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Anoctamin 1 (ANO1) or TMEM16A gene encodes a member of Ca2+ activated Cl– channels (CaCCs) that are critical for physiological functions, such as epithelial secretion, smooth muscle contraction and sensory signal transduction. The attraction and interest in ANO1/TMEM16A arise from a decade long investigations that abnormal expression or dysfunction of ANO1 is involved in many pathological phenotypes and diseases, including asthma, neuropathic pain, hypertension and cancer. However, the lack of specific modulators of ANO1 has impeded the efforts to validate ANO1 as a therapeutic target. This review focuses on the recent progress made in understanding of the pathophysiological functions of CaCC ANO1 and the current modulators used as pharmacological tools, hopefully illustrating a broad spectrum of ANO1 channelopathy and a path forward for this target validation., Graphical abstract The abnormal expression or dysfunction of Ca2+ activated Cl– channel anoctamin 1 (ANO1) is involved in pathological phenotypes and diseases, suggesting that pharmacological modulation of ANO1 may serve as therapeutic potential and strategy.Image 1

Rupioid skin lesions usually develop on a background of immunosuppression and are grossly hyperkeratotic cone-shaped plaques with thick, dark, adherent, and lamellate crusts resembling limpet shells.1 Relatively few etiologies, mainly infectious, are relevant to the differential diagnosis of rupioid presentations, including syphilis, HIV, scabies, histoplasmosis, rupioid psoriasis (RupP), or reactive arthritis.1 RupP is an uncommon condition resulting from a pronounced inflammatory response, leading to abnormal keratinized scale mixing with copious sero-exudate.2 The lesions exhibit classic histopathologic findings of psoriasis.1 Drug-provoked psoriasis (either drug-aggravated or drug-induced) is similarly infrequent, with lithium, beta-blockers, and antimalarials being the most common causative agents.3 Drug-induced RupP is extremely rare, with only a few reports in the literature (Table I). Table I Summary of drug-provoked rupioid psoriasis (RupP) cases identified in PubMed

Objectives This meta-analysis evaluates assessment of pulmonary arterial hypertension (PAH), with a focus on clinical worsening and mortality. Background Cardiac magnetic resonance (CMR) has prognostic value in the assessment of patients with PAH. However, there are limited data on the prediction of clinical worsening, an important composite endpoint used in PAH therapy trials. Methods The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science databases were searched in May 2020. All CMR studies assessing clinical worsening and the prognosis of patients with PAH were included. Pooled hazard ratios of univariate regression analyses for CMR measurements, for prediction of clinical worsening and mortality, were calculated. Results Twenty-two studies with 1,938 participants were included in the meta-analysis. There were 18 clinical worsening events and 8 deaths per 100 patient-years. The pooled hazard ratios show that every 1% decrease in right ventricular (RV) ejection fraction is associated with a 4.9% increase in the risk of clinical worsening over 22 months of follow-up and a 2.2% increase in the risk of death over 54 months. For every 1 ml/m2 increase in RV end-systolic volume index or RV end-diastolic volume index, the risk of clinical worsening increases by 1.3% and 0.7%, respectively, and the risk of mortality increases by 0.9% and 1%. Every 1 ml/m2 decrease in left ventricular end-systolic volume index or left ventricular end-diastolic volume index increased the risk of death by 2.1% and 2.3%. Left ventricular parameters were not associated with clinical worsening. Conclusions This review confirms CMR as a powerful prognostic marker in PAH in a large cohort of patients. In addition to confirming previous observations that RV function and RV and left ventricular volumes predict mortality, RV function and volumes also predict clinical worsening. This study provides a strong rationale for considering CMR as a clinically relevant endpoint for trials of PAH therapies., Central Illustration

Background Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. Objectives This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. Methods Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. Results From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. Conclusions COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity., Central Illustration

A 48-year-old woman who had been receiving long-term interferon-β for 8 years for multiple sclerosis developed drug-induced World Health Organization group I pulmonary arterial hypertension. Triple therapy for pulmonary arterial hypertension and suspension of interferon-β led to improvement from a high-risk to low-risk state and improvement in exercise hemodynamics, including vascular distensibility, and right ventricle–pulmonary artery coupling. (Level of Difficulty: Advanced.), Central Illustration

We describe the use of direct percutaneous cardiac access to recanalize an atretic right pulmonary artery in an adolescent with complex congenital heart disease and right heart failure. This case highlights the problems associated with loss of central venous access and potential advantages of a direct cardiac approach to catheterization. (Level of Difficulty: Intermediate.), Graphical abstract

This paper reports a unique case of anomalous origin of the left coronary artery from the right pulmonary artery associated with scimitar syndrome. The presence of pulmonary hypertension may have contributed to maintain coronary perfusion, which likely prevented early significant coronary steal. This study reports the clinical course, diagnosis challenges, and management strategy. (Level of Difficulty: Intermediate.), Graphical abstract, This paper reports a unique case of anomalous origin of the left coronary artery from the right pulmonary artery associated with scimitar syndrome. The…

Management of pregnancy in patients with complex congenital heart disease and pulmonary arterial hypertension has always been a challenge. We are presenting a patient with complex congenital heart disease and borderline pulmonary arterial hypertension who complicated with pulmonary embolism during pregnancy. (Level of Difficulty: Beginner.), Graphical abstract, Management of pregnancy in patients with complex congenital heart disease and pulmonary arterial hypertension has always been a challenge…

Pulmonary arterial hypertension is a progressive vascular disease with a high mortality rate without proper therapy. Identification of the appropriate treatment for each patient is critical in regard to adverse effects, health care costs, ease of treatment, and the potential for prognostication. Treatment strategies typically begin with acute vasoreactivity testing, which is performed during a right heart catherization. If positive, a calcium channel blocker may work; however, another pulmonary arterial hypertension–specific medication is necessary when testing is negative. Acute vasoreactivity testing is currently recommended to be performed only in certain subgroups of pulmonary arterial hypertension, but not when related to connective tissue disease. In this report, we describe a patient who had systemic sclerosis–related pulmonary arterial hypertension with a positive acute vasoreactivity test result. The patient was placed on calcium channel blocker monotherapy that has been well tolerated for 12 years, resulting in improved symptoms and exercise capacity. The long-term response to calcium channel blocker therapy in systemic sclerosis–associated pulmonary arterial hypertension has not been previously described. In addition, pulmonary artery pressures have been well controlled. The absence of genetic smooth muscle variants prevalent in vasoresponsive idiopathic pulmonary arterial hypertension is also unique.

Background: Although balloon pulmonary angioplasty (BPA) improves symptoms and pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH), the effects of riociguat on hemodynamics and exercise capacity in patients after BPA remain to be elucidated. Methods and Results: This study was a single-center, prospective, randomized, open-label trial. From November 2015 to November 2018, we prospectively examined 21 patients with CTEPH (65 ± 9 years old, M/F 2/19) who showed hemodynamic improvement with mean pulmonary arterial pressure (mPAP)

Highlights • Long-term overall survival of CTEPH patients receiving PH-specific medial therapy is very reasonable. • Despite worse baseline characteristics at baseline, combination therapy showed similar survival as monotherapy. • Combination therapy strategy showed no difference in survival outcome., Objective The current experience with combination therapy in chronic thromboembolic pulmonary hypertension (CTEPH) is limited. We present the first survival results up to 5 years for dual combination therapy versus monotherapy in CTEPH. Methods All consecutive, non-operated CTEPH or residual PH after pulmonary endarterectomy patients treated with PH-specific medical therapy between January 2002 and November 2019 were included. We report and compare survival between monotherapy and (upfront or sequential) dual combination therapy until five years after medication initiation. Results In total, 183 patients (mean age 65 ± 14 years, 60% female, 66% WHO FC III/IV, 86% non-operated) were included, of which 83 patients received monotherapy and 100 patients received dual combination therapy. At baseline, patients receiving combination therapy had a higher NT-proBNP (p = 0.02) mean pulmonary artery pressure (p = 0.0001) and pulmonary vascular resistance (p = 0.02), while cardiac index was lower (p = 0.03). Total follow-up duration was 3.3 ± 1.8 years, during which 31 (17%) patients died. Estimated 1-, 3- and 5-year survival for monotherapy were 99%, 92% and 79%, respectively. For combination therapy percentages were 98%, 89% and 70%, respectively. Survival did not significantly differ between both groups (p = 0.22). Conclusion Survival up to 5 years for patients treated with combination therapy, regardless of the combination strategy, was similar as patients with monotherapy, despite worse clinical and haemodynamic baseline characteristics.

Obesity has reached epidemic proportions in the United States and in much of the westernized world, contributing to considerable morbidity. Several of these obesity-related morbidities are associated with greater risk for death with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 penetrates human cells through direct binding with angiotensin-converting enzyme 2 receptors on the cell surface. Angiotensin-converting enzyme 2 expression in adipose tissue is higher than that in lung tissue, which means that adipose tissue may be vulnerable to COVID-19 infection. Obese patients also have worse outcomes with COVID-19 infection, including respiratory failure, need for mechanical ventilation, and higher mortality. Clinicians need to be more aggressive when treating obese, especially severely obese, patients with COVID-19 infection.

Visual Abstract, Highlights • G protein-coupled receptors and tyrosine kinase receptors signal through the phosphoinositide 3-kinase/Akt/mTOR pathway to induce cell proliferation, survival, and growth. mTOR is a kinase present in 2 functionally distinct complexes, mTORC1 and mTORC2. • Functional disruption of mTORC1 by knockout of Raptor (regulatory associated protein of mammalian target of rapamycin) in smooth muscle cells ameliorated the development of experimental PH. • Functional disruption of mTORC2 by knockout of Rictor (rapamycin insensitive companion of mammalian target of rapamycin) caused spontaneous PH by up-regulating platelet-derived growth factor receptors. • Use of mTOR inhibitors (e.g., rapamycin) to treat PH should be accompanied by inhibitors of platelet-derived growth factor receptors (e.g., imatinib)., Summary Concentric lung vascular wall thickening due to enhanced proliferation of pulmonary arterial smooth muscle cells is an important pathological cause for the elevated pulmonary vascular resistance reported in patients with pulmonary arterial hypertension. We identified a differential role of mammalian target of rapamycin (mTOR) complex 1 and complex 2, two functionally distinct mTOR complexes, in the development of pulmonary hypertension (PH). Inhibition of mTOR complex 1 attenuated the development of PH; however, inhibition of mTOR complex 2 caused spontaneous PH, potentially due to up-regulation of platelet-derived growth factor receptors in pulmonary arterial smooth muscle cells, and compromised the therapeutic effect of the mTOR inhibitors on PH. In addition, we describe a promising therapeutic strategy using combination treatment with the mTOR inhibitors and the platelet-derived growth factor receptor inhibitors on PH and right ventricular hypertrophy. The data from this study provide an important mechanism-based perspective for developing novel therapies for patients with pulmonary arterial hypertension and right heart failure.

Visual Abstract, Highlights • Autonomic imbalance has been documented in patients with PAH. • Electrical VNS is known to restore autonomic balance and improve heart failure. • This study aimed to elucidate the therapeutic effects of VNS on severe PAH in a rat model. • VNS significantly restored autonomic balance, decreased mean pulmonary arterial pressure, attenuated pulmonary vascular remodeling, and preserved right ventricular function. In addition, VNS markedly improved the survival of rats with PAH. • Our findings may contribute greatly to the development of device therapy for PAH and widen the clinical applicability of VNS., Summary This study aimed to elucidate the therapeutic effects of electrical vagal nerve stimulation (VNS) on severe pulmonary arterial hypertension in a rat model. In a pathophysiological study, VNS significantly restored autonomic balance, decreased mean pulmonary arterial pressure, attenuated pulmonary vascular remodeling, and preserved right ventricular function. In a survival study, VNS significantly improved the survival rate in both the prevention (VNS from 0 to 5 weeks after a SU5416 injection) and treatment (VNS from 5 to 10 weeks) protocols. Thus, VNS may serve as a novel therapeutic strategy for pulmonary arterial hypertension.

Objective To study the echocardiographic features of criss-cross heart (CCH), a congenital cardiac anomaly characterized by crossed ventricular inflow streams, in Indian patients. Methods In this retrospective observational study, all pediatric echocardiograms performed in a single tertiary care institution in South India over a three-year period were scrutinized for a diagnosis of CCH. Demographic, clinical and echocardiographic data were collected from patients’ medical records and echocardiographic database. Crossed ventricular inflow streams was identified when there was inability to visualize both atrio-ventricular valves in a single imaging plane in cardiac four chamber view. Results CCH was diagnosed in five patients from 10,500 pediatric echocardiographic studies. The age at diagnosis ranged from one month to 8 years. Cyanosis was present in all but one of the five cases. Crossed ventricular inflow streams was present by definition in all cases, whereas superior-inferior ventricular relationship was present in only three cases. All cases were associated with ventricular septal defects. Atrio-ventricular discordance was seen in three cases and concordance in two. Ventriculo-arterial discordance was seen in three cases, concordance in one and double outlet right ventricle in one. Three cases had pulmonary stenosis and the other two had pulmonary arterial hypertension. Straddling of AV valve was observed in four cases and hypoplastic aortic arch in one case. Conclusion CCH is an extremely rare congenital cardiac anomaly. Superior-inferior ventricular relationship often co-exists with CCH, but is not necessarily present in all cases. CCH requires early diagnosis because of its common association with diverse cardiac anomalies.

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is one type under group 1 PH. Undiagnosed or delayed diagnosis of significant CHD might lead to significant PAH and at the end might lead to Eisenmenger syndrome. We could expect the degree of PAH in patients with CHD by proper clinical assessment as well as by the basic assessment tools including the chest x-ray (CXR), ECG, and transthoracic echocardiography (TTE). We are presenting a three and half years old child with a delayed/missed diagnosis of large patent ductus arteries (PDA) who present with significant PAH. Clinical evaluation, CXR, ECG, TTE, as well as cardiac catheterization data are presented, with a review of the current guidelines regarding the management of pediatric patients with PAH-CHD.

Background: To improve clinical outcome, patients with inoperable and residual chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with riociguat. The aim of this study is to explore long-term outcomes and to compare our ‘real world’ data with previous research. Methods: We included all consecutive patients with technical inoperable and residual CTEPH, in whom riociguat therapy was initiated from January 2014 onwards, with patients followed till January 2019. Survival, clinical worsening (CW), functional class (FC), N-terminal pro brain natriuretic peptide (NT-proBNP) and 6-minute walking distance (6MWD) were described yearly after riociguat initiation. Results: Thirty-six patients (50% female, mean age 64.9 ± 12.1 years, 54% WHO FC III/IV and 6MWD 337 ± 138 m could be included, with a mean follow-up of 2.3 ± 1.2 years. Survival and CW-free survival three years after initiation of riociguat were 94% and 78%, respectively. The 6MWD per 10 m at baseline was a significant predictor (HR 0.90 [0.83–0.97], p = 0.009) for CW. At three years follow-up the WHO FC and 6MWD improved and NT-proBNP decreased compared to baseline. Conclusion: Our study confirms that riociguat is an effective treatment in patients with technical inoperable and residual CTEPH at long-term follow-up. Although our results are consistent with previous studies, more ‘real world’ research is necessary to confirm long-term results. Keywords: Chronic thromboembolic pulmonary hypertension, Riociguat, Clinical outcome, Survival, Clinical worsening

Introduction Patients with mixed connective tissue disease (MCTD) have higher rates of pulmonary arterial hypertension (PAH) than the general population. PAH is a risk for perioperative respiratory and heart failure, and marked edema of colonic stoma after sigmoidectomy. We report a case of sigmoidectomy for sigmoid colon cancer in a patient with PAH associated with MCTD for whom perioperative treatment was planned to control pulmonary arterial pressure (PAP), and a surgical strategy to avoid complications attributable to PAH and MCTD was employed. Case presentation A 52-year-old woman with sigmoid cancer and severe PAH associated with MCTD underwent surgery. We controlled PAH by using intravenous epoprostenol. We selected open surgery without laparoscopy and Hartmann's operation. After surgery, severe perioperative complications were not detected, and the patient discharged from hospital 17 days after the operation. Discussion During surgery under general anesthesia, the mortality rate of PAH is high because of heart and respiratory failure. We planned to switch the PAH treatment from an oral agent to intravenous epoprostenol only in the preoperative period, and selected open surgery. We ligated the inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) below the branch of LCA to avoid marked edema of stoma. Consequently, we could avoid severe intraoperative and postoperative complications. Conclusions Controlling PAP using epoprostenol, open surgery, stoma and the ligation level for the IMA and IMV preventing are important to avoid perioperative complications of sigmoid colon cancer complicated by severe PAH., Highlights • The patient with PAH complicated by MCTD underwent Hartman’s operation for sigmoid colon cancer. • Control of PAH by epoprostenol preoperatively is important to prevent perioperative cardiac complications. • The level of ligation of the IMA and the LCA is important to avoid severe edema of stoma.

Pulmonary arterial hypertension (PAH) is a rare multifactorial disease with an unfavorable prognosis. Sildenafil therapy can improve functional capacity and pulmonary hemodynamics in PAH patients. Nowadays, it is increasingly recognized that the effects of sildenafil are pleiotropic and may also involve changes of the pro-/antioxidant balance, lipid peroxidation and autonomic control. In present study we aimed to assess the effects of sildenafil on the fatty acids (FAs) status, level of hydroxynonenal (HNE) and heart rate variability (HRV) in PAH patients. Patients with PAH were characterized by an increase in HNE and changes in the FAs composition with elevation of linoleic, oleic, docosahexanoic acids in phospholipids as well as reduced HRV with sympathetic predominance. Sildenafil therapy improved exercise capacity and pulmonary hemodynamics and reduced NT-proBNP level in PAH. Antioxidant and anti-inflammatory effects of sildenafil were noted from the significant lowering of HNE level and reduction of the phopholipid derived oleic, linoleic, docosahexanoic, docosapentanoic FAs. That was also associated with some improvement of HRV on account of the activation of the neurohumoral regulatory component. Incomplete recovery of the functional metabolic disorders in PAH patients may be assumed from the persistent increase in free FAs, reduced HRV with the sympathetic predominance in the spectral structure after treatment comparing to control group. The possibilities to improve PAH treatment efficacy through mild stimulation of free radical reactions and formation of hormetic reaction in the context of improved NO signaling are discussed., Highlights • Sildenafil showed antioxidant and anti-inflammatory effects in pulmonary hypertension. • Sildenafil reduced hydroxynonenal level and improved fatty acid profile in serum. • Improvement of heart rate variability and functional capacity was noted after therapy. • Mild prooxidant activity is suggested as the mechanism to improve sildenafil efficacy.

Graphical abstract, The renin-angiotensin system (RAS) is crucial for the physiology and pathology of all the organs. Angiotensin-converting enzyme 2 (ACE2) maintains the homeostasis of RAS as a negative regulator. Recently, ACE2 was identified as the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus that is causing the pandemic of Coronavirus disease 2019 (COVID-19). Since SARS-CoV-2 must bind with ACE2 before entering the host cells in humans, the distribution and expression of ACE2 may be critical for the target organ of the SARS-CoV-2 infection. Moreover, accumulating evidence has demonstrated the implication of ACE2 in the pathological progression in tissue injury and several chronic diseases, ACE2 may also be essential in the progression and clinical outcomes of COVID-19. Therefore, we summarized the expression and activity of ACE2 in various physiological and pathological conditions, and discussed its potential implication in the susceptibility of SARS-CoV-2 infection and the progression and prognosis of COVID-19 patients in the current review.

Background: Several cardiopulmonary exercise test (CPET) parameters (peak VO2, PetCO2 and VE/VCO2) emerged as tools for the prediction of pulmonary arterial hypertension (PAH). Less is known on ventilatory power (VP) in patients with suspect PAH. Aim: To ascertain possible correlations between VP derived at CPET and hemodynamic parameters at right heart catheterization (RHC) indicative of PH. Methods: Forty-seven consecutive outpatients with suspect of PAH were assessed by CPET and RHC; VP was defined as peak SBP divided by the minute ventilation-CO2 production slope at CPET and Diastolic Pressure Gradient (DPG), Trans-pulmonary Pressure Gradient (TPG), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) at RHC were also assessed and compared with VP. Results: VP values were inversely related to mPAP (r −0.427, p 0.003), DPG (r −0.36, p 0.019), TPG (r: −0.43, p 0.004), and PVR (r −0.52, p 0.001). Correlations remained significant even after correction at multivariate analysis for age and gender. VP values below median identified subjects with mPAP ≥ 25 mmHg with an odds ratio of 4.5 (95% confidence interval 1.05–19.36, p

Background: Catheter based treatment has gained wide acceptance for management of patent ductus arteriosus (PDA) ever since its introduction. Percutaneous closure in adults can be challenging because of anatomical factors including large sizes, associated pulmonary arterial hypertension (PAH) and co-morbidities. This study aimed to provide comprehensive contemporary data on the safety and efficacy of percutaneous device closure of PDA in adult and adolescent population at a large referral center. Methods: This single-center retrospective analysis included 70 patients (33 adolescents and 37 adults) who underwent successful percutaneous device closure of PDA between January 2011 and February 2017.Baseline patient demographics, clinical characteristics, procedural and device related variables, and immediate outcomes during hospital stay were recorded. Patients were followed up for residual shunt and complications. Results: Of 70 PDA device closure cases, 71.4% were females; the mean age was 23 years (range:10-58years). Devices used were 4-Cook’s detachable coils, 64-occluders (ADO-I and II, Lifetech, Cardi-O-Fix), 1-vascular plug and 1-ventricular septal occluder device. Device success was achieved in all including those with very large PDAs. At 24-h post-procedure, the success rate of transcatheter intervention was 95.7%. At 6-months follow up, complete closure was observed in all (mean follow up duration-531 days). In patients with severe PAH, significant immediate and sustained reduction of the mean pulmonary pressure was observed(77 mmHg to 33 mmHg;P = 0.014). No procedure-related complications including death, device embolization and stenosis of aorta or pulmonary artery occurred. Conclusions: In contemporary practice, percutaneous device closure is an effective and safe treatment option for adolescent and adult PDA patients. Keywords: Patent ductus arteriosus, Amplatzer duct occluder, Lifetech duct occluder, Cera device, Residual shunt

Background Numerous clinical trials have contributed to rapid advancements in the diagnosis and management of pulmonary arterial hypertension (PAH), yet patients often do not undergo right heart catheterization (RHC) with vasoreactivity testing and may receive a delayed or incorrect diagnosis. Efforts to improve standards of care include the designation of Pulmonary Hypertension Association (PHA)-Accredited PH Care Centers (PHCCs). This study evaluated current practices in the diagnosis and assessment of PAH. Methods A survey of 167 physicians who had ≥1 claim for PAH in the past 3 months was conducted. Results Of 167 respondents, 15% were affiliated with a PHCC, 40% had referred ≥1 patient with diagnosed PAH, and 79% had ≥1 patient referred to them by another physician who they then newly diagnosed with PAH. More than half (52%) reported having ≥1 patient who was previously misdiagnosed with PAH referred to them by another physician. RHC and vasoreactivity testing, respectively, were performed in 43% and 33% of patients with PAH who respondents referred to another physician, 86% and 67% of patients newly diagnosed by respondents, and 84% and 57% of patients who respondents considered accurately diagnosed prior to being referred to them. Respondents affiliated with a PHCC were more likely to try to refer to another physician affiliated with a PHCC, and to perform RHC and vasoreactivity testing. Conclusions Self-reported clinical practices often deviated from established guidelines. Future research should focus on both clinical efficacy and ways to encourage clinicians to bring their practices in line with well-supported, evidence-based recommendations.

Adult onset Still’s disease (AOSD) is an autoimmune disease characterized by systemic inflammation and is a rarely reported cause of pulmonary arterial hypertension (PAH). We describe the clinical course of a 40-year-old woman who presented with PAH 19 months after a diagnosis of AOSD. Sildenafil and immunosuppressive therapy with cyclosporine resulted in clinical and hemodynamic improvement with long-term survival 15 years after her initial presentation of AOSD. We review the literature for published cases of PAH due to AOSD and discuss the potential mechanisms relating inflammatory diseases and PAH.