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Atrial cardiomyopathy contributes to thrombogenesis. Unlike in the healthy atrium (left side), in the cardiomyopathic atrium (right side), pathological structural and functional changes (e.g., contractile dysfunction, atrial dilation, fibrosis, and fat infiltration) lead to aberrant blood flow and stasis in the atria cavity, endothelial dysfunction (and structural changes), and Atrial cardiomyopathy contributes to thrombogenesis. Unlike in the healthy atrium (left side), in the cardiomyopathic atrium (right side), pathological structural and functional changes (e.g., contractile dysfunction, atrial dilation, fibrosis, and fat infiltration) lead to aberrant blood flow and stasis in the atria cavity, endothelial dysfunction (and structural changes), and hypercoagulability, predisposing patients to thrombogenic events within the atrial cavity. Furthermore, hypoxic conditions, together with vascular leakage, may contribute to the activation of the coagulation cascade within the myocardial tissue. Abbreviations: NO = nitic oxide; vWF = von Willebrand factor; TF = tissue factor.
Source publication
Heart disease, as well as systemic metabolic alterations, can leave a ‘fingerprint’ of structural and functional changes in the atrial myocardium, leading to the onset of atrial cardiomyopathy. As demonstrated in various animal models, some of these changes, such as fibrosis, cardiomyocyte hypertrophy and fatty infiltration, can increase vulnerabil...
Citations
... Feline hypertrophic cardiomyopathy (HCM) usually presents with left ventricular stiffness, abnormal movement of the anterior mitral leaflet during systoles, diastolic relaxation disorder, enlargement of the left atrium (LA), and spontaneous echocardiographic contrast [1,2]. Cardiomyopathy associated with arterial thromboembolism is a significant cause of thrombogenesis, which can partially or entirely block blood vessels [3]. The thrombus usually restricts blood flow to the lower extremities, provoking and causing tissue ischemia and paresis. ...
Background and Aim: Cardiogenic embolism (CE) is a common complication of feline hypertrophic cardiomyopathy
(HCM), leading to severe clinical symptoms. This study compared the effects of rivaroxaban and enoxaparin combined with
clopidogrel on cats.
Materials and Methods: This was a single-center, prospective, randomized controlled trial. In this study, rivaroxaban
or enoxaparin plus clopidogrel was prescribed to 23 cats for at least one of the following events: Abnormal movement
of the anterior mitral leaflet during systole, enlargement of the left atrium, spontaneous echocardiographic contrast, or
presence of arterial thromboembolism. Oral rivaroxaban (2.5 mg, q24 h) was prescribed to six cats. Subcutaneous injections
of enoxaparin (1 mg/kg, q24 h) plus oral clopidogrel (3 mg/kg, PO q24 h) for 60 days were administered to 17 cats.
Renal insufficiency and bleeding complications were observed. Plasma concentrations of D-dimer, prothrombin time (PT),
partial thromboplastin time, and international normalized ratio (INR) were evaluated. We analyzed the relationship between
echocardiography parameters and the effects of coagulation. Blood samples were collected from all cats at baseline and at
1 and 2 months post-treatment.
Results: Rivaroxaban alone and in combination with enoxaparin and clopidogrel significantly affected PT and INR. In cats
treated with 2.5 mg/kg rivaroxaban for 60 days, no bleeding or recurrence of thrombus formation was observed. These data
support the use of rivaroxaban for the treatment of HCM-associated thromboembolism in cats.
Conclusion: Treatment of HCM-associated thromboembolism with rivaroxaban alone demonstrated clinical effectiveness
with no clinical complications in cats.
... It is recognized that atrial fibrillation and atrial cardiomyopathy are associated with a risk of atrial thrombogenesis and cardiogenic embolization [56,57]. Ineffective atrial contraction and low flow conditions promote thrombus formation, most commonly in the left atrial appendage, thereby increasing the risk of stroke and peripheral embolization [58] ( Figure 1). ...
... Previous studies have revealed substantial prothrombogenic changes in atrial fibrillation disease with the expression of von Willebrand factor and adhesion molecules in the atrial endocardium [59]. Moreover, cardiovascular risk factors may further increase the expression of pro-thrombogenic and pro-inflammatory factors [57,[60][61][62][63]. New data are emerging on the relationship between cardiovascular risk factors, inflammation, thrombogenesis, and atrial fibrillation [57,[60][61][62][63]. Watanabe et al. have shown that C-reactive protein (CRP) levels and atrial diameter size were higher in atrial fibrillation than in sinus rhythm, which decreased after successful cardioversion [64,65]. ...
... Previous studies have revealed substantial prothrombogenic changes in atrial fibrillation disease with the expression of von Willebrand factor and adhesion molecules in the atrial endocardium [59]. Moreover, cardiovascular risk factors may further increase the expression of pro-thrombogenic and pro-inflammatory factors [57,[60][61][62][63]. New data are emerging on the relationship between cardiovascular risk factors, inflammation, thrombogenesis, and atrial fibrillation [57,[60][61][62][63]. Watanabe et al. have shown that C-reactive protein (CRP) levels and atrial diameter size were higher in atrial fibrillation than in sinus rhythm, which decreased after successful cardioversion [64,65]. ...
This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease.
... [4] Ventricular cardiomyopathy can cause structural and functional changes in the atrial myocardium, which in turn leads to the onset of atrial cardiomyopathy. [5] Some of these changes, such as fibrosis, cardiomyocyte hypertrophy and fatty infiltration, predisposes the patients to ischemic stroke as well as increases their vulnerability to AF. For patients with cardiomyopathies, left atrial appendage is probably not the only site where thrombosis occurred. ...
Hypertrophic cardiomyopathy (HCM) patients with atrial fibrillation (AF) are at high risk for stroke. Left atrial appendage closure (LAAC) is a promising alternative for stroke prevention in AF patients. We aimed to review the clinical outcomes of patients with AF and HCM at our center. We reviewed 673 patients who underwent LAAC implantation from 2014 to 2021 in a tertiary center, of whom 15 had HCM. AF Patients with HCM were compared with sex and age matched controls who also underwent LAAC. From 2014 to 2021, 673 AF patients received LAAC in a single center, of whom, 15 patients had HCM. LAAC devices were successfully implanted in 14 HCM patients and 59 patients in the control group. During the follow-up period (median 1151 days range: 132-2457 days), 2 HCM patient had ischemic strokes. There were another 2 HCM patients who had sudden cardiac death (SCD). Compared with the control, HCM patients had higher cumulative rate of combined death and stroke (26.67% vs 3.33%, P = .024). In our initial clinical experience, the cumulative stroke and death rate of the HCM patients was significantly higher than that of the non-HCM patients.
Background
Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase.
Methods
We performed a retrospective analysis on a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of 2 tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF).
Results
After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia, advanced atrioventricular block, heart failure, and cardiogenic shock. In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p<0.001), without differences in stroke incidence (10.1% vs. 9.3%).
Conclusions
As a conclusion, patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-year follow-up, they exhibit a high risk of AF recurrence and mortality, with no significant differences in stroke incidence.
Aims
Atrial fibrillation (AF), the most common cardiac arrhythmia favoring ischemic stroke and heart failure involves left atrial remodeling, fibrosis and a complex interplay between cardiovascular risk factors. This study examined whether activated factor X (FXa) induces pro-remodeling and pro-fibrotic responses in atrial endothelial cells (AECs) and human atrial tissues and determined the underlying mechanisms.
Methods and Results
AECs were from porcine hearts and human right atrial appendages (RAA) from patients undergoing heart surgery. Protein expression levels were assessed by Western blot and immunofluorescence staining, mRNA levels by RT-qPCR, formation of reactive oxygen species (ROS) and NO using fluorescent probes, thrombin and angiotensin II generation by specific assays, fibrosis by Sirius red staining and senescence by senescence-associated beta-galactosidase (SA-β-gal) activity.
In AECs, FXa increased ROS formation, senescence (SA-β-gal activity, p53, p21), angiotensin II generation and the expression of pro-inflammatory (VCAM-1, MCP-1), pro-thrombotic (tissue factor), pro-fibrotic (TGF-β and collagen-1/3a) and pro-remodeling (MMP-2/9) markers whereas eNOS levels and NO formation were reduced. These effects were prevented by inhibitors of FXa but not thrombin, protease-activated receptors antagonists (PAR-1/2) and inhibitors of NADPH oxidases, ACE, AT1R, SGLT1/SGLT2. FXa also increased expression levels of ACE1, AT1R, SGLT1/2 proteins which was prevented by SGLT1/2 inhibitors. Human RAA showed tissue factor mRNA levels that correlated with markers of endothelial activation, pro-remodeling and pro-fibrotic responses and SGLT1/2 mRNA levels. They also showed protein expression levels of ACE1, AT1R, p22phox, SGLT1/2, and immunofluorescence signals of nitrotyrosine and SGLT1/2 colocalized with those of CD31. FXa increased oxidative stress levels which were prevented by inhibitors of the AT1R/NADPH oxidases/SGLT1/2 pathway.
Conclusions
FXa promotes oxidative stress triggering premature endothelial senescence and dysfunction associated with pro-thrombotic, pro-remodeling and pro-fibrotic responses in AECs and in human RAA involving the AT1R/NADPH oxidases/SGLT1/2 pro-oxidant pathway. Targeting this pathway may be of interest to prevent atrial remodeling and the progression of atrial fibrillation substrate.
