15 Contrast Echocardiography

Overview

Despite improvements in ultrasound imaging techniques, including harmonic imaging, an estimated 5% to 10% of resting echocardiograms and 20% to 30% of stress echocardiograms are suboptimal. To overcome these limitations and improve echocardiographic image quality, ultrasound contrast agents have been developed that, unlike the agitated saline contrast used to detect intracardiac and intrapulmonary shunts, freely cross the pulmonary circulation and readily opacify the left heart after an intravenous injection (Fig. 15-1).^1,² These contrast agents consist of microbubbles (2–5 μm, smaller than red blood cells), containing an inert gas within a biodegradable shell (albumin/lipid/polymer/surfactant-based) (Table 15-1). These agents are not radioactive and are non-nephrotoxic, and they pass unimpeded through the microcirculation without causing hemodynamic effects.² Specific imaging techniques, including harmonic imaging, have been developed to enhance the acoustic signal from microbubbles, while eliminating surrounding tissue signal.³ In this fashion, a sharp delineation between the blood pool and endocardial border is obtained, thus enabling the acquisition of transthoracic echocardiographic images of improved quality, with greater definition of intracardiac structures and better delineation of the left ventricular (LV) endocardial border. Extensive research also has been performed studying the use of these contrast agents to assess myocardial perfusion in many settings, with multicenter phase II and III clinical trials recently completed.⁴

Indications

Intravenous microbubble ultrasound contrast agents are indicated for left ventricular opacification and improvement of LV endocardial border delineation in patients with suboptimal acoustic windows (see Fig. 15-1), with several agents approved for this indication.^5,⁶ Ultrasound contrast agents have been proven to be safe and effective in numerous clinical studies (Box 15-1), are relatively simple and easy to use, and can be used with all currently available echocardiographic systems. Use of these agents during transthoracic echocardiography has been shown in clinical studies to

Improve the qualitative assessment of global LV systolic function ^1,⁷

Improve the accuracy of quantification of LV volumes and LV ejection fraction (Fig. 15-2)^8,⁹

Improve the accuracy and interobserver agreement for the assessment of regional wall motion (Fig. 15-3)¹⁰

Increase the diagnostic accuracy of exercise and dobutamine stress echocardiography (Fig. 15-4), reduce the interobserver variability, improve interpreter confidence, and enhance the reproducibility of stress echocardiographic studies^11,¹²

Improve the echocardiographic detection rates of myocardial rupture, pseudoaneurysms, intracardiac thrombi (Figs. 15-5 and 15-6), aortic dissection (Fig. 15-7), apical hypertrophic cardiomyopathy (Fig. 15-8), and LV noncompaction (Fig. 15-9)¹³^–¹⁵

Enhance left-sided Doppler velocity signals in the assessment of intracardiac pressures and transvalvular gradients ¹⁶

Safety Issues

Based on post-marketing data, the estimated risk of an anaphylactoid reaction with microbubble contrast administration is 1:10,000, and the risk of an associated severe fatal allergic reaction is 1:500,000.¹⁷ Although the United States Food and Drug Administration (FDA) attached a “black box” warning to the monograph of perflutren-based microbubble ultrasound contrast agents, this was subsequently revised in May 2008.¹⁷ Initial concerns were raised over four cases of cardiac arrest within 30 minutes of contrast administration. All four cases were patients with documented heart disease and serious comorbidities, where a direct cause-and-effect relationship could not be established. Retrospective studies have since demonstrated that the overall risks of ultrasound contrast agents are very low, and fatal event rates are similar to those of non–contrast-enhanced echocardiography, suggesting that the adverse fatal events were unlikely to be directly related to the administration of these agents.^18,¹⁹ Prospective registries to monitor and determine the safety of these agents have been initiated. The current contraindications to ultrasound contrast use are listed in Box 15-2. It is also recommended that patients with potentially unstable cardiac or pulmonary conditions (Box 15-3) be monitored both during and for at least 30 minutes after microbubble contrast administration.