Cause Of Pulmonary Hypertension Research Articles

Abstract 12982: Between a Rock and a Hard Place: Stiff Left Atrial Syndrome in a Patient With Hereditary Rickets

Introduction: Stiff left atrial syndrome (SLAS) is an uncommon cause of pulmonary hypertension (PH) that has been described as a complication of ablation for atrial fibrillation; here we describe a unique case of SLAS in the setting of extensive left atrial calcification from the treatment of hereditary hypophosphatemia (HH). Case Presentation: A 44-year-old woman with a history of HH presented for evaluation of progressive exertional dyspnea. Previous treatment with calcitriol and phosphate had been complicated by severe calcific mitral and aortic stenosis requiring aortic and mitral valve replacement eight years prior. She reported initial improvement in her symptoms after surgery, but more recently had noted worsening dyspnea and edema despite escalating her home diuretic dose. TTE was notable for moderately severe PH with no evidence of valvular or ventricular dysfunction. Chest CT showed extensive left atrial mural calcification (Figure A) with corresponding calcium visible in the wall of the left atrium on TTE (Figure B). The patient was admitted and underwent IV diuresis followed by RHC confirming mPAP of 41mmHg with a PCWP of 20mmHg and prominent V waves to 33mmHg (Figure C-D). PCWP was confirmed by wedge oxyhemoglobin saturation. Symptoms were improved but not resolved with additional diuresis. Discussion: In this patient with metastatic calcinosis related to the treatment of her HH, we believe her PH is most likely secondary to SLAS due to marked circumferential left atrial calcification. SLAS is characterized by decreased left atrial compliance, leading to large V waves in the absence of mitral regurgitation or an elevated LVEDP. Beyond diuresis, there are no proven treatments for PH due to SLAS.

Exercise hemodynamics by echocardiography and right heart catheterization in patients with chronic thromboembolic pulmonary disease

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is an important cause of pulmonary hypertension (PH). A subclinical form of PH is referred to as exercise-induced pulmonary hypertension (EIPH), and its prevalence in patients with chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension at rest is unknown. Purpose To explore the occurrence of exercise-induced pulmonary hypertension (PH) in patients with CTEPD and compare exercise echocardiography with right heart catheterization (RHC). Methods In total, 16 patients with CTEPD, all diagnosed after pulmonary embolism, underwent exercise echocardiography and exercise RHC with dynamic supine leg exercise using a cycle ergometer. CTEPH at rest was defined as mean pulmonary artery pressure (mPAP) >20 mmHg and pulmonary vascular resistance (PVR) ≥3WU. EIPH by RHC was defined as mPAP >30 mmHg with total pulmonary resistance (TPR) ≥3 WU. Based on these criteria, our patients with CTEPD are presented by a flow chart (Figure 1). Systolic pulmonary artery pressure by echocardiography was calculated by tricuspid regurgitation peak velocity (TR V max) and the Bernoulli formula: 4 × (TR V)2. The RHC examination followed the exercise echocardiography within 2 hours. Groups were compared with independent sample t-test. Results Four patients (25%) were diagnosed with EIPH by exercise RHC. Patients with EIPH had a mean mPAP at peak exercise of 40.5 mmHg (range 38 to 43mmHg) and TPR of 3.7 WU (range 3.0 to 4.3 WU). The same patients also had a higher TR V max at peak exercise during exercise echocardiography compared to the patients without EIPH (Table 2). None of the patients had signs of elevated left-sided filling pressure during exercise by RHC, and none had left ventricular diastolic dysfunction during exercise by echocardiography. Conclusion In total, 4 of 16 patients with CTEPD were diagnosed with EIPH. The same four patients also had abnormal pulmonary artery pressure rise during exercise echocardiography and invasive RHC. These findings suggest that exercise echocardiography may be useful for screening patients with CTEPD and suspected EIPH. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Ostfold Hospital Trust

PULMONARY CAPILLARY HEMANGIOMATOSIS: A CONUNDRUM FOR EXPERTS

PULMONARY CAPILLARY HEMANGIOMATOSIS: A CONUNDRUM FOR EXPERTS

A case of transient right ventricular failure secondary to severe pulmonary hypertension in setting of methamphetamine use

Methamphetamine has been documented to be associated with pulmonary hypertension. Past studies have shown the association of methamphetamine abuse with pulmonary hypertension; however, cases of isolated acute to subacute right heart failure secondary to methamphetamine use have not been documented. Acute to subacute right heart failure, secondary to methamphetamine use itself represents a diagnostic challenge as there is no specific protocol in place for evaluation for pulmonary hypertension secondary to methamphetamine use and high degree of suspicion is needed to differentiate it from other cardio-pulmonary conditions. Echocardiographic findings of increased right ventricular systolic pressure along with morphological findings suggesting cardiac remodeling in the setting of methamphetamine use is highly suspicious of acute to subacute right heart failure. Early recognition and management, along with long-term abstinence from methamphetamine use is critical to prevent chronic effects on myocardium and to prevent further cardiac remodeling. Although dedicated cardiothoracic imaging and cardiac catheterization can be beneficial; neither of these modalities are needed to establish the diagnosis and to initiate primary interventions. Computed tomography (CT) scan however would be beneficial in excluding other causes of pulmonary hypertension, such as primary pulmonary conditions and pulmonary embolism.

Pulmonary vascular disease and exercise hemodynamics in chronic liver disease

Background & aimsPortopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown in patients with stable chronic liver disease. MethodsWe assessed the pulmonary hypertension (PH) and HPS prevalence in a prospective registry study of our liver out-patient clinic in a tertiary center. Between 2011 and 2016, consecutive patients with cirrhosis or non-cirrhotic portal hypertension were prospectively enrolled after written informed consent. We excluded patients with acute decompensation of liver disease and other causes of PH like severe chronic heart or lung diseases and chronic thromboembolic PH. HPS was diagnosed using contrast enhanced echocardiography and blood gas analysis. Patients were screened for PH using an algorithm implementing severity of dyspnea, echocardiography, cardiopulmonary exercise testing and exercise echocardiography employing a threshold of systolic pulmonary arterial pressure (SPAP) = 50 mmHg at peak exercise. If the algorithm indicated an increased PH risk, patients were invited for invasive investigations by means of right heart and hepatic vein catheter. We defined POPH as resting mPAP≥21 mmHg and PVR>3WU and PAWP<15 mmHg, mild PH as resting mPAP = 21–24 mmHg, and exercise PH as mPAP>30 mmHg and TPR >3 WU at peak exercise. ResultsTwo-hundred-five patients were enrolled (male 75%; cirrhosis 96%; median age 57 yrs). Sixty-seven patients (33%) fulfilled HPS criteria but only two (1.0%) for severe (PaO2:50–60 mmHg) or very severe HPS (PaO2<50 mmHg). In 18/77 patients (23%) undergoing exercise echocardiography, SPAP at peak exercise exceeded 50 mmHg. Finally, n = 3 (1.5%) patients were invasively diagnosed with POPH, n = 4 (2.9%) with mild PH and n = 2 with exercise PH. ConclusionIn chronic liver disease, excluding acute decompensation and other causes of PH, POPH and severe HPS are rare findings while mild to moderate HPS and mild PH or exercise PH are more frequent.

Correlation between Pulmonary Artery Pressure and Vortex Duration Determined by 4D Flow MRI in Main Pulmonary Artery in Patients with Suspicion of Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the causes of pulmonary hypertension (PH) and requires invasive measurement of the mean pulmonary artery pressure (mPAP) during right heart catheterisation (RHC) for the diagnosis. 4D flow MRI could provide non-invasive parameters to estimate the mPAP. Twenty-five patients with suspected CTEPH underwent cardiac MRI. Mean vortex duration (%), pulmonary distensibility, right ventricular volumes and function were measured using 4D flow MRI and cine sequences, and compared with the mPAP measured by RHC. The mPAP measured during RHC was 33 ± 16 mmHg (10–66 mmHg). PH (defined as mPAP > 20 mmHg) was present in 19 of 25 patients (76%). A vortical flow was observed in all but two patients (92%) on 4D flow images, and vortex duration showed good correlation with the mPAP (r = 0.805; p < 0.0001). Youden index analysis showed that a vortex duration of 8.6% of the cardiac cycle provided a 95% sensitivity and an 83% specificity to detect PH. Reliability for the measurement of vortex duration was excellent for both intra-observer ICC = 0.823 and inter-observer ICC = 0.788. Vortex duration could be a useful parameter to non-invasively estimate mPAP in patients with suspected CTEPH.

Intensive ultrafiltration strategy restores kidney transplant candidacy for patients with echocardiographic evidence of pulmonary hypertension.

Pulmonary hypertension (PH) is prevalent in those with end-stage kidney disease (ESKD) and poses a barrier to kidney transplant due to its association with poor outcomes. Studies examining these adverse outcomes are limited and often utilize echocardiographic measurements of pulmonary artery systolic pressure (PASP) instead of the gold standard right heart catheterization (RHC). We hypothesized that in ESKD patients deemed ineligible for kidney transplant because of an echocardiographic diagnosis of PH the predominant cause of PH is hypervolemia and is potentially reversible. We conducted a prospective study of 16 patients with ESKD who were denied transplant candidacy. Prior echocardiograms and RHCs were reviewed for confirmation of PH. Patients were admitted for daily sessions of ultrafiltration for volume removal and repeat RHCs were performed following intervention. RHC parameters and body weight were compared before and after intervention. Statistical analysis was performed using PRISM GraphPad software. A p-value <.05 was considered statistically significant. Following intervention, the mean pulmonary artery pressure (mPAP) and pulmonary arterial wedge pressure decreased from 45.0 ± 3.06 to 29.1 ± 7.77 mmHg (p<.0001) and 22.2±5.06 to 13.1±7.25mmHg (p=.003), respectively. The pulmonary vascular resistance decreased from 4.73±1.99 to 4.28±2.07WU (p=.30). Eleven patients from the initial cohort underwent successful kidney transplantationpost-intervention with 100% survival at 1-year. In ESKD patients, diagnoses of PH made by echocardiography may be largely due to hypervolemia and may be optimized using an intensive ultrafiltration strategy to restore transplant candidacy.

Cardiac Amyloidosis Presenting as Isolated Severe Pulmonary Artery Hypertension

A 58-year-old woman presented with dyspnea on exertion and bilateral pedal edema for 3 months. She was found to have severe pulmonary hypertension (PH) with the right ventricular failure. The detailed evaluation did not reveal any secondary cause for PH (cardiac disease, pulmonary embolism, interstitial or other lung disease, collagen vascular disease, portal hypertension, or chronic liver disease). Meanwhile, her workup revealed multiple myeloma. Abdominal fat pad biopsy was performed because PH as an isolated manifestation of cardiac amyloidosis was previously reported. Thus, she was diagnosed to have systemic amyloidosis secondary to myeloma. PH was attributed to cardiac amyloidosis. We present a patient with PH and amyloidosis secondary to multiple myeloma. PH and primary systemic amyloidosis without cardiac or parenchymal lung involvement are extremely rare with only a few cases reported in the past.

Pulmonary hypertension in interstitial lung disease: an area of unmet clinical need.

Pulmonary hypertension (PH) is present in an important proportion of patients with interstitial lung diseases (ILDs), encompassing a large, heterogeneous group of diffuse parenchymal lung diseases. Development of ILD-related PH is associated with reduced exercise capacity, increased need for supplemental oxygen, decreased quality of life and earlier death. Diagnosis of ILD-related PH is important and requires a high index of suspicion. Noninvasive diagnostic assessment can suggest the presence of PH, although right heart catheterisation remains the gold standard to confirm the diagnosis and to assess its severity. A comprehensive assessment is needed to make sure reversible causes of PH have been ruled out, including thromboembolic events, untreated hypoxaemia and sleep disordered breathing. The results of trials concerning pulmonary vasodilators in this particular patient group have been disappointing and, in some cases, were even associated with an increased risk of harm. Newer strategies such as medications administered through inhalation and combinations with antifibrotic drugs show encouraging results. Moreover, unravelling the role of the vasculature in the pathophysiology of pulmonary fibrosis and ILD-related PH may potentially unlock new therapeutic opportunities.

A curious case of pulmonary hypertension in a child

BackgroundPulmonary hypertension in young children can be due to a myriad of conditions. Few aetiologies of pulmonary hypertension are potentially reversible. An extensive workup for the cause of pulmonary hypertension is a must before attributing it to idiopathic pulmonary hypertension. We describe an uncommon aetiology of pulmonary hypertension in a young boy.Case presentationA 12-year-old child, with past history of tubercular pleural effusion, presented with dyspnoea on exertion and easy fatiguability for 2 years. He was evaluated elsewhere and was being treated as primary pulmonary hypertension with pulmonary vasodilators. The child was revaluated since the clinical features were not completely favouring the diagnosis. On detailed evaluation, a diagnosis of constrictive pericarditis was made. He was referred for pericardiectomy.ConclusionsConstrictive pericarditis presenting with severe pulmonary hypertension without congestive symptoms is very rare. In patients presenting with pulmonary hypertension, always look for a reversible cause before labeling them as idiopathic PAH.

LncRNA GAS5 promotes spermidine‑induced autophagy through the miRNA‑31‑5p/NAT8L axis in pulmonary artery endothelial cells of patients with CTEPH

Chronic thromboembolic pulmonary hypertension (CTEPH) is a leading cause of pulmonary hypertension. The present study investigated the mechanisms of long non-coding RNA growth arrest-specific transcript 5 (GAS5) on spermidine (SP)-induced autophagy. Pulmonary artery endothelial cells (PAECs) were collected from patients with CTEPH and the rat model. Immunofluorescence, Western blots, reverse transcription-quantitative polymerase chain reaction, bioinformatics, rapid amplification of cDNA ends assays, luciferase reporter assays, RNA-binding protein immunoprecipitation assays, GFP-LC3 adenoviruses, tfLC3 assays and transmission electron microscopy were performed. The results revealed that SP-induced autophagy increased GAS5 in PAECs. The upregulation of GAS5 enhanced and the downregulation of GAS5 reversed the roles of SP in PAECs. Furthermore, GAS5 promoted SP-induced autophagy in PAECs by targeting miRNA-31-5p. The miRNA-31-5p mimic suppressed and the inhibitor promoted SP-induced autophagy. Furthermore, N-Acetyltransferase 8 Like (NAT8L) was a target gene of miRNA-31-5p and knockdown of NAT8L inhibited the autophagic levels of PAECs. In vivo, SP treatment decreased miRNA-31-5p and increased NAT8L levels, which was reversed by the knockdown of GAS5. The downregulation of GAS5 abolished the stimulatory role of SP in PAECs of CTEPH rats. In conclusion, GAS5 promoted SP-induced autophagy through miRNA-31-5p/NAT8L signaling pathways in vitro and in vivo and GAS5 may be a promising molecular marker for therapies of CTEPH.

Update in approaches to pulmonary hypertension because of left heart disease.

Left heart disease is the most common cause of pulmonary hypertension. This review summarizes the current care of patients with pulmonary hypertension caused by left heart disease (PH-LHD) and discusses recent and active clinical trials in this patient population. The primary focus of interventions aimed at treating PH-LHD address the treatment of left heart disease. Significant advancements in the treatment of heart failure with preserved ejection fraction (HFpEF), a frequent cause of PH-LHD, are supported in the current literature. Patients with residual pulmonary hypertension despite optimal treatment of left heart disease have poor outcomes. Yet, interventions targeting the pulmonary vasculature in PH-LHD patients have not demonstrated significant benefits in studies to date. Current work focuses on differentiating isolated postcapillary pulmonary hypertension (IpcPH) from combined precapillary and postcapillary pulmonary hypertension (CpcPH) in a clinically consistent manner. It is hopeful that thorough phenotyping of PH-LHD patients will translate into effective treatment strategies addressing pulmonary vascular disease. Referral to centers of excellence, considerations for enrollment in clinical trials, and evaluation for transplant is recommended for patients with residual pulmonary hypertension despite optimal treatment of left heart disease, particularly those with CpcPH.

Hsa_circ_0016070/micro-340-5p Axis Accelerates Pulmonary Arterial Hypertension Progression by Upregulating TWIST1 Transcription Via TCF4/β-Catenin Complex.

Background Hypoxia is considered a major leading cause of pulmonary hypertension (PH). In this study, the roles and molecular mechanism of circ_0016070 in PH were studied. Methods and Results The expression of circ_0016070 in serum samples, human pulmonary artery smooth muscle cells and hypoxia/monocrotaline-treated rats was determined by real-time quantitative polymerase chain reaction. Cell viability, migration, and apoptosis were analyzed by Cell Counting Kit-8, wound healing, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays, respectively. The molecular interactions were validated using RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase reporter assays. The levels of phenotype switch-related proteins were evaluated by Western blot and immunohistochemistry. The pathological characteristics were assessed using hematoxylin and eosin staining. circ_0016070 was highly expressed in the serum samples, hypoxia-induced pulmonary artery smooth muscle cells and pulmonary arterial tissues of PH rats. Downregulation of circ_0016070 ameliorated the excessive proliferation, migration, vascular remodeling, and phenotypic transformation but enhanced cell apoptosis in the PH rat model. In addition, micro (miR)-340-5p was verified as a direct target of circ_0016070 and negatively regulated TCF4 (transcription factor 4) expression. TCF4 formed a transcriptional complex with β-catenin to activate TWIST1 (Twist family bHLH transcription factor 1) expression. Functional rescue experiments showed that neither miR-340-5p inhibition nor TWIST1 or TCF4 upregulation significantly impeded the biological roles of circ_0010670 silencing in PH. Conclusions These results uncovered a novel mechanism by which circ_0016070 play as a competing endogenouse RNA of miR-340-5p to aggravate PH progression by promoting TCF4/β-catenin/TWIST1 complex, which may provide potential therapeutic targets for PH.

Vascular anomaly diagnosis by central venous catheter misplacement: a case report

BackgroundCongenital heart diseases rarely have a primary manifestation in adulthood. They are a rare cause of pulmonary hypertension in adults.Case presentationA 70-year-old woman of Eurasian descent underwent emergency surgery for bowel ischemia. Her history of mild pulmonary hypertension likely correlates with a peculiar diagnosis of an anatomic anomaly on the postoperative x-ray and computed tomography scan. The central venous catheter was misplaced. Initial management consisted of removal of the catheter. The diagnosis, partial anomalous pulmonary venous return, may pose a clinical therapeutic dilemma.ConclusionsPartial anomalous pulmonary venous return is a potentially treatable cause of pulmonary hypertension. With the current trend toward more medical imaging, we expect this diagnosis to be made more often in the future.

Partial anomalous pulmonary venous return in adults. Insight into pulmonary hypertension

Partial anomalous pulmonary venous return (PAPVR) is a rare congenital heart disease (CHD) where pulmonary veins drain into pulmonary circulation leading to a left-to-right shunt. PAPVR can lead to serious consequences, ie pulmonary hypertension (PH). To date, predictors of PH are not well established. The aims of this study were (1) to determine the prevalence of PAPVR (2) to identify the impact of PAPVR on the right ventricle, (3) to determine the prevalence of PH in the PAPVR population and to identify its predictive factors. Patients aged ≥18 years with a non-operated PAPVR and patients operated after the age of 18 were enrolled. Patients with other potential causes of PH were excluded. PH was defined based on right heart catheterization (RHC). For patients without RHC, PH was considered when echocardiographic systolic transtricuspid peak velocity was ≥ 3.4 m/s. Fifty patients were included. Mean patient age was 50 ± 18 years with a 60% female predominance. PAPVR was mostly arising from the right lung (76% of cases) and was associated with CHD in 18 patients (36%). Most of them (83%) were sinus venosus atrial septal defect (ASD). PAPVR was diagnosed by chest computed tomography (CT) in 37 patients (74%). The reported prevalence of PAPVR was 0.2% (23/13606 chest CT reports). PH was identified in 7 patients of the cohort (14%) and 2 of them had Eisenmenger syndrome. All the echocardiographic parameters of RV dimensions were increased. PH group compared to group without PH had a decreased RV FAC (35 ± 13% vs 43 ± 10%, P = 0.049), a decreased RV endoGLS (−18 ± 5% vs −23 ± 4%, P = 0.01) and a significantly higher Qp/Qs ratio (2.2 [1.5;3.0] vs 1.1 [1.0;1.4], P = 0.013). Qp/Qs ratio was the only significant predictive factor for PH (OR = 4.87; P = 0.025), with an AUC of 0.87 ( P = 0.016) and the optimal threshold value was 1.95. Prevalence of PAPVR is 0.2% based on chest CT database. 14% of the patients with PAPVR developed PH and 30% of them had Einsenmenger syndrome. RV function parameters (FAC and endoGLS) were significantly decreased in PH group. Qp/Qs was the only significant predictive factor for PH.

P430 TUMORAL THROMBOTIC MICROANGIOPATHY: A RARE CAUSE OF ACUTE PULMONARY HYPERTENSION

Abstract Introduction Among the causes of acute pulmonary hypertension, the occlusion of the little pulmonary vessels caused by tumoral microemboli, even from an unknown neoplasm, is an infrequent condition with a very poor prognosis. Clinical Case A 55–years old woman with no relevant past medical history presented to the Emergency Department with dyspnea at rest, desaturation, palpitations and a brief episode of chest pain, after several days of fatigue and exertional dyspnea. ECG showed sinus tachycardia and signs of right ventricle pressure overload with inverted T waves in V3–V4 and in the inferior leads (Fig. 1). On laboratory tests there were high D–dimer values and a slightly elevated TnI. Blood gas analysis showed hypoxemic hypocapnic respirstory alkalosis. An Echocardiogram revealed severe dilatation and dysfunction of the right ventricle and signs of high probability of pulmonary hypertension (Fig. 2). Pulmonary CT scan ruled out embolism and showed irregular thickening of the interstitium and mediastinal lymphoadenopathy. Then, a rapid clinical deterioration happened, refractory to inotropes infusion and larger volumes of oxygen. The programmed diagnostic pathway cannot be pursued. On day 4, there was respiratory distress and pulseless electrical activity cardiac arrest during endotracheal intubation. ECMO mechanical support was positioned but on day 7 the patient died. Autopsy, made to discover the cause of pulmonary hypertension, revealed the presence of a colonic invasive adenocarcinoma with micropapillary pattern and thoracic and pelvic lymph–nodal metastases. Microscopic evaluation of the lungs showed a widespread neoplastic vascular invasion with microthromboemboli (Fig. 3). Discussion Tumoral thrombotic microangiopathy is a cause of pulmonary hypertension of multifactorial origin and should be suspected in cases of pulmonary hypertension without pulmonary embolism or interstitial lung disease. The rarity of this condition and the absence of an oncological medical history make difficult the diagnostic hypothesis. Besides, the lacking of an effective therapy makes the prognosis poor.

Twenty-Year Experience and Outcomes in a National Pediatric Pulmonary Hypertension Service.

Rationale: Pediatric pulmonary hypertension is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases, contributions of different pulmonary hypertension subtypes, therapeutic strategies, and clinical outcomes in children. Objectives: To report the 20-year experience of a large UK National Pediatric Pulmonary Hypertension Service focusing on epidemiology and clinical outcomes. Methods: Consecutive patients presenting between 2001 and 2021 were included, and survival analysis was performed for incident patients. Measurements and Main Results: Of 1,353 patients assessed, a pulmonary hypertension diagnosis was made in 1,101 (81.4%) patients (51% female, median age, 2.6 [interquartile range, 0.8-8.2] years). The most common form was pulmonary arterial hypertension in 48%, followed by 32.3% with pulmonary hypertension due to lung disease. Multiple contributory causes of pulmonary hypertension were common, with 16.9% displaying features of more than one diagnostic group. The annual incidence of childhood pulmonary hypertension was 3.5 (95% confidence interval [CI], 3.3-3.8) per 1 million children, and the prevalence was 18.1 (95% CI, 15.8-20.4) per 1 million. The incidence was highest for pulmonary hypertension due to lung disease in infancy (15.0 [95% CI, 12.7-17.2] per 1 million per year). Overall, 82.4% patients received pulmonary arterial hypertension therapy, and escalation to triple therapy during follow-up was required in 13.1%. In 970 (88.1%) incident patients, transplant-free survival was 86.7% (95% CI, 84.5-89%) at 1 and 68.6% (95% CI, 64.7-72.6%) at 10 years. Pulmonary hypertension due to left heart disease had the lowest survival (hazard ratio, 2.0; 95% CI, 1.36-2.94; P < 0.001). Conclusions: Clinical phenotypes of pediatric pulmonary hypertension are heterogeneous and overlapping, with clinical phenotypes that evolve throughout childhood. Despite widespread use of pulmonary arterial hypertension therapy, the prognosis remains poor.

Lung Transplant Outcomes in Patients with Pulmonary Veno-Occlusive Disease

<h3>Purpose</h3> Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Prognosis of PVOD is worse than PAH. Most patients need lung transplantation. Previous study showed that PVOD patients had higher waitlist mortality compared to PAH patients. To date, there are no study report outcomes of lung transplant in this population. We would like to study the outcome and compare with IPAH patients. <h3>Methods</h3> This is a retrospective observational study. Patients with a diagnosis of PVOD and PAH underwent lung transplant between 2005 and 2018 were identified from SRTR database. Numerical data were reported in mean and standard deviation. Categorical data were reported in count and percent. T-test and Chi-square test were performed to compare variables between 2 groups. Survival was compared using Kaplan-Meier (K-M) method. <h3>Results</h3> 61 PVOD patients and 970 PAH patients underwent lung transplant were identified. There was no significant difference in age and BMI. Patients with PVOD had significant lower post-transplant systolic, diastolic and mean PA pressure and higher cardiac output. LAS at matching were not significantly different. PVOD patients had shorter time on waiting list (152.7±263.34 vs 337.56±511.14, p<0.01). Proportion of patients requiring ECMO post lung transplant were higher in PVOD group (13.11% vs 4.23%, p<0.01). Proportion of patients developing primary graft dysfunction (PGD) were lower in PVOD group (37.5% vs 61.93%, p=0.056). There was no difference of length of stay, FEV1, FVC, PCO2 post lung transplant and acute rejection between 2 groups. Survivals were not different between 2 groups using K-M method (p=0.33). <h3>Conclusion</h3> We found that PVOD patients who underwent lung transplant had shorter waiting time compared to PAH patients which suggest that disease severity of PVOD is higher than PAH. Despite that more PVOD patients required ECMO support post-operative, patient survival and other long-term outcomes such as lung function or rejection were not different between from PAH patients.

Pulmonary Capillary Hemangiomatosis and Refractory Hypoxemia During PH Therapy

<h3>Introduction</h3> Pulmonary capillary hemangiomatosis (PCH), a rare cause of pulmonary hypertension (PH), presents clinically with right heart dysfunction and may be indistinguishable from typical pulmonary arterial hypertension. Vasodilator therapy exacerbates hypoxemia in PCH despite improvement in heart failure symptoms. Lung transplant is the only definitive therapy. We present the case of a patient succumbing to progressive hypoxemia on PH therapy during lung transplant evaluation. Autopsy revealed PCH. <h3>Case Report</h3> A 42-year-old female with PH due to undifferentiated connective tissue disease presented with acute respiratory distress. She was diagnosed 2 years prior and initially treated with macitentan, tadalafil and diuretics with clinical improvement; however, worsening shortness of breath and new finding of hypoxemia developed after 1 year. Imaging revealed faint patchy nodular opacities initially attributed to UCTD-associated pneumonitis. Steroids and mycophenolate failed to achieve radiographic improvement. Repeat right heart catheterization showed continued elevation in pulmonary artery pressure and stably reduced cardiac output. Subcutaneous infusion of Treprostinil was initiated 2 months prior to admission, which worsened hypoxemia. Clinical diagnosis of pulmonary veno-occlusive disease (PVOD) vs PCH was suspected and lung transplant evaluation initiated. On admission, patient presented with syncope and was found to have refractory hypoxemia despite high-flow oxygen supplementation. Cardiogenic shock and hypoxemic respiratory failure ensued, resulting in hepatic and renal failure, leading to cardiac arrest and unsuccessful resuscitation. Autopsy showed PCH. <h3>Summary</h3> Refractory hypoxemia during up-titration of vasodilator therapy for PH should prompt clinical suspicion for atypical causes of PH such as PCH. Early lung transplant referral is essential if PCH/PVOD is suspected given its poor prognosis and potentially harmful responses associated with traditional PH therapy.

Expression of apoptotic proteins in the pulmonary artery of dogs with pulmonary hypertension secondary to degenerative mitral valve disease

Degenerative mitral valve disease (DMVD) is a common cause of pulmonary hypertension (PH) in dogs. Medial thickening of the pulmonary artery is a common histopathological change in PH. The cause of medial thickening could be a decrease in apoptosis of pulmonary arterial smooth muscle cells (SMCs). This study aimed to detect the expression of apoptosis-related proteins in the pulmonary artery of dogs with PH secondary to DMVD (DMVD+PH) compared with DMVD without PH (DMVD) and healthy dogs (control). Lung samples were collected from three groups, including the control (n = 5), DMVD (n = 7) and DMVD+PH (n = 7) groups. Masson trichrome, α-SMA and apoptotic proteins including Bax, Bcl2 and caspase-3 and -8 were stained. The results showed that the percentage of medial thickness (%MT) and the average number of pulmonary arterial SMCs were greater in the DMVD and DMVD+PH groups than in the control group, and they were greatest in the DMVD+PH group. Bax, Bcl2, and caspase-3 and -8 were mainly expressed in the medial layer of the pulmonary artery. The percentage of Bax and caspase-3 and -8 positive cells was higher in the DMVD group than in the DMVD+PH group, whereas the percentage of Bcl2 positive cells was increased in the DMVD+PH group. These results suggested that the pro-apoptotic activity of pulmonary arterial SMCs occurred mainly in the DMVD group and decreased dramatically in the DMVD+PH group. In conclusion, an increase in medial thickness in dogs with PH secondary to DMVD may relate to a decrease in pro-apoptotic activity of pulmonary arterial SMCs.