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Background and Objectives: The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown., Design, Setting, Participants, & Measurements: Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%)., Results: Among the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively)., Conclusions: Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.

We compared clinical outcomes following percutaneous transluminal coronary angioplasty (PTCA) for 77 chronic renal failure (CRF) (dialysis and nondialysis) patients and a control group matched for history of myocardial revascularization, specific revascularization procedure, gender, age, diabetes, number of native vessels diseased, number of vessels dilated, and the specific vessel(s) dilated. CRF patients had a higher incidence of peripheral vascular disease, hypertension, and more complex PTCA target lesion types than controls: 5% vs. 16% Type A, 12% vs. 28% Type B1, 44% vs. 41% Type B2, 39% vs. 15% Type C (p < 0.001). The primary success rate for PTCA in CRF patients and controls was 89% and 97% (p < 0.05). Survival analysis 24 months following PTCA showed a lower composite cardiac event-free survival (angiographic restenosis, myocardial infarction, coronary artery bypass surgery, and cardiac death) for those with CRF than controls, 54% vs. 69% (p = 0.002). Over the study period, 26 CRF patients died (11 from cardiac causes) compared to only 3 control patients (one from a cardiac cause); p < 0.001 for all cause and p < 0.003 for cardiac mortality. We also compared PTCA results between two categories of CRF patients. The first consisted of 49 end-stage renal disease (ESRD) patients on dialysis and the second included 28 patients not on dialysis (13 with creatinine > 2. 0 mg/dL and 15 with ESRD post-renal transplant). Both subgroups had similar coronary anatomy, including PTCA, target lesion type, and acute and long-term outcomes. In conclusion, we observed acceptable primary success and complication rates for PTCA in CRF patients compared with controls matched for comorbid features despite more complex target lesion morphology. Poorer long-term outcomes, however, were apparent for those with CRF regardless of dialysis dependence and likely relate to more extensive atherosclerosis and complex target coronary lesions at index PTCA as well as other features related to CRF.

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.

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.

Background and Purpose: Thoracic aortic plaque identified by transesophageal echocardiography heightens the risk of stroke associated with atrial fibrillation (AF). We sought to identify the prevalence, predictors, and implications of aortic plaque in patients with nonvalvular AF., Methods: Thoracic aortic plaque was prospectively sought in 770 persons with AF with the use of transesophageal echocardiography and classified as simple or complex on the basis of thickness >/=4 mm, ulceration, or mobility. Clinical and echocardiographic features of thromboembolism were correlated by multivariate analysis., Results: Aortic plaque was detected in 57% of the cohort, and complex plaque was detected in 25%. Both were found more frequently in the descending than in the proximal aorta. Potentially etiologic patient characteristics independently associated with complex plaque included advanced age, history of hypertension, diabetes, and past or present tobacco use. Comorbidities associated with aortic plaque were prior thromboembolism, increased pulse pressure, ischemic heart disease, stenosis or sclerosis of the aortic valve, mitral annular calcification (>10%), elevated serum creatinine concentration, spontaneous echo contrast in the left atrium or appendage, and left atrial appendage thrombus. The prevalence of complex plaque in patients aged <70 years with <10% mitral annular calcification, without ischemic heart disease, or without pulse pressure >/=65 mm Hg was 4% (95% CI, 1% to 6%)., Conclusions: Aortic plaque is prevalent in patients with AF and is associated with atherosclerosis risk factors and with left atrial stasis or thrombosis, which are themselves independent stroke risk factors. Since the predominant location of complex plaque was in the descending aorta, the role of aortic plaque as a source of embolism in AF is uncertain.

Objectives: This study explored the mechanisms linking clinical and precordial echocardiographic predictors to thromboembolism in atrial fibrillation (AF) by assessing transesophageal echocardiographic (TEE) correlations., Background: Clinical predictors of thromboembolism in patients with nonvalvular AF have been identified, but their mechanistic links remain unclear. TEE provides imaging of the left atrium, its appendage and the proximal thoracic aorta, potentially clarifying stroke mechanisms in patients with AF., Methods: Cross-sectional analysis of TEE features correlated with low, moderate and high thromboembolic risk during aspirin therapy among 786 participants undergoing TEE on entry into the Stroke Prevention in Atrial Fibrillation III trial., Results: TEE features independently associated with increased thromboembolic risk were appendage thrombi (relative risk [RR] 2.5, p = 0.04), dense spontaneous echo contrast (RR 3.7, p < 0.001), left atrial appendage peak flow velocities < or = 20 cm/s (RR 1.7, p = 0.008) and complex aortic plaque (RR 2.1, p < 0.001). Patients with AF with a history of hypertension (conferring moderate risk) more frequently had atrial appendage thrombi (RR 2.6, p < 0.001) and reduced flow velocity (RR 1.8, p = 0.003) than low risk patients. Among low risk patients, those with intermittent AF had similar TEE features to those with constant AF., Conclusions: TEE findings indicative of atrial stasis or thrombosis and of aortic atheroma were independently associated with high thromboembolic risk in patients with AF. The increased stroke risk associated with a history of hypertension in AF appears to be mediated primarily through left atrial stasis and thrombi. The presence of complex aortic plaque distinguished patients with AF at high risk from those at moderate risk of thromboembolism.

Two-dimensional echocardiography successfully displayed the location and extent of aortic root complications, annular abscess or mycotic aneurysm in nine patients with aortic valve endocarditis. Five of the nine patients had prosthetic valve endocarditis and four had native valve endocarditis. The infective process extended into the paravalvular structures, including the interventricular septum (seven patients), right ventricular outflow tract (three patients), interatrial septum (one patient) and anterior mitral valve leaflet (four patients). The amount of aorto-left ventricular discontinuity caused by these complications was quantitated in degrees of annular circumference on the parasternal short axis image and in distance on the parasternal long axis image. The echocardiographic findings were confirmed at surgery and were helpful in the preoperative anticipation of the type of surgical procedure required: aortic valve replacement or composite aortic valve and root replacement. Five patients had prosthetic valve endocarditis with calculated aorto-left ventricular discontinuity of 173 +/- 55 degrees on parasternal short axis images and 1.36 +/- 0.72 cm on parasternal long axis images. Initial surgical repair included three composite aortic root-valve prosthesis implants, one reconstructive procedure with valve replacement and one simple aortic valve replacement. During a follow-up period of 18 months (range 1 to 35), a second reparative procedure was required for only one patient to repair an aortic conduit to coronary artery venous bypass graft. Four patients had native valve endocarditis with calculated aorto-left ventricular discontinuity of 100 +/- 17 degrees on parasternal short axis images and 0.88 +/- 63 cm on parasternal long axis images. Initial surgical repair included two reconstructive procedures with valve replacement and two simple aortic valve replacements. During a follow-up period of 30 months (range 16 to 42), three of these four patients required a second reparative procedure: one each for repair of a paraprosthetic leak, a ventricular septal defect and persistent aorto-left ventricular discontinuity. Two-dimensional echocardiography accurately detected aortic annular abscess and mycotic aneurysm complicating aortic valve endocarditis and the resultant degree of aorto-left ventricular discontinuity. Circumferential aorto-left ventricular discontinuity with these complications is greater for prosthetic than native valve endocarditis and predicts a more extensive surgical repair.(ABSTRACT TRUNCATED AT 400 WORDS)

Five patients with pulmonary embolism, in whom right-sided intracardiac thromboembolus was detected by echocardiography and confirmed by either angiography, surgery or postmortem examination, are described. One of these patients died from massive pulmonary embolism after right heart catheterization. In two patients treated medically, either partial or total lysis of the thromboembolus was demonstrated echocardiographically; in another two patients, the right atrial thromboembolus was successfully removed surgically. Typical locations and echocardiographic characteristics of right-sided thromboemboli are described. The potential usefulness of two-dimensional echocardiography in both the diagnosis and the management of patients with right-sided intracardiac thromboembolism is discussed.

Flecainide acetate, a new antiarrhythmic agent, was given orally to 11 hospitalized patients with chronic high-frequency ventricular ectopic depolarizations. Drug effectiveness was evaluated with a dose-ranging single-blind protocol, which included placebo control and washout periods. Twice-daily dosing (average daily dose 436 mg) completely suppressed all ventricular ectopic activity in five of 11 patients; average suppression in the 11 patients was 96.3%. Complex ventricular arrhythmias, which were present in all 11 patients during the placebo control period, were completely suppressed in eight patients and markedly suppressed in the other three patients during flecainide therapy. Ejection fraction and velocity of circumferential fiber shortening measured by M-mode echocardiography did not change significantly during flecainide dosing. Ventricular arrhythmias returned in all patients during the placebo washout period. During subsequent outpatient therapy with flecainide, significant suppression was present after 1 and 2 weeks of treatment (94.4% and 93.3%, respectively). Drug elimination was slow (average plasma half-life 20 hours). Ninety-five percent suppression of ventricular ectopic depolarization during dosing and 5% reappearance of arrhythmias during washout occurred with flecainide concentrations of 200-800 ng/ml. Side effects occurred in five of 11 patients, but did not require discontinuation of the drug. These results indicate that flecainide is a very effective antiarrhythmic agent that merits further clinical investigation.

We sought to determine whether an association existed between the echocardiographic appearance of left ventricular thrombi and systemic embolization. We reviewed the clinical and echocardiographic characteristics of 60 patients who underwent diagnostic two-dimensional echocardiography for left ventricular thrombi. Sixteen of these 60 patients (27%) had evidence of systemic embolization. Multiple echocardiographic characteristics of left ventricular thrombi were analyzed, including mobility, shape, heterogeneity, echo density, layering, central echo lucency, presence within an aneurysm, and association with low-density swirling echoes. Incidence of embolization was significantly higher in patients with thrombi that were mobile or protruded into the left ventricular cavity (p less than .002 and p less than .05, respectively). Bayesian analysis indicated that the pretest likelihood for embolization was 27% and increased in the presence of mobility, central echo lucency, and protrusion to 60%, 50%, and 40%, respectively. A stepwise regression indicated that mobility was the first and protrusion the second most helpful echocardiographic characteristic in identifying patients with embolic phenomena. Clinical features were of less help in identifying the risk for embolization of patients with left ventricular thrombi. Nine of 31 patients (29%) with recent myocardial infarction (less than 3 weeks) has emboli in contrast to five of 26 patients (19%) with remote myocardial infarction (greater than 3 weeks) (p = NS). The three patients without infarction had congestive cardiomyopathy and two had emboli.

Although M-mode echocardiography (MME) is not a reliable method for detecting left atrial thrombi, recent reports suggest that two-dimensional echo (2DE) may be more effective than MME in identifying intracardiac thrombi. In three patients with prosthetic mitral valves who presented with either arterial embolization or prosthetic valvular dysfunction, 2DE demonstrated left atrial masses consistent with thrombi, while MME was either negative (two patients) or suspicious (one patient) for left atrial thrombus. Thrombi were documented by surgical or postmortem examination in all cases. Clear delineation of the atrial cavity and the margins of the masses, visualization on multiple echocardiographic views and comparison of serial examinations were helpful in identifying these masses as thrombi. In addition, the masses visualized had certain patterns of motion which seem unique and may allow characterization of atrial masses as thrombi.