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The Feasibility and Clinical Utility of Myocardial Contrast Echocardiography in Clinical Practice: Results from the Incorporation of Myocardial Perfusion Assessment into Clinical Testing with Stress Echocardiography Study
Abstract
Background
This prospective study investigated whether the incorporation of myocardial contrast echocardiography (MCE) into a clinical stress echocardiography service reproduces the benefits of assessing myocardial perfusion proved previously in research studies.
Methods
MCE was performed during physiologic and pharmacologic clinical stress echocardiographic studies, and the value of myocardial perfusion to the reporting echocardiologists was categorized as of benefit (subclassified as incremental benefit over wall motion [WM] or greater confidence with WM) or of no added benefit. The presence and extent of inducible ischemia by WM and myocardial perfusion were documented and correlated with angiographic results in patients who underwent cardiac catheterization.
Results
In total, 220 patients underwent simultaneous MCE during stress echocardiography by eight different operators. Overall, MCE was of benefit in 193 patients (88%), providing incremental benefit over WM in 25% and greater confidence with WM evaluation in 62%. MCE provided no added benefit in 27 patients (12%). MCE detected significantly more cases of ischemia than WM in the left anterior descending coronary artery territory (65% vs 53%, P = .02) and detected a greater ischemic burden than WM on a per patient basis (median, 5 [interquartile range, 3–8] vs 4 [interquartile range, 2–7] segments; P < .001) and across all coronary territories. MCE correctly identified a greater proportion of patients with multivessel disease than WM (76% vs 56%, P = .02) and a greater ischemic burden in patients with multivessel disease (median, 7 [interquartile range, 4–9] vs 5 [interquartile range, 1–8] segments; P < .001).
Conclusions
This prospective study is the first to demonstrate that the excellent feasibility and diagnostic utility of MCE, which have been documented in the research arena, are reproducible in the clinical arena.
... Seit Einsatz der neuen UKM ist die Kombination aus DSE [47,49] oder ASE [10,49] mit den Kontrastmitteln sehr erfolgreich gewesen, was die Beurteilung der KHK anbetrifft, und gilt als eine Alternative zu den aufwendigeren radiologischen Untersuchungsmethoden. ...
... Seit Einsatz der neuen UKM ist die Kombination aus DSE [47,49] oder ASE [10,49] mit den Kontrastmitteln sehr erfolgreich gewesen, was die Beurteilung der KHK anbetrifft, und gilt als eine Alternative zu den aufwendigeren radiologischen Untersuchungsmethoden. ...
... Perfusionsdefizite können analysiert werden. Hier bestehen aber trotz vielversprechender Berichte[5,10,[47][48][49][50] nach wie vor die bekannten Limitationen[9]. Bei der Aortenklappenstenose kann mittels Dopplereinsatz festgestellt werden, ob der Gradient an der Aortenklappe ansteigt und mittels der 2-D-Bildgebung, ob sich die Ventrikelgröße oder die Kontraktionen verändern und ob es zu einer Vergrößerung des linken Vor-hofs (LA) unter Belastung kommt. ...
Die Stressechokardiographie (SE) stellt eine zentrale kardiologische diagnostische Methode dar. Die SE ist nicht nur bei der Diagnostik und Führung der Patienten mit koronarer Herzkrankheit (KHK) von immenser Bedeutung, sondern auch bei der Beurteilung der kardialen Funktion außerhalb der KHK. Gerade durch die richtungsweisende und enorme Entwicklung der technologischen Möglichkeiten (Doppler, digitale Verarbeitung, neue Ultraschallanalysemöglichkeiten mit Gewebedoppler [TDI], „Strain“-Technologie, 3‑D-Echo) wie auch durch den Einsatz der neuen Kontrastmittel ergeben sich sehr weite diagnostische Möglichkeiten. Mittels SE besteht nicht nur die Möglichkeit, eine evtl. koronare Verengung festzustellen, sondern es lässt sich die Funktion der Mikrovaskulatur und der Herzklappen beurteilen, eine evtl. pulmonale Hypertonie feststellen und auch die diastolische/systolische Reaktion/Mechanik des linken/rechten Ventrikels (LV/RV) und des linken Vorhofs (LA) auf die Belastung überprüfen. Die weiteren Entwicklungen der Technologie versprechen eine noch weitere und bessere Analyse der kardialen Mechanik sowohl des LV/RV wie auch des LA sowie eine verbesserte laterale Auflösung. Medikamentöse Stressmöglichkeiten erweitern das diagnostische Feld bei den Patienten, die nicht in der Lage sind, sich körperlich zu belasten. Die SE stellt eine umweltfreundliche, kostengünstige, patientennahe und einfach verfügbare Untersuchungsmethode dar. Sie erfordert allerdings eine sehr weitgehende Grundausbildung des Untersuchers und eine ständige Weiterbildung, damit sich alle möglichen Vorteile der Methode auch wirklich beim Patienten als nützlich erweisen können.
... We recently reported the findings from the Incorporation of Myocardial Perfusion Assessment into Clinical Testing with Stress Echocardiography study, a single-center, prospective study of 220 patients representing our experience of incorporating MCE into clinical practice. 12 In that study, we established criteria for our echocardiography laboratory for determining who should undergo MCE, based in part on previous research that has demonstrated that MCE has the most incremental value when images are analyzed at low work level. Our study, a prospective report of our clinical experience, demonstrated that MCE has excellent feasibility when performed by multiple operators within the time constraints of a clinical SE service. ...
... Our study, a prospective report of our clinical experience, demonstrated that MCE has excellent feasibility when performed by multiple operators within the time constraints of a clinical SE service. 12 We also found that MCE has superior sensitivity for detection of left anterior descending CAD and multivessel disease and detects a larger ischemic burden compared with WM alone. The present study has now followed these same 220 patients of the Incorporation of Myocardial Perfusion Assessment into Clinical Testing with Stress Echocardiography study to determine whether the superior diagnostic value of MCE translates into improved prognostic impact of MCE over WM alone when incorporated into a routine clinical SE service. ...
... This study involved follow-up of a recently studied patient cohort, for whom the criteria for performing MCE have recently been described. 12 In brief, we performed MCE in consecutive adult patients referred for SE for the evaluation of CAD receiving pharmacologic stress and consecutive patients undergoing treadmill exercise in whom the cardiologist was not certain that a high workload or target heart rate (THR) would be achieved (and thus it was anticipated that additional MP data would be helpful in addition to WM). 7 This was a judgement made at the time of the stress echocardiographic study on the basis of the patient's general level of fitness and limitations to exercise, such as orthopedic or respiratory disorders or significant obesity. ...
The authors recently demonstrated that simultaneous assessment of myocardial perfusion (MP) and wall motion (WM) by myocardial contrast echocardiography (MCE) is feasible and accurate when incorporated into a clinical stress echocardiography (SE) service. However, it is unknown whether the incremental prognostic value of MP beyond WM, previously shown in research studies, is reproducible when MCE is performed in the clinical arena.
In this prospective study, MCE was performed by multiple operators during routine clinical SE, whose results were classified as normal WM and MP, abnormal WM and MP, or normal WM but abnormal MP. Patients were followed for the prospectively determined combined primary outcome of all-cause mortality, nonfatal myocardial infarction, and late revascularization. Cox regression analyses were performed to identify predictors of outcome.
Of 220 patients undergoing simultaneous MCE during SE, 197 patients (90%) with interpretable WM and MP images were available for follow-up at a mean time period of 17 ± 7 months. There were 35 events (six deaths, six myocardial infarctions, and 23 revascularizations). Among prognostic clinical variables, resting left ventricular function, and WM and MP data, abnormal MP at peak stress was the only independent predictor of primary outcome (hazard ratio, 4.41; 95% confidence interval, 1.37-14.20; P = .02). Sequential Cox regression models showed that abnormal MP also carried incremental prognostic value over clinical variables, resting left ventricular function and abnormal WM.
In keeping with previous research studies, this prospective study demonstrates the incremental prognostic benefit of MP assessment beyond WM when MCE is incorporated into a clinical SE service.
Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
... It is used mostly for the LVO, for segmental or global LV wall motion analysis and for identification of cardiac masses. The indications of CE are defined by the European and by the American Society of Echocardiography 1,2,9,11 . ...
... Regional wall motion disturbances were registered with CE in rest and stress. The accuracy of CE was not compared to noncontrast study's results in our PTS, but according to the published papers of other investigators, there is a significantly higher accuracy in stress with CE for the detection of CAD, especially if they are done as multiparametric stress echocardiograpahies not only for endocardial enhancement and wall motion analysis, but for coronary flow registration and MP and viability assessment, too 11,27 . CE can improve interobserver agreement for wall motion analysis 28 . ...
Background/Aim. Contrast echocardiography (CE) is an echocardiographic modality where ultrasound contrast echocardiographic agent (CEA) is introduced peripherally for the image enhancement. The aim of this study was to present the initial clinical experience of the use of CEA Optison? (GE Healthcare, Princeton, NJ) at the Institute for Cardiovascular Diseases of Vojvodina, Serbia and prospectively monitor the occurrence of possible side effects. Methods. A total of 357 patients were referred for resting or stress echocardiographic examinations, with an approved indication for CEA administration. The average age of patients was 63.3 years (range, 21?92 years), 62% of them were men. Most of the patients (77.31%) had some form of ischemic heart diseases. Hypertension was the most frequent risk factor (77.03%), but 57 patients had diabetes mellitus and 33 patients had chronic kidney disease as comorbidity. Most (90.5%) of the patients were on beta blocker therapy, 83.5% of them on angiotensin converting enzyme/angiotensin receptor blockers. Majority (80.3%) of the patients received single or dual (49.5%) antiagregation therapy, 74 (26.3%), of them were on anticoagulation therapy, 55.1% of the patients were taking diuretics. The global ejection fraction (EF) was preserved in 39.85% of them, the majority (136 of them), had left ventricle (LV) impairment, with an EF less than 50%. Patients were followed up for 30 minutes after CEA administration for potential side effects. In 118 patients, vital signs (heart rate, oxygen saturation, body temperature, systolic and diastolic blood pressure) were measured before and 30 minutes after CEA administration. Results. The administration of CEA was not associated with side effects. Diastolic blood pressure drop and heart rate increase were statistically, but not clinically significant (p = 0.027 and p = 0.028, respectively). Conclusion. Changes in analyzed vital signs were clinically non relevant. CE is a safe noninvasive diagnostic modality for patients undergoing rest and stress echocardiography.
... Technological advances and the use of contrast agents provided echocardiography the ability to increase and match the perfusion information to the classic evaluation of WM abnormalities that are induced by adrenergic or adenosinic mechanisms [47] . The use of echocardiographic contrast agents improved the accuracy of stress echocardiography [48][49][50] . Shah et al [48] demonstrated the usefulness of myocardial contrast stress echocardiography in 193 patients (88%) in a prospective clinical study, and it provided an incremental benefit over WM analysis in 25% of patients and greater confidence with WM evaluations in 62% of patients. ...
... The use of echocardiographic contrast agents improved the accuracy of stress echocardiography [48][49][50] . Shah et al [48] demonstrated the usefulness of myocardial contrast stress echocardiography in 193 patients (88%) in a prospective clinical study, and it provided an incremental benefit over WM analysis in 25% of patients and greater confidence with WM evaluations in 62% of patients. Thomas et al [51] randomized 1776 patients to real-time myocardial contrast (RTMCE) dobutamine, physical stress echocardiography or standard stress echocardiography in which contrast was used for opacification of the left ventricle only (non-RTMCE). ...
Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking.
... Although the wide array of functional and anatomic approaches to detecting CAD in patients with stable ischemic heart disease makes it unlikely that MCE will supplant any of the currently used technologies, it has been shown that the location of perfusion abnormalities and their physiological relevance in terms of reversibility is similar to that provided by single-photon emission computed tomography [29,30]. Yet, because the complex relationship between blood flow during inotropic stress and wall thickening makes visual identification of inducible ischemia by standard echocardiography difficult when CAD is moderate [31], MCE perfusion imaging can improve sensitivity for detecting moderate CAD and the presence of multivessel disease [23,32]. When using echocardiography for the detection of CAD, MCE perfusion imaging has been advocated in situations where wall motion evaluation during stress is difficult, such as in the presence of dyssynchrony from cardiac conduction abnormality or pre-existing wall motion abnormalities. ...
Purpose of Review
Improvements in ultrasound methods for detecting microbubble ultrasound enhancing agents have led to an increase in the use of perfusion imaging with myocardial contrast echocardiography (MCE). This technique is now beginning to play an important role in specific clinical scenarios, which is the focus of this review.
Recent Findings
MCE was originally conceived as a technique for detecting resting perfusion abnormalities related to ischemia at rest or during stress from coronary artery disease. More recently, MCE has increasingly been used in circumstances where the technique’s ability to provide rapid, quantitative, or bedside assessment of perfusion is advantageous. Quantitative MCE is also increasingly being used as a research technique for evaluating pathobiology and therapy that involve changes in the myocardial microcirculation.
Summary
While MCE was developed and validated decades ago, it is only now beginning to be used by an increasing number of clinicians due to improvements in imaging technology and recognition of specific situations where the technique is impactful.
... MCE is a validated method to assess myocardial reperfusion [194,195] and the CNR diagnosed by this technique correlates closely with adverse left ventricular remodeling and poor prognosis after AMI [19]. MCE is limited by moderate spatial resolution and dependence on operator's experience [65], poor echocardiographic window preventing reliable measurements in 8% of patients [196] and an inability to detect vasodilatation or vasoconstriction within a previously ischemic myocardial area [192]. ...
Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently, the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.
... There is now a large body of evidence supporting the added value of myocardial perfusion imaging over wall motion assessment alone in stress echocardiography [55,[60][61][62][63][64][65][66]. When using vasodilator stress, the use of high-power flash-replenishment technique is likely more important than during dobutamine or exercise stress, where wall motion abnormalities and perfusion defects may be more evident because of the higher oxygen demand during this type of stress [67]. ...
Contrast-enhanced ultrasound imaging is a radiation-free clinical diagnostic tool that uses biocompatible contrast agents to enhance ultrasound signal, in order to improve image clarity and diagnostic performance. Ultrasound enhancing agents (UEA), which are usually gas microbubbles, are administered intravenously either by bolus injection or continuous infusion. UEA increase the accuracy and reliability of echocardiography, leading to changes in treatment, improving patient outcomes and lowering overall health care costs. In this review we describe: (1) the current clinical applications of ultrasound enhancing agents in echocardiography, with a brief review of the evidence underlying each of these applications; (2) emerging diagnostic and therapeutic applications of microbubble enhanced echocardiography (MEE), which rely either on the specific properties and composition of ultrasound enhancing agents or on the technical advances of clinical ultrasound systems; and (3) safety of MEE.
... This is traditionally performed either by looking at LV wall motion abnormalities during physical or pharmacological stress by echocardiography [42], or, less frequently, by gated single-photon emission tomography (SPECT), or CMR cine-loops. Left heart echo contrast application improves the diagnostic accuracy of stress echocardiography, and should be strongly considered even in patients with acceptable image quality at rest [43]. The injection of contrast, besides opacification of the chambers, leads to myocardial opacification, and this can be used to assess myocardial perfusion. ...
Heart failure is becoming the central problem in cardiology. Its recognition, differential diagnosis, and the monitoring of therapy are intimately coupled with cardiac imaging. Cardiac imaging has witnessed an explosive growth and differentiation, with echocardiography continuing as the first diagnostic step; the echocardiographic exam itself has become considerably more complex than in the last century, with the assessment of diastolic left ventricular function and strain imaging contributing important information, especially in heart failure. Very often, however, echocardiography can only describe the fact of functional impairment and morphologic remodeling, whereas further clarification of the underlying disease, such as cardiomyopathy, myocarditis, storage diseases, sarcoidosis, and others, remains elusive. Here, cardiovascular magnetic resonance and perfusion imaging should be used judiciously to arrive as often as possible at a clear diagnosis which ideally enables specific therapy.
... On the basis of ischemic cascade, where abnormal perfusion precedes wall motion abnormalities during increased demand induced ischemia, a large number of MCE studies have demonstrated that perfusion analysis provides an incremental benefit for CAD detection over wall motion abnormalities alone in the setting of stress echocardiography (62)(63)(64). However, it has been frequently encountered in clinical practice that an inducible defect within a given coronary artery territory does not have a significant obstructive lesion detected at angiography. ...
With growing evidence in clinical practice, the understanding of coronary syndromes has gradually evolved out of focusing on the well-established link between stenosis of epicardial coronary artery and myocardial ischemia to the structural and functional abnormalities at the level of coronary microcirculation, known as coronary microvascular dysfunction (CMD). CMD encompasses several pathophysiological mechanisms of coronary microcirculation and is considered as an important cause of myocardial ischemia in patients with angina symptoms without obstructive coronary artery disease (CAD). As a result of growing knowledge of the understanding of CMD assessed by multiple non-invasive modalities, CMD has also been found to be involved in other cardiovascular diseases, including primary cardiomyopathies as well as heart failure with preserved ejection fraction (HFpEF). In the past 2 decades, almost all the imaging modalities have been used to non-invasively quantify myocardial blood flow (MBF) and promote a better understanding of CMD. Myocardial contrast echocardiography (MCE) is a breakthrough as a non-invasive technique, which enables assessment of myocardial perfusion and quantification of MBF, exhibiting promising diagnostic performances that were comparable to other non-invasive techniques. With unique advantages over other non-invasive techniques, MCE has gradually developed into a novel modality for assessment of the coronary microvasculature, which may provide novel insights into the pathophysiological role of CMD in different clinical conditions. Moreover, the sonothrombolysis and the application of artificial intelligence (AI) will offer the opportunity to extend the use of contrast ultrasound theragnostics.
... 16 17 The 21st century advances include three-dimensional (3D) echocardiography, 18-21 strain imaging and tissue Doppler. 22 These now 'basic' technologies remain the cornerstone of assessing anatomical, functional and pathophysiological effects of cardiovascular disease, with further recent UK research advances in contrast echocardiography [23][24][25] and the application of 3D printing 26 and artificial intelligence. 27 Finally, the role of echocardiography in the development of new treatment options for structural heart diseases has grown ...
Imaging plays a central role in modern cardiovascular practice. It is a field characterised by exciting technological advances that have shaped our understanding of pathology and led to major improvements in patient diagnosis and care. The UK has played a key international role in the development of this subspecialty and is the current home to many of the leading global centres in multimodality cardiovascular imaging. In this short review, we will outline some of the key contributions of the British Cardiovascular Society and its members to this rapidly evolving field and look at how this relationship may continue to shape future cardiovascular practice.
... Improved assessment in terms of both improved sensitivity and the extent of ischaemia have been corroborated in several independent studies. 126,129,130,147,150,158 A large body of evidence now exist (5679 patients) confirming the improved prognostic value of perfusion when performed simultaneously during SE ( Table 8). This includes a large (over 2000 patients) randomized study, which showed that perfusion assessment provided improved prognostic information beyond wall motion assessment during SE. ...
Contrast echocardiography is widely used in cardiology. It is applied to improve image quality, reader confidence and reproducibility both for assessing left ventricular (LV) structure and function at rest and for assessing global and regional function in stress echocardiography. The use of contrast in echocardiography has now extended beyond cardiac structure and function assessment to evaluation of perfusion both of the myocardium and of the intracardiac structures. Safety of contrast agents have now been addressed in large patient population and these studies clearly established its excellent safety profile. This document, based on clinical trials, randomized and multicentre studies and published clinical experience, has established clear recommendations for the use of contrast in various clinical conditions with evidence-based protocols.
... Although myocardial perfusion imaging is not an approved indication for ultrasound contarst agents, it has been used in multiple clinical studies to examine perfusion to improve the detection of coronary artery disease in the emergency department, improve the detection of coronary artery disease during stress echocardiography and improve the diagnostic evaluation of cardiac masses [26]. Shah et al. showed that the incorporation of myocardial contrast echocardiography into a clinical stress echocardiography service is either of incremental benefit over wall motion (WM) analysis or gives added confidence with WM analysis in the majority of cases [33]. ...
Transthoracic echocardiographic examination is known to be a safe, non-invasive and reproducible method, used in every day clinical practice to obtain important information about cardiac structure and function. Unfortunately, a significant proportion of studies have highlighted the considerable technically difficultly in producing diagnostic images due to a poor acoustic window and more than 33% of patients undergoing stress echocardiography have suboptimal echocardiographic images. All these limitations have led to the use of contrast agents to improve the quality of standard ultrasound examination to provide a better delineation of left ventricle endocardial borders or to obtain information that cannot be achieved by using standard echocardiography, such as assessing myocardial microcirculation and therefore perfusion. This paper sought to review the clinical efficacy and safety of ultrasound contrast agents focusing on stress echocardiography.
... 25 In clinical practice, WM evaluation remains the cornerstone of ischemia assessment during stress echocardiography, and MP data should be viewed as complementary data rather than replacement of clinical WM data. 26 An additional unique advantage of real-time MCE over other assessment techniques (e.g., magnetic resonance imaging, single-photon emission computed tomography) is that it allows the simultaneous assessment of both MP and WM. 7,22 Perfusion abnormalities precede contractile abnormalities in the ischemic cascade; therefore, superior prognostic value of MP over WM is anticipated. ...
Background:
Myocardial perfusion (MP) imaging during stress myocardial contrast echocardiography (MCE) improves the detection of coronary artery disease (CAD). However, its prognostic value to predict cardiac events in patients with known or suspected CAD is still undefined.
Methods:
A search was conducted for single- or multicenter prospective studies that evaluated the prognostic value of stress MCE in patients with known or suspected CAD. A database search was performed through June 2015. Effect sizes of relative risk ratios (RRs) with their corresponding 95% CIs were used to evaluate the association between the occurrence of total cardiac events (cardiac death, nonfatal myocardial infarction, coronary revascularization) and hard cardiac events (cardiac death and nonfatal myocardial infarction) in subjects with normal and abnormal MP measured by MCE. The Cochran Q statistic and the I(2) statistic were used to assess heterogeneity.
Results:
A comprehensive literature search of the MEDLINE, Google Scholar, Cochrane, and Embase databases identified 11 studies enrolling a total of 4,045 patients. The overall analysis of RRs revealed that patients with abnormal MP were at higher risk for total cardiac events compared with patients with normal MP (RR, 5.58; 95% CI, 3.64-8.57; P < .001), with low heterogeneity among trials (I(2) = 48.15%, Q = 7.71, P = .103). Similarly, patients with abnormal MP were at higher risk for hard cardiac events compared with patients with normal MP (RR, 4.99; 95% CI, 1.75-14.32; P = .003), with significant heterogeneity among trials (I(2) = 81.48%, Q = 21.59, P < .001).
Conclusions:
The results of this meta-analysis suggest that MP assessment using stress MCE is an effective prognostic tool for predicting the occurrence of cardiac events in patients with known or suspected CAD.
... Myocardial contrast echocardiography is a good alternative technique to assess patients with LBBB as it provides information of myocardial ischaemia and LV function with a high degree of accuracy while being a bedside technique. 18,19 Other studies had shown the prognostic value of SE. 7,17 However, these studies did not address the issue of feasibility and it is not clear whether the data were derived from consecutive patients in routine day-to-day clinical practice. ...
Aims
Patients with symptomatic left bundle branch block (LBBB) may have myocardial ischaemia due to both coronary artery disease and/or cardiomyopathy (microcirculatory abnormalities) and may have concomitant left ventricular (LV) dysfunction. We aimed to assess the feasibility and prognostic value of contemporary stress echocardiography (SE), which can uncover both pathophysiologies in LBBB patients in routine clinical practice, and also aimed to assess the additive value of contrast SE.
Methods and results
Accordingly, 190 consecutive patients (age 70.5 ± 11.3 years, LV ejection fraction = 50.1 ± 10%) with symptomatic LBBB who underwent SE over 6 years were assessed, of which 142 (75%) underwent contrast SE and 176 (92.6%) had diagnostic SE. Inducible ischaemia was present in 25 (14.2%) patients. During follow-up (35.4 ± 20.2 months) there were 32 deaths (18%) and 18 (10.2%) first cardiovascular (CV) events (acute myocardial infarction/mortality) in the 176 patients with diagnostic studies. Wall thickening score index at peak stress (WTSIpeak), which measures combined LV function and inducible ischaemia, was an independent predictor of mortality (HR = 3.78, 95% CI = 1.39–10.31, P = 0.01) and CV events (HR = 3.96, 95% CI = 1.1–14.3, P = 0.036). An abnormal SE (myocardial ischaemia and/or abnormal LV function) predicted an almost three-fold increase in all-cause mortality and CV events compared with normal SE. Amongst the confounders affecting assessment of wall thickening in LBBB and conventional prognostic variables, use of contrast was an independent predictor (P = 0.034) of WTSI1.16 (optimal predictor of mortality/CV outcome).
Conclusion
SE in patients with LBBB demonstrated high feasibility and the combination of LV systolic function and myocardial ischaemia provided important prognostic information. Contrast-enhanced SE improved the prediction of outcome.
... Thus, when incorporating assessment of perfusion during stress echocardiography, a completely normal perfusion is very reassuring while abnormal perfusion with or without normal wall motion portends worse outcome. These results were replicated in a recent study 20 when MCE was incorporated into the routine clinical stress echocardiography service. It provided incremental diagnostic information not only for the detection of CAD but also for the assessment of the extent of ischemia compared to wall motion abnormality alone. ...
... commercial contrast agents in patients known to have small right-to-left shunts through a patent foramen ovale (PFO) (saline contrast in the left atrium (LA) or LV that is transient and does not fill the LA or LV cavity) (14). Also in 2014, Shah et al. (54) showed that MCE provided incremental benefit over wall motion analysis in 25% of patients undergoing stress echocardiography and greater confidence with wall motion analysis in 62%. MCE detected significantly more cases of ischemia and detected a greater ischemic burden than did wall motion analysis on a per patient basis. ...
Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs.
... Slow replenishment of myocardial microbubbles during low power imaging following a transient increase in acoustic power (flash imaging) can indicate decreased perfusion, which occurs prior to abnormal wall motion, with reliable spatial and temporal resolution [23][24][25]. In one study of 220 patients, the addition of myocardial contrast echocardiography improved the identification of ischemia in the left anterior descending (LAD) coronary artery territory and in multivessel disease as compared with wall motion assessment alone [26]. In a multi-center study of 628 intermediate risk patients, myocardial contrast echocardiography was more sensitive (75 versus 49 %, p<0.0001) although less specific (52 versus 81 %, p<0.0001) than single-photon emission computed tomography (SPECT) for detecting CAD [23]. ...
Cardiovascular disease is a leading cause of morbidity and mortality, and noninvasive strategies to diagnose and risk stratify patients remain paramount in the evaluative process. Stress echocardiography is a well-established, versatile, real-time imaging modality with advantages including lack of radiation exposure, portability, and affordability. Innovative techniques in stress echocardiography include myocardial contrast echocardiography, deformation imaging, three-dimensional (3D) echocardiography, and assessment of coronary flow reserve. Myocardial perfusion imaging with single-photon emission computed tomography (SPECT) or positron emission tomography (PET) are imaging alternatives, and stress cardiac magnetic resonance imaging and coronary computed tomography (CT) angiography, including CT perfusion imaging, are emerging as newer approaches. This review will discuss recent and upcoming developments in the field of stress testing, with an emphasis on stress echocardiography while highlighting comparisons with other modalities.
The currently available ultrasound-enhancing agents are approved for left ventricle opacification and Doppler enhancement. The current recommendation for stress echo is mainly focused on contrast enhancement of endocardial contour for analysis of regional wall motion abnormalities and left ventricular volumes, although a possible application is also in the enhancement of pulsed wave Doppler signal for left anterior descending flow detection in 5% of patients without readable signal at rest. Regarding the most attractive application of perfusion imaging, despite its tremendous proven potential, perfusion imaging with real-time myocardial contrast echocardiography is not a Food and Drug Administration-approved technique. Also, the European Medicine Agency did not approve ultrasound contrast agents for this specific application. As a result, real-time myocardial contrast echocardiography is seldom used. The key points of ultrasound-enhancing agents suggested utilization in stress echo have been summarized by the American Society of Echocardiography recommendations as follows: (1) whenever two or more contiguous segments cannot be visualized or a coronary artery territory cannot be completely visualized, (2) use of very low-dose bolus injections followed by slow saline flushes is optimal for reducing cavity shadowing, and (3) very low mechanical index pulse sequence schemes that detect nonlinear fundamental frequency responses at <0.2 mechanical indexes are recommended for optimal left ventricular opacification and reduced basal segment attenuation. Brief high mechanical index (>0.8) impulses (5–15 frames) can be used to clear the myocardium and improve endocardial border resolution. In the stress echo 2030 study network, a pragmatic approach is used. Contrast is used in its easiest single bolus administration both at rest and during stress, after standard acquisition without contrast, and such enhancement duration is sufficient for regional wall motion, left ventricular cavity, and coronary flow velocity assessment.
Over the last decades, echocardiography has progressively become an irreplaceable diagnostic technique for the assessment of patients with IHD. Echocardiography applied in conjunction with exercise or pharmacologic stress is used for the detection of inducible myocardial ischemia, and it is an essential supporting tool for clinicians in the evaluation, risk stratification, and follow-up of patients with IHD. Moreover, it is applied in the acute setting for the management of patients with AMI. Various new ultrasound techniques have been established in the last several years, including contrast echocardiography, three-dimensional echocardiography, and speckle tracking echocardiography, which advantages in IHD evaluation are extensively recognized. In this chapter, the authors will describe the use of standard and new echocardiographic techniques in the diagnosis and prognosis of IHD either in the chronic or in the acute settings.KeywordsEchocardiographyAcute myocardial infarctionIschemic heart failureMechanical ischemic complications
Contrast echocardiography is a family of ultrasound-based procedures, whereby acoustic enhancing agents, usually microbubbles, are administered by intravenous route and detected in order to improve diagnostic performance. This review describes: (1) the agents that have been designed for diagnostic imaging, (2) current clinical applications where either left ventricular opacification or microvascular perfusion imaging with myocardial contrast echocardiography have been demonstrated to provide incremental information to non-contrast echocardiography and (3) future diagnostic and therapeutic applications of contrast ultrasound that rely on unique compositional design of ultrasound-enhancing agents.
Background
Many patients with chronic angina experience anginal episodes despite successful recanalization, antianginal and antiischemic medications. Empirical observations suggested that Shenzhu Guanxin Recipe Granules (参术冠心方颗粒, SGR), a Chinese herbal compound, exerted potential impacts on increased treadmill exercise performance and angina relieve. However, there has been no systematic study to clarify the impact of SGR on exercise tolerance in patients with stable angina. The SERIES (ShEnzhu guanxin Recipe for Improving Exercise tolerance in patients with Stable angina) trial is designed to determine the effects of SGR on exercise duration, electrocardiographic (ECG) evidence of myocardial ischemia, and incidence of major adverse cardiac events (MACE) in stable anginal patients.
Methods
A total of 184 eligible patients with stable angina will be randomly assigned to receive placebo or SGR (10 g/day for 12 weeks) in a 1:1 ratio. The primary outcome will be the change from baseline in total exercise tolerance duration, time to onset of angina and ECG ischemia during exercise treadmill testing performed over a 12-week study period. The secondary outcome will include ECG measures, the occurrence and composite of MACE and the Seattle Angina Questionnaire score. Moreover, the coronary microcirculation will be evaluated to explore the possible effects in response to treatment of SGR. After the procedure, all participants will be followed up by interview at 3 and 6 months, enquiring about any cardiac events, hospitalizations, cardiac functional level and medication usage. Additionally, the occurrence of adverse events will be evaluated at each follow-up.
Discussion
This study may provide novel evidence on the efficacy of SGR in improving exercise tolerance and potentially reducing clinical adverse events. (Trial registration No. ChiCTR-TRC-14004504)
Stress echocardiography is an established tool to assess for both myocardial ischemia and viability. However, the utility of exercise echocardiography extends beyond the evaluation of coronary artery disease. Assessing the cardiovascular response to exercise can also be used to unmask the presence of, and to assess the severity of, valvular heart disease, heart failure (HF), hypertrophic cardiomyopathy (HCM), and pulmonary hypertension (PH). Resting echocardiography may not fully capture the dynamic nature of these diseases, which are influenced by loading conditions and changes in cardiac output. In this chapter, we review the use of exercise and pharmacologic stress echocardiography for evaluation of myocardial ischemia and viability. We also discuss the most relevant exercise echocardiographic assessments for individual valvular lesions, HCM, PH, and HF with preserved ejection fraction, along with the existing data supporting these assessments.
Stress echocardiography is a widely utilised test in patients with known or suspected coronary artery disease (CAD), valvular heart disease and cardiomyopathies. Its advantages include the ubiquitous availability of echocardiography, lack of ionising radiation, choice of physiological or pharmacological stressors, good diagnostic accuracy and robust supporting evidence base. SE has evolved significantly as a technique over the past three decades and has benefitted considerably from improvements in overall image quality (superior resolution), machine technology (e.g. digital cine-loop acquisition and side-by-side image display) and development of second generation ultrasound contrast agents that have improved reader confidence and diagnostic accuracy. The purpose of this article is to review the breadth of SE in contemporary clinical cardiology and discuss the recently launched British Society of Echocardiography (BSE) Stress Echocardiography accreditation scheme.
Background and objectives:
Automatic delineation of the myocardium in echocardiography can assist radiologists to diagnosis heart problems. However, it is still challenging to distinguish myocardium from other tissue due to a low signal-to-noise ratio, low contrast, vague boundary, and speckle noise. The purpose of this study is to automatically detect myocardium region in left ventricle myocardial contrast echocardiography (LVMCE) images to help radiologists' diagnosis and further measurement on infarction size.
Methods:
The LVMCE image is firstly mapped into neutrosophic similarity (NS) domain using the intensity and homogeneity features. Then, a neutrosophic active contour model (NACM) is proposed and the energy function is defined by the NS values. Finally, the ventricle is detected using the curve evolving results. The ventricle's boundary is identified as the endocardium. To speed up the evolution procedure and increase the detection accuracy, a clustering algorithm is employed to obtain the initial ventricle region. The curve evolution procedure in NACM is utilized again to obtain the epicardium, where the initial contour uses the detected endocardium and the anatomy knowledge on the thickness of the myocardium.
Results:
Echocardiographic studies are performed on 10 male Sprague-Dawley rats using a Vivid 7 system including 5 normal cases and 5 rats with myocardial infarction. The myocardium boundaries manually outlined by an experienced radiologist are used as the reference standard for the performance evaluation. Two metrics, Hdist and AvgDist, are employed to evaluate the detection results. The NACM method was compared with those from the eliminated particle swarm optimization (EPSO) and active contour model without edges (ACMWE) methods. The mean and standard deviation of the Hdist and AvgDist on endocardium are 6.83 ± 1.12mm and 0.79 ± 0.28mm using EPSO method, 7.12 ± 0.98mm and 0.82 ± 0.32mm using ACMWE method, and 4.55 ± 0.9mm and 0.58 ± 0.18mm using NACM method, respectively. The improvement on epicardium is much more significant, and two metrics are decreased from 7.45 ± 1.24mm, and 1.47 ± 0.34mm using EPSO method, and 8.21±0.43mm, and 1.73±0.47mm using ACMWE method, to 4.94 ± 0.82mm, and 0.84 ± 0.22mm using NACM method, respectively.
Conclusions:
The proposed method can automatically detect myocardium accurately, and is helpful for clinical therapeutics to measure myocardial perfusion and infarct size.
Patients with previous coronary artery bypass grafting (CABG) are susceptible to the development of recurrent myocardial ischemia due to incomplete revascularization, progression of epicardial coronary artery disease of the native vessels, and/or development of new disease in bypass grafts. Imaging stress testing allows the accurate detection of myocardial ischemia in these patients.
The presence of myocardial ischemia on stress echocardiography predicts adverse outcomes both in symptomatic and asymptomatic patients with prior revascularization and can impact the further management of the patients.
This chapter covers the indications, diagnostic accuracy, prognostic value, and specific issues regarding methodology, safety, and tolerability of stress echocardiography in patients with previous coronary artery bypass grafting.
Aims:
Ultrasound contrast agents may be used for the assessment of regional wall motion and myocardial perfusion, but are generally considered not suitable for deformation analysis. The aim of our study was to assess the feasibility of deformation imaging on contrast-enhanced images using a novel methodology.
Methods and results:
We prospectively enrolled 40 patients who underwent stress echocardiography with continuous intravenous infusion of SonoVue for the assessment of myocardial perfusion imaging with flash replenishment technique. We compared longitudinal strain (Lε) values, assessed with a vendor-independent software (2D CPA), on 68 resting contrast-enhanced and 68 resting noncontrast recordings. Strain analysis on contrast recordings was evaluated in the first cardiac cycles after the flash. Tracking of contrast images was deemed feasible in all subjects and in all views. Contrast administration improved image quality and increased the number of segments used for deformation analysis. Lε of noncontrast and contrast-enhanced images were statistically different (-18.8 ± 4.5% and -22.8 ± 5.4%, respectively; P < 0.001), but their correlation was good (ICC 0.65, 95%CI 0.42-0.78). Patients with resting wall-motion abnormalities showed lower Lε values on contrast recordings (-18.6 ± 6.0% vs. -24.2 ± 5.5%, respectively; P < 0.01). Intra-operator and inter-operator reproducibility was good for both noncontrast and contrast images with no statistical differences.
Conclusions:
Our study shows that deformation analysis on postflash contrast-enhanced images is feasible and reproducible. Therefore, it would be possible to perform a simultaneous evaluation of wall-motion abnormalities, volumes, ejection fraction, perfusion defects, and cardiac deformation on the same contrast recording.
Stress echocardiography (SE) is an established tool not only for the assessment of coronary artery disease (CAD), but also for the evaluation of valvular disease and cardiomyopathy. New techniques, namely contrast echocardiography for function and perfusion including assessment of coronary flow reserve, strain imaging, 3-dimensional echocardiography, Doppler-derived coronary flow reserve and multimodality echocardiography, have been incorporated into stress protocols for improving assessment of cardiac disease. In this review, the advantages and disadvantages of these novel SE techniques are examined in terms of feasibility, accuracy, reproducibility and applications.
En este artículo se realiza una revisión de las aportaciones de las técnicas de imagen más relevantes a la cardiología que se han publicado durante este año. El ecocardiograma sigue siendo la piedra angular en el diagnóstico y el seguimiento de las valvulopatías, con un esfuerzo continuo para mejorar su cuantificación y obtener parámetros pronósticos de seguimiento. El estudio de la función miocárdica regional se afianza en el diagnóstico de la disfunción ventricular subclínica, y el ecocardiograma transesofágico tridimensional se ha convertido en el perfecto aliado del intervencionismo en las cardiopatías estructurales. La cardiorresonancia y la tomografía computarizada cardiaca acaparan la mayoría de las publicaciones en imagen cardiaca relativas a la cardiopatía isquémica, reflejo de unas técnicas más que consolidadas en la práctica clínica. La medicina nuclear destaca en el estudio de la viabilidad miocárdica tras el intervencionismo en el síndrome coronario agudo y refuerza su rendimiento en el diagnóstico de la cardiopatía isquémica.
Transthoracic echocardiography is the most widely used imaging test in cardiology. Although completely noninvasive, transthoracic echocardiography has a well-established role in the diagnosis of numerous cardiovascular diseases, and also provides critical qualitative and quantitative information on their prognosis and pathophysiological processes. The aim of this Review is to outline the broad principles of transthoracic echocardiography, including the traditional techniques of two-dimensional, colour, and spectral Doppler echocardiography, and newly developed advances including tissue Doppler, myocardial deformation imaging, torsion, stress echocardiography, contrast and three-dimensional echocardiography. The advantages and disadvantages, clinical application, prognostic value, and salient research findings of each modality are described. Advances in complex imaging techniques are expected to continue unabated, and this Review highlights technical improvements that will influence the diagnosis and improve our understanding of cardiovascular function and disease.
Background:
In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease.
Methods:
In this randomized trial, we assigned patients with diabetes and multivessel coronary artery disease to undergo either PCI with drug-eluting stents or CABG. The patients were followed for a minimum of 2 years (median among survivors, 3.8 years). All patients were prescribed currently recommended medical therapies for the control of low-density lipoprotein cholesterol, systolic blood pressure, and glycated hemoglobin. The primary outcome measure was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.
Results:
From 2005 through 2010, we enrolled 1900 patients at 140 international centers. The patients' mean age was 63.1±9.1 years, 29% were women, and 83% had three-vessel disease. The primary outcome occurred more frequently in the PCI group (P=0.005), with 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by differences in rates of both myocardial infarction (P<0.001) and death from any cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03).
Conclusions:
For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infarction, with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood Institute and others; FREEDOM ClinicalTrials.gov number, NCT00086450.).
To determine if perfusion stress echocardiography (PSE) with Imagify (perflubutane polymer microspheres) is comparable to stress perfusion imaging using (99m)Tc single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD.
Chronic, stable, chest pain patients (n=662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha=0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66-71%, P<or=0.004). Four demonstrated non-inferior sensitivity (68-77%, P<or=0.002), three demonstrated non-inferior specificity (72-88%, P<or=0.013). Three PSE readers (RAMP-2) were superior for sensitivity. Two PSE readers (RAMP-1) were superior for specificity. Area under the multi-reader receiver operating characteristics curve (0.72) was equal for both modalities. Majority of adverse events followed dipyridamole dosing, and were mild, transient, and required no treatment.
Imagify PSE was well-tolerated. Its diagnostic performance in chest pain patients is comparable with SPECT perfusion imaging.
This work is part of a collaborative clinical trial supported by contracts from the National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Background It remains difficult to distinguish an athlete's heart (physiological left ventricular hypertrophy (LVH) from hypertrophic cardiomyopathy (HCM) (pathological LVH) especially when subjects fall into Maron's grey zone ventricular wall thickness of 12–15 mm. Pathological LVH is one of the common causes of sudden death in young athletes. We hypothesised that pathological LVH due to HCM will have more fibrosis and reduced myocardial blood flow reserve (MBFR) compared to athletes. Capillary blood volume (CBV) which is reduced in fibrosis and MBFR can be assessed at the bedside by flash-replenishment myocardial contrast echocardiography (MCE).
Methods 25 subjects with genetically proven septal HCM and 25 athletes all with grey zone septal hypertrophy (13.7±1.2 mm) were recruited. There were no significant differences in age (p=0.57, 33±8 years/32±8 years), gender(males-HCM:21, Atheletes:25) and degree of septal LVH (p=0.71, 14±0.89 vs 13.7±1.03) between HCM and athletes. All subjects underwent rest and stress vasodilator myocardial contrast echocardiography and quantitative analysis of CBV (dâ), blood velocity (dâ/s), myocardial blood flow (db/s2) and MBFR(stress MBF/rest MBF) of the septum and apex was performed.
Results Patients with HCM had significantly lower CBV (15.56±12.45 vs 18.30±12.6; p value=0.01) at rest and significantly lower resting MBF (14.10±15 vs 36.1±14.7; p=0.032) compared to athletes. MBFR was also significantly reduced compared to athletes (2.49 vs 5.67; p value=0.027). The receiver-operator characteristics(ROC) curve for CBV and MBFR demonstrated areas under the curve of 0.65 and 0.84 respectively. A cut-off of MBFR of 4.8 provides a sensitivity and specificity of 99% and 81% respectively for the detection of pathological LVH. The positive predictive value for predicting pathological LVH was 88% with a negative predictive value of 92%.
Conclusions Quantitative MCE reliably distingisuishes physiological from pathological LVH in patients with grey zone hypertrophy who pose a diagnostic dilemma.
Objectives:
The purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD).
Background:
Small-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking.
Methods:
Patients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard (99m)Tc-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader.
Results:
Of 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular [CV] risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had ≥70% stenosis (131 had single-vessel disease [SVD]; 30 had multivessel disease), and 310 (60.1%) had ≥50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for ≥70% stenosis. Similar findings were obtained for patients with ≥50% stenosis. Sensitivity levels for detection of SVD and proximal disease for ≥70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively).
Conclusions:
SonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue® enhanced myocardial echocardiography [MCE] to single photon emission computerized tomography [ECG-GATED SPECT], at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease [CAD] in patients with suspect or known CAD using Coronary Angiography as Gold Standard-SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR).
Objectives:
The study sought to prospectively compare patient outcome after stress real-time myocardial contrast echocardiography (RTMCE) versus conventional stress echo (CSE), where contrast is used to optimize wall motion (WM) analysis.
Background:
Myocardial perfusion imaging with RTMCE may improve the detection of coronary artery disease (CAD), and predict patient outcome.
Methods:
Patients with intermediate to high pre-test probability referred for dobutamine or exercise stress echocardiography were prospectively randomized to either RTMCE or CSE. Definity contrast was used for CSE only when endocardial border delineation was inadequate (63% of studies). Studies were interpreted by either an experienced contrast reviewer (R1; n = 1257), or 4 Level 3 echocardiographers (R2) with basic contrast training (n = 806). Death, nonfatal myocardial infarction (MI), and revascularizations were recorded at follow-up.
Results:
Follow-up was available in 2,014 patients (median 2.6 years). Mean age was 59 ± 13 years (53% women). An abnormal RTMCE was more frequently observed than an abnormal CSE (p < 0.001), and more frequently resulted in revascularization (p = 0.004). Resting WM abnormalities were also more frequently seen with RTMCE (p < 0.01), and were an independent predictor of death/nonfatal MI (p = 0.005) for RTMCE, but not CSE. The predictive value of a positive study, whether with CSE or RTMCE, was significant for both R1 and R2 reviewers in predicting the combined endpoint, but R1 was better than R2 at predicting patients at risk for death or nonfatal MI.
Conclusions:
Perfusion imaging with RTMCE improves the detection of CAD during stress echocardiography, and identifies those more likely to undergo revascularization following an abnormal study.
Background:
Clinical assessment often cannot reliably or rapidly risk stratify patients hospitalized with suspected acute coronary syndrome. The real-world clinical value of stress echocardiography (SE) in these patients is unknown. Thus, we undertook this study to assess the feasibility, safety, ability for early triaging, and prediction of hard events of SE incorporated into a chest pain unit for patients admitted with acute chest pain, nondiagnostic ECG, and negative 12-hour troponin.
Methods and results:
Accordingly, 839 consecutive patients who underwent clinical, ECG, and SE assessments within 24 hours of admission were assessed for feasibility, safety, impact on triaging and discharge, and 30-day readmission rate and were followed up for hard events (all-cause mortality and acute myocardial infarction). Of the 839 patients, 811 (96.7%) had diagnostic SE results. Median time to SE and median length of stay for normal SE patients (77%) were both 1 day. The 30-day readmission rate was 0.5%. During long-term follow-up of 27±11 months, 39 hard events (30 deaths and 9 acute myocardial infarctions) occurred. Kaplan-Meier estimates of hard events were 0.5% versus 6.6% in the normal versus abnormal SE groups, respectively, in the first year of follow-up (15 events in the first year). Among all prognostic variables, only abnormal SE (hazard ratio, 4.08; 95% confidence interval, 2.15-7.72; P<0.001) and advancing age (hazard ratio, 1.78; 95% confidence interval, 1.39-2.37; P<0.001) predicted hard events in multivariable regression analysis.
Conclusions:
SE incorporated into a chest pain unit has excellent feasibility and provides rapid assessment and discharge with accurate risk stratification of patients with suspected acute coronary syndrome but nondiagnostic ECG and negative 12-hour troponin.
The addition of myocardial perfusion (MP) imaging during dipyridamole real-time contrast echocardiography improves the sensitivity to detect coronary artery disease, but its prognostic value to predict hard cardiac events in large numbers of patients with known or suspected coronary artery disease remains unknown.
We studied 1252 patients with the use of dipyridamole real-time contrast echocardiography and followed them for a median of 25 months. The prognostic value of MP imaging regarding death and nonfatal myocardial infarction was determined and related to wall motion (WM), clinical risk factors, and rest ejection fraction by the use of Cox proportional-hazards models, C index, and risk reclassification analysis. A total of 59 hard events (4.7%) occurred during the follow-up (24 deaths, 35 myocardial infarctions). The 2-year event-free survival was 97.9% in patients with normal MP and WM, 91.9% with isolated reversible MP defects but normal WM, and 67.4% with both reversible MP and WM abnormalities (P<0.001). By multivariate analysis the independent predictors of events were age (hazard ratio 1.05, 95% confidence interval [CI], 1.02-1.08), sex (hazard ratio, 2.36; 95% CI, 1.32-4.23), reversible MP defects (hazard ratio, 3.88; 95% CI, 1.83-8.21), and reversible WM abnormalities with reversible MP defects (hazard ratio, 4.51; 95% CI, 2.25-9.07). Reversible MP defects added incremental predictive value and reclassification benefit over WM response and clinical factors (P=0.001).
MP imaging using real-time perfusion echocardiography during dipyridamole real-time contrast echocardiography provides independent, incremental prognostic information regarding hard cardiac events in patients with known or suspected coronary artery disease. Patients with normal MP responses have better outcome than patients with normal WM; patients with both reversible WM and MP abnormalities have the worst outcome.
The cumulative published literature dealing with the most frequently utilized noninvasive cardiac stress imaging modalities (radionuclide myocardial perfusion scintigraphy and echocardiography) was reviewed to gain insight on their comparative diagnostic accuracies. To be included, studies had to be performed in conjunction with exercise or a commonly used intravenous pharmacologic stress agent (dipyridamole, adenosine or dobutamine) and had to report temporally related coronary angiography findings. A total of >75 studies were included, involving >7,000 patients. Exercise single-photon emitted computed tomographic (SPECT) scintigraphy was more sensitive than exercise echocardiography for detecting coronary artery disease (CAD), localizing it to the proper coronary artery distribution and correctly identifying the presence of multivessel CAD. Adenosine, dipyridamole, and dobutamine provided similar diagnostic accuracy when performed in conjunction with SPECT scintigraphy, and all were more accurate than dobutamine echocardiography. Clinical specificity was similarly high with adenosine SPECT, dipyridamole echocardiography, and exercise echocardiography, and lower with exercise SPECT. Normalcy rate was high for exercise SPECT and similar to clinical specificity for echocardiography.
Single photon-emission computed tomography (SPECT) is widely used for the assessment of hibernating myocardium (HM). The aim of this study was to test the hypothesis that myocardial contrast echocardiography (MCE), because of its better spatial and temporal resolution, would be superior to SPECT for the detection of HM.
Thirty-nine consecutive patients with symptomatic ischemic cardiomyopathy underwent rest and vasodilator SPECT and MCE. Of these, 23 survived to undergo assessment 3 months after revascularization for the recovery of left ventricular (LV) function (spontaneous recovery or dobutamine induced), which is the definition of HM.
Of the 214 dysfunctional segments, 156 segments demonstrated HM in the 23 patients, of whom 16 showed significant improvement in LV function. Logistic regression analysis showed that both qualitative and quantitative MCE were independent predictors for the detection of HM (P < .0001 vs P = .06 for qualitative MCE vs qualitative SPECT, respectively, and P < .01 vs P = .25 for all quantitative myocardial contrast echocardiographic parameters vs quantitative SPECT, respectively). Using clinical and LV functional data, SPECT, and MCE for predicting the recovery of LV function, MCE was the only independent predictor (P = .03).
MCE was superior to SPECT for the assessment of HM in ischemic cardiomyopathy.
This paper examines the evidence for contrast echocardiography, both for improving assessment of left ventricular structure and function compared with unenhanced echocardiography and for the identification of myocardial perfusion. Based on the evidence, recommendations are proposed for the clinical use of contrast echocardiography.
ACCREDITATION STATEMENT: The American Society of Echocardiography (ASE) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASE designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.trade mark Physicians should only claim credit commensurate with the extent of their participation in the activity. The American Registry of Diagnostic Medical Sonographers and Cardiovascular Credentialing International recognize the ASE's certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The ASE is committed to resolving all conflict-of-interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. TARGET AUDIENCE: This activity is designed for all cardiovascular physicians, cardiac sonographers, and nurses with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, sonographers, and other medical professionals having a specific interest in contrast echocardiography may be included. OBJECTIVES: Upon completing this activity, participants will be able to: 1. Demonstrate an increased knowledge of the applications for contrast echocardiography and their impact on cardiac diagnosis. 2. Differentiate the available ultrasound contrast agents and ultrasound equipment imaging features to optimize their use. 3. Recognize the indications, benefits, and safety of ultrasound contrast agents, acknowledging the recent labeling changes by the US Food and Drug Administration (FDA) regarding contrast agent use and safety information. 4. Identify specific patient populations that represent potential candidates for the use of contrast agents, to enable cost-effective clinical diagnosis. 5. Incorporate effective teamwork strategies for the implementation of contrast agents in the echocardiography laboratory and establish guidelines for contrast use. 6. Use contrast enhancement for endocardial border delineation and left ventricular opacification in rest and stress echocardiography and unique patient care environments in which echocardiographic image acquisition is frequently challenging, including intensive care units (ICUs) and emergency departments. 7. Effectively use contrast echocardiography for the diagnosis of intracardiac and extracardiac abnormalities, including the identification of complications of acute myocardial infarction. 8. Assess the common pitfalls in contrast imaging and use stepwise, guideline-based contrast equipment setup and contrast agent administration techniques to optimize image acquisition.
The development of an ischemic event, whether silent or painful, represents the cumulative impact of a sequence of pathophysiologic events. Each ischemic episode is initiated by an imbalance between myocardial oxygen supply and demand that may ultimately be manifested as angina pectoris. This sequence of events can be termed the ischemic cascade. The significance of this concept resides in the fact that it redirects the focus from the end result--angina--to the more fundamental, underlying pathophysiologic factors that precede it. Specifically, these events include diminished left ventricular compliance, decreased myocardial contractility, increased left ventricular end-diastolic pressure, ST-segment changes and, occasionally, angina pectoris.
The purpose of this study was to determine whether myocardial contrast echocardiography (MCE) can be used to detect coronary artery disease (CAD) during rest and pharmacological stress in humans through the use of venous injections of contrast.
Thirty patients with known or suspected CAD underwent MCE and 99mTc-sestamibi single-photon emission computed tomography (SPECT) at baseline and after dipyridamole (0.56 mg x kg(-1)) infusion. Ten myocardial segments (5 each in the apical two- and four-chamber views) from the two sets of images using both methods were scored for myocardial perfusion as follows: 1=normal, 0.5=mildly reduced, and 0=severely reduced. The information from baseline and postdipyridamole images was then used to determine whether an abnormal segment was irreversible (similar abnormal perfusion at baseline and after dipyridamole) or reversible (perfusion better at baseline compared with after dipyridamole). Concordance between segmental scores was 92% (kappa=.99) for both methods. Concordance between normal perfusion and reversible or irreversible segmental defects was 90% (kappa=.80). Agreem between the two methods for each of the three vascular territories in each patient was 90% (kappa=.77), while agreement for the presence or absence of CAD in each patient was 86% (kappa=.86). In the 4 patients with disagreement, the perfusion scores were 0.5 for SPECT and 1.0 for MCE.
This study shows that MCE, with venous injection of contrast, can define the presence of CAD during rest and pharmacological stress. The location of perfusion abnormalities and their physiologic relevance (reversible or irreversible) by MCE is similar to that provided by SPECT. MCE, therefore, holds promise for the noninvasive assessment of myocardial perfusion in humans.
This study sought to determine the basis of detection of stenosis by myocardial contrast echocardiography using venous administration of microbubbles and to define the relative merits of bolus injection versus continuous infusion.
The degree of video intensity (VI) disparity in myocardial beds supplied by stenosed and normal coronary arteries can be used to quantify stenosis severity after venous administration of microbubbles. However, the comparative merits of administering microbubbles as a bolus injection or continuous infusion has not been studied.
Coronary stenoses of varying severity were created in either the left anterior descending or the left circumflex coronary artery in 18 dogs. Imagent US (AF0150) was given as a bolus injection in 10 dogs (Group I) and as both a bolus injection and a continuous infusion in 8 dogs (Group II). For bolus injections, peak VI was derived from time-intensity plots. During continuous infusion, microbubble velocity and microvascular cross-sectional area were derived from pulsing interval versus VI plots. Myocardial blood flow (MBF) was determined using radiolabeled microspheres.
During hyperemia, VI ratios from the stenosed versus normal beds correlated with radiolabeled microsphere-derived MBF ratios from those beds for both bolus injections (r = 0.81) and continuous infusion (r = 0.79). The basis for detection of stenosis common to both techniques was the decrease in myocardial blood volume distal to the stenosis during hyperemia. The advantage of continuous infusion over bolus injection was the abolition of posterior wall attenuation and the ability to quantify MBF.
Both bolus injection and continuous infusion provide quantitative assessment of relative stenosis severity. Compared with bolus injection, continuous infusion also allows quantification of MBF and data acquisition without attenuation of any myocardial bed.
Our results demonstrate that a significant number of patients referred for stress echocardiography have suboptimal images, and that appropriate use of contrast for image enhancement is cost-effective because it substantially improves the image quality and favorably impacts the practice of performing additional tests for the same clinical indication.
In seeking an imaging solution to the limitations of standard exercise stress testing, echocardiography is attractive on practical grounds. It is the most widely disseminated and inexpensive technique for non-invasive imaging of the heart. It is "patient friendly" because it is rapidly performed, and is highly versatile, being usable in a variety of environments, in combination with various stressors, echocardiography provides a means of identifying myocardial ischaemia by detection of stress induced wall motion abnormalities. Indeed, an impressive clinical evidence base matches these theoretical benefits. The accuracy of stress echocardiography for detection of significant coronary stenoses ranges from 80-90%, exceeding that of the exercise ECG (especially in women and patients with left ventricular hypertrophy), and being comparable to that of stress myocardial perfusion scintigraphy. Stress echocardiography is a powerful prognostic tool in chronic coronary disease, after myocardial infarction, and in evaluation of patients before major non-cardiac surgery. It is an accurate test for prediction of functional recovery of dyssynergic zones after revascularisation, and also provides valuable physiologic information in patients under consideration for valve surgery. Unfortunately, however, the disadvantages of the technique are not trivial. Advances in imaging and image processing have solved most - but not all - problems of image quality. Test interpretation remains very much in the eye of the beholder. The only mainstream marker of ischaemia is abnormal wall motion, and the need to induce ischaemia in the metabolic sense limits the accuracy of stress echocardiography in detecting coronary artery disease in patients who exercise submaximally or who are on antianginal treatment. This article reviews the methodology and the favourable and unfavourable aspects of stress echocardiography. Technological advances in ultrasound and digital technology are likely to refine further the technique and move from a simple test of wall motion to portraying local contractile behaviour and perfusion. The automation of these processes will realise the vision of stress echocardiography as the stress imaging test of choice.
This study sought to compare the accuracy of myocardial contrast echocardiography (MCE) and wall motion analysis (WMA) during submaximal and peak dobutamine stress echocardiography (DSE) for the diagnosis of coronary artery disease (CAD).
The relative merits of MCE and WMA for the detection of CAD during DSE have not been studied in a large number of patients.
We studied 170 patients who underwent dobutamine (up to 50 microg/kg/min)-atropine stress testing and coronary angiography. The WMA and MCE (using repeated boluses of Optison [Mallinckrodt, St. Louis, Missouri] or Definity [Bristol-Myers Squibb, New York, New York]) were performed at rest, at intermediate stress (65% to 75% of maximal heart rate), and at peak stress. The diagnosis of CAD (>/=50% stenosis in >/=1 coronary artery) was based on reversible wall motion and perfusion abnormalities.
Coronary artery disease was detected in 127 (75%) patients. Sensitivity of MCE was higher than that of WMA at maximal stress (91% vs. 70%; p = 0.001) and at intermediate stress (84% vs. 20%; p = 0.0001). Specificity was lower for MCE compared with WMA (51% vs. 74%; p = 0.01). Overall accuracy was higher for MCE than for WMA (81% vs. 71%; p = 0.01). Sensitivity for detection of CAD based on abnormalities in >/=2 vascular regions was higher for MCE than for WMA (67% vs. 28%; p < 0.01).
The majority of inducible perfusion abnormalities occur at an intermediate phase of the stress test, without wall motion abnormalities. Myocardial contrast echocardiography provides better sensitivity than WMA, particularly in patients with submaximal stress and in identifying patients with multivessel CAD.
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.
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.
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.
The purpose of this study was to compare myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) for the detection of significant coronary artery disease (CAD) in patients with symptoms suggestive of CAD.
Single-photon emission computed tomography is a well-established method of assessing patients with CAD. Myocardial contrast echocardiography is a new technique allowing bedside assessment of myocardial perfusion. We hypothesized that MCE was comparable to SPECT in the assessment of patients with known or suspected CAD.
A total of 123 patients scheduled for coronary angiography underwent intermediate (mechanical index 0.5) triggered replenishment MCE and SPECT imaging at rest and after vasodilator stress. Coronary angiography was performed within four weeks of stress imaging.
In total, 96 of 123 (78%) patients demonstrated CAD (stenosis >/=50%). There was no difference in the sensitivity of MCE compared with SPECT in the detection of CAD (84% vs. 82%; p = NS), and both demonstrated similar specificity (56% vs. 52%, respectively). In patients with multivessel disease, MCE and SPECT also demonstrated similar sensitivity (91% and 88%, respectively) for the detection of CAD. Agreement between MCE and SPECT for the presence or absence of CAD was 73%.
Myocardial contrast echocardiography is comparable to SPECT in the detection of CAD not only on a patient basis but also in the localization of disease by vascular territory in a relatively high-risk population.
This study sought to determine whether residual myocardial viability determined by myocardial contrast echocardiography (MCE) after acute myocardial infarction (AMI) can predict hard cardiac events.
Myocardial viability detected by MCE has been shown to predict recovery of left ventricular (LV) function in patients with AMI. However, to date no study has shown its value in predicting major adverse outcomes in AMI patients after thrombolysis.
Accordingly, 99 stable patients underwent low-power MCE at 7 +/- 2 days after AMI. Contrast defect index (CDI) was obtained by adding contrast scores (1 = homogenous; 2 = reduced; 3 = minimal/absent opacification) in all 16 LV segments divided by 16. At discharge, 65 (68%) patients had either undergone or were scheduled for revascularization independent of the MCE result. The patients were subsequently followed up for cardiac death and nonfatal AMI.
Of the 99 patients, 95 were available for follow-up. Of these, 86 (87%) underwent thrombolysis. During the follow-up time of 46 +/- 16 months, there were 15 (16%) events (8 cardiac deaths and 7 nonfatal AMIs). Among the clinical, biochemical, electrocardiographic, echocardiographic, and coronary arteriographic markers of prognosis, the extent of residual myocardial viability was an independent predictor of cardiac death (p = 0.01) and cardiac death or AMI (p = 0.002). A CDI of < or = 1.86 and < or = 1.67 predicted survival and survival or absence of recurrent AMI in 99% and 95% of the patients, respectively.
The extent of residual myocardial viability predicted by MCE is a powerful independent predictor of hard cardiac events in patients after AMI.
Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS).
Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean=374+/-50 days) after randomization using paired exercise (n=84) or vasodilator stress (n=230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered > or = 10% myocardium. The primary end point was > or = 5% reduction in ischemic myocardium at follow-up. Treatment groups had similar baseline characteristics. At follow-up, the reduction in ischemic myocardium was greater with PCI+OMT (-2.7%; 95% confidence interval, -1.7%, -3.8%) than with OMT (-0.5%; 95% confidence interval, -1.6%, 0.6%; P<0.0001). More PCI+OMT patients exhibited significant ischemia reduction (33% versus 19%; P=0.0004), especially patients with moderate to severe pretreatment ischemia (78% versus 52%; P=0.007). Patients with ischemia reduction had lower unadjusted risk for death or myocardial infarction (P=0.037 [risk-adjusted P=0.26]), particularly if baseline ischemia was moderate to severe (P=0.001 [risk-adjusted P=0.08]). Death or myocardial infarction rates ranged from 0% to 39% for patients with no residual ischemia to > or = 10% residual ischemia on follow-up MPS (P=0.002 [risk-adjusted P=0.09]).
In COURAGE patients who underwent serial MPS, adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Our findings suggest a treatment target of > or = 5% ischemia reduction with OMT with or without coronary revascularization.
Pro-spective Evaluation of Outcomes With Stress Perfusion Imaging Versus Stress Wall Motion Imaging During Dobutamine or Exercise Echocardiog-raphy (POISE) trial
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Porter TR, Smith LM, Wu J, Thomas D, Haas JT, Mathers DH, et al. Pro-spective Evaluation of Outcomes With Stress Perfusion Imaging Versus Stress Wall Motion Imaging During Dobutamine or Exercise Echocardiog-raphy (POISE) trial. J Am Coll Cardiol 2013;61:2446-55.
Prospective Evaluation of Outcomes With Stress Perfusion Imaging Versus Stress Wall Motion Imaging During Dobutamine or Exercise Echocardiography (POISE) trial.
- Porter T.R.
- Smith L.M.
- Wu J.
- Thomas D.
- Haas J.T.
- Mathers D.H.
Porter TR, Smith LM, Wu J, Thomas D, Haas JT, Mathers DH, et al. Prospective Evaluation of Outcomes With Stress Perfusion Imaging Versus
Stress Wall Motion Imaging During Dobutamine or Exercise Echocardiography (POISE) trial. J Am Coll Cardiol 2013;61:2446-55.
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