Stress Echo Ultrasound Contrast in an Urban Safety Net Hospital to Refine Ischemia Evaluation (SECURE)

The current study is designed to have broad generalizability and inform a potential shift toward greater utilization of stress echocardiography with UCA. This will be accomplished by comparing UCA stress echocardiography with myocardial SPECT among hospitalized patients presenting with atraumatic chest pain. This study seeks to demonstrate: clinical comparability of the 2 modalities (based on non-diagnostic test rates), improved care efficiency (based on length of stay), lower costs, improved provider satisfaction, and a presumed improved safety profile through the elimination of radiation exposure.

Primary Hypothesis: A strategy of routine UCA (Optison™) enhanced stress echocardiography will result in a clinically non-diagnostic test rate comparable to myocardial SPECT among patients hospitalized (inpatient or hospital observation status) with atraumatic chest pain.

Study Overview

• Status: Completed
• Conditions: Chest Pain; Symptomatic Ischemic Equivalent
• Intervention / Treatment: Other: UCA stress echocardiography or myocardial SPECT

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must meet all of the following inclusion criteria to be eligible for participation in this study:

  1. Males or females aged ≥ 18 years
  2. Evaluated for symptoms of chest discomfort or ischemic equivalent

  3. Clinical indication for stress imaging, defined as one of the following clinical risk estimates for CAD based upon the Diamond and Forrester classification7:

     • Intermediate pretest probability of CAD and electrocardiogram (ECG) is clinically interpretable and patient is able to exercise
     • Intermediate pretest probability of CAD and ECG is clinically interpretable or patient is unable to exercise
     • High pretest probability of CAD regardless of ECG interpretability and ability to exercise
  4. Willing and able to provide written informed consent to participate in this study
  5. Agrees to remain under observation (e.g., inpatient or observational status) until all study procedures from the hospital stay are completed, and to complete a 30-day follow up call

Exclusion Criteria:

• Patients who meet any of the following exclusion criteria are not to be enrolled in this study:

  1. Documented medical history or discovery during screening and/or admission of any of the following:

     • Severe aortic or mitral stenosis
     • Significant resting left ventricular outflow tract obstruction (velocity > 3 cm/s)
     • Mobile left ventricular apical thrombus
     • Acute pericarditis or pericardial tamponade
     • Ascending or thoracic aortic aneurysm that is not stable or meets surgical criteria
     • Acute decompensated congestive heart failure
     • Established severe left ventricular systolic dysfunction (left ventricular ejection fraction < 35%)
  2. Definite acute coronary syndrome (e.g., unstable angina, acute myocardial infarction) as confirmed by elevated Troponin I (>0.6 ng/L) on two successive measurements or ECG changes diagnostic for unstable angina (e.g. localized ST changes) in conjunction with clinical appraisal

  3. Any of the following other abnormalities on the ECG at screening:

     • Paced ventricular rhythm or complete left bundle branch block
     • Uncontrolled arrhythmias defined by frequent premature ventricular complexes (PVCs) > 10/minute, non-sustained ventricular tachycardia, or atrial fibrillation with rapid ventricular response
     • 2nd or 3rd degree heart block
  4. Uncontrolled hypertension defined as systolic blood pressure ≥ 200 mmHg and/or diastolic blood pressure ≥ 110 mmHg at screening
  5. Hemoglobin (Hb) < 7.5 mg/dL at screening or within 3 months prior to screening
  6. Potassium < 3.0 mmol/L or > 5.5 mmol/L or severe electrolyte abnormality at screening that, in the opinion of the supervising physician or Investigator, makes stress testing unsafe
  7. Females who are pregnant or nursing
  8. Known intolerance to any of the study stress agents (dipyridamole, dobutamine) or study cardiac imaging agents (Optison, Cardiolite)
  9. Weight ≥ 350lbs
  10. Any physical or psychological condition that, in the opinion of the Investigator, may adversely affect the safety of the patient if enrolled in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: stress echocardiography; Comparative effectiveness	Other: UCA stress echocardiography or myocardial SPECT; Comparative Effectiveness of cardiac stress imaging modalities
Other: Myocardial SPECT; CER	Other: UCA stress echocardiography or myocardial SPECT; Comparative Effectiveness of cardiac stress imaging modalities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of non-diagnostic tests between ultrasound contrast enhanced stress echocardiography and myocardial SPECT	Non-diagnostic test rates will be the principal outcome of interest and are defined as those studies that do not allow a clinical decision for patient disposition (alternative non-invasive modality ordered, imaging inadequate to exclude ischemia, target heart rate not achieved, adverse side effects and test was terminated, discharge, further invasive testing such as coronary angiography) or require cardiology consultation for further evaluation.	Within 5 days of stress imaging

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Similarity in rates of cardiac catheterization and acute coronary syndrome events between UCA stress echocardiography and myocardial SPECT	30-day rates of cardiac catheterization between the two imaging modalities; Difference in the 30-day composite rate of acute coronary syndrome re-hospitalization, revascularization, and death between the two imaging modalities; Similarity in positive predictive value (PPV) of the two imaging modalities; Inter-rater reliability estimates for non-diagnostic echocardiogram studies	by 30 +/- 7 days post-discharge
Shorter length of stay and lower cost of inpatient hospital care for UCA stress echocardiography than for myocardial SPECT	Length of inpatient hospital stay of UCA stress echocardiography versus myocardial SPECT; Difference in time-to-cardiac catheterization beginning from time of admission; Differences in time-to-stress test completion beginning from time of admission30-day hospital costs of UCA stress echocardiography versus myocardial SPECT	30 day assesment
Greater physician satisfaction when using UCA stress echocardiography than for myocardial SPECT	•Physician satisfaction as assessed on questionnaire with UCA stress echocardiography versus myocardial SPECT. Physician(s) will be the provider(s) who supervised patient care during inpatient hospital stay.	5 days

Collaborators and Investigators

• Sponsor: Denver Health and Hospital Authority
• Collaborators: General Electric
• Investigators: Principal Investigator: Mori Krantz, MD FACC FACP, Denver Health Medical Center

Publications and helpful links

General Publications

• Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med. 1999 May 4;130(9):719-28. doi: 10.7326/0003-4819-130-9-199905040-00003.
• Berrington de Gonzalez A, Mahesh M, Kim KP, Bhargavan M, Lewis R, Mettler F, Land C. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009 Dec 14;169(22):2071-7. doi: 10.1001/archinternmed.2009.440.
• Fazel R, Krumholz HM, Wang Y, Ross JS, Chen J, Ting HH, Shah ND, Nasir K, Einstein AJ, Nallamothu BK. Exposure to low-dose ionizing radiation from medical imaging procedures. N Engl J Med. 2009 Aug 27;361(9):849-57. doi: 10.1056/NEJMoa0901249.
• Kisacik HL, Ozdemir K, Altinyay E, Oguzhan A, Kural T, Kir M, Kutuk E, Goksel S. Comparison of exercise stress testing with simultaneous dobutamine stress echocardiography and technetium-99m isonitrile single-photon emission computerized tomography for diagnosis of coronary artery disease. Eur Heart J. 1996 Jan;17(1):113-9. doi: 10.1093/oxfordjournals.eurheartj.a014669.
• Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979 Jun 14;300(24):1350-8. doi: 10.1056/NEJM197906143002402.
• Salame G, Juselius WE, Burden M, Long CS, Bendelow T, Beaty B, Masoudi FA, Krantz MJ. Contrast-Enhanced Stress Echocardiography and Myocardial Perfusion Imaging in Patients Hospitalized With Chest Pain: A Randomized Study. Crit Pathw Cardiol. 2018 Jun;17(2):98-104. doi: 10.1097/HPC.0000000000000141.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: April 3, 2012
• First Submitted That Met QC Criteria: April 5, 2012
• First Posted (Estimate): April 6, 2012

Study Record Updates

• Last Update Posted (Actual): December 11, 2017
• Last Update Submitted That Met QC Criteria: December 7, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Hospitalized patients
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Ischemia; Chest Pain
• Other Study ID Numbers: 12-0009