Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators.

OBJECTIVE: This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation (AF). BACKGROUND: Although intermittent AF is common, relatively little is known about the attendant risk of stroke. METHODS: A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis. RESULTS: Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%). In patients with intermittent AF, independent predictors of ischemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% confidence interval 4.5 to 14). CONCLUSIONS: In this large cohort of AF patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors. Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation. High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF.

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: II. Dense spontaneous echocardiographic contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study).

We analyzed transesophageal echocardiograms from 772 participants in the Stroke Prevention in Atrial Fibrillation (SPAF-III) study, characterizing spontaneous echocardiographic contrast (SEC) in the left atrium or appendage as faint or dense. The association of dense SEC with stroke risk factors and anatomic, hemodynamic, and hemostatic parameters related to specific thromboembolic mechanisms was evaluated by multivariate analysis. Spontaneous echocardiographic contrast was present in 55% of patients and was dense in 13%. Age (odds ratio [OR] 2.4/decade, P <.001), constant atrial fibrillation (OR 6.9, P <.001), history of hypertension (OR 3. 2, P <.001), and current tobacco smoking (OR 2.6, P =.04) were independent clinical predictors of dense SEC. Multivariate analysis of clinical, echocardiographic, and hemostatic parameters yielded age as the sole independent clinical predictor of dense SEC (OR 2. 4/decade, P <.001). Other independent predictors were measures of left atrial/appendage flow dynamics, left atrial size (OR 2.4/cm diameter, M-mode, P <.001), atherosclerotic aortic plaque (OR 2.8, P =.002), and plasma fibrinogen >350 mg/dL (P <.001). Results were similar when SEC of any density was analyzed. In conclusion, SEC occurred in more than half of these patients with prospectively defined nonvalvular atrial fibrillation but was usually faint. Dense SEC was strongly associated with previously reported clinical predictors of stroke, linking them to thromboembolism through atrial stasis. Diverse pathophysiologic factors including atrial stasis, fibrinogen level, and aortic plaque influence SEC.

Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators.

BACKGROUND AND PURPOSE: Nonvalvular atrial fibrillation (AF) is a strong, independent risk factor for stroke, but the absolute rate of stroke varies widely among AF patients, importantly influencing the potential benefit of antithrombotic prophylaxis. We explore factors associated with ischemic stroke in AF patients taking aspirin. METHODS: We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low, inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years, during which 130 ischemic strokes were observed. RESULTS: Age (relative risk [RR]=1.8 per decade, P<0.001), female sex (RR=1.6, P=0.01), history of hypertension (RR=2.0, P<0.001), systolic blood pressure >160 mm Hg (RR=2.3, P<0.001), and prior stroke or transient ischemic attack (RR=2.9, P<0.001) were independently associated with increased stroke risk. Regular consumption of >/=14 alcohol-containing drinks per week was associated with reduced stroke risk (adjusted RR=0.4, P=0.04). Among SPAF III participants, estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke (adjusted RR=3.2, P=0.007). With the use of these variables, a risk stratification scheme for primary prevention separated participants into those with high (7.1%/y, 22% of the cohort), moderate (2.6%/y, 37% of the cohort), and low (0.9%/y, 41% of the cohort) rates of stroke. Ischemic strokes in low-risk participants were less often disabling (P<0.001). CONCLUSIONS: Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified. However, validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management. Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF, but these findings require confirmation.

Left atrial diameter in nonvalvular atrial fibrillation: An echocardiographic study. Stroke Prevention in Atrial Fibrillation Investigators.

BACKGROUND: The left atrium (LA) is usually enlarged in patients with nonvalvular atrial fibrillation (AF), but factors associated with LA diameter are incompletely defined. METHODS AND RESULTS: This transthoracic echocardiographic cohort study includes 3465 participants with nonvalvular AF in 3 multicenter clinical trials. LA diameter determined by M-mode echocardiography was correlated with clinical and echocardiographic features by cross-sectional multivariate regression analyses. The mean LA diameter was 47 +/- 8 mm, on average 6 mm larger in those with AF at the time of echocardiography than in those with sinus rhythm (48 vs 42 mm, P <. 001). Patient age and body weight were independently predictive of LA diameter (P <.0001), but sex, body surface area, and body mass index were not. The estimated independent contribution of atrial rhythm to LA diameter was approximately 2.5 mm. Prolonged duration of AF, left ventricular dilatation and increased muscle mass, mitral regurgitation, annular calcification, and hypertension were additional independent predictors of LA diameter. CONCLUSIONS: Multiple factors appear to contribute to LA enlargement in patients with nonvalvular AF, including the presence and persistence of the dysrhythmia.

Clinical and echocardiographic features of intermittent atrial fibrillation that predict recurrent atrial fibrillation. Stroke Prevention in Atrial Fibrillation (SPAF) Investigators.

In addition to antithrombotic therapy, 2 treatment strategies for intermittent atrial fibrillation (AF) are evolving: suppression of AF or control of the ventricular response during AF. Clinical and echocardiographic features that predict recurrent AF may influence the choice of management. In this study, clinical, echocardiographic, and electrocardiographic data from 486 patients with intermittent AF enrolled in the Stroke Prevention in Atrial Fibrillation studies were analyzed. Patients with intermittent AF were younger (p < 0.001), had fewer incidences of systemic hypertension (p < 0.007) and heart failure (p < 0.001), and had more recent-onset AF than patients with constant AF. They also had a smaller mean left atrial diameter, a lower prevalence of a large (> 5 cm) left atrium, better left ventricular performance by echo, and less mitral regurgitation. After a mean follow-up of 26 months, 51% of patients remained in sinus rhythm and 49% of patients developed recurrent AF, including 12% who had AF, as seen on all follow-up electrocardiograms. Clinical factors predicting recurrent AF were age, heart failure, and myocardial infarction. An enlarged left atrium was associated with recurrent intermittent AF; an enlarged left ventricle predicted conversion to constant AF. Thus, clinical and echocardiographic parameters predict recurrent AF in patients with intermittent nonvalvular AF.

Determination of aortic valve area by two-dimensional and Doppler echocardiography in patients with normal and stenotic bioprosthetic valves.

To assess the feasibility and accuracy of determining bioprosthetic aortic valve area from two-dimensional and Doppler echocardiographic measurements, three partially overlapping groups were selected from 55 patients with such bioprosthetic valves and adequate Doppler studies. These were Group 1, 37 patients with recent aortic valve replacement surgery and no clinical or echocardiographic evidence of valve dysfunction; Group 2, 12 patients with prosthetic valve stenosis documented by cardiac catheterization; and Group 3, 22 patients with both Doppler and catheterization studies in whom noninvasive and invasive determinations of aortic valve area could be directly compared. Left ventricular outflow tract diameter was measured from two-dimensional still frame images. Flow velocity proximal to the aortic valve, transvalvular velocity and acceleration time were determined from pulsed and continuous wave Doppler spectra. Aortic valve gradient was calculated with the modified Bernoulli equation and valve area by the continuity equation. In the 37 patients with a normally functioning valve, the calculated mean gradient ranged from 5 to 25 mm Hg (average 13.6 +/- 5.2) and valve area from 1.0 to 2.3 cm2 (mean 1.6 +/- 0.31). Linear regression analysis of prosthetic aortic valve area determined by Doppler imaging and cardiac catheterization demonstrated a high correlation (r = 0.93) between the two techniques. Comparison of the patients with and without prosthetic valve stenosis revealed statistically significant differences in mean gradient (42.8 +/- 12.3 versus 13.6 +/- 5.2 mm Hg; p = 0.0001), acceleration time (116 +/- 15 versus 80 +/- 13 ms; p = 0.0001) and valve area by the continuity equation (0.80 +/- 0.16 versus 1.6 +/- 0.31 cm2; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis.

A 2-part prospective study was performed to evaluate the clinical outcome of patients with hemodynamically confirmed asymptomatic valvular aortic stenosis (AS). During phase 1, linear regression analysis showed continuous wave Doppler to be highly accurate in predicting catheterization measured peak systolic aortic valve pressure gradients in 101 consecutive patients aged 36 to 83 years (mean 65 +/- 8) with symptomatic AS. During phase 2, 90 additional patients (51 asymptomatic and 39 symptomatic) with Doppler-derived peak systolic aortic valve gradients greater than or equal to 50 mm Hg (range 50 to 132 [mean 68 +/- 19]) were followed for 1 to 45 months. Both groups of patients in phase 2 had similar Doppler gradients and clinical and auscultatory evidence of moderate to severe AS at baseline. Asymptomatic patients were younger (p = 0.01), had higher ejection fractions (p = 0.001) and were less likely to have an electrocardiographic strain pattern (p = 0.01) and left atrial enlargement (p = 0.02). End-diastolic wall thickness, left ventricular cross-sectional myocardial area and estimated left ventricular mass were 18% (p = 0.0001), 20% (p = 0.0008), and 29% (p = 0.002) greater in symptomatic patients. During 17 +/- 9 months of follow-up, 21 asymptomatic patients (41%) became symptomatic. Dyspnea was the most common initial complaint, occurring 2.5 and 4.8 times more often than angina and syncope, respectively. Compared with the 39 symptomatic patients, the 51 asymptomatic patients had a lower cumulative life table incidence of death from any cause (p = 0.002), and from cardiac causes (p = 0.0001) including sudden death (p = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective comparison of continuous wave versus high pulse repetition frequency Doppler echocardiography for quantifying transvalvular pressure gradients in adults with aortic stenosis.

To evaluate the relative accuracy of continuous wave (CW) and high pulse repetition frequency (HPRF) Doppler for estimating aortic transvalvular pressure gradients, Doppler examinations with both devices were obtained in 87 consecutive patients with aortic valve disease. Thirty-seven (43%) also underwent catheterization and direct determination of the pressure gradient. The correlation between CW Doppler and catheterization measurements was high (r = 0.91) and significantly superior to HPRF Doppler (r = 0.72; p less than 0.005). Disparities between the Doppler measurements predominantly occurred in patients with gradients exceeding 50 mm Hg in whom underestimation by the HPRF instrument was frequent. These data suggest that continuous wave Doppler is the preferred modality for the estimation of transvalvular pressure gradients in adult patients with moderate or severe aortic stenosis.

The timing of CNV resolution in a memory retrieval task.

Twelve men performed the Sternberg memory retrieval task while the EEG and EOG were recorded. Subjects saw a target set of 1 to 4 digits followed by a warning tone that was followed after 1.5 sec by a probe digit. Subjects indicated by pressing one of two levers whether the probe digit was in or out of the target set. The timing of contingent negative variation (CNV) resolution was measured as the latency of 50% resolution in stimulus-synchronized waveforms (SSWs), response-synchronized waveforms (RSWs), and model waveforms (MWs). The MWs were constructed by adding each RSW to itself using time displacements derived from the reaction times of the single trials of which the RSW was an average. The results indicated that CNV resolution is related to the timing of the motor response. MWs had resolution latencies close to those of the SSWs. In SSWs the N1 and P3 to the warning tone also varied with target set size.

Parameters of temporal recovery of the human auditory evoked potential.

Auditory evoked potentials (AEPs) to tone pips at three monopolar scalters were systematically varied: tone intensity (3.0, 1.5 and 0.75 sec), and direction of attention. Interstimulus intervals were computed separately for the 9 different combinations of the three possible first prior intervals (intervals between the test stimulus and the stimulus immediately preceding it) and the three possible second prior intervals (intervals between the stimulus preceding the test stimulus and the stimulus prior to that). Our results show that temporal amplitude recovery of N1 and P2 can be based solely on the first prior interval had not effect on amplitude. Furthermore, they show that it is inadvisable to use combined N1-P2 amplitude measures since the two peaks appear to be governed by separate processes. Recovery for N1 was different from that of P2, N1 showed no intensity effects while P2 did, and N1 and P2 had different topographic distributions. Directing attention to the tones did not affect N1 or P2 amplitudes but caused a highly significant increase in both N1 and P2 latency. Attention to the tones also produced a frontal negative baseline shift following them.