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The SAMe-TT 2 R 2 score predicts optimal long-term oral Vitamin K Antagonist (VKA) anticoagulation for homogenous Caucasian and homogenous Asian populations for non-valvular atrial fibrillation but at different score thresholds. The score that predicts optimal VKA anticoagulation in significantly diverse populations for multiple indications for systemic anticoagulation has not been reported. We determined whether optimal VKA anticoagulation is predicted by SAMe-TT 2 R 2 score in a diverse inner-city population for non-valvular atrial fibrillation (NVAF), unprovoked venous and pulmonary thromboembolic disease (VTE), mechanical prosthetic heart valves and all other indications. All patients on long term VKA's that attended an inner-city anticoagulation clinic between February 2016 and October 2017 were included in this study. Eligible patients were grouped according to oral anticoagulation indication: (1) NVAF, (2) VTE, (3) prosthetic valves and (4) other indications. Each patient's SAMe-TT 2 R 2 score and percent time of INR in the therapeutic range (TTR) was calculated with optimal international normalized ratio (INR) control defined as TTR ≥ 65%. The correlation between SAMe-TT 2 R 2 score and TTR was determined by logistic regression for each oral anticoagulant indication. Receiver operating characteristic curves were then used to identify the best cutoff for prediction of ≥ 65% TTR. Of 316 patients meeting study criteria, 54% were non-Caucasian and there was a significant negative correlation between the SAMe-TT 2 R 2 score and TTR (coefficient - 0.35, P < 0.0001) for all patients. A SAMe-TT 2 R 2 score < 4 was identified as the best threshold for predicting optimal TTR (Youden's J-statistics = 0.238) with accuracy and positive likelihood ratio of 63.4% and 1.73, respectively. The SAMe-TT 2 R 2 score predicts optimal VKA anticoagulation for systemic anticoagulation for multiple indications in a diverse urban population at a higher score than the original report for non-valvular atrial fibrillation of a cohort where < 10% non-Caucasians., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The spectrum, prevalence, and prognostic implications of abnormal left ventricular geometry (LVG) in patients with lacunar stroke are unknown. We examined the spectrum of LVG and its relationship with vascular risk factors and outcomes after lacunar stroke., Methods: LVG was determined with transthoracic echocardiography for 1961 patients with magnetic resonance imaging-verified recent lacunar stroke participating in the Secondary Prevention of Small Subcortical Strokes trial. Multivariable logistic regression and Cox proportional hazards models were used to identify characteristics independently associated with LVG and to estimate risk from abnormal LVG for recurrent stroke and death., Results: Abnormal LVG was present in 77%. Hispanic (odds ratio [OR], 1.4; 95% confidence interval, 1.1-1.8) or black (OR, 2.0; 1.3-2.9) race-ethnicity, diabetes (OR, 1.3; 1.0-1.7), hypertension, impaired renal function (OR, 1.8; 1.2-2.5), intracranial stenosis (OR, 1.5; 1.1-2.1), and abnormal left ventricular function (OR, 2.0; 1.4-3.0) were independently associated with abnormal LVG. Subjects with abnormal LVG also more frequently had advanced manifestations of small-vessel disease specifically previous subcortical infarcts and white matter hyperintensities. After adjusting for assigned treatments, clinical risk factors, and advanced manifestations of small-vessel disease, subjects with abnormal LVG remained at increased risk of stroke recurrence (hazard ratio, 1.5; confidence interval, 1.0-2.4). There was no interaction between LVG and assigned antiplatelet or blood pressure target. Abnormal LVG was not associated with mortality., Conclusions: LVG consistent with chronic hypertensive changes was highly prevalent and correlated with neuroradiologic manifestations of small-vessel disease in lacunar stroke patients. These results support the constructs that both cerebral small-vessel disease and LVG represent end-organ consequences of chronic hypertension., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

What Is Known and Objective: Patients with non-valvular atrial fibrillation (NVAF) are at risk for stroke and systemic embolism (SSE), and this risk can be decreased with adjusted-dose warfarin. Warfarin, however, is cumbersome to use and requires at least monthly laboratory monitoring. Three new oral anticoagulants (NOACs) that are less cumbersome have been approved as alternatives to warfarin for SSE prevention in NVAF. Selecting a patient-specific alternative to warfarin can be confusing for pharmacists and clinicians. This review details clinical parameters to consider when choosing an alternative to warfarin for a specific patient and summarizes them in a Comparison Table., Methods: Using available clinical evidence from pivotal trials, US FDA- and Health Canada-approved prescribing information and post-marketing observations, this review provides a summary of important clinical variables for clinicians to consider when choosing patient-centred anticoagulant alternatives to warfarin for prevention of SSE in NVAF., Results and Discussion: Dabigatran, rivaroxaban and apixaban are approved alternatives to warfarin for primary and secondary prevention of SSE in patients with NVAF. Additionally, apixaban has also been compared to aspirin in patients with NVAF that were considered unsuitable for vitamin K antagonist therapy. Prospective consideration of age, weight, hepatic function, renal function and drug interactions are important clinical parameters to consider when selecting patient-centred alternatives to adjusted-dose warfarin., What Is New and Conclusion: Several NOACs are now alternatives to warfarin for SSE prevention in NVAF but require providers to make a shift in strategy from tailoring anticoagulant dose based on anticoagulant effect to selection of the anticoagulant based on clinical variables that affect anticoagulant exposure. These variables and their interactions should be considered in choosing an alternative to warfarin and are summarized in a simple table comparing the new anticoagulants., (© 2014 John Wiley & Sons Ltd.)

Tramadol is a commonly prescribed synthetic opioid analgesic. In humans, electrocardiogram (ECG) changes consistent with sodium-channel blockade have not been described in overdoses with tramadol. We report a case of isolated tramadol overdose associated with a Brugada ECG pattern. A review of the literature reveals no previous human cases of tramadol overdose causing ECG changes consistent with sodium-channel blockade. However, in vitro blockade of sodium-channels has been demonstrated with high concentrations of tramadol. Tramadol overdose should be recognized as a cause for the manifestation of a Brugada ECG pattern in the setting of suicidal intoxication., (©2010, The Authors. No claim to original US government works.)

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.

Purpose: Characteristics of the amiodarone-warfarin interaction during long-term follow-up were studied., Methods: Medical records from patients seen in the anticoagulation clinic at the Hennepin County Medical Center between April 1998 and March 2003 were retrospectively reviewed. Patients were included if they were older than 18 years, used the anticoagulation clinic as their primary clinic for anticoagulation therapy, and were receiving combined amiodarone and warfarin therapy for at least one month. The primary study endpoint was the occurrence of International Normalized Ratios (INRs) of >5 at any time during combined warfarin-amiodarone therapy. The secondary endpoint was the frequency of warfarin dosage changes., Results: A total of 70 patients met study inclusion criteria. Of these 70, 7 had amiodarone started before warfarin initiation. Of the 2434 INR values analyzed, 43% (n = 1043) were in the target therapeutic range, 34% (n = 820) were below target range, and 23% (n = 571) were above target range. A total of 102 INR values (4%) were above 5. The relative risk of having an INR of >5 for patients on concurrent warfarin and amiodarone versus those on warfarin alone was 1.366 (p = 0.005). INRs of >5 were most common during the first 12 weeks of combined therapy, with no subsequent large peaks evident., Conclusion: Among patients treated in an anticoagulation clinic, INR values of >5 were most common during the first 12 weeks of combined therapy with amiodarone and warfarin and necessitated reduction in warfarin dosage. No other notable changes in INR or amiodarone or warfarin dosage occurred throughout the remainder of the 80-week study period.

Bigeminy is an often encountered arrhythmia in clinical practice. There are common and uncommon mechanisms for bigeminy. Typical examples are illustrated with their salient electrocardiographic and clinical features. When one encounters a bigeminal rhythm, an awareness of these numerous possibilities will facilitate arriving at the correct diagnosis, which is where quality patient care begins.

Background: The American College of Cardiology, American Heart Association, and European Society of Cardiology Board (ACC/AHA/ESC) 2001 guidelines for management of patients with atrial fibrillation (AF) include a new classification system consisting of 4 categories: first-detected episode; recurrent paroxysmal (self-terminating); recurrent persistent (requiring cardioversion); and permanent. The frequency of hospital discharges within these categories has not been reported., Methods: The new classification system was applied to 135 consecutive hospital discharges with a principal diagnosis of AF., Results: Classification of AF in these discharged patients included 74 (55%) with first-detected episode; 28 (21%) with recurrent paroxysmal AF; 17 (13%) with recurrent persistent AF; and 16 (12%) with permanent AF. Hypertension (n = 48; 35%) was the most common primary cause of AF, followed by alcohol related (n = 23; 17%), coronary artery disease (n = 20; 15%), and valvular heart disease (n = 17; 12%). For the 102 patients with first-detected and recurrent paroxysmal AF, 71 (69%) converted spontaneously to normal sinus rhythm within 48 hours of admission. Of the 48 patients with a discharge diagnosis of AF, 32 (67%) were receiving anticoagulation therapy., Conclusions: Most hospital discharges with a principal diagnosis of AF represent the first-detected episode. Diverse causes contribute to AF, and to examine them would help direct therapy. Importantly, in our analysis, 69% of those patients with first-detected or recurrent paroxysmal AF converted spontaneously to normal sinus rhythm within 48 hours of admission.

Background: Patients referred for stress echocardiography may differ significantly from those referred for stress myocardial perfusion imaging (MPI). Such differences, if present, should be considered when comparing the accuracy and discriminatory performance of these tests., Methods: We prospectively collected demographic and clinical information on all stress imaging studies performed at our institution between 1998 and 2001. The data were reviewed, summarized, and compared using the t test and chi2 test where appropriate., Results: Of 5320 stress imaging studies performed, 3383 were stress echocardiographies and 1937 were MPI studies. Patients referred for MPI were older (59 vs 54, P < .0001), and more likely to have diabetes (32% vs 20%, P < .0001), prior myocardial infarction (39% vs 15%, P < .0001), and prior revascularization (38% vs 12%, P < .0001). Pharmacologic stress testing was much more common in the MPI group (66% vs 17%, P < .0001). More patients referred for MPI had decreased left ventricular function (23% vs 7%, P < .0001) and abnormal stress test results (41% vs 18%, P < .0001)., Conclusions: Patients with a history of myocardial infarction, revascularization, or higher risk profiles are more likely to be referred for MPI compared to stress echocardiography at our institution. These differences in referral patterns are likely to exist in other centers, and it is reasonable to assume that systematic differences in test selection occur, resulting in patient populations with differing clinical risk profiles. Caution in interpreting analyses comparing the accuracy of stress imaging modalities is appropriate.

Left ventricular thrombus (LVT) is a frequent complication in patients with acute anterior myocardial infarction (MI) and in those with dilated cardiomyopathy (DCM). The clinical importance of LVT lies in its potential to embolize. The current treatment of patients with acute MI centers on reperfusion, and although controversial, the incidence of LVT complicating acute anterior MI is probably reduced when compared with historical controls. Nevertheless, stroke continues to be a clinically important complication of acute MI and is most common in patients with anterior MI, in part secondary to embolization of LVT. Therapeutic anticoagulation during acute MI reduces the incidence of LVT, and long-term anticoagulation has been associated with a reduction in recurrent infarction and ischemic stroke, but carries hemorrhagic risk. Primary treatment strategies for patients with acute MI center on reperfusion therapy followed by antiplatelet agents and pharmacologic blockade of abnormal neurohumoral mechanisms. Strategies to prevent stroke following infarction include risk stratification for development of LVT and embolism. For patients with anterior MI, particularly those with apical akinesis or dyskinesis, therapeutic anticoagulation reduces the number of LVT and cardioembolic strokes. However, the absolute number of ischemic strokes prevented with this strategy may only be marginal, given the anticoagulation risk, particularly if antiplatelet agents are used concurrently. An attractive alternative strategy is echocardiographic evaluation following anterior infarction with therapeutic anticoagulation reserved for those with demonstrable thrombus. The efficacy of this strategy, however, never has been proven in a clinical study. Primary prevention of cardioembolic stroke through therapeutic anticoagulation is controversial in patients with DCM; the greatest benefit would be expected for those with severe left ventricular dysfunction. If LVT is detected during the course of MI or DCM, therapeutic anticoagulation is usually indicated with the expectation that the majority of thrombi will resolve without clinical evidence of systemic embolism. Additional therapeutic intervention is rarely needed.

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.

Atrial fibrillation is a major clinical problem that is predicted to be encountered more frequently as the population ages. The clinical management of atrial fibrillation has become increasingly complex as new therapies and strategies have become available for ventricular rate control, conversion to sinus rhythm, maintenance of sinus rhythm, and prevention of thromboembolism. Clinical and transthoracic echocardiographic features are important in determining etiology and directing therapy for atrial fibrillation. Left atrial size, left ventricular wall thickness, and left ventricular function have independent predictive value for determining the risk of developing atrial fibrillation. Left atrial size may have predictive value in determining the success of cardioversion and maintaining sinus rhythm in selected clinical settings but has less value in the most frequently encountered group, patients with nonvalvular atrial fibrillation, in whom the duration of atrial fibrillation is the most important feature. When selecting pharmacological agents to control ventricular rate, convert to sinus rhythm, and maintain normal sinus rhythm, transthoracic echocardiography (TTE) allows noninvasive evaluation of left ventricular function and hence guides management. The combination of clinical and transthoracic echocardiographic features also allows risk stratification for thromboembolism and hemorrhagic complications in atrial fibrillation. High-risk clinical features for thromboembolism supported by epidemiological observations, results of randomized clinical trials, and meta-analyses include rheumatic valvular heart disease, prior thromboembolism, congestive heart failure, hypertension, older (> 75 years old) women, and diabetes. Small series of cases also suggest those with hyperthyroidism and hypertrophic cardiomyopathy are at high risk. TTE plays a unique role in confirming or discovering high-risk features such as rheumatic valvular disease, hypertrophic cardiomyopathy, and decreased left ventricular function. Validation of the risk stratification scheme used in the Stroke Prevention in Atrial Fibrillation-III trial is welcomed by clinicians who are faced daily with balancing the benefit and risks of anticoagulation to prevent thromboembolism in patients with atrial fibrillation.

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.

Stroke associated with atrial fibrillation (AF) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage (LAA). Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography (TEE) in patients with AF have not been defined. To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events, we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation (SPAF-III) study. Patient features, TEE findings, and subsequent cardioembolic events were correlated with velocity by multivariate analysis. Patients in AF during TEE displayed lower peak antegrade (emptying) flow velocity (Anu(p)) than those with intermittent AF in sinus rhythm during TEE (33 cm/s vs 61 cm/s, respectively, P <.0001). Anu(p) < 20 cm/s was associated with dense spontaneous echocardiographic contrast (P <.001), appendage thrombus (P <.01), and subsequent cardioembolic events (P <.01). Independent predictors of Anu(p) < 20 cm/s included age (P =.009), systolic blood pressure (P <.001), sustained AF (P =.01), ischemic heart disease (P =.01), and left atrial area (P =.04). Multivariate analysis found both Anu(p) <20 cm/s (relative risk 2.6, P =.02) and clinical risk factors (relative risk 3.3, P =.002) independently associated with LAA thrombus. LAA Anu(p) is reduced in AF and associated with spontaneous echocardiographic contrast, appendage thrombus, and cardioembolic stroke. Systolic hypertension and aortic atherosclerosis, independent clinical predictors of stroke in patients with AF, also correlated with LAA Anu(p). Our results support the role of reduced LAA Anu(p) in the generation of stasis, thrombus formation, and embolism in patients with AF, although other mechanisms also contribute to stroke.

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.

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.

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.

Background: After case reports of cardiac-valve abnormalities related to the use of appetite suppressants were published, we undertook a study to determine the prevalence of the problem using transthoracic echocardiography., Methods: We examined patients who had taken dexfenfluramine alone, dexfenfluramine and phentermine, or fenfluramine and phentermine for various periods. We enrolled obese patients who had taken or were taking these agents during open-label trials from January 1994 through August 1997. We also recruited subjects who had not taken appetite suppressants and who were matched to the patients for sex, height, and pretreatment age and body-mass index. The presence of cardiac-valve abnormalities, defined by the Food and Drug Administration and Centers for Disease Control and Prevention as at least mild aortic-valve or moderate mitral-valve insufficiency, was determined independently by at least two cardiologists. Multivariate logistic-regression analysis was used to identify factors associated with cardiac-valve abnormalities., Results: Echocardiograms were available for 257 patients and 239 control subjects. The association between the use of any appetite suppressant and cardiac-valve abnormalities was analyzed in a final matched group of 233 pairs of patients and controls. A total of 1.3 percent of the controls (3 of 233) and 22.7 percent of the patients (53 of 233) met the case definition for cardiac-valve abnormalities (odds ratio, 22.6; 95 percent confidence interval, 7.1 to 114.2; P<0.001). The odds ratio for such cardiac-valve abnormalities was 12.7 (95 percent confidence interval, 2.9 to 56.4) with the use of dexfenfluramine alone, 24.5 (5.9 to 102.2) with the use of dexfenfluramine and phentermine, and 26.3 (7.9 to 87.1) with the use of fenfluramine and phentermine., Conclusions: Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or dexfenfluramine and phentermine had a significantly higher prevalence of cardiac valvular insufficiency than a matched group of control subjects.

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.

Ten patients with isolated right atrial tamponade complicating open heart surgery were identified over a 3.5-year period at three institutions. Clinical manifestations varied but were typically those of decreased perfusion with elevated central venous pressure. Hemodynamically these patients had systemic hypotension and tachycardia with elevated central venous pressure but without elevation of pulmonary artery or pulmonary artery wedge pressures. The correct diagnosis in each case was established by echocardiography; 7 via the transthoracic and 3 via the transesophageal approach. The typical echocardiographic feature was an extrinsic extracardiac mass compressing the atrium. Doppler findings included high flow velocities through the right atria, and color flow demonstrated narrow color jets through compressed, slit-like right atria. Surgical exploration confirmed these findings in each case. We conclude that the combination of clinical awareness and appropriate hemodynamic evaluation can alert the physician to the possibility of isolated right atrial hematoma causing decreased perfusion and/or shock following open heart surgery. Echocardiography using either the transthoracic or transesophageal approach can establish the diagnosis and lead to timely surgical intervention.

Cardioembolism is responsible for a significant number of systemic emboli including approximately 15% of all ischemic strokes. Transthoracic echocardiography has contributed to the understanding of cardioembolism and has been used to detect specific and potential cardiac sources of systemic emboli and risk stratify patients with specific clinical findings for subsequent cardiovascular events. Findings from transthoracic echocardiography indicate that stasis is an important prerequisite for intracardiac thrombosis while reversal of stasis and thrombolysis appear operative in embolism of existing thrombus. Transthoracic echocardiography allows a sensitive and specific noninvasive means to detect left ventricular thrombus, valvular vegetation, and intracardiac tumor, lesions that are directly responsible for cardioembolism. Transthoracic echocardiography can also detect lesions that could potentially contribute to cardioembolism but are not specific causes. Examples of these potential lesions include mitral valve prolapse, patent foramen ovale, and interatrial septal aneurysm. Finally, population-based studies and prospective clinical trials have indicated that the results of transthoracic echocardiography have predictive value for subsequent cardiovascular events and hence provide a means for stratification of patients at risk for cardioembolism. The latter is most notable for the group of patients with nonvalvular atrial fibrillation where left ventricular dysfunction and increased left atrial size are independent predictors for subsequent stroke.

Blood pressure (BP) may increase in hemodialysis patients during treatment of anemia with recombinant human erythropoietin (r-HuEPO). Since fluid volume is a determinant of BP in dialysis patients, changes in body fluid spaces during r-HuEPO therapy could affect BP. Thus, 51Cr-labeled red blood cell (RBC) volume, inulin extracellular fluid (ECF) volume, and urea total body water (TBW), as well as cardiac output, plasma renin activity (PRA), and plasma aldosterone concentration were determined postdialysis before and after r-HuEPO therapy in patients in whom changes in BP could be managed by ultrafiltration alone. Eleven patients entered the study: one had a renal transplant and two required addition of antihypertensive drug therapy and were excluded; eight, of whom two required antihypertensive drug therapy following the study, were included in the analyses. Results revealed an increase in predialysis hemoglobin from 67 to 113 g/L (6.7 to 11.3 g/dL) (P = 0.001) during 18 +/- 6 weeks of therapy. Predialysis diastolic BP increased from 80 to 85 mm Hg (P = 0.07), while postdialysis diastolic BP was unchanged at 73 mm Hg. 51Cr-RBC volume increased, from 0.7 to 1.3 L (P = 0.004). ECF tended to decrease, from 13.7 to 10.8 L (P = 0.064), while TBW decreased to a similar extent, but not significantly, 34.3 to 31.2 L (P = 0.16). Postdialysis ECF volume was positively correlated with mean arterial BP at baseline (r = 0.89, P = 0.007) and after therapy (r = 0.74, P = 0.035). However, the regression lines for this relationship were different (P = 0.022) before and after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

To study the incidence of left-ventricular thrombosis after transmural myocardial infarction, we performed serial two-dimensional echocardiography in 70 consecutive patients. Thirty-five patients had inferior-wall infarction: none had a left-ventricular thrombus. The other 35 had anterior-wall infarction: 12 had left-ventricular thrombi. Thrombi were diagnosed an average of five days after the infarction (range, one to 11 days). All patients with left-ventricular thrombi had severe apical-wall-motion abnormalities (akinesis or dyskinesis). Twenty-six of the 35 patients with anterior infarctions had apical akinesis or dyskinesis on echocardiography; left-ventricular thrombi developed in 12 of these 26 (46 per cent). We conclude that patients with severe apical-wall-motion abnormalities during acute transmural anterior myocardial infarction are at high risk for left-ventricular thrombosis. This high-risk group can be identified before the development of left-ventricular thrombi. Patients with inferior infarction or anterior infarction without a severe apical-wall-motion abnormality are at low risk.

Although ischemic involvement of the interventricular septum (IVS) may occur in patients with right ventricular infarction (RVI), the potential functional significance of such involvement has not been explored. In 10 patients with hemodynamically evident RVI, ischemic involvement of the IVS was assessed by measuring IVS systolic thickening on M-mode echocardiography. Six patients (group I) had decreased IVS systolic thickening, an echocardiographic indicator of ischemia, or infarction, while four (group II) did not. Group I had significantly higher right ventricular filling pressures (19 +/- 3 vs 12 +/- 5 mm Hg, p = 0.04) and right ventricular end-diastolic echocardiographic dimensions (32 +/- 8 vs 20 +/- 3 mm; p = 0.02) than group II. Paradoxic septal motion was noted only in group I patients (p = 0.01). Left ventricular filling pressures, left ventricular end-diastolic dimensions, and systolic thickening of the left ventricular posterior wall (LVPW) were not significantly different between the groups. Three group I patients died; all had decreased systolic thickening of both the IVS and LVPW. In each, autopsy confirmed infarction of the right ventricular free wall, IVS, and LVPW. In patients with right ventricular infarction, ischemic involvement of the interventricular septum may have important consequences for both right and left ventricular function.

The recent availability of two-dimensional echocardiography (2DE) has fostered the expectation that cardiac embolic sources could be identified or excluded with certitude in ischemic stroke patients. As a screening procedure, 2DE has had a low yield. In selected patients, 2DE holds promise as a useful diagnostic test. Stroke patients who may benefit from 2DE include patients under age 45, patients with suspected left atrial myxoma, and patients with known infective endocarditis, prosthetic heart valves, or rheumatic valvular heart disease. In patients with ischemic heart disease, the yield of useful information from 2DE will be low but may, on occasion, influence management.