Cases Of Pulmonary Arterial Hypertension Research Articles

A Very Uncommon Case of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) describes a rare, progressive disease of the pulmonary vasculature, involving a group of clinical conditions that result in precapillary pulmonary hypertension (PH). PAH is characterized by proliferative vasculopathy, and subsequent right heart failure. For the past several decades research has focused on identification of underlying molecular causes of this disease. Recently, there have been a number of reported cases of patients with scurvy developing pulmonary arterial hypertension. Thus, it has been hypothesized that vitamin C deficiency results in non-hypoxic activation of hypoxia inducible transcription factors (HIF) and low nitric oxide (NO) level in the pulmonary vasculature, leading to subsequent pulmonary vasculopathy and an exaggerated pulmonary vasoconstrictive response. Immediate supplementation of vitamin C is considered the definitive treatment, preventing an otherwise fatal outcome. In this paper, we describe a patient with a fatal case of scurvy related PAH, who was admitted with ecchymosis, oral ulceration, and dyspnea.

Incidence and survival impact of pulmonary arterial hypertension among patients with systemic lupus erythematosus: a nationwide cohort study

BackgroundNo population-based study has investigated the cumulative incidence of pulmonary arterial hypertension (PAH) in patients with newly diagnosed systemic lupus erythematosus (SLE) or the survival impact of PAH in this population.MethodWe used a nationwide database in Taiwan and enrolled incident SLE patients between January 1, 2000, and December 31, 2013. The cumulative incidence of PAH in the SLE patients and the survival of these patients were estimated by the Kaplan-Meier method. Potential predictors of the development of PAH were determined using a Cox proportional hazards regression model.ResultsOf 15,783 SLE patients, 336 (2.13%) developed PAH. The average interval from SLE diagnosis to PAH diagnosis was 3.66 years (standard deviation [SD] 3.36, range 0.1 to 13.0 years). Seventy percent of the patients developed PAH within 5 years after SLE onset. The 3- and 5-year cumulative incidence of PAH were 1.2% and 1.8%, respectively. Systemic hypertension was an independent predictor of PAH occurrence among the SLE patients (adjusted hazard ratio 2.27, 95% confidence interval 1.59–2.97). The 1-, 3-, and 5-year survival rates of SLE patients following the diagnosis of PAH were 87.7%, 76.8%, and 70.1%, respectively.ConclusionsPAH is a rare complication of SLE and the majority of PAH cases occur within the first 5 years following SLE diagnosis. Systemic hypertension may be a risk factor for PAH development in the SLE population. The overall 5-year survival rate after PAH diagnosis was 70.1%.

THE PATH OF LEAST RESISTANCE: A CASE OF METHAMPHETAMINE ASSOCIATED PULMONARY ARTERIAL HYPERTENSION AND SECUNDUM ATRIAL SEPTAL DEFECT MANIFESTING IN THE POSTPARTUM PERIOD

Methamphetamine use, known to cause oxidative stress and dysregulation of vascular tone, is increasingly seen in association with pulmonary arterial hypertension (PAH). We present a case of methamphetamine-associated PAH with severe hypoxemia and right to left shunt from a secundum ASD in a

Role of BRCA1-associated protein (BRAP) variant in childhood pulmonary arterial hypertension.

Although mutations in several genes have been reported in pulmonary arterial hypertension (PAH), most of PAH cases do not carry these mutations. This study aimed to identify a novel cause of PAH. To determine the disease-causing variants, direct sequencing and multiplex ligation-dependent probe amplification were performed to analyze 18 families with multiple affected family members with PAH. In one of the 18 families with PAH, no disease-causing variants were found in any of BMPR2, ACVRL1, ENG, SMAD1/4/8, BMPR1B, NOTCH3, CAV1, or KCNK3. In this family, a female proband and her paternal aunt developed PAH in their childhood. Whole-exome next-generation sequencing was performed in the 2 PAH patients and the proband’s healthy mother, and a BRCA1-associated protein (BRAP) gene variant, p.Arg554Leu, was identified in the 2 family members with PAH, but not in the proband’s mother without PAH. Functional analyses were performed using human pulmonary arterial smooth muscle cells (hPASMCs). Knockdown of BRAP via small interfering RNA in hPASMCs induced p53 signaling pathway activation and decreased cell proliferation. Overexpression of either wild-type BRAP or p.Arg554Leu-BRAP cDNA constructs caused cell death confounding these studies, however we observed higher levels of p53 signaling inactivation and hPASMC proliferation in cells expressing p.Arg554Leu-BRAP compared to wild-type BRAP. In addition, p.Arg554Leu-BRAP induced decreased apoptosis of hPASMCs compared with wild-type BRAP. In conclusion, we have identified a novel variant of BRAP in a Japanese family with PAH and our results suggest it could have a gain-of-function. This study sheds light on new mechanism of PAH pathogenesis.

Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases.

Heritable forms of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH) diverge by lung histopathological lesions, clinical and para-clinical presentation, their responsible genes, and mode of transmission. Since the identification of the BMPR2 gene in families affected by PAH, mutations in several other genes have been discovered for both forms. The mutation landscape in these new genes is not yet well known. We set up a next-generation sequencing-based targeted sequencing gene panel allowing known genes for PAH and PVOD/PCH to be analysed simultaneously. Genetic analysis was prospectively performed on 263 PAH and PVOD/PCH patients (adult and paediatric cases). Pathogenic mutations were identified in 19.5% of sporadic PAH patients (n=180), 54.5% of familial PAH patients and 13.3% of PVOD/PCH patients. BMPR2 was the most frequently mutated gene, followed by TBX4 in both paediatric and adult PAH. BMP9 mutations were identified in 1.2% of adult PAH cases. EIF2AK4 biallelic mutations were restricted to PVOD/PCH. A truncating mutation and a predicted loss-of-function variant were also identified in BMP10 in two severely affected sporadic PAH female patients. Our results confirm that mutations are found in genes beyond BMPR2 in heritable PAH, emphasise the role of TBX4 and BMP9, and designate BMP10 as a new PAH gene.

Demographics, treatment trends, and survival rate in incident pulmonary artery hypertension in Korea: A nationwide study based on the health insurance review and assessment service database.

Epidemiologic data regarding pulmonary arterial hypertension (PAH) have relied on registries from Western countries. We assessed the current status of PAH in the Korean population. The Health Insurance Review and Assessment Service (HIRA) claim database, which comprises nationwide medical insurance data of Koreans from 2008–2016, was assessed to determine the current status of PAH. Overall, 1,307 patients were newly diagnosed with PAH from 2008–2016 (0.0005%, annual incidence: 4.84 patients/1 million people/year). The mean age at diagnosis was 44±13 years (range 18–65) and patients were mostly women (n = 906, 69.3%). Cases of idiopathic PAH (51.6%) accounted for the largest proportion, followed by acquired PAH (APAH) associated with congenital heart disease (25.8%) and APAH with connective tissue disease (17.2%). Overall, 807 (61.7%) patients received a single PAH-specific treatment based on their last prescription, of which bosentan (50.6%) was the most frequently used. Only 240 (18.4%) patients received combination therapy, with the bosentan-beraprost combination (32.9%) being the most common. During the mean follow-up of 1.9 years, the 1-, 2-, 3-, and 5-year estimated survival rates were 85%, 62%, 54%, and 46%, respectively. The prevalence and incidence of PAH in the Korean population is currently comparable with that in previous registries. The 5-year survival rate was slightly higher in the Korean population than previously reported.

A NOVEL MUTATION IN A PATIENT WITH PULMONARY VENO-OCCLUSIVE DISEASE MASQUERADING AS PULMONARY ARTERIAL HYPERTENSION

A NOVEL MUTATION IN A PATIENT WITH PULMONARY VENO-OCCLUSIVE DISEASE MASQUERADING AS PULMONARY ARTERIAL HYPERTENSION

New cases of Glucose-6-Phosphate Dehydrogenase deficiency in Pulmonary Arterial Hypertension.

Pulmonary Arterial Hypertension (PAH) is a fatal disorder with limited treatment options and reduced life expectancy after diagnosis. Complex genetic backgrounds in PAH complicates identification of causative mutations that is essential for an understanding of the disease diagnostics and etiology especially for idiopathic PAH (iPAH). Hemolysis has been implicated as contributing to the pathobiology of PAH. Glucose-6-Phosphate Dehydrogenase (G6PD) expression and activity define erythrocyte’s antioxidant capacity, and its decrease contributes to erythrocyte fragility. As G6PD deficiency was previously reported in a limited number of PAH cases, we tested whether iPAH patients exhibit underlying G6PD alterations in erythrocytes. A cohort of 22 PAH patients and 8 non-PAH patients were recruited for this study. DNA isolated from Peripheral Blood Mononuclear Cells (PBMC) was used for detection of mutations in the coding region of the G6PD gene. RNA isolated from PBMC was used for determination of G6PD mRNA expression level. G6PD activity was measured in Red Blood Cell (RBC) pellets. Three patients had missense mutations in G6PD (Val291Met, Asn126Asp, Asp194Glu), however, only one mutation (Val291Met) results in a severe G6PD deficiency. A single patient with mutation (Asn126Asp) showed a 21% decrease in G6PD activity, two subjects showed G6PD deficiency without mutations, and one patient had a decreased level of G6PD mRNA and reduced enzyme levels. This study demonstrates that a moderate decrease in G6PD activity is associated with PAH. Screening for G6PD activity and mutations in the G6PD gene may provide early detection of individuals predisposed to PAH.

Lower DHEA-S levels predict disease and worse outcomes in post-menopausal women with idiopathic, connective tissue disease- and congenital heart disease-associated pulmonary arterial hypertension.

High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL-1) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH.

Exome Sequencing in Children With Pulmonary Arterial Hypertension Demonstrates Differences Compared With Adults

Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary arteriole remodeling, elevated arterial pressure and resistance, and subsequent heart failure. Compared with adult-onset disease, pediatric-onset PAH is more heterogeneous and often associated with worse prognosis. Although BMPR2 mutations underlie ≈70% of adult familial PAH (FPAH) cases, the genetic basis of PAH in children is less understood. We performed genetic analysis of 155 pediatric- and 257 adult-onset PAH patients, including both FPAH and sporadic, idiopathic PAH (IPAH). After screening for 2 common PAH risk genes, mutation-negative FPAH and all IPAH cases were evaluated by exome sequencing. We observed similar frequencies of rare, deleterious BMPR2 mutations in pediatric- and adult-onset patients: ≈55% in FPAH and 10% in IPAH patients in both age groups. However, there was significant enrichment of TBX4 mutations in pediatric- compared with adult-onset patients (IPAH: 10/130 pediatric versus 0/178 adult-onset), and TBX4 carriers had younger mean age-of-onset compared with BMPR2 carriers. Mutations in other known PAH risk genes were infrequent in both age groups. Notably, among pediatric IPAH patients without mutations in known risk genes, exome sequencing revealed a 2-fold enrichment of de novo likely gene-damaging and predicted deleterious missense variants. Mutations in known PAH risk genes accounted for ≈70% to 80% of FPAH in both age groups, 21% of pediatric-onset IPAH, and 11% of adult-onset IPAH. Rare, predicted deleterious variants in TBX4 are enriched in pediatric patients and de novo variants in novel genes may explain ≈19% of pediatric-onset IPAH cases.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life

Background:Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis.Aims and Objective:The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life.Materials and Methods:It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires.Results:Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH.Conclusion:The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH.

Abstract 24015: Genome-Wide Association Study of Vasodilator Response in Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a rare and fatal disease associated with variable therapeutic response, suggesting a genetic contribution. Vasodilator-responsive PAH accounts for a minority of PAH cases and is associated with dramatically improved survival over vasodilator-nonresponsive PAH. The objective of our study was to identify genetic influences on vasodilator drug response in PAH. Methods: Two cohorts of patients with Group I PAH confirmed by right heart catheterization were derived from the PAH Biobank (NHLBI R24HL105333), representing over 40 US institutions. Differences between hemodynamics at rest (baseline mean pulmonary arterial pressure, mPAP) and after vasodilator (nitric oxide, prostacyclin) administration were determined to define acute vasodilator drug response (with unchanged cardiac index) as a continuous measure. All cases were genotyped using HumanOmni5 with single nucleotide polymorphism (SNP) call rate &gt;99%, minor allele frequency (MAF)&gt;3%, and Hardy-Weinberg p-value&gt;0.01. Analysis was restricted to cases with European ancestry. We performed linear regressions in an additive model for acute vasodilator drug response with adjustment for baseline mPAP, age, gender, and first 3 principal components. A Bonferroni-corrected alpha=5x10 -8 was used in the discovery cohort and alpha=0.05 was used in the replication cohort. Results: The discovery cohort included 434 PAH cases and the replication cohort included 49 less severe PAH cases. QQ-plots showed no evidence of genomic inflation (lambda=1.00). Association of the intronic SNP rs8057488 (MAF 0.05) in the sorting nexin 29 gene ( SNX29 ) with acute vasodilator drug response reached genome-wide significance in the discovery cohort (beta= -7.03 mmHg, p=3.39x10 -8 ). A significant association between rs8057488 and acute vasodilator drug response was also observed in the replication cohort (beta = -6.48 mmHg, p=0.03). Conclusion: These findings implicate a novel association between SNX29 variation and differential responses to vasodilator treatment in Group I PAH. While requiring further replication in a larger independent cohort, these observations advance our understanding of the molecular underpinnings in PAH.

Long-term outcome and prognostic factors in pregnant women with pulmonary arterial hypertension associated with congenital heart disease

Objective: To investigate the perinatal outcome, risk factors and long-term outcome of pregnancy complicated with pulmonary arterial hypertension(PAH) and congenital heart diseases (CHD). Methods: Clinical data of 110 pregnant women who were diagnosed as PAH-CHD were retrospectively analyzed in the Department of Obstetrics and Gynecology and Surgical Intensive Care Unit at Beijing Anzhen Hospital from 2004 to 2013. The survival and treatment status were followed up. Results: 110 subjects consisted of 11 mild PAH, 33 moderate and 66 severe ones. The incidences of deterioration in New York Heart Association (NYHA) classes (≥2) during pregnancy, respiratory failure, pulmonary hypertension crisis and arrhythmia were 25.5% (28/110), 7.3% (8/110), 10.0% (11/110), 10.0% (11/110) respectively. Among them, the difference of deterioration in NYHA classes (≥2) during pregnancy among the three groups was statistically significant. A total of 8 (7.3%) maternal deaths occurred during hospitalization, all of whom were severe PAH cases. Multivariate analysis showed that pulmonary artery systolic pressure was a risk factor of perioperative death (OR=1.042, P=0.005). There were 55 cases (50.0%) of term delivery, and 35 cases (31.8%) of iatrogenic abortion. The proportion of term delivery in the severe PAH group was significantly lower. The proportion of iatrogenic abortion and small for gestational age infant (SGA) were higher in severe group. The incidence of neonatal malformations was 8.0% (6/75). The follow-up rate was 61.8% (63/102). Sudden death was reported in a parturient a few days after discharge. The remaining 62 patients survived during follow-up, while 53 patients (85.5%) were functional class (FC) Ⅰ-Ⅱ, 9 (14.5%) were FC Ⅲ-Ⅳ at follow-up. The cardiac function deterioration during pregnancy was not significantly correlated with long-term deterioration (P=0.767). Conclusions: Perinatal mortality and the incidence of maternal and fetal adverse events were high in pregnancy with PAH-CHD. Pulmonary artery systolic pressure is a major risk factor for perioperative mortality in pregnant women. PAH-CHD woman had good overall outcome after puerperium.

Genetics of Pulmonary Arterial Hypertension.

Tremendous progress has been made in understanding the genetics of pulmonary arterial hypertension (PAH) since its description in the 1950s as a primary disorder of the pulmonary vasculature. Heterozygous germline mutations in the gene coding bone morphogenetic receptor type 2 (BMPR2) are detectable in the majority of cases of heritable PAH, and in approximately 20% of cases of idiopathic pulmonary arterial hypertension (IPAH). However, recent advances in gene discovery methods have facilitated the discovery of additional genes with mutations among those with and without familial PAH. Heritable PAH is an autosomal dominant disease characterized by reduced penetrance, variable expressivity, and female predominance. Biallelic germline mutations in the gene EIF2AK4 are now associated with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. Growing genetic knowledge enhances our capacity to pursue and provide genetic counseling, although the issue remains complex given that the majority of carriers of PAH-related mutations will never be diagnosed with the disease.

Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era in Australia and New Zealand

Epidemiology and treatment strategies continue to evolve in pulmonary arterial hypertension (PAH). We sought to define the characteristics and survival of patients with idiopathic, heritable and drug-induced PAH in the current management era. Consecutive cases of idiopathic, heritable and drug-induced PAH were prospectively enrolled into an Australian and New Zealand Registry. Between January 2012 and December 2016, a total of 220 incident cases were enrolled (mean age 57.2±18.7years, female 69.5%) and followed for a median duration of 26 months (IQR17-39). Co-morbidities were common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1-year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6-minute distance at diagnosis independently predicted worse survival, whereas obesity was associated with improved survival. Co-morbidities other than obesity did not impact survival. Initial dual oral combination therapy was associated with a trend towards better survival compared with initial oral monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The epidemiology and survival of patients with idiopathic PAH in Australia and New Zealand are similar to contemporary registries reported in Europe and North America. Male sex and poorer exercise capacity are predictive of mortality whereas obesity appears to exert a protective effect. Despite current therapies, PAH remains a life-threatening disease associated with significant early mortality.

Long-term outcomes of dasatinib-induced pulmonary arterial hypertension: a population-based study.

This study aimed to describe the long-term outcomes of pulmonary arterial hypertension (PAH) induced by dasatinib.21 incident, right heart catheterisation-confirmed cases of dasatinib-induced PAH were identified from the French Pulmonary Hypertension Registry. Clinical and haemodynamic variables were compared from baseline to last follow-up (median (range) 24 (1-81) months).Median age was 52 years and 15 patients were female (71%). 19 patients received dasatinib for chronic myelogenous leukaemia for a median (range) duration of 42 (8-74) months before PAH diagnosis. No bone morphogenic protein receptor-2 (BMPR2) mutations were found in the 10 patients tested. Dasatinib was uniformly discontinued and 11 patients received PAH medications. Four patients died during follow-up. NewYork Heart Association functional class improved from 76% in class III/IV to 90% in class I/II (p<0.01). Median (range) 6-min walk distance improved from 306 (0-660) to 430 (165-635) m (p<0.01). Median (range) mean pulmonary arterial pressure improved from 45 (30-70) to 26 (17-50) mmHg (p<0.01) and pulmonary vascular resistance from 6.1 (3.2-27.3) to 2.6 (1.2-5.9) Wood units (p<0.01). Patients treated with PAH medications had worse baseline haemodynamics but similar long-term outcomes to untreated patients. PAH persisted in 37% of patients.Dasatinib-induced PAH frequently improves after discontinuation but persisted in over one-third of patients, therefore systematic follow-up is essential.

Rescuing BMPR2-driven endothelial dysfunction in PAH: a novel treatment strategy for the future?

Pulmonary arterial hypertension (PAH) may be idiopathic and corresponds to sporadic disease without any familial history or identified risk factors, or heritable when it occurs in the hereditary context; germline mutations in the bone morphogenetic protein receptor type 2 ( BMPR2 ) gene, are detected in 70% of heritable PAH cases (1). Even in sporadic cases, PAH is associated with impaired BMPRII signalling, occurring through small mothers against decapentaplegic (SMAD) proteins (2).

Three novel BMPR2 mutations associated with advanced pulmonary arterial hypertension

Mutations in the bone morphogenetic protein receptor type II (BMPR2) gene may result in the development of pulmonary arterial hypertension (PAH). However, the contribution of disease-causing mutations to the disease characteristics and responsiveness to recent treatment remains to be elucidated. We report three Japanese cases of advanced PAH with novel BMPR2 mutations, including two splicing mutations (IVS8-6_7delTTinsA and IVS9-2A>G) and one deletion (c.1279delG) mutation.

Role for Functional SOD2 Polymorphism in Pulmonary Arterial Hypertension in a Chinese Population

The superoxide dismutase 2 (SOD2) gene is a pivotal part of oxidative stress system, which could induce the onset of pulmonary arterial hypertension (PAH). In this study, we quantified the influence of a SOD2 exonic polymorphism (rs4880) on PAH susceptibility. We genotyped this single nucleotide polymorphism (SNP) by TaqMan, and evaluated its association with PAH susceptibility in a case-control study of 460 patients and 530 controls in China. There were significant differences between PAH cases and controls in both CC and TC+CC genotypes (p = 0.013 and p = 0.010, respectively). Furthermore, the number of variant alleles followed a dose-response manner (p trend was 0.023). Besides, the mRNA level and protein expression also indicated that the C allele of this variant decreased the expression of SOD2 gene (p = 0.004 in mRNA level and p = 0.012 in protein level) after the transfection of plasmids containing the different genotype of rs4480. There is significant association between SOD rs4880 polymorphism and the PAH susceptibility, and this polymorphism influenced PAH susceptibility by altering the expression of SOD2.

A Case Series of Young Patients with Completely Reversed Severe Pulmonary Hypertension

Pulmonary Arterial Hypertension (PAH) is a progressive symptomatic disorder, which may ultimately lead to death if left untreated. Although majority of PAH cases are idiopathic, pulmonary hypertension resulting due to certain underlying conditions are also observed frequently. In such cases, it becomes essential to identify any potentially treatable or reversible causes for PAH. There have been significant advances in the medical management of PAH and various medicines have been approved by US Food and Drug Administration (FDA) for various stages of PAH. With these therapies, there can be varying degrees of improvement in the pulmonary artery pressures and hemodynamic profile. Therefore, physiologic reversal can and does occur, sometimes to the point of normalization. We hereby present three such cases of severe PAH in patients below 50 years of age due to various aetiologies like left heart disease, isolated unilateral absence of right pulmonary artery with hypoplastic right lung and factor V Leiden mutation associated pulmonary thromboembolism, all of whose pulmonary artery pressures are completely normalised with adequate treatment of the underlying disease and with optimised medications for PAH, ultimately leading to tapering and stoppage of PAH medications.