Jeane Mike Tsutsui

Prognostic Value of Dobutamine Stress Myocardial Contrast Perfusion Echocardiography

Background—Myocardial perfusion (MP) imaging with real-time contrast echocardiography (RTCE) improves the sensitivity of dobutamine stress echocardiography for detecting coronary artery disease. Its prognostic value is unknown. We sought to determine the value of MP and wall motion (WM) analysis during dobutamine stress echocardiography in predicting the outcome of patients with known or suspected coronary artery disease. Methods and Results—We retrospectively studied 788 patients with RTCE during dobutamine stress echocardiography using intravenous commercially available contrast agents. The incremental prognostic value of MP imaging over clinical risk factors and other echocardiographic data was examined through the use of a log-likelihood test (Cox model). During a median follow-up of 20 months, 75 events (9.6%) occurred (58 deaths, 17 nonfatal myocardial infarctions). Abnormal MP had significant incremental value over clinical factors, resting ejection fraction, and WM responses in predicting events (P<0.001). By multivariate analysis, the independent predictors of death and nonfatal myocardial infarction were resting left ventricular ejection fraction <50% (relative risk [RR], 1.9; 95% CI, 1.2 to 3.2; P=0.01), hypercholesterolemia (RR, 0.5; 95% CI, 0.3 to 0.9; P=0.01), and abnormal MP (RR, 5.2; 95% CI, 3.0 to 9.0; P<0.0001). The 3-year event free survival was 95% for patients with normal WM and MP, 82% for normal WM and abnormal MP, and 68% for abnormal WM and MP. Conclusion—MP imaging during dobutamine stress RTCE provides incremental prognostic information in patients with known or suspected coronary artery disease. Patients with normal MP have a better outcome than patients with normal WM.

Cardiopulmonary Manifestations of Hepatosplenic Schistosomiasis

Background— Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. Methods and Results— All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). Conclusions— Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease.

The use of microbubbles to target drug delivery

Ultrasound-mediated microbubbles destruction has been proposed as an innovative method for noninvasive delivering of drugs and genes to different tissues. Microbubbles are used to carry a drug or gene until a specific area of interest is reached, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. Furthermore, the ability of albumin-coated microbubbles to adhere to vascular regions with glycocalix damage or endothelial dysfunction is another possible mechanism to deliver drugs even in the absence of ultrasound. This review focuses on the characteristics of microbubbles that give them therapeutic properties and some important aspects of ultrasound parameters that are known to influence microbubble-mediated drug delivery. In addition, current studies involving this novel therapeutical application of microbubbles will be discussed.

Guidelines for the Cardiac Sonographer in the Performance of Contrast Echocardiography: A Focused Update from the American Society of Echocardiography

Thomas R. Porter, MD, FASE (Chair), Sahar Abdelmoneim, MD, J. Todd Belcik, BS, RCS, RDCS, FASE, Marti L. McCulloch,MBA, RDCS, FASE, Sharon L.Mulvagh,MD, FASE, Joan J. Olson, BS, RDCS, RVT, FASE, Charlene Porcelli, BS, RDCS, RDMS, FASE, Jeane M. Tsutsui, MD, and Kevin Wei, MD, FASE, Omaha, Nebraska; Rochester, Minnesota; Portland, Oregon; Houston, Texas; Charleston, South Carolina; S~ ao Paulo, Brazil

Effects of Transcranial Ultrasound and Intravenous Microbubbles on Blood Brain Barrier Permeability in a Large Animal Model

We sought to determine whether transtemporal-applied 1-MHz ultrasound-induced microbubble destruction may be a safe method of transiently altering blood brain barrier (BBB) permeability for drug delivery in a large animal model. Endothelial cells are an integral component of the BBB but also prevent passage of potentially therapeutic drugs. Ultrasound-mediated destruction (UMD) of microbubbles has been shown to disrupt this barrier in small animals when ultrasound is delivered through bone windows. However, the effects of temporal bone attenuation and scattering in a large animal may limit the clinical application of such a technique. Twenty-four pigs were studied. One-MHz pulsed-wave ultrasound at 2.0 W/cm(2) (20% duty cycle) across the temporal bone was applied for 30 min after intravenous injections of either albumin-coated perfluorocarbon microbubble (PESDA, 8 pigs), lipid-encapsulated perfluorocarbon microbubbles (LEMB, 8 pigs) or ultrasound alone (8 pigs). BBB leak was quantified at 30 and 120 min after insonation using Evans blue. Serial magnetic resonance imaging (MRI) was performed in nine of the pigs (3 for each group) to quantify Gadolinium leak within the parenchyma. Peak negative pressures decreased ten-fold when ultrasound was transmitted across the pig temporal bone. Despite this, spectrophotometric analysis showed that both IV LEMB and PESDA combined with transtemporal ultrasound resulted in a significant increase in Evans blue extravasation across BBB of the treated side at 30 min after insonation (p < 0.001; compared with ultrasound alone) but not at 120 min. There was significant retention of Gadolinium within the insonified parenchyma at 60 and 90 min after insonation, but not at 120 min. Oxygen saturation and arterial pressures were not changed after any microbubble injection. Intravenous microbubbles, combined with transtemporal ultrasound, can transiently increase BBB permeability in a large animal. This induced opening of BBB is reversible and may be a safe noninvasive method of achieving drug or gene delivery across the BBB.

Value of Real Time Three-Dimensional Echocardiography in Patients with Hypertrophic Cardiomyopathy: Comparison with Two-Dimensional Echocardiography and Magnetic Resonance Imaging

Real time three‐dimensional echocardiography (RT3DE) has been demonstrated to be an accurate technique to quantify left ventricular (LV) volumes and function in different patient populations. We sought to determine the value of RT3DE for evaluating patients with hypertrophic cardiomyopathy (HCM), in comparison with cardiac magnetic resonance imaging (MRI). Methods: We studied 20 consecutive patients with HCM who underwent two‐dimensional echocardiography (2DE), RT3DE, and MRI. Parameters analyzed by echocardiography and MRI included: wall thickness, LV volumes, ejection fraction (LVEF), mass, geometric index, and dyssynchrony index. Statistical analysis was performed by Lin agreement coefficient, Pearson linear correlation and Bland‐Altman model. Results: There was excellent agreement between 2DE and RT3DE (Rc = 0.92), 2DE and MRI (Rc = 0.85), and RT3DE and MRI (Rc = 0.90) for linear measurements. Agreement indexes for LV end‐diastolic and end‐systolic volumes were Rc = 0.91 and Rc = 0.91 between 2DE and RT3DE, Rc = 0.94 and Rc = 0.95 between RT3DE and MRI, and Rc = 0.89 and Rc = 0.88 between 2DE and MRI, respectively. Satisfactory agreement was observed between 2DE and RT3DE (Rc = 0.75), RT3DE and MRI (Rc = 0.83), and 2DE and MRI (Rc = 0.73) for determining LVEF, with a mild underestimation of LVEF by 2DE, and smaller variability between RT3DE and MRI. Regarding LV mass, excellent agreement was observed between RT3DE and MRI (Rc = 0.96), with bias of−6.3 g (limits of concordance = 42.22 to−54.73 g). Conclusion: In patients with HCM, RT3DE demonstrated superior performance than 2DE for the evaluation of myocardial hypertrophy, LV volumes, LVEF, and LV mass.

Diagnostic accuracy and prognostic value of dobutamine stress myocardial contrast echocardiography in patients with suspected acute coronary syndromes.

Background: Both early stress testing and cardiac troponin I (cTnI) measurements are useful in assessing the prognosis of patients with acute coronary syndrome (ACS). We sought to determine the accuracy and prognostic value of wall motion analysis (WMA) and myocardial perfusion analysis (MPA) with real‐time myocardial contrast echocardiography (RTMCE) during dobutamine stress in this patient population. Methods: We performed dobutamine stress RTMCE to assess perfusion in 158 consecutive patients (mean age: 61 ± 13 years) with chest pain and possible ACS. Of these, 119 had normal cTnI, while 39 had isolated elevations of cTnI (range: 0.5–9.0 ng/ml). Quantitative angiography was performed within 1 month of RTMCE in 61 patients. Patients were followed for 16 months (range: 6–46 months). Cardiac events included death, nonfatal myocardial infarction, recurrent unstable angina, or need for urgent revascularization. Results: The sensitivity, specificity, and accuracy of MPA for detecting a >50% coronary stenosis were 92%, 77%, and 88%, respectively, while they were 62%, 85%, and 67% for WMA. Three‐year event‐free survival was 87% in patients with negative WMA and MPA, 49% in those with positive WMA and MPA, and 51% in patients with negative WMA but positive MPA. Age‐adjusted multivariate analysis demonstrated that the only independent predictors of cardiac events were a positive MPA (hazard ratio = 3.23; 95% CI = 1.23–8.49) and male sex (hazard ratio = 3.29; 95% CI = 1.21–8.97). Conclusions: In patients suspected of having an ACS, RTMCE improved the accuracy of dobutamine stress echocardiography for detecting coronary artery disease, and was an independent predictor of outcome.

The Clinical Use of Stress Echocardiography in Non-Ischaemic Heart Disease: Recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography

A unique and highly versatile technique, stress echocardiography (SE) is increasingly recognized for its utility in the evaluation of non-ischaemic heart disease. SE allows for simultaneous assessment of myocardial function and haemodynamics under physiological or pharmacological conditions. Due to its diagnostic and prognostic value, SE has become widely implemented to assess various conditions other than ischaemic heart disease. It has thus become essential to establish guidance for its applications and performance in the area of non-ischaemic heart disease. This paper summarizes these recommendations.

Exercise Training and Caloric Restriction Prevent Reduction in Cardiac Ca2+-Handling Protein Profile in Obese Rats

Previous studies show that exercise training and caloric restriction improve cardiac function in obesity. However, the molecular mechanisms underlying this effect on cardiac function remain unknown. Thus, we studied the effect of exercise training and/or caloric restriction on cardiac function and Ca2+ handling protein expression in obese rats. To accomplish this goal, male rats fed with a high-fat and sucrose diet for 25 weeks were randomly assigned into 4 groups: high-fat and sucrose diet, high-fat and sucrose diet and exercise training, caloric restriction, and exercise training and caloric restriction. An additional lean group was studied. The study was conducted for 10 weeks. Cardiac function was evaluated by echocardiography and Ca2+ handling protein expression by Western blotting. Our results showed that visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels were higher in rats on the high-fat and sucrose diet compared with the lean rats. Cardiac nitrate levels, reduced/oxidized glutathione, left ventricular fractional shortening, and protein expression of phosphorylated Ser2808-ryanodine receptor and Thr17-phospholamban were lower in rats on the high-fat and sucrose diet compared with lean rats. Exercise training and/or caloric restriction prevented increases in visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels and prevented reduction in cardiac nitrate levels and reduced:oxidized glutathione ratio. Exercise training and/or caloric restriction prevented reduction in left ventricular fractional shortening and in phosphorylation of the Ser2808-ryanodine receptor and Thr17-phospholamban. These findings show that exercise training and/or caloric restriction prevent cardiac dysfunction in high-fat and sucrose diet rats, which seems to be attributed to decreased circulating neurohormone levels. In addition, this nonpharmacological paradigm prevents a reduction in the Ser2808-ryanodine receptor and Thr17-phospholamban phosphorylation and redox status.

Value of rapid beta-blocker injectionat peak dobutamine-atropine stressechocardiography for detection of coronary artery disease

OBJECTIVES We studied the value of a rapid beta-blocker injection at peak dobutamine-atropine stress echocardiography (DASE) for the detection of coronary artery disease (CAD). BACKGROUND The presence of tachycardia and hyperdynamic wall motion may make it difficult to recognize a new wall motion abnormality (NWMA) at peak stress. METHODS We studied 101 patients (mean age 58.2 +/- 9.8 years) who underwent effective DASE and coronary angiography. All patients received a rapid intravenous injection of metoprolol immediately after peak DASE image acquisition. Positivity in combined peak plus post-metoprolol images was defined when there was only peak NWMA, maintenance of peak NWMA, or NWMA detected only after metoprolol injection. Significant CAD was defined as >or=50% stenosis by quantitative angiography. RESULTS There were 37 patients without and 64 with CAD. The sensitivity, specificity, accuracy, and positive and negative predictive values for the detection of CAD at peak stress were 84%, 92%, 87%, 95%, and 77%, respectively. Five patients with CAD had negative peak images that became positive only after metoprolol. Extension of peak NWMA during metoprolol was observed in 14 patients, and multivessel CAD was detected in 10 of them. The sensitivity, specificity, accuracy, and positive and negative predictive values for peak plus metoprolol images were 92%, 89%, 91%, 94%, and 87%, respectively. CONCLUSIONS The use of metoprolol injected at peak of dobutamine infusion improved the detection of CAD by DASE.