Impact of diabetes mellitus on disease severity and patient survival in idiopathic pulmonary arterial hypertension: data from the Polish multicentre registry (BNP-PL).

BACKGROUND: Recent studies revealed that alterations in glucose and lipid metabolism in idiopathic pulmonary arterial hypertension (IPAH) are associated with disease severity and poor survival. However, data regarding the impact of diabetes mellitus (DM) on the prognosis of patients with IPAH remain scarce. The aim of our study was to determine that impact using data from a national multicentre prospective pulmonary hypertension registry. METHODS: We analysed data of adult patients with IPAH from the Database of Pulmonary Hypertension in the Polish population (BNP­PL) between March 1, 2018 and August 31, 2020. Upon admission, clinical, echocardiographic, and haemodynamic data were collected at 21 Polish IPAH reference centres. The all-cause mortality was assessed during a 30-month follow-up period. To adjust for differences in age, body mass index (BMI), and comorbidities between patients with and without DM, a 2-group propensity score matching was performed using a 1:1 pairing algorithm. RESULTS: A total of 532 patients with IPAH were included in the study and 25.6% were diagnosed with DM. Further matched analysis was performed in 136 patients with DM and 136 without DM. DM was associated with older age, higher BMI, more advanced exertional dyspnea, increased levels of N-terminal pro-brain natriuretic peptide, larger right atrial area, increased mean right atrial pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and all-cause mortality compared with no DM. CONCLUSIONS: Patients with IPAH and DM present with more advanced pulmonary vascular disease and worse survival than counterparts without DM independently of age, BMI, and cardiovascular comorbidities.

Catheter-directed mechanical aspiration thrombectomy in a real-world pulmonary embolism population: a multicenter registry.

AIMS: High- (HR) and intermediate-high risk (IHR) pulmonary embolisms (PEs) are related to high early mortality and long-term sequelae. We aimed to describe clinical outcomes and adverse events in IHR and HR pulmonary embolism (PE) treated with catheter-directed mechanical thrombectomy (CDMT) in a real-world population. METHODS AND RESULTS: This study is a multicenter, prospective registry enrolling 110 PE patients treated with CDMT between 2019 and 2022. The CDMT was performed using the 8F Indigo (Penumbra, Alameda, CA, USA) system bilaterally in pulmonary arteries (PAs). The primary safety endpoints included device or PE-related death during the 48-h after CDMT, procedure-related major bleeding, or other major adverse events. Secondary safety outcomes were all-cause mortality during hospitalization or the follow-up. The primary efficacy outcomes were the reduction of PA pressures and change in the right-to-left ventricular (RV/L) ratio assessed in the imaging 24-48 h after the CDMT.71.8% of patients had IHR PE and 28.2% HR PE. 11.8% of patients had a failure and 34.5% had contraindications to thrombolysis, and 2.7% had polytrauma. There was 0.9% intraprocedural death related to RV failure and 5.5% deaths within the first 48 h. CDMT was complicated by major bleeding in 1.8%, pulmonary artery injury in 1.8%, and ischaemic stroke in 0.9%. Immediate haemodynamic improvements included a 10.4 ± 7.8 mmHg (19.7%) drop in systolic PAP (P < 0.0001), a 6.1 ± 4.2 mmHg (18.8%) drop in mean PAP, and 0.48 ± 0.4 (36%) drop in RV/LV ratio (P < 0.0001). CONCLUSION: These observational findings suggest that CDMT may improve hemodynamics with an acceptable safety profile in patients with IHR and HR PE.

Role of catheter-directed therapies in the treatment of acute pulmonary embolism. Expert opinion of the Polish PERT Initiative, Working Group on Pulmonary Circulation, Association of Cardiovascular Interventions, and Association of Intensive Cardiac Care of the Polish Cardiac Society.

Thanks to advances in interventional cardiology technologies, catheter-directed treatment has become recently a viable therapeutic option in the treatment of patients with acute pulmonary embolism at high risk of early mortality. Current transcatheter techniques allow for local fibrinolysis or embolectomy with minimal risk of complications. Therefore, these procedures can be considered in high-risk patients as an alternative to surgical pulmonary embolectomy when systemic thrombolysis is contraindicated or ineffective. They are also considered in patients with intermediate-high-risk pulmonary embolism who do not improve or deteriorate clinically despite anticoagulation. The purpose of this article is to present the role of transcatheter techniques in the treatment of patients with acute pulmonary embolism. We describe current knowledge and expert opinions in this field. Interventional treatment is described in the broader context of patient care organization and therapeutic modalities. We present the organization and responsibilities of pulmonary embolism response team, role of pre-procedural imaging, periprocedural anticoagulation, patient selection, timing of intervention, and intensive care support. Currently available catheter-directed therapies are discussed in detail including standardized protocols and definitions of procedural success and failure. This expert opinion has been developed in collaboration with experts from various Polish scientific societies, which highlights the role of teamwork in caring for patients with acute pulmonary embolism.

'Should I Buy Her a Doll'? Motherhood and Turner Syndrome in Poland.

Turner syndrome (TS) is a genetic condition that affects only girls and women, leading to health issues including infertility. Patients usually require recombinant growth hormone, and sex hormone therapy. Based on our anthropological research in Poland, we posit questions regarding the management of societal expectations by female parents regarding the femininity of their daughters, especially within the context of infertility. We query: Is it possible to understand TS and its consequences as not only being an obstacle to future plans, but also having emancipatory potential? To answer this question, we refer to the concept of hope and analyze the interpretative work of mothers of girls with TS.

Novel Hybrid Treatment for Pulmonary Arterial Hypertension with or without Eisenmenger Syndrome: Double Lung Transplantation with Simultaneous Endovascular or Classic Surgical Closure of the Patent Ductus Arteriosus (PDA).

Patients with pulmonary arterial hypertension (PAH) become candidates for lung or lung and heart transplantation when the maximum specific therapy is no longer effective. The most difficult challenge is choosing one of the above options in the event of symptoms of right ventricular failure. Here, we present two female patients with PAH: (1) a 21-year-old patient with Eisenmenger syndrome, caused by a congenital defect-patent ductus arteriosus (PDA); and (2) a 39-year-old patient with idiopathic PAH and coexistent PDA. Their common denominator is PDA and the hybrid surgery performed: double lung transplantation with simultaneous PDA closure. The operation was performed after pharmacological bridging (conditioning) to transplantation that lasted for 33 and 70 days, respectively. In both cases, PDA closure effectiveness was 100%. Both patients survived the operation (100%); however, patient no. 1 died on the 2nd postoperative day due to multi-organ failure; while patient no. 2 was discharged home in full health. The authors did not find a similar description of the operation in the available literature and PubMed database. Hence, we propose this new treatment method for its effectiveness and applicability proven in our practice.

CTLA-4 Expression Is a Promising Biomarker of Idiopathic Pulmonary Arterial Hypertension and Allows Differentiation of the Type of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is an increasingly frequently diagnosed disease, the molecular mechanisms of which have not been thoroughly investigated. The aim of our study was to investigate subpopulations of lymphocytes to better understand their role in the molecular pathomechanisms of various types of PAH and to find a suitable biomarker that could be useful in the differential diagnosis of PAH. Using flow cytometry, we measured the frequencies of lymphocyte subpopulations CD4+CTLA-4+, CD8+ CTLA-4+ and CD19+ CTLA-4+ in patients with different types of PAH, namely pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH), pulmonary arterial hypertension associated with connective tissue disorders (CTD-PAH), chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH), and in an age- and sex-matched control group in relation to selected clinical parameters. Patients in the iPAH group had the significantly highest percentage of CD4+CTLA-4+ T lymphocytes among all PAH groups, as compared to those in the control group (p < 0.001), patients with CTEPH (p < 0.001), CTD-PAH (p < 0.001) and CHD-PAH (p < 0.01). In iPAH patients, the percentages of CD4+CTLA-4+ T cells correlated strongly positively with the severity of heart failure New York Heart Association (NYHA) Functional Classification (r = 0.7077, p < 0.001). Moreover, the percentage of B CD19+CTLA-4+ cells strongly positively correlated with the concentration of NT-proBNP (r = 0.8498, p < 0.001). We have shown that statistically significantly higher percentages of CD4+CTLA-4+ (p ≤ 0.01) and CD8+ CTLA-4+ (p ≤ 0.001) T cells, measured at the time of iPAH diagnosis, were found in patients who died within 5 years of the diagnosis, which allows us to consider both of the above lymphocyte subpopulations as a negative prognostic/predictive factor in iPAH. CTLA-4 may be a promising biomarker of noninvasive detection of iPAH, but its role in planning the treatment strategy of PAH remains unclear. Further studies on T and B lymphocyte subsets are needed in different types of PAH to ascertain the relationships that exist between them and the disease.

Impact of the COVID-19 Pandemic on Pulmonary Hypertension Patients: Insights from the BNP-PL National Database.

We aimed to evaluate the clinical course and impact of the SARS-CoV-2 pandemic on the rate of diagnosis and therapy in the complete Polish population of patients (pts) with pulmonary arterial hypertension (PAH-1134) and CTEPH (570 pts) treated within the National Health Fund program and reported in the national BNP-PL database. Updated records of 1704 BNP-PL pts collected between March and December 2020 were analyzed with regard to incidence, clinical course and mortality associated with COVID-19. Clinical characteristics of the infected pts and COVID-19 decedents were analyzed. The rates of new diagnoses and treatment intensification in this period were studied and collated to the proper intervals of the previous year. The incidence of COVID-19 was 3.8% (n = 65) (PAH, 4.1%; CTEPH, 3.2%). COVID-19-related mortality was 28% (18/65 pts). Those who died were substantially older and had a more advanced functional WHO class and more cardiovascular comorbidities (comorbidity score, 4.0 ± 2.1 vs. 2.7 ± 1.8; p = 0.01). During the pandemic, annualized new diagnoses of PH diminished by 25-30% as compared to 2019. A relevant increase in total mortality was also observed among the PH pts (9.7% vs. 5.9% pre-pandemic, p = 0.006), whereas escalation of specific PAH/CTEPH therapies occurred less frequently (14.7% vs. 21.6% pre-pandemic). The COVID-19 pandemic has affected the diagnosis and treatment of PH by decreasing the number of new diagnoses, escalating therapy and enhancing overall mortality. Pulmonary hypertension is a risk factor for worsened course of COVID-19 and elevated mortality.

An expert opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation on screening for chronic thromboembolic pulmonary hypertension patients after acute pulmonary embolism: Update.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (APE). Both pharmacological and invasive treatments for CTEPH are available in Poland, and awareness of the disease among physicians is growing. It has been suggested that the COVID-19 pandemic may increase the incidence of CTEPH and facilitate disease detection during more advanced stages of the illness. Thus, the Polish Cardiac Society's Working Group on Pulmonary Circulation, in cooperation with independent experts in this field, launched the updated statement on the algorithm to guide a CTEPH diagnosis in patients with previous APE. CTEPH should be suspected in individuals after APE with dyspnea, despite at least 3 months of effective anticoagulation, particularly when specific risk factors are present. Echocardiography is the main screening tool for CTEPH. A diagnostic workup of patients with significant clinical suspicion of CTEPH and right ventricular overload evident on echocardiography should be performed in reference centers. Pulmonary scintigraphy is a safe and highly sensitive screening test for CTEPH. Computed tomography pulmonary angiography with precise detection of thromboembolic residues in the pulmonary circulation is important for the planning of a pulmonary thromboendarterectomy. Right heart catheterization definitively confirms the presence of pulmonary hypertension and direct pulmonary angiography allows for the identification of lesions suitable for thromboendarterectomy or balloon pulmonary angioplasty. In this document, we propose a diagnostic algorithm for patients with suspected CTEPH. With an individualized and sequential diagnostic strategy, each patient can be provided with suitable and tailored therapy provided by a dedicated CTEPH Heart Team.

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: a multicentre registry.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is a promising therapy for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy. AIMS: The present study aimed to evaluate the safety and efficacy of BPA for CTEPH using the first multicentre registry of a single European country. METHODS: Data were obtained from the Database of Pulmonary Hypertension in the Polish Population (NCT03959748), a prospective, multicentre registry of adult and paediatric pulmonary arterial hypertension (PAH) and CTEPH, for a total of 236 patients with confirmed CTEPH (124 women; mean age 67 years) who underwent 1,056 BPA procedures at eight institutions in Poland. RESULTS: In 156 patients who underwent follow-up assessments after a median of 5.9 (IQR: 3.0-8.0) months after final BPA, the mean pulmonary arterial pressure decreased from 45.1±10.7 to 30.2±10.2 mmHg (p<0.001) and pulmonary vascular resistance from 642±341 to 324±183 dynes (p<0.001), and the six-minute walking test (6MWT) improved from 341±129 to 423±136 m (p<0.001). Pulmonary injury related to the BPA procedure occurred in 6.4% of all sessions. Eighteen patients (7.6%) died during follow-up, including 4 (1.7%) who died within 30 days after BPA. Overall survival was 92.4% (95% confidence interval [CI]: 87.6%-94.9%) three years after the initial BPA procedure. CONCLUSIONS: This multicentre registry confirmed significant improvement of haemodynamic, functional, and biochemical parameters after BPA. Complication rates were low and overall survival comparable to the results of another registry. Therefore, BPA may be an important therapeutic option in patients with CTEPH in Poland.

An expert opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation and the Polish Society for Rheumatology on the diagnosis and treatment of pulmonary hypertension in patients with connective tissue disease.

Systemic connective tissue diseases (CTDs) comprise a large group of diseases that are auto-immune in nature and characterized by the involvement of multiple systems and organs. Pul-monary hypertension (PH) of various etiologies may develop in the course of CTD, including pulmonary arterial hypertension (PAH), PH secondary to the lung disease, postcapillary PH in the course of left heart disease, and chronic thromboembolic pulmonary hypertension (CTEPH). In addition, the different forms of PH may coexist with each other. Among patients with CTD, PAH occurs most commonly in those with systemic sclerosis, where it affects ap-proximately 8%-12% of patients. The prognosis in patients with untreated PAH is very poor. It is particularly important to identify the high-risk CTD-PAH population and to perform effi-cient and accurate diagnostics so that targeted therapy of the pulmonary arteries can be intro-duced. Echocardiography is used to screen for PH, but clinical and echocardiographic suspicion of PH always requires confirmation by right heart catheterization. Confirmation of PAH ena-bles the initiation of life-prolonging pharmacological treatment in this group of patients, which should be administered in referral centers. Drugs available for pharmacological management include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclins.

Characteristics and outcomes of patients with chronic thromboembolic pulmonary hypertension in the era of modern therapeutic approaches: data from the Polish multicenter registry (BNP-PL).

BACKGROUND: Significant achievements in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) have provided effective therapeutic options for most patients. However, the true impact of the changed landscape of CTEPH therapies on patients' management and outcomes is poorly known. We aimed to characterize the incidence, clinical characteristics, and outcomes of CTEPH patients in the modern era of CTEPH therapies. METHODS: We analyzed the data of CTEPH adults enrolled in the prospective multicenter registry. RESULTS: We enrolled 516 patients aged 63.8 ± 15.4 years. The incidence rate of CTEPH was 3.96 per million adults per year. The group was burdened with several comorbidities. New oral anticoagulants (n = 301; 58.3%) were preferred over vitamin K antagonists (n = 159; 30.8%). Pulmonary endarterectomy (PEA) was performed in 120 (23.3%) patients and balloon pulmonary angioplasty (BPA) in 258 (50%) patients. PEA was pretreated with targeted pharmacotherapy in 19 (15.8%) patients, and BPA in 124 (48.1%) patients. Persistent CTEPH was present in 46% of PEA patients and in 65% of patients after completion of BPA. Persistent CTEPH after PEA was treated with targeted pharmacotherapy in 72% and with BPA in 27.7% of patients. At a mean time period of 14.3 ± 5.8 months, 26 patients had died. The use of PEA or BPA was associated with better survival than the use of solely medical treatment. CONCLUSIONS: The modern population of CTEPH patients comprises mostly elderly people significantly burdened with comorbid conditions. This calls for treatment decisions that are tailored individually for every patient. The combination of two or three methods is currently a frequent approach in the treatment of CTEPH. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT03959748.

Characterization of Patients with Pulmonary Arterial Hypertension: Data from the Polish Registry of Pulmonary Hypertension (BNP-PL).

Current knowledge of pulmonary arterial hypertension (PAH) epidemiology is based mainly on data from Western populations, and therefore we aimed to characterize a large group of Caucasian PAH adults of Central-Eastern European origin. We analyzed data of incident and prevalent PAH adults enrolled in a prospective national registry involving all Polish PAH centers. The estimated prevalence and annual incidence of PAH were 30.8/mln adults and 5.2/mln adults, respectively and they were the highest in females ≥65 years old. The most frequent type of PAH was idiopathic (n = 444; 46%) followed by PAH associated with congenital heart diseases (CHD-PAH, n = 356; 36.7%), and PAH associated with connective tissue disease (CTD-PAH, n = 132; 13.6%). At enrollment, most incident cases (71.9%) were at intermediate mortality risk and the prevalent cases had most of their risk factors in the intermediate or high risk range. The use of triple combination therapy was rare (4.7%). A high prevalence of PAH among older population confirms the changing demographics of PAH found in the Western countries. In contrast, we found: a female predominance across all age groups, a high proportion of patients with CHD-PAH as compared to patients with CTD-PAH and a low use of triple combination therapy.

Treatment of chronic thromboembolic pulmonary hypertension in a multidisciplinary team.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) may be treated with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapy (MT). Assessment in a multidisciplinary team of experts (CTEPH team) is currently recommended for treatment decision making. The aim of the present study was to report the effects of such an interdisciplinary concept. METHODS AND RESULTS: A total of 160 patients were consulted by the CTEPH team between December 2015 and September 2018. Patient baseline characteristics, CTEPH team decisions and implementation rates of diagnostic and therapeutic procedures were analysed. Change in World Health Organization (WHO) functional class and survival rates were evaluated by treatment strategy. A total of 51 (32%) patients were assessed as operable and 109 (68%) were deemed inoperable. Thirty-one (61% of operable patients) underwent PEA. Patients treated with PEA, BPA(+MT) and MT alone were 50.9 ± 14.7, 62.9 ± 15.1 and 68.9 ± 12.7 years old, respectively. At the follow-up, PEA patients had the highest WHO functional class improvement. Patients treated with BPA(+MT) had significantly better survival than PEA (p = 0.04) and MT patients (p = 0.04; 2-year survival of 92%, 79% and 79%, respectively). CONCLUSIONS: The CTEPH team ensures that necessary diagnostic procedures are performed. A relatively low proportion of patients was assessed by the CTEPH team as operable and underwent surgery, which in survivors resulted in the best functional improvement. Although patients undergoing BPA(+MT) were older than patients treated with PEA, their survival was better than patients subjected to PEA or MT alone. The reviews of this paper are available via the supplemental material section.

[A statement the Polish Cardiac Society Working Group on Pulmonary Circulation on screening for CTEPH patients after acute pulmonary embolism]. / Opinia Sekcji Krazenia Plucnego Polskiego Towarzystwa Kardiologicznego dotyczaca badan przesiewowych w kierunku CTEPH u chorych po przebytej ostrej zatorowosci plucnej.

Both pharmacological and invasive treatment of chronic thromboembolic pulmonary hypertension (CTEPH) is now available in Poland and the awareness of the disease among physicians is growing. Thus, the Polish Cardiac Society's Working Group on Pulmonary Circulation in cooperation with independent experts in this field, have launched the statement on algorithm to guide a CTEPH diagnosis in patients with previous acute pulmonary embolism (APE). In Poland, every year this disease affects about 250 patients. CTEPH should be suspected in individuals after APE with dyspnea, despite at least 3 months period of effective anticoagulation, particularly when specified risk factors are present. Echocardiography is a main screening tool. The authors suggest that a diagnostic process of patients with significant clinical suspicion of CTEPH and right ventricle overload in echocardiography should be performed in reference centres. The document contains a list of Polish centres diagnosing patients with suspected CTEPH. Pulmonary scintigraphy is a safe and highly sensitive screening test for CTEPH. Multi-detector computed tomography with precise detection of thromboembolic residues in pulmonary circulation is important for planning of pulmonary endarterectomy. Right heart catheterisation definitely confirms the presence of pulmonary hypertension and direct pulmonary angiography allows for identification of lesions suitable for thromboendarterectomy or pulmonary balloon angioplasty. In this document a diagnostic algorithm in patients with suspected CTEPH is also proposed. With individualised sequential diagnostic strategy each patient can be finally qualified for a particular mode of therapy by dedicated CTEPH Heart Team. Moreover the document contains short information for the primary care physician about the management of patients after APE.

Summary of recommendations for the haemodynamic and angiographic assessment of the pulmonary circulation. Joint statement of the Polish Cardiac Society's Working Group on Pulmonary Circulation and Association of Cardiovascular Interventions.

Right heart catheterisation (RHC) is the 'gold standard' for haemodynamic assessment of the pulmonary circulation. For the diagnosis of pulmonary hypertension (PH), the guidelines of the European Society of Cardiology require a mean pulmonary arterial pressure ≥ 25 mm Hg to be confirmed by direct haemodynamic measurement. Additionally, RHC provides a lot of valuable information about the differential diagnosis and severity of PH, and also helps determine the patient's prognosis. Acute vasoreactivity testing performed in patients with pulmonary arterial hypertension is intended to identify the group of patients who should be treated with calcium channel blockers. Patients referred for heart transplantation require advanced pulmonary vascular disease to be ruled out either on resting examination or during vasoreactivity testing. RHC is a component of such interventional procedures as balloon atrial septostomy, closure of intracardiac shunts in congenital heart and great vessel defects, valvuloplasty for pulmonary valve stenosis, and pulmonary angioplasty. Pulmonary angiography is an examination recommended when selecting patients for pulmonary endarterectomy or balloon pulmonary angioplasty in thromboembolic PH. Due to the dynamic growth in the number of patients diagnosed with and treated for PH in Poland, the Boards of the Polish Cardiac Society's Working Group on Pulmonary Circulation and Association of Cardiovascular Interventions have undertaken a joint project to develop recommendations to standardise guidelines for RHC procedure, acute vasoreactivity testing and pulmonary angiography at cardiac wards and haemodynamic laboratories in Poland. This document has been prepared by experts delegated by the Working Group on Pulmonary Circulation and the Association of Cardiovascular Interventions, and subsequently approved by the Boards of both organs of the Polish Cardiac Society.