Patients and Controls

The Hartford Hospital stroke registry records a standard series of clinical and demographic variables for all patients presenting to the neurology service for evaluation for stroke or TIA. Since 2003 (the first year digitized echocardiograms were permanently stored), the registry has recorded a total of 6,190 individual patient encounters; of these, the diagnosis of stroke or TIA was confirmed by clinical assessment of a board-certified neurologist combined with computed tomographic or magnetic resonance imaging findings in 5,490 patients; stroke or TIA was ruled out in 1,163 patients. A history of paroxysmal AF or electrocardiographic evidence of AF within 24 hours of the event was confirmed in 615 patients. Within this group, 75 patients with imaging or clinical findings suggestive of thromboembolic stroke or TIA, CHADS ₂ scores ≤ 1 before the index events, and technically adequate transthoracic echocardiograms within 24 hours of presentation were identified retrospectively. Five patients whose echocardiograms were technically inadequate for strain analysis were excluded. Because the following conditions independently qualify patients for oral anticoagulation or produce LA dysfunction, patients with LV ejection fractions < 35% ( n = 8), mitral stenosis ( n = 4), or the presence of a prosthetic heart valve or valve repair ( n = 6) were excluded, leaving 57 patients available for analysis. Controls were selected from patients within the registry ( n = 48) or the inpatient echocardiography laboratory database ( n = 9) with electrocardiographically documented AF or documented histories of paroxysmal AF with otherwise identical inclusion criteria but without evidence or history of stroke or TIA or any history of oral anticoagulation before the index echocardiographic assessment. Patients and controls were matched for sex, age (±3 years), and aspirin use before presentation. Patients underwent standard, digitized echocardiography within 72 hours of presentation. The study was approved by the Hartford Hospital Institutional Review Board.

Data

Age, sex, international normalized ratio (INR), and CHADS ₂ and CHA ₂ DS ₂ -VASc scores immediately before stroke or TIA were recorded. CHADS ₂ scores were calculated by adding 1 point for congestive heart failure, hypertension, age ≥ 75 years, and diabetes mellitus, and CHA ₂ DS ₂ -VASc scores were compiled by adding 1 more point for female sex, documented vascular disease, or age 64 to 75 years. Body surface area was recorded for each patient and control. All echocardiographic images were obtained from Siemens Sequoia 512 (Siemens Medical Solutions USA, Inc., Mountain View, CA), Philips iE33 (Philips Medical Systems, Andover, MA), or Philips 7500 (Philips Medical Systems) sonographs, translated into Digital Imaging and Communications in Medicine format, and transferred to an offline analysis system (Heartlab; Agfa, Hackensack, NJ). Echocardiographic dimensions were measured, and LV mass index was calculated. LV ejection fraction was measured from apical four-chamber and two-chamber views using Simpson’s biplane method. LA volume was calculated using the biplane method of discs. Maximum LA volume was measured just before mitral valve opening, minimum LA volume was measured just before mitral valve closure, and LA emptying volume was calculated as the difference. All echocardiographic measurements were made by a level 3–trained, board-certified echocardiographer blinded to the presence or absence of stroke or TIA. Strain measurements were made by a single blinded investigator (V.M.R.).

LA strain was measured from Digital Imaging and Communications in Medicine images imported into a previously validated grayscale analysis system (Axius Velocity Vector Imaging; Siemens Medical Solutions USA, Inc) ( Figure 1 ). Velocity Vector Imaging is a software program that translates any Digital Imaging and Communications in Medicine echocardiographic image into a grayscale image in a manner analogous to speckle tracking. Angle-independent vectors are constructed along the entire length of the atrial (or ventricular) wall (solid arrow in Figure 1 ). Vectors representing both relative velocity and direction throughout the cardiac cycle are displayed as a sequence of tracking arrows. The program displays segmental or global velocity, strain, or strain rate ( Figure 1 ). LA strain has been evaluated in both sinus rhythm and AF, and LA strain in AF measured by both methods is closely correlated.

LA strain analysis. LA strain tracings were constructed from Digital Imaging and Communications in Medicine images using a grayscale imaging and analysis program. The tracing represents LA strain in the four-chamber view through three cardiac cycles of a patient with stroke. Six individual tracings, one from each segment of the atrium, are shown. The program automatically calculates peak positive strain in the reservoir phase in ventricular systole ( black dotted arrow ) and peak negative strain at end-diastole or during atrial contraction when sinus rhythm is present, ( solid black arrow and table of values in the figure). The average values for all six segments are calculated automatically ( dotted white arrow ). The electrocardiogram below the two-dimensional image in the upper left-hand corner demonstrates AF ( solid white arrow ).

The endocardial border of the left atrium was traced in the apical four-chamber and two-chamber views. Manual readjustments were made as necessary to ensure that endocardial borders were accurately traced. Regional LA strain and strain rate data were obtained from the annular, mid, and superior segments along the septal lateral, anterior, and inferior LA walls using apical four-chamber and two-chamber views ( Figure 1 ). Global LA strain data were computed by taking the average of longitudinal strain data obtained from a total of 12 LA segments (six segments from each view). Peak positive LA strain and strain rate were measured during LV systole (dotted arrow in Figure 1 ), and peak negative strain and strain rate were measured at LV end-diastole or during LA contraction (solid arrow in Figure 1 ). Mean frame rates for each echocardiogram were identical for both patients and controls (43 Hz) and were similar to those used in previous studies. Assessment of LA strain was regarded as suboptimal ( n = 5) when either strain analysis could not be performed for at least four of the six LA segments in each view or a theoretically unacceptable value or values were obtained.

Data Analysis

All data are expressed as mean ± SD or as percentages. Using previous published data describing the distribution of LA strain and strain rate for patients with AF and stoke, and accepting a 20% decrease in peak systolic strain as significant, we estimated that a sample of 51 patient-control pairs would provide 80% power with an α error of 0.05. After testing each distribution for normality, differences between relevant demographic, clinical, and echocardiographic variables were compared between patients and controls using paired t tests. Differences in the frequency of categorical variables were tested using χ ² tests. Correlation was tested using Pearson’s correlation coefficient. Binary logistic regression was constructed using the presence of stroke or TIA as the dependent variable and all significant echocardiographic variables as covariates in the model. Statistical calculations were performed using SPSS version 19.0 (SPSS, Inc., Chicago, IL).