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This research aims to investigate whether symptoms of chest pain or shortness of breath among the study population are arising due to a heart problem, particularly any reduction of blood flow to the heart muscle from blockages in the coronary blood vessels or inflammation of the heart using cardiac magnetic resonance imaging that measures the amount of blood flow during a stress state meant to simulate vigorous exercise. At present, doctors use standard magnetic resonance imaging pictures of blood flow patterns to treat heart disease. The investigators want to study if detailed blood flow measurements, in addition to the standard blood flow pattern, could diagnose heart disease more accurately and allow more doctors to understand the severity of heart disease. Early research has demonstrated that detailed blood flow measurements may be more accurate in diagnosing heart disease in some patients, but doctors need more information to know how to use these measurements.
In this proposal of the Multicenter Stress Cardiac Magnetic Resonance Quantitative Perfusion Imaging in the United States (SPINS2) study, the investigators seek to assess the prognostic utility of myocardial blood flow and flow reserve by quantitative stress cardiac magnetic resonance imaging compared to patients with normal quantitative perfusion indices. The investigators hypothesize that patients with abnormal myocardial blood flow and flow reserve will have higher adverse cardiac events, incremental to demographic risks and qualitative perfusion, and they should be considered for invasive workup or early institution of goal-directed medical therapies. In addition, the investigators hypothesize that quantitative perfusion by cardiac magnetic resonance imaging will characterize the myocardial extent and severity of multivessel disease and the participants' risk of adverse cardiac outcomes.
Patients with chest pain syndromes and suspected ischemic heart disease who meet both inclusion and exclusion criteria will be prospectively recruited among 20 sites across the United States over the course of 1.5 years. Participants will receive standardized quantitative stress cardiac magnetic resonance imaging protocol with Gadavist (Bayer, Germany) 0.05 mmol/kg dose for each stress and rest perfusion imaging (total dose of 0.1 mmol/kg) as per Food and Drug Administration (FDA)-approved indication. All participants will receive vasodilator stress with regadenoson or adenosine depending on local site practice. A single (7-10 ml tube) whole blood sample will be collected from each patient for processing of blood biomarkers.
All participants will have demographics and imaging characteristics recorded at baseline visits. Follow-up will occur via email or telephone at 3 months, 12 months, and 24 months from baseline. At each follow-up visit, medications, treatment, and adverse events will be recorded. In addition, all available electronic patient records will be reviewed in detail to capture all follow-up data which will be entered into an outline database using clearly defined data definitions. Participants will be followed for a total of 2 years from baseline cardiac magnetic resonance imaging study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Myocardial Blood Flow Evaluation | Active Comparator | Qualitative stress cardiac magnetic resonance imaging only. |
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| New Myocardial Blood Flow Evaluation | Experimental | Quantitative + Qualitative stress cardiac magnetic resonance imaging. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Quantitative Myocardial Blood Flow Evaluation | Diagnostic Test | The perfusion sequence will produce on-the-fly additional quantitative perfusion maps with segmental myocardial blood flow values. |
| Measure | Description | Time Frame |
|---|---|---|
| Primary composite outcome of major cardiovascular adverse events (MACE) | Composite MACE includes cardiovascular death, non-fatal acute myocardial infarction, stroke, resuscitated cardiac arrest, unnecessary invasive coronary angiography, and any cardiac hospitalization. Unnecessary invasive coronary angiography is defined as any invasive coronary angiography performed within 6 months after study enrollment, which reviews no obstructive coronary disease and no revascularization performed. | From cardiac magnetic resonance imaging to the end of follow-up in 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Procedure-related complications | Serious complications from a coronary procedure (e.g., procedure-related myocardial infarction, stroke/Transient Ischemic Attack, major periprocedural bleeding, 50% reduction of estimated glomerular filtration rate (eGFR), or anaphylactic reaction). | From cardiac magnetic resonance imaging to the end of follow-up in 24 months |
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Inclusion Criteria:
male or female at age 35-85 years,
presence of either of the following sign/symptom that led to a referral to stress cardiac magnetic resonance imaging:
Intermediate or high risk of significant coronary disease based on at least 1 of the following conditions:
a) patient age > 45 for male, 50 for female b) Diabetes, hypertension, or hypercholesterolemia: by either history or medical treatment c) family history of premature coronary disease: first degree relative at age <= 55 male and <=65 female d) history of smoking of > 10 packed-years e) post-menopausal state >5 years f) any chronic inflammatory conditions d) Body mass index > 30 e) Any medical documentation of coronary or peripheral artery disease
Exclusion Criteria:
Acute myocardial infarction within the past 30 days prior to cardiac magnetic resonance imaging
Confirmed diagnosis of any significant non-coronary cardiac conditions below:
active pregnancy,
any competing conditions leading to an expected survival of < 2 years
contraindication to vasodilator (regadenoson or adenosine)
metallic device or object that poses an magnetic resonance imaging safety hazard
metallic device with a high likelihood of non-diagnostic cardiac magnetic resonance images
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Raymond Y Kwong, MD, MPH | Contact | 857-307-1960 | rykwong@bwh.harvard.edu | |
| Bobby Heydari, MD, MPH | Contact | bheydari@bwh.harvard.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco | Recruiting | San Francisco | California | 94107 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20579539 | Background | Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010 Jun 22;55(25):2825-32. doi: 10.1016/j.jacc.2010.01.054. | |
| 20220183 |
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| Qualitative Myocardial Blood Flow Evaluation | Diagnostic Test | The perfusion sequence will not produce additional quantitative perfusion maps. |
|
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| Gadavist | Drug | Participants will receive Gadavist 0.05 mmol/kg dose for each stress and rest perfusion imaging (total dose of 0.1 mmol/kg). |
|
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| Vasodilator | Drug | All participants will receive vasodilator (regadenoson or adenosine depending on local site practice). |
|
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| Blood draw for the laboratory assessment | Diagnostic Test | A single (7-10 ml tube) whole blood sample will be collected from each patient for processing of blood biomarkers. |
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| Cost outcomes for Comparative Cost-effectiveness | Costs of performing coronary artery disease-related tests or procedures during the follow-up period, namely invasive coronary angiography; coronary revascularization procedure or surgery; any noninvasive stress imaging, stress electrocardiogram, or coronary computed tomography angiography imaging. Costs of performing these tests or procedures will be determined by national averaged Medicare cost of reimbursement adjusted across the years for rate of inflation. | From cardiac magnetic resonance imaging to the end of follow-up in 24 months |
| UofL Health - Heart Hospital | Recruiting | Louisville | Kentucky | 40202 | United States |
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| Brigham and Women's Hospital | Recruiting | Boston | Massachusetts | 02115 | United States |
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| Beth Israel Deaconess Medical Center | Recruiting | Boston | Massachusetts | 02215 | United States |
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| St. Francis Hospital and Heart Center | Recruiting | Roslyn | New York | 11576 | United States |
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| Atrium Health - Sanger Heart & Vascular Institute | Recruiting | Charlotte | North Carolina | 28204 | United States |
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| Cleveland Clinic | Recruiting | Cleveland | Ohio | 44195 | United States |
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| The Ohio State University | Recruiting | Columbus | Ohio | 43210 | United States |
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| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37203 | United States |
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| Houston Methodist Hospital | Recruiting | Houston | Texas | 77030 | United States |
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| University of Virginia | Recruiting | Charlottesville | Virginia | 22908 | United States |
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| Virginia Commonwealth University | Recruiting | Richmond | Virginia | 23298 | United States |
|
| Background |
| Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, Brindis RG, Douglas PS. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010 Mar 11;362(10):886-95. doi: 10.1056/NEJMoa0907272. |
| 29153572 | Background | Sammut EC, Villa ADM, Di Giovine G, Dancy L, Bosio F, Gibbs T, Jeyabraba S, Schwenke S, Williams SE, Marber M, Alfakih K, Ismail TF, Razavi R, Chiribiri A. Prognostic Value of Quantitative Stress Perfusion Cardiac Magnetic Resonance. JACC Cardiovasc Imaging. 2018 May;11(5):686-694. doi: 10.1016/j.jcmg.2017.07.022. Epub 2017 Nov 15. |
| 33011115 | Background | Kotecha T, Chacko L, Chehab O, O'Reilly N, Martinez-Naharro A, Lazari J, Knott KD, Brown J, Knight D, Muthurangu V, Hawkins P, Plein S, Moon JC, Xue H, Kellman P, Rakhit R, Patel N, Fontana M. Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping. JACC Cardiovasc Imaging. 2020 Dec;13(12):2546-2557. doi: 10.1016/j.jcmg.2020.06.041. Epub 2020 Oct 1. |
| 28982571 | Background | Patel AR, Kramer CM. Role of Cardiac Magnetic Resonance in the Diagnosis and Prognosis of Nonischemic Cardiomyopathy. JACC Cardiovasc Imaging. 2017 Oct;10(10 Pt A):1180-1193. doi: 10.1016/j.jcmg.2017.08.005. |
| 21076898 | Background | Rozanski A, Gransar H, Hayes SW, Friedman JD, Hachamovitch R, Berman DS. Comparison of long-term mortality risk following normal exercise vs adenosine myocardial perfusion SPECT. J Nucl Cardiol. 2010 Dec;17(6):999-1008. doi: 10.1007/s12350-010-9300-9. Epub 2010 Nov 13. |
| 37914512 | Background | Arai AE, Schulz-Menger J, Shah DJ, Han Y, Bandettini WP, Abraham A, Woodard PK, Selvanayagam JB, Hamilton-Craig C, Tan RS, Carr J, Teo L, Kramer CM, Wintersperger BJ, Harisinghani MG, Flamm SD, Friedrich MG, Klem I, Raman SV, Haverstock D, Liu Z, Brueggenwerth G, Santiuste M, Berman DS, Pennell DJ. Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease. J Am Coll Cardiol. 2023 Nov 7;82(19):1828-1838. doi: 10.1016/j.jacc.2023.08.046. |
| 37162723 | Background | Nayfeh M, Ahmed AI, Saad JM, Alahdab F, Al-Mallah M. The Role of Cardiac PET in Diagnosis and Prognosis of Ischemic Heart Disease: Optimal Modality Across Different Patient Populations. Curr Atheroscler Rep. 2023 Jul;25(7):351-357. doi: 10.1007/s11883-023-01107-0. Epub 2023 May 10. |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C090600 | gadobutrol |
| D014665 | Vasodilator Agents |
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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