Specific Pulmonary Hypertension Research Articles

Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension

Abstract Background The treatment of pulmonary hypertension (PH) has improved rapidly in recent years, and there is increasing evidence to support the role of early intervention. However, studies demonstrate that timely intervention is often still lagging which affects clinical outcomes in patients with PH. Purpose To assess treatment effects after escalation of specific PH treatments using continuous heart monitoring via a Reveal LINQ loop recorder. Methods The patients change in heart rate variability (HRV), heart rate (HR), and physical activity were assessed before and after treatment escalation. Treatment escalation was defined as an additional PAH drug, pulmonary endarterectomy (PEA), percutaneous balloon angioplasty (PBA), or bilateral lung transplantation (BLTX). Results In this prospective study, 41 patients (27 with PAH and 14 with chronic thromboembolic pulmonary hypertension) were enrolled. Among them, 15 patients (36.6%) underwent PH treatment escalation. Prior to escalation, patients were monitored for a median of 100 (range: 68–100) days and after therapy escalation for a median duration of 165 (range: 89–308) days. In the escalation group, a significant increase in HRV (Figure), physical activity indexed by daytime HR was observed, while a significant decrease was seen in nighttime HR assessed at baseline and after treatment escalation. These changes were found both in the PAH and CTEPH group. In parallel a significant improvement in WHO functional class, 6-minute walking distance, and N-terminal pro-b-type natriuretic peptide (NT-proBNP) was observed. Conclusions This is the first study to demonstrate a direct association between specific PH therapies and changes in HRV, HR nighttime and physical activity in patients with PAH and CTEPH. Continuous monitoring allows for an early intervention with supplementary treatment for PH. This is especially relevant considering the increasing availability of wearables that allow for a convenient measurement of relevant prognostic parameters in PH.

Pulmonary Hypertension and Survival among Non-Small Cell Lung Cancer Patients: A Retrospective Cohort Study in the U.S. Military Health System.

Background: Lung cancer is one of the most lethal cancers with survival being closely related to stage and influenced by comorbid illness. The survival implications of pulmonary hypertension (PH) on patients with non-small cell lung cancer (NSCLC) have only been evaluated in small cohorts, with limited long-term follow-up. Methods: We conducted a retrospective cohort study of 7946 patients with NSCLC diagnosed in the MHS. This study evaluated the survival impact of PH in patients diagnosed with NSCLC in the MHS. Patients were classified as having and not having PH. We stratified PH into those diagnosed before the diagnosis of NSCLC and those diagnosed after NSCLC diagnosis. Results: Relative to patients without PH, patients with PH diagnosed before NSCLC had an increased risk of death (HR = 1.15 [95% CI, 1.02-1.29]). The increased risk of death was more obvious for patients with PH diagnosed after NSCLC compared with those without PH (HR = 2.74 [95% CI, 2.51-2.99]). The results were similar when stratified by patient demographics. Conclusions: In the MHS, PH is associated with worsened NSCLC survival, regardless of when it is diagnosed. When PH is diagnosed after NSCLC, it is associated with a marked reduction in survival, and this finding may suggest a potential role for monitoring pulmonary pressures in NSCLC patients. Furthermore, as specific PH therapy exists, some NSCLC patients with PH may be candidates for therapy.

Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension

BackgroundThe treatment of pulmonary hypertension (PH) has improved rapidly in recent decades. There is increasing evidence to support the role of early intervention and treatment in affecting clinical outcomes in...

Specific therapies of pulmonary hypertension and prognosis in COVID-19: 18-months analysis of BNP-PL national database

Abstract Introduction The SARS-CoV-2 pandemic had a significant impact on mortality in the group of patients (pts) with pulmonary hypertension (PH). Specific therapies offer the potential to improve COVID-19 survival in this vulnerable population, but data on COVID-19 mortality according to specific PH therapies are scarce. Aim To assess mortality in the course of COVID-19 among pts diagnosed with PH, treated under the Polish ministry therapeutic program and registered in the national BNP-PL database, according to the intensity of specific PH therapy used in Poland. Methods We analyzed the records of the complete population of Polish pts treated under the National Drug Program of PH (PAH and CTEPH) and registered in the national database of BNP-PL from 01 March 2020 to 31 August 2022. The clinical severity of COVID-19 course and mortality were reviewed. Clinical characteristics of infected and deceased patients were compared in relation to the specific therapy used. Results The analysis included 188 pts with SARS-CoV-2 infection (mean age 59 ± 17,7 years; 61% female). 45 patients (24%) required hospitalization. Mortality rate was 18% (34/188, including 15 out-of-hospital deaths) vs. 2,6% for estimated in the general population. Those who died due to COVID-19 were slightly older (mean age 63 ± 18.4 vs. 58 ± 17.5 yrs; p=0,13). There was no significant difference in mortality in subsets receiving monotherapy (13.8%), 2 drugs (25.4%) or 3 drugs(15%)- p=0.18. There was a trend towards higher mortality in pts on double regimen. Pts treated with prostacyclin analogues had significantly higher risk of dying from COVID-19 (30% vs 11.4% in others, p=0.002). Conclusions COVID-19 infection in pulmonary hypertension pts was related to high mortality and prostacyclin analogues users are at highest risk. Considering that this analysis suggests that COVID-19 mortality was equalized between less sick patients suitable for monotherapy and those qualified for double/triple regimens. The finding of numerically highest risk in double therapy users might signify needs for earlier escalation to triple regimen.Characteristics of pts with PH and Covid

Metabolomics in Pulmonary Hypertension-A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology.

Pulmonary hypertension (PH) is a multifaceted illness causing clinical manifestations like dyspnea, fatigue, and cyanosis. If left untreated, it often evolves into irreversible pulmonary arterial hypertension (PAH), leading to death. Metabolomics is a laboratory technique capable of providing insights into the metabolic pathways that are responsible for a number of physiologic or pathologic events through the analysis of a biological fluid (such as blood, urine, and sputum) using proton nuclear magnetic resonance spectroscopy or mass spectrometry. A systematic review was finalized according to the PRISMA scheme, with the goal of providing an overview of the research papers released up to now on the application of metabolomics to PH/PAH. So, eighty-five papers were identified, of which twenty-four concerning PH, and sixty-one regarding PAH. We found that, from a metabolic standpoint, the hallmarks of the disease onset and progression are an increase in glycolysis and impaired mitochondrial respiration. Oxidation is exacerbated as well. Specific metabolic fingerprints allow the characterization of some of the specific PH and PAH subtypes. Overall, metabolomics provides insights into the biological processes happening in the body of a subject suffering from PH/PAH. The disarranged metabolic pathways underpinning the disease may be the target of new therapeutic agents. Metabolomics will allow investigators to make a step forward towards personalized medicine.

Precapillary pulmonary hypertension: RVOT systolic flow profile as a usuful tool

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In patients (pts) with pulmonary hypertension (PH), right ventricular outflow tract (RVOT) systolic Doppler flow envelope is frequently abnormal, showing a mid-systolic notch that suggests elevation of pulmonary vascular resistance (PVR). Recent studies have demonstrated that other parameters, such as time-to-notch, may be indicators of elevated pulmonary artery pressures (PAP) and disease severity, conveying an important prognostic value. Purpose To evaluate the correlation between RVOT systolic flow morphology and hemodynamic parameters in pts with PH. Methods Retrospective, single-center study of consecutive pts diagnosed with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). We included pts who performed right heart catheterization (RHC) and transthoracic echocardiogram (TTE) within a six month period. RVOT systolic Doppler flow envelope was analyzed by measuring the ejection time (ET), time-to-notch (TN), pulmonary acceleration time (PAT), deceleration slope, pre- and post-notching velocity peak. Clinical, epidemiological, TTE and RHC data were recorded. For statistical analysis, Student's T tests, Chi-square and non-parametric tests were performed when appropriate. Results We included 79 pts, 42 with PAH (53%) and 37 with CTEPH (47%). 52 pts were women (66%) with a mean age of 58.06 ± 15.3 years. The mean follow-up (FUP) was 3.6±2.8 years. Most pts (92.3%) were symptomatic with a WHO functional status of II or III, despite specific PH treatment (69.4% PDE5 inhibitors, 63% endothelin receptor antagonists). In our analysis a higher TN correlated negatively with hemodynamic parameters such as mPAP (p = 0.02), PVR (p = 0.015), and mean right atrial pressure (mRAP), (p = 0.02). Similarly, pts with higher ET showed lower mPAP and sPAP in right ventricular catheterization (p = 0.044, p = 0.05 respectively). As previously reported, lower PAT showed a positive association with sPAP (p = 0.008), pulse pressure in pulmonary artery (p = 0.028), mRAP (p = 0.022), cardiac index (p = 0.01) and pulmonary vascular resistance (p = 0.04). When attempting to stratify TN and ET we noted a positive correlation with higher COMPERA score during FUP and lower clinical events, despite lack of clear statistical significance (p = 0.1). Regarding the remaining RVOT flow variables no statistically significant correlations were found. Conclusion This study shows that TN and ET accurately correlate with PAP and PVR, mirroring disease severity. Therefore, RVOT systolic flow profile is a non-invasive parameter that can be used as a valid tool when evaluating patients with PH.

P395 PULMONARY HYPERTENSION OUTPATIENT CLINIC IN CUNEO: SUMMARY OF THE FIRST TWO YEARS OF ACTIVITY

Abstract Backgroung: Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and may be associated with a variety of cardiovascular and respiratory diseases. PH is defined by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg at rest,assessed by right heart catheterization (RHC). Methods The Cardiology Rare Disease Outpatient Clinic was opened in 2021 in the Cardiology Division of S. Croce and Carle Hospital, Cuneo. In this ambulatory setting, patients with suspected or confirmed PH diagnosis were screened and followed up. The outpatient evaluation included cardiological physical examination, electrocardiogram (ECG) and transthoracic echocardiogram. In case of echocardiographic PH suspicion (intermediate or high probability) a comprehensive work–up was performed with first level diagnostic tools (respiratory function tests with DLCO, high–resolution chest CT, arterial blood gases, blood tests and overnight oximetry or polysomnography). Eventually, lung scintigraphy was performed and work up was completed with RHC with vasoreactivity test with nitric oxide (NO) if indicated. Multidisciplinary team approach proved to be an essential requirement for good practice in this setting. Results Between January 2021 and December 2022, 95 patients were evaluated in the PH outpatient clinic; Sixty–one (63%) patients were female, mean age was 66 years. Forty–two (42%) patients were referred from Rheumatology, 9 (9%) from Pulmonologiy, 13 (14%) from Emergency Medicine or Internal Medicine, 20 (21%) from Cardiology, and the remaining 13 (14%) patients from other departments or from other hospitals. Following clinical and echocardiographic evaluation, patients were stratified into low, intermediate and high PH–risk levels. In 23 (24%) patients RHC was performed and in one case it was associated with vasoreactivity test with NO. Eight (8%) patients with chronic thromboembolic PH (CTEPH) suspicion were referred to the Hub Center in Pavia to evaluate pulmonary endarterectomy. Seven (7%) patients were treated with specific therapy for group 1 PH and 3 (3%) patients for CTEPH. Two (2%) patients died during follow–up. Conclusions The aim of the dedicated PH outpatient clinic is to screen patients and identify those who need a complete work–up for diagnosis and classification of PH subtypes, in order to select those patients who could benefit from specific PH therapies, and to monitor the response at FU.

Pulmonary hypertension associated with lung disease

Pulmonary hypertension (PH) is amultifactorial pulmonary vascular disease. PH associated with pre-existing lung disease is common and classified as group3 in the clinical classification. Patients with chronic obstructive or interstitial lung disease are most likely to develop PH, with up to 20% of patients showing signs of PH. Distinguishing between the symptoms of the underlying lung disease and concomitant PH can be difficult. Clinical assessment, lung function tests, laboratory tests, and echocardiography can be helpful. The hemodynamic definition of PH has recently been changed. PH associated with lung disease is apre-capillary form by definition. A special sub-stratification in group3 is the differentiation of hemodynamic severity. Severe PH in group3 is defined as apulmonary vascular resistance (PVR) greater than 5Wood units (WU). This pulmonary vascular phenotype is characterized by rather mild to moderate impairment of lung function or lung parenchymal destruction but with severe pulmonary vascular disease or right heart strain. Currently, there are no specific PH medications approved for group3. However, the use of specific PH medications for the pulmonary vascular phenotype is being discussed in studies or on acase-by-case basis, while in patients with aPVR below 5WU treatment focuses on the underlying disease.

Pulmonary hypertension in connective tissue diseases: epidemiology, pathogenesis, and treatment.

Pulmonary hypertension (PH) is a clinical condition characterized by increased pulmonary arterial pressure arising from a heterogeneous range of diseases that has a deteriorating effect on the quality of life and may cause early mortality if left untreated. Connective tissue disorders (CTD)-associated PH is the second most common cause of pulmonary arterial hypertension (PAH), after the idiopathic form, categorized as group I. Systemic scleroderma (SSc) accounts for 75% of CTD-associated PH cases. Although SSc ranks first place for CTD-associated PH, SSc is followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD), having a lesser frequency of PH occurrence, while it occurs as a rare complication in cases with rheumatoid arthritis (RA) and inflammatory myositis. PH may also occur during non-SSc CTDs and even other rheumatic diseases, including Behcet's disease and adult-onset Still's disease, albeit to a lesser extent. The prognosis of CTD-associated PH is worse than the other forms of PH. Although, as in idiopathic pulmonary arterial hypertension (IPAH), the mechanism of CTD-related PH is associated with an increase in vasoconstrictors like endothelin-1 and a decrease in vasodilators like prostacyclin and nitric oxide production, inflammation, and autoimmune mechanisms also play a role in the development and progression of PH. This may lead to the involvement of more than one mechanism in CTD-associated PH. Knowing which mechanism is dominant is very important in determining the treatment option. This review will primarily focus on the epidemiology, risk factors, and prognosis of PH that develops during rheumatic diseases; the pathogenesis and treatment will be briefly mentioned in light of the newly published guidelines. Key Points • Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) in Western countries is the second most common type of PAH after idiopathic PAH (IPAH). • CTD-PH can be seen most often in systemic scleroderma (SSc), less in systemic lupus erythematosus (SLE), mixed CTD (MCTD), and rarely in other CTDs. • While current guidelines recommend annual transthoracic echocardiography as a screening test for asymptomatic SSc patients, screening for PH is not advised in the absence of symptoms suggestive of PH in other CTDs. • CTD-PH treatment can be divided into specific vasodilator PH treatments and immunosuppressive therapy. Current treatment guidelines recommend the same treatment algorithm for patients with CTD-associated PH as for patients with IPAH. Several case series have shown the beneficial effect of immunosuppressive agents in patients with SLE-PH and MCTD-PH.

Pulmonary Hypertension Definition, Classification, and Epidemiology in Asia.

Pulmonary hypertension (PH) is caused by a range of conditions and is important to recognize as it is associated with increased mortality. Pulmonary arterial hypertension refers to a group of PH subtypes affecting the distal pulmonary arteries for which effective treatment is available. The hemodynamic definition of pulmonary arterial hypertension has recently changed which may lead to greater case recognition and earlier treatment. The prevalence of specific PH etiologies may differ depending on geographic region. PH caused by left heart disease is the most common cause of PH worldwide. In Asia, there is greater proportion of congenital heart disease- and connective tissue disease- (especially systemic lupus erythematosus) related PH relative to the West. This review summarizes the definition, classification, and epidemiology of PH as it pertains to Asia.

Алгоритми діагностики та лікування ідіопатичної легеневої артеріальної гіпертензії

Визначення. Легенева гіпертензія (ЛГ) — це гемодинамічний та патофізіологічний стан, що характеризується підвищенням середнього тиску в легеневій артерії > 20 мм рт.ст. та оцінюється за даними катетеризації правих відділів серця (КПС). У більшості випадків ЛГ не самостійне захворювання, а є проявом інших хвороб. Ідіопатична легенева артеріальна гіпертензія (ІЛАГ) — діагноз, який встановлюється методом виключення усіх інших причин ЛГ (ураження лівих відділів серця, захворювання сполучної тканини, ВІЛ-інфекція, захворювання легень, портальна гіпертензія, вроджені вади серця, легенева тромбоемболія в анамнезі та ін.). При ІЛАГ етіологія захворювання невідома. Патогенез та симптоми ЛГ. Вазоконстрикція, мікротромбоз та ремоделювання судин — три основні патофізіологічні елементи при ЛГ. Симптоми ЛГ неспецифічні: задишка, швидка втомлюваність, біль у грудях при фізичному навантаженні, іноді спостерігаються синкопальні стани. У декомпенсованих пацієнтів наявні ознаки правосторонньої серцевої недостатності (нябряки, асцит, здуття живота, пульсація яремних вен). Діагностика. Діагностичний алгорим при ЛГ складається з двох етапів. Перший — поза межами експертного центру, другий — безпосередньо в експертному центрі ЛГ. При підозрі на це захворювання та за наявності типових симптомів та ознак усім хворим проводиться ехокардіографічне обстеження (ЕхоКГ). Далі, за певних умов (наприклад, відсутність основної причини ЛГ), хворий направляється до експертного центру ЛГ, де можливе проведення КПС. Оцінка прогнозу. Оцінка хворих з ІЛАГ необхідна для покращення контролю захворювання та переходу з більш високого ризику до більш низького. Оцінка прогнозу є комплексною та визначається на основі: клінічного статусу, прогресування симптомів, наявності синкопе, результатів тесту 6-хвилинної ходьби та NT-proBNP, результатів методів обстеження (кардіопульмональний тест із фізичним навантаженням, ЕхоКГ або МРТ серця, оцінка гемодинаміки). Лікування. Основними завданнями лікування ІЛАГ є зменшення вираженості симптомів, уповільнення прогресування захворювання, поліпшення якості та збільшення тривалості життя хворих. У першу чергу це загальні заходи (фізична активність, запобігання та ведення вагітності), запобігання інфекційним захворюванням, соціально-психологічна допомога, контроль дотримання режиму, рекомендації щодо подорожей/поїздок, підтримуюча терапія (пероральні антикоагулянти, діуретики, дигоксин, оксигенотерапія). Хворим із позитивним вазореактивним тестом призначаються блокатори кальцієвих каналів. У всіх інших хворих специфічна терапія ЛГ може включати простагландини (інгаляційна, внутрішньовенна та підшкірна форма), антагоністи простациклінових рецепторів, антагоністи рецепторів ендотеліну, інгібітори фосфодіестерази-5, стимулятори розчинної гуанілатциклази. Хірургічне лікування. Одним із варіантів хірургічного лікування ІЛАГ є передсердна септостомія — створення перфорації в міжпередсердній перегородці. Це призводить до декомпресії правих камер серця і збільшує перед-навантаження на лівий шлуночок, що веде до збільшення серцевого викиду. У разі неефективності всіх вищеописаних методів лікування та значного прогресування захворювання пацієнтам показана трансплантація легень або комплексу серце — легені.

Clinical features and survival in pulmonary Takayasu's arteritis associated pulmonary hypertension: a national registry study

Abstract Background The clinical features and long-term outcomes of patients with pulmonary Takayasu's arteritis associated pulmonary hypertension (PTA-PH) have not been well studied. Purpose To assess the clinical characteristics and long-term survival outcome in patients with PTA-PH. Methods We conducted a multi-center cohort study using the clinical, functional, and hemodynamic data from the National Rare Diseases Registry System of China. Patients with Takayasu's arteritis and pulmonary artery involvement, who fulfilled the 1990 American College of Rheumatology and/or modified Ishikawa criteria, from 13 referral centers of China, were included. The diagnosis of pulmonary hypertension (PH) was confirmed by right heart catheterization findings. The primary outcome was time from diagnosis of PTA-PH to the occurrence of all-cause death. Results Between Jan. 2007 and Jan. 2019, a total of 140 patients with PTA-PH were included, with a mean age of 41.4±14.3 years at diagnosis, and a female predominance (81%). The most common symptoms were exertional dyspnea (91%) and hemoptysis (36%). The majority of patients (87%) exhibited bilateral pulmonary artery involvement. Pulmonary lobar artery was the most frequently affected vessel (100%), followed by segmental artery (82%) and left/right pulmonary artery trunk (49%). Severely compromised hemodynamic profiles were identified in these patients, indicating by elevated mean pulmonary artery pressure (48, interquartile range [IQR] 38–59 mm Hg) and pulmonary vascular resistance (9.4, IQR 5.7–13.3 Wood U). The overall 1-year, 3-year, and 5-year survival rates in PTA-PH were 94.0%, 83.2%, and 77.2%, respectively (Figure). Predictors associated with increased risk of all-cause death were the presence of syncope (hazard ratio [HR]: 4.88; 95% CI: 1.62–14.74; p=0.005), N-terminal pro-B type natriuretic peptide level (HR: 1.04; 95% CI: 1.02–1.06; p<0.001), and right atrial pressure (HR: 1.07; 95% CI: 1.02–1.73; p=0.009). Conclusions In this national registry study, the reported clinical features and long-term prognosis of patients with PTA-PH are novel findings. These findings may provide new insights on this specific pulmonary hypertension entity. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The National Key Research and Development Program of China Kaplan-Meier plot for survival rate

Impact of COVID-19 pandemics upon pulmonary hypertension patients: insights from BNP-PL national database

Abstract Introduction COVID-19 pandemic has caused not only an increase in overall and cardiovascular mortality, but also hindered access to health care, diagnosis and treatment of diseases other than coronavirus infection. Aim Assessment of the impact of the SARS-CoV-2 pandemic on the rate of diagnosis and therapy of pulmonary hypertension (PH) in Poland, along with an analysis of the incidence and course of COVID-19 among patients (pts) diagnosed with PH, treated under the National Health Fund program, registered in the national BNP-PL database. Methods The records of the complete population of Polish pts treated under the National Drug Program of PH (PAH and CTEPH), registered in the national database of BNP-PL, updated on an ongoing basis by all PH centers, were analyzed. The frequency of SARS-CoV-2 infections, the clinical severity of their course and the mortality were reviewed, taking into account the specific therapies used. The basic clinical characteristics of the group of sick and deceased patients were compared to the remaining patients registered in the BNP-PL database. The rate of increase of new diagnoses ended with inclusion in the Drug Program between March and December 2020, compared to the corresponding periods of the previous year, and the change in the treatment profile were compared. Results The analysis included 1704 pts (PAH 1134, CTEPH 570). The incidence of SARS-CoV-2 infections was 3.8% (n=65), including PAH 2.7% (n=46) and CTEPH 3,2% (n=18). 32 patients (49%) required hospitalization. Mortality rate was 28% (18/65) – including 7/18 outside of hospital. Those who died due to COVID-19 were older (mean age 68.4±15.8 vs. 50.8±18.8 yrs; p<0,001), had higher WHO class and more cardiovascular comorbidities (4±2,06 vs. 2,66±1,8; p=0,01) (Table 1). During the pandemic the number of new diagnoses of PH markedly decreased compared to the corresponding period in 2019 (total 150 vs. 203, PAH 90 vs. 123, CTEPH 60 vs. 80, respectively). A significant increase in total mortality was also observed in the PH group (9,72 vs. 5,85%). Moreover, escalation of specific PH therapy decreased significantly (14,7% vs. 21,6%). Incidence of COVID-19 study group was lower than estimated for general Polish adult population (3,8% vs. 6,5%). Conclusions COVID-19 pandemic deeply influenced the diagnostic and therapeutic process of pulmonary hypertension by reducing the number of new diagnoses, escalation therapy and increased overall mortality in this population. This may be due in part to the conversion of some PAH centers into hospitals treating patients infected with SARS-CoV-2, as well as to patients' fear of admitting to hospital despite clinical deterioration. Pulmonary hypertension is linked to markedly increased mortality in COVID-19, similarly for PAH and CTEPH. Intriguing finding of lower infection rate may be linked to protective lifestyle or specific therapies. Funding Acknowledgement Type of funding sources: None.

Short-Term Impact of Iron Deficiency in Different Subsets of Patients with Precapillary Pulmonary Hypertension from an Eastern European Pulmonary Hypertension Referral Center.

BackgroundOver the last few decades, interest in the role of iron status in pulmonary hypertension (PH) has grown considerably due to its potential impact on symptoms, exercise capacity (as assessed by the 6-minute walk distance [6MWD]), prognosis, and mortality. The aim of the present study was to identify iron deficiency (ID) prevalence in specific precapillary PH subgroups of Romanian patients and its short-term impact on 6MWD.Patients and MethodsComplete datasets from 25 precapillary PH adults were examined and included in the analysis. Data were collected at baseline and after continuous follow-up of an average of 13.5 months. Enrolled patients were assigned to group 1 (pulmonary arterial hypertension) or subgroup 4.1 (chronic thromboembolic pulmonary hypertension), and individualized targeted therapy was prescribed. General characteristics, World Health Organization functional class, 6MWD, pulse oximetry, laboratory parameters, and echocardiographic and hemodynamic parameters were recorded. Ferritin values and transferrin saturation were used to assess ID.ResultsAt baseline, 16 out of 25 patients were iron deficient. The univariate linear regression analysis did not show a statistically significant impact of ID on 6MWD (p=0.428). In multivariate regression analysis, possible predictors of 6MWD, including ID, were not statistically significant at baseline or after an average of 13.5 months follow-up (p=0.438, 0.361, respectively) and ID indicates a negative impact on 6MWD independent of applied corrections.ConclusionThe results of this study demonstrate that 1.4.1 subgroup PAH patients have an increased prevalence of ID compared with other etiologies. ID has a negative impact on the functional status (assessed by 6MWD), in specific groups and subgroups of patients with precapillary PH, albeit not independently nor significant to other known predictors such as age, gender, oxygen saturation, and hemoglobin value. These data can be integrated with global research and are consistent with phenotypes of patients diagnosed with PH of different etiologies.

Impact de l’exposition à la fumée de cigarette sur la réponse hémodynamique à l’exercice de patients sous traitement spécifique de l’HTAP

Pulmonary hypertension (PH) is a life-threatening haemodynamic condition associated with many disorders. In pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension, several treatments acting against pulmonary endothelial dysfunction have been shown to be effective. Exposure to cigarette smoke leads to endothelial dysfunction which is comparable to that observed in patients with PAH. The main objective was to investigate the difference in the haemodynamic changes during exercise in patients under specific treatment, from diagnosis (T0) to the first reassessment visit with a right heart catheterisation (T1), between those exposed or not exposed to cigarette smoke. Between January 2002 and December 2018, all patients under specific treatment for PAH or chronic thromboembolic PH who underwent supine submaximal exercise assessment at T0 and T1 in our institution were asked specific questions about tobacco smoking. Overall (n=109), difference in mean isoflow mPAP was 19.0±15.4mmHg in patients exposed to tobacco smoke versus 21.3±16.6mmHg in unexposed patients (P=0.59). Median survival in exposed group was 83 months while in the unexposed group, median survival was 100 months (P=0.099). Our study did not show any significant difference in terms of haemodynamic changes during exercise between a group of patients under specific PH treatment exposed to cigarette smoke and a group unexposed. Endothelial dysfunction induced by smoke exposure does not appear to have a major impact on the response to the specific PH treatment.

Klippel-Trenaunay syndrome as a rare cause of chronic thromboemboembolic pulmonary hypertension

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum–maximum 26–50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension: A Population-Based Cohort Study in Ontario, Canada.

The World Health Organization recognizes 5 groups of pulmonary hypertension (PH), categorized by pathogenesis or comorbidity: 1-pulmonary arterial hypertension 2-left-heart disease, 3-lung disease and hypoxia 4-chronic thromboembolic disease, and 5-miscellaneous. The epidemiology of PH, apart from group 1, is largely unknown. We describe incidence, prevalence, comorbidities, mortality and prescribing patterns for groups 1 to 4 PH from 1993 to 2012. Case definitions are based on hospitalizations and emergency department visits, using the Institute for Clinical Evaluative Sciences data, which comprises linked databases of universal coverage health service records for Ontario residents. This cohort included 50 529 patients with PH. The annual incidence of adult PH increased from 2003 to 2012 from 24.1 to 28.7 cases/100 000 population and the annual prevalence from 1993 to 2012 from 99.8 to 127.3 cases/100 000 population, respectively. The most common form of adult PH was group 2, alone (34.2%) or combined with group 3 PH (29.3%). A diagnosis of PH increased the 1-year standardized mortality ratio 7.2-fold. Mortality in adults with PH was 13.0%, 36.4%, and 62.4%, at 30 days, 1 year, and 5 years, respectively. Mortality was highest in groups 2 and 3 and lowest in group 1. PH was present in only 3.6% of people with left heart disease, 0.7% with lung disease, and 1.4% with thromboembolic disease, suggesting that PH is a relatively rare complication of these common diseases. Children (age<16 years) accounted for 3.6% of the cohort. In children group 1 PH was most common (65.2%), and 5-year mortality was lower (21.4%) than in adults. Group 1-specific PH therapies were increasingly prescribed over time and paradoxically were often used in patients who seemed to have group 2, PH based on diagnostic codes indicating left heart disease. The incidence and prevalence of adult PH are increasing. Groups 2 and 3 are the most common and lethal forms of PH. This study identifies an emerging epidemic of PH that likely has substantial adverse health and economic implications.

Angiogenic and inflammatory biomarkers in the differentiation of pulmonary hypertension

Objectives. Pulmonary hypertension (PH) is a serious condition where diagnosis often is delayed due to unspecific symptoms. New methods to diagnose and differentiate PH earlier would therefore be of great value. The aim of this study was therefore to evaluate the relationship between circulating angiogenic and inflammatory biomarkers and various hemodynamic variables in relation to different causes of PH. Design. Plasma samples from 63 patients at diagnosis were extracted from Lund Cardio Pulmonary Register, separated into pulmonary arterial hypertension (PAH, n = 22), chronic thromboembolic pulmonary hypertension (CTEPH, n = 15) and left heart disease (LHD) with (n = 21) and without (n = 5) PH. Blood samples from eight control subjects devoid of PH were additionally evaluated. Plasma concentrations of angiogenic (PlGF, Tie2, VEGF-A, VEGF-D, bFGF, sFlt-1) and inflammatory (IL-6, IL-8, TNF-α) biomarkers were analysed and related to hemodynamic variables. Results. SFlt-1 (p < .004) and VEGF-A (p < .035) were higher in all PH groups compared to controls. TNF-α (p < .030) were elevated in PAH patients in relation to the other PH groups as well as controls. Likewise, plasma VEGF-D (p < .008) were elevated in LHD with PH compared to the other groups with PH and controls. In PAH, higher sFlt-1 concentrations correlated to a worse state of hemodynamics. Conclusions. Our findings indicate that sFlt-1 and VEGF-A may be future tools when discriminating PH from non-PH. Moreover, TNF-α may differentiate PAH and VEGF- D may differentiate LHD with PH, from the other groups with PH, as well as controls. SFlt-1 may furthermore play a role as a future marker of disease severity.

Limited Cutaneous Scleroderma-Related Pulmonary Arterial Hypertension — a Case Report

Abstract Background: Pulmonary hypertension (PH), defined by mean pulmonary arterial pressure (PAPm) ≥25 mm Hg, can lead to increasing pulmonary vascular resistance, which eventually results in right ventricle failure. Scleroderma, as an autoimmune connective tissue disease, is associated with PH as a sub-group according to the 2015 ESC/ERS PH classification. Pulmonary arterial hypertension (PAH) associated with scleroderma (SSc-PAH) can often result in poor prognosis with increased mortality. Early diagnosis and specific treatment of PH can significantly improve the prognosis of these patients. Case report: We present the case of a 50 year-old male, with no relevant family history, with a 2-year history of echocardiography-based diagnosis of PH (PAPm 78 mmHg). Physical examination revealed limited hand and forearm areas of non-folding thick skin, vital signs in the normal range and peripheral oxygen saturation of 96%. Severity and risk assessment were performed based on clinical and imaging tests, and hemodynamics. 12-lead rest ECG revealed sinus tachycardia and right bundle branch block, the six-minute walk test confirmed limited exertion capacity, Borg scale 9. Transthoracic echocardiography pointed to dilated right heart cavities and moderate pericardial effusion. Right heart catheterization confirmed the PAH (PAPm: 36 mmHg), and pulmonary CT angiography excluded massive pulmonary embolism. Rheumatologic examination and immune serology identified a scleroderma subset, limited cutaneous sclerosis form (lcSSc) with early onset PH. Combined specific PH drug therapy was initiated, followed by clinical and functional improvement in clinical status, prognosis and life quality. Conclusions: In clinical group 1 of PH, the subgroup etiology of PAH associated with connective tissue disease (1.4.1) often goes undiagnosed, mainly due to the diminish of lung involvement symptoms in early CTD stages. Multidisciplinary approach is essential in order to refine the diagnosis and set out the treatment algorithm.

Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK

Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular...