Secondary Pulmonary Arterial Hypertension Research Articles

Bronchopulmonary Dysplasia in a Tertiary Level Neonatal Unit of North India: Risk Factors and Outcome: A Case-control Study

Background: Bronchopulmonary dysplasia (BPD) in preterm neonates is a dreadful complication that increases the length of neonatal intensive care unit (NICU) stay, increases the cost of treatment, and poses long-term respiratory morbidity. Methods: This was a case-control study to determine risk factors for BPD among preterm neonates (gestational age <32 weeks). Also, the proportion of BPD neonates developing secondary pulmonary arterial hypertension (PAH), vitamin D levels, and their outcomes were studied. Results: Of 70 neonates with a mean birth weight of 1392 ± 544.28 grams and a mean gestational age of 30.14 ± 1.12 weeks, 35 cases of BPD (mild 42%, moderate 27%, severe 31%) and 35 controls were enrolled. After multivariate analysis, SGA (adjusted odds ratio [AOR] 12.6 with 95% CI 1.5-109.3; 0.022), lack of antenatal steroids (AOR 9.4 with 95% CI 1.8-50.7; 0.009), mechanical ventilation [MV] within the first 48 hours of life (AOR 8.7 with 95% CI 1.4-54.1; 0.021), and lack of surfactant administration (AOR 16.5% CI 3-89.1; 0.005) were independent risk factors. No significant difference was reported in vitamin D levels between BPD and non-BPD neonates (33.89 ± 22.50 ng/mL vs. 27.00 ± 8.17 ng/mL; 0.356). 14.3 % of BPD neonates expired, and 23% developed PAH. Neonates had a longer NICU stay than controls (46.66 ± 7.96 vs. 21 ± 8.82 days; <0.001) Conclusion: We found SGA, lack of antenatal steroids, MV, and lack of surfactant administration to be independent risk factors for BPD. BPD neonates had dismal outcomes (one-fourth expired and left against medical advice), and one-fifth had PAH among survivors, increasing the length of their NICU stay.

KL-6 in adult polymyositis and dermatomyositis patients and its correlation with interstitial lung disease

BackgroundPulmonary involvement is still regarded as a common cause of morbidity in Polymyositis/Dermatomyositis. Interstitial lung disease can result in potentially fatal consequences such as ventilatory failure, secondary pulmonary arterial hypertension, or cor pulmonale. Early diagnosis of interstitial lung disease is hence a top priority in Polymyositis/Dermatomyositis patients. Krebs von den Lungen-6 is a transmembrane mucoprotein that has recently been identified as a promising marker for interstitial lung disease diagnosis and progression. As a result, it is regarded as a powerful predictor of interstitial lung disease severity. Thirty polymyositis/dermatomyocitis patients were enrolled in this study. Thirty age and sex matched healthy individuals were selected as control group. Cutaneous Dermatomyositis Disease Area Severity index(CDASI) was used for evaluation of skin severity, KL6 was measured using Elisa kit, High-resolution computed tomography, pulmonary function tests were made.ResultsSixteen female and 14 male patients had a mean age of 41.64–8.02 and amedian of the disease duration of 4 years. Fifteen patients (50%) had normal readings on High-resolution computed tomography of the chest HRCT chest, while the other half had significant HRCT chest findings. KL-6 concentrations were seen to be higher in Polymyositis/Dermatomyositis patients mainly those with ILD (mean ± SD 38.66 ± 22.98), compared to the control group (Mean ± S 589.04 ± 409) and in patients without ILD (Mean ± SD 86.70 ± 8.99), (p < 0.001). KL-6 serum concentrations were shown to have a significant connection with the HRCT score (r = 0.803, P < 0.001). Forced vital capacity (FVC%) (r = − 0.910, P < 0.001), forced expiratory volume in 1 s (FEV1%) (r = − 0.767, P < 0.001), and FEV1/FVC% (r = − 0.228, P = 0.112) were all inversely related to KL-6 concentrations.ConclusionIndividuals with PM and DM with concomitant ILD have increased KL-6 serum concentrations in comparison to myositis individuals without ILD, denoting its potential role in diagnosis and follow up of PM/DM with ILD. Further studies are needed to discuss the role of KL6 in large sample of the patient's population, and its correlation with other organ affection rather than ILD. Also to clarify the potentiality of adding the KL6 biomarker to the guidelines of treat to target for Rheumatic diseases with lung affection and to see the effect of treatment on KL6 serum level.

Assess the pulmonary arterial pressure in patients with group 1 pulmonary arterial hypertension by echocardiography

Objective: We assess the right ventricular in patients with group 1 pulmonary arterial hypertension by echocardiography.&#x0D; Method and Results: 45 patients with group 1 pulmonary arterial hypertension was measured the right ventricular by echocardiography between September 2021 and October 2022. Right ventricular diameter and Right ventricular area in patients with idiopathic pulmonary arterial hypertension were not significantly different in patients with secondary pulmonary arterial hypertension (35.7 ± 10.1 mm versus 30.8 ± 9 mm; p=0,12) và (24.1 ± 11.6 cm2 versus 19.7 ± 7 cm2; p=0,12). However, right ventricular function in patients with idiopathic pulmonary arterial hypertension were significantly lower than in patients with secondary pulmonary arterial hypertension via %FAC (28.3 ± 8.5 versus 38.8 ± 8.3; p&lt;0,001), TAPSE (14.2 ± 3.1 mm versus 19.4 ± 3.5 mm; p&lt;0,001), S’tricuspid (9.6 ± 2.2 cm/s versus 11.7 ± 1.9;p=0,002).[1]&#x0D; Conclusion: Right ventricular function in patients with idiopathic pulmonary arterial hypertension was significantly lower than in patients with secondary arterial pulmonary hypertension.

A neonatal rat model of pulmonary vein stenosis

ObjectivesPulmonary vein stenosis (PVS), one of the most challenging clinical problems in congenital heart disease, leads to secondary pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy. Due to the lack of a rodent model, the mechanisms underlying PVS and its associated secondary effects are largely unknown, and treatments are minimally successful. This study developed a neonatal rat PVS model with the aim of increasing our understanding of the mechanisms and developing possible treatments for PVS.MethodsPVS was created at postnatal day 1 (P1) by banding pulmonary veins that receive blood from the right anterior and mid lobes. The condition was confirmed using echocardiography, computed tomography (CT), gross anatomic examination, hematoxylin and eosin (H&E) staining, fibrosis staining, and immunofluorescence. Lung and RV remodeling under the condition of PVS were evaluated using H&E staining, fibrosis staining, and immunofluorescence.ResultsAt P21, echocardiography revealed a change in wave form and a decrease in pulmonary artery acceleration time—indicators of PAH—at the transpulmonary valve site in the PVS group. CT at P21 showed a decrease in pulmonary vein diameter in the PVS group. At P30 in the PVS group, gross anatomic examination showed pulmonary congestion, H&E staining showed wall thickening and lumen narrowing in the upstream pulmonary veins, and immunofluorescence showed an increase in the smooth muscle layers in the upstream pulmonary veins. In addition, at P30 in the PVS group, lung remodeling was evidenced by hyperemia, thickening of pulmonary small vessel walls and smooth muscle layers, and reduction of the number of alveoli. RV remodeling was evidenced by an increase in RV free wall thickness.ConclusionsA neonatal rat model of PVS was successfully established, showing secondary lung and RV remodeling. This model may serve as a useful platform for understanding the mechanisms and treatments for PVS.

Anatomy and Physiology of Right Heart Adaptation to Pulmonary Arterial Hypertension Along with Treatment

Background: Right ventricular (RV) performance is directly correlated with staying alive in individuals with the pulmonary arterial hypertension (PAH). There is still large degree of heterogeneity in the RV's response to pulmonary hypertension, despite the fact that the load of pulmonary i.e. lung, is a key factor in determining RV systolic performance in PAH. Objective: The main reason why this study was conducted to find out the normal differential function, interrelationships, and response to pulmonary arterial hypertension apical, right ventricular (RV) input and outflow compartments (PAH). Methods:40 individuals were examined using echocardiography which was 2-dimensional (2D) and also 3-dimensional (3D) in addition to traditional Doppler methods, including 15 controls, with the number of patients with left-sided heart failure was 25, 13 without secondary PAH which was named group-1 (G1) and 12 with secondary PAH was calledgroup-2 (G2). Results: The apical ejection percent was lower in controls than in patients for example the ejection of control was p≤0.01 and p≤0.01, for G1 it was: p≤0.05 and p≤0.01 and the ejection fraction forG2 was: p≤0.05 and p≤0.01, as well as in patients. The Inflow was decreased i.e.: p≤0.001 for both, same in the case of the apical: p≤0.01 for both, and again also in outflow tract: p≤0.05 for both patients showed decreased ejection percent. In G2, however, the inflow compartment achieved the minimal volume simultaneously with the outflow and apex, as opposed to controls where it took 20 ms for it to do so. In patients (in G1: the apical ejection percent was p=0.02 and p=0.01 and forG2 it was: p=0.01 for both), the times for both isovolumic contraction and that of relaxation were lengthened. In controls, volumetric outflow rate decline and the peak RV ejection time were associated (r=0.6, p0.05), however G2's peak RV ejection time was connected with the apex. Conclusion: The inflow of the right side ventricular, apical, and also the outflow tract compartments each have distinctive characteristics and share to the total combined systolic function to varying degrees. The ventricle of the right side becomes one non synchronous compartment in PAH, that can lead to a long-term impact on systemic cardiac dysfunction.

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a serious disease with reduced systemic circulation and low bioavailability associated with conventional and dosed therapy, which inhaled drugs can avoid. A mean pulmonary artery pressure (mPAP) of ≥25 mmHg (1 mmHg = 0.133 kPa) at rest or ≥30 mmHg during exercise and a pulmonary capillary pressure or left atrial pressure (PLA) of ≤15 mmHg can be diagnosed with PAH. Pulmonary hypertension is classified into primary PAH and secondary PAH according to the presence or absence of principles or risk factors. The main symptoms of pulmonary hypertension include dyspnoea, syncope, weakness, chest pain, and the presence of varying degrees of peripheral oedema. It is a highly pathogenic and life-threatening disease and can lead to delays in treatment if not diagnosed in time. In the past few years, the studies related to this progressed slowly, which brought great harm to patients with PAH. Reports showed that patients diagnosed with PAH should receive routine preventative care, such as pneumococcal and influenza vaccinations. Inhalation therapy is mainly used for the treatment of respiratory diseases and is of great interest due to the concentration of the drug in the airways and lung tissues. Therefore, the present situation of pulmonary hypertension and the characteristics of inhalation preparation were reviewed in this paper to provide some related cue for the treatment of pulmonary hypertension. In the future, it is necessary to develop more treatment methods for pulmonary hypertension.

Tracheal Diverticulum as a Cause of Recurrent Infection in Post–Lung Transplant Patients: A Report of 2 Cases

Tracheal diverticulum (TD) is a rare entity in clinical practice, accidentally found by imaging methods. It is a potential factor for the development of chronic respiratory infections, contributing to the progression of preexisting lung diseases and putting the success of lung transplantation at risk. This paper reports 2 cases of TD with atypical clinical presentation in post-lung transplant patients with recurrent infections and aims to present the importance of this differential diagnosis. Case 1: A 30-year-old man with terminal lung disease underwent bilateral lung transplantation with a satisfactory postoperative period. He presented with TD as a focus of recurrent infection associated with persistent hemoptysis. Indicated for surgical resection (cervicotomy with resection of tracheal diverticulum), without complications. He evolved uneventfully in the postoperative period and was clinically stable at follow-up. Case 2: A 57-year-old woman with hypersensitivity pneumonia associated with secondary pulmonary arterial hypertension and bronchiectasis underwent bilateral lung transplantation without complications. She presented with TD as a focus of infection associated with esophageal symptoms. Indicated for the surgical approach(cervicotomy with resection of tracheal diverticulum), she was asymptomatic at follow-up. Conservative treatment is recommended in elderly and asymptomatic patients. Surgical resection is based on the recurrence of symptoms and failure of clinical therapy and is the preferred approach for reported cases.

Diagnostic and Therapeutic Challenges in Treating an Esophago-Pleural Fistula Following Lung Transplantation

Introduction Esophago-pleural fistula (EPF) is a rare surgical complication with important morbidity and mortality. Generally, EPFs present as a recurrent or chronic respiratory infection, empyema, or hemorrhage. Diverse diagnostic and multimodal treatment strategies can be considered including stenting, endoluminal clipping, as well as surgical repair. We present the diagnostic and therapeutic challenges of a unique case of EPF after bilateral lung transplantation (BLTx). Case Report A 62-year-old male with scleroderma and secondary pulmonary arterial hypertension underwent BLTx under VA-ECMO for acute deterioration of his underlying lung fibrosis. Early recovery was uncomplicated with weaning from ECMO on post-operative day (POD) 2, successful extubation on POD 3 and discharge to the ward on POD 13. However, 2 days later he developed acute respiratory distress due to a right-sided pneumothorax. Chest drainage did not suffice and on POD 18 a thoracoscopic exploration for empyema was performed. On POD 26, semi-digested food was seen in the chest tube. Esophagogastroscopy with methylene blue confirmed leakage and two separate EPFs. Nil per os policy was started. On POD 32 endoluminal clipping was attempted and esophagogastroscopy showed healing of the upper fistula, though persistence of the lower one. Additional clipping of the distal EPF was performed. Despite clinical improvement, a new esophagogastroscopy on POD 71 revealed a new fistula between the endoluminal clips. Ultimately, the EPF was primarily closed and covered with an intercostal muscle flap trough right-sided thoracotomy on POD 105. Nine days after surgical closure, a contrast esophagogram showed no residual leakage. The patient experienced a slow but gradual recovery and oral intake was started successfully. At 2.5 years post-BLTx, the patient has a normal oral intake and spirometry shows a good pulmonary function without signs of rejection or chronic lung allograft dysfunction. Summary Post-operative EPF is a life-threatening situation, especially in immunocompromised patients. A low threshold of clinical suspicion and esophagogastroscopy are warranted to impede the diagnosis of EPF. In our experience, minimal invasive endoscopic strategies should be considered first, however, surgical treatment with primary suture and muscle coverage has the highest chance to be effective. Esophago-pleural fistula (EPF) is a rare surgical complication with important morbidity and mortality. Generally, EPFs present as a recurrent or chronic respiratory infection, empyema, or hemorrhage. Diverse diagnostic and multimodal treatment strategies can be considered including stenting, endoluminal clipping, as well as surgical repair. We present the diagnostic and therapeutic challenges of a unique case of EPF after bilateral lung transplantation (BLTx). A 62-year-old male with scleroderma and secondary pulmonary arterial hypertension underwent BLTx under VA-ECMO for acute deterioration of his underlying lung fibrosis. Early recovery was uncomplicated with weaning from ECMO on post-operative day (POD) 2, successful extubation on POD 3 and discharge to the ward on POD 13. However, 2 days later he developed acute respiratory distress due to a right-sided pneumothorax. Chest drainage did not suffice and on POD 18 a thoracoscopic exploration for empyema was performed. On POD 26, semi-digested food was seen in the chest tube. Esophagogastroscopy with methylene blue confirmed leakage and two separate EPFs. Nil per os policy was started. On POD 32 endoluminal clipping was attempted and esophagogastroscopy showed healing of the upper fistula, though persistence of the lower one. Additional clipping of the distal EPF was performed. Despite clinical improvement, a new esophagogastroscopy on POD 71 revealed a new fistula between the endoluminal clips. Ultimately, the EPF was primarily closed and covered with an intercostal muscle flap trough right-sided thoracotomy on POD 105. Nine days after surgical closure, a contrast esophagogram showed no residual leakage. The patient experienced a slow but gradual recovery and oral intake was started successfully. At 2.5 years post-BLTx, the patient has a normal oral intake and spirometry shows a good pulmonary function without signs of rejection or chronic lung allograft dysfunction. Post-operative EPF is a life-threatening situation, especially in immunocompromised patients. A low threshold of clinical suspicion and esophagogastroscopy are warranted to impede the diagnosis of EPF. In our experience, minimal invasive endoscopic strategies should be considered first, however, surgical treatment with primary suture and muscle coverage has the highest chance to be effective.

Diagnostic value of cardiac natriuretic peptide on pulmonary hypertension in systemic sclerosis: A systematic review and meta-analysis.

Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in systemic sclerosis (SSc). Many risk factors and predictors of outcomes have been identified in these patients. B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) serum levels are often elevated in SSc patients with early PAH. We conducted this systematic review and meta-analysis to estimate the diagnostic value of BNP/NT-proBNP in systemic sclerosis secondary pulmonary arterial hypertension (SSc-PAH). A systematic search was performed through PubMed, Embase, and Cochrane Library databases up to January 30, 2021. Stata 16.0 (Stata Corp, College Station, TX) was used to conduct the meta-analysis. A total of 9 studies involving 220 SSc-PAH patients and 259 non-SSc-PAH controls were included. The values of sensitivity and specificity using BNP and NT-ProBNP as diagnostic tools were pooled in the diagnostic meta-analysis. The overall performance of BNP/NT-ProBNP detection was: pooled sensitivity, 0.67 (95% CI: 0.52 to 0.79); pooled specificity, 0.84 (95% CI: 0.75 to 0.91); pooled positive likelihood ratio, 4.3 (95% CI: 3 to 6.1); and pooled negative likelihood ratio, 0.39 (95% CI: 0.28 to 0.55). The subgroup analysis showed similar results. Funnel plots indicate that there is no evidence for publication bias. Our results revealed that NT-proBNP has certain diagnostic value for PAH due to its better specificity and moderate sensitivity, but its clinical application value remains suboptimal and can not be a stand-alone decision-making diagnostic tool of SSc-PAH.

Rare Cause of Secondary Pulmonary Arterial Hypertension

Abstract Unilateral absent pulmonary artery (UAPA) is a rare congenital disorder. Most of the patients will be diagnosed in the early childhood because of recurrent respiratory tract infections and hemoptysis, but adult presentation is not uncommon. We report a 47-year-old female who was earlier diagnosed as bronchiectasis with pulmonary artery hypertension but now presented with complaints of typical angina and dyspnea on exertion. During right heart catheterization we failed to enter right pulmonary artery (RPA), and conventional coronary angiogram showed a large left atrial branch of left circumflex giving collateral blood supply to the right lung. Computed tomography angiogram showed absent RPA. We report this case not only because the patient was misdiagnosed but also because of rarity of coronary collaterals in UAPA patients and unusual bilateral bronchiectasis. According to reported literature, ours is the 28th case of this nature.

Is Veno-Arterial ECMO as Safe and Effective as Veno-Venous ECMO for Bridging to Lung Transplantation?

Purpose Veno-venous Extra-corporeal Membrane Oxygenation (VV ECMO) has been used as a bridge to lung transplantation with acceptable outcomes. Patients with primary or secondary pulmonary arterial hypertension and/or right ventricular dysfunction have a higher risk profile and will need Veno-arterial ECMO (VA ECMO) as a bridge to lung transplantation. There is limited information on outcome of lung transplantation after VA ECMO. We hypothesized that VA ECMO, as part of a multidisciplinary ECMO program yields similar outcomes as VV ECMO as a bridge in lung transplantation. Methods Records of all patients who had undergone ECMO with the intention to bridge to lung transplantation from January 1, 2012 to January 1, 2020 were reviewed. VV ECMO was performed via a single site dual lumen cannula or via dual peripheral cannulation sites. VA ECMO was performed via peripheral vessels or central cannulation without sternotomy. Results During this interval, 58 patients were placed on ECMO with the intention to bridge to lung transplantation: 27 on VV ECMO, and 31 on VA ECMO. 84% of patients on ECMO as a bridge were breathing spontaneously and ambulatory. Median duration of VV and VA ECMO were 7 days and 21 days, respectively. Incidence of ECMO-related complications were similar in the two groups. 81% of VV ECMO and 81% of VA ECMO patients underwent lung transplantation. Incidence of Primary Graft Dysfunction III at 72 hours in the VV ECMO and the VA ECMO cohorts were 0% and 4%, respectively. Median Intensive Care Unit and hospital stay of the two groups were similar. 30 days and in-hospital survival of the VV ECMO and VA ECMO groups were 100% and 96%, (p=NS). 1-year and 3-year survival of the two groups were also similar, AND did not differ when compared to the contemporary cohort of lung transplant recipients that were not bridged with ECMO. Conclusion VA ECMO, as part of a multi-disciplinary ECMO team, can be used as a bridge to lung transplantation, with similar outcomes as VV ECMO. Moreover, in this selected cohort, the short and medium term survival of bridged patients is similar to non-bridged patients.

Single Lung Transplant Remains a Viable Alternative to Double Lung Transplantation for the Patients with Severe Secondary Pulmonary Hypertension

<h3>Purpose</h3> Whereas double lung transplantation (LTx) is a preferred surgical option for the patients with secondary pulmonary arterial hypertension (SPH: defined as a mean pulmonary artery pressure (mPAP) above 25 mmHg), our institutional experiences have demonstrated the unique values of single LTx for SPH. Here, we review our experiences prioritizing single LTx for SPH in an attempt to optimize their opportunities and decrease mortality while waiting. <h3>Methods</h3> A retrospective review of the LTx database was used to identify patients who underwent single LTx. SPH patients were stratified into mild SPH (mPAP: 25-40 mmHg) and severe SPH (mPAP > 40 mmHg). Recipients without PH transplanted over the same time period were used as controls. Data are reported as severe SPH vs. mild SPH vs. controls. <h3>Results</h3> Three hundred eighteen patients received single LTx between January 2017 and December 2019. There were 217 patients with mild SPH (mPAP of 32 mmHg), 59 patients with severe SPH (mPAP of 46 mmHg) and 42 patients without PH (controls). There were no significant differences among the groups in their patients' characteristics except higher pulmonary vascular resistance noted in severe SPH group and morbid obesity noted in mild and severe SPH groups. While severe SPH group required more intraoperative cardiopulmonary support (37.3% vs. 11.1% vs. 5.0%, <i>p</i> < 0.05), there were no significant differences in major postoperative complications including postoperative duration mechanical ventilation and incidences of severe primary graft dysfunction. Actual survival at 1 year was not significantly different among the groups (93.2% vs. 88.9% vs. 92.9%, <i>p</i> = 0.683). <h3>Conclusion</h3> Our experience supports the option of single LTx for the patients with even severe SPH by utilizing appropriate mechanical circulatory support intraoperatively. In light of the ongoing donor lung shortage, this strategy should be considered for optimizing organ utilization and decreasing waitlist mortality.

Клиническая эффективность применения ривароксабана у пациента с идиопатическим легочным фиброзом и тромбозом правого желудочка

Purpose of the study. To study effectiveness of rivaroxaban therapy, dynamics of renal function and cytokine status in a patient with idiopathic pulmonary fibrosis and right ventricular thrombosis. Material and methods. A clinical case of patient B., 49, suffering from slowly progressing idiopathic pulmonary fibrosis (IPF) complicated by chronic respiratory failure, secondary pulmonary arterial hypertension, pulmonary heart and right ventricular thrombosis, is analyzed. Laboratory (determination of creatinine, cystatin C, TNF-α and IL-10) and instrumental (echocardiography and ultrasound scanning of carotid arteries) examinations were performed initially and in the dynamics of treatment with the combination of rivaroxaban and acetylsalicylic acid (ASA). Throughout the follow-up period, the patient took rivaroxaban 20 mg, ASA 100 mg, lisinopril 5 mg, bisoprolol 2.5 mg per day and oxygen therapy on an outpatient basis. Results. Combination therapy of rivaroxaban 20 mg and acetylsalicylic acid 100 mg per day led to dissolution of the thrombus in this patient. In the dynamics of the observation, a decrease of cystatin C (1.10 mg/L vs. 1.13 mg/L) and an increase (72 ml/min versus 66,7 ml/min) of the estimated glomerular filtration rate were noted. The concentration IL-10 concentration increased (initially 8.904 pg/ml versus 16.216 pg/ml in dynamics, respectively), TNF-α level decreased (initially 3.750 pg/ml versus 1.957 pg/ml in dynamics, respectively). During the treatment, a decrease in the right ventricular cavity (3.2 cm vs. 3.5 cm), pulmonary artery diameter (3.1 cm vs. 3.5 cm), pulmonary artery pressure (63 mm Hg vs. 74 mm Hg) and an increase in the size of the systolic excursion of the tricuspid valve ring (2.1 cm vs. 2.0 cm) was found compared with the baseline data. Conclusion. Use of rivaroxaban at a dose of 20 mg and acetylsalicylic acid of 100 mg per day in a patient with right ventricular thrombosis as a result of idiopathic pulmonary fibrosis complicated by chronic heart failure is effective and safe for the prevention of systemic embolism of cerebral stroke. The combination of rivaroxaban and low doses of acetylsalicylic acid in the traditional therapy has a positive cardio and nephroprotective effect.

Using A 21-Year Real-World Database from a Private Cardiologist's Practice to Test the Hypothesis that Combining Pharmacological Therapies (Carvedilol, Spironolactone and Statins) with Weight Loss May Benefit Patients with HFpEF

Heart Failure with preserved Ejection Fraction (HFpEF) is a clinical syndrome in which patients have symptoms of Heart Failure (HF), such as dyspnea and fatigue, a Left Ventricular Ejection Fraction (LVEF) ≥ 50% and evidence of cardiac dysfunction as a cause of symptoms, such as abnormal Left Ventricular (LV) diastolic dysfunction with elevated filling pressures. Besides LV diastolic dysfunction, recent investigations suggest a more complex and heterogeneous pathophysiology, including systolic reserve abnormalities, chronotropic incompetence, stiffening of ventricular tissue, atrial dysfunction, secondary Pulmonary Arterial Hypertension (PAH), impaired vasodilatation and endothelial dysfunction. Unlike Heart Failure with Reduced Ejection Fraction (HFrEF), clinical trials over the years have not yet identified effective treatments that reduce mortality in patients with HFpEF. A database on use of carvedilol in a private cardiologist's practice was begun in 1997 and concluded at the end of 2018. We used this database to test the hypothesis that combining pharmacological interventions to address diastolic dysfunction (carvedilol), volume overload (spironolactone/eplerenone) and endothelial dysfunction (statins) with weight loss may benefit patients with HFpEF. We report analysis of 335 patients with HFpEF comprised of 61% female (mean age 74 ± 8) and 39% males (mean age 72 ± 7). Initial EF ranged between 50 and 77% with mean EF of 57 ± 6%. Only 15 patients were changed to metoprolol succinate, verapamil or diltiazem because of adverse side effects. Two hundred and twenty of the patients were in normal sinus rhythm when started on carvedilol, spironolactone/eplerenone and statin therapy with weight loss counseling. After 5 years, 191 patients were still on combination therapy, and only 31 (17%) had developed Atrial Fibrillation (AF). Compared to previous HFpEF trials reporting a 32% risk of developing atrial fibrillation after 4 years, our combination therapy significantly (p &lt; 0.05) reduced the risk of developing AF over 5 years. Thus, irrespective of age and sex with comorbidities of type 2 Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD), patients with HFpEF can be managed successfully with carvedilol, spironolactone/eplerenone and statins with a clinical benefit being a reduced risk of developing AF. We consider these data hypothesis-generating and hope these results will be tested further in database analyses and clinical trials.

Diagnostic value of nailfold videocapillaroscopy in systemic sclerosis secondary pulmonary arterial hypertension: a meta-analysis.

Microvascular changes play a decisive role in systemic sclerosis (SSc) and occur early in the course of the disease. Pulmonary arterial hypertension (PAH) represents one of the main clinical expressions of the vascular changes in SSc, and the abnormal changes, especially capillary density and capillary width, are detectable at nailfold videocapillaroscopy (NVC). To investigate the differences in capillary nailfold changes in SSc patients with and without PAH and to estimate the early diagnostic value of NVC in SSc secondary PAH (SSc-PAH). A comprehensive literature search of MEDLINE and PUBMED was performed to identify published studies without language restrictions. The methodological quality of the included studies was evaluated. The pooled specificity, sensitivity, positive likelihood rate, negative likelihood rate, diagnostic odds ratio, area under the curve and Q value were found using Meta-Disc version 1.4 software packages. Finally, seven studies were included in this meta-analysis. The meta-analysis demonstrated that the diagnostic odds ratio, area under the curve and Q value were 5.84 (95% confidence interval: 1.95-17.54), 0.79 and 0.72 respectively. It indicated that the microvascular changes detected at NVC were significant in SSc-PAH and especially showed significantly lower capillary density and higher capillary width. The NVC may be a valuable tool for the early diagnosis of SSc-PAH. It can detect the early microvascular changes associated with the risk of PAH and has a significant role in the early prediction of SSc-PAH.

Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia

Secondary pulmonary arterial hypertension: to treat or not to treat?

The purpose of this review is to review recent literature related to mechanisms and treatment options for 'secondary' (i.e., WHO Groups 3 and 5) pulmonary arterial hypertension (PAH). Published randomized controlled trials, in general, do not support the use of approved therapies for 'primary' (i.e., WHO Group 1) PAH patients in patients with Group 3 PAH because of the small numbers of patients and inconsistent benefit. Therefore, we currently recommend against the use of these medications for Group 3 PAH. Similarly, there is limited evidence supporting the use of Group 1 PAH medications in Group 5 patients. In most patients with Group 5 PAH, treatment should be directed to the underlying disease. The utility of PAH-specific therapy in WHO Group 3 PAH is unclear because of the small numbers of patients evaluated and inconsistent beneficial effects observed. There is limited evidence supporting the use of PAH medications in Group 5 patients, and they may be harmful in some cases.

Pulmonary Arterial Hypertension: A Review Article

Pulmonary arterial hypertension (PAH) is characterized by the mean pulmonary artery pressure of more than 25 mmHg and pulmonary artery wedge pressure of less than 15 mmHg evidenced by right-heart catheterization. In the classification of PAH, some subgroups are defined as primary or secondary PAH based on the underlying etiologies of the disease. Early episodes of PAH have been reported to occur at younger ages and in women in idiopathic or familial forms with the survival rate of 1-3 years. According to recent registries, the affected patients are older and have better survival rates. Some of the key elements in the pathophysiology of PAH include intima and media proliferation, vascular remodeling, and blood coagulation, which could increase the defiance of pulmonary vascularity, so that the cellular and molecular pathways would be able to induce PAH through specific mechanisms. Although no pathognomonic signs and symptoms have been reported in the literature, the most prominent manifestations of PAH are associated with disorders such as heart failure. Currently, PAH is known as a severe and occasionally life-threatening multifactorial clinical condition. Considering endothelial dysfunction, vasoconstriction, inflammatory reactions, and platelet aggregation as the main pathophysiological arms of the disease, specific treatment approaches have been proposed to inhibit these manifestations. These methods result in the effective treatment response, as well as the proper early and late outcomes of PAH. Due to the high incidence of cardiovascular diseases and the associated progressive life-threatening conditions, such as heart failure and PAH in the Iranian population, identification of the etiological, pathophysiological, diagnostic, and novel therapeutic approaches for PAH is essential to the proper management of this clinical condition.

Differentially methylated regions in patients with rheumatic heart disease and secondary pulmonary arterial hypertension.

The aim of the present study was to identify differentially methylated regions (DMRs) in patients with rheumatic heart disease and secondary pulmonary arterial hypertension (RHD-PAH). A genome-wide DNA methylation assay was performed between 6 patients with RHD-PAH and 6 healthy controls using an Illumina Infinium HumanMethylation450 BeadChip kit. The Limma software package was subsequently used to identify significant DMRs. A total of 40 hypome-thylated and 64 hypermethylated CpG sites were identified between the RHD-PAH group and the control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term and signaling pathway enrichment analyses revealed that the DMRs, mapped to the genes including protein kinase C α, protein kinase AMP-activated non-catalytic subunit γ2, sprouty related EVH1 domain containing 2 and LIF interleukin 6 family cytokine, were significantly enriched in the negative regulation of protein kinase/transferase activity and the positive regulation of protein amino acid phosphorylation/phosphate metabolic process. The identified DMRs may provide novel insights into the pathogenesis of RHD-PAH.

Incidence of Pulmonary Arterial Hypertension in Patients with Psoriasis: A Retrospective Cohort Study.

Inflammatory signaling may play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). To assess the incidence of PAH in patients with mild and severe psoriasis compared with their respective controls. From January 2004 to November 2012, we performed a retrospective cohort study of patients with psoriasis in the Kaiser Permanente Southern California Health Plan. Patients with an International Classification of Diseases, Ninth Revision Clinical Modification diagnostic code for psoriasis (696.1) or psoriatic arthritis (696.0) without a prior diagnosis of primary PAH (416.0) or secondary PAH (416.8) were eligible for inclusion. Patients who had never received a diagnosis of psoriasis were frequency-matched by age, sex, and race to form the control cohorts. Incidence of PAH in patients with psoriasis compared with matched controls. There were 10,115 patients with mild psoriasis, 3821 with severe psoriasis, and 69,360 matched controls. On multivariable analysis, there was a significantly increased risk of PAH developing in the severe psoriasis cohort vs their controls (hazard ratio = 1.46, 95% confidence interval = 1.09-1.94). The systemic inflammatory process underlying psoriasis may be a cause for an increased risk of PAH, but there are numerous secondary causes of PAH, some of which were not accounted for in our study. Further prospective, randomized controlled trials are necessary to establish psoriasis as a risk factor for PAH.