Hemodynamic and hemorheologic determinants of left atrial spontaneous echo contrast and thrombus formation in patients with idiopathic dilated cardiomyopathy

doi:10.1016/0002-8703(93)90022-2

American Heart Journal

Volume 125, Issue 2, Part 1, February 1993, Pages 430-434

https://doi.org/10.1016/0002-8703(93)90022-2 Get rights and content

Abstract

The purpose of the present study was to evaluate the specific role of hemorheologic and hemodynamic parameters for spontaneous echo contrast and thrombus formation in vivo. We therefore investigated the association between the presence of left atrial spontaneous echo contrast and thrombus formation by transesophageal echocardiography and multiple clinical, hemodynamic, and hemorheologic parameters in 70 patients with idiopathic dilated cardiomyopathy. Transesophageal echocardiography showed left atrial spontaneous echo contrast and left atrial thrombi in 33% and 19% of patients, respectively. Patients with left atrial spontaneous echo contrast had a lower cardiac index (2.1 ± 0.9 versus 2.6 ± 0.9 L/min/m²; p < 0.02), a lower left atrial (21 ± 8 versus 38 ± 10 cm/sec; p < 0.001) and left atrial appendage flow velocity (17 ± 14 versus 39 ± 13 cm/sec; p < 0.001), a larger left atrial diameter (53 ± 6 versus 46 ± 10 mm; p < 0.002), and more often presented with atrial fibrillation (62% versus 32%; p < 0.02). Plasma fibrinogen concentration (4.0 ± 1.1 versus 3.5 ± 0.7 gm/L; p < 0.02) and plasma viscosity (1.83 ± 0.10 versus 1.76 ± 0.15 mPa · sec; p < 0.05) were higher in patients with spontaneous echo contrast. Multivariate analysis revealed an association between the presence of spontaneous echo contrast and left atrial flow velocity (p < 0.0001) and plasma viscosity (p < 0.01). In patients with left atrial (appendage) thrombus or a history of embolism, left atrial appendage flow velocity was lower (15.0 ± 8.2 versus 29.6 ± 14.5 cm/sec; p < 0.005) and spontaneous echo contrast was more frequently observed (52% versus 23%; p < 0.05). Hemorheologic parameters were not significantly different between patients with and without left atrial thrombus. In conclusion, left atrial thrombi and spontaneous echo contrast represent frequent findings in idiopathic dilated cardiomyopathy. They are both primarily related to a low left atrial blood flow velocity. Hemorheologic factors may contribute to spontaneous echo contrast formation in vivo, but are unlikely to play a significant role for thrombus formation.

References (25)

WC Roberts et al.
Idiopathic dilated cardiomyopathy: analysis of 152 necropsy patients
Am J Cardiol
(1987)
V Fuster et al.
The natural history of idiopathic dilated cardiomyopathy
Am J Cardiol
(1981)
IW Black et al.
Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis
J Am Coll Cardiol
(1991)
WG Daniel et al.
Left atrial spontaneous echo contrast in mitral valve disease: an indicator for an increased thromboenbolic risk
J Am Coll Cardiol
(1988)
R Castello et al.
Prevalence and clinical implications of atrial spontaneous contrast in patients undergoing transesophageal echocardiography
Am J Cardiol
(1990)
P Siostrzonek et al.
Abnormal blood rheology in idiopathic dilated cardiomyopathy
Am J Cardiol
(1992)
J Harkness
A new instrument for the measurement of plasma viscosity
Lancet
(1963)
GB Thurston
Viscoelasticity of human blood
Biophys J
(1972)
HJ Klose
A rheological method for quantification of platelet aggregation in vitro and its kinetics under defined flow conditions
Thromb Res
(1975)
S Iliceto et al.
Dynamic intracevitary left atrial echoes in mitral stenosis
Am J Cardiol
(1985)

MA Garcia-Fernandez et al.

Two-dimensional echocardiographic identification of blood stasis in the left atrium

Am Heart J

(1985)

CW Chiang et al.

“Sand-drift” echoes and thrombus formation in the left atrium

Am Heart J

(1988)

Cited by (69)

Prothrombotic State in Atrial Fibrillation Patients With One Additional Risk Factor of the CHA <inf>2</inf> DS <inf>2</inf> -VASc Score (Beyond Sex)
2019, Canadian Journal of Cardiology
It is unclear whether a prothrombotic state occurs in atrial fibrillation (AF) with low stroke risk.
We studied 118 patients with AF with the Congestive Heart Failure, Hypertension, Age (≥ 75 years), Diabetes, Stroke/Transient Ischemic Attack/Systemic Embolism, Vascular Disease, Age (65-74 years), Sex (Female) (CHA₂DS₂-VASc) score of 1 in men or 2 in women vs 52 patients with AF with the CHA₂DS₂-VASc score of 0 in men or 1 in women. Plasma clot permeability (K_s), a measure of fibrin clot density, and clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor antigen, and plasminogen activator inhibitor-1 were evaluated in nonanticoagulated subjects.
Patients with the CHA₂DS₂-VASc score of 1 (beyond sex), compared with those with 0, had lower K_s, prolonged CLT, increased ETP, von Willebrand factor antigen, and plasminogen activator inhibitor-1 (all P < 0.001), without any sex-dependent differences. Heart failure (odds ratio [OR]: 10.28; 95% confidence interval [CI]: 2.32-45.41), age 65-74 years (OR: 4.37; 95% CI: 1.76-10.83), and hypertension (OR: 5.03; 95% CI: 1.81-13.94) were independently associated with low K_s (the lowest quartile, ≤ 6.4 × 10⁻⁹ cm²), whereas only age 65-74 years (OR: 3.33; 95% CI: 1.59-6.96) significantly predicted prolonged CLT (the top quartile, ≥ 108 minutes). Age 65-74 years (OR: 5.21; 95% CI: 2.12-12.80), heart failure (OR: 6.58; 95% CI: 1.49-29.06), and hypertension (OR: 4.33; 95% CI: 1.54-12.15) were independently associated with high ETP (the top quartile, ≥ 1681.3 nM × minutes).
A prothrombotic state (increased thrombin generation, denser fibrin clots, impaired fibrinolysis, and endothelial injury) characterizes patients with AF with 1 additional clinical stroke risk factor (beyond sex), with age 65-74 years being particularly associated with prothrombotic indices.
La question de savoir si un état prothrombotique survient chez les patients atteints de fibrillation auriculaire (FA) à faible risque d’accident vasculaire cérébral (AVC) n’a pas été élucidée.
Nous avons étudié 118 patients atteints de FA présentant un score CHA₂DS₂-VASc (insuffisance cardiaque congestive, hypertension, âge ≥ 75 ans, diabète, accident vasculaire cérébral/ischémie cérébrale transitoire, maladie vasculaire, âge compris entre 65 et 74 ans, sexe féminin) de 1 chez les hommes ou de 2 chez les femmes comparativement à 52 patients atteints de FA et présentant un score CHA₂DS₂-VASc de 0 chez les hommes ou de 1 chez les femmes. La perméabilité du caillot plasmatique (K_s), une mesure de la densité des caillots de fibrine, ainsi que le temps de lyse du caillot (TLC), le potentiel endogène de thrombine (PET), et la concentration d’antigène du facteur de von Willebrand et d’inhibiteur 1 des activateurs du plasminogène ont été évalués chez les patients non traités par un anticoagulant.
Les patients ayant un score CHA₂DS₂-VASc de 1 (sans égard au sexe), comparativement à ceux chez qui ce score était de 0, affichaient un K_s moins élevé, un TLC plus long, et des valeurs plus élevées de PET et d’antigènes du facteur de von Willebrand et d’inhibiteurs 1 des activateurs du plasminogène (p < 0,001 dans tous les cas), sans aucune différence liée au sexe. L’insuffisance cardiaque (rapport des cotes [RC]: 10,28; intervalle de confiance [IC] à 95 % : de 2,32 à 45,41), l’âge compris entre 65 et 74 ans (RC : 4,37; IC à 95 % : de 1,76 à 10,83) et l’hypertension (RC : 5,03; IC à 95 % : de 1,81 à 13,94) étaient associés de manière indépendante à une faible valeur de K_s (le quartile inférieur, ≤ 6,4 × 10⁻⁹ cm²), tandis que seul l’âge compris entre 65 et 74 ans (RC : 3,33; IC à 95 % : de 1,59 à 6,96) était associé de façon significative à l’allongement du TLC (le quartile supérieur, ≥ 108 minutes). L’âge compris entre 65 et 74 ans (RC: 5,21; IC à 95 % : de 2,12 à 12,80), l’insuffisance cardiaque (RC : 6,58; IC à 95 % : de 1,49 à 29,06) et l’hypertension (RC : 4,33; IC à 95 % : de 1,54 à 12,15) étaient associés de manière indépendante avec un PET élevé (le quartile supérieur, ≥ 1681,3 nM × minutes).
Un état prothrombotique (production accrue de thrombine, caillots de fibrine plus denses, perturbation de la fibrinolyse et lésions endothéliales) caractérise les patients atteints de FA qui présentent 1 facteur de risque d’AVC clinique additionnel (sans égard au sexe), l’âge compris entre 65 et 74 ans présentant une association particulièrement élevée avec les indices d’un tel état.
Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation
2015, Thrombosis Research
Citation Excerpt :
The major risk factors for stroke in AF include cardiac failure, hypertension, age, diabetes, and previous stroke/transient ischemic attack/thromboembolism [2]. Prothrombotic mechanisms underlying AF–related thromboembolism are multiple and include impaired blood rheology, endothelial dysfunction, blood coagulation activation, platelet activation, and altered fibrinolytic activity [3–5]. Elevated plasma fibrinogen, von Willebrand factor (vWF), and soluble P-selectin have been shown to be linked to thromboembolic events in AF patients [6,7].
Formation of compact and poorly lysable fibrin clots have been demonstrated in patients following ischemic stroke. Recently, it has been shown that denser fibrin networks and impaired fibrinolysis occurs in subjects with permanent atrial fibrillation (AF). Fibrin clot phenotype in other types of AF remains to be established. We evaluated fibrin clot properties in paroxysmal (PAF) and persistent AF (PsAF).
We studied 88 non-anticoagulated patients with AF on sinus rhythm and free of stroke (41 with PAF, 47 with PsAF) versus 50 controls. Ex-vivo plasma fibrin clot permeability (K_s) and clot lysis time (CLT) were evaluated along with von Willebrand factor (vWF), peak thrombin generation (TG), platelet factor 4 (PF4) and fibrinolytic proteins.
Compared with control subjects, clots obtained from plasma of patients with PAF and PsAF had similarly lower K_s (− 7.7%, P = 0.01; − 8.6%, P = 0.005, respectively) and prolonged CLT (+ 10.8%, P = 0.006; + 7.8% P = 0.04, respectively). No associations of K_s and CLT with CHA₂DS₂-VASc and HAS-BLED score were observed. Patients with AF had higher TG, vWF, PF4 and plasminogen activator inhibitor-1 (PAI-1) antigen compared with controls. Multiple linear regression adjusted for age, gender, body mass index and fibrinogen showed that TG (β = − 0.41), vWF (β = − 0.29) and PF4 (β = − 0.28) are the independent predictors of K_s (R² = 0.78), while CLT was independently predicted by TG (β = 0.37), PAI-1 antigen (β = 0.29) and vWF (β = 0.26) in the AF group (R² = 0.39).
Patients with PAF and PsAF while on sinus rhythm display unfavorably altered fibrin clot properties, which might contribute to thromboembolic complications.
Long-term outcome of multiform premature ventricular complexes in structurally normal heart
2015, International Journal of Cardiology
Multiform premature ventricular complexes (PVCs) are common electrocardiographic abnormalities in patients with structurally normal hearts. However, the prognostic value of these complexes remains unclear. This study aimed to clarify the role of PVC polymorphism in predicting adverse outcomes.
We examined the database for 24-hour electrocardiography monitoring between January 1, 2002 and December 31, 2004. We analyzed 3351 individuals with apparently normal hearts. Kaplan–Meier curves and multivariate Cox proportional hazards models were employed to estimate the effect of multiform PVC and uniform PVC on the number of incident adverse events. Average follow-up time was 10 ± 1 years. Patients with multiform PVC were older and had a higher prevalence of comorbidities. In multivariate analysis, patients with multiform PVC had an increased incidence of mortality (hazard ratio [HR]: 1.642, 95% confidence interval [CI]: 1.327–2.031), hospitalization (HR: 1.196, 95% CI: 1.059–1.350), cardiovascular hospitalization (HR: 1.289, 95% CI: 1.030–1.613), new-onset heart failure (HF; HR: 1.456, 95% CI: 1.062–1.997), transient ischemic accident (HR: 1.411, 95% CI 1.063–1.873), and new-onset atrial fibrillation (AF; HR: 1.546, 95% CI: 1.058–2.258) compared to the group without PVC. Patients with multiform PVC had a higher rate of mortality (HR: 1.231, 95% CI: 1.033–1.468) and all cause-hospitalization (HR: 1.147, 95% CI: 1.025–1.283) compared with patients with uniform PVC.
The presence of multiform PVC was associated with a higher incidence of mortality, hospitalization, transient ischemic attack, new-onset AF, and new-onset HF independent of other clinical risk factors.
Left atrial strain as evaluated by two-dimensional speckle tracking predicts left atrial appendage dysfunction in patients with acute ischemic stroke
2014, BBA Clinical
Left atrial appendage (LAA) dysfunction predisposes patients with atrial fibrillation (AF) to cardioembolic stroke. Two-dimensional (2D) speckle tracking was reported to be useful for evaluating left atrial (LA) regional function, as well as left ventricular function. However, it remains unclear whether 2D speckle tracking is useful for evaluating LAA dysfunction. Therefore, we investigated whether decreased LA strain may predict LAA dysfunction and thrombus formation in patients with acute ischemic stroke.
We performed transthoracic and transesophageal echocardiography in 120 patients (83 males, mean age 72 ± 11 years) within 7 days of onset of an acute ischemic stroke. Longitudinal LA strain was evaluated using 2D speckle tracking imaging at each LA segment, and peak systolic strain was calculated by averaging the results for each segment.
Forty-eight patients had LAA dysfunction as defined by the presence of LAA thrombus and/or severe spontaneous echo contrast. LA peak systolic strain was significantly decreased in patients with LAA dysfunction compared to those without (32.3 ± 13.7% vs. 12.1 ± 7.2%, p < 0.0001). LA peak systolic strain was significantly correlated with LAA emptying flow velocity (r = 0.693, p < 0.0001). The optimum LA peak systolic strain cut-off value for predicting LAA dysfunction was 19%. Multivariate logistic regression analysis showed that LA peak systolic strain was an independent predictor of LAA dysfunction (odds ratio 0.059, 95% confidence interval 0.018–0.146; p < 0.0001).
Decreased LA peak systolic strain was independently associated with LAA dysfunction in patients with acute ischemic stroke.
Assessment of left atrial appendage function by speckle tracking
2014, Revista Colombiana de Cardiologia
Caracterizar la función del apéndice auricular izquierdo por speckle tracking bidimensional, en pacientes en ritmo sinusal y en fibrilación auricular.
Se realizó ecocardiografía transesofágica para valorar la deformación longitudinal, la tasa de deformación longitudinal, las velocidades del tejido, el volumen y la fracción de eyección del apéndice auricular izquierdo a través de speckle tracking bidimensional, en pacientes en ritmo sinusal y con fibrilación auricular.
Se incluyeron 91 pacientes de quienes fue posible analizar 80 (88%). El 25% estaba en fibrilación auricular y de éstos el 9% tenía trombo en el apéndice auricular izquierdo; el 46% correspondía a hombres con edad media de 60 años (18–93). Se encontraron diferencias significativas entre los pacientes con fibrilación auricular vs. ritmo sinusal en la facción de eyección del apéndice auricular izquierdo (26,7% vs. 50,1%), las velocidades de vaciamiento por Doppler (28,5 vs. 55,6 cm/s), las velocidades tisulares (3,6 vs. 9,9 cm/s), la deformación longitudinal (5,7% vs. 17%), la tasa de deformación longitudinal (0,9 vs. 3,1) y los volúmenes mínimos del apéndice auricular izquierdo (6,3 vs. 3,0 mL). No se encontraron diferencias significativas entre los pacientes en fibrilación auricular con trombo o sin éste.
La valoración de la función del apéndice auricular izquierdo por medio de speckle tracking, es una herramienta útil para caracterizar la función de esta estructura; su alteración se podría relacionar con el riesgo de desarrollar trombos y eventos embólicos secundarios.
To characterize the function of the left atrial appendage by two-dimensional speckle tracking in patients in sinus rhythm and atrial fibrillation.
Transesophageal echocardiography was performed to assess the longitudinal deformation, the rate of longitudinal deformation, tissue velocities, volume, and ejection fraction of the left atrial appendage through two-dimensional speckle tracking in patients in sinus rhythm and atrial fibrillation.
91 patients were included and it was possible to analyze 80 (88%). 25% had atrial fibrillation and of these 9% had thrombus in the left atrial appendage; 46% were men with a mean age of 60 years (18–93). Significant differences were found between patients with atrial fibrillation vs. sinus rhythm in the left atrial appendage ejection fraction (26.7% vs. 50.1%), the Doppler emptying velocities (28.5 vs. 55.6 cm/s), tissue velocities (3.6 vs. 9.9 cm/s), the longitudinal deformation (5.7% vs.17%), the longitudinal deformation rate (0.9 vs. 3.1) and minimum volumes of the left atrial appendage (6.3 vs. 3.0 mL). No significant differences were found between patients with atrial fibrillation with or without thrombus.
The assessment of left atrial appendage function by speckle tracking is a useful tool to characterize the function of this structure. Its alteration could be related to the risk of the development of thrombus and secondary embolic events.
Left atrial appendage dysfunction in a patient with premature ventricular contractions - A risk factor for stroke?
2013, Indian Pacing and Electrophysiology Journal
Citation Excerpt :
It is unknown whether the PVCs themselves create LAA dysfunction or an intermediate pathogenic step involves relatively persistently elevated left atrial pressures. Regardless, however, the potential for enhanced stroke risk likely exists in this situation [17]. Thus, to our knowledge, this is the first report of documented PVC-related LAA dysfunction in a patient with an embolic cerebrovascular event.
A 16-year-old female with ventricular dysfunction and frequent ventricular arrhythmia presented with a cardioembolic stroke. Prior electrophysiology study and ablation was performed for ventricular tachycardia (VT). For remaining ventricular ectopy, the patient was maintained on carvedilol and mexiletine. After one year on this regimen, she presented with an acute stroke. Transesophageal echocardiography revealed no evidence of an intracardiac or ventricular thrombus but demonstrated markedly decreased left atrial appendage (LAA) flow velocity worsened during frequent premature ventricular contractions (PVC). In the absence of atrial fibrillation (AF), the LAA dysfunction was considered secondary to the frequent PVCs and was thought to be the underlying cause for the stroke. We present this case to highlight a potential under recognized association between LAA dysfunction and ventricular arrhythmia, similar to that observed with atrioventricular dyssynchronous pacing.

View all citing articles on Scopus

View full text

Hemodynamic and hemorheologic determinants of left atrial spontaneous echo contrast and thrombus formation in patients with idiopathic dilated cardiomyopathy

Abstract

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Lancet

Biophys J

Thromb Res

Am J Cardiol

Am Heart J

Am Heart J