Clot lysis time and thrombin generation in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Aortic valve stenosis (AS) is the most prevalent valvular heart disease and is associated with a significant increase in mortality. AS has been shown to be linked with numerous coagulation system abnormalities, including increased fibrin deposition on the stenotic aortic valves. Transcatheter aortic valve implantation (TAVI) is the primary treatment method for patients at high surgical risk. OBJECTIVES: The aim of the study was to assess the impact of treating severe AS with TAVI on thrombin generation and clot lysis time (CLT). METHODS: We studied 135 symptomatic AS patients recommended for TAVI by the local Heart Team. All measurements were performed before and 5-7 days after TAVI. Alongside clinical assessment and echocardiographic analysis, we assessed clot lysis time (CLT) and thrombin generation parameters, including lag time, peak thrombin generation, time to peak thrombin generation (ttPeak), and endogenous thrombin potential (ETP). RESULTS: 70 patients were included in the final analysis. After TAVI, there was a significant 9% reduction in CLT despite a 12% increase in fibrinogen concentration. We observed significant increase in lag time and ttPeak (20% and 12%, respectively), and 13% decrease in peak thrombin concentration compared to pre-procedural levels. Multivariable linear regression analysis demonstrated that baseline CLT and C-reactive protein (CRP) levels were independent predictors of significant reduction in mean aortic gradient, defined as TAVI procedure success. CONCLUSIONS: CLT and peak thrombin concentration decreased, while Lag time and ttPeak increased significantly after TAVI. Multivariable linear regression analysis demonstrated CLT and CRP levels as independent predictors of achieving a reduction in mean aortic gradient, defining TAVI procedure success.

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.

Blood clot properties, thrombin generation, and platelet activation in patients with dysglycemia and established atherosclerotic cardiovascular disease: The CASCARA study.

BACKGROUND: There is a strong link between coronary artery disease (CAD), type 2 diabetes (T2D) on one hand, and altered fibrin clot properties, including increased clot density, and unfavorable fibrin clot structure on the other. T2D-related changes in fibrin clots can increase cardiovascular (CV) disease risk, including future CV events. We aimed to assess fibrin clot properties, thrombin generation, and platelet activation in CAD patients with prediabetes (PD) or T2D, compared to CAD patients without glycemic disorders. METHODS: We allocated patients to three groups: 1) Those with angiographically established CAD but without glycemic abnormalities (CAD group); 2) individuals with PD and established CAD (CAD+PD group); and 3) patients with T2D and CAD (CAD+T2D group). We conducted comparisons across these groups for thrombin generation, fibrin clot permeability, fibrin clot lysis, and platelet activation. RESULTS: The final analysis included 116 eligible patients: 1) CAD group (n = 31); 2) CAD+PD (n = 42); and 3) CAD+T2D (n = 43). The CAD+T2D patients enrolled had well-controlled T2D (median HbA1c level of 5.90%; IQR: 5.7%-6.3%). We found no significant differences in thrombin generation, fibrin clot properties, or platelet activation markers across the three analyzed groups (all P-values >0.20). However, elevated interleukin-6 (IL-6) levels were noted in both the highest and lowest glucose concentration quartiles. Additionally, a substantial increase in endogenous thrombin potential (ETP) was observed in patients in the highest glycated hemoglobin quintile. CONCLUSIONS: Individuals with established CAD and concomitant PD or well-controlled T2D exhibited comparable fibrin clot phenotypes, thrombin generation potential, and platelet activation when compared to CAD patients without dysglycemia.

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: Intricate management of heart failure (HF), especially in the context of reduced ejection fraction, is further complicated by an elevated risk of thromboembolic events. Studies published so far offer inconclusive insight into the interplay between mitral regurgitation (MR) and the coagulation system. OBJECTIVES: This study aimed to investigate the impact of transcatheter edge­to­edge repair (TEER) on specific coagulation parameters in HF patients. PATIENTS AND METHODS: A cohort of 31 HF patients with severe MR treated with TEER underwent a systematic evaluation at 3 visits (V1, V2, and V3). Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability, and clot lysis time (CLT) were assessed (n = 27 at V2; n = 25 at V3). RESULTS: TEER induced changes in fibrinogen levels (P = 0.01; V3 vs V2) and improved fibrin clot properties over 50­day follow­up (P = 0.01; V3 vs V2). No significant differences were observed between time points in the analyzed blood clot parameters. Correlation analysis showed that baseline CLT was associated with ΔN­terminal pro-B­type natriuretic peptide (NT­proBNP) level (P = 0.049; r = 0.4). Multivariable analysis identified baseline CLT as an independent predictor of early post­TEER NT­proBNP change (R2 = 0.55; P = 0.02). CONCLUSIONS: We found decreased level of fibrinogen and increased permeation coefficient over a median 50 (interquartile range, 32.5-75.5)-day post­TEER follow­up, as compared with early postprocedural assessments. Other blood coagulation parameters remained unchanged from baseline at both follow­up time points after TEER. Finally, CLT was an independent predictor of early NT­proBNP increase, emphasizing its role as an indicator of hemodynamic response to TEER.

Coagulation Disorders and Thrombotic Complications in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with multiple cardiovascular and noncardiovascular comorbidities and risk factors which increase the risk of thrombotic complications, such as atrial fibrillation, chronic kidney disease, arterial hypertension and type 2 diabetes mellitus. Subsequently, thromboembolic risk stratification in this population poses a great challenge. Since date from the large randomized clinical trials mostly include both patients with truly preserved EF, and those with heart failure with mildly reduced ejection fraction, there is an unmet need to characterize the patients with truly preserved EF. Considering the significant evidence gap in this area, we sought to describe the coagulation disorders and thrombotic complications in patients with HFpEF and discuss the specific thromboembolic risk factors in patients with HFpEF, with the goal to tailor risk stratification to an individual patient.