Isoprostane-8 and GDF-15 as novel markers of post-PE syndrome: Relation with prothrombotic factors.

BACKGROUND: Post-pulmonary embolism (PE) syndrome occurs in up to 50% of PE patients. The pathophysiology of this syndrome is obscure. OBJECTIVE: We investigated whether enhanced oxidative stress and prothrombotic state may be involved in post-PE syndrome. METHODS: We studied 101 normotensive noncancer PE patients (aged 56.5 ± 13.9 years) on admission, after 5-7 days and after a 3-month anticoagulation, mostly with rivaroxaban. A marker of oxidative stress, 8-isoprostane, endogenous thrombin potential, fibrinolysis proteins, clot lysis time (CLT) and fibrin clot permeability (Ks ), along with PE biomarkers, were determined. RESULTS: Patients who developed the post-PE syndrome (n = 31, 30.7%) had at baseline 77.6% higher N-terminal brain natriuretic propeptide and 46.8% higher growth differentiation factor 15, along with 14.1% longer CLT associated with 34.4% higher plasminogen activator inhibitor-1 as compared to subjects without post-PE syndrome (all P < .05). After 5-7 days, only hypofibrinolysis was noted in post-PE syndrome patients. When measured at 3 months, prolonged CLT and reduced Ks were observed in post-PE syndrome patients, accompanied by 23.8% higher growth differentiation factor 15 and 35.8% higher plasminogen activator inhibitor-1 (all P < .05). 8-isoprostane levels ≥108 pg/ml (odds ratio=4.36; 95% confidence interval 1.63-12.27) and growth differentiation factor 15 ≥ 1529 pg/ml (odds ratio=3.89; 95% confidence interval 1.29-12.16) measured at 3 months were associated with higher risk of developing post-PE syndrome. CONCLUSIONS: Enhanced oxidative stress and prothrombotic fibrin clot properties could be involved in the pathogenesis of the post-PE syndrome. Elevated growth differentiation factor 15 assessed at 3 months might be a new biomarker of this syndrome.

Reversal of Platelet Inhibition in Patients Receiving Ticagrelor.

Antiplatelet treatment is one of the pillars of contemporary therapy in acute coronary syndromes. It is based on dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 receptor inhibitor. Antiaggregatory treatment reduces ischemic events, but at cost of increased bleeding rates. As a result of irreversible inhibition of platelet P2Y12 receptors, the antiplatelet action of clopidogrel and prasugrel is prolonged for the lifespan of thrombocytes and lasts up to 7 days. The antiaggregatory effect of ticagrelor may persist up to 5 days despite its reversible nature of P2Y12 receptor inhibition. These pharmacodynamic properties may prove problematic in patients requiring immediate reversal of antiplatelet effects due to severe or life-threatening bleeding, or in presence of indications for an urgent surgery. The current review summarizes available knowledge on different strategies of restoring platelet function in patients treated with ticagrelor. Non-specific methods are discussed, including platelet transfusion, human albumin supplementation and hemadsorption. Finally, bentracimab, the first specific antidote for ticagrelor, and in fact against any antiplatelet agent, is described.

Longer Hospitalizations and Higher In-Hospital Mortality for Acute Heart Failure during the COVID-19 Pandemic in Larger vs. Smaller Cardiology Departments: Subanalysis of the COV-HF-SIRIO 6 Multicenter Study.

Background: The coronavirus disease-2019 (COVID-19) pandemic is surging across Poland, leading to many direct deaths and underestimated collateral damage. We aimed to compare the influence of the COVID-19 pandemic on hospital admissions and in-hospital mortality in larger vs. smaller cardiology departments (i.e., with ≥ 2000 vs. < 2000 hospitalizations per year in 2019). Methods: We performed a subanalysis of the COV-HF-SIRIO 6 multicenter retrospective study including all patients hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, focusing on patients with acute heart failure (AHF) and COVID-19. Results: Total number of hospitalizations was reduced by 29.2% in larger cardiology departments and by 27.3% in smaller cardiology departments in 2020 vs. 2019. While hospitalizations for AHF were reduced by 21.8% and 25.1%, respectively. The length of hospital stay due to AHF in 2020 was 9.6 days in larger cardiology departments and 6.6 days in smaller departments (p < 0.001). In-hospital mortality for AHF during the COVID-19 pandemic was significantly higher in larger vs. smaller cardiology departments (10.7% vs. 3.2%; p < 0.001). In-hospital mortality for concomitant AHF and COVID-19 was extremely high in larger and smaller cardiology departments accounting for 31.3% vs. 31.6%, respectively. Conclusions: During the COVID-19 pandemic longer hospitalizations and higher in-hospital mortality for AHF were observed in larger vs. smaller cardiology departments. Reduced hospital admissions and extremely high in-hospital mortality for concomitant AHF and COVID-19 were noted regardless of department size.

Minor bleeding affects the level of knowledge in patients with atrial fibrillation on oral anticoagulant therapy.

BACKGROUND: Anticoagulant therapy in patients with atrial fibrillation (AF) increases the risk of minor bleeding, which is mostly accepted by patients. We aimed to assess whether continuation of anticoagulation despite minor bleeding is associated with a higher level of knowledge on AF and anticoagulation. METHODS AND RESULTS: In 1525 patients with AF on oral anticoagulation who completed the Jessa AF Knowledge Questionnaire (JAKQ) (median age: 72 years [range, 65-79 years]; men: 54.6%), persistent self-reported minor bleeding was recorded. Minor bleeding was observed in 567 patients (37.2%) including 224 patients (39.5%) on vitamin K antagonists (VKAs) and 343 (60.5%) on non-vitamin K antagonist oral anticoagulants (NOACs). The risk of minor bleeding was lower among patients on NOACs than on VKAs (33.5% vs 44.6%; P < .0001). Multiple logistic regression showed that minor bleeding was associated with the use of NOACs (odds ratio [OR] 0.75; 95% CI 0.59-0.97), female gender (OR 2.19; 95% CI, 1.74-2.75; P < .0001), history of major bleeding (OR 2.85; 95% CI, 1.96-4.14; P < .0001), time since AF diagnosis (OR 1.04; 95% CI, 1.01-1.06; P < .0001), concomitant vascular disease (OR 1.43; 95% CI, 1.10-1.87; P = .0008) and diabetes mellitus (OR 1.3; 95% CI, 1.02-1.65, P = .03). Patients with minor bleeding, compared with the remaining subjects scored higher on the JAKQ (median, 62.5% vs 56.2%, respectively, P < .0001). The former group knew more about the purpose of anticoagulant therapy (71.8% vs 65.7%, P = .01) and bleeding as its key side effect (66.1% vs 52.7%, P < .0001), and were better informed on the safest painkillers to use in combination with anticoagulation (48% vs 35%, P < .0001). CONCLUSION: This study suggests that AF patients who accept persistent minor bleeding have better knowledge on the disease and anticoagulation therapy compared with those free of these side effects.

Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study.

BACKGROUND: The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. METHODS: Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. RESULTS: Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. CONCLUSIONS: There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers' release.

Comparison of reorganized versus unaltered cardiology departments during the COVID-19 era: A subanalysis of the COV-HF-SIRIO 6 study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous cardiology departments were reorganized to provide care for COVID-19 patients. We aimed to compare the impact of the COVID-19 pandemic on hospital admissions and in-hospital mortality in reorganized vs. unaltered cardiology departments. METHODS: The present research is a subanalysis of a multicenter retrospective COV-HF-SIRIO 6 study that includes all patients (n = 101,433) hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, with a focus on patients with acute heart failure (AHF). RESULTS: Reduction of all-cause hospitalizations was 50.6% vs. 21.3% for reorganized vs. unaltered cardiology departments in 2020 vs. 2019, respectively (p < 0.0001). Considering AHF alone respective reductions by 46.5% and 15.2% were registered (p < 0.0001). A higher percentage of patients was brought in by ambulance to reorganized vs. unaltered cardiology departments (51.7% vs. 34.6%; p < 0.0001) alongside with a lower rate of self-referrals (45.7% vs. 58.4%; p < 0.0001). The rate of all-cause in-hospital mortality in AHF patients was higher in reorganized than unaltered cardiology departments (10.9% vs. 6.4%; p < 0.0001). After the exclusion of patients with concomitant COVID-19, the mortality rates did not differ significantly (6.9% vs. 6.4%; p = 0.55). CONCLUSIONS: A greater reduction in hospital admissions in 2020 vs. 2019, higher rates of patients brought by ambulance together with lower rates of self-referrals and higher all-cause in-hospital mortality for AHF due to COVID-19 related deaths were observed in cardiology departments reorganized to provide care for COVID-19 patients vs. unaltered ones.

Impact of COVID-19 pandemic on acute heart failure admissions and mortality: a multicentre study (COV-HF-SIRIO 6 study).

AIMS: The coronavirus disease-2019 (COVID-19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID-19 pandemic on hospital admissions and in-hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study. METHODS AND RESULTS: From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P < 0.001). We noted a significant reduction of self-referrals in the times of COVID-19 pandemic accounting 27.8% (P < 0.001), with increased number of AHF patients brought by an ambulance by 15.9% (P < 0.001). The length of hospital stay was overall similar (7.7 ± 2.8 vs. 8.2 ± 3.7 days; P = not significant). The in-hospital all-cause mortality in AHF patients was 444 (5.2%) in 2019 vs. 406 (6.5%) in 2020 (P < 0.001). A total number of AHF patients with concomitant COVID-19 was 239 (3.2% of AHF patients hospitalized in 2020). The rate of in-hospital deaths in AHF patients with COVID-19 was extremely high accounting 31.4%, reaching up to 44.1% in the peak of the pandemic in November 2020. CONCLUSIONS: Our study indicates that the COVID-19 pandemic led to (i) reduced hospital admissions for AHF; (ii) decreased number of self-referred AHF patients and increased number of AHF patients brought by an ambulance; and (iii) increased in-hospital mortality for AHF with very high mortality rate for concomitant AHF and COVID-19.

Loose Fibrin Clot Structure and Increased Susceptibility to Lysis Characterize Patients with Central Acute Pulmonary Embolism: The Impact of Isolated Embolism.

BACKGROUND: Prothrombotic fibrin clot properties are associated with higher early mortality risk in acute pulmonary embolism (PE) patients. It is unknown whether different types of PE are associated with particular clot characteristics. METHODS: We assessed 126 normotensive, noncancer acute PE patients (median age: 59 [48-70] years; 52.4% males), who were categorized into central versus peripheral PE with or without concomitant deep vein thrombosis (DVT). Plasma fibrin clot permeability (K s), clot lysis time (CLT), thrombin generation, platelet-derived markers, and fibrinolytic parameters were measured on admission. Plasma fibrin clot morphology was assessed by scanning electron microscopy (SEM). RESULTS: Patients with central PE (n = 76; 60.3%) compared with peripheral PE (n = 50; 39.7%) had 17.8% higher K s and 14.3% shortened CLT (both p < 0.01 after adjustment for potential confounders including fibrinogen), with no differences between segmental and subsegmental PE. SEM analysis demonstrated larger fibrin fiber diameter and pore size in central PE compared with peripheral PE (both p < 0.01). For isolated PE, there was 23.3% higher K s in central PE than in peripheral PE (n = 24; 19%) with no differences in other variables. Central PE combined with DVT (n = 45; 35.7%), as compared with central isolated PE (n = 31; 24.6%), was associated with shortened CLT (all p < 0.05). CONCLUSION: Our findings suggest that looser fibrin networks composed of thicker fibers with increased susceptibility to lysis characterize patients with central PE, suggesting that fibrin clot phenotype affects the size of thrombi occluding the pulmonary arteries, highlighting the role of fibrin structures in thrombus formation and stability.

Polish Multicenter Registry (Pol-LAS-SE registry). Stress echocardiography in low-gradient aortic stenosis in Poland: numbers, settings, results, complications and clinical practice.

BACKGROUND: The diagnostic workup of low-gradient aortic stenosis (LG AS) is a challenge in clinical practice. AIMS: Our goal was to assess the diagnostic value of stress echocardiography (SE) performed in patients with undefined LG AS with low and preserved ejection fraction (EF) and the impact of its result on therapeutic decisions in Polish third level of reference. METHODS: All the patients with LG AS and with SE performed were recruited in 16 Polish cardiology departments between 2016 and 2019. The main exclusion criteria were as follows: moderate or severe aortic or mitral regurgitation and mitral stenosis. RESULTS: The study group included 163 patients (52% males) with LG AS who underwent SE for adequate diagnostic and therapeutic decision. In 14 patients DSE was non-diagnostic. The mean aortic valve (AV) pressure gradient was 24.1 (7.3) mm Hg, while an AV area was 0.86 (0.2) cm2. Among 149 patients with conclusive DSE, severe AS was found in 59.8%, pseudo-severe in 22%, and moderate AS in 18%. There were no cases of death or vascular events related to DSE. Among 142 patients 63 (44%) patients had an aortic valve intervention in a follow-up (median: 208 days; lower-upper quartile: 73-531 days). Based on the result of the DSE test, severe AS was significantly more often associated with qualification to interventional treatment compared to the moderate and pseudo-severe subgroups (P <0.0001). CONCLUSIONS: The DSE test in severe AS is a valuable diagnostic tool in patients with LG AS in Poland.

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

Comparison of temperature measurements in esophagus and urinary bladder in comatose patients after cardiac arrest undergoing mild therapeutic hypothermia.

BACKGROUND: Mild therapeutic hypothermia (MTH) is a recommended method of treatment for comatose out-of-hospital cardiac arrest (OHCA) survivors. However, the proper site of temperature measurement in MTH is still not defined. The aim of this study was to compare temperature measurements in the esophagus and urinary bladder in comatose post-OHCA patients treated with MTH. METHODS: This temperature comparison protocol was a part of a prospective, observational, multicenter cohort study. The study population included 36 unconscious patients after resuscitation for OHCA. The patient's core temperature was independently measured every hour during MTH in the urinary bladder and in the esophagus. RESULTS: The mean temperature was lower in the esophagus (differences during induction phase: 1.04 ± 0.92°C, p < 0.0001; stabilization phase: 0.54 ± 0.39°C, p < 0.0001; rewarming phase: 0.40 ± 0.47°C, p < 0.0001). Nevertheless, a strong correlation between both sites was found (R2 = 0.83, p < 0.001). The decrease in temperature observed in the esophagus during the induction phase was faster when compared with the urinary bladder (1.09 ± 0.71°C/h vs. 0.83 ± 0.41°C/h; p = 0.002). As a consequence, time to reach temperature < 34.0°C was longer when temperature was measured in the urinary bladder (the difference between medians of the time 1.0 [0-1.5] h, p < 0.001). CONCLUSIONS: Urinary bladder temperature measurements may lag behind temperature changes measured in the esophagus. Monitoring temperature simultaneously in the esophagus and in the urinary bladder is an accessible and reliable combination, although esophageal measurements seem to better reflect the dynamics of temperature changes, thus it seems to be more appropriate for MTH control. ClinicalTrials.gov Identifier: NCT02611934.

Prothrombotic fibrin clot properties associated with NETs formation characterize acute pulmonary embolism patients with higher mortality risk.

Venous thromboembolism is associated with formation of denser fibrin clots resistant to lysis. We investigated whether prothrombotic plasma clot properties are associated with the severity of acute pulmonary embolism (PE). We enrolled 126 normotensive acute PE patients (aged 58 ± 14 years) and 25 age- and sex-matched healthy controls. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1), and citrullinated histone H3 (citH3) were evaluated on admission. PE patients compared to controls had 370% higher citH3 levels, 41% higher ETP, 16.5% reduced Ks, and 25.6% prolonged CLT. Patients with intermediate-high (n = 29) and intermediate-low (n = 77) PE mortality risk had reduced Ks and prolonged CLT, increased PAI-1 and ETP as compared to low-risk PE (n = 20) patients. Prolonged CLT was predicted by PAI-1 and citH3, while low Ks by C-reactive protein. During a 12-month follow-up 9 (7.1%) patients who had 24% higher ETP, 45% higher citH3 levels, and 18% prolonged CLT at baseline died. High ETP combined with elevated citH3 levels and prolonged CLT was associated with eightfold increased risk of PE-related death. Prothrombotic fibrin clot properties and enhanced neutrophil extracellular traps formation are associated with higher early mortality risk in acute PE patients, which suggests a prognostic role of these biomarkers.

Polish regional differences in patient knowledge on atrial fibrillation and its management as well as in patterns of oral anticoagulant prescription.

BACKGROUND The Jessa Atrial Fibrillation Knowledge Questionnaire (JAKQ) was successfully used to assess knowledge gaps in patients with atrial fibrillation (AF). AIMS To evaluate the regional differences among Polish patients in their awareness of AF diagnosis and oral anticoagulation use. METHODS A total of 1583 patients with AF at a median (IQR) age of 72 (66-79) years completed the JAKQ in 3 cardiology centers (center I, Kraków; center II, Torun; center III, Kielce) from January 2017 to June 2018. The final analysis included 1525 patients, 32.9% were on vitamin K antagonists (VKAs) and 67.1% on non-VKA oral anticoagulants (NOACs), that is, rivaroxaban and dabigatran (28.9% each), and apixaban (9.3%). RESULTS The mean (SD) score on the JAKQ was 55.5% (18.4%) with better results among patients on VKAs compared with NOACs (58% [18.3%] vs 54.3% [18.4%]; P = 0.0002) with time from AF diagnosis more than 12 months (57.4% [17.5%] vs 50% [19.9%]; P <0.0001). There was a significant difference in the knowledge scores between the 3 centers (I, 59.5%; II, 48.5%; III, 54.3%; P <0.0001). In all centers the number of correct answers correlated inversely with patient's age (r = -0.20; P <0.0001). NOACs were more frequently used in center III. The percentage of correct responses was lower in patients on reduced NOAC doses (35.4% of patients on NOACs), compared with the full-dose NOAC groups in center I (56.9% vs 62.5%; P = 0.012) and II (48.1% vs 56.2%; P = 0.003). CONCLUSIONS Patients from a high-volume academic center showed better knowledge than their peers from district hospitals. There are large regional differences in prescription patterns of oral anticoagulants, including the preferred NOAC.

[Aortic dissection type B with aortic arch involvement surgically treated--a case report]. / Rozwarstwienie aorty typu B z objeciem luku leczone operacyjnie.

A case of a 56-year-old male with acute aortic dissection type B is presented. The patient underwent successful surgery which was very difficult due to the extent of aortic dissection.