográficos, ecocardiográficos, de cateter e sanguíneos, foram comparados entre os dois grupos. Um valor de p <0,05 foi considerado estatisticamente significativo. RESULTADOS: Na análise multivariada de Cox, os parâmetros que se mostraram independentemente associados à sobrevida foram o teste de caminhada de 6 minutos, pressão média da artéria pulmonar, presença de derrame pericárdico e tempo entre o início do QRS e o pico da onda S (tempo de RS) (p<0,05 para cada). De todos os parâmetros, o tempo de RS demonstrou o melhor desempenho diagnóstico (AUC: 0,832). Na análise de sobrevida, foi encontrada correlação significativa entre o tempo de RS e a sobrevida ao utilizar o valor de corte de 59,5 ms (HR: 0,06 [0,02-0,17], p < 0,001). CONCLUSÕES: De acordo com os resultados do nosso estudo, um tempo de RS mais longo está associado a um pior prognóstico em pacientes com hipertensão arterial pulmonar. Podemos obter informações sobre o curso da doença com um parâmetro simples e não invasivo.
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Electrocardiografía , Humanos , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Factores de Tiempo , Ecocardiografía , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/mortalidad , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/mortalidad , Anciano , Valores de Referencia , Prueba de PasoRESUMEN
BACKGROUND: There are limited data assessing the spectrum of systemic sclerosis-associated pulmonary hypertension (PH). METHODS: Data for 912 systemic sclerosis patients assessed between 2000 and 2020 were retrieved from the Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry and classified based on 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines and multimodality investigations. RESULTS: Reduction in pulmonary vascular resistance (PVR) diagnostic threshold to >2WU resulted in a 19% increase in precapillary PH diagnoses. Patients with PVR ≤2WU had superior survival to PVR >2-3WU which was similar to PVR >3-4WU. Survival in pulmonary arterial hypertension (PAH) was superior to PH associated with lung disease. However, patients with mild parenchymal disease on CT had similar characteristics and outcomes to patients without lung disease. Combined pre- and postcapillary PH had significantly poorer survival than isolated postcapillary PH. Patients with mean pulmonary arterial wedge pressure (PAWP) 13-15 mm Hg had similar haemodynamics and left atrial volumes to those with PAWP >15 mm Hg. Unclassified-PH had more frequently dilated left atria and higher PAWP than PAH. Although Unclassified-PH had a similar survival to No-PH, 36% were subsequently diagnosed with PAH or PH associated with left heart disease. The presence of 2-3 radiological signs of pulmonary veno-occlusive disease was noted in 7% of PAH patients and was associated with worse survival. Improvement in incremental shuttle walking distance of ≥30 m following initiation of PAH therapy was associated with superior survival. PAH patients diagnosed after 2011 had greater use of combination therapy and superior survival. CONCLUSION: A number of systemic sclerosis PH phenotypes can be recognized and characterized using haemodynamics, lung function and multimodality imaging.
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Hipertensión Pulmonar , Sistema de Registros , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/fisiopatología , Masculino , Femenino , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico , Persona de Mediana Edad , Tasa de Supervivencia/tendencias , Estudios Retrospectivos , Resistencia Vascular/fisiología , Presión Esfenoidal Pulmonar/fisiología , Adulto , Estudios de SeguimientoAsunto(s)
Antihipertensivos , Hipertensión Pulmonar , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/metabolismo , Animales , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/metabolismo , Terapia Molecular Dirigida , Transducción de Señal/efectos de los fármacos , Presión Arterial/efectos de los fármacosRESUMEN
Induction of resistin-like molecule ß (Relm-ß) and mitofusin 2 (MFN2) mediated aberrant mitochondrial fission have been found to be involved in the pathogenesis of pulmonary arterial hypertension (PAH). However, the molecular mechanisms underlying Relm-ß regulation of MFN2 therefore mitochondrial fission remain unclear. This study aims to address these issues. Primary cultured PASMCs and monocrotaline (MCT)-induced PAH rats were applied in this study. The results showed that Relm-ß promoted cells proliferation in PASMCs, this was accompanied with the upregulation of USP18, Twist1 and miR-214, and downregulation of MFN2. We found that Relm-ß increased USP18 expression which in turn raised Twist1 by suppressing its proteasome degradation. Elevation of Twist1 increased miR-214 expression and then reduced MFN2 expression and mitochondrial fragmentation leading to PASMCs proliferation. In vivo study, we confirmed that Relm-ß was elevated in MCT-induced PAH rat model, and USP18/Twist1/miR-214/MFN2 axis was altered similar as in vitro. Targeting this cascade by Relm-ß receptor inhibitor Calhex231, proteasome inhibitor MG-132, Twist1 inhibitor Harmine or miR-214 antagomiR prevented the development of pulmonary vascular remodeling and therefore PAH in MCT-treated rats. In conclusion, we demonstrate that Relm-ß promotes PASMCs proliferation and vascular remodeling by activating USP18/Twist1/miR-214 dependent MFN2 reduction and mitochondrial fission, suggesting that this signaling pathway might be a promising target for management of PAH.
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Proliferación Celular , GTP Fosfohidrolasas , MicroARNs , Mitocondrias , Ratas Sprague-Dawley , Transducción de Señal , Proteína 1 Relacionada con Twist , Ubiquitina Tiolesterasa , Animales , Masculino , Ratas , Proliferación Celular/efectos de los fármacos , GTP Fosfohidrolasas/metabolismo , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas Mitocondriales , Monocrotalina/toxicidad , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/patología , Hipertensión Arterial Pulmonar/fisiopatología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/patología , Arteria Pulmonar/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína 1 Relacionada con Twist/metabolismo , Proteína 1 Relacionada con Twist/genética , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genéticaRESUMEN
ABSTRACT: Pulmonary arterial hypertension (PAH) is characterized by persistently elevated pulmonary artery pressure and vascular resistance. Sympathetic overactivity in hypertension participates in pulmonary vascular remodeling and heart failure. The present study aims to explore the efficacy of highly selective thoracic sympathectomy (HSTS) on lowering pulmonary artery pressure, reversing pulmonary vascular remodeling, and improving right ventricular function in rats. A total of 24 Sprague-Dawley rats were randomly assigned into the control group ( n = 8) and experimental group ( n = 16). Rats in the control group were intraperitoneally injected with 0.9% normal saline, and those in the experimental group were similarly administered with received monocrotaline (MCT) injections at 60 mg/kg. Two weeks later, rats in the experimental group were further subdivided randomly into the MCT-HSTS group ( n = 8) and MCT-sham group ( n = 8), and they were surgically treated with HSTS and sham operation, respectively. Two weeks later, significantly lowered mean pulmonary artery pressure (mPAP), pulmonary artery systolic pressure (sPAP), and the ratio of sPAP to femoral artery systolic pressure (sFAP) were detected in the MCT-HSTS group than those of the MCT-sham group. In addition, rats in the MCT-HSTS group presented a significantly lower ratio of vascular wall area to the total vascular area (WT%), right ventricular hypertrophy index, and degrees of right ventricular fibrosis and lung fibrosis in comparison to those of the MCT-sham group. HSTS significantly downregulated protein levels of inflammasomes in pulmonary artery smooth muscle cells (PASMCs). Collectively, HSTS effectively reduces pulmonary artery pressure, pulmonary arteriolar media hypertrophy, and right ventricular hypertrophy in MCT-induced PAH rats. It also exerts an anti-inflammatory effect on PASMCs in PAH rats by suppressing inflammasomes and the subsequent release of inflammatory cytokines.
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Monocrotalina , Hipertensión Arterial Pulmonar , Ratas Sprague-Dawley , Simpatectomía , Animales , Simpatectomía/métodos , Masculino , Ratas , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/patología , Remodelación Vascular , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Progresión de la Enfermedad , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/patologíaRESUMEN
Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by increased pulmonary vascular resistance because of vascular remodeling and vasoconstriction. Subsequently, PAH leads to right ventricular hypertrophy and heart failure. Cell death mechanisms play a significant role in development and tissue homeostasis, and regulate the balance between cell proliferation and differentiation. Several basic and clinical studies have demonstrated that multiple mechanisms of cell death, including pyroptosis, apoptosis, autophagy, ferroptosis, anoikis, parthanatos, and senescence, are closely linked with the pathogenesis of PAH. This review summarizes different cell death mechanisms involved in the death of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs), the primary target cells in PAH. This review summarizes the role of these cell death mechanisms, associated signaling pathways, unique effector molecules, and various pro-survival or reprogramming mechanisms. The aim of this review is to summarize the currently known molecular mechanisms underlying PAH. Further investigations of the cell death mechanisms may unravel new avenues for the prevention and treatment of PAH.
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Células Endoteliales , Miocitos del Músculo Liso , Hipertensión Arterial Pulmonar , Arteria Pulmonar , Transducción de Señal , Humanos , Células Endoteliales/patología , Miocitos del Músculo Liso/patología , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/patología , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Muerte Celular , Animales , Apoptosis , Autofagia/fisiología , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatologíaRESUMEN
Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.
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MicroARNs , Hipertensión Arterial Pulmonar , Arteria Pulmonar , Función Ventricular Derecha , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Humanos , Ratones , Masculino , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/metabolismo , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Modelos Animales de Enfermedad , Monocrotalina , Proliferación Celular/genética , Miocitos del Músculo Liso/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/genética , Hipertrofia Ventricular Derecha/fisiopatología , Hipertrofia Ventricular Derecha/metabolismo , Remodelación Vascular/genética , Ratas Sprague-DawleyRESUMEN
PURPOSE: Pulmonary thromboendarterectomy (PTE) is the treatment for patients with chronic thromboembolic disease. In the immediate postoperative period, some patients may still experience life-threatening complications such as reperfusion lung injury, airway bleeding, and persistent pulmonary hypertension with consequent right ventricular dysfunction. These issues may require support with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or lung transplantation. This study aims to analyze our series of PTEs that require ECMO. METHODS: A descriptive and retrospective analysis of all PTE performed at the Favaloro Foundation University Hospital was conducted between March 2013 and December 2023. RESULTS: A total of 42 patients underwent PTE with a median age of 47 years (interquartile range: 26-76). The incidence of patients with ECMO was 26.6%, of which 53.6% were veno-venous (VV) ECMO. Preoperatively, a low cardiac index (CI), high right and left filling pressures, and high total pulmonary vascular resistances (PVRs) were associated with ECMO with a statistically significant relationship. The hospital mortality was 11.9%, and the mortality in the ECMO group was 45.5%, with a statistically significant relationship. Veno-arterial ECMO has a worse prognosis than VV ECMO. CONCLUSIONS: Preoperatively, a low CI, high right and left filling pressures, and high total PVRs were associated with ECMO after PTE.
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Endarterectomía , Oxigenación por Membrana Extracorpórea , Mortalidad Hospitalaria , Embolia Pulmonar , Humanos , Oxigenación por Membrana Extracorpórea/mortalidad , Oxigenación por Membrana Extracorpórea/efectos adversos , Persona de Mediana Edad , Endarterectomía/efectos adversos , Endarterectomía/mortalidad , Masculino , Estudios Retrospectivos , Femenino , Resultado del Tratamiento , Adulto , Anciano , Embolia Pulmonar/mortalidad , Embolia Pulmonar/cirugía , Embolia Pulmonar/fisiopatología , Factores de Tiempo , Factores de Riesgo , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/cirugía , Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/cirugíaRESUMEN
Pulmonary arterial hypertension (PAH) is a well-known complication of congenital heart disease (CHD). The lack of a satisfactory animal model for PAH associated with CHD (PAH-CHD) has limited progress in understanding the pathogenesis of PAH and the development of therapeutic agents. The development of a rat model for PAH associated with atrial septal defect (ASD) was achieved through atrial septal puncture and thermal ablation. Two and 4 weeks after modeling, hematoxylin and eosin staining showed that the vascular thickness, vascular thickness index, vascular area, and vascular area index in pulmonary arteries with an outer diameter of 50-300 µm in the PAH-ASD 2 and 4 weeks group were higher than those in the sham group (all P < 0.05). Alpha-smooth muscle actin (É-SMA) staining showed that the medial thickness, medial thickness index, medial area, and medial area index in pulmonary arteries with an outer diameter of 50-300 µm at 2 and 4 weeks after modeling were significantly higher than those in the sham group (all P < 0.05). Additionally, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in the PAH-ASD 2 and 4 weeks groups were significantly higher than those in the sham group (both P < 0.05). Elastin van Gieson staining showed that the vascular obstruction score in the PAH-ASD 2 and 4 weeks group was significantly higher than that in the sham group (both P < 0.05). The PAH-ASD rats were successfully generated. These findings suggest that our model would be useful for further research into the pathogenesis, prevention, and treatment of PAH-ASD.
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Modelos Animales de Enfermedad , Defectos del Tabique Interatrial , Hipertensión Arterial Pulmonar , Arteria Pulmonar , Animales , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/patología , Defectos del Tabique Interatrial/fisiopatología , Ratas , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Masculino , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/patología , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Ratas Sprague-Dawley , Resistencia VascularRESUMEN
Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD-associated drug targets for PH.
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Apoptosis , Hipertensión Pulmonar , Remodelación Vascular , Humanos , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Animales , Necroptosis , Transducción de Señal , Autofagia , Ferroptosis , Arteria Pulmonar/patología , Arteria Pulmonar/metabolismo , PiroptosisRESUMEN
Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls. NC-Measurements were repeated after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in CTEPH patients. We examined whether NC-measurements were related to markers of disease severity and predictive of time to clinical worsening (TTCW) as tested by univariate linear/logistic regression and cox-regression analysis, respectively. Capillary density was significantly lower in PAH (7.5 ± 1.1, p < 0.001) and in CTEPH (8.4 ± 1.5, p < 0.001) compared to asymptomatic controls (10.3 ± 1.0 capillaries/mm). Capillary density was similar in iPAH and hPAH and unrelated to hemodynamics in either PAH or CTEPH. A lower capillary density was predictive of clinical worsening in PAH (p 0.05). After normalization of pulmonary artery pressures by PEA or BPA, capillary density remained reduced in CTEPH patients. Capillary loop apex, capillary and venous- and arterial limb diameter were increased in patients with PAH and CTEPH compared to controls. Nailfold capillary density is reduced to a similar extent in iPAH, hPAH and CTEPH. Normalization of hemodynamics by PEA or BPA does not lead to a restoration of capillary density in CTEPH. Capillary dimensions were increased in both patients with PAH and CTEPH. Lower capillary density was predictive of clinical worsening in PAH. Our findings indicate that a loss of peripheral capillaries is not specific to PAH and is not related to the hemodynamic disturbance per se, but that shared mechanisms may account for a simultaneous development of a systemic microangiopathy and pulmonary vascular remodeling.
Asunto(s)
Capilares , Hipertensión Pulmonar , Humanos , Femenino , Masculino , Persona de Mediana Edad , Capilares/patología , Capilares/fisiopatología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Anciano , Biomarcadores , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/complicaciones , Angioscopía Microscópica/métodos , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/cirugía , Endarterectomía/métodos , Densidad Microvascular , Enfermedad Crónica , Uñas/irrigación sanguínea , Estudios de Casos y ControlesRESUMEN
OBJECTIVES: Right ventricular (RV) output reserve, defined as increase of cardiac output during exercise, is reduced in patients with pulmonary arterial hypertension (PAH). Aim of this study was to evaluate the association of right heart size measured by echocardiography and invasively measured RV function at rest and during exercise in PAH patients. METHODS: Adult PAH-patients who received routine haemodynamic assessment at rest and during exercise by right heart catheterisation and echocardiographic measurement of right heart size (right atrial (RA) and RV area) were included in this study. Clinical, echocardiographic, laboratory, exercise and invasive haemodynamic parameters were retrospectively analysed. The primary endpoint was to assess the association between right heart size and right ventricular function. RESULTS: Data from 215 PAH patients (age 58.9 ± 15.9 years, 63.3% female, 62.2% double or triple combination treatment) were analysed in this cross-sectional study. Cardiac index was significantly lower for patients with enlarged RA-area > 18 cm2 at rest, and at 25 and 50 W (all p < 0.001) and for patients with enlarged RV area > 20 cm2 at rest, 25, 50 and 75 W (all p < 0.001). Furthermore, pulmonary vascular resistance and mPAP/CO slope (all p < 0.001) were significantly higher and pulmonary arterial compliance (all p < 0.05) was significantly lower in patients with enlarged RA or RV area. RA and RV area correlated with TAPSE/sPAP (both p < 0.001, R - 0.570 and - 0.530). CONCLUSION: This study could underline that an enlargement of RA- and RV-area is associated with an impaired RV function at rest and during exercise in patients with PAH.
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Gasto Cardíaco , Hipertensión Arterial Pulmonar , Función Ventricular Derecha , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Estudios Transversales , Gasto Cardíaco/fisiología , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Función Ventricular Derecha/fisiología , Adulto , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Ecocardiografía/métodos , Cateterismo Cardíaco , Tamaño de los Órganos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico por imagen , Prueba de Esfuerzo/métodosRESUMEN
BACKGROUND: High levels of lactate are positively associated with prognosis and mortality in pulmonary hypertension (PH). Lactate dehydrogenase A (LDHA) is a key enzyme for the production of lactate. This study is undertaken to investigate the role and molecular mechanisms of lactate and LDHA in PH. METHODS: Lactate levels were measured by a lactate assay kit. LDHA expression and localization were detected by western blot and Immunofluorescence. Proliferation and migration were determined by CCK8, western blot, EdU assay and scratch-wound assay. The right heart catheterization and right heart ultrasound were measured to evaluate cardiopulmonary function. RESULTS: In vitro, we found that lactate promoted proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) in an LDHA-dependent manner. In vivo, we found that LDHA knockdown reduced lactate overaccumulation in the lungs of mice exposed to hypoxia. Furthermore, LDHA knockdown ameliorated hypoxia-induced vascular remodeling and right ventricular dysfunction. In addition, the activation of Akt signaling by hypoxia was suppressed by LDHA knockdown both in vivo and in vitro. The overexpression of Akt reversed the inhibitory effect of LDHA knockdown on proliferation in PASMCs under hypoxia. Finally, LDHA inhibitor attenuated vascular remodeling and right ventricular dysfunction in Sugen/hypoxia mouse PH model, Monocrotaline (MCT)-induced rat PH model and chronic hypoxia-induced mouse PH model. CONCLUSIONS: Thus, LDHA-mediated lactate production promotes pulmonary vascular remodeling in PH by activating Akt signaling pathway, suggesting the potential role of LDHA in regulating the metabolic reprogramming and vascular remodeling in PH.
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Proliferación Celular , Hipertensión Pulmonar , L-Lactato Deshidrogenasa , Lactato Deshidrogenasa 5 , Ácido Láctico , Ratones Endogámicos C57BL , Arteria Pulmonar , Remodelación Vascular , Animales , Humanos , Masculino , Ratones , Ratas , Hipoxia de la Célula , Movimiento Celular , Técnicas de Silenciamiento del Gen , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Hipoxia/complicaciones , Hipoxia/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Lactato Deshidrogenasa 5/metabolismo , Ácido Láctico/metabolismo , Pulmón/patología , Pulmón/irrigación sanguínea , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Arteria Pulmonar/patología , Arteria Pulmonar/metabolismo , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Arrhythmias are increasingly recognized as severe complications of precapillary pulmonary hypertension, encompassing pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Despite their significant contribution to symptoms, morbidity, in-hospital mortality, and potentially sudden death in PAH/CTEPH, there remains a lack of comprehensive data on epidemiology, pathophysiology, and outcomes to inform the management of these patients. This review provides an overview of the latest evidence on this subject, spanning from the molecular mechanisms underlying arrhythmias in the hypertrophied or failing right heart to the clinical aspects of epidemiology, diagnosis, and treatment.
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Arritmias Cardíacas , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/complicaciones , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/complicaciones , Enfermedad Crónica , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicacionesRESUMEN
Acute pulmonary embolism (APE) is one of the leading causes of cardiovascular emergencies and the third leading cause of death. Although efforts focus on treating the acute event, patients who survive APE may develop long-term sequelae. Research reveals that approximately half of patients who have suffered an APE do not regain their previous level of function and experience a reduction in their quality of life for several years after the episode. Acute pulmonary embolism can be classified according to the risk of short-term mortality, with most mortality and morbidity concentrated in high-risk and intermediate-risk cases. The first-line treatment for APE is systemic anticoagulation. However, identifying and more aggressively treating people with intermediate to high risk, who have a more favorable risk profile for reperfusion treatments, could reduce short-term mortality and mitigate post-pulmonary embolism syndrome (PPES). Post-pulmonary embolism syndrome refers to a variety of persistent symptoms and functional limitations that occur after an APE. The presence of persistent dyspnea, functional limitations, and/or decreased quality of life after an APE has been recently termed "PPES," although this entity encompasses different manifestations. The most severe cause of persistent dyspnea is chronic thromboembolic pulmonary hypertension, where increased pulmonary artery pressure is due to the fibrotic organization of unresolved APE. Post-PE Syndrome is not always systematically addressed in management guidelines, and its prevalence may be underestimated. More research is needed to fully understand its causes and risk factors. Interventions such as cardiopulmonary rehabilitation have been suggested to improve the quality of life of patients with PPES. A comprehensive, evidence-based approach is essential to effectively prevent and manage PPES and improve the long-term outcomes and well-being of affected patients.