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The Long-Term Prognostic Value of Negative Contrast Stress Echocardiography

John Lisko, Shuang Lin, Ioannis Parastatidis and Stamatios Lerakis*

Department of Internal Medicine, Division of Cardiology, Emory University School of Medicine, USA

*Corresponding Author:
Stamatios Lerakis
Department of Internal Medicine
Division of Cardiology
Emory University School of Medicine, USA
Tel: +1(404) 727 6123
E-mail: [email protected]

Received date: April 26, 2016; Accepted date: June 26, 2016; Published date: June 28, 2016

Copyright: © 2016 Lerakis S, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

 
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Abstract

Stress echocardiography is a sensitive and specific noninvasive technique for evaluation of my-ocardial ischemia. Stress echocardiography is portable and does not involve ionizing radiation. A known limitation of stress echocardiography is inadequate definition of the endocardial border, especially in patients with suboptimal imaging windows.

Contrast echocardiography is indicated for detection or definition in these patients or in cases where more than two cardiac segments are not adequately visualized. To date, few studies have evaluated the long-term prognostic value of contrast stress echocardiography. This study sought to determine the prognostic value of contrast stress echocardiography in patients at low to intermediate risk of coronary atherosclerotic disease.

Methods: Patients referred to the Emory University Hospital echocardiography lab for stress echocardiography and received Optison (R) contrast for left ventricular (LV) endocardial enhancement were included in this study. Patients received contrast when two or more cardiac segments were not adequately visualized. Demographic data and indication for examination was collected for each patient. Each study was classified as either negative for ischemia or positive if there was a new wall motion abnormality or worsening of a baseline abnormality.

The comprehensive electronic medical record was subsequently reviewed for major adverse cardiovascular events including death from any cause, death from a cardiovascular cause, myocardial infarction, congestive heart failure exacerbation, need for hospitalization for anginal chest pain, need for revascularization. This study was approved by the Emory University Hospital institutional review board.

Results: Fifty-one patients met the inclusion criteria for this study. Three patients had a positive stress echocardiogram. Of these three patients, one was treated with optimal medical therapy and the other two underwent angiography with percutaneous coronary intervention. During the mean follow-up period of 2.2 +/- 1.02 years (median 1.95 years) there was one death attributed to a patient discharge to Hospice, and there were no deaths attributable to a cardiac etiology.

There was one hospitalization for unstable angina and one hospitalization for a congestive heart failure exacerbation in the same patient. No patients underwent revascularization or had a myocardial infarction. Three cardiac catheterizations were performed during the follow-up period with no significant coronary artery disease.

Conclusions: Contrast stress echocardiography is useful for the noninvasive assessment of myocardial is-chemia. A negative contrast stress echocardiogram conveys a favorable prognosis over a two year period with a 98.0% negative predictive value.

Keywords

Stress echocardiography, Demographic data, Ischemia, Myocardial infarction, Coronary intervention

Introduction

Coronary artery disease is the leading cause of morbidity and mortality in the US [1]. While invasive coronary angiography is the gold standard for evaluation of coronary stenosis, the invasive nature of the test, radiation dose, and contrast load limit its routine use in low and intermediate risk patients.

For patients at intermediate risk of coronary artery disease, current guidelines recommend the use of non-invasive testing as the first line diagnostic modality [2].

In the US the most common non-invasive tests are nuclear myocardial perfusion imaging (MPI) and stress echocardiography. Stress echocardiography and MPI have comparable sensitivities and specificities [3]. Compared to nuclear imaging, stress-echocardiography does not require any degree of ionizing radiation, is portable, and relatively less expensive.

An inherent limitation of stress echocardiography is the ability to define the endocardial borders in approximately 20% of the patient population. Contrast echocardiography is commonly per-formed to better delineate the left ventricular endocardium, which allows for better evaluation of wall motion.

Current American Society of Echocardiography guidelines recommend contrast echocardiography to assess segmental wall motion abnormalities, increase the proportion of diagnostic studies, and increase reader confidence in interpretation [4].

Optison (Perflutren Protein-Type A Microspheres, injectable suspension, GE Healthcare) is indicated for enhancement of the left ventricle endocardium in patients with suboptimal echocardiograms. The agent is stable at room temperature for 24 hours, does not require a vial mixture, and can be injected at any stage of the echo procedure.

While multiple studies have assessed the diagnostic utility and safety of Optison for contrast stress echocardiography [5], to date few studies have evaluated the long-term prognostic value of contrast stress echocardiography. The reported negative predictive value of stress echocardiography is greater than 95% [6].

This study sought to determine the prognostic value of contrast stress echocardiography in patients at low to intermediate risk of coronary atherosclerotic disease.

Methods

This study was approved by the Emory University institutional review board. This is a single-center study based on review of the Emory University Hospital echocardiography database. Patients included in the study were referred to the Emory University Hospital echocardiography lab for stress echocardiography and received Optison (R) contrast for LV endocardial enhancement. Contrast was used when 2 or more segments could not be adequately visualized. Study enrollment began in 2012.

Sample size was determined using a one group Chi-Squared test. Approximating that the echo contrast would improve the technically inadequate stress echo to only 5% compared to 15-20%, a one group Chi-Squared test with a 0.050 one-sided significance level would have 80% power to detect the difference between the null hypothesis proportion and the alternative proportion at a sample size between 42-79 patients.

The echocardiographic images were acquired on either Phillips or GE scanners and analyzed with either Phillips and GE software. Data was collected and analyzed using SPSS 22.0.0 for Macintosh.

Patient's demographic data was collected including-age, sex, history of-congestive heart failure, hypertension, diabetes mellitus, hyperlipidemia, tobacco use, myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. The indication for each study was collected using ICD codes.

Each study was classified as either negative for ischemia or positive if there was either a new wall motion abnormality or worsening of a baseline abnormality. The comprehensive electronic medical record was subsequently reviewed for major adverse cardiovascular events including death from any cause, death from a cardiovascular cause, myocardial infarction, congestive heart failure exacerbation, need for hospitalization for anginal chest pain, need for revascularization.

Results

Fifty-one patients met the inclusion criteria for this study (21 female; 30 male). Stress was induced with Dobutamine in 41 patients and exercise in 10 patients. Baseline patient demographics are shown in Table 1 and indications for examination are outlined in Table 2. Table 3 summarizes the cardiovascular medications prescribed to patients. Mean follow-up time for all patients was 2.2 +/- 1.02 years (median 1.95 years).

Age 59.6 years
Sex 41.1% Female
History of CHF 2
History of HTN 33
History of Diabetes Mellitus 17
History of Tobacco Use 23
History of Dysplipidemia 16
History of MI 2
History of PCI 2
History of CABG 2
Describes the baseline characteristics of patients included in the study. The risk factors in this population place those who underwent contrast stress echocardiography at intermediate risk for coronary artery disease

Table 1: Baseline study population characteristics.

Indication for Exam Number of Exams
Cardiomyopathy 1
Chest Pain 16
Dyspnea 1
Evaluate Cardiac Function 1
Family History of Ischemic HeartDisease 1
Palpitations 1
Pre-Operative Evaluation 28
Screening for CardiovascularConditions 2
Details the indication for each contrast stress echocardiogram by ICD code.

Table 2: Indications for contrast stress echocardiogram.

Medication/Medication Class Negative Stress Cohort Positive Stress Cohort
Aspirin 16 3
Statin 8 2
ACE/ARB 17 2
Clopidogrel 1 1
Beta-Blocker 13 2
Calcium Channel Blocker 15 2
Diuretic 9 1
Details cardiovascular medications taken by patients in the follow-up period

Table 3: Cardiovascular medications during follow-up period.

The patient outcomes are summarized in Figure 1. Specifically, three patients had a positive stress echocardiogram. Of these three patients, one had known coronary artery disease and was treated with optimal medical therapy without a cardiac catheterization performed, and the other two underwent angiography that revealed obstructive coronary artery disease requiring percutaneous coronary intervention.

interventional-cardiology-Patient-outcomes-results

Figure 1: Patient outcomes based on the results of the contrast stress echocardiogram. There was a low event rate in the group with a negative result over them mean 2.2 +/- 1.02 years (median 1.95 years) follow-up period.

During the follow-up period there was one non-cardiac death attributed to a patient discharge to Hospice, and there were no deaths attributable to a cardiac etiology.

There was one hospitalization for unstable angina and one hospitalization for a congestive heart failure exacerbation in the same patient. No patients underwent revascularization or had a myocardial infarction.

Three cardiac catheterizations were performed during the follow-up period with no significant coronary artery disease. Furthermore, in the negative stress group 3 patients underwent cardiac catheterization during the follow up period with no significant coronary artery disease.

Discussion

This small study summarizes the Emory University Hospital experience with Optison contrast stress echocardiography from 2012 onward. The majority of patients in this study had a normal Optison stress echo, paralleling the trend in decreasing stress induced ischemia during SPECT-MPI studies, previously published by Rozanski [7]. The study was conducted at a tertiary referral center; however the baseline demographics approximate the severity and prevalence of illness seen across practice settings. While multiple studies have evaluated the prognostic role of stress echocardiography [8,9] there are limited studies in patients exclusively undergoing contrast stress echocardiograms [10].

This study further delineated the value of contrast stress echocardiography in patients at intermediate risk for coronary artery disease. Notably, in this study cohort, patients without evidence of inducible ischemia had a favorable prognosis during the follow-up period. This can be at least partially explained by the enhanced delineation of the endocardial border using Optison. The negative predictive value of 98.0% over approximately a two year period emphasizes the utility of contrast stress echocardiography. Following a negative study, patients can be reassured of the low-likelihood of a major adverse cardiovascular event. Additionally, the addition of Optison contrast led to 100% interpretability of stress echocardiograms, eliminating the need for repeat or invasive studies.

Contrast stress echocardiography is a portable and radiation free non-invasive evaluation of cardiac structure, function, and assessment for ischemia. It conveys meaningful diagnostic and prognostic information in patients at intermediate risk of coronary artery disease. The low event rate following a negative study underscores the value of a negative contrast stress echocardiogram.

Limitations

This was a single center study with a relatively small number of patients. Despite being performed at one center, multiple cardiologists were involved in the interpretation of the studies. Additionally, as the study was performed in a tertiary setting there is a diverse case mix to avoid bias in an overly low risk population. Further studies are warranted with a larger sample population.

Acknowledgements

This work was supported by a research grant from GE Healthcare.

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