Mulvagh, Sharon L.

The recent introduction of novel anticancer therapies, including bevacizumab (BVZ) and sunitinib (SNT), is associated with an increased risk of cardiotoxicity. However, early identification of left ventricular (LV) systolic dysfunction may facilitate dose modification and avoid the development of advanced heart failure. Using a murine model of BVZ- and SNT-mediated cardiotoxicity, we investigated whether cardiac biomarkers and/or tissue velocity imaging (TVI) using echocardiography can detect early changes in cardiac function, before a decrease in LV ejection fraction is identified. A total of 75 wild-type C57Bl/6 male mice were treated with either 0.9% saline, BVZ, or SNT. Serial monitoring of blood pressure, high-sensitivity troponin I, and echocardiographic indexes were performed over a 14-day study period, after which the mice were euthanized for histological and biochemical analyses. Mice treated with either BVZ or SNT developed systemic hypertension as early as day 7, which increased by day 14. Cardiac biomarkers, specifically high-sensitivity troponin I, were not predictive of early LV systolic dysfunction. Although conventional LV ejection fraction values decreased at day 13 in mice treated with either BVZ or SNT, TVI confirmed early LV systolic dysfunction at day 8. Histological and biochemical analysis demonstrated loss of cellular integrity, increased oxidative stress, and increased cardiac apoptosis in mice treated with BVZ or SNT therapy at day 14. In a murine model of BVZ- or SNT-mediated cardiomyopathy, noninvasive assessment by TVI detected early LV systolic dysfunction before alterations in conventional echocardiographic indexes.

Background: A women-based formula for calculation of age-predicted maximum heart rate [age-predicted maximum heart rate=206−(0.88×age)] was established in asymptomatic volunteer women undergoing treadmill exercise tolerance testing (ETT). We sought to perform a comparison of the performance of this women-based formula for prediction of peak heart rate to the traditional formula [220−age] and our own database-generated prediction formula in a large database of women undergoing ETT. Methods: We performed a retrospective analysis of all consecutive women who underwent symptom-limited Bruce protocol ETT at the Mayo Clinic from 1994 to 2010. Women with known cardiovascular disease or those using beta blockers, calcium channel blockers, or digitalis were excluded. Separate analyses were performed according to symptomatic status. Results: The study included 11,029 women (89.4% Caucasian) with a mean age 52±12 years; 3,632 (33%) were referred specifically for evaluation of symptoms. Age-predicted maximum heart rate calculated by the traditional formula was achieved by 49.7% of women versus 69.9% by the women-based formula with most of the underestimation observed in older women. Average absolute deviation between achieved and predicted peak heart rate (HR) was 10.85±9.18 bpm for traditional versus 11.98±9.00 for women-based formulas (dependent t =−16.64, p <0.0001). The linear regression line calculated from our population [HR=201−(0.67×age)] was closer to the women-based formula, both in terms of intercept and slope than the traditional formula. Peak HR was shown to be slightly affected (−2.5 bpm) by symptom status at referral, whereas smoking and diabetes more significantly reduced achieved peak HR. Conclusions: The women-based formula underestimated peak HR, especially in older women, but was observed to be closer in both intercept and slope to the regression line determined from our study in this large population of female patients. These sex-unique observations should be taken into account when determining adequacy and targets for ETT in women.

To study the relationship between glycosylated hemoglobin (HgbA1c) and myocardial perfusion in type 2 diabetes mellitus (T2DM) patients, we prospectively enrolled 24 patients with known or suspected coronary artery disease (CAD) who underwent adenosine stress by real-time myocardial perfusion echocardiography (RTMPE). HgbA1c was measured at time of RTMPE. Microbubble velocity (β min−1), myocardial blood flow (MBF, mL/min/g), and myocardial blood flow reserve (MBFR) were quantified. Quantitative MCE analysis was feasible in all patients (272/384 segments, 71%). Those with HgbA1c > 7.1% had significantly lowerβreserveand MBFR than those with HgbA1c ≤ 7.1%(P<0.05). In patients with suspected CAD, there was a significant inverse correlation between MBFR and HgbA1c (r=-0.279,P=0.01); however, in those with known CAD, this relationship was not significant (r=-0.117,P=0.129). Using a MBFR cutoff value > 2 as normal, HgbA1c > 7.1% significantly increased the risk for abnormal MBFR, (adjusted odds ratio: 1.92, 95% CI: 1.12–3.35,P=0.02). Optimal glycemic control is associated with preservation of MBFR as determined by RTMPE, in T2DM patients at risk for CAD.

ObjectivesThe aim of our study was to demonstrate that the use of contrast microbubbles during transesophageal echocardiography (TEE) guided cardioversion will improve interpretation of the TEE images.BackgroundTEE‐guided cardioversion of atrial flutter or fibrillation (AF) is a safe and proven method to restore sinus rhythm. However, artifacts and dense spontaneous echo contrast in the left atrial appendage (LAA) can sometimes decrease the level of confidence in excluding the presence of thrombus.MethodsOne hundred patients referred for TEE‐guided cardioversion were prospectively enrolled and microbubble contrast agent (DEFINITY) was administered after the clinical decision had been made regarding suitability for cardioversion. Noncontrast and contrast images were compared during subsequent offline analysis.ResultsLAA dimensions and contractility indices were higher, artifacts were significantly differentiated, previously unsuspected LAA filling defects were identified, and the level of confidence in excluding thrombus was enhanced in the contrast images when compared to the noncontrast images. After 4 months follow‐up, 1 stroke‐associated death occurred in a patient who had LAA thrombus recognized only by contrast. Left atrial appendage visualization is enhanced with microbubble contrast agent use during transesophageal echocardiography guided cardioversion and is useful in identification of intracardiac thrombus.

Background: Cardiovascular (CV) disease is the leading cause of death in U.S. women. Although women are becoming more aware of CV disease, there remains a dichotomy between awareness and perceived risk. We sought to characterize this dichotomy in women attracted to a CV health–screening event, in order to improve strategies to reduce CV risk. Methods: During CV health events held in Rochester, Minnesota, from 2007 through 2011, 294 women underwent screening for blood chemistry, body mass index, and blood pressure. Participants also completed surveys about knowledge of CV disease, risk factors, and perceived risk. Risk level was determined from the 2011 American Heart Association Effectiveness-Based Guidelines for Women. Results: Among participants (age, mean [standard deviation], 53 [15.3] years; white, 98%), 99% were aware that CV disease is the leading cause of death in women. Almost half (47%) perceived themselves to be at personal risk, although 65% were determined to be “at risk” and 12% to be at “high risk” according to guidelines, while 22% were uncategorized. Of the 228 participants “at risk” or “high risk,” 48% and 21%, respectively, did not perceive themselves to be at any risk. Conclusions : Women attracted to CV health events were aware that CV disease is the leading cause of death for women. However, the magnitude of awareness did not directly translate into perception or understanding of actual personal risk. To decrease the rate of CV disease in women, continued efforts are needed to personalize the importance of, and the methods for reducing, CV risk factors.

Background— Real-time myocardial contrast echocardiography permits the detection of myocardial perfusion abnormalities during stress echocardiography, which may improve the accuracy of the test in detecting coronary artery stenoses. We hypothesized that this technique could be used after a bolus injection of the selective A2A receptor agonist regadenoson to rapidly and safely detect coronary artery stenoses. Methods and Results— In 100 patients referred for quantitative coronary angiography, real-time myocardial contrast echocardiography was performed during a continuous intravenous infusion of 3% Definity at baseline and at 2-minute intervals for up to 6 minutes after a regadenoson bolus injection (400 μg). Myocardial perfusion was assessed by examination of myocardial contrast replenishment after brief high mechanical index impulses. A perfusion defect was defined as a delay (>2 seconds) in myocardial contrast replenishment in 2 contiguous segments. Wall motion was also analyzed. The overall sensitivity/specificity/accuracy for myocardial perfusion analysis in detecting a >50% diameter stenosis was 80%/74%/78%, whereas for wall motion analysis it was 60%/72%/66% ( P <0.001 for differences in sensitivity). Sensitivity for myocardial perfusion analysis was highest on images obtained during the first 2 minutes after regadenoson bolus ( P <0.001 compared with wall motion), whereas wall motion sensitivity was highest at the 4-to-6–minute period after the bolus. No significant side effects occurred after regadenoson bolus injection. Conclusions— Regadenoson real-time myocardial contrast echocardiography appears to be a feasible, safe, and rapid noninvasive method for the detection of significant coronary artery stenoses. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT0087369.

Purrpose: To evaluate myocardial microvascular disease in patients with type 2 diabetes mellitus (DM) using myocardial contrast echocardiography (MCE) and to report on its diagnostic accuracy using single photon emission tomography (SPECT) as reference test. Methods: We prospectively enrolled 79 patients (25 DM; 66±11 years) who underwent simultaneous SPECT and MCE with contrast agent during adenosine stress. MCE and SPECT were visually analyzed using 17 segments. Quantitative MCE parameters were derived from replenishment curves. Microbubble velocity (β min −1 ), absolute myocardial blood flow (MBF ml/min/g), and reserve values were calculated. Diagnostic accuracy and area under curve (AUC) was reported. Results: Patients with DM had higher BMI vs non DM (33±7 vs 28±5kg/m 2 P=0 .007), with more prior myocardial infarction (40 vs 15% P=.01). Visual MCE was abnormal in 40 (51%) patients (60% in DM vs 46% in non DM P=0.04). SPECT was abnormal in 38 (48%) patients [60% in DM vs 42% non DM, P=0.01]. Reserve parameters were lower in DM vs. non DM patients: (β 1.77±1.12 vs 2.20±1.4, P<0.001 and MBF 2.86± 2.62 vs. 3.67±2.84, P<0.001). DM patients without CAD on SPECT had significantly lower β, and MBF reserve compared to non DM patients without CAD. Compared to SPECT, β reserve cutoff 1.6 had AUC 0.817, sensitivity 81%, and specificity 66% while MBF reserve cutoff 1.9 had AUC 0.760, sensitivity 79%, and specificity 63% in DM patients. Conclusion: Diabetes is associated with myocardial microvascular abnormalities as evidenced by abnormal myocardial perfusion on visual and quantitative MCE.

Background— Microbubble safety concerns led to changes in product recommendations for patients with pulmonary hypertension. Noninvasive estimation of right ventricular systolic pressure (RVSP) is equivalent to pulmonary artery systolic pressure in the absence of pulmonary outflow obstruction. We analyzed the short- and long-term outcomes of patients who received microbubble contrast and those who did not during stress echocardiography (SE) according to resting RVSP. Methods and Results— From November 2003 to December 2007, 26 774 patients underwent SE. RVSP (mean, 32.6�9.6 mm Hg) was measured in 16 434 patients. Of these, 6164 (37.5%) received contrast for left ventricular opacification and 10 270 (62.5%) did not. Short-term (≤72 hours and ≤30 days) and long-term (4.3 years) end points were death and myocardial infarction. Analysis was done for rest RVSP cut-points ≥35, ≥50, and ≥60 mm Hg and tricuspid regurgitant velocities ≥2.7 ms −1 and ≥3.5 ms −1 . Adjusted Cox regression models were used. The contrast cohort comprised older patients (age, 67�12 versus 64�14 years; P <0.001), who were more likely to have positive SE results (35% versus 30%, P <0.001) compared with the noncontrast cohort. Using RVSP ≥50 mm Hg, there was no significant difference in short-term events between the contrast and noncontrast cohorts. For long-term events, there was no significant difference between both cohorts (adjusted hazard ratios [95% confidence intervals] for death, 1.10 [0.80 to 1.50], P =0.56; and myocardial infarction, 0.34 [0.11 to 1.03], P =0.06). Similar results were obtained at different RVSP and tricuspid regurgitant cut-points. Contrast agent–related adverse effects occurred in <1% of patients. Conclusion— RVSP had no impact on predisposition to adverse outcomes in patients undergoing contrast SE in the population studied.