Publications by authors named "Grzegorz Kopeć"

134 Publications

The Impact of COVID-19 Pandemic on Children with Pulmonary Arterial Hypertension. Parental Anxiety and Attitudes. Follow-Up Data from the Polish Registry of Pulmonary Hypertension (BNP-PL).

J Clin Med 2021 Apr 12;10(8). Epub 2021 Apr 12.

Pulmonary Circulation Centre, Department of Cardiac and Vascular Diseases, Faculty of Medicine, Medical College Jagiellonian University, John Paul II Hospital in Krakow, u. Pradnicka 80, 31-202 Krakow, Poland.

The COVID-19 pandemic has impacted healthcare systems worldwide. Little is known about the impact of the pandemic on medical and psycho-social aspects of children with rare diseases such as pulmonary arterial hypertension and their parents. The study is based on children registered in The Database of Pulmonary Hypertension in the Polish Population and a parent-reported survey deployed during the first 6 months of the pandemic. The questionnaire consisted of six question panels: demographic data, fear of COVID-19, General Anxiety Disorder-7 (GAD-7), social impact of pandemic, patients' medical status, and alarming symptoms (appearance or exacerbation). Out of 80 children registered, we collected 58 responses (72.5% response rate). Responders (parents) were mostly female ( = 55; 94.8%) at a mean age of 40.6 ± 6.9 years. Patients (children) were both females ( = 32; 55%) and males with a mean age of 10.0 ± 5.1 years. Eleven (19%) children had symptoms of potential disease exacerbation. Eight parents (72.7%) decided for watchful waiting while others contacted their GPs or cardiologists ( = 6; 54.5%). Three children had to be hospitalized (27.3%). Most planned hospitalizations (27/48; 56.2%) and out-patient visits (20/35; 57.1%) were cancelled, delayed, or substituted by telehealth services. Among the participating parents, the study shows very high levels of anxiety ( = 20; 34.5%) and concern ( = 55; 94.8%) and the need for detailed information (52; 89.6%) regarding COVID-19 and medical service preparedness during the pandemic. The COVID-19 pandemic has influenced child healthcare and caused high levels of anxiety among parents.
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http://dx.doi.org/10.3390/jcm10081640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069741PMC
April 2021

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).

Ther Adv Chronic Dis 2021 25;12:20406223211002961. Epub 2021 Mar 25.

Pulmonary Circulation Centre Department of Cardiac and Vascular Diseases, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Kraków, Poland, Department of Medical Education, Center for Innovative Medical Education, Jagiellonian University Medical College, Krakow, Poland.

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 ( = 301; 58.3%) were preferred over vitamin K antagonists ( = 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.
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http://dx.doi.org/10.1177/20406223211002961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010818PMC
March 2021

High CD200 Expression on T CD4+ and T CD8+ Lymphocytes as a Non-Invasive Marker of Idiopathic Pulmonary Hypertension-Preliminary Study.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Pulmonary Circulation Center, Department of Cardiac and Vascular Diseases, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Kraków, Poland.

Pulmonary arterial hypertension (PAH) can develop subsequently to disorganized endothelial cell proliferation within the pulmonary arteriolar layers that provide mechanical limits to the pulmonary vascular bed. Although the actual factor triggering vascular endothelial proliferation remains unknown to date, genetic susceptibility, hypoxia, inflammation, as well as response to drugs and toxins have been proposed as possible contributors. Since inflammation contributes to vascular remodeling, the changed immune response is increasingly considered a plausible cause of this cardiovascular disease. The interaction of a membrane glycoprotein cluster of differentiation 200 (CD200) and its structurally similar receptor (CD200R) plays a crucial role in the modulation of the inflammatory response. Our previous studies have shown that the overexpression of the other negative co-stimulatory molecule (programmed death cell-PD-1) and its ligand-1 (PD-L1) is closely related to iPAH and the presence of Epstein-Barr virus (EBV) reactivation markers. Therefore, we considered it necessary to analyze the different types of PAH in terms of CD200 and CD200R expression and to correlate CD200/CD200R pathway expression with important clinical and laboratory parameters. The CD200/C200R-signaling pathway has not been subject to much research. We included 70 treatment-naïve, newly diagnosed patients with PAH in our study. They were further divided into subsets according to the pulmonary hypertension classification: chronic thromboembolic pulmonary hypertension (CTEPH) subset, pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH), pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH), and idiopathic pulmonary arterial hypertension (iPAH). The control group consisted of 20 healthy volunteers matched for sex and age. The highest percentages of T CD200+CD4+ and T CD200+CD8+ lymphocytes were observed in the group of patients with iPAH and this finding was associated with the presence of EBV DNA in the peripheral blood. Our assessment of the peripheral blood lymphocytes expression of CD200 and CD200R indicates that these molecules act as negative co-stimulators in the induction and persistence of PAH-associated inflammation, especially that of iPAH. Similar results imply that the dysregulation of the CD200/CD200R axis may be involved in the pathogenesis of several immune diseases. Our work suggests that CD200 and CD200R expression may serve to distinguish between PAH cases. Thus, CD200 and CD200R might be useful as markers in managing PAH and should be further investigated.
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http://dx.doi.org/10.3390/jcm10050950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957729PMC
March 2021

Associations between Pharmacotherapy for Cardiovascular Diseases and Periodontitis.

Int J Environ Res Public Health 2021 01 18;18(2). Epub 2021 Jan 18.

Department of Conservative Dentistry with Endodontics, Institute of Dentistry, Jagiellonian University Medical College, 31-155 Kraków, Poland.

The goal of the study was to assess the relationship between cardioprotective medications, i.e., beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), statins, acetylsalicylic acid (ASA), and periodontitis (PD).

Background: Xerostomia increases the risk of PD and is a side effect of some pharmacotherapies. Information about the effect of cardioprotective treatment of periodontal status is scarce.

Methods: We studied 562 dentate residents of Krakow at the age of 50 to 70 years. Information about treatment was collected using a standardized questionnaire. The pocket depth and clinical attachment level (CAL) were used to ascertain PD. Multivariate logistic regression was applied to assess the relation between cardioprotective medications and PD.

Results: PD was found in 74% of participants. The range of cardioprotective drug use among participants was 7% (ARBs) to 32% (beta-blockers). After adjusting for age, sex, number of teeth, smoking, and education, ASA's use was related to a lower prevalence of PD in all dentate participants (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.40-0.99). The use of ARBs and statins was found to be associated with a higher prevalence of PD in persons having ≥6 teeth (odds ratio (OR) = 3.57, 95% CI: 1.06-11.99 and OR = 1.81, 95% CI: 1.03-3.16, respectively). Further adjustment for CVD risk factors, history of coronary heart disease, and other chronic diseases did not attenuate the results. There was no significant relation between PD and the use of other cardioprotective drugs.
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http://dx.doi.org/10.3390/ijerph18020770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831110PMC
January 2021

Associations between Pharmacotherapy for Cardiovascular Diseases and Periodontitis.

Int J Environ Res Public Health 2021 01 18;18(2). Epub 2021 Jan 18.

Department of Conservative Dentistry with Endodontics, Institute of Dentistry, Jagiellonian University Medical College, 31-155 Kraków, Poland.

The goal of the study was to assess the relationship between cardioprotective medications, i.e., beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), statins, acetylsalicylic acid (ASA), and periodontitis (PD).

Background: Xerostomia increases the risk of PD and is a side effect of some pharmacotherapies. Information about the effect of cardioprotective treatment of periodontal status is scarce.

Methods: We studied 562 dentate residents of Krakow at the age of 50 to 70 years. Information about treatment was collected using a standardized questionnaire. The pocket depth and clinical attachment level (CAL) were used to ascertain PD. Multivariate logistic regression was applied to assess the relation between cardioprotective medications and PD.

Results: PD was found in 74% of participants. The range of cardioprotective drug use among participants was 7% (ARBs) to 32% (beta-blockers). After adjusting for age, sex, number of teeth, smoking, and education, ASA's use was related to a lower prevalence of PD in all dentate participants (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.40-0.99). The use of ARBs and statins was found to be associated with a higher prevalence of PD in persons having ≥6 teeth (odds ratio (OR) = 3.57, 95% CI: 1.06-11.99 and OR = 1.81, 95% CI: 1.03-3.16, respectively). Further adjustment for CVD risk factors, history of coronary heart disease, and other chronic diseases did not attenuate the results. There was no significant relation between PD and the use of other cardioprotective drugs.
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http://dx.doi.org/10.3390/ijerph18020770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831110PMC
January 2021

Hemodynamic Effects of Ultrasound-Assisted, Catheter-Directed, Very Low-Dose, Short-Time Duration Thrombolysis in Acute Intermediate-High Risk Pulmonary Embolism (from the EKOS-PL Study).

Am J Cardiol 2021 02 18;141:133-139. Epub 2020 Nov 18.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Institute of Cardiology, John Paul II Hospital, Krakow, Poland.

Ultrasound-assisted, catheter-directed, low-dose thrombolysis (USAT) at an average alteplase dose of 20 mg infused over 12 to 24 hours reversed right ventricular disfunction and improved pulmonary hemodynamics in intermediate-high-risk pulmonary embolism patients. As bleeding risk increases with the thrombolytic dose, establishing a minimal effective USAT dosing regimen is of clinical importance. We aimed to investigate hemodynamic effects and safety of a very low-alteplase-dose USAT of 10 mg administered within 5 hours. We included 12 consecutive intermediate-high-risk pulmonary embolism patients with symptoms duration of <14 days and proximal thrombi location in pulmonary arteries. Pulmonary Embolism Response Team decision-based fixed, bilateral ultrasound-assisted alteplase infusions at the rate of 1mg/hour/catheter for 5 hours through EKOS system catheters were made. The primary efficacy measure was the change in invasive systolic and mean pulmonary arteries pressure, and in cardiac index from USAT start to termination. Safety measures were 180-day all-cause death or cardiopulmonary decompensation and bleeding complications. The systolic pulmonary arteries pressure and mean pulmonary arteries pressure decreased from 53 (45.5 to 59) to 37.5 (27.5 to 40.5) mm Hg (p = 0.02) and from 29.5 (27.5 to 32) to 21.5 (15.5 to 25) mm Hg (p = 0.02), respectively. The cardiac index increased from 1.6 (1.5 to 1.8) to 2.2 (1.9 to 2.4) l/min/m, (p = 0.02). No deaths, decompensations, or need for therapy intensification occurred. There was 1 episode of access-site bleeding, which subsided after conservative management. No intracranial hemorrhages appeared. In conclusion, reduced dose and duration USAT improved pulmonary hemodynamics and cardiac function leading to cardiopulmonary stabilization in intermediate-high risk pulmonary embolism patients at a low periprocedural risk.
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http://dx.doi.org/10.1016/j.amjcard.2020.11.004DOI Listing
February 2021

Myocardial proteomic profile in pulmonary arterial hypertension.

Sci Rep 2020 09 1;10(1):14351. Epub 2020 Sep 1.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Kraków, Poland.

Pulmonary arterial hypertension (PAH) is a rare, fatal, and incurable disorder. Although advances in the understanding of the PAH pathobiology have been seen in recent years, molecular processes underlying heart remodelling over the course of PAH are still insufficiently understood. Therefore, the aim of this study was to investigate myocardial proteomic profile of rats at different stages of monocrotaline-induced PAH. Samples of left and right ventricle (LV and RV) free wall collected from 32 Wistar rats were subjected to proteomic analysis using an isobaric tag for relative quantitation method. Hemodynamic parameters indicated development of mild elevation of pulmonary artery pressure in the early PAH group (27.00 ± 4.93 mmHg) and severe elevation in the end-stage PAH group (50.50 ± 11.56 mmHg). In early PAH LV myocardium proteins that may be linked to an increase in inflammatory response, apoptosis, glycolytic process and decrease in myocardial structural proteins were differentially expressed compared to controls. During end-stage PAH an increase in proteins associated with apoptosis, fibrosis and cardiomyocyte Ca currents as well as decrease in myocardial structural proteins were observed in LV. In RV during early PAH, especially proteins associated with myocardial structural components and fatty acid beta-oxidation pathway were upregulated. During end-stage PAH significant changes in RV proteins abundance related to the increased myocardial structural components, intensified fibrosis and glycolytic processes as well as decreased proteins related to cardiomyocyte Ca currents were observed. At both PAH stages changes in RV proteins linked to apoptosis inhibition were observed. In conclusion, we identified changes of the levels of several proteins and thus of the metabolic pathways linked to the early and late remodelling of the left and right ventricle over the course of monocrotaline-induced PAH to delineate potential therapeutic targets for the treatment of this severe disease.
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http://dx.doi.org/10.1038/s41598-020-71264-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462861PMC
September 2020

The coronavirus disease 2019 pandemic prevents patients with pulmonary hypertension from seeking medical help.

Kardiol Pol 2020 09 6;78(9):916-918. Epub 2020 Jul 6.

Department of Cardiac and Vascular Diseases, Institute of Cardiology,Faculty of Medicine, Jagiellonian University Medical College, John Paul II Hospital, Kraków, Poland

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http://dx.doi.org/10.33963/KP.15488DOI Listing
September 2020

Changes in heart morphometric parameters over the course of a monocrotaline-induced pulmonary arterial hypertension rat model.

J Transl Med 2020 06 30;18(1):262. Epub 2020 Jun 30.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, Kraków, Poland.

Background: Aim of this study was to assess changes in cardiac morphometric parameters at different stages of pulmonary arterial hypertension (PAH) using a monocrotaline-induced rat model.

Methods: Four groups were distinguished: I-control, non-PAH (n = 18); II-early PAH (n = 12); III-end-stage PAH (n = 23); and IV-end-stage PAH with myocarditis (n = 7).

Results: Performed over the course of PAH in vivo echocardiography showed significant thickening of the right ventricle free wall (end-diastolic dimension), tricuspid annular plane systolic excursion reduction and decrease in pulmonary artery acceleration time normalized to cycle length. No differences in end-diastolic left ventricle free wall thickness measured in echocardiography was observed between groups. Significant increase of right ventricle and decrease of left ventricle systolic pressure was observed over the development of PAH. Thickening and weight increase (241.2% increase) of the right ventricle free wall and significant dilatation of the right ventricle was observed over the course of PAH (p < 0.001). Reduction in the left ventricle free wall thickness was also observed in end-stage PAH (p < 0.001). Significant trend in the left ventricle free wall weight decrease was observed over the course of PAH (p < 0.001, 24.3% reduction). Calculated right/left ventricle free wall weight ratio gradually increased over PAH stages (p < 0.001). The reduction of left ventricle diameter was observed in rats with end-stage PAH both with and without myocarditis (p < 0.001).

Conclusions: PAH leads to multidimensional changes in morphometric cardiac parameters. Right ventricle morphological and functional failure develop gradually from early stage of PAH, while left ventricle changes develop at the end stages of PAH.
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http://dx.doi.org/10.1186/s12967-020-02440-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325143PMC
June 2020

Overexpression of PD-1 on Peripheral Blood Lymphocytes in Patients with Idiopathic Pulmonary Arterial Hypertension and Its Association with High Viral Loads of Epstein-Barr Virus and Poor Clinical Parameters.

J Clin Med 2020 Jun 24;9(6). Epub 2020 Jun 24.

Department of Cardiac and Vascular Diseases, Faculty of Medicine, Jagiellonian University Medical College, Centre for Rare Cardiovascular Diseases, John Paul II Hospital, 31-202 Krakow, Poland.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but severe disease with the elevated blood pressure in the pulmonary arteries without a known trigger of vascular remodelling. It leads to the right heart failure with reduced survival. Changes in the immunological landscape of the lungs and the periphery are common in IPAH patients, suggesting an immune system dysfunction. A cohort of 25 IPAH patients was enrolled in our study to investigate a link between the patient's clinical status, immune parameters of the blood, and the Epstein-Barr virus (EBV) infection. We found significant alterations of the patients' peripheral blood parameters. Therein, T lymphocytes and NK cell counts were decreased in the IPAH patients' blood, while the proportion of regulatory T cells was increased. Additionally, levels of proinflammatory cytokines interleukin-6 (IL-6), IL-2, and interferon-gamma (IFN-γ) were elevated. We identified a weak correlation between EBV loads and IPAH patients' clinical state (r = 0.54) and between EBV loads and overexpression of PD-1 on helper T cells (r = 0.56). We speculate that a significant dysregulation of the immune system homeostasis observed in IPAH patients may contribute to increased susceptibility of those patients to EBV infection, yet further longitudinal studies are required to characterize this relation in detail.
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http://dx.doi.org/10.3390/jcm9061966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355537PMC
June 2020

Guidance for anticoagulation management in venous thromboembolism during the coronavirus disease 2019 pandemic in Poland: an expert opinion of the Section on Pulmonary Circulation of the Polish Cardiac Society.

Kardiol Pol 2020 06 8;78(6):642-646. Epub 2020 Jun 8.

Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland

The coronavirus disease 2019 (COVID-19) pandemic affects anticoagulation not only in those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also in most patients who require daily anticoagulant therapy and are facing substantial limitations in medical care these days. Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has frequently been reported in patients with COVID-19, but its management is still challenging due to the complexity between antithrombotic therapy and hematological alterations. In the era of COVID-19 pandemic, it is highly recommended for patients who require chronic anticoagulation to continue therapy to prevent thromboembolic events. To avoid regular and frequent blood tests and unnecessary exposure to SARS-CoV-2 during contacts with medical personnel, direct oral anticoagulants should be strongly preferred whenever possible. Current evidence is insufficient to recommend routine pharmacological antithrombotic prophylaxis in all hospitalized patients with COVID-19. In patients with COVID-19 who are suspected of VTE or in whom the diagnosis is confirmed, parenteral therapy with low-molecular-weight heparin should be initiated in the absence of contraindications. If heparin-induced thrombocytopenia is suspected, nonheparin anticoagulants should be used such as bivalirudin or fondaparinux. In case of confirmed acute pulmonary embolism, treatment should be guided by risk stratification as defined in the current guidelines.
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http://dx.doi.org/10.33963/KP.15425DOI Listing
June 2020

Children and Adolescents with Pulmonary Arterial Hypertension: Baseline and Follow-Up Data from the Polish Registry of Pulmonary Hypertension (BNP-PL).

J Clin Med 2020 Jun 3;9(6). Epub 2020 Jun 3.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital in Krakow, 31-202 Krakow, Poland.

We present the results from the pediatric arm of the Polish Registry of Pulmonary Hypertension. We prospectively enrolled all pulmonary arterial hypertension (PAH) patients, between the ages of 3 months and 18 years, who had been under the care of each PAH center in Poland between 1 March 2018 and 30 September 2018. The mean prevalence of PAH was 11.6 per million, and the estimated incidence rate was 2.4 per million/year, but it was geographically heterogeneous. Among 80 enrolled children (females, = 40; 50%), 54 (67.5%) had PAH associated with congenital heart disease (CHD-PAH), 25 (31.25%) had idiopathic PAH (IPAH), and 1 (1.25%) had portopulmonary PAH. At the time of enrolment, 31% of the patients had significant impairment of physical capacity (WHO-FC III). The most frequent comorbidities included shortage of growth ( = 20; 25%), mental retardation ( = 32; 40%), hypothyroidism ( = 19; 23.8%) and Down syndrome ( = 24; 30%). The majority of children were treated with PAH-specific medications, but only half of them with double combination therapy, which improved after changing the reimbursement policy. The underrepresentation of PAH classes other than IPAH and CHD-PAH, and the geographically heterogeneous distribution of PAH prevalence, indicate the need for building awareness of PAH among pediatricians, while a frequent coexistence of PAH with other comorbidities calls for a multidisciplinary approach to the management of PAH children.
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http://dx.doi.org/10.3390/jcm9061717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356296PMC
June 2020

Virtual Histology to Evaluate Mechanisms of Pulmonary Artery Lumen Enlargement in Response to Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension.

J Clin Med 2020 Jun 1;9(6). Epub 2020 Jun 1.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital, Prądnicka 80, 31-202 Krakow, Poland.

Chronic thromboembolic pulmonary hypertension (CTEPH) results from an obstruction of pulmonary arteries (PAs) by organized thrombi. The stenosed PAs are targeted during balloon pulmonary angioplasty (BPA). We aimed to evaluate the mechanism of BPA in inoperable patients with CTEPH. We analyzed stenosed PAs with intravascular grey-scale ultrasound (IVUS) to determine the cross-sectional area (CSA) of arterial lumen and of organized thrombi. The composition of organized thrombi was assessed using virtual histology. We distinguished two mechanisms of BPA: Type A with dominant vessel stretching, and type B with dominant thrombus compression. PAs were assessed before ( = 159) and after ( = 98) BPA in 20 consecutive patients. Organized thrombi were composed of dark-green (57.1 (48.0-64.0)%), light-green (34.0 (21.4-46.4)%), red (6.4 (2.9-11.7)%;) and white (0.2 (0.0-0.9)%) components. The mechanism type depended on vessel diameter (OR = 1.09(1.01-1.17); = 0.03). In type B mechanism, decrease in the amount of light-green component positively correlated with an increase in lumen area after BPA ( = 0.50; = 0.001). The mechanism of BPA depends on the diameter of the vessel. Dilation of more proximal PAs depends mainly on stretching of the vessel wall while dilation of smaller PAs depends on compression of the organized thrombi. The composition of the organized thrombi contributes to the effect of BPA.
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http://dx.doi.org/10.3390/jcm9061655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355673PMC
June 2020

Time from symptom onset to final diagnosis of pulmonary arterial hypertension in Polish patients.

Kardiol Pol 2020 08 7;78(7-8):750-752. Epub 2020 May 7.

Department of Cardiac and Vascular Diseases, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Kraków, Poland.

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http://dx.doi.org/10.33963/KP.15344DOI Listing
August 2020

Pulmonary arterial hypertension and pulmonary hypertension due to left heart disease: so near and yet so far. Authors' reply.

Pol Arch Intern Med 2020 04 30;130(4):350-351. Epub 2020 Apr 30.

Department of Cardiac and Vascular Diseases, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, John Paul II Hospital, Kraków, Poland.

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http://dx.doi.org/10.20452/pamw.15329DOI Listing
April 2020

Pregnancy in a Patient With Chronic Thromboembolic Pulmonary Hypertension After Successful Treatment with Balloon Pulmonary Angioplasty.

Can J Cardiol 2020 04 1;36(4):589.e13-589.e16. Epub 2019 Nov 1.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland.

Pulmonary hypertension has been recognized as a contraindication to pregnancy. Recently, several groups have shown promising results with the use of balloon pulmonary angioplasty (BPA) in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) patients with distally located organized thrombi who were not candidates for pulmonary endarterectomy. We present the case report of a 26-year-old woman who became pregnant after successful treatment of severe CTEPH with the use of BPA. We conclude that patients undergoing effective BPA for CTEPH can consider becoming pregnant if followed closely by a multidisciplinary team, including experts in thrombosis, pulmonary hypertension, and obstetrics.
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http://dx.doi.org/10.1016/j.cjca.2019.10.029DOI Listing
April 2020

Expert opinion on the creating and operating of the regional Pulmonary Embolism Response Teams (PERT). Polish PERT Initiative.

Cardiol J 2019 ;26(6):623-632

Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology European Health Centre Otwock, Medical Centre for Postgraduate Education, Otwock, Poland.

Pulmonary Embolism Response Team (PERT) is a multidisciplinary team established to stratify risk and choose optimal treatment in patients with acute pulmonary embolism (PE). Established for the first time at Massachusetts General Hospital in 2013, PERT is based on a concept combining a Rapid Response Team and a Heart Team. The growing role of PERTs in making individual therapeutic decisions is identified, especially in hemodynamically unstable patients with contraindications to thrombolysis or with co-morbidities, as well as in patients with intermediate-high risk in whom a therapeutic decision may be difficult. The purpose of this document is to define the standards of PERT under Polish conditions, based on the experience of teams already operating in Poland, which formed an agreement called the Polish PERT Initiative. The goals of Polish PERT Initiative are: improving the treatment of patients with PE at local, regional and national levels, gathering, assessing and sharing data on the effectiveness of PE treatment (including various types of catheter-directed therapy), education on optimal treatment of PE, creating expert documents and supporting scientific research, as well as cooperation with other communities and scientific societies.
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http://dx.doi.org/10.5603/CJ.2019.0127DOI Listing
August 2020

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

J Clin Med 2020 Jan 8;9(1). Epub 2020 Jan 8.

Department of Congenital Heart Disease Institute of Cardiology, 04-628 Warsaw, Poland.

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 ( = 444; 46%) followed by PAH associated with congenital heart diseases (CHD-PAH, = 356; 36.7%), and PAH associated with connective tissue disease (CTD-PAH, = 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.
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http://dx.doi.org/10.3390/jcm9010173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019268PMC
January 2020

A challenging phenotype of pulmonary arterial hypertension.

Pol Arch Intern Med 2020 01 13;130(1):85-86. Epub 2019 Dec 13.

Department of Cardiac and Vascular Diseases, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Kraków, Poland.

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http://dx.doi.org/10.20452/pamw.15103DOI Listing
January 2020

Prognostic role of traditional cardiovascular risk factors in patients with idiopathic pulmonary arterial hypertension.

Arch Med Sci 2019 Oct 25;15(6):1397-1406. Epub 2018 Oct 25.

Department of Cardiac and Vascular Diseases, Faculty of Medicine, Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland.

Introduction: Metabolic alterations have been recently associated with onset and progression of idiopathic pulmonary arterial hypertension (IPAH). We aimed to determine the prevalence and prognostic role of cardiovascular risk factors in patients with IPAH.

Material And Methods: Between February 2009 and January 2015 we recruited consecutive IPAH patients. Clinical assessment included medical history, fasting glucose, lipid profile, N-terminal pro-brain natriuretic peptide concentration, 6-minute walk test distance, WHO functional class and hemodynamic evaluation. Patients' risk was estimated based on the Swedish PAH Register grading system.

Results: The study group included 61 IPAH patients, and the control group included 2413 Polish residents. When compared to the general population, IPAH patients had lower low-density lipoprotein cholesterol (LDL-C) and a higher triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio. Female patients were characterized by elevated glucose level, higher prevalence of diabetes and lower HDL-C than controls. PAH severity grade correlated positively with age and TG/HDL-C ratio ( = 0.29, = 0.02) and inversely with LDL-C ( = -0.28, = 0.03) and HDL-C ( = -0.39, = 0.02) concentrations. After a follow-up of 48 (23-79) months we recorded 28 deaths in the IPAH group. In the regression analysis lower LDL-C ( = 0.002) and HDL-C ( = 0.0002) levels, and higher TG/HDL-C ratio ( = 0.003) and glucose level ( = 0.003) were associated with all-cause mortality after adjustment for age, sex or PAH severity grade.

Conclusions: Patients with IPAH are characterized by an altered profile of lipid and glucose metabolism. Lowered levels of LDL-C and HDL-C and increased TG/HDL-C ratio correlate with disease severity and together with elevated plasma glucose level predict poor survival in IPAH.
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http://dx.doi.org/10.5114/aoms.2018.79242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855165PMC
October 2019

Electrocardiography in pulmonary hypertension.

Authors:
Grzegorz Kopeć

Pol Arch Intern Med 2019 Aug 29;129(7-8):440-441. Epub 2019 Aug 29.

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http://dx.doi.org/10.20452/pamw.14952DOI Listing
August 2019

HDL Cholesterol as a Marker of Disease Severity and Prognosis in Patients with Pulmonary Arterial Hypertension.

Int J Mol Sci 2019 Jul 18;20(14). Epub 2019 Jul 18.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital, 31-202 Krakow, Poland.

The impact of high-density lipoprotein (HDL) cholesterol on the development of atherosclerosis and diseases of systemic circulation has been well documented both in experimental and registry studies. Recent discoveries in pulmonary arterial hypertension (PAH) revealed a significant impact of HDL on pulmonary artery vasoreactivity and patients' prognosis. The vasoprotective activity of HDL primarily involves vascular endothelium that also plays a central role in pulmonary arterial hypertension (PAH) pathobiology. However, the exact mechanism in which this lipoprotein fraction exerts its effect in pulmonary circulation is still under investigation. This paper reviews potential vasoprotective mechanisms of HDL in pulmonary circulation and presents current clinical reports on the role of HDL in PAH patients.
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http://dx.doi.org/10.3390/ijms20143514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678550PMC
July 2019

Diastolic dyssynchrony and its exercise-induced changes affect exercise capacity in patients with heart failure with reduced ejection fraction.

Cardiol J 2019 Apr 17. Epub 2019 Apr 17.

Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital in Kraków, Prądnicka 80, 31-202 Krakow, Poland.

Background: Left ventricular (LV) diastolic dyssynchrony is common in patients with heart failure with reduced ejection fraction (HFREF). Little is known however, about its pathophysiology and clinical effects. Herein is hypothesized that presence of diastolic dyssynchrony at rest or at exercise may importantly contribute to HF symptoms. The aim was to investigate the influence of diastolic dyssynchrony and its exercise-induced changes on exercise capacity in HFREF patients.

Methods: Patients with stable, chronic HF, LV ejection fraction < 35%, sinus rhythm and QRS ≥ 120ms were eligible for the study. Rest and cyclo-ergometer exercise echocardiography were performed. Diastolic dyssynchrony was defined as opposing-wall-diastolic-delay ≥ 55 ms measured in tissue-Doppler imaging. Exercise capacity was assessed by peak oxygen consumption (VO2peak). Association between diastolic dyssynchrony and VO2peak was assessed in univariate regression analysis and further adjusted for possible confounders.

Results: 48 patients were included (aged 63.7 ± 12.2). Twenty-seven (56.25%) had diastolic dyssynchrony at rest and 13 (27%) at exercise. Twenty-two (46%) experienced a change in diastolic dyssynchrony status during exercise. In univariate models diastolic dyssynchrony at rest or at exercise were associated with lower VO2peak (beta coefficient = -3.8, p = 0.004; beta coefficient = -3.6, p = 0.02, respectively). However, the ability to restore diastolic synchronicity during exercise was associated with higher VO2peak (beta coefficient = 3.4, p = 0.04) and remained an important predictor of exercise capacity after adjustment for age and HF etiology.

Conclusions: The ability to restore diastolic synchronicity at exercise predicts exercise capacity in patients with HFREF.
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http://dx.doi.org/10.5603/CJ.a2019.0032DOI Listing
April 2019

Pulmonary Artery Elastic Properties After Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension.

Can J Cardiol 2019 04 2;35(4):422-429. Epub 2019 Feb 2.

Department of Cardiac and Vascular Diseases, Faculty of Medicine, Jagiellonian University Medical College at John Paul II Hospital, Krakow, Poland. Electronic address:

Background: A significant proportion of the right ventricular afterload is determined by the elastic properties of the pulmonary artery (PA). We aimed to assess the effect of balloon pulmonary angioplasty (BPA) on PA elastic properties in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: We enrolled adult patients with CTEPH treated with BPA and controls without PH. Total PA compliance (CPa) was calculated as stroke volume/PA pulse pressure. PA distensibility (DC) and compliance (CC) coefficients were assessed by intravascular ultrasound to denote local elastic properties of the treated PA segments.

Results: We performed 103 BPA sessions in 17 patients with CTEPH (5 men [29%], aged 66 [64 to 73] years) who were followed for 6 (5 to 7) months after the last BPA. The median time between BPA sessions was 39 (28 to 52) days. The CPa, CC, and DC were lower in patients with CTEPH than in controls without PH (n = 10). Complete BPA treatment led to increase of CPa from 1.02 (0.70 to 1.39) to 2.08 (1.49 to 2.39) mL/mm Hg (P < 0.001) at the 6-month follow up, and this increase was in proportion to a decrease in pulmonary vascular resistance (PVR) (R = 0.74; P = 0.001). CPa increased immediately after BPA session by 0.13 (-0.05; 0.33) mL/mm Hg (P = 0.001) and remained unchanged until the next BPA session. CC and DC exhibited no immediate change after catheter balloon inflation (Δ=0 [-0.03; 0.02] mm/mm Hg, P = 0.52, and Δ = 0 [-0.13; 0.13] %/mm Hg, P = 0.91, respectively) and remained unchanged at the 6-month follow-up.

Conclusions: BPA improved total CPa in proportion to a decrease in PVR despite no improvement in local elastic properties of the treated PA segments.
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http://dx.doi.org/10.1016/j.cjca.2019.01.016DOI Listing
April 2019

Clinical classification of rare cardiac arrhythmogenic and conduction disorders, and rare arrhythmias.

Pol Arch Intern Med 2019 03 19;129(3):154-159. Epub 2019 Feb 19.

Centre for Rare Cardiovascular Diseases, John Paul II Hospital, Kraków, Poland.

INTRODUCTION Rare cardiovascular diseases and disorders (RCDDs) constitute an important clinical problem, and their proper classification is crucial for expanding knowledge in the field of RCDDs. OBJECTIVES The aim of this paper is to provide an updated classification of rare arrhythmogenic and conduction disorders, and rare arrhythmias (RACDRAs). METHODS We performed a search for RACDRAs using the Orphanet inventory of rare diseases, which includes diseases with a prevalence of no more than 5 per 10 000 in the general population. We supplemented this with a search of PubMed and Scopus databases according to a wider definition proposed by the European Parliament and the Council of the European Union. RESULTS RACDRAs are categorized into 2 groups, primary electrical disorders of the heart and arrhythmias in specific clinical settings. The first group is further divided into subgroups of major clinical presentation: disorders predisposing to supraventricular tachyarrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and others. The second group includes iatrogenic arrhythmias or heart rhythm disturbances related to medical treatment, arrhythmias associated with metabolic disorders, and others. We provide a classification of RACDRAs and supplement them with respective RCDDs codes. CONCLUSION The clinical classification of RACDRAs may form a basis to facilitate research and progress in clinical practice, both in diagnostic and therapeutic approaches.
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http://dx.doi.org/10.20452/pamw.4451DOI Listing
March 2019

Association between carotid-femoral pulse wave velocity and overall cardiovascular risk score assessed by the SCORE system in urban Polish population.

Kardiol Pol 2019;77(3):363-370. Epub 2019 Feb 11.

John Paul II Hospital, Krakow, Poland.

Background: The Systemic COronary Risk Estimation (SCORE) system is recommended for the assessment of cardiovascular disease (CVD) death risk in individuals free of CVD.

Aim: We sought to determine the association between carotid-femoral pulse wave velocity (CFPWV) and SCORE.

Methods: The study involved 1008 Krakow residents, and a random subsample of 3424 men and 3205 women who participated in Wave 2 of the Polish part of the Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study. At baseline we performed a medical interview, physical examination, evaluation of present comorbidities, medications using standardised methods. A follow-up of 4.9 years included measurement of CFPWV using an automatic, computerised Complior® system.

Results: Final analysis included 720 patients (378 women), aged 58.5 ± 6.5 years at baseline. In 488 individuals without his- tory of CVD and/or diabetes, SCORE was calculated. Median CFPWV was higher (p = 0.002) in men (12.5 m/s; interquartile range [IQR] 10.3-15.7) than in women (11.7 m/s; IQR 10.1-13.7). High CFPWV (> 10 m/s) was observed in 270 men (78.9%) and in 285 women (75.4%). We observed a strong association between high CVD risk (SCORE ≥ 5%) and high CFPWV (odds ratio 2.29; 95% confidence interval 1.17-4.46). The CFPWV cut-off value to differentiate between patients with low and high CVD risk was 11.7 m/s (with 58.6% sensitivity and 71.3% specificity, AUC = 0.68).

Conclusions: Our study is the first to describe the distribution of CFPWV in the adult Polish population. SCORE ≥ 5% pre- dicted high CFPWV in 4.9 years of follow-up, which was independent of other risk factors. CFPWV > 11.7 m/s was most valid in relation to high CVD risk.
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http://dx.doi.org/10.5603/KP.a2019.0028DOI Listing
August 2019

Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio and Systemic Inflammation in Patients with Idiopathic Pulmonary Arterial Hypertension.

Med Sci Monit 2019 Jan 26;25:746-753. Epub 2019 Jan 26.

Department of Cardiac and Vascular Diseases, Faculty of Medicine, Jagiellonian University Medical College, John Paul II Hospital in Cracow, Cracow, Poland.

BACKGROUND Idiopathic pulmonary arterial hypertension (IPAH) patients are characterized by elevated triglyceride (TG)-to-HDL cholesterol (HDL-C) ratio, which has been proposed to be an important prognostic factor in this population. The mechanism of this phenomenon remains unknown. We therefore investigated the potential determinants of increased TG/HDL-C ratio in IPAH patients. MATERIAL AND METHODS We prospectively recruited consecutive clinically stable IPAH patients between January 2016 and February 2017. Patients with diabetes or using statins were excluded. Anthropometric measurements included body mass index (BMI) and skinfold thickness; body fat mass was calculated using age and sex-specific equations. We assessed lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), serum adipokine levels (adiponectin, resistin, leptin, and visfatin), and circulating cytokines (IL-1β, IL-6, MCP-1, and TNF-α). RESULTS We assessed 47 IPAH patients: 9 of them had been diagnosed with diabetes and 10 were treated with statins; therefore, were excluded them from further analysis. Age, sex distribution, and BMI were similar irrespectively of TG/HDL-C ratio. Patients with increased TG/HDL-C ratio (>3) as compared to patients with TG/HDL-C ≤3 were characterized by higher levels of IL-1β, MCP-1, and IL-6. TG level was correlated with IL-1β (R=0.76, p<0.001), IL-6 (R=0.52, p=0.005), TNF-α (R=0.62, p<0.001), and MCP-1 (R=0.63, p<0.001). IL-1β was also inversely correlated with HDL-C (R=-0.44, p=0.02). We found no differences in concentration of fasting glucose, insulin, HOMA-IR, body fat content, or adipokine levels between patients with higher and lower TG/HDL-C ratios. CONCLUSIONS In IPAH patients, elevated TG/HDL-C ratio is a marker of systemic inflammation.
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http://dx.doi.org/10.12659/MSM.912766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359883PMC
January 2019