Blood stasis imaging predicts cerebral microembolism during acute myocardial infarction

Background: Cardioembolic stroke is a major source of mortality and disability worldwide. The authors hypothesized that quantitative characterization of intracardiac blood stasis may be useful to determine cardioembolic risk in order to personalize anticoagulation therapy. The aim of this study was to assess the relationship between image-based metrics of blood stasis in the left ventricle and brain microembolism, a surrogate marker of cardiac embolism, in a controlled animal experimental model of acute myocardial infarction (AMI). -- Methods: Intraventricular blood stasis maps were derived from conventional color Doppler echocardiography in 10 pigs during anterior AMI induced by sequential ligation of the mid and proximal left anterior descending coronary artery (AMI-1 and AMI-2 phases). From these maps, indices of global and local blood stasis were calculated, such as the average residence time and the size and ratio of contact with the endocardium of blood regions with long residence times. The incidence of brain microemboli (high-intensity transient signals [HITS]) was monitored using carotid Doppler ultrasound. -- Results: HITS were detected in 0%, 50%, and 90% of the animals at baseline and during AMI-1 and AMI-2 phases, respectively. The average residence time of blood in the left ventricle increased in parallel. The residence time performed well to predict microemboli (C-index = 0.89, 95% CI, 0.75–1.00) and closely correlated with the number of HITS (R = 0.87, P < .001). Multivariate and mediation analyses demonstrated that the number of HITS during AMI phases was best explained by stasis. Among conventional echocardiographic variables, only apical wall motion score weakly correlated with the number of HITS (R = 0.3, P = .04). Mural thrombosis in the left ventricle was ruled out in all animals. -- Conclusions: The degree of stasis of blood in the left ventricle caused by AMI is closely related to the incidence of brain microembolism. Therefore, stasis imaging is a promising tool for a patient-specific assessment of cardioembolic risk.This study was supported by grant PI15/02211, Rio Hortega (CM17/00144), and Juan Rodés fellowships (JR15/00039) from Instituto de Salud Carlos III; grant DPI2016-75706-P and a Juan de la Cierva fellowship (IJCI-2014-19507) from Ministerio de Economía y Competitividad; synergy grant Y2018/BIO-4858-PREFI-CM from Comunidad Autónoma de Madrid; the European Union - European Regional Development Fund; by the Spanish Society of Cardiology (ISBI-DCM); by the University of California,San Diego, CTRI Galvanizing Engineering and Medicine Program; American Heart Association grant 16GRNT27250262; and National Institutes of Health UC CAI grant CII4560. P.M.-L. was also funded by CIBERCV. P.M.-L., L.R., J.C.A., and J.B. are inventors of a method for quantifying intracardiac stasis from imaging data under a Patent Cooperation Treaty patent application (WO2017091746A1)

Age-Dependence of Flow Homeostasis in the Left Ventricle

Background: Intracardiac flow homeostasis requires avoiding blood stasis and platelet activation during its transit through the cardiac chambers. However, the foundations of intraventricular blood washout and its exposure to shear stresses have been poorly addressed. We aimed to characterize and quantify these features in a wide population of healthy subjects and assess the relationships of these indices with age.Methods: We used color-Doppler echocardiography and custom post-processing methods to study 149 healthy volunteers from 26 days to 80 years old. From the intraventricular flow-velocity fields we obtained personalized maps of (1) the residence time of blood in the LV, and (2) the shear index, a metric accounting for the strongest occurrence of shear stresses inside the chamber. From these maps we derived quantitative indices of the overall intraventricular blood washout and shear exposure. We addressed the age-dependence of these indices and analyzed their relationship with age-related changes in filling-flow.Results: The entire intraventricular blood pool was replaced before 8 cycles. Average residence time of blood inside the LV was <3 cycles in all subjects and followed an inverse U-shape relationship with age, increasing from median (IQR) of 1.0 (0.7 to 1.2) cycles in the 1st year of life to 1.8 (1.4–2.2) cycles in young adults (17–30 years old), becoming shorter again thereafter. Shear index showed no relation with age and was bounded around 20 dyn·s/cm2. Regions with the longest residence time and highest shear index were identified near the apex. Differences in the degree of apical penetration of the filling waves and the duration of the late-filling phase explained the age-dependence of residence time (Radj2 = 0.48, p < 0.001).Conclusions: In average, blood spends 1 to 3 beats inside the LV with very low shear stress rates. The apical region is the most prone to blood stasis, particularly in mid-aged adults. The washout of blood in the normal LV is age-dependent due to physiological changes in the degree of apical penetration of the filling waves