Acute Pulmonary Arterial Hypertension Research Articles

Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increased Mitochondrial Fission In Vitro and Atherosclerosis in High-Fat-Diet-Fed ApoE-/- Mice.

Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), have been recently described, and their potential therapeutic targets for treating cardiovascular disease have been shown, including acute myocardial infarction (AMI), anthracycline cardiomyopathy and pulmonary arterial hypertension (PAH). Here, we examined the role of MiD49 and MiD51 in atherosclerosis. MiD49/51 expression was increased in the aortic valve endothelial cells (ECs) of high-fat diet-induced atherosclerosis in ApoE-/-mice and IL-8-induced human umbilical vein endothelial cells (HUVECs), which accelerated dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Silencing MiD49/51 reduced atherosclerotic plaque size, increased collagen content, and decreased the IL-8-induced adhesion and proliferation of HUVECs. MiD51 upregulation resulted from decreased microRNA (miR)-107 expression and increased hypoxia-inducible factor-1a (HIF-1a) expression. Treatment with miR-107 mimics decreased atherosclerotic plaque size by reducing HIF-1α and MiD51 production. Both MiD49 and MiD51 were involved in atherosclerotic plaque formation through Drp1-mediated mitochondrial fission, and the involvement of MiD51 in this process was the result of decreased miR-107 expression and increased HIF-1α expression. The miR-107-HIF-1α-MiD51 pathway might provide new therapeutic targets for atherosclerosis.

Transcatheter Ductus Arteriosus Stenting for Acute Pediatric Pulmonary Arterial Hypertension is Associated with Improved Right Ventricular Echocardiography Strain.

Interventional therapies for severe pulmonary arterial hypertension (PAH) can provide right ventricular (RV) decompression and preserve cardiac output. Transcatheter stent placement in a residual ductus arteriosus (PDA) is one potentially effective option in critically ill infants and young children with PAH. We sought to assess recovery of RV function by echocardiographic strain in infants and young children following PDA stenting for acute PAH. Retrospective review of patients < 2years old who underwent PDA stenting for acute PAH. Clinical data were abstracted from the electronic medical record. RV strain (both total and free wall components) was assessed from echocardiographic images at baseline and 3, 6, and 12months post-intervention, as well as at last echocardiogram. Nine patients underwent attempted ductal stenting for PAH. The median age at intervention was 38days and median weight 3.7kg. One-third (3of 9) of patients had PAH associated with a congenital diaphragmatic hernia. PDA stents were successfully deployed in eight patients. Mean RV total strain was - 14.9 ± 5.6% at baseline and improved to - 23.8 ± 2.2% at 6 months post-procedure (p < 0.001). Mean free wall RV strain was - 19.5 ± 5.4% at baseline and improved to - 27.7 ± 4.1% at 6 months (p = 0.002). Five patients survived to discharge, and four patients survived 1 year post-discharge. PDA stenting for severe, acute PAH can improve RV function as assessed by strain echocardiography. The quantitative improvement is more prominent in the first 6 months post-procedure and stabilizes thereafter.

Clinical Significance of MicroRNAs, Long Non-Coding RNAs, and CircRNAs in Cardiovascular Diseases.

Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY

Efficacy of interatrial shunt devices: an opening window to acute pulmonary hypertensive crisis and chronic pulmonary arterial hypertension.

The current study aimed to elucidate the efficacy of interatrial shunt device (IASD) for the treatment of acute pulmonary hypertensive crisis (PHC) and chronic pulmonary arterial hypertension (PAH). After establishing chronic PAH models using dehydrogenized monocrotaline (DHMCT), PAH dogs were implanted with IASDs (group A) or received no intervention (group B). One month later, DHMCT was injected again to establish an acute PHC. The prognosis, hemodynamics, ultrasound cardiography, electrocardiogram, and lung pathology of the dogs were observed. The baseline mean pulmonary arterial pressure increased from 12.70 ± 1.03 to 19.95 ± 1.75mmHg and established a chronic PAH model 2 months after DHMCT injection (1.50mg/kg). After an additional injection of DHMCT (1.50mg/kg) in the chronic PAH model, acute PHC occurred. Mean PAP, sPAP, and pulmonary vascular resistance increased to 22.67 ± 1.80mmHg, 35.70 ± 1.66mmHg, and 12.50 ± 3.50 WOOD U, respectively. Cardiac output (CO) decreased to 1.31 ± 0.26 L/min, and the right-to-left shunt caused hypoxemia. The survival rates of the dogs with and those without IASD were 70.0% and 22.2% (P = 0.037), respectively. Six months after PHC, the CO between the dogs with and those without IASD were 1.44 ± 0.11 L/min and 1.18 ± 0.04 L/min (P = 0.028). The long-term survival rates were 50.0% and 22.2%, respectively (P = 0.21). IASD might be efficacious and beneficial for treating acute PHC and chronic PAH, as well as improving prognosis.

Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta-analysis.

Preclinical studies suggest mesenchymal stromal cell extracellular vesicles (MSC‐EVs) reduce inflammation and improve organ function in lung diseases; however, an objective analysis of all available data is needed prior to translation. Using rigorous meta‐research methods, we determined the effectiveness of MSC‐EVs for preclinical respiratory diseases and identified experimental conditions that may further refine this therapy. A systematic search of MEDLINE/Embase identified 1167 records. After screening, 52 articles were included for data extraction and evaluated for risk of bias and quality of reporting in study design. A random effects meta‐analysis was conducted for acute lung injury (ALI; N = 23), bronchopulmonary dysplasia (BPD; N = 8) and pulmonary arterial hypertension (PAH; N = 7). Subgroup analyses identified EV methods/characteristics that may be associated with improved efficacy. Data is presented as standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CI). For ALI, MSC‐EVs markedly reduced lung injury (SMD ‐4.33, CI ‐5.73 to ‐2.92), vascular permeability (SMD ‐2.43, CI ‐3.05 to ‐1.82), and mortality (RR 0.39, CI 0.22 to 0.68). Small EVs were more consistently effective than large EVs whereas no differences were observed between tissue sources, immunocompatibility or isolation techniques. For BPD, alveolarization was improved by MSC‐EVs (SMD ‐1.45, CI ‐2.08 to ‐0.82) with small EVs more consistently beneficial then small/large EVs. In PAH, right ventricular systolic pressure (SMD ‐4.16, CI ‐5.68 to ‐2.64) and hypertrophy (SMD ‐2.80, CI ‐3.68 to ‐1.91) were significantly attenuated by EVs. In BPD and PAH, EVs isolated by ultracentrifugation demonstrated therapeutic benefit whereas tangential flow filtration (N = 2) displayed minimal efficacy. Lastly, risk of bias and quality of reporting for experimental design were consistently unclear across all studies. Our findings demonstrate clear potential of MSC‐EVs to be developed as therapy for acute and chronic lung diseases. However, greater transparency in research design and direct comparisons of isolation technique and EV subtypes are needed to generate robust evidence to guide clinical translation.Protocol Registration: PROSPERO CRD42020145334

Modeling of Acute Pulmonary Arterial Hypertension in Pigs Using a Stable Thromboxane A2 Analogue (U46619): Dose Adjustment and Assessment of Hemodynamic Reactions

U46619, a synthetic analogue of thromboxane A2 was used for modeling acute stable and reversible pulmonary arterial hypertension. Administration of U46619 in high doses led to vascular collapse and inhibition of cardiac function. The doses of U46619 were empirically selected that allow attaining the target level of pulmonary hypertension without systemic hemodynamic disturbances. The possibility of attaining the target level of pulmonary hypertension and reversibility of changes after termination of U46619 infusion make this model attractive for evaluation of the efficiency of different therapeutic methods of treatment of pulmonary hypertension in large animals.

Dual-Functional MN-08 Attenuated Pulmonary Arterial Hypertension Through Vasodilation and Inhibition of Pulmonary Arterial Remodeling.

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WHAT'S LUPUS GOT TO DO WITH IT? A CASE OF ACUTE HYPERCAPNIC RESPIRATORY FAILURE IN A PATIENT UNDERGOING KIDNEY TRANSPLANTATION

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is classically associated with constitutional symptoms, joint pain, and erythematous rash. However, patients with SLE can also have multiple cardiopulmonary comorbidities, making management difficult. In this report we present a patient with severe pulmonary arterial hypertension (PAH) and obstructive lung disease due to SLE who experienced a brief arrest during kidney transplantation. CASE PRESENTATION: A 41-year-old female with PAH and end-stage renal disease (ESRD) secondary to SLE presented in 2015 with the following right heart catheter (RHC) findings: RA 5, PAP 73/24 (40), PCWP of 9 mmHg, cardiac index of 1.93 L/min, and PVR of 9.7 Wood units. Alternative causes of PAH were assessed and ruled out via standard diagnostic testing. Treatment was initiated with sildenafil and inhaled treprostinil, but side effects eventually necessitated transition to ambrisentan and selexipag. A repeat RHC in 2017 showed the following: RA 5, PAP 30/17 (21), PCWP of 12 mmHg, cardiac output 3.12 L/min, PVR of 1.8. These improvements strongly suggested a component of Group 1 PAH that responded well to therapy. The patient was listed for renal transplant, and in Feb 2018 this was attempted but aborted due to intraoperative difficulty ventilating, yielding acute hypercapnic respiratory failure and brief cardiac arrest. After recovery and hospital discharge, repeat evaluation showed stable echocardiogram and RHC findings, but severe obstructive lung disease (FEV1/FVC 54, FEV 1 of .92 (40%), RV 161%, and DLCO 57%). Because the pathophysiology of acute hypercapnic respiratory failure does not correspond with acute PAH exacerbation or right ventricular failure, we suspected that severe air trapping secondary to SLE-induced bronchial inflammation led to her intraoperative respiratory arrest. Treatment of obstructive lung disease was then initiated with a fluticasone/salmeterol inhaler and advanced to 500/50 dosage, which led to significant improvement in subsequent FEV1. The patient was then relisted for renal transplant and underwent successful renal transplantation in Oct 2019. She did not require hemodialysis following the transplant, recovered quickly, and was discharged. At this time, 6 months after surgery, she remains functional class II and continues to do very well in the posttransplant setting. DISCUSSION: In this report, despite successful management of our patient's PAH, it was only after treatment of her concurrent SLE-related bronchitis that she was able to successfully receive a renal transplant. CONCLUSIONS: SLE is a systemic condition that can have multiple concurrent cardiopulmonary abnormalities, including obstructive lung disease due to bronchial inflammation and pulmonary arterial hypertension. Therefore, it is important for clinicians to look carefully at treatment options for each related cardiopulmonary condition. Reference #1: Hachulla E, Jais X, Cinquetti G, et al. Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus. Chest. 2018;153(1):143-151. https://doi.org/10.1016/j.chest.2017.08.014https://doi.org/10.1016/j.chest.2017.08.014 Reference #2: Kimoto M, Sharma TS, Manzi S. 35 - Lupus and the Cardiopulmonary System. In: Wallace DJ, Hahn BH, eds. Dubois' Lupus Erythematosus and Related Syndromes (Ninth Edition). Content Repository Only!; 2019:418-433. https://doi.org/10.1016/B978-0-323-47927-1.00035-9 Reference #3: Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD. Manifestations of systemic lupus erythematosus. Maedica (Buchar). 2011;6(4):330-336. DISCLOSURES: No relevant relationships by dan grinnan, source=Web Response No relevant relationships by Meagan Shinbashi, source=Web Response

A rare case of intestinal perforation in patient with acute decompensated pulmonary artery hypertension and acquired coagulopathy

A rare case of intestinal perforation in patient with acute decompensated pulmonary artery hypertension and acquired coagulopathy

Моделирование острой лёгочной артериальной гипертензии у свиней с помощью синтетического аналога тромбоксана А2 (U46619): подбор дозовых значений и оценка гемодинамических реакций

Моделирование острой лёгочной артериальной гипертензии у свиней с помощью синтетического аналога тромбоксана А2 (U46619): подбор дозовых значений и оценка гемодинамических реакций

Pulmonary Circulation in Obesity, Diabetes, and Metabolic Syndrome.

Obesity, diabetes mellitus, and the metabolic syndrome are important risk factors for the development of cardiovascular disease, with significant impact on human morbidity and mortality. Several decades of research have accumulated considerable knowledge about the mechanisms by which metabolic conditions precipitate systemic cardiovascular diseases. In short, these mechanisms are thought to involve changes in the external environment of vascular cells, which are mediated by the pro-inflammatory effects of adipokines, free fatty acids, and hyperglycemia. Thus, it has been hypothesized that the pulmonary circulation, witnessing similar insults as the systemic circulation, may be equally vulnerable to the development of vascular disease. Accordingly, recent attention has focused on exploring the mechanistic and epidemiological relationships among obesity, type 2 diabetes mellitus, metabolic syndrome, and pulmonary vascular diseases. In this article, we discuss in detail the preclinical evidence showing a modest but perceivable impact of metabolic disorders on the pulmonary circulation. In addition, we review the existing epidemiological studies examining the relationship among cardiovascular risk factors and pulmonary vascular diseases, using the acute respiratory distress syndrome and pulmonary arterial hypertension as examples. We conclude by discussing areas of limitations in the field and by suggesting future directions for investigation, including the notion that the pulmonary circulation may, in fact, be a resilient entity in the setting of some metabolic perturbations. © 2020 American Physiological Society. Compr Physiol 10:297-316, 2020.

Inhaled epoprostenol utilization pattern after implementation of an administration policy

Epoprostenol, a pulmonary vasodilator, is used to reduce pulmonary artery pressure. Its inhaled administration results in ventilation and perfusion matching with oxygenation improvement. Epoprostenol is used as treatment for various conditions, particularly acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension. In 2018, Baylor University Medical Center implemented a policy for inhaled epoprostenol utilization aimed at standardizing clinical practice. This study analyzed epoprostenol utilization patterns in patients with ARDS after implementation of this administration policy. Drug responders and nonresponders were compared for clinical outcomes and physiologic changes before and after use, and policy compliance was evaluated. Of 79 eligible patients, 30 fulfilled inclusion criteria: 14 (47%) had ARDS and 16 (53%) had non-ARDS. In all patients with ARDS, epoprostenol was a second rescue agent after neuromuscular blockade, prone positioning, corticosteroids, and extracorporeal membrane oxygenation. Epoprostenol was associated with statistically significant improvement of oxygenation before and after utilization in patients with ARDS (ratio of arterial oxygen partial pressure to fractional inspired oxygen 70 vs 140, respectively; P = 0.04). Overall, 10 (71%) ARDS patients were epoprostenol responders; 9 (56%) were deemed responders among subjects with non-ARDS. Comparison of outcomes between responders and nonresponders showed no statistically significant variations. Policy compliance was obtained in 24 (80%) patients.

28. Acute pulmonary arterial hypertension in primary Sjögren’s syndrome with known cryptogenic organising pneumonia

28. Acute pulmonary arterial hypertension in primary Sjögren’s syndrome with known cryptogenic organising pneumonia

Exercise cardiac MRI unmasks right ventricular dysfunction in acute hypoxia and chronic pulmonary arterial hypertension.

Coupling of right ventricular (RV) contractility to afterload is maintained at rest in the early stages of pulmonary arterial hypertension (PAH), but exercise may unmask depleted contractile reserves. We assessed whether elevated afterload reduces RV contractile reserve despite compensated resting function using noninvasive exercise imaging. Fourteen patients with PAH (mean age: 39.1 yr, 10 women and 4 men) and 34 healthy control subjects (mean ageL 35.6 yr, 17 women and 17 men) completed real-time cardiac magnetic resonance imaging during submaximal exercise breathing room air. Control subjects were then also exercised during acute normobaric hypoxia (fraction of inspired O2: 12%). RV contractile reserve was assessed by the effect of exercise on ejection fraction. In control subjects, the increase in RV ejection fraction on exercise was less during hypoxia (P = 0.017), but the response of left ventricular ejection fraction to exercise did not change. Patients with PAH had an impaired RV reserve, with half demonstrating a fall in RV ejection fraction on exercise despite comparable resting function to controls (PAH: rest 53.6 ± 4.3% vs. exercise 51.4 ± 10.7%; controls: rest 57.1 ± 5.2% vs. exercise 69.6 ± 6.1%, P < 0.0001). In control subjects, the increase in stroke volume index on exercise was driven by reduced RV end-systolic volume, whereas patients with PAH did not augment the stroke volume index, with increases in both end-diastolic and end-systolic volumes. From baseline hemodynamic and exercise capacity variables, only the minute ventilation-to-CO2 output ratio was an independent predictor of RV functional reserve (P = 0.021). In conclusion, noninvasive cardiac imaging during exercise unmasks depleted RV contractile reserves in healthy adults under hypoxic conditions and patients with PAH under normoxic conditions despite preserved ejection fraction at rest.NEW & NOTEWORTHY Right ventricular (RV) reserve was assessed using real-time cardiac magnetic resonance imaging in patients with pulmonary arterial hypertension and in healthy control subjects under normobaric hypoxia, which has been previously associated with acute pulmonary hypertension. Hypoxia caused a mild reduction in RV reserve, whereas chronic pulmonary arterial hypertension was associated with a marked reduction in RV reserve.

Computer simulated modeling of healthy and diseased right ventricular and pulmonary circulation.

We have previously developed a simulated cardiovascular physiology model for in-silico testing and validation of novel closed-loop controllers. To date, a detailed model of the right heart and pulmonary circulation was not needed, as previous controllers were not intended for use in patients with cardiac or pulmonary pathology. With new development of controllers for vasopressors, and looking forward, for combined vasopressor-fluid controllers, modeling of right-sided and pulmonary pathology is now relevant to further in-silico validation, so we aimed to expand our existing simulation platform to include these elements. Our hypothesis was that the completed platform could be tuned and stabilized such that the distributions of a randomized sample of simulated patients' baseline characteristics would be similar to reported population values. Our secondary outcomes were to further test the system in representing acute right heart failure and pulmonary artery hypertension. After development and tuning of the right-sided circulation, the model was validated against clinical data from multiple previously published articles. The model was considered 'tuned' when 100% of generated randomized patients converged to stability (steady, physiologically-plausible compartmental volumes, flows, and pressures) and 'valid' when the means for the model data in each health condition were contained within the standard deviations for the published data for the condition. A fully described right heart and pulmonary circulation model including non-linear pressure/volume relationships and pressure dependent flows was created over a 6-month span. The model was successfully tuned such that 100% of simulated patients converged into a steady state within 30s. Simulation results in the healthy state for central venous volume (3350 ± 132ml) pulmonary blood volume (405 ± 39ml), pulmonary artery pressures (systolic 20.8 ± 4.1mmHg and diastolic 9.4 ± 1.8mmHg), left atrial pressure (4.6 ± 0.8mmHg), PVR (1.0 ± 0.2 wood units), and CI (3.8 ± 0.5l/min/m2) all met criteria for acceptance of the model, though the standard deviations of LAP and CI were somewhat narrower than published comparators. The simulation results for right ventricular infarction also fell within the published ranges: pulmonary blood volume (727 ± 102ml), pulmonary arterial pressures (30 ± 4mmHg systolic, 12 ± 2mmHg diastolic), left atrial pressure (13 ± 2mmHg), PVR (1.6 ± 0.3 wood units), and CI (2.0 ± 0.4l/min/m2) all fell within one standard deviation of the reported population values and vice-versa. In the pulmonary hypertension model, pulmonary blood volume of 615 ± 90ml, pulmonary arterial pressures of 80 ± 14mmHg systolic, 36 ± 7mmHg diastolic, and the left atrial pressure of 11 ± 2mmHg all met criteria for acceptance. For CI, the simulated value of 2.8 ± 0.4l/min/m2 once again had a narrower spread than most of the published data, but fell inside of the SD of all published data, and the PVR value of 7.5 ± 1.6 wood units fell in the middle of the four published studies. The right-ventricular and pulmonary circulation simulation appears to be a reasonable approximation of the right-sided circulation for healthy physiology as well as the pathologic conditions tested.

Idiopathic acute onset pulmonary artery hypertension in infancy need for research

Background: The aim of this study was to study the clinical outcome of infants beyond neonatal period who presented with acute onset pulmonary artery hypertension of unknown etiology.Methods: This is a retrospective case record analysis of all the babies admitted to pediatric intensive care unit between January 2013 to March 2017 at Rajarajeswari Medical College with signs and symptoms of Pulmonary Arterial Hypertension on clinical examination and ECHO. Descriptive and inferential statistical analysis has been carried out in the present study. Results: Out of 49 infants beyond neonatal period who presented with Pulmonary Arterial Hypertension, 9 were females and 40 were males. 43 babies required ventilator support and 6 babies required only supplemental oxygen. Out of 33 babies who expired, cardiogenic shock and severe hypoxia was the main cause of death in 19, pulmonary hemorrhage in 4, acute kidney injury and fluid overload in 2, multi organ dysfunction in 1, septicemia in 4 and disseminated intravascular coagulation in 3. Babies who survived less than 72 hours cardiogenic shock and severe hypoxia was the main cause of death and babies who survived more than a week, pulmonary hemorrhage, acute kidney injury and fluid overload, multi organ dysfunction, septicemia and disseminated intravascular coagulation were the main cause of death. Conclusions: There is a need for research in infants beyond neonatal period with pulmonary arterial hypertension, to find out the etiology.

Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice.

The diagnostic value of serum copeptin levels in an acute pulmonary embolism.

Acute pulmonary embolism (APE) is a common disease which is associated with high mortality and morbidity. Circulating level of copeptin, which was demonstrated to be elevated in heart failure, acute myocardial infarction and pulmonary arterial hypertension, were reported to be independent predictors of poor outcome in recent studies. The aim of the present study was to investigate the clinical utility of copeptin in the diagnosis of APE. A total of 90 consecutive patients, admitted to emergency service due to acute chest pain and/or dyspnea and who underwent pulmonary computerized tomography angiography (CTA) due to suspicion of APE, were included in this prospective study. The patients diagnosed with APE were defined as APE (+) group and the remaining individuals with normal pulmonary CTA result were defined as APE (-) group. Copeptin levels (7.76 ± 4.4 vs. 3.81 ± 1.34 ng/dL; p < 0.001) were higher in the APE (+) group as compared to the APE (-) group. Copeptin was significantly positively correlated with B-type natriuretic peptide (r = 0.434, p < 0.001), D-dimer (r = 0.315, p = 0.003) and troponin I (r = 0.300, p = 0.004) and inversely correlated with arterial oxygen saturations (r = -0.533, p < 0001). When the correlation of copeptin with right ventricular dysfunction parameters was investigated, it was significantly inversely correlated with the tricuspid annular plane systolic excursion (r = -0.521, p < 0.001) and positively correlated with right to left ventricle ratio (r = 0.329, p = 0.024). Copeptin (OR 1.836, 95% CI 1.171-2.878, p = 0.008) was found as a significant independent predictor of APE in a multivariate analysis, after adjusting for other risk parameters. Copeptin is a promising new biomarker, which may be used to support the need for further investigations and to improve the diagnosis of patients with APE.

Lupus-Associated Pulmonary Arterial Hypertension: Variable Course and Importance of Prompt Recognition.

We describe a critically ill young woman with systemic lupus erythematosus (SLE) presenting with circulatory shock, multiorgan dysfunction, and elevated right-sided heart pressures. She was found to have recurrent acute severe pulmonary arterial hypertension (PAH) in the setting of an SLE flare. Our report highlights the variable course that SLE-associated PAH can take in the same patient and the implications of this for instituting the most effective treatment approach with each episode. This report also highlights the potential for SLE-associated PAH to present with life-threatening symptoms requiring critical care level interventions. We also describe evidence-based therapies, which can result in significant improvement in symptoms, function, and long-term outcomes.