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Acute heart ischemia followed by reperfusion leads to overproduction of reactive oxygen/ /nitrogen species (ROS/RNS), disrupted expression of nitric oxide synthase (NOS) and unbalanced glucose metabolism. Klotho is a membrane-bound or soluble protein that exerts protective activity in many organs. While Klotho is produced mainly in the kidneys and brain, it has been recently proven that Klotho is expressed in the cardiomyocytes as well. This study aimed to show the influence of the Klotho protein on oxidative/nitrosative stress and metabolic function of the cardiomyocytes subjected to ischemia/reperfusion (I/R) injury.Human cardiac myocytes underwent in vitro chemical I/R (with sodium cyanide and 2-deoxyglucose), in the presence or absence of the recombinant human Klotho protein. The present study included an investigation of cell injury markers, level of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), level of oxidative/nitrosative stress and metabolic processes of the cardiomyocytes.Administration of Klotho protein resulted in mitigation of injury, decreased level of NOX2 and NOX4, reduced generation of ROS/RNS and hydrogen peroxide (H2O2), decreased expression of inducible NOS and limited production of nitrates/nitrites in cells under I/R. Glucose uptake and lactate production in the cardiomyocytes subjected to I/R were normalized after Klotho supplementation.The Klotho protein participates in the regulation of redox balance and supports metabolic homeostasis of the cardiomyocytes and hence, contributes to protection against I/R injury.

Ischaemia, followed by reperfusion, causes the generation of reactive oxygen species, overproduction of peroxynitrite, activation of matrix metalloproteinases (MMPs), and subsequently the degradation of heart contractile proteins in the cardiomyocytes. Klotho is a membrane-bound or soluble protein that regulates mineral metabolism and has antioxidative activity. This study aimed to examine the influence of Klotho protein on the MMP-mediated degradation of contractile proteins during ischaemia/reperfusion injury (IRI) to the cardiomyocytes. Human cardiac myocytes (HCM) underwent in vitro chemical IRI (with sodium cyanide and deoxyglucose), with or without the administration of recombinant Klotho protein. The expression of MMP genes, the expression and activity of MMP proteins, as well as the level of contractile proteins such as myosin light chain 1 (MLC1) and troponin I (TnI) in HCM were measured. Administration of Klotho protein resulted in a decreased activity of MMP-2 and reduced the release of MLC1 and TnI that followed in cells subjected to IRI. Thus, Klotho protein contributes to the inhibition of MMP-dependent degradation of contractile proteins and prevents injury to the cardiomyocytes during IRI.

Background Ischemia/reperfusion injury (IRI) of heart involves activation of oxidative and apoptotic pathways. Klotho protein has potential protective activity since it supports redox balance and metabolic functions of cardiomyocytes. This study aimed to evaluate effect of Klotho protein on oxidative stress and apoptosis in hearts subjected to IRI. Material and methods Isolated rat hearts perfused with the Langendorff method were subjected to ischemia, followed by reperfusion, in presence or absence of Klotho protein. Heart mechanical function and factors involved in the activation of insulin-like growth factor 1 receptor (IGFR-1)/phosphoinositide 3-kinase (PI3K) signaling pathway were evaluated. Results Infusion supply of Klotho significantly increased (P = 0.001) mechanical function of hearts injured by IRI. IRI caused activation of IGFR-1/PI3K signalling pathway (P = 0.004; P = 0.003), while Klotho suppressed phosphorylation of IGFR-1 (P = 0.208) and PI3K (P = 0.022). Transcriptional activity of forkhead box protein O1 (FOXO1) and FOXO3 was reduced (P = 0.002; P < 0.001) in IRI hearts. Administration of Klotho decreased phosphorylation of FOXO1 (P = 0.587) and FOXO3 (P = 0.027) in IRI + Klotho group, while activity of glutathione peroxidase and superoxide dismutase was increased (P = 0.045; P = 0.006), and level of hydrogen peroxide and lipid peroxidation was slightly decreased (P = 0.502; P = 0.436), as compared to IRI hearts. Klotho protein contributed to reduction in caspase-9 level (P = 0.009) during IRI. Conclusion Administration of Klotho resulted in full preservation of heart mechanical function, and suppression of oxidative stress and apoptosis in IRI hearts. Thus, Klotho can be recognized as a novel cardiopreventive agent in ischemic damage. Funding Ministry of Science and Higher Education in Poland [grant number SUBK.D010.22.035].

Background The injury of the myocardium during ischemia/reperfusion (IRI) involves metabolic, morphological, and contractile disorders. Klotho is a membrane or soluble anti-aging protein. Recent studies have proven the correlation between Klotho deficiency and the occurrence and development of cardiovascular diseases. The study aimed to evaluate the effect of Klotho protein on hearts subjected to IRI. Material and methods Isolated Wistar rat hearts perfused with the Langendorff method were subjected to ischemia, followed by reperfusion, in the presence or absence of Klotho protein. Hemodynamic parameters and the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Κb), nitrate/nitrite, inducible nitric oxide synthase (iNOS), asymmetric dimethylarginine (ADMA), matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of MMP type 4 (TIMP-4) were evaluated. Results Infusion supply of Klotho during IRI resulted in the recovery of contractile function (P = 0.031) and heart rate (P = 0.02). IRI activated MMP-2 (P = 0.042) and MMP-9 (P = 0.041) in hearts, as compared to aerobic control. Klotho contributed to increase in iNOS level (P = 0.02), and decreased levels of NF-Κb (P = 0.006), ADMA (P = 0.007), nitrate/nitrite (P = 0.022), MMP-2 (P = 0.024) and MMP-9 (P < 0.001), as compared to IRI group. Conclusions Klotho protein preserved heart mechanical function and reduced the level of proteolytic enzymes in the heart. Thus, Klotho can be recognized as a novel cardiopreventive/cardioprotective agent in ischemic damage. This work was supported by the National Science Centre, Poland [grant number 2019/33/N/NZ3/01649].

Platelets play a fundamental role in myocardial infarction and the pathogenesis of ischemia/reoxygenation (I/R) injuries. They contain matrix metalloproteinases (MMPs) that are involved in arterial thrombosis. The MMP inhibitor doxycycline has been shown to exert protective effects in I/R injuries involving various organs and mechanisms.To explore the influence of doxycycline on platelet activation and MMP-2 activity during I/R.Platelets isolated from the blood of healthy human volunteers were subjected to chemical I/R conditions. The study included aerobic controls (AERO), I/R platelets and I/R platelets pretreated with doxycycline (I/R+D). The concentration of doxycycline used was standardized to 10 μM. The analysis of platelet activation markers and platelet microvesicles (PMVs) was performed using flow cytometry. Adenosine diphosphate (ADP)-induced and collagen-induced aggregation, as well as MMP-2 activity and its concentration in platelets were evaluated.Doxycycline decreased the expression of activated glycoprotein IIb/IIIa on platelets (p = 0.043). Additionally, an increased expression of CD63 was observed in buffers containing PMVs after doxycycline administration (p = 0.043). The ADP-dependent aggregation of I/R platelets was significantly lower in comparison to AERO (p = 0.022). Furthermore, there was a stronger tendency of enhanced ADP-dependent aggregation in I/R platelets pretreated with doxycycline compared to platelets that underwent I/R without doxycycline. Higher MMP-2 activity was observed in I/R+D platelets compared to I/R platelets (p0.01).The inhibition of platelet MMP-2 by doxycycline attenuated platelet activation and protected platelets by preserving their aggregation ability.

(1) Background: Pulmonary embolism (PE) is the third most frequent acute cardiovascular condition worldwide. PE response teams (PERTs) have been created to facilitate treatment implementation in PE patients. Here, we report on the 5-year experience of PERT operating in Warsaw, Poland, with regard to the characteristics and outcomes of the consulted patients. (2) Methods: Patients diagnosed with PE between September 2017 and December 2021 were included in the study. Clinical and treatment data were obtained from medical records. Patient outcomes were assessed in-hospital, at a 1- and 12-month follow-up. (3) Results: There were 235 PERT activations. The risk of early mortality was low in 51 patients (21.8%), intermediate–low in 83 (35.3%), intermediate–high in 80 (34.0%) and high in 21 (8.9%) patients. Anticoagulation alone was the most frequently administered treatment in all patient subgroups (altogether 84.7%). Systemic thrombolysis (47.6%) and interventional therapy (52%) were the prevailing treatment options in high-risk patients. The in-hospital mortality was 6.4%. The adverse events during 1-year follow-up included five deaths, two recurrent VTE and two minor bleeding events. (4) Conclusions: Our initial 5-year experience showed that the activity of the local PERT facilitated patient-tailored decision making and the access to advanced therapies, with subsequent low overall mortality and treatment complication rates, confirming the benefits of PERT implementation.

Restoration of blood flow to ischaemic heart inflicts ischaemia/reperfusion (I/R) injury, which manifests in metabolic and morphological disorders. Klotho is a protein with antioxidative and antiapoptotic activity, and is involved in the regulation of inflammation and fibrosis. The aim of the current research was to determine the role of Klotho in the heart subjected to I/R injury, as well as to study Klotho as a potential cardioprotective agent. Human cardiomyocytes and Wistar rat hearts perfused using Langendorff method subjected to I/R have been used. Hemodynamic parameters of heart function, markers of I/R injury, and gene and protein expression of Klotho were measured. Human cardiomyocytes were also incubated in the presence of recombinant Klotho protein, and the viability of cells was measured. There was a higher expression of Klotho gene and protein synthesis in the cardiomyocytes subjected to I/R injury. The compensatory production and release of Klotho protein from cardiac tissue during I/R were also shown. The treatment of cardiomyocytes subjected to I/R with Klotho protein resulted in increased viability and metabolic activity of cells. Thus, Klotho contributes to compensatory mechanism during I/R, and could be used as a marker of injury and as a potential cardiopreventive/cardioprotective agent.

Pulmonary hypertension (PH) is a serious hemodynamic condition, characterized by increased pulmonary vascular resistance (PVR), leading to right heart failure (HF) and death when not properly treated. The prognosis of PH depends on etiology, hemodynamic and biochemical parameters, as well as on response to specific treatment. Biomarkers appear to be useful noninvasive tools, providing information about the disease severity, treatment response, and prognosis. However, given the complexity of PH, it is impossible for a single biomarker to be adequate for the broad assessment of patients with different types of PH. The search for novel emerging biomarkers is still ongoing, resulting in a few potential biomarkers mirroring numerous pathophysiological courses. In this review, markers related to HF, myocardial remodeling, inflammation, hypoxia and tissue damage, and endothelial and pulmonary smooth muscle cell dysfunction are discussed in terms of diagnosis and prognosis. Extracellular vesicles and other markers with complex backgrounds are also reviewed. In conclusion, although many promising biomarkers have been identified and studied in recent years, there are still insufficient data on the application of multimarker strategies for monitoring and risk stratification in PH patients.

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

Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds ofTwo experimental models were used: isolated rat hearts perfused with the Langendorff method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwentΔ9-THC protected the heart, as evidenced by the improved recovery of cardiac function (Δ9-THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of Δ9-THC as a cardioprotective drug to be, administered before onset of I/R protocol.

Background: Balloon pulmonary angioplasty (BPA) is a form of therapy for chronic thromboembolic pulmonary hypertension (CTEPH). The study objective is to assess the clinical usefulness of resting ECG (PH-ECG score) in monitoring the efficacy of BPA in CTEPH patients. Methods and results: Ninety-four (n = 94) CTEPH patients were included in the analysis. A standard 12-lead-ECG was performed before the first BPA session and after completion of treatment. The whole analysed population (n = 94) was divided into the following two groups: derivation cohort (n = 41) and validation cohort (n = 53). The derivation cohort was divided into the following two subgroups: patients with mean pulmonary artery pressure (mPAP) after the completion of therapy &lt, 25 mmHg (n = 21) and patients with mPAP after the completion of therapy ≥ 25 mmHg (n = 20). In the first subgroup, four (R-wave V1 + S-wave V5/V6 &gt, 10.5 mm, QRS-wave axis &gt, 110 degrees, R-wave V1 &gt, S-wave V1, SIQIII pattern) of the six ECG parameters of overload of the right cardiac chambers showed statistically significant differences (p &lt, 0.005). That was followed by a determination of the sensitivity and specificity, positive (PPV) and negative predictive value (NPV), and ROC curve (AUC 0.9, 95% CI: 0.792–1.000) for the variable that was a sum of the above four ECG parameters (PH-ECG score). The absence of all of the four ECG parameters at rest (PH-ECG score = 0) well reflected patients with mPAP &lt, 25 mmHg (sensitivity, 100%, specificity, 80%, PPV, 84%, NPV, 100%). In the validation cohort with mPAP &lt, 25 mmHg and PH-ECG score = 0, sensitivity, specificity, PPV, and NPV were 86%, 77%, 73%, and 89%, respectively. Conclusions: Resting ECG trace is clinically useful in the monitoring of therapeutical effects of BPA in CTEPH patients.

Background: Percutaneous pulmonary interventions require extensive and accurate navigation planning and guidance, especially in regard to the three-dimensional (3D) relationships between anatomical structures. In this study, we are demonstrating the feasibility of novel visualization techniques: 3D printing (3DP) and augmented reality (AR) in planning transcatheter pulmonary interventions. Methods: Two patients were qualified for balloon pulmonary angioplasty (BPA) for treatment of chronic thromboembolic pulmonary hypertension (CTEPH) and stent implantation for pulmonary artery stenosis, respectively. Computed tomography images of both patients were processed with segmentation algorithms and subsequently submitted to 3D modelling software. Microsoft HoloLens ® AR headsets with dedicated CarnaLife Holo ® software were utilized to display surface and volume rendering of pulmonary vessels as holograms. Results: Personalized life-sized models of the same structures were additionally 3D-printed for preoperative planning. Holograms were shown to physicians throughout the procedure and were used as a guidance and navigation tool. Operative team was able to manipulate the hologram and multiple users of the AR system could share the same image in real time. Clinicians expressed their satisfaction with the quality of imaging and potential clinical benefits. Conclusions: This study reports the potential value of AR in pulmonary interventions, however, prospective trials need to be conducted to decide on whether novel 3D visualization techniques affect perioperative treatment and outcomes.

Atrial light chains (ALC1) are naturally present in adult heart atria, while ventricular light chains (VLC1) are predominant in ventricles. Degradation of VLC1 and re‑expression of ALC1 in heart ventricles are associated with heart disorders in response to pressure overload. The aim of the current study was to investigate changes in myosin light chain expression after simulated ischemia and simulated reperfusion (sI/sR). Human cardiomyocytes (HCM) isolated from adult heart ventricles were subjected to chemical ischemia. The control group was maintained under aerobic conditions. Myocyte injury was determined by testing lactate dehydrogenase (LDH) activity. The gene expression of ALC1, VLC1 and MMP‑2 were assessed by reverse transcription‑quatitive PCR. Additionally, protein synthesis was measured using ELISA kits and MMP‑2 activity was measured by zymography. The results revealed that LDH activity was increased in sI/sR cell‑conditioned medium (P=0.02), confirming the ischemic damage of HCM. ALC1 gene expression and content in HCM were also increased in the sI/sR group (P=0.03 and P

Background: The aim of the study was to assess soluble ST2 (sST2) concentration and its dynamic changes in the periprocedural period in patients with chronic thromboembolic pulmonary hypertension (CTEPH) treated with balloon pulmonary angioplasty (BPA). Methods: We prospectively analyzed 57 procedures of BPA performed in 37 patients with CTEPH. Biomarkers, such as N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T (TnT), and sST2 were assessed at four time points: Before the BPA procedure, 24 h and 48 h after the procedure, and at the discharge from hospital. Each postprocedural period was assessed for complications. Results: Before the BPA procedure, median sST2 concentration was 26.56 ng/mL (IQR: 16.66&ndash, 40.83 ng/mL). sST2 concentration was significantly higher 24 h and 48 h after the BPA compared to the baseline measurements (33.31 ng/mL (IQR: 20.81&ndash, 62.56), p = 0.000 and 27.45 ng/mL (IQR: 17.66&ndash, 54.45), p = 0.028, respectively). sST2 level 24 h after the BPA procedure was significantly higher in the group with complications compared to the group without complications in the postprocedural period (97.66 ng/mL (IQR: 53.07&ndash, 126.18) vs. 26.86 ng/mL (IQR: 19.10&ndash, 40.12), p = 0.000). Conclusions: sST2 concentration in patients with CTEPH treated with BPA changes significantly in the postprocedural period and is significantly higher in the group with complications in postprocedural period.

IntroductionNon-invasive tests that may improve clinical evaluation of pulmonary hypertension (PH) are needed. The purpose of this study was to assess the role of soluble ST2 (sST2) in patients with PH.Material and methodsA total of 57 patients with chronic thromboembolic PH and 43 patients with idiopathic arterial PH were enrolled in this study. All patients were evaluated for World Health Organization (WHO) functional class (FC), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), troponin T (TnT), and hemodynamics. Plasma sST2 was assessed by an immu­nofluorescent in vitro diagnostic assay. All patients were followed up from the date of blood sampling. The endpoint was all-cause death.ResultsThe median sST2 concentration was 32.8 ng/ml (IQR: 21.6–48.5 ng/ml) in the whole study population. Significant differences were found between median sST2 in successive WHO FCs (FC II vs. FC III, p = 0.002; FC III vs. FC IV, p = 0.12; FC II vs. FC IV, p = 0.008). Significant correlations were found between sST2 and hemodynamic parameters: mean right atrial pressure (r = 0.56; p ConclusionssST2 seems to be a marker of poor clinical prognosis in patients with PH.

An essential procedure for the treatment of myocardial infarction is restoration of blood flow in the obstructed infarct artery, which may cause ischaemia/reperfusion (I/R) injury. Heart I/R injury manifests in oxidative stress, metabolic and morphological disorders, or cardiac contractile dysfunction. Klotho protein was found to be produced in the heart tissue and participate in antioxidation or ion homeostasis. The aim of this study was to examine an influence of Klotho protein on the heart subjected to I/R injury. Wistar rats served as a surrogate heart model ex vivo. Rat hearts perfused using the Langendorff method were subjected to global no-flow ischaemia, and isolated rat cardiomyocytes underwent chemical I/R in vitro, with or without recombinant Klotho protein administration. Haemodynamic parameters of heart function, cell contractility, markers of I/R injury and oxidative stress, and the level of contractile proteins such as myosin light chain 1 (MLC1) and troponin I (TnI) were measured. The treatment of hearts subjected to I/R injury with Klotho protein resulted in a recovery of heart mechanical function and ameliorated myocyte contractility. This improvement was associated with decreased tissue injury, enhanced antioxidant capacity, and reduced release of MLC1 and TnI. The present research showed the contribution of Klotho to cardioprevention during I/R. Thus, Klotho protein may support the protection from I/R injury and prevention of contractile dysfunction in the rat heart.

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.

Background. Arterial hypertension (HT) is a serious and prevalent epidemiological factor in the development of coronary artery disease (CAD). Metalloproteinases (MMPs), especially MMP-2 and MMP-9, and their natural endogenous tissue inhibitors (TIMPs) are involved in the pathogenesis of HT and its complications. MMPs are also involved in the development of diabetes (DM), a risk factor for CAD. The aim of the study was to explore the influence of CAD, HT, and DM on changes in plasma levels of MMP-2 and MMP-9 and their inhibitor TIMP-4. Methods and Results. The study involved 70 patients with stable CAD admitted for coronary angiography and 15 healthy subjects. Whole blood samples were collected prior to angiography. MMP-2, MMP-9, and TIMP-4 levels in plasma were estimated using ELISA tests. CAD patients showed a significantly increased level of TIMP-4 and decreased level of MMP-2 in comparison to healthy controls (p=0.011 and p=0.037, respectively). Concentration of MMP-2, MMP-9, and TIMP-4 did not differ in the group with and without hypertension. Patients with DM presented higher MMP-2 level than patients without DM (p<0.001). Multiple regression analysis of the influence of independent variables such as CAD stage, DM, and HT on MMP-2, MMP-9, and TIMP-4 showed that only DM was independently associated with a higher level of MMP-2 (β = 0.42, R2 = 0.17, p<0.001). Conclusion. Data showed that patients with CAD presented higher TIMP-4 and lower MMP-2 concentration regardless of HT and DM. HT had no effect on MMP-2, MMP-9, and TIMP-4 levels in serum. DM was independently associated with higher MMP-2 concentration; however, co-occurrence of CAD and DM was associated with the balance in the MMP-2 level. Concentration of MMP-9 did not change significantly in any of the analysed groups.

Background: In this study, we aimed to assess the efficacy and safety of balloon pulmonary angioplasty (BPA) in patients with technically inoperable distal-type chronic thromboembolic pulmonary hypertension (d-CTEPH) and technically operable proximal-type disease (p-CTEPH) by analyzing the results of BPA treatment in two collaborating CTEPH referral centers. Methods and results: We assessed hemodynamic results, functional efficacy, complication and survival rate after BPA treatment in 70 CTEPH patients (median age 64 years, (interquartile range (IQR): 52–73 years)), of whom 16 (median age 73 years, (QR 62–82 years)) were in the p-CTEPH subgroup. Altogether, 377 BPA procedures were performed, resulting in significant (p &lt, 0.001) improvement in mean pulmonary artery pressure (mPAP 48.6 ± 10 vs. 31.3 ± 8.6 mmHg), pulmonary vascular resistance (694 ± 296 vs. 333 ± 162 dynes*s*cm−5), six-minute walk test (365 ± 142 vs. 433 ± 120 metres) and N-terminal pro B-type natriuretic peptide (1307 (510–3294) vs. 206 (83–531) pg/mL). The rate of improvement did not differ between the sub-groups. Lung injury episodes and severe hemoptysis were similarly infrequent in d-CTEPH and p-CTEPH (6.4% vs. 5%, p = 0.55 and 1.0% vs. 2.5, p = 0.24, respectively). There was no significant difference between the sub-groups regarding survival (p = 0.53 by log-rank test). Conclusion: BPA may be beneficial in patients with p-CTEPH who cannot undergo pulmonary endarterectomy (PEA). Larger long-term studies are needed to better define the efficacy, safety, and optimal BPA procedural standards in this population.

Ischemia/reperfusion (I/R) injury induces post-translational modifications of myosin light chains (MLCs), increasing their susceptibility to degradation by matrix metalloproteinase 2 (MMP-2). This results in the degradation of ventricular light chains (VLC1) in heart ventricles. The aim of the study was to investigate changes in MLCs content in the mechanism of adaptation to oxidative stress during I/R. Rat hearts, perfused using the Langendorff method, were subjected to I/R. The control group was maintained in oxygen conditions. Lactate dehydrogenase (LDH) activity and reactive oxygen/nitrogen species (ROS/RNS) content were measured in coronary effluents. Atrial light chains (ALC1) and ventricular light chains (VLC1) gene expression were examined using RQ-PCR. ALC1 and VLC1 protein content were measured using ELISA tests. MMP-2 activity was assessed by zymography. LDH activity as well as ROS/RNS content in coronary effluents was higher in the I/R group (p = 0.01, p = 0.04, respectively), confirming heart injury due to increased oxidative stress. MMP-2 activity in heart homogenates was also higher in the I/R group (p = 0.04). ALC1 gene expression and protein synthesis were significantly increased in I/R ventricles (p &lt, 0.01, 0.04, respectively). VLC1 content in coronary effluents was increased in the I/R group (p = 0.02), confirming the increased degradation of VLC1 by MMP-2 and probably an adaptive production of ALC1 during I/R. This mechanism of adaptation to oxidative stress led to improved heart mechanical function.

We present a case of a 67-year-old female with proximal chronic thromboembolic pulmonary hypertension (CTEPH), disqualified from pulmonary endarterectomy due to multiple comorbidities and high risk-to-benefit ratio as assessed by multidisciplinary CTEPH team. She was referred for balloon pulmonary angioplasty (BPA) and underwent three sessions with balloon catheters up to 8 mm diameter. During the second procedure, the elastic recoil phenomenon was observed in the treated post-thrombotic lesion of the right lower lobe artery, which made the balloon angioplasty ineffective. It was decided to implant a self-expanding stent for the prevention of restenosis. The procedure resulted in significant improvement of regional perfusion, as confirmed by control angiography. We feel that it contributed to the significant improvement of hemodynamic parameters and exercise capacity, as assessed three months after the last BPA procedure. In conclusion, pulmonary artery stenting may be an option in proximal CTEPH when elastic recoil phenomenon makes balloon angioplasty of a large vessel ineffective.

Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). However, persistent pulmonary hypertension continues in 5-35% of patients after PEA. Recently, balloon pulmonary angioplasty (BPA) showed promise as a strategy for patients with non-operable CTEPH. Therefore, we investigated the usefulness of BPA for residual pulmonary hypertension after PEA.Fifteen patients with residual pulmonary hypertension after PEA received 71 BPA sessions (4.7 ± 1.4 sessions/patient). The mean time between the PEA and the first BPA session was 28.1 ± 25.8 months. All patients underwent a comprehensive diagnostic work-up, including right heart catheterization, functional and laboratory tests, before, and 6-4 weeks after the BPA sessions.After BPA, the mean pulmonary arterial pressure decreased from 44.7 ± 6.4 to 30.8 ± 7.5 mm Hg (31% decline; p 0.001). Pulmonary vascular resistance decreased from 551.9 ± 185.2 to 343.8 ± 123.8 dyn∗s/cmBPA could be a promising therapeutic strategy for persistent pulmonary hypertension after PEA in patients with CTEPH.

This study evaluated the incremental effect of riociguat on pulmonary hemodynamics in patients with inoperative or persistent chronic thromboembolic pulmonary hypertension (CTEPH) treated previously with sildenafil.The retrospective study included 28 patients diagnosed with CTEPH who were ineligible for surgical treatment due to distal thrombi location or who suffered from persistent CTEPH after pulmonary endarterectomy and who were treated with sildenafil at a dose of 25 mg TID for a minimum of 3 months. Sildenafil was subsequently discontinued, and riociguat therapy was started with gradually increasing doses. Right heart catheterization was performed and WHO functional class (FC) was assessed in each patient at three time points: before starting sildenafil therapy (baseline), before the transition to riociguat, and after 3 to 6 months of therapy with riociguat.Compared to baseline, the use of sildenafil and riociguat significantly decreased pulmonary vascular resistance (PVR) (10.47 ± 3.56 vs. 7.81 ± 3.58 Wood units, p 0.001) and mean pulmonary arterial pressure (PAP) (54.1 ± 11.6 vs. 46.1 ± 13.2 mm Hg; p 0.001) while increasing cardiac output (CO) (4.31 ± 0.88 vs. 4.85 ± 0.87 L/min; p = 0.007). Switching from sildenafil to riociguat reduced PVR by 14% (p = 0.005) and the mean PAP by 6% (p = 0.03) while increasing CO by 11% (p = 0,002). The number of patients with WHO FC III and IV symptoms decreased from 71,4% to 57,1% (p = 0,02) after the change from sildenafil to riociguat.Replacing sildenafil with riociguat in patients with inoperable or persistent CTEPH may improve pulmonary hemodynamics and FC.