The study of myocardial perfusion and coronary anatomy imaging roles in CAD (SPARC): design, rationale, and baseline patient characteristics of a prospective, multicenter observational registry comparing PET, SPECT, and CTA for resource utilization and clinical outcomes

Abstract

Objectives

To design a multicenter study comparing the prognostic value and post-test resource utilization of PET, CT Coronary Angiography (CTA), and SPECT in clinical practice.

Background

Although PET, CTA, and SPECT are widely used, their relative clinical- and cost-effectiveness are undefined.

Methods

The Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in CAD (SPARC) is a prospective, multicenter, observational registry that has enrolled 3019 patients undergoing clinically referred SPECT, PET, and CTA with the goal of comparing post-test resource utilization and comparative prognostic value. Resource utilization assessment will enroll intermediate-high likelihood patients without prior CAD, while prognostic assessment will include both these patients and patients with prior CAD. Secondary analyses include assessments of diagnostic accuracy, cost, and referral to revascularization. Sites recruited into at least two of the three imaging arms. Except for semi-quantitative interpretation, site protocols will be used for all imaging studies and images forwarded to an image repository. Follow-up for catheterization, revascularization, cardiac death, myocardial infarction, all-cause death and medication use changes will be performed at 90-day, 1, and 2 years. Standard statistical methods will be used to risk-adjust results within and between study arms. SPARC will have >85% power (two-sided test, α = 0.01) to detect a 5% catheterization rate difference at 90 days between the three arms and >90% power to detect a 2% difference in cardiac death, or nonfatal MI within 2 years of the index test.

Conclusions

SPARC will be the first study comparing outcomes and resource utilization between SPECT, PET, and CTA in daily practice. In addition, the study design offers insights into inter-site and geographic differences in referral patterns and resource utilization.

Appendices

Appendix I: Clinical Endpoints Committee

Clinical Events Committee (CEC): The mission of the CEC will be to define and adjudicate all primary endpoints in a consistent, timely, and unbiased manner throughout the entire course of the study. CEC members will include:

• Robert Giugliano, MD, MSc, Chairman

• Mariya Gaber, Coordinator

• Julie Williams, Coordinator

• To Be Named, Physician Reviewer

• To Be Named, Physician Reviewer

• To Be Named, Physician Reviewer

• To Be Named, Physician Reviewer

Documentation confirming that an event occurred may include, but is not limited to the following:

• Narrative from investigator or informed physician.

• Death certificate.

• Autopsy report.

• Hospital discharge summary.

• History and physical examination.

• Cardiovascular intervention or surgical procedure reports or logs.

• Medications administration record.

• Progress notes.

• Laboratory reports (including cardiac enzymes, with laboratory reference ranges).

• Electrocardiograms.

• Bills from funeral homes, hospitals, or doctors that clearly indicate that the Patient experienced the event.

• Insurance company statements that clearly indicate that the Patient experienced the event.

Outcome Measures

The primary outcome measures of this study will be adjudicated by the Clinical Endpoints Committee (CEC) and include:

• (1) occurrence of cardiac catheterization in a patient without prior CAD.

• (2) the time from randomization until first occurrence of a component of the primary survival endpoint: all-cause death or myocardial infarction.

Endpoint definitions

Death classification. Death will be classified in the following categories:

I. Atherosclerotic Coronary Heart Disease

A. Acute Myocardial Infarction:

Fatal myocardial infarction may be adjudicated in any one of the following three scenarios:

• Death occurring after a documented MI in which there is not conclusive evidence of another cause of death. Patients who are being treated for MI and have a sudden death, as the terminal event related to the MI will be classified as having a myocardial infarction related death.

• Autopsy evidence of a recent infarct with no other conclusive evidence of another cause of death.

• A fatal myocardial infarction may be adjudicated for an abrupt death that has suggestive criteria for an infarct but does not meet the strict definition of a myocardial infarction. The suggestive criteria are as follows:

  • Presentation of chest pain AND one of the following:

    • – ECG changes indicative of a myocardial injury or

    • – Abnormal markers without evolutional changes (i.e., patient died before a subsequent draw) or

    • – Other evidence of new wall motion abnormality

B. Sudden Death

Defined as death that occurred suddenly and unexpectedly in which the time of death is known:

• Within 1 hour of being seen: Death within 1 hour of being seen preceded by a change in the cardiovascular status of the patient. This refers to a patient who has had the appearance of worsening cardiovascular symptoms such as chest pain or arrhythmias or heart failure or other cardiovascular problem within 1 week before the patient dies suddenly. “No preceding symptoms” would apply to patients who die suddenly without preceding change in the cardiovascular status.

• Within 24 hours of being seen: Death within greater than 1 but less than 24 hours of being seen with either a change in cardiovascular status or no change. For example, a patient who had had increasing angina for the previous 5 days prior to death and has been seen to be in his usual state by his wife at bed time, but is found dead the next morning 10 hours later. The same may occur with no preceding change in cardiovascular symptoms.

C. Nonsudden Death

This category refers to a patient who had had symptoms of a cardiovascular nature and has had gradual deterioration prior to death. For example, a patient admitted with worsened heart failure who despite therapy gradually deteriorates and ultimately dies. This would imply a deterioration in a patient who may have started off at New York Class I or II but deteriorated over time. It could also apply to a class III or IV patient who also deteriorates with time

D. Unwitnessed death (not seen >24 hours)

Death that occurred unexpectedly and had no known other major causes of death.

E. Procedural

Related to any of the usual coronary artery procedures such as surgery, PTCA, or angiography. This applies to any or all complications occurring during the same hospitalization, or within 7 days of the event.

II. Atherosclerotic vascular disease, excluding coronary disease

Excluding CAD. These categories are straight forward, but as much detail should be provided as possible. See the sheets regarding cerebrovascular disease. With respect to aortic mesenteric, renal vascular, peripheral vascular disease or other, as much detail should be provided as possible about the nature of the condition, the time-course and the event causing death. If possible, one should try to describe whether coronary or cerebrovascular disease also contributed to the fatal demise.

• A. Cereberovascular disease, including stroke and hemorrhage

• B. Aortic, mesenteric, renal vascular, or peripheral vascular disease

• C. Other

• D. Procedural; death occurring during a hospitalization for or after a vascular procedure (i.e., carotid endarterectomy, AAA repair), when the circumstances surrounding the death can be linked to a vascular procedure.

III. Other Cardiovascular Disease (nonatherosclerotic)

In all of these conditions, one should provide as much detail as possible, and to specify whether in the investigator’s opinion, atherosclerotic disease played a part and if so, how.

• A. Pulmonary embolism

• B. Endocarditis

• C. Valvular disease

• D. Procedural

• E. Other

IV. Noncardiovascular

These are straightforward categories and need no description except to say that as much detail as possible is required. The extent to which atherosclerotic disease played a part should be addressed.

• A. Infectious

• B. Malignancy

• C. Pulmonary

• D. Gastrointestinal

• E. Accidental

• F. Suicide

• G. Diabetes

• H. Renal

• I. Other

V. Unknown

All other death will be classified as unknown.

Nonfatal endpoint definitions

Myocardial infarction. The current ACC/AHA and ACC/ESC practice guidelines for myocardial infarction will be used to classify an event as MI. Nonfatal MI will be defined as a clinical syndrome consistent with an acute ischemic syndrome. Symptoms must be accompanied by at least one of the following objective criteria:

• A. ECG changes:

  • New, or presumed new, ST segment elevation (>1 mm) at the J point in two contiguous leads, or

  • ST segment depression >1 mm in two contiguous leads, or

  • New T wave inversions in at least 2 leads, or

  • New Q waves in the absence of left bundle branch block, or

  • Presence of new left bundle branch block.

AND/OR

• B. Elevated enzymes:

  • Increased creatine kinase (CK) × 2 the upper limit of normal, or

  • Increase in CK-myocardial isoenzyme (MB) >10–13 U/L or >5% of total activity, or

  • Increase in troponin-T (TnT) above the site’s clinical laboratory’s upper limit of normal, or

  • Increase in troponin-I (TnI) above the site’s clinical laboratory’s upper limit of normal

Appendix II

Steering Committee: Rory Hachamovitch, MD, MSc (Co-Chair); Marcelo F. Di Carli, MD (Co-Chair); James R. Johnson, PhD (lead Statistician).

SPARC Coordinating Center and Image Repository Lab

Brigham and Women’s Hospital, Boston, MA

Project Manager: Mariya Gaber

IT Manager: Jon Hainer

Webmaster: Jeselle Gierbolini

SPARC Data Coordinating Center

Cary, North Carolina

Data Management Center PI: James R. Johnson, Ph.D.

Project Manager: Barbara H. Johnson, MS, RPh

IT Image Data Transfer Company

AGMednet

Region	Site ID	Institution	Investigator(s)
SPARC sites and investigators
Northeast	101	Brigham and Women’s Hospital	Sharmila Dorbala, MD
	102	Hartford Hospital	Gary Heller, MD
	103	Sinai Hospital of Baltimore	Stuart Rabinowitz, MD
	104	Massachusetts General Hospital	Tsunehiro Yasuda, MD
	105	Washington Hospital Center	Guy Weigold, MD
	106	NYU Medical Center	Jill Jacobs, MD
	107	Lahey Clinic	Shanker Raja, MD
	108	Mount Sinai Medical Center	Josef Machac, MD
	109	Yale-New Haven VA Hospital	Aseem Vashist, MD
	112	Rhode Island Hospital	James Arrighi, MD
	113	St. Francis Hospital-The Heart Center	Nathaniel Reichek, MD
	114	Holy Name Hospital	Jacqueline Brunetti, MD; Jakey Patwari, MD
	115	Columbia University Medical Center	Subahat Bokhari, MD
	118	Cardiac Specialists (CT)	Adam Schussheim, MD
	119	Montefiore Medical Center	Mark Travin, MD
Southeast	126	Medical University of South Carolina	Joseph Schoepf, MD
	127	Emory Crawford Long Hospital	Steven Sigman, MD
	128	Cardiovascular Associates (Birmingham, Alabama)	Elizabeth Branscomb, MD
	129	Fuqua Heart Center-Piedmont Hospital	Szilard Voros, MD
	130	University of Florida-Jacksonville	Norbert Wilke, MD
	131	Vanderbilt Hospital	Dominique Delbeke, MD
	132	Duke University Medical Center	Salvador Borges-Neto, MD
	133	University of Alabama-Birmingham	Ami Iskandrian, MD
	134	Tennessee Heart and Vascular Institute	Tracy Q. Callister, MD
	136	The Heart Center (Huntsville, Alabama)	Michael L. Ridner, MD
Midwest	151	Cleveland Clinic Foundation	Richard C. Brunken, MD
	152	Oklahoma Foundation-Cardiovascular Research	Carolyn Corn, MD
	154	Wisconsin Heart Hospital	Samuel Wann, MD
	156	Ohio State University Medical Center	Subha V. Raman, MD
	157	Minneapolis Heart Institute Foundation	John Lesser, MD
	158	University of Michigan	Ella Kazerooni, MD; Milton Gross, MD
	159	University of Chicago	Kim Williams, MD
	161	Mayo Clinic	Panithaya Chareonthaitawee, MD
	162	Meritcare Hospital (Fargo, ND)	Susan Farkas, MD
West	176	Cedars-Sinai Medical Center	Daniel Berman, MD
	177	University of Washington	James Caldwell, MD
	178	Los Angeles Biomedical Research Institute (Torrance, CA)	Matthew Budoff, MD
	182	Scottsdale Medical Imaging (Scottsdale, AZ)	Ronald Korn, MD
	183	Scripts Center-Integrative Medicine	Erminia Guarneri, MD
	185	University of California-Irvine	Jagat Narula, MD
Canada	199	University of Ottawa Heart Institute	Rob Beanlands, MD; Benjamin Chow, MD