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In patients with cardiac amyloidosis, pericardial involvement is common, with up to half of patients presenting with pericardial effusions. The pathophysiological mechanisms of pericardial pathology in cardiac amyloidosis include chronic elevations in right-sided filling pressures, myocardial and pericardial inflammation due to cytotoxic effects of amyloid deposits, and renal involvement with subsequent uremia and hypoalbuminemia. The pericardial effusions are typically small; however, several cases of life-threatening cardiac tamponade with hemorrhagic effusions have been described as a presenting clinical scenario. Constrictive pericarditis can also occur due to amyloidosis and its identification presents a clinical challenge in patients with cardiac amyloidosis who concurrently manifest signs of restrictive cardiomyopathy. Multimodality imaging, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, is useful in the evaluation and management of this patient population. The recognition of pericardial effusion is important in the risk stratification of patients with cardiac amyloidosis as its presence confers a poor prognosis. However, specific treatment aimed at the effusions themselves is seldom indicated. Cardiac tamponade and constrictive pericarditis may necessitate pericardiocentesis and pericardiectomy, respectively., Competing Interests: Declaration of competing interest Dr. Klein reports serving on the advisory boards for Sobi and Pfizer. The other authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Left ventricular (LV) diastolic dysfunction results from a combination of impaired relaxation, reduced restoring forces, and increased chamber stiffness. Noninvasive assessment of diastology uses a multiparametric approach involving surrogate markers of increased filling pressures, which include mitral inflow, septal and lateral annular velocities, tricuspid regurgitation velocity, and left atrial volume index. However, these parameters must be used cautiously. This is because the traditional algorithms for evaluating diastolic function and estimation of LV filling pressures (LVFPs), as recommended by the American Society of Echocardiography and European Association of Cardiovascular Imaging 2016 guidelines, do not apply to unique patients with underlying cardiomyopathies, significant valvular disease, conduction abnormalities, arrhythmias, LV assist devices, and heart transplants, which alter the relation between the conventional indexes of diastolic function and LVFP. The purpose of this review is to provide solutions for evaluating LVFP through illustrative examples of these special populations, incorporating supplemental Doppler indexes, such as isovolumic relaxation time, mitral deceleration time, and pulmonary venous flow analysis, as needed to formulate a more comprehensive approach., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Infective endocarditis (IE) is associated with marked morbidity and mortality in the United States and parallels the opioid pandemic. Few studies explore this interaction and its effect on clinical outcomes. We analyzed contemporary patients admitted with IE to determine predictors of readmission in the United States. The 2017 National Readmission Database was used to identify index admissions in adults with the diagnosis of IE, based on the International Classification of Disease, 10th Revision codes. The primary outcome of interest was 30-day readmission. Secondary outcomes were mortality, hospital charges, and predictors of hospitalization readmission. Of 40,413 index admissions for IE, 5,558 patients (13.8%) were readmitted within 30 days. Patients who were readmitted were younger (55 ± 20 vs 61 ± 19 years, p <0.001) and more likely to have end-stage renal disease (12.2% vs 10.5%, p <0.001), hepatitis C virus (19.4% vs 12.6%, p <0.001), HIV (1.8% vs 1.2%, p = 0.001), opioid abuse (23.9% vs 15%, p <0.001), cocaine use (7.3% vs 4.4%, p <0.001), and other substance abuse (8.5 vs 5.6, p <0.001). Patients readmitted were less likely to have diabetes mellitus (27.8% vs 29.4%, p = 0.01), hypertension (56.9% vs 64%, p <0.001), heart failure (37.7% vs 40%, p <0.001), chronic kidney disease (31.2% vs 32%, p <0.001), and peripheral vascular disease (3.6% vs 4.6%, p = 0.001). The median cost of index admission for the total cohort was $84,325 (39,922 to 190,492). After adjusting for age, diabetes mellitus, heart failure, hypertension, and end-stage renal disease, opioid abuse (odds ratio [OR] 1.34; 95% confidence interval [CI] 1.23 to 1.46; p <0.001), cocaine use (OR 1.32; 95% CI 1.17 to 1.48; p <0.001), other substance abuse (OR 1.16; 95% CI 1.04 to 1.30; p = 0.008), and hepatitis C virus (OR 1.32; 95% CI 1.21 to 1.43; p <0.001) correlated with higher odds of 30-day readmission. These factors may present targets for future intervention., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pericardial disease secondary to sarcoidosis is a rare clinical entity with no observational studies in previous research. Therefore, we evaluated reported cases of pericarditis because of sarcoidosis to further understand its diagnosis and management. We performed a systematic review of previous research until December 16, 2020 in MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. Case reports and case series demonstrating pericardial involvement in sarcoidosis were included. Fourteen reports with a total of 27 patients were identified. Dyspnea (82%) was the most common presentation, with the lungs being the primary site of sarcoidosis in most patients (77%). The most frequently encountered pericardial manifestations were pericardial effusion (89%), constrictive pericarditis and cardiac tamponade (48%). Management of these patients included use of corticosteroids (82%), colchicine (11%), and nonsteroidal anti-inflammatory agents (7%). Similar to the general population, the most common intervention in these patients was pericardiocentesis (59%), pericardial window (30%), and pericardiectomy (19%). Overall, the majority of this population (70%) achieved clinical improvement during median follow-up time of 8 months. In conclusion, the prevalence and incidence of sarcoid-induced pericarditial disease remain unclear. Clinical manifestations of pericardial involvement are variable, though many patients present with asymptomatic pericardial effusions. No consensus exists on the treatment of this special population, but corticosteroids and combination therapies are considered first-line therapies because of their efficacy in suppressing pericardial inflammation and underlying sarcoidosis. Patients with refractory cases of pericarditis may also benefit therapeutically from the addition of nonsteroidal anti-inflammatory agents, colchicine, and/or biologics., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nonsteroidal anti-inflammatory drugs and colchicine remain the standard of care as the initial treatment of acute pericarditis. Corticosteroids and traditional immunosuppressive medications are often added if patients develop recurrent symptoms and remain medically refractory. There has been growing interest in the use of interleukin-1 receptor antagonists (IL-1RAs) in managing pericarditis, especially, in medically refractory cases. Anakinra-Treatment for Recurrent Idiopathic Pericarditis is a recent pilot trial showing a benefit of using the IL-1RA, anakinra, in recurrent pericarditis. Publications remain limited and more outcomes trials are needed. This review focuses on the mechanism of action, clinical utility, current, and future studies that investigate the role of IL-1RAs in the management of recurrent pericarditis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Constrictive Pericarditis (CP) is a curable and reversible form of severe diastolic heart failure. We aimed to investigate the diagnostic accuracy of published echocardiographic Mayo Clinic Criteria in differentiating 107 patients with surgically proven CP from 30 patients with restrictive cardiomyopathy due to cardiac Amyloidosis. Five principal echocardiographic and Doppler variables were remeasured on preoperative transthoracic echocardiogram namely (1) respiration-related ventricular septal shift; (2) respiratory variation in mitral inflow E pulsed Doppler velocity; 3) tissue Doppler medial mitral annular e' velocity; (4) ratio of medial mitral annular e' to lateral mitral annular e' velocity; and 5) hepatic vein (HV) pulsed Doppler diastolic flow reversal ratio. Etiology of CP included viral/idiopathic or autoimmune (75%), postcardiac surgery (13%) and postradiation (7%). Univariate logistic regression analysis showed that (1) respiration related ventricular septal shift, (2) percentage change in Mitral E velocity, (3) medial e' velocity ≥9 cm/sec, (4) medial e'/lateral e' ratio ≥0.91, (5) HV diastolic reversal ratio ≥0.79 were associated with the diagnosis of CP. Multivariable logistic regression analyses showed that medial e' velocity ≥9 cm/s was independently associated with the diagnosis of CP. Respiration related ventricular septal shift had the highest sensitivity, whereas medial e' velocity ≥9 cm/s has the highest specificity to diagnose CP (Areas under curves 0.99, p 0.001). Combining respiration related ventricular septal shift with medial e' velocity ≥9 cm/s gave a desirable sensitivity (80%) and specificity (92%). Adding reversal ratio to this combination further increased the specificity (97%) but dropped the sensitivity (70%) to diagnose CP., (Copyright © 2019 Elsevier Inc. All rights reserved.)

With the increased use of medical imaging, there has been an increase in the numbers of pericardial cysts identified. However, there is a paucity of data regarding the clinical course for pericardial cysts. Hence, we aimed to study the clinical features and natural history of pericardial cysts. We retrospectively studied all patients with the diagnosis of pericardial cysts based on computed tomography (CT) chest or cardiac magnetic resonance imaging (CMR) between 2008 and 2014. The maximum diameter of the cyst was measured at the initial study (CT/CMR) and was compared with the most recent follow-up imaging modality of the same type if available. A change in the maximum diameter more than 10% was considered significant. We included 103 patients in the study; 89% were asymptomatic and 67% were females. Twenty-nine asymptomatic patients had repeat imaging with the same modality (CT/CMR) with a mean follow-up of 23 months. The maximum cyst diameter decreased by a mean of 25% in 34% of the patients and increased by a mean of 13% in 17% of the patients. The remaining patients (48%) had no significant change. All 29 patients remained asymptomatic. In conclusion, most pericardial cyst cases were asymptomatic. On repeat imaging, approximately 1/3 of pericardial cysts were found to decrease in size, whereas interval enlargement was infrequent and unlikely to be clinically relevant. Therefore, within the limitations of our study, serial imaging in asymptomatic patients with CT or CMR does not appear to impact management decisions., (Copyright © 2018. Published by Elsevier Inc.)

Comparative outcomes of patients undergoing pericardiocentesis or pericardial window are limited. Development of pericardial effusion after cardiac surgery is common but no data exist to guide best management. Procedural billing codes and Cleveland Clinic surgical registries were used to identify 1,281 patients who underwent either pericardiocentesis or surgical pericardial window between January 2000 and December 2012. The 656 patients undergoing an intervention for a pericardial effusion secondary to cardiac surgery were also compared. Propensity scoring was used to identify well-matched patients in each group. In the overall cohort, in-hospital mortality was similar between the group undergoing pericardiocentesis and surgical drainage (5.3% vs 4.4%, p = 0.49). Similar outcomes were found in the propensity-matched group (4.9% vs 6.1%, p = 0.55). Re-accumulation was more common after pericardiocentesis (24% vs 10%, p <0.0001) and remained in the matched cohorts (23% vs 9%, p <0.0001). The secondary outcome of hemodynamic instability after the procedure was more common in the pericardial window group in both the unmatched (5.2% vs 2.9%, p = 0.036) and matched cohorts (6.1% vs 2.0%, p = 0.022). In the subgroup of patients with a pericardial effusion secondary to cardiac surgery, there was a lower mortality after pericardiocentesis in the unmatched group (1.5% vs 4.6%, p = 0.024); however, after adjustment, this difference in mortality was no longer present (2.6% vs 4.5%, p = 0.36). In conclusion, both pericardiocentesis and surgical pericardial window are safe and effective treatment strategies for the patient with a pericardial effusion. In our study there were no significant differences in mortality in patients undergoing either procedure. Observed differences in outcomes with regard to recurrence rates, hemodynamic instability, and in those with postcardiac surgery effusions may help to guide the clinician in management of the patient requiring therapeutic or diagnostic drainage of a pericardial effusion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recurrent pericarditis (RP) affects 10% to 50% of patients with acute pericarditis. The use of steroids has been associated with increased recurrence rate of pericarditis, along with known major side effects. Cardiac magnetic resonance imaging (CMR) is more frequently used to assess pericardial inflammation and less commonly to guide therapy. The aim of this study was to assess the utility of CMR in the management of RP compared with standard therapy. A total of 507 consecutive patients with RP after the first attack, all of whom were treated with colchicine and nonsteroidal anti-inflammatory drugs as first-line therapy, were retrospectively evaluated. There were 257 patients who were treated with medications and received CMR-guided therapy (group 1) and 250 patients who were treated with medications without CMR (group 2). The 2 groups had similar baseline characteristics and follow-up periods (17 ± 7.9 vs 16.3 ± 16.2 months, respectively, p = 0.97). CMR was used to assess the presence of pericardial inflammation, and on the basis of the results, the clinician made changes to the steroid dose dictated by the severity of inflammation. There was no significant difference in the incidence of constrictive pericarditis, pericardial window, or pericardiectomy between groups during the follow-up. However, group 2 patients had a larger number of steroid pulse therapies (defined as prednisone 50 mg/day orally for 10 days and tapering to none over 4 weeks), and higher overall total milligrams of steroid administered compared with the CMR group (p = 0.003 and p = 0.001, respectively). Recurrence and pericardiocentesis rates were lower in group 1 (p <0.0001). In conclusion, CMR-guided therapy modulates the management of RP. This approach decreased pericarditis recurrence and exposure to steroids., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Postpericardiotomy syndrome (PPS) may be associated with tamponade and pericardial constriction that may require procedural intervention. The aim of this study was to identify clinical features associated with adverse events requiring procedural intervention in patients with PPS. A total of 239 patients who developed PPS after cardiac surgery were monitored for 12 months. PPS was diagnosed if 2 of the 5 following findings were present: fever without infection, pleuritic pain, friction rub, pleural effusion, and pericardial effusion (<60 days after surgery). The primary end point was the development of pericardial effusion or pericardial constriction requiring procedural intervention. Among 239 patients with PPS, 75 (31%) required procedural intervention. In a univariate analysis, the odds of a procedural intervention were decreased with older age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96 to 0.99) and with colchicine used in combination with anti-inflammatory agents (OR 0.45, 95% CI 0.26 to 0.79). However, the odds were increased in patients with preoperative heart failure (OR 1.84, 95% CI 1 to 3.39) and early postoperative constrictive physiology (OR 5.77, 95% CI 2.62 to 12.7). After multivariate adjustment, treatment with colchicine along with anti-inflammatory agents was associated with lower odds of requiring intervention (OR 0.43, 95% CI 0.95 to 0.99). Independent positive predictors of procedural intervention included age (OR 0.97, 95% CI 0.95 to 0.99), time to PPS (OR 0.97, 95% CI 0.95 to 0.99), and early postoperative constrictive physiology (OR 6.23, 95% CI 2.04 to 19.07). In conclusion, younger age, early-onset PPS, and postoperative constrictive physiology were associated with the need for procedural intervention in patients with PPS, whereas colchicine was associated with reduced odds of adverse events and procedural intervention., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The ratio of early transmitral flow velocity (E) to mitral annular velocity (E') is considered a predictor of pulmonary capillary wedge pressure (PCWP). In a previous small study, the paradoxical relation between PCWP and E/E' ratio has been described in patients with constrictive pericarditis (CP). We sought to test this paradoxical relation in a larger cohort. We retrospectively identified 49 patients with surgically confirmed CP (40 men; mean age 61 ± 10 years) who underwent right-sided cardiac catheterization with PCWP measurement, preceded by an echocardiographic study. Of these, 48 patients underwent either computed tomography or magnetic resonance imaging to measure pericardial thickness on the lateral side of the left ventricular wall. Mean interval time between echocardiogram and right-sided cardiac catheterization was 1.5 ± 3.8 days. There were no significant correlations between mean, medial, or lateral E/E' and PCWP (r = -0.17, 95% confidence interval [CI] -0.43 to -0.12; r = -0.17, 95% CI -0.43 to -0.12; and r = -0.12, 95% CI -0.39 to -0.17, respectively). Similarly, there was no correlation between mean E/E' and brain natriuretic peptide (Spearman r = -0.17, p = NS). Patients with increased pericardial thickness (defined as >4 mm) had both lower lateral peak systolic annular velocity (S') and lower lateral S' integral (7.8 ± 2.4 vs 9.6 ± 2.4, p = 0.02 and 13.2 ± 4.2 vs 15.9 ± 4.7, p = 0.04, respectively). In patients with CP, there were no correlations between septal, lateral, or mean E/E' and PCWP. In conclusion, E/E' is not predictive of filling pressures in patients with CP, and perhaps the "annulus paradoxus" phenomenon should be revisited. The relation between the mitral annular velocity and thickness of the parietal pericardium may affect this phenomenon., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The relation between left atrial (LA) mechanics and left ventricular (LV) diastolic function and adverse cardiovascular events are not well established in chronic systolic heart failure (HF). In 108 patients, we performed comprehensive echocardiography with an assessment of LA global longitudinal strain (LAε) by Velocity Vector Imaging. We also performed complete diastolic examinations including mitral inflow, pulmonary vein flow, and tissue Doppler. Death, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort (age 57 ± 15 years, LV ejection fraction 25 ± 6%), mean global LA negative (εnegative), positive (εpositive), and total ε (εtotal) were -6.8 ± 4.4%, 7.7 ± 5.7%, and 14.5 ± 8.2%, respectively. All LAε indexes correlated with individual indexes of LV diastolic dysfunction, including mitral flow early (E) to late diastolic velocity ratio (p <0.05 for all), mitral deceleration time (p <0.01 for all), E to early diastolic velocity of the septal mitral annulus (e') ratio (p <0.05 for all), pulmonary vein flow systolic to diastolic velocity ratio (p <0.001 for all), and maximal LA volume index (p <0.01 for all). All LAε indexes increased across diastolic stage (p <0.001 for all). In multivariate logistic regression analysis, LAεnegative and LAεtotal were associated with the presence of LV diastolic dysfunction grade III even after adjustment for E/e' septal and LA volume index. In Cox proportional hazards analysis, lower magnitude LAεnegative predicted long-term adverse clinical events. In conclusion, more impaired LA mechanics are associated with more severe diastolic dysfunction and predict long-term adverse events in patients with chronic systolic HF., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The CHADS₂ scoring system was found to be a good predictor for risk stratification of stroke in patients with atrial fibrillation. The effectiveness of this scoring system in assessing thrombogenic milieu before direct-current cardioversion has not yet fully been established on a large scale. In this study, data from 2,369 consecutive patients in whom transesophageal echocardiography was performed for screening before direct-current cardioversion from 1999 to 2008 were analyzed. Left atrial (LA) or LA appendage (LAA) thrombogenic milieu (spontaneous echo contrast, sludge, and thrombus) was investigated. The results were correlated with CHADS₂ score findings. The mean age was 66 ± 13 years, and the ratio of men to women was 2.2:1. CHADS₂ scores of 0, 1, 2, 3, 4, 5 and 6 were present in 11%, 25%, 30%, 22%, 8%, 3%, and 1% of the studies, respectively. The prevalence of LA or LAA sludge or thrombus increased with increasing CHADS₂ scores (2.3%, 7%, 8.5%, 9.9%, 12.3%, and 14.1% for scores of 0, 1, 2, 3, 4, and 5 or 6, respectively, p = 0.01). In a multivariate model, an ejection fraction ≤20% was the best predictor of LA or LAA sludge or thrombus (odds ratio 2.99, p <0.001). In conclusion, transesophageal echocardiographic markers of thrombogenic milieu were highly correlated with increasing CHADS₂ scores in patients who underwent transesophageal echocardiography-guided cardioversion. Giving more value to echocardiographic findings, such as the left ventricular ejection fraction, and its different levels (especially an ejection fraction ≤20%) might improve the precision of the CHADS₂ scoring scheme to predict thrombogenic milieu in the left atrium or LAA as a surrogate to cardioembolic risk in patients with atrial fibrillation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The CHADS(2) (congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke or transient ischemic attack [2 points]) scoring scheme has been found to be a good predictor of stroke risk in patients with nonvalvular atrial fibrillation (AF). However, the value of the CHADS(2) scoring system in the risk stratification of patients with AF who undergo direct-current cardioversion has not yet been specifically investigated. In this study, a subgroup of 541 patients from the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study who had AF for >48 hours and planned to undergo transesophageal echocardiography before direct-current cardioversion were enrolled. Each patient had a CHADS(2) score calculated. Of the patients with CHADS(2) scores of 0, 14 (10%) were found to have left atrial appendage thrombi on transesophageal echocardiography. After 6 months of follow up, patients with CHADS(2) scores of 3 to 6 showed a significantly higher mortality rate in comparison with patients with lower CHADS(2) scores (4.3% vs 0.5%, p = 0.004), despite their similar prevalence of left atrial appendage thrombus and stroke (thrombus: 13.4% vs 11.6%, p = 0.60; stroke: 0% vs 0.3%, p = 0.70). In conclusion, the CHADS(2) scoring system may be useful for predicting short-term mortality risk in patients with AF receiving elective direct-current cardioversion. However, in the preprocedural risk assessment of these patients, the CHADS(2) scoring system is not reliable in predicting risk for left atrial appendage thrombus formation, especially in patients with low CHADS(2) scores., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Galectin-3 plays an important role in fibroblast activation and fibrosis in animal models. Increased galectin-3 levels are associated with poor long-term survival in heart failure (HF). We examined the relation between plasma galectin-3 levels and myocardial indexes of systolic HF. We measured plasma galectin-3 in 133 subjects with chronic HF and 45 with advanced decompensated HF using echocardiographic and hemodynamic evaluations. In the chronic HF cohort, median plasma galectin-3 level was 13.9 ng/ml (interquartile range 12.1 to 16.9). Higher galectin-3 was associated with more advanced age (r = 0.22, p = 0.010), poor renal function (estimated glomerular filtration rate, r = -0.24, p = 0.007; cystatin C, r = 0.38, p <0.0001) and predicted all-cause mortality (hazard ratio 1.86, 95% confidence interval 1.36 to 2.54, p <0.001). In multivariate analysis, galectin-3 remained an independent predictor of all-cause mortality after adjusting for age, estimated glomerular filtration rate, left ventricular (LV) ejection fraction, and mitral early diastolic myocardial relaxation velocity at septal mitral annulus (hazard ratio 1.94, 95% confidence interval 1.30 to 2.91, p = 0.001). However, galectin-3 did not predict the combined end point of all-cause mortality, cardiac transplantation, or HF hospitalization (p >0.05). Furthermore, there were no relations between galectin-3 and LV end-diastolic volume index (r = -0.05, p = 0.61), LV ejection fraction (r = 0.10, p = 0.25), or LV diastolic function (mitral early diastolic myocardial relaxation velocity at septal mitral annulus, r = 0.06, p = 0.52; left atrial volume index, r = 0.08, p = 0.41). In the advanced decompensated HF cohort, we did not observe any relation between galectin-3 and echocardiographic or hemodynamic indexes. In conclusion, high plasma galectin-3 levels were associated with renal insufficiency and poorer survival in patients with chronic systolic HF. However, we did not observe a relation between galectin-3 and echocardiographic or hemodynamic indexes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Definity and Optison are perflutren-based ultrasound contrast agents used in echocardiography. United States Food and Drug Administration warnings regarding serious cardiopulmonary reactions and death after Definity administration highlighted the limited safety data in patients who undergo contrast stress echocardiography. From 1998 and 2007, 2,022 patients underwent dobutamine stress echocardiography and 2,764 underwent exercise stress echocardiography with contrast at the Cleveland Clinic. The echocardiographic database, patient records, and the Social Security Death Index were reviewed for the timing and cause of death, severe adverse events, arrhythmias, and symptoms. Complication rates for contrast dobutamine stress echocardiography and exercise stress echocardiography were compared with those in a control group of 5,012 patients matched for test year and type who did not receive contrast. Ninety-five percent of studies were performed in outpatients. There were no differences in the rates of severe adverse events (0.19% vs 0.17%, p = 0.7), death within 24 hours (0% vs 0.04%, p = 0.1), cardiac arrest (0.04% vs 0.04%, p = 0.96), and sustained ventricular tachycardia (0.2% vs 0.1%, p = 0.32) between patients receiving and not receiving intravenous contrast, respectively. In conclusion, severe adverse reactions to intravenous contrast agents during stress echocardiography are uncommon. Contrast use does not add to the baseline risk for severe adverse events in patients who undergo stress echocardiography.

The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) II study compared enoxaparin with unfractionated heparin (UFH) as bridging therapy in patients with atrial fibrillation >2 days in duration who underwent transesophageal echocardiography-guided cardioversion. In the present study, the anticoagulant and anti-inflammatory effects of enoxaparin and UFH were compared at prespecified time points. In a randomized substudy of 155 patients from 17 clinical sites, the anticoagulant activity of enoxaparin (n = 76) was compared with that of UFH (n = 79). Blood samples were drawn at enrollment, on day 2, and on day 4 in the 2 groups. Blood samples were evaluated for anticoagulant activity by measuring the activated partial thromboplastin time, anti-Xa, anti-IIa, and tissue factor pathway inhibitor levels. In addition, levels of coagulation activation (by thrombin antithrombin complex) and inflammation (by highly sensitive C-reactive protein) were measured. The results of this substudy showed that the anti-Xa levels in the 2 groups increased on day 2. Similar increases in anti-Xa were observed on day 4. The anti-Xa levels and tissue factor pathway inhibitor levels were higher in the enoxaparin group compared with the UFH group on days 2 and 4. However, as expected, the anti-IIa levels in the UFH group were higher. In addition, markers of coagulation activation and inflammation were increased in patients with atrial fibrillation. Treatment with enoxaparin significantly decreased thrombin antithrombin complex levels compared with treatment with UFH. Highly sensitive C-reactive protein levels were also decreased after treatment in the 2 groups. In conclusion, the ACUTE II study showed that the use of enoxaparin for bridging therapy in patients with atrial fibrillation who underwent transesophageal echocardiography-guided cardioversion resulted in a more predictable and stronger anticoagulant response than that observed with UFH. Markers of inflammation were also decreased in the 2 groups.

High-sensitivity C-reactive protein (hs-CRP) is a hepatocyte-derived inflammatory cytokine shown to be increased in the setting of acute heart failure (HF), particularly with increased intracardiac filling pressures. In the chronic HF setting, the relation between hs-CRP and echocardiographic indexes of left ventricular (LV) diastolic performance has not been examined. We measured plasma hs-CRP levels using a particle-enhanced immunonephelometry assay (Dade Behring, Inc., Deerfield, Illinois) in 136 subjects with chronic HF (LV ejection fraction [EF]

In 1997, the US Food and Drug Administration (FDA) reported valvular regurgitation (aortic regurgitation [AR] mild or greater and/or mitral regurgitation [MR] moderate or greater) in 32.8% of patients treated with anorexigens. This study sought to determine the natural history of valvular regurgitation in patients who were included in the FDA's original report. This was a nonrandomized, natural history study of these subjects. Cohort I consisted of 155 of 186 patients (83%) who were reported to the FDA. Cohort II consisted of a similar group of 311 patients who were not included. Initial echocardiograms were obtained for medical indications before the study initiation, and study echocardiograms were standardized and obtained at 3-month intervals. Level III echocardiographers performed blinded, side-by-side comparison of the first and last study echocardiograms at a core laboratory. Cohorts I and II consisted of predominantly female, middle-aged, obese subjects. At enrollment, patients in cohorts I and II had mild or greater AR (17.9%, 13.5%) and moderate or greater MR (3.3%, 4.0%), respectively, which was less than in the FDA's report. At follow-up, there were no statistically significant changes in the degree of valvular regurgitation in either cohort when the first and last study echocardiograms were read side by side. In conclusion, this natural history follow-up study demonstrates that MR and AR in long-term anorexigen-treated patients was less than reported to the FDA, did not progress, and remained echocardiographically stable during the 10-month duration of the study.

The ACUTE trial randomly assigned patients who had atrial fibrillation (AF) of >2 days' duration to a transesophageal echocardiographically guided or a conventional strategy before cardioversion. In the 571 patients who underwent transesophageal echocardiography (TEE) in the ACUTE trial, we assessed the relative predictive value of baseline data derived by history, transthoracic echocardiography, and TEE for prediction of thrombus and adjudicated embolism (thromboembolism) as a composite end point. TEE was performed at 70 centers in 571 patients, 549 in the transesophageal echocardiographically guided group and 22 crossovers in the conventional group. Six patients (1.1%) who had embolism and 79 (13.8%) who had thrombi were identified in this group. Thrombus was completely resolved in 76.5% of patients who had repeat transesophageal echocardiographic procedures after 31.7 +/- 7.5 days of anticoagulation. For patients who had embolic events, none had a transesophageal echocardiographically identified thrombus; 5 of 6 (83.3%) had >/=1 transesophageal echocardiographic risk factors (including spontaneous echocardiographic contrast, aortic atheroma, patent foramen ovale, atrial septal aneurysm, mitral valve strands), and 4 of 6 (66.66%) had subtherapeutic anticoagulation or no anticoagulation. Clinical, transthoracic echocardiographic, and transesophageal echocardiographic risk factors contributed significantly to the prediction of composite thrombus/embolism. However, transesophageal echocardiographic thromboembolic risk factors were the strongest predictors of thromboembolism and provided statistically significant incremental value (chi-square 38.0, p <0.001) for identification of risk. Thus, in addition to thrombus identification, TEE has significant incremental value in the identification of patients who had high thromboembolic risk. In conclusion, this study supports the role of TEE and anticoagulation monitoring in patients who have atrial fibrillation and is useful for identifying thromboembolic risk factors.

The prognostic values of tissue Doppler imaging and color M-mode diastolic indexes were studied in 225 patients who had symptomatic systolic heart failure in the ADEPT study. The primary end point of death, transplantation, or hospitalization due to heart failure occurred in 65 patients and was independently predicted by shorter deceleration time, lower ratio of pulmonary vein systolic to diastolic velocity, and increasing levels of the ratios of early transmitral velocity to early annular velocity or velocity of propagation. For the ratio of early transmitral velocity to early annular velocity, this prediction was additive to deceleration time. Newer diastolic indexes provide an independent prediction of clinical outcomes.

The relation between C-reactive protein, an inflammatory marker, and thromboembolic risk factors was investigated in 104 patients with atrial fibrillation and found that patients with transesophageal echocardiography identified thromboembolic risk factors had greater C-reactive protein levels than those without (1.00 vs 0.302 mg/dl). C-reactive protein also correlated with clinical stroke risk factors. Increased C-reactive protein levels were also independently associated with transesophageal echocardiographic thromboembolic risk factors.

In a multicenter randomized trial, we studied a transesophageal echocardiography (TEE) guided strategy with short-term anticoagulation compared with a conventional strategy for patients with atrial fibrillation >2 days' duration and undergoing cardioversion. Composite major and minor bleeding was a predetermined secondary end point of the study. The objective of the study was to assess the incidence, location, and predictors of bleeding in the 2 treatment groups. A total of 1,222 patients were assigned to a TEE guided or conventional strategy and followed over 8 weeks. We present data on major and minor adjudicated bleeding complications for the 2 study groups during the 8-week study period. Composite major and minor bleeding complications occurred in 51 of 1,222 patients (4.2%) and were significantly lower in the TEE guided group compared with the conventional group (2.9 vs 5.5%, p = 0.025). The TEE group had fewer cancellations of cardioversion as a result of bleeding (0% vs 0.7%, p = 0.003). Major (n = 14) and minor (n = 38) bleeding complications were predominantly gastrointestinal (71.4% and 31.6%, respectively) and were associated with warfarin use. Predictors of bleeding included patient age, conventional group assignment, inpatient status, and functional status. Thus, composite major and minor bleeding complications occurred in 4.2% of the 1,222 patients and were significantly lower in the TEE guided group compared with the conventional group. Treatment variables affecting length of anticoagulant therapy in the conventional arm combined with advancing age and functional status are important concerns in patients who undergo cardioversion of atrial fibrillation.

With or without contrast, echocardiographic evaluation of left ventricular (LV) function is qualitative, subjective, and experience dependent, because it is mostly based on visual interpretation of gray-scale 2-dimensional images or, at best, relies on tedious and time-consuming manual tracing of the endocardial boundaries. Adequate endocardial visualization is essential for accurate interpretation of regional wall thickening abnormalities, which constitute the diagnostic hallmark of coronary artery disease, and for reproducible assessment of LV ejection fraction. Studies performed in the last decade have estimated the number of patients with suboptimal endocardial delineation by fundamental imaging at 30%. These studies have highlighted the problem of variable image quality as a major limitation of transthoracic echocardiography because failure to adequately visualize a segment, either at rest or during stress, may compromise the ability of this technique to identify areas of dysfunctional myocardium. Several remedies based on different technologic and methodologic approaches have been tested over the years with variable success. In this review we discuss the most recent techniques that have had a positive impact on endocardial visualization, as well as the potential benefits of these approaches.