Howard J. Willens

Echocardiographic epicardial fat: a review of research and clinical applications.

Epicardial fat plays a role in cardiovascular diseases. Because of its anatomic and functional proximity to the myocardium and its intense metabolic activity, some interactions between the heart and its visceral fat depot have been suggested. Epicardial fat can be visualized and measured using standard two-dimensional echocardiography. Standard parasternal long-axis and short-axis views permit the most accurate measurement of epicardial fat thickness overlying the right ventricle. Epicardial fat thickness is generally identified as the echo-free space between the outer wall of the myocardium and the visceral layer of pericardium and is measured perpendicularly on the free wall of the right ventricle at end-systole. Echocardiographic epicardial fat thickness ranges from a minimum of 1 mm to a maximum of almost 23 mm. Echocardiographic epicardial fat thickness clearly reflects visceral adiposity rather than general obesity. It correlates with metabolic syndrome, insulin resistance, coronary artery disease, and subclinical atherosclerosis, and therefore it might serve as a simple tool for cardiometabolic risk prediction. Substantial changes in echocardiographic epicardial fat thickness during weight-loss strategies may also suggest its use as a marker of therapeutic effect. Echocardiographic epicardial fat measurement in both clinical and research scenarios has several advantages, including its low cost, easy accessibility, rapid applicability, and good reproducibility. However, more evidence is necessary to evaluate whether echocardiographic epicardial fat thickness may become a routine way of assessing cardiovascular risk in a clinical setting.

Aortic Pressure Augmentation Predicts Adverse Cardiovascular Events in Patients With Established Coronary Artery Disease

Pulse pressure (PP), a marker of arterial stiffness, predicts cardiovascular risk. We aimed to determine whether augmentation pressure (AP) derived from the aortic pressure waveform predicts major adverse cardiovascular events (MACE) and death independently of PP in patients with established coronary artery disease (CAD). We prospectively followed-up 297 males undergoing coronary angiography for 1186±424 days. Ascending aortic pressure tracings obtained during catheterization were used to calculate AP (difference between the second and the first systolic peak). Augmentation index (AIx) was defined as AP as a percentage of PP. We evaluated whether AP and AIx can predict the risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke, or death) and death using Cox regression. All models evaluating AP included PP to assess whether AP adds to the information already provided by PP. Both AP and AIx significantly predicted MACE. The hazard ratio (HR) per 10 mm Hg increase in AP was 1.20 (95% confidence interval [CI], 1.08 to 1.34; P<0.001); the HR for each 10% increase in AIx was 1.28 (95% CI, 1.11 to 1.48; P=0.004). After adjusting for other univariate predictors of MACE, age, and other potential confounders, AP remained a significant predictor of MACE (HR per 10 mm Hg increase=1.19; 95% CI, 1.06 to 1.34; P=0.002), as did AIx (adjusted HR, 1.28; 95% CI, 1.09 to 1.50; P=0.003). AP was a significant predictor of death (HR per 10 mm Hg increase=1.18; 95% CI, 1.02 to 1.39; P=0.03). Higher AIx was associated with a trend toward increased mortality (HR=1.22; 95% CI, 0.98 to 1.52; P=0.056). Aortic AP predicts adverse outcomes in patients with CAD independently of PP and other risk markers.

Transendocardial Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells for Ischemic Cardiomyopathy: The TAC-HFT Randomized Trial

IMPORTANCE Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. OBJECTIVE To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. DESIGN, SETTING, AND PATIENTS A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. INTERVENTIONS Injections in 10 LV sites with an infusion catheter. MAIN OUTCOMES AND MEASURES Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. RESULTS No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. CONCLUSIONS AND RELEVANCE Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00768066.

Threshold Values of High-risk Echocardiographic Epicardial Fat Thickness

Objective: Echocardiographic epicardial adipose tissue is a new index of cardiac and visceral adiposity with great potential as a diagnostic tool and therapeutic target. In this study, we sought to provide threshold values of echocardiographic epicardial fat thickness associated with metabolic and anthropometric risk factors.

Adherence to appropriateness criteria for transthoracic echocardiography: comparisons between a regional department of Veterans Affairs health care system and academic practice and between physicians and mid-level providers.

We compared adherence to appropriateness criteria for transthoracic echocardiography in a Veterans Administration Medical Center (VAMC) and an academic practice and, within the VAMC, between physicians and mid-level providers. We reviewed 201 outpatient echocardiograms performed in the laboratory of an academic practice and 424 outpatient and inpatient studies performed at a VAMC. Echocardiographic examinations requested for indications addressed in the criteria were considered classified, and those for indications not addressed were considered unclassified. Classified studies were further rated as appropriate or inappropriate. Of 625 echocardiograms reviewed, 99 (16%) were unclassified. Approximately 80% of the indications for these could be assigned to 4 categories. Of the remaining 526 echocardiograms, indications were appropriate in 481 (91.4%) and inappropriate in 45 (8.6%). Among classified outpatient studies at the VAMC, mid-level providers requested significantly more studies for inappropriate indications than physicians (16.0% vs 7%, P = .024). There was no significant difference in the frequency of outpatient studies requested for inappropriate indications by VAMC and academic practice physicians (7.0% vs 9.5%, P = .558). The appropriateness criteria perform reasonably well at evaluating variations in use of echocardiography between health care systems and providers. The large majority of studies are requested for appropriate indications, although there is room for improvement.

Mobile Components Associated With Rapidly Developing Mitral Annulus Calcification in Patients With Chronic Renal Failure: Review of Mobile Elements Associated With Mitral Annulus Calcification

Mitral annulus calcification may directly cause cerebrovascular accidents by serving as a source of calcific or thrombotic emboli. This hypothesis has been supported by recent reports of mobile components associated with mitral annulus calcification detected by echocardiography. Cardiovascular calcifications, including mitral annulus calcification, are common in end‐stage renal disease and may develop and progress over a short period of time. We report two patients with mobile components associated with mitral annulus calcification and end‐stage renal disease. Serial echocardiography documented that the mitral annulus calcification in these two patients had developed rapidly. Follow‐up echocardiography in one patient demonstrated resolution of the mobile elements. (ECHOCARDIOGRAPHY, Volume 20, May 2003)

Appropriateness use criteria for transthoracic echocardiography: Relationship with radiology benefit managers preauthorization determination and comparison of the new (2010) criteria to the original (2007) criteria

BACKGROUND In response to growth in cardiac imaging, medical societies have published appropriateness use criteria (AUC) and payers have introduced preauthorization mandates, largely through radiology benefits managers (RBM). The correlation of algorithms used to determine preauthorization with the AUC is unknown. In addition, studies applying the 2007 AUC for transthoracic echocardiography revealed that many echocardiograms could not be classified. We sought to examine the impact of the revised 2010 AUC on appropriateness ratings of transthoracic echocardiograms previously classified by the 2007 AUC and the relationship of preauthorization determination to AUC rating. METHODS We reclassified indications for transthoracic echocardiography as appropriate, inappropriate, uncertain, or unclassifiable using the 2010 AUC in the same 625 patients previously reported using 2007 AUC. We also evaluated the relationship between preauthorization status by 2 RBM precertification algorithms and appropriateness rating by 2007 AUC. RESULTS The appropriateness classification of 148 (24%) transthoracic echocardiograms was changed by the updated AUC (P < .001). The number of unclassifiable echocardiograms was markedly reduced from 99 (16%) to 8 (1%), and more echocardiograms were classified as inappropriate (95 [15%] vs 45 [7%]) or uncertain (43 [7%] vs 0 [0%]). Limited correlation between the 2007 AUC rating and RBM preauthorization determinations was noted, with only moderate agreement with RBM no. 1 (90%, κ = 0.480, P < .001) and poor agreement with RBM no. 2 (72%, κ = 0.177, P < .001). CONCLUSION The updated AUC (2010) provide enhanced clinical value compared with 2007 AUC. There is limited agreement between RBM preauthorization determination and 2007 AUC rating.

Diagnosis of a Bilobed Left Atrial Appendage and Pectinate Muscles Mimicking Thrombi on Real-time 3-Dimensional Transesophageal Echocardiography

Objective. Transesophageal echocardiography (TEE)‐guided cardioversion is an established strategy for managing atrial arrhythmias and is commonly used as an alternative to the conventional approach of administering several weeks of anticoagulation before cardioversion. However, the safety of this approach depends on the exclusion of left atrial appendage (LAA) thrombi with a high level of diagnostic confidence. The objective of this case series is to explore the use of real‐time 3‐dimensional (RT3D) TEE in the precardioversion evaluation of patients with complex anatomy in their LAAs. Methods. We used RT3D TEE to further assess the LAAs of 3 patients being evaluated for cardioversion who had inconclusive 2‐dimensional (2D) TEE studies because of complex anatomic variants of the LAA. We imaged the LAA using the 3D zoom mode and rotated this image to view the LAA en face from the perspective of its ostium. Further cropping was performed as needed. Results. In all 3 patients, the additional views of the appendage obtained by RT3D TEE were decisive in excluding contraindications to cardioversion. The unique en face view of the LAA acquired with 3D TEE, which was previously unobtainable using 2D TEE, was particularly useful. In 1 patient, a bilobed LAA mimicked a thrombus. In 2 other patients, prominent pectinate muscles masqueraded as thrombi. Conclusions. Three‐dimensional TEE is valuable for the precardioversion evaluation of patients with complex anatomic variants of the LAA.

A Technique for Performing Transesophageal Echocardiography Safely in Patients With Zenker's Diverticulum

Transesophageal echocardiography was indicated for evaluation of mitral valve pathology in a patient with a Zenkers diverticulum. However, transesophageal echocardiography is potentially dangerous and therefore relatively contraindicated in such patients. Our gastroenterologist directly intubated the esophagus with a fiberoptic endoscope and introduced an overtube through which transesophageal echocardiography was performed without incident.

Cor triatriatum sinister in an adult: management guided by real time three-dimensional transesophageal echocardiography and stress echocardiography.

A 39‐year‐old female had cor triatriatum (CT) detected as an incidental finding on transthoracic echocardiography performed to evaluate chest pain. By conventional two‐ and real time three‐dimensional transesophageal echocardiography, the CT membrane had a communicating orifice connecting the accessory and main left atrial chambers that measured 1.3 × 0.8 cm. The resting mean transmembrane gradient was 2 mm Hg. The postexercise mean transmembrane gradient and pulmonary artery pressure were 6 and 40 mm Hg. Extrapolating from cutoff values for postexercise gradients and pulmonary pressures in patients with mitral stenosis, we advised deferring surgery and close clinical and echocardiographic follow up. (Echocardiography 2010;27:E132‐E136)