Michael L. Main

Acute Mortality in Hospitalized Patients Undergoing Echocardiography With and Without an Ultrasound Contrast Agent (Multicenter Registry Results in 4,300,966 Consecutive Patients)

We sought to define acute mortality in a large multicenter cohort of hospitalized patients undergoing clinically indicated echocardiography with and without use of an ultrasound contrast agent. Although the United States Food and Drug Administration recently relaxed the issued warnings for perflutren-containing ultrasound contrast agents on May 13, 2008, concerns still exist regarding the safety of these compounds, particularly in critically ill patients. A retrospective analysis was performed using the Premier Perspective Database. Patients undergoing echocardiography during hospitalization were separated into those performed without contrast enhancement and those performed with perflutren lipid microsphere (PLM) injectable suspension contrast agent (Definity, Lantheus Medical Imaging, North Billerica, Massachusetts). Vital status within 1 day of the echocardiogram was available for all patients using hospital billing data. Between January 1, 2002 and October 31, 2007, 4,300,966 patients underwent transthoracic echocardiography at rest during hospitalization (unenhanced studies n = 4,242,712 and contrast-enhanced studies n = 58,254). Multivariate logistic regression analysis was used to compare 24-hour mortality, controlling for case mix and clinical covariates; 1-day mortality rates were 1.08% (n = 45,789 deaths) for patients undergoing noncontrast studies and 1.06% (n = 616 deaths) for patients undergoing contrast-enhanced examinations (p = 0.613). Multivariate logistic regression analysis revealed that, in patients undergoing an echocardiogram, patients receiving PLM injectable suspension contrast agent were 24% less likely to die within 1-day than patients not receiving a contrast agent (adjusted odds ratio = 0.76, 95% confidence interval 0.70 to 0.82). In conclusion, acute crude mortality was not increased in patients receiving PLM injectable suspension contrast agent. Multivariate logistic regression analysis revealed that, compared with patients not receiving a contrast agent, administration of PLM injectable suspension contrast agent during echocardiography was associated with a 24% decreased risk of mortality.

Acute Mortality in Hospitalized Patients Undergoing Echocardiography With and Without an Ultrasound Contrast Agent : Results in 18,671 Consecutive Studies

OBJECTIVES We sought to define acute mortality in hospitalized patients undergoing clinically indicated echocardiography with and without use of an ultrasound contrast agent. BACKGROUND The U.S. Food and Drug Administration recently issued a boxed warning and new contraindications for the perflutren-containing ultrasound contrast agents following post-marketing reports of 4 patient deaths that were temporally related to Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) administration. To appreciate the incremental risk of any medical procedure, the ambient risk of untoward outcome in the population in question must first be defined. There are no published data on short-term major adverse cardiac events in hospitalized patients undergoing echocardiography, either with or without administration of an ultrasound contrast agent. METHODS A retrospective analysis of hospitalized patients undergoing clinically indicated echocardiography between January 2005 and October 2007, within Saint Lukes Health System, Kansas City, Missouri, was performed. Studies were separated into 2 groups, those performed without contrast enhancement (n = 12,475) and those performed with Definity (n = 6,196). Vital status within 24 h of the echocardiographic study was available for all patients using a combination of the Social Security Death Master File and Saint Lukes Health System medical records. Incidence of death within 24 h was compared by chi-square test between Definity and unenhanced procedures. RESULTS Of the 18,671 patient events, 72 patients died within 24 h. Of those that underwent unenhanced echocardiography, 46 died within 24 h (0.37%). Of patients receiving Definity during the echocardiogram, 26 died within 24 h (0.42%). There was no statistical difference between these 2 groups (p = 0.60). No patient died within 1 h of the echocardiographic study. In a random sampling from the unenhanced (n = 201) and Definity groups (n = 202), patients who underwent Definity-enhanced echocardiography exhibited higher clinical acuity, and more significant comorbidities. CONCLUSIONS Approximately 0.4% of hospitalized patients die within 24 h of echocardiography. There is no increased mortality risk associated with Definity-enhanced examinations, despite evidence for higher clinical acuity and more comorbid conditions in patients undergoing contrast studies.

Full-motion pulse inversion power Doppler contrast echocardiography differentiates stunning from necrosis and predicts recovery of left ventricular function after acute myocardial infarction ☆

OBJECTIVES The goal of this study was to determine, in patients with a recent myocardial infarction (MI) and residual wall motion abnormalities within the distribution of the infarct-related artery, whether normal perfusion by myocardial contrast echocardiography (MCE) would accurately predict recovery of segmental left ventricular (LV) function. BACKGROUND Left ventricular dysfunction after acute MI may be secondary to myocardial stunning or necrosis. Recent technical innovations in contrast echocardiography, including pulse inversion imaging and power Doppler, now allow full-motion echocardiographic perfusion assessment from a venous injection of fluorocarbon-based contrast agent. METHODS Thirty-four patients with recent MI underwent baseline wall motion assessment and MCE two days after admission and follow-up echocardiography a mean of 55 days later. RESULTS Perfusion by MCE predicted recovery of segmental function with a sensitivity of 77%, specificity of 83%, positive predictive value of 90% and overall accuracy of 79%. The mean wall motion score at follow-up was significantly better in perfused, compared with nonperfused, segments (1.4 vs. 2.2, p < 0.0001). Additionally, 90% of perfused segments improved, while the majority of nonperfused segments remained unchanged. CONCLUSIONS Full-motion MCE utilizing an intravenous fluorocarbon-based agent and pulse inversion power Doppler techniques, identifies stunned myocardium, and accurately predicts recovery of segmental LV function in patients with recent MI.

Sudden Cardiac Arrest in Hypertrophic Cardiomyopathy in the Absence of Conventional Criteria for High Risk Status

Two patients with hypertrophic cardiomyopathy are reported from the recent experience of the Hypertrophic Cardiomyopathy Center of the Minneapolis Heart Institute Foundation, demonstrating limitations in the risk stratification algorithm currently used for this disease. One patient, an asymptomatic 21-year-old male college student, was prophylactically implanted with a cardioverter-defibrillator. This decision was based largely on the presence of apparent extensive myocardial fibrosis identified by contrast-enhanced cardiovascular magnetic resonance imaging, currently not considered a risk factor in this disease. Fifteen months later, ventricular fibrillation was interrupted by an appropriate defibrillator shock. The other patient, an asymptomatic 15-year-old male subject without any apparent high-risk markers, died suddenly at home. Necropsy examination of the heart identified scarring confined to portions of both left ventricular papillary muscles, possibly representing a substrate for ventricular tachyarrhythmias. In conclusion, these 2 cases demonstrate that present strategies for assessing high-risk status in hypertrophic cardiomyopathy are inadequate to identify all such patients. However, while the anecdotal nature of these observations cannot yet justify altering the general guidelines for implantation of defibrillators for the primary prevention of sudden death related to hypertrophic cardiomyopathy, 1 of our 2 cases suggests a future role for contrast-enhanced cardiovascular magnetic resonance in the risk stratification of this complex disease.

Cardiovascular screening with electrocardiography and echocardiography in collegiate athletes.

BACKGROUND Current guidelines for preparticipation screening of competitive athletes in the US include a comprehensive history and physical examination. The objective of this study was to determine the incremental value of electrocardiography and echocardiography added to a screening program consisting of history and physical examination in college athletes. METHODS Competitive collegiate athletes at a single university underwent prospective collection of medical history, physical examination, 12-lead electrocardiography, and 2-dimensional echocardiography. Electrocardiograms (ECGs) were classified as normal, mildly abnormal, or distinctly abnormal according to previously published criteria. Eligibility for competition was determined using criteria from the 36(th) Bethesda Conference on Eligibility Recommendations for Competitive Athletes with Cardiovascular Abnormalities. RESULTS In 964 consecutive athletes, ECGs were classified as abnormal in 334 (35%), of which 95 (10%) were distinctly abnormal. Distinct ECG abnormalities were more common in men than women (15% vs 6%, P<.001) as well as black compared with white athletes (18% vs 8%, P<.001). Echocardiographic and electrocardiographic findings initially resulted in exclusion of 9 athletes from competition, including 1 for long QT syndrome and 1 for aortic root dilatation; 7 athletes with Wolff-Parkinson-White patterns were ultimately cleared for participation. (Four received further evaluation and treatment, and 3 were determined to not need treatment.) After multivariable adjustment, black race was a statistically significant predictor of distinctly abnormal ECGs (relative risk 1.82, 95% confidence interval, 1.22-2.73; P=.01). CONCLUSIONS Distinctly abnormal ECGs were found in 10% of athletes and were most common in black men. Noninvasive screening using both electrocardiography and echocardiography resulted in identification of 9 athletes with important cardiovascular conditions, 2 of whom were excluded from competition. These findings offer a framework for performing preparticipation screening for competitive collegiate athletes.

Clinical applications of transpulmonary contrast echocardiography

BACKGROUND The recent development of new fluorocarbon-based echocardiographic contrast agents that are capable of opacification of the left-sided cardiac chambers after intravenous injection is a major new advance in diagnostic cardiac imaging. METHODS AND RESULTS This is a review article focusing on these novel contrast agents, new echocardiographic imaging techniques to optimize their efficacy, and their clinical applications. Specific clinical applications of these agents are (1) enhancement of endocardial border definition to improve assessment of regional and global left ventricular function, (2) myocardial perfusion imaging by intravenous contrast echocardiography, (3) augmentation of spectral and color flow Doppler images, and (4) tissue-specific targeting of microbubbles for delivery of therapeutic agents. CONCLUSIONS New intravenous contrast agents offer the possibility to assess myocardial perfusion echocardiographically. It is also possible to use these agents for delivery of therapeutic agents, including gene therapy.

Combined assessment of microvascular integrity and contractile reserve improves differentiation of stunning and necrosis after acute anterior wall myocardial infarction.

OBJECTIVES We sought to determine the relative accuracy of myocardial contrast echocardiography (MCE) and low-dose dobutamine echocardiography (LDDE) in predicting recovery of left ventricular (LV) function in patients with a recent anterior wall myocardial infarction (MI). BACKGROUND Left ventricular dysfunction after acute MI may be secondary to myocardial stunning or necrosis. Myocardial contrast echocardiography allows real-time echocardiographic perfusion assessment from a venous injection of a fluorocarbon-based contrast agent. Although this technique is promising, it has not been compared with LDDE. METHODS Forty-six patients underwent baseline wall motion assessment, MCE, and LDDE two days after admission, as well as follow-up echocardiography after a mean period of 53 days. RESULTS Perfusion by MCE predicted recovery of segmental function with a sensitivity of 69%, specificity of 85%, positive predictive value of 74%, negative predictive value of 81%, and overall accuracy of 78%. Contractile reserve by LDDE predicted recovery of segmental function with a sensitivity of 50%, specificity of 88%, positive predictive value of 72%, negative predictive value of 73%, and overall accuracy of 73%. Concordant test results occurred in 74% of segments and further increased the overall accuracy to 85%. The mean wall motion score at follow-up was significantly better in perfused versus nonperfused segments (1.9 vs. 2.6, p < 0.0001) and in segments with contractile reserve, compared with segments lacking contractile reserve (1.9 vs. 2.5, p < 0.0001). CONCLUSION Myocardial contrast echocardiography compares favorably with LDDE in predicting recovery of regional LV dysfunction after acute anterior wall MI. Concordant contractile reserve and myocardial perfusion results further enhance the diagnostic accuracy.

A Retrospective Comparison of Mortality in Critically Ill Hospitalized Patients Undergoing Echocardiography With and Without an Ultrasound Contrast Agent

OBJECTIVES To compare acute mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (UCA). BACKGROUND Because of serious cardiopulmonary reactions reported immediately after administration of perflutren-containing UCAs, the FDA required a black box safety warning for this class of agents, including perflutren protein-type A microspheres injectable suspension. METHODS This study used the largest hospital service-level database in the U.S. All adult patients undergoing in-patient echocardiography between January 2003 and October 2005 were identified (n = 2,588,722, of which 22,499 received perflutren protein-type A microspheres injectable suspension). Of the 22,499 contrast echocardiography patients, 2,900 had diagnoses meeting criteria for critical illness (heart failure, acute myocardial infarction, arrhythmia, respiratory failure, pulmonary embolism, emphysema, and pulmonary hypertension). To control for the differences between the contrast and noncontrast patients, we used propensity score matching. Variables used in the construction of the propensity score included comorbidities, demographic factors, hospital-specific factors, level of care, and mechanical ventilation status. Patients receiving contrast echocardiography were matched to 4 control patients who received noncontrast echocardiography. Conditional logistic regression was used to estimate mortality effects. RESULTS There were 167 deaths in the study among critically ill patients, 38 of 2,900 from the contrast group and 129 of 11,600 from the control group. The contrast agent was not associated with an increase in same-day mortality (odds ratio: 1.18; 95% confidence interval: 0.82 to 1.71; p = 0.37). Before matching, contrast patients showed greater morbidity than noncontrast patients (Deyo-Charlson comorbidity score 2.45 vs. 2.25, p < 0.0001). After propensity score matching, these differences were significantly reduced, showing that both groups were well balanced. CONCLUSIONS There is no increase in mortality in critically ill patients undergoing echocardiography with the UCA compared with case-matched control patients.

Ultrasound contrast agents: balancing safety versus efficacy

In October, 2007, the FDA issued a new ‘black box’ warning, several new disease state contraindications and a mandated 30-min post-procedure monitoring period for the ultrasound contrast agents Definity® (perflutren lipid microsphere injectable suspension, Lantheus Medical Imaging, North Billerica, MA, USA) and Optison™ (perflutren protein type A microspheres for injectable suspension, GE Healthcare, Buckinghamshire, UK). These labeling changes were largely secondary to reports of 4 patient deaths, and ∼ 190 other ‘serious cardiopulmonary reactions’ that were temporally related but not clearly causally attributable to Definity administration. Contrast agent use in the US plummeted in the immediate aftermath of this FDA action, with many hospitals, physician offices and outpatient imaging centers suspending contrast echocardiography altogether. This review will focus on the immediate response from the international physician community, new contrast agent safety data published within the past year, results of a special meeting of the FDA Cardio-Renal panel devoted to contrast agent safety in June 2008, recently issued revised product labeling for both agents and future prospects for contrast echocardiography.

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF.