Cell Death in Pulmonary Arterial Hypertension.

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.

Animal models of pulmonary arterial hypertension associated with atrial septal defect.

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 (ɑ-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.

ECG changes following balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension: a retrospective study.

PURPOSE: This research evaluates the effect of balloon pulmonary angioplasty (BPA) on cardiac electrophysiological changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Involving a retrospective analysis of 39 CTEPH patients (average age 61 ± 11), who had at least two BPAs and paired ECGs pre- and post-surgery, we examined changes in ECG indicators of right ventricular hypertrophy and their correlation with hemodynamic results. RESULTS: BPA yielded marked improvements in cardiac function and hemodynamics. ECG parameters, specifically the Lewis criteria and Butler-Leggett score, correlated strongly with hemodynamics and were predictive of a mean pulmonary arterial pressure (mPAP) ≥ 35mmHg. Notably, QRS complex axis normalization was observed in 25 patients, with 14 fully normalizing (range - 30° to + 90°). The qR pattern in V1 vanished in 9 cases, and 75% of the patients in qR pattern in V1 group had QRS complex electrical axis completely returned to normal range. The qR V1 group had higher mPAP and pulmonary vascular resistance (PVR), and lower cardiac output and index compared to the non-qR V1 group, alongside a higher Butler-Leggett score. CONCLUSIONS: BPA enhances cardiac function and hemodynamics in CTEPH patients, with certain ECG measures such as Lewis criteria and Butler-Leggett score reflecting the severity of hemodynamic impairment. The reversal of QRS axis deviation and the disappearance of the qR pattern in lead V1 may serve as valuable indicators for assessing post-BPA satisfaction in CTEPH patients.

TGFß1, SMAD and ß-catenin in pulmonary arteries of smokers, patients with small airway disease and COPD: potential drivers of EndMT.

We previously reported pulmonary arterial remodelling and active endothelial-to-mesenchymal transition (EndMT) in smokers and patients with early chronic obstructive pulmonary disease (COPD). In the present study, we aimed to evaluate the role of different drivers of EndMT. Immunohistochemical staining for EndMT drivers, TGF-ß1, pSMAD-2/3, SMAD-7, and ß-catenin, was performed on lung resections from 46 subjects. Twelve were non-smoker-controls (NC), six normal lung function smokers (NLFS), nine patients with small-airway diseases (SAD), nine mild-moderate COPD-current smokers (COPD-CS) and ten COPD-ex-smokers (COPD-ES). Histopathological measurements were done using Image ProPlus softwarev7.0. We observed lower levels of total TGF-ß1 (P<0.05) in all smoking groups than in the non-smoking control (NC). Across arterial sizes, smoking groups exhibited significantly higher (P<0.05) total and individual layer pSMAD-2/3 and SMAD-7 than in the NC group. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared with NC. Total ß-catenin expression was significantly higher in smoking groups across arterial sizes (P<0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased total ß-catenin was positively correlated with total S100A4 in small and medium arteries (r = 0.35, 0.50; P=0.02, 0.01, respectively), with Vimentin in medium arteries (r = 0.42, P=0.07), and with arterial thickness of medium and large arteries (r = 0.34, 0.41, P=0.02, 0.01, respectively). This is the first study uncovering active endothelial SMAD pathway independent of TGF-ß1 in smokers, SAD, and COPD patients. Increased expression of ß-catenin indicates its potential interaction with SMAD pathway, warranting further research to identify the deviation of this classical pathway.

Extracorporeal Mechanical Circulatory Support after Pulmonary Thromboendarterectomy: Experience of One Center.

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.

Effects of Ranolazine and Ivabradine on Pulmonary Microhemodynamics in Experimental Model of Pulmonary Thromboembolism.

We studied changes of pulmonary microhemodynamics when modeling pulmonary artery thromboembolism on perfused isolated rabbit lungs after pretreatment with ranolazine and ivabradine. The increase in pulmonary artery pressure, pulmonary vascular resistance, and pre- and postcapillary resistance was less pronounced than in control animals, but was close to that in case of pulmonary thromboembolism after pretreatment with voltage-gated Na+ channel blockers lidocaine and ropivacaine. The increase of capillary filtration coefficient inversely correlated with values of capillary hydrostatic pressure. Thus, ranolazine and ivabradine exhibit the properties of voltage-gated Na+ channel blockers mainly in smooth muscles of pulmonary arterial vessels and promote the decrease in endothelial permeability.

ß-catenin mediates monocrotaline-induced pulmonary hypertension via glycolysis in rats.

BACKGROUND: Metabolic abnormalities and immune inflammation are deeply involved in pulmonary vascular remodelling and the development of pulmonary hypertension (PH). However, the regulatory mechanisms of glycolysis in macrophages are still elusive. Cumulative evidence indicates that ß-catenin plays a crucial role in metabolic reprogramming. This study aimed to investigate the effect of ß-catenin on macrophage glycolysis in PH. METHODS: LPS-induced BMDMs were generated via in vitro experiments. A monocrotaline (MCT)-induced PH rat model was established, and the ß-catenin inhibitor XAV939 was administered in vivo. The role of ß-catenin in glycolysis was analysed. The degree of pulmonary vascular remodelling was measured. RESULTS: ß-catenin was significantly increased in both in vitro and in vivo models. In LPS-induced BMDMs, ß-catenin increased the levels of hexokinase 2 (HK2), phosphofructokinase (PFK), M2-pyruvate kinase (PKM2), lactate dehydrogenase (LDH), and lactate (LA) and the expression of inflammatory cytokines and promoted PASMC proliferation and migration in vitro. XAV939 decreased the level of glycolysis and downregulated the expression of inflammatory cytokines in vivo. MCT promoted pulmonary arterial structural remodelling and right ventricular hypertrophy, and XAV939 alleviated these changes. CONCLUSIONS: Our findings suggest that ß-catenin is involved in the development of PH by promoting glycolysis and the inflammatory response in macrophages. Inhibition of ß-catenin could improve the progression of PH.

Extravascular protrusion of the Alterra adaptive prestent identified on surveillance computed tomography imaging.

BACKGROUND: The Alterra adaptive prestent is a novel self-expanding device designed to provide a landing zone for the 29 mm SAPIEN 3 valve to treat pulmonary regurgitation in patients with a right ventricular outflow tract that is too large for a balloon expandable valve alone. The mechanism of fixation for the Alterra prestent is radial force from the self-expanding stent frame, combined with a unique set of flared "tines" that protrude from both ends of the stent. AIMS, METHODS, AND RESULTS: In this report, we describe 6 patients who underwent uncomplicated transcatheter pulmonary valve replacement with an Alterra adaptive prestent and SAPIEN 3 valve and had surveillance chest computed tomography (CT) scans performed 1 day to 21 months after implant. In each patient, the CT scan demonstrated extravascular extension of a portion of the Alterra prestent, without clinical sequelae, but with extension into the ascending aorta in 1 patient and contact with the ascending aorta, left pulmonary vein, or left atrial appendage in 3 others. CONCLUSIONS: Surveillance CT imaging shows that the Alterra prestent can perforate the pulmonary artery and/or right ventricle. Although no sequelae were seen in these patients, prestent perforation has the potential to be clinically important. Implanters should be aware of this finding and its potential implications. As experience with the Alterra prestent grows, it will be important to further define the risk factors, incidence, and implications of this phenomenon.

Percutaneous pulmonary aspiration thrombectomy in an adolescent fontan patient using a large-bore system.

We describe the safe and effective percutaneous pulmonary thrombectomy in an 18-year-old female with a Fontan circulation using the FlowTriever® device (Inari Medical®, Irvine, US). Aspiration thrombectomy of both pulmonary arteries was performed using 24 and 16 F FlowTriever® catheters retrieving large amounts of thrombus material resulting in near total angiographic recanalization.

Transcatheter Fontan completion: Creation of an extracardiac Fontan.

Patients with functionally univentricular hearts are usually palliated surgically. There have been several reports of successful attempts to complete the Fontan procedure without surgery. The pathways created at the time of the preconditioning were largely reminiscent of the lateral tunnel Fontan. However, this approach is still confidentially limited to a small number of centers. In 2013, we designed a circuit that mimics the actual surgical technique of extracardiac total cavopulmonary connection to allow for transcatheter completion in an animal study. A polytetrafluoroethylene conduit was connected between the pulmonary artery and the inferior vena cava (IVC). The superior anastomosis was occluded to avoid flow between IVC and superior vena cava (SVC). The conduit was connected to the right atrium (RA) and a large fenestration was created to allow free flow from the IVC to the RA. Extrapolating our approach, a center reported the successful transcatheter completion of an extracardiac Fontan in a 6-year-old child. However, this technique is not directly transposable to our population of patients who require preconditioning in infancy. We report here an innovative extension of this technique that may allow preparing patients in infancy, ideally at the time of the Glenn in the future, to receive an extracardiac Fontan at 2 years/11 kg without additional surgery.

Differential effects of balloon pulmonary angioplasty on chronic thromboembolic pulmonary disease.

BACKGROUND: Decreased diffusing capacity of the lungs for carbon monoxide (DLco) is associated with microvascular damage in chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an effective treatment for CTEPH, but the efficacy of BPA in patients with CTEPH with low DLco remains unclear because BPA does not directly address microvascular damage. This study investigates the influence of microvasculopathy on BPA in CTEPH according to DLco. METHODS: We retrospectively analysed data from patients with inoperable CTEPH who underwent BPA at the University of Tokyo Hospital from July 2011 to August 2023. The patients were classified into two groups based on their preprocedural DLco (normal DLco (ND) and low DLco (LD) groups), with a DLco cut-off value of 80%. We compared the patient characteristics and effectiveness of BPA between the groups. RESULTS: Among the 75 patients, 36 were in the LD group. The LD group had a shorter 6-minute walking distance (324±91 vs 427±114 m) than the ND group but the mean pulmonary artery pressure (mPAP) was similar (38.9±7.3 vs 41.1±9.2 mm Hg) before BPA. BPA improved the haemodynamic status and exercise tolerance in both groups. The LD group exhibited a higher mPAP (25.1±7.4 vs 21.5±5.6 mm Hg) and required more sessions of BPA (median 6 vs 4). Based on the analysis of covariance adjusted for baseline values, low DLco significantly correlated with mPAP (sß=-0.304, 95% CI -7.015 to -1.132, p=0.007) and pulmonary vascular resistance (sß=-0.324, 95% CI -141.0 to -29.81, p=0.003). CONCLUSIONS: BPA was associated with an improvement in the haemodynamic status and exercise tolerance in patients with CTEPH even with low DLco. However, low DLco may attenuate the effect of BPA on mPAP and pulmonary vascular resistance and require more treatment sessions.

Pulmonary Hypertension Induced by Right Pulmonary Artery Occlusion: Hemodynamic Consequences of Bmpr2 Mutation.

BACKGROUND: The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the BMPR2 gene. The incomplete penetrance of BMPR2 mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers pulmonary hypertension (PH) in rats with Bmpr2 mutations. METHODS AND RESULTS: Male and female rats with a 71 bp monoallelic deletion in exon 1 of Bmpr2 and their wild-type siblings underwent acute and chronic RPAO. They were subjected to full high-fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced precapillary PH in male and female rats, both acutely and chronically. Bmpr2 mutant and male rats manifested more severe PH compared with their counterparts. Although wild-type rats adapted to RPAO, Bmpr2 mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male Bmpr2 rats. Chronic RPAO resulted in elevated pulmonary IL-6 (interleukin-6) expression and decreased Gdf2 expression (corrected P value<0.05 and log2 fold change>1). In this context, male rats expressed higher pulmonary levels of endothelin-1 and IL-6 than females. CONCLUSIONS: Our novel 2-hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex- and gene-related effects.

Prevalence and Clinical Characteristics of Heterozygous RNF213 p.Arg4810Lys Variant Carriers Diagnosed With Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Ring finger protein 213 (RNF213) p.Arg4810Lys is a susceptibility gene for moyamoya disease, peripheral pulmonary artery stenosis (PPS), and other vascular diseases and thrombosis. We investigated the prevalence and clinical characteristics of RNF213 variant carriers diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: We retrospectively analyzed the prevalence of the RNF213 p.Arg4810Lys variant in patients diagnosed with CTEPH (n=112) and PPS (n=10). Clinical and angiographic characteristics were evaluated between RNF213 variant carriers diagnosed with CTEPH and noncarriers with CTEPH and homozygous variant carriers with PPS. Eight heterozygous RNF213 p.Arg4810Lys variant carriers (7.1%) were identified among patients diagnosed with CTEPH, while 5 patients with PPS (50%) carried the homozygous variant. The clinical characteristics of heterozygous variant carriers with CTEPH were not remarkably different from those of noncarriers with CTEPH. All heterozygous variant carriers with CTEPH showed webs/bands lesions at the segmental/subsegmental level, with 75% showing distal tortuous vessels. None of the heterozygous variant carriers with CTEPH exhibited the string-of-beads pattern or elongated stenosis. Homozygous variant carriers with PPS showed the string-of-beads pattern, elongated stenosis, and distal tortuous vessels without webs/bands lesions. CONCLUSIONS: A subset of patients diagnosed with CTEPH (7.1%) carried the heterozygous RNF213 p.Arg4810Lys variant. Clinical and angiographic characteristics of heterozygous variant carriers were not remarkably different from those of noncarriers of CTEPH. However, both heterozygous variant carriers with CTEPH and homozygous variant carriers with PPS showed tortuous vessels on angiography.

Systemic hemodynamics and pediatric lung disease: mechanistic links and therapeutic relevance.

Chronic lung disease, also known as bronchopulmonary dysplasia, affects thousands of infants worldwide each year. The impact on resources is second only to bronchial asthma, with lung function affected well into adolescence. Diagnostic and therapeutic constructs have almost exclusively focused on pulmonary architecture (alveoli/airways) and pulmonary hypertension. Information on systemic hemodynamics indicates major artery thickness/stiffness, elevated systemic afterload, and/or primary left ventricular dysfunction may play a part in a subset of infants with severe neonatal-pediatric lung disease. Understanding the underlying principles with attendant effectors would aid in identifying the pathophysiological course where systemic afterload reduction with angiotensin-converting enzyme inhibitors could become the preferred treatment strategy over conventional pulmonary artery vasodilatation.NEW & NOTEWORTHY Extremely preterm infants are at a higher risk of developing severe bronchopulmonary dysplasia. In a subset of infants, diuretic and pulmonary vasodilator therapy is ineffective. Recent information points toward systemic hemodynamic disease (systemic arterial stiffness and left ventricular dysfunction) as a contributor via back-pressure changes. Mechanistic links include heightened renin angiotensin aldosterone system activity, inflammation, and oxygen toxicity. Angiotensin-converting enzyme inhibition may be operationally more suited compared with induced pulmonary artery vasodilatation.

Effect of caspase inhibitors on hemodynamics and inflammatory factors in ARDS model rats.

To study the effects of caspase inhibitors on hemodynamics and inflammatory factors in acute respiratory distress syndrome (ARDS) model rats. Sixty healthy male Wistar rats were randomly divided into three groups, namely, the control group, ARDS group and ARDS + Caspase inhibitor group, with 20 rats in each group. The control group was intraperitoneally injected with 2 mL/kg saline, and the ARDS model group was established by intraperitoneally injecting 4 mg/kg Lipopolysaccharide (LPS), ARDS + Caspase inhibitor group was adminstered 20 mg/kg caspase inhibitor after intraperitoneal LPS injection. Changes in pulmonary arterial pressure (PAP) and mean arterial pressure (MAP) at 6 and 12 h before and after administration were recorded. Moreover, arterial blood gas was evaluated with a blood gas analyzer and changes in the partial pressure of O2 (PaO2), partial pressure of CO2 (PaCO2), partial pressure of O2/fraction of inspired O2 (PaO2/FiO2) were evaluated. In addition, the lung wet/dry weight (W/D) ratio and inflammatory factor levels in lung tissue were determined. Finally, pathological sections were used to determine the pulmonary artery media thickness (MT), MT percentage (MT%), and the degree of muscle vascularization. The pulmonary arterial pressure of rats was determined at several time points. Compared with the control group, the model group had a significantly increased pulmonary arterial pressure at each time point (P < 0.01), and the mean arterial pressure significantly increased at 6 h (P < 0.05). Compared with that of rats in the model group, the pulmonary arterial pressure of rats in drug administration group was significantly reduced at each time point after administration (P < 0.01), and the mean arterial pressure was significantly reduced at 6 h (P < 0.05). The arterial blood gas analysis showed that compared with those in the control group, PaO2, PaCO2 and PaO2/FiO2 in the model group were significantly reduced (P < 0.01), and PaO2, PaCO2 and PaO2/FiO2 were significantly increased after caspase inhibitor treatment (P < 0.05 or 0.01). The levels of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the model group were significantly higher than those in the control group (P < 0.01), and they were significantly decreased after caspase inhibitor treatment (P < 0.01). In the model group, pulmonary artery MT, MT% and the degree of muscle vascularization were significantly increased (P < 0.05 or 0.01), and pulmonary artery MT and the degree of muscle vascularization were significantly reduced after caspase inhibitor treatment (P < 0.05 or 0.01). Apoptosis Repressor with a Caspase Recuitment Domain (ARC) can alleviate the occurrence and development of pulmonary hypertension (PH) by affecting hemodynamics and reducing inflammation.

Pulmonary Artery Pressures and Mortality During Venoarterial ECMO: An ELSO Registry Analysis.

BACKGROUND: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (ECMO). How the right heart (the right ventricle and pulmonary artery) affect survival during venoarterial ECMO is unknown. We aimed to identify the relationship between right heart function with mortality and the duration of ECMO support. METHODS: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization Registry between 2010 and 2022 were queried. Right heart function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for modified Society for Cardiovascular Angiography and Interventions stage, age, sex, and concurrent clinical data (ie, pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality. RESULTS: A total of 4442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; nonsurvivors were more likely to be older, have a worse Society for Cardiovascular Angiography and Interventions stage, and have longer pre-ECMO endotracheal intubation times (P<0.05 for all) than survivors. Increasing PAPP from pre-ECMO to on-ECMO time (ΔPAPP) was associated with reduced mortality per 2 mm Hg increase (odds ratio, 0.98 [95% CI, 0.97-0.99]; P=0.002). Higher on-ECMO PAPP was associated with mortality reduction across quartiles with the greatest reduction in the third PAPP quartile (odds ratio, 0.75 [95% CI, 0.63-0.90]; P=0.002) and longer time on ECMO per 10 mm Hg (beta, 15 [95% CI, 7.7-21]; P<0.001). CONCLUSIONS: Early on-ECMO right heart function and interval improvement from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of right heart metrics into risk prediction models should be considered.

[Clinical features of pulmonary hypertension in lymphangioleiomyomatosis].

Objective: To describe the prevalence of lymphangioleiomyomatosis-pulmonary hypertension (LAM-PH), to explore the clinical features of patients with LAM-PH, and to evaluate the role of pulmonary artery optical coherence tomography (OCT) in the diagnosis of LAM-PH. Methods: Among 234 patients diagnosed with LAM in our center from June 2017 to August 2023, echocardiography was performed in 167 patients, 15 patients with PH indicated by echocardiography were selected as the LAM-PH group. From the remaining 152 patients, 32 patients were randomly selected as the control group. We compared the demographic data, clinical manifestations, pulmonary function, blood gas analysis, and serum vascular endothelial growth factor D (VEGF-D) levels between the two groups. We also evaluated the data from right heart catheterization in five patients and the images from optical coherence tomography of pulmonary arteries in two patients. Results: Echocardiography showed pulmonary hypertension in 15 patients (8.98%). Compared with the control group, LAM-PH group had a higher proportion of patients receiving oxygen therapy. Patients with PH had lower FEV1, FVC, FEV1/FVC, DLCO and higher serum VEGF-D levels compared with those without PH. Right heart catheterization was performed in five patients. Five patients had a pre-capillary pattern and three of these patients had severe pulmonary hypertension. Optical coherence tomography showed that there were no obvious abnormalities in the intima and lumen of the blood vessels in the two patients. Conclusions: The prevalence of PH in LAM is low. Patients in the LAM-PH group had more severe hypoxemia, worse lung function and higher serum VEGF-D levels than those in the control group. PH in LAM is mainly pre-capillary. Optical coherence tomography can evaluate the pulmonary artery vascular condition and help to identify the cause of pulmonary hypertension in LAM patients.