Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: Mitral Fibrin Study.

INTRODUCTION: The intricate management of heart failure (HF), especially in the context of reduced ejection fraction, is compounded by an elevated risk of thromboembolic events. Existing studies offer inconclusive insights into the interplay between MR and the coagulation system. OBJECTIVES: This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on specific coagulation parameters in HF patients. PATIENTS AND METHODS: A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points (V1, V2, and V3). Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed (n = 27 [V2], and n = 25 [V3]). RESULTS: TEER induced changes in fibrinogen levels (P = 0.01, V3 vs. V2) and improved fibrin clot properties over a 50-day follow-up (Ks, P = 0.01, V3 vs. V2). No significant differences were observed among time points in analyzed blood clot parameters. Correlation analysis showed that baseline CLT was significantly associated with delta NT-proBNP, (P = 0.049; r = 0.40). Multivariable analysis demonstrated that baseline CLT was an independent predictor of the early post-TEER NT-proBNP change (R2 = 0.55, P = 0.02). CONCLUSIONS: We found that fibrinogen levels decreased, and permeation coefficient increased over a median 50-day post-TEER follow-up, compared to early post-procedure assessments. Other blood coagulation parameters remained unchanged from baseline to both follow-up periods after TEER. Finally, CLT was an independent predictor of early NT-proBNP increase, emphasizing its role as an indicator of the hemodynamic response to TEER.

Clinical characteristics and long-term outcomes of patients with heart failure with improved ejection fraction. First Polish experience from LECRA-HF registry.

PURPOSE: Heart failure (HF) with improved ejection fraction (HFimpEF) is a new category of HF introduced in the newest European Society of Cardiology guidelines. However, clinical characteristics and long-term outcomes of HFimpEF patients remain insufficiently elucidated. We sought to characterize Polish HFimpEF patients and determine their long-term mortality. MATERIAL AND METHODS: Of 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) registry between 2009 and 2019 and hospitalized due to HF decompensation, 340 (28.7%) were those with HF with reduced ejection fraction (HFrEF). Based on follow-up echocardiography, 61 (17.9%) of them were classified as HFimpEF and the remaining as HFnon-impEF. RESULTS: HFimpEF patients were more frequently females (P â€‹< â€‹0.001), had higher baseline left ventricular ejection fraction (LVEF, P â€‹< â€‹0.001), had less often a history of diabetes (P â€‹= â€‹0.024), severe chronic kidney disease (P â€‹= â€‹0.026) or prior myocardial infarction (P â€‹= â€‹0.008) than HFnon-impEF patients. By multivariable analysis the HFimpEF diagnosis was independently predicted by baseline NYHA I/II (odds ratio [OR] 2.347, 95% confidence interval [95%CI] 1.020-5.405), non-ischemic etiology (OR 3.096, 95%CI 1.587-6.024), lack of diabetes mellitus (OR 2.016, 95%CI 1.059-3.846) and higher baseline LVEF (OR 1.084, 95%CI 1.042-1.126, per 1%). Within the median 49 (25-77) months all-cause mortality was lower in HFimpEF than in HFnon-impEF (10.8 vs 16.4%/year, P â€‹= â€‹0.004). CONCLUSIONS: Our findings indicate that every sixth Polish patient with HFrEF has a chance to improve LVEF during follow-up and to become a HFimpEF patient. Baseline characteristics of HFimpEF patients are different from HFnon-impEF. Simultaneously, the HFimpEF diagnosis is associated with higher long-term survival.

Endothelial Cell Apoptosis but Not Necrosis Is Inhibited by Ischemic Preconditioning.

This study aimed to assess the influence of ischemic preconditioning (IP) on hypoxia/reoxygenation (HR)-induced endothelial cell (EC) death. Human umbilical vein endothelial cells (HUVECs) were subjected to 2 or 6 h hypoxia with subsequent reoxygenation. IP was induced by 20 min of hypoxia followed by 20 min of reoxygenation. Necrosis was assessed by the release of lactate dehydrogenase (LDH) and apoptosis by double staining with propidium iodide/annexin V (PI/AV), using TUNEL test, and Bcl-2 and Bax gene expression measured using RT-PCR. In PI/AV staining, after 24 h of reoxygenation, 30-33% of EC were necrotic and 16-21% were apoptotic. In comparison to HR cells, IP reduced membrane apoptosis after 24 h of reoxygenation by 50% but did not influence EC necrosis. Nuclear EC apoptosis affected about 15-17% of EC after 24 h of reoxygenation and was reduced with IP by 55-60%. IP was associated with a significantly higher Bcl-2/Bax ratio, at 8 h 2-4 times and at 24 h 2-3 times as compared to HR. Longer hypoxia was associated with lower values of Bcl-2/Bax ratio in EC subjected to HR or IP. IP delays, without reducing, the extent of HR-induced EC necrosis but significantly inhibits their multi-level evaluated apoptosis.

Coronary Slow-Flow Phenomenon in Takotsubo Syndrome: The Prevalence, Clinical Determinants, and Long-Term Prognostic Impact.

Patients with takotsubo syndrome (TTS) may present coronary slow flow (CSF) in angiography performed in the acute myocardial infarction (MI). However, the detailed clinical relevance and its long-term impact remain poorly understood. Among 7771 MI patients hospitalized between 2012 and 2019, TTS was identified in 82 (1.1%) subjects. The epicardial blood flow was assessed with thrombolysis in myocardial infarction (TIMI) scale and corrected TIMI frame count (TFC), whereas myocardial perfusion with TIMI myocardial perfusion grade (TMPG). CSF was defined as TIMI-2 or corrected TFC > 27 frames in at least one epicardial vessel. CSF was identified in 33 (40.2%) TTS patients. In the CSF-TTS versus normal-flow-TTS group, lower values of left ventricular ejection fraction on admission (33.5 (25-40) vs. 40 (35-45)%, p = 0.019), more frequent midventricular TTS (27.3 vs. 8.2%, p = 0.020) and the coexistence of both physical and emotional triggers (9.1 vs. 0%, p = 0.032) were noted. Within a median observation of 55 months, higher all-cause mortality was found in CSF-TTS compared with normal-flow TTS (30.3 vs. 10.2%, p = 0.024). CSF was identified as an independent predictor of long-term mortality (hazard ratio 10.09, 95% confidence interval 2.12-48.00, p = 0.004). CSF identified in two-fifths of TTS patients was associated with unfavorable long-term outcomes.

Reduced fibrin clot permeability on admission and elevated E-selectin at 3 months as novel risk factors of residual pulmonary vascular obstruction in patients with acute pulmonary embolism.

BACKGROUND: Residual pulmonary vascular obstruction (RPVO) is common following pulmonary embolism (PE) but its association with fibrin clot properties is poorly understood. We investigated whether prothrombotic state and hypofibrinolysis markers can identify patients with RPVO. METHODS: In 79 normotensive noncancer patients (aged 56 ± 13.3 years) with acute PE, we determined fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), fibrinolysis proteins, oxidative stress markers, and E-selectin on admission before initiation of anticoagulant therapy, after 5-7 days, and 3 months of anticoagulation. RPVO was diagnosed using computed tomography angiography 3-6 months since PE. RESULTS: Patients with RPVO (n = 23, 29.1%) had at baseline higher simplified Pulmonary Embolism Severity Index (sPESI) (P = 0.004), higher N-terminal brain natriuretic propeptide (P = 0.006) and higher D-dimer (P = 0.044). Patients with versus without RPVO had lower Ks (P < 0.001) and longer CLT (P < 0.05), both at baseline and 5-7 days since admission, but not at 3 months. Patients with RPVO showed 40.6% higher E-selectin (P < 0.001) solely at 3 months. By multivariable logistic regression, baseline Ks (odds ratio [OR] 0.010, 95% confidence interval [CI] 0.001-0.837, P = 0.042, per 10- 9 cm2), baseline D-dimer (OR 1.105, 95% CI 1.000-1.221, P = 0.049, per 100 ng/ml), and E-selectin levels after 3 months (OR 3.874, 95% CI 1.239-12.116, P = 0.020, per 1 ng/ml) were associated with RPVO. CONCLUSIONS: RPVO patients despite anticoagulation characterize with the formation of denser fibrin clots on admission and higher E-selectin at 3 months. Those parameters could be the potential novel RPVO risk factors that warrant further evaluation in an independent cohort.

Effect of Three-Day Atorvastatin Administration on Coagulation Factors in Patients With Prior Venous Thromboembolism and Healthy Subjects: A Preliminary Study.

ABSTRACT: Statins exert antithrombotic effects, which might contribute to reduced risk of venous thromboembolism (VTE). Rosuvastatin 20 mg/d administered for 4 weeks has been reported to decrease coagulation factors (F) VII, FVIII, and FXI in VTE patients. Moreover, in accordance with recent registry data in non-VTE subjects, statins usage was associated with lower FXI. We investigated whether 3 doses of a statin decrease coagulation factors activity and if such changes can alter fibrin clot properties in VTE patients and healthy subjects. We enrolled 28 consecutive first-ever prior VTE patients after 6 months of anticoagulation and 25 healthy controls well-matched for demographics and lipid profiles (aged 44 [interquartile range 34-51] years) in an interventional nonrandomized study. Before and after 3 doses of atorvastatin 40 mg/d, activity of FVII, FVIII, FIX, and FXI was measured, along with fibrin clot properties, including permeability (Ks) and clot lysis using 3 various assays. After a 3-day statin administration, we observed the decrease of FVII (by 6.2%, P = 0.046) and FXI (by 8.6%, P = 0.044), irrespective of low-density lipoprotein cholesterol reduction (by 24%, P < 0.001), whereas other coagulation factors remained unaltered. Reduction of FVII and FXI activity was inversely correlated with Ks alterations (R = -0.292, P = 0.034 and R = -0.335, P = 0.014, respectively). After adjustment for age, studied group, and fibrinogen level, the reduction of FXI was independently associated with an increase of fibrin clot permeability (B = -0.084, P = 0.027). In conclusion, a 3-day 40 mg atorvastatin administration is sufficient to reduce FVII and FXI activity in our pilot study, which is associated with favorable fibrin clot properties modification.

Effect of high-dose statin therapy on coagulation factors: Lowering of factor XI as a modifier of fibrin clot properties in coronary artery disease.

BACKGROUND: Multiple pleiotropic effects of statins include antithrombotic properties with formation of looser fibrin networks more susceptible to lysis. Recently, rosuvastatin 20 mg/d has been reported to decrease coagulation factors (F) VII, FVIII and FXI in venous thrombosis patients. OBJECTIVES: We investigated how high-dose statin therapy recommended in coronary artery disease (CAD) alters plasma levels of coagulation factors and if such changes might affect fibrin clot properties. METHODS: We studied 130 advanced CAD patients, who initially did not achieve the target low-density lipoprotein cholesterol (LDL-C). Before high-dose statin therapy (rosuvastatin 40 mg/d or atorvastatin 80 mg/d) and 6-12 months after its initiation, FII, FV, FVII, FVIII, FIX, FX, FXI and fibrinogen were assessed. We evaluated the impact of statin-induced alterations to the factors on plasma fibrin clot permeability (Ks) reflecting a fibrin pore size, and clot lysis time (CLT) reflecting fibrinolytic potential. RESULTS: At baseline LDL-C (median 3.2, interquartile range 2.7-3.7 mmol/L) was independently associated solely with FXI (ß = 0.58, P < 0.001). Median LDL-C reduction by 25% (P < 0.001) on high-dose statin treatment was accompanied by lowering of FVII, FVIII, and FXI (for all P < 0.001). On high-dose statin treatment, Ks (R = 0.65, P < 0.001) inversely associated with CRP (ß = -0.41, P < 0.001), LDL-C (ß = -0.26, P = 0.001), and FXI (ß = -0.18, P = 0.016). In turn, CLT (R = 0.45, P < 0.001) was positively associated with LDL-C (ß = 0.19, P = 0.043) and FXI (ß = 0.17, P = 0.049). CONCLUSIONS: High-dose statin therapy in CAD patients decreases FVII, FVIII, and FXI. The statin-induced reduction in FXI may contribute to less prothrombotic fibrin clot phenotype, indicating additional antithrombotic effect of high-dose statins.

Thin-cap fibroatheroma and increased coronary intima-media thickness are associated with an altered balance of arginine metabolites.

INTRODUCTION: Arginase inhibition increases plasma citrulline and citrulline / ornithine (C/O) ratio, and reduces plasma ornithine and ornithine / arginine (O/A) ratio in an animal model of myocardial infarction (MI). OBJECTIVES: We hypothesized that the presence of thin­cap fibroatheroma (TCFA) in the culprit lesion and increased non­culprit intima­media thickness of an infarct­related artery (IRA) are associated with an altered balance of arginine metabolites. PATIENTS AND METHODS: Arginine and its metabolites were measured using liquid chromatography and tandem mass spectrometry in 100 consecutive MI patients upon admission and at 6­month follow­up. TCFA and adjacent to culprit lesion proximal and distal 10­mm segments were assessed with optical coherence tomography in the acute phase. Twenty five patients without coronary lesions on angiography served as controls. RESULTS: The C/O ratio increased 5.33 times (P <0.001), while the O/A ratio decreased 2.53 times (P <0.001) at the 6­month follow­up, as compared with the acute phase of MI. The patients with (n = 75) vs without (n = 25) TCFA had lower C/O ratio by 29% (P = 0.003), while the mean intima­media diameter of adjacent non­culprit region correlated with the follow­up O/A ratio (R = 0.337; P = 0.003). In a multivariable analysis, a higher acute phase C/O ratio was associated with a lower risk of TCFA presence (odds ratio, 0.978; 95% CI, 0.962-0.994; P = 0.006), whereas a higher follow­up O/A ratio correlated with larger intima­media diameter of the adjacent segments (ß coefficient, 0.227; 95% CI for ß coefficient, 0.045-0.409; P = 0.018). CONCLUSIONS: Enhanced arginase activity over nitric oxide synthase following ischemia was associated with the presence of TCFA in the culprit lesion, while a similar metabolic shift in the chronic phase correlated with a greater thickness of the intima­media in the adjacent non­culprit IRA segments.

Screening diagnosis of dementia in patients following heart failure decompensation is associated with a higher relative wall thickness.

BACKGROUND: The usefulness of echocardiographic characteristics for dementia prediction in patients with heart failure decompensation (HFD) is not determined. Therefore, we sought to investigate the echocardiographic features of patients with HFD and screening diagnosis of dementia (SDD). METHODS: 139 patients aged over 65 years were hospitalized with the diagnosis of HFD. Clinical characteristics and echocardiographic characteristics were recorded during hospitalization. SDD was defined based on the result of ALFI- MMSE of <17 points. RESULTS: Patients with SDD were older (p=0.013), had thicker IVSd (p=0.021), thicker PWd (p=0.005) and had a higher RWT (0.40 vs 0.35, p=0.004) than patients without SDD, without differences in LVMI (p=0.13). There was no correlation between RWT and LVMI (r=-0.01, p=0.88). In the multivariate analysis, an older age (ß=-0.116, 95% CI -0.224 - -0.008, p=0.035, per year) and a higher RWT (ß=-0.069, 95% CI -0.137 - -0.002, p=0.045, per 0.01) influenced a lower ALFI-MMSE. For a prediction of SDD, the RWT reached the area under a ROC curve of 0.67 (95% CI 0.56-0.77, p=0.004 with sensitivity of 60% and specificity of 70% for RWT of ≥0.375). CONCLUSIONS: Apart from age, RWT reflecting left ventricular geometry changes but not hypertrophy was independently but moderately associated with SDD in patients following HFD (Tab. 4, Fig. 1, Ref. 35).

Cardiometabolic predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots in patients at high cardiovascular risk: an 8-year prospective cohort study.

INTRODUCTION: Adiposity has a few phenotypes associated with various levels of risk for diabetes mellitus (DM), but their exact predictive value is not well understood. OBJECTIVES: We aimed to assess the predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots for long­term cardiometabolic risk. PATIENTS AND METHODS: A total of 150 patients with chronic coronary syndrome (CCS) scheduled for elective coronary angiography were enrolled and a comprehensive clinical and ultrasound assessment of adiposity was performed (2012-2013). Of them, 143 individuals were followed for 8 years for insulin resistance (IR) and / or DM development. RESULTS: At baseline, DM and prediabetes were found in 22% and 8% of the patients, respectively. It was established that 11.7% of the participants died during the follow­up. The rate of DM increased to 46% with a decrease in the prediabetes rate (3.5%). Significant correlations with the Homeostatic Model Assessment of Insulin Resistance and glycated hemoglobin were observed for major anthropometric and ultrasound variables. In the multivariable analysis, independent predictors of IR were preperitoneal fat thickness (PreFT) (per 10mm increase: odds ratio [OR], 1.63; 95% CI, 1.22-2.33; P = 0.003) and body surface area (per 0.1m2 increase: OR, 1.59; 95% CI, 1.11-2.39; P = 0.02). DM was independently predicted by the high­density lipoprotein cholesterol concentration (OR, 0.93; 95% CI, 0.87-0.97; P = 0.005) and body fat mass (OR, 1.09; 95% CI, 1.03-1.17; P = 0.003). CONCLUSIONS: A complex assessment of the adipose tissue in patients with CCS is a valuable method for improving metabolic risk stratification. Some anthropometric and ultrasound parameters, such as PreFT or body surface area, were associated with IR and DM development.

Statin Use in Cancer Patients with Acute Myocardial Infarction and Its Impact on Long-Term Mortality.

Statin use and its impact on long-term clinical outcomes in active cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated. Of the 1011 consecutive acute MI patients treated invasively between 2012 and 2017, cancer was identified in 134 (13.3%) subjects. All patients were observed within a median follow-up of 69.2 (37.8−79.9) months. On discharge, statins were prescribed less frequently in MI patients with cancer as compared to the non-cancer MI population (79.9% vs. 91.4%, p < 0.001). The most common statin in both groups was atorvastatin. The long-term mortality was higher in MI patients not treated vs. those treated with statins, both in non-cancer (29.5%/year vs. 6.7%/year, p < 0.001) and cancer groups (53.9%/year vs. 24.9%/year, p < 0.05), respectively. Patient's age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.03−1.05, p < 0.001, per year), an active cancer (HR 2.42, 95% CI 1.89−3.11, p < 0.001), hemoglobin level (HR 1.14, 95% CI 1.09−1.20, p < 0.001, per 1 g/dL decrease), and no statin on discharge (HR 2.13, 95% CI 1.61−2.78, p < 0.001) independently increased long-term mortality. In MI patients, simultaneous diagnosis of an active cancer was associated with less frequently prescribed statins on discharge. Irrespective of cancer diagnosis, no statin use was found as an independent predictor of increased long-term mortality.

Clinical Characteristics and Long-Term Outcomes of MINOCA Accompanied by Active Cancer: A Retrospective Insight Into a Cardio-Oncology Center Registry.

Background: Clinical characteristics and long-term outcomes of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and cancer are insufficiently elucidated. Objectives: We sought to characterize these patients hospitalized in a tertiary cardio-oncology center and to find the potential determinants affecting their long-term mortality. Methods: MINOCA was diagnosed in 72 of the 1,011 patients with consecutive myocardial infarction who underwent coronary angiography. Mortality rates and their determinants were analyzed within a median follow-up of 69.2 (37.8-79.9) months. Results: Active cancer was identified in 21 (29.2%) of patients with MINOCA and in 113 (12.0%) patients with myocardial infarction and obstructive coronary artery disease (MI-CAD) (p < 0.001). MINOCA patients with cancer were characterized by a higher incidence of anemia (47.6 vs. 21.6%, p = 0.03) and more frequently Takotsubo syndrome (19.1 vs. 2.0%, p = 0.01) than in non-cancer MINOCA. The troponin T/hemoglobin ratio was higher in both cancer MINOCA and MI-CAD groups when compared with their respective non-cancer patients (both p < 0.05). The age and sex-standardized mortality rates were significantly higher in cancer MINOCA (26.7%/year) when compared with non-cancer MINOCA (2.3%/year, p = 0.002) and in cancer MI-CAD (25.0%/year) vs. non-cancer MI-CAD (3.7%/year, p < 0.001). Active cancer (HR 3.12, 95% CI 2.41-4.04) was independently associated with higher long-term mortality, while higher hemoglobin levels (HR 0.93, 95% CI 0.88-0.99, per g/dl) and a MINOCA diagnosis (HR 0.69, 95% CI 0.47-0.97) improved long-term survival. Conclusion: Patients with MINOCA were comorbid with cancer more frequently than MI-CAD. In turn, an active malignancy was associated with an unfavorable long-term survival both in MI-CAD population and in patients with MINOCA.