Edward O'Leary

Real-Time Assessment of Myocardial Perfusion and Wall Motion During Bicycle and Treadmill Exercise Echocardiography: Comparison With Single Photon Emission Computed Tomography

OBJECTIVES We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography. BACKGROUND Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WVM) simultaneously and in real time. METHODS One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography. Segmental perfusion with MCE and WM w ere assessed in real time before and at peak exercise using low mechanical index (0.3) and frame rates of 10 to 20 Hz after 0.3 ml bolus injections of intravenous Optison (Mallinckrodt Inc., San Diego, California). All patients had a dual isotope (rest thallium-201, stress sestamibi) study performed during the same exercise session, and 44 patients had subsequent quantitative coronary angiography. RESULTS In the 100 patients, agreement between MCE and single photon emission computed tomography (SPECT) was 76%, while it was 88% between MCE and WM assessment. Compared with quantitative angiography, sensitivity of MCE, SPECT and WM was comparable (75%), with a specificity ranging from 81% to 100%. The combination of MCE and WM had the best balance between sensitivity and specificity (86% and 88%,respectively) with the highest accuracy (86%). CONCLUSIONS The real-time assessment of myocardial perfusion during exercise stress echocardiography can be achieved with imaging at low mechanical index and frame rates. The combination of WM and MCE correlates well with SPECT and is a promising important addition to conventional stress echocardiography.

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.

Value of dobutamine stress myocardial contrast perfusion echocardiography in patients with advanced liver disease

Although dobutamine stress echocardiography has been used for the preoperative evaluation of patients with advanced liver disease (ALD), no data exist regarding the value of myocardial perfusion imaging (MPI) with real‐time myocardial contrast echocardiography (RTMCE) in this patient population. We sought to determine the value of MPI during dobutamine stress RTMCE for predicting prognosis in patients with ALD. We examined both wall motion and MPI in 230 patients with ALD who underwent dobutamine stress RTMCE using intravenous commercially available contrast agents (Optison, GE‐Amersham, Princeton, NJ; or Definity, Bristol‐Myers Squibb Medical Imaging, North Billerica, MA). The prognostic value of clinical variables, including the Model for End‐Stage Liver Disease (MELD) score, and echocardiographic data were examined using a Cox Hazard model. The primary endpoint was mortality of all causes. Among the 85 patients who underwent orthotopic liver transplantation, 4 had abnormal MPI and 81 had normal perfusion. The hospital mortality rate was 50% (2/4) in patients with abnormal MPI and 2% (2/81) in patients with normal MPI (P = 0.01). Among patients with abnormal MPI, 1 died from myocardial infarction in the first postoperative day and the second 1 from hemorrhagic shock. During a median follow‐up of 15 months, 53 (23%) patients died. The independent predictors of death were an age of ≥65 yr (RR = 2.2; 95% confidence interval (CI) = 1.1–4.4; P = 0.03), MELD score of ≥25 (RR = 3.2; 95% CI = 1.8–5.5; P < 0.0001), and abnormal MPI (RR = 2.4; 95% CI = 1.1–5.2; P = 0.02). The 2‐yr mortality was 24% for patients with normal MPI and 45% for those with inducible MPI abnormalities (P = 0.003). In conclusion, MPI obtained by RTMCE appears to be a useful tool in predicting mortality in patients with ALD. Further studies are required to verify its independent value. Liver Transpl 12:592–599, 2006.

Rapid Detection of Coronary Artery Stenoses With Real-Time Perfusion Echocardiography During Regadenoson Stress

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 &mgr;g). 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.

Detection of Subendocardial Ischemia in the Left Anterior Descending Coronary Artery Territory With Real-Time Myocardial Contrast Echocardiography During Dobutamine Stress Echocardiography

OBJECTIVES The purpose of this study was to test whether the transmural delineation of myocardial perfusion during dobutamine stress imaging with real-time myocardial contrast echocardiography (RTMCE) might permit visualization of dobutamine-induced subendocardial ischemia. BACKGROUND Significant coronary artery disease can be present despite normal transmural wall thickening (WT) responses during dobutamine stress echocardiography (DSE). One potential reason is dobutamine-induced recruitment of epicardial WT in the presence of subendocardial ischemia. METHODS Myocardial perfusion and WT were examined with RTMCE during DSE with a continuous infusion of ultrasound contrast in 94 patients with normal resting WT. Fifty-five of the patients had a >50% diameter stenosis in the left anterior descending coronary artery (LAD). The WT was visually assessed by a blinded reviewer at 2 time periods: initially after a high mechanical index impulse before myocardial contrast replenishment (MCR), and again during MCR. Subendocardial %WT was measured during MCR, if a subendocardial perfusion defect was visually evident, whereas transmural WT was quantified on the pre-MCR images. RESULTS Fifty patients (91%) with LAD stenoses exhibited a myocardial contrast defect at peak stress, with 45 defects being subendocardial. Transmural WT pre-MCR appeared normal in 35 of the 45 patients with subendocardial perfusion defects (78%). However, a subendocardial WT abnormality was apparent during MCR in 18 of these 35 patients, even though transmural WT was not different from the 17 patients with normal subendocardial WT (33 +/- 15% vs. 36 +/- 14%). Quantitative measurements of WT within the subendocardium were significantly less in the patients with visually evident subendocardial WT abnormalities, when compared with those who seemed to have normal WT during MCR (17 +/- 8% vs. 25 +/- 10%, p < 0.01). CONCLUSIONS In patients with significant LAD disease, RTMCE during DSE detects subendocardial ischemia even when transmural WT appears normal. Real-time myocardial contrast echocardiography should be the preferred ultrasound imaging method when using contrast to detect coronary artery disease during DSE.

Real Time Perfusion Echocardiography during Treadmill Exercise and Dobutamine Stress Testing

Background Real-time perfusion (RTP) echocardiographic imaging with a continuous infusion of microbubbles has improved the sensitivity of dobutamine stress echocardiography (DSE) in detecting coronary artery disease (CAD). The impact of RTP on treadmill exercise stress echocardiography (TESE) is unclear. Design Retrospective database review. Setting/patients/interventions RTP was utilised in 254 DSE and TESE patients being examined for the presence of significant CAD. A continuous infusion of 3% Definity (Lantheus Medical Imaging) was used for all studies, and contrast replenishment (MCR), plateau intensity (PMCE) and wall motion (WM) were examined for the detection of CAD. Main outcome measures Sensitivity/specificity/accuracy to detect CAD. Results For DSE, the sensitivity of myocardial perfusion (MP) imaging with RTP was 85%, which was significantly higher than WM analysis (72%; p<0.05). The improvement in sensitivity with MP analysis during DSE was primarily the result of better detection of left anterior descending disease. MP sensitivity during TESE was significantly better than MP sensitivity during DSE (98% versus 85%; p<0.05), and WM sensitivity during TESE was better than WM sensitivity during DSE (89% versus 72%; p<0.05). The improvement in WM sensitivity during TESE was due to detection of subendocardial wall thickening abnormalities in 48% of the patients with induced subendocardial perfusion defects. Conclusion Myocardial perfusion imaging with RTP improves the detection of CAD during both DSE and TESE. During TESE, the subendocardial perfusion defects improve WM sensitivity by delineating subendocardial WM abnormalities.

Comparison of Fractional Flow Reserve Assessment With Demand Stress Myocardial Contrast Echocardiography in Angiographically Intermediate Coronary Stenoses.

Background—Real-time myocardial contrast echocardiography (RTMCE) directly measures capillary flow (CBF), which in turn is a major regulator of coronary flow and resistance during demand or hyperemic stress. Although fractional flow reserve (FFR) was developed to assess the physiological relevance of an epicardial stenosis, it assumes maximal microvascular vasodilation and minimal resistance during vasodilator stress. Therefore, we sought to determine the relationship between CBF assessed with RTMCE during stress echocardiography and FFR in intermediate coronary lesions. Methods and Results—Sixty-seven vessels with 50% to 80% diameter stenoses by quantitative coronary angiography in 58 consecutive patients were examined with FFR and RTMCE (mean age, 60±13 years). RTMCE was performed using an incremental dobutamine (n=32) or exercise (n=26) stress protocol, and myocardial perfusion was assessed using a continuous infusion of ultrasound contrast. The presence or absence of inducible perfusion defects and wall motion abnormalities were correlated with FFR. Mean percent diameter stenosis was 60±9%. Eighteen stenoses (27%) had an FFR ⩽ 0.8. Although 17 of the 18 stenoses that were FFR+ had abnormal CBF during RTMCE, 28 of the 49 stenoses (57%) that were FFR had abnormal CBF, and 24 (49%) had abnormal wall motion in the corresponding coronary artery territory during stress echocardiography. Conclusions—In a significant percentage of intermediate stenoses with normal FFR values, CBF during demand stress is reduced, resulting in myocardial ischemia.

Regadenoson Stress Real-Time Myocardial Perfusion Echocardiography for Detection of Coronary Artery Disease: Feasibility and Accuracy of Two Different Ultrasound Contrast Agents

BACKGROUND The aim of this study was to compare the efficacy of myocardial perfusion (MP) and wall motion (WM) analysis obtained with real-time myocardial contrast echocardiography (RTMCE) and two widely used contrast agents in detecting coronary artery disease after injection of the vasodilator regadenoson. METHODS One hundred fifty patients were studied at two academic centers using regadenoson (400-μg intravenous bolus) vasodilator stress RTMCE (7.5% Optison infusion [n = 50] or 1.5% Definity infusion [n = 100]). Both MP and WM with RTMCE were analyzed at rest and after regadenoson bolus. Comparisons of WM and MP sensitivity, specificity, and accuracy were made. Quantitative angiography was performed in all patients within 1 month of the regadenoson stress study (>50% and >70% diameter stenosis was considered significant). Reviewers were blinded to all clinical and quantitative angiographic data. RESULTS Rate-pressure product after regadenoson was higher in Optison than Definity patients (P = .004). Using a 50% diameter stenosis on quantitative angiography as a reference standard, overall sensitivity, specificity, and accuracy for combined WM and MP analysis were not different for both agents (Optison, 77%, 64%, and 73%; Definity, 80%, 74%, and 78%; P = NS). The sensitivity, specificity, and accuracy of WM analysis alone for Optison were 68%, 71%, and 69% compared with 60%, 72%, and 66% for Definity (P = NS). Adding MP analysis improved the sensitivity and accuracy of Definity for detecting both >50% and >70% stenoses (P < .001 vs WM), while MP analysis did not improve the sensitivity of Optison for detecting either >50 or >70% stenoses. CONCLUSIONS RTMCE during regadenoson stress using either Optison or Definity is a rapid and effective method for the detection of coronary artery disease. The ability of MP imaging to improve WM accuracy may depend on the rate-pressure product achieved.

Evaluation of restenosis and extent of coronary artery disease in patients with previous percutaneous coronary interventions by dobutamine stress real-time myocardial contrast perfusion imaging

Objectives: To assess the accuracy of real-time myocardial contrast perfusion imaging (MCPI) for the diagnosis of restenosis and extent of coronary artery disease (CAD) in patients with previous percutaneous coronary intervention (PCI). Methods: 56 patients were studied 1.9 (SD 1.4) years after PCI. They underwent MCPI with commercially available ultrasound contrast agents (Optison or Definity) at rest and at peak dobutamine–atropine stress. Coronary angiography was performed within one month. Significant CAD was defined as ⩾ 50% stenosis in ⩾ 1 major epicardial coronary artery. Significant restenosis was defined as ⩾ 50% stenosis in a coronary segment with previous intervention. Results: Reversible perfusion abnormalities were detected in 40 of 43 patients with significant CAD and in 4 of 13 patients without (overall sensitivity 93%, 95% CI 85% to 99%; specificity 69%, 95% CI 44% to 94%; and accuracy 88%, 95% CI 79% to 96%). Significant restenosis in ⩾ 1 coronary artery with previous PCI was detected in 38 (68%) patients. Reversible perfusion abnormalities were present in 35 of them (sensitivity 92%, 95% CI 84% to 99%). Reversible perfusion abnormalities were detected in ⩾ 2 vascular distributions in 20 of 28 patients with multivessel CAD and in 3 of 28 patients without (sensitivity 71%, 95% CI 55% to 88%; specificity 89%, 95% CI 78% to 99%; and accuracy 80%, 95% CI 70% to 91%). Restenosis was detected in 41 coronary arteries. Sensitivity of MCPI for regional diagnosis of restenosis was 73% (95% CI 60% to 87%), specificity was 75% (95% CI 60% to 90%), and accuracy was 74% (95% CI 64% to 84%). Conclusion: Dobutamine stress MCPI is a useful technique for the evaluation of restenosis and extent of CAD after PCI.

A Method of Detecting and Quantifying Severity of Myocardial Perfusion Defects With Intravenous Ultrasound Contrast and Breath Holding During Stress Echocardiography

Although breath holding is commonly used to improve and maintain image quality during stress echocardiography, its effects on the qualitative and quantitative analysis of myocardial contrast enhancement (MCE) following intravenously injected microbubbles is unknown. The purpose of this study was to determine how breath holding affects MCE following either an intravenous bolus or continuous infusion of perfluorocarbon containing microbubbles. In 48 patients, intravenous Optison was given at peak dobutamine stress to assess myocardial perfusion. The degree of myocardial opacification was assessed immediately following a breath hold in inspiration (BHini), at the end of a breath hold (BHterm), and following expiration and a subsequent second breath hold (BHreinsp). Pulmonary venous time velocity integrals were recorded during these different phases as well. Eleven patients had quantitative coronary angiography. Mean duration of the breath hold was 7 ± 1 seconds. Pulmonary venous return fell by 29%± 18% at BHterm (P < 0.001) . There was complete disappearance of MCE at BHterm in 27 of 35 bolus injection patients at peak stress, and no return of MCE following flash destruction during breath holding in 11 of 13 patients receiving continuous infusions. BHreinsp resulted in a boluslike return of contrast, with a transient, bright MCE in 44 of 48 patients, and a time intensity plot that resembled a gamma variate function. Perfusion defects were visualized in 25 patients during BHini and 28 patients during BHreinsp. Coronary artery territory agreement between perfusion assessed during BHini and BHreinsp and quantitative coronary angiography was 76% and 81%, respectively. (ECHOCARDIOGRAPHY, Volume 20, July 2003)