NON-CULPRIT: DSE vs Invasive FFR vs CT-FFR
Study Details
Study Description
Brief Summary
Data are limited regarding the optimal treatment of the non-culprit lesions (NCL) after myocardial infarction (MI). The NON-CULPRIT study is a prospective cohort study with a primary aim to compare invasive fractional flow reserve (FFR) and dobutamine stress echocardiography (DSE) for the evaluation and treatment of NCL in patients with MI.
As a secondary aim the investigators will assess the diagnostic performance of CT derived FFR as compared to invasive FFR and DSE measurements.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Myocardial ischemia and coronary artery disease (CAD) burden both provide valuable prognostic information for adverse cardiac events. More than 50% of patients with acute myocardial infarction have multi-vessel coronary artery disease. However current evidence regarding the optimal treatment of the non-culprit lesions (NCL) after myocardial infarction (MI) is still limited.
The revascularization of NCL with at least moderate severity is associated with improved clinical outcomes, if significant ischemia was detected previously. Currently, there is no strict recommendation on the methods for detecting ischemia, therefore the current study aims to compare Dobutamine stress echocardiography (DSE) and invasive FFR for the evaluation and management of patients with MI and multi-vessel disease.
DSE and FFR measurements will be perfomed in patinets with at least one intermediate NCL. If both results are positive (new wall motion abnormality of at least two segments related to the examined coronary artery on DSE and FFR≤0,8 are declared as positive), stent implantation will be performed, if both results are negative or in case of mismatch, optimal medical treatment will be chosen.
Recent studies demonstrated the discrepancy between anatomical severity and hemodynamic relevance. Invasive fractional flow reserve (FFR) has emerged as the gold standard technique for the detection of lesion specific ischemia. The utilization of FFR in stable and acute chest pain patients can help in the selection of proper treatment strategy. The recently published Compare-Acute and DANAMI-Primulti trials have shown that in STEMI patients FFR-guided complete revascularization of NCL is beneficial as compared to infarct related lesion revascularization only.
However, in light of recent studies involving post-MI patients, invasive FFR might be limited for the assessment of NCL due to vessel remodeling, microvascular changes and altered hemodynamics.
Recent advancements in CT imaging allows for improved image quality and novel post-processing algorithms. Beyond anatomical data, functional information using coronary CT angiography (CTA) dataset and computational fluid dynamics simulations can be derived. CT derived FFR allows for the functional assessment of CAD in a non-invasive fashion.
Data regarding the diagnostic accuracy of CT-FFR as compared to other widely utilized functional tests are limited. Also, high-risk plaque features might affect lesion specific ischemia as detected by invasive FFR. Coronary CTA plus CT-FFR may help to identify patients requiring revascularization, even with controversial DSE and FFR results.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 1 PCI Group Patients after acute myocardial infarction and at least one moderate stenosis on the non-culprit vessels with positive dobutamine stress echocardiography and positive Fractional Flow Reserve recieving revascularization (PCI or CABG) Drug: Standard of care after acute myocardial infarction |
Procedure: Revascularization
PCI or CABG
|
| Group 2 OMT group Patients after acute myocardial infarction and at least one moderate stenosis on the non-culprit vessels with negative dobutamine stress echocardiography and negative Fractional Flow Reserve or the mismatching cases Standard of care after acute myocardial infarction |
Outcome Measures
Primary Outcome Measures
- Acute myocardial infarction [From baseline to at least 2 years]
Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin (cTn)] with at least one value above the 99th percentile upper reference limit (URL) and with at least one of the following: Symptoms of ischaemia. New or presumed new significant ST-segment-T wave (ST-T) changes or new left bundle branch block (LBBB).
- Cardiovascular death [From baseline to at least 2 years]
Death occurs due to cardiovascular cause
- Target vessel revascularization [From baseline to at least 2 years]
The Investigated Vessel needs Revascularisation due to angina
Secondary Outcome Measures
- Diagnostic performance of CT-FFR vs invasive FFR [From baseline to 3 months]
Diagnostic performance of CT-FFR as compared to invasive FFR
- Diagnostic performance of CT-FFR vs DSE [From baseline to 3 months]
Diagnostic performance of CT-FFR as compared to DSE
Eligibility Criteria
Criteria
Inclusion Criteria:
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Acute myocardial infarction
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Moderate (40-80 %) stenosis of a non-culprit coronary artery
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Signed informed consent
Exclusion Criteria:
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Age under 18 years
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Age over 80 years
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Incurable malignant disease
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Patients for whom coronary CTA is contraindicated (History of severe and/or anaphylactic contrast reaction, severe renal insufficiency, inability to cooperate with scan acquisition and/or breathhold instructions)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Bajcsy-Zsilinszky Hospital | Budapest | Pest | Hungary | 1106 |
| 2 | Heart and Vascular Center, Semmelweis University | Budapest | Hungary | 1122 |
Sponsors and Collaborators
- Semmelweis University Heart and Vascular Center
- Bajcsy-Zsilinszky Hospital
Investigators
- Principal Investigator: Peter Andrassy, MD PhD, Bajcsy-Zsilinszky Hospital
- Study Director: Pal Maurovich-Horvat, MD PhD MPH, Heart and Vascular Center, Semmelweis University
Study Documents (Full-Text)
None provided.More Information
Publications
- Brown OI, Clark AL, Chelliah R, Davison BJ, Mather AN, Cunnington MS, John J, Alahmar A, Oliver R, Aznaouridis K, Hoye A. Cardiogoniometry Compared to Fractional Flow Reserve at Identifying Physiologically Significant Coronary Stenosis: The CARDIOFLOW Study. Cardiovasc Eng Technol. 2018 Sep;9(3):439-446. doi: 10.1007/s13239-018-0354-1. Epub 2018 Apr 12.
- Christou MA, Siontis GC, Katritsis DG, Ioannidis JP. Meta-analysis of fractional flow reserve versus quantitative coronary angiography and noninvasive imaging for evaluation of myocardial ischemia. Am J Cardiol. 2007 Feb 15;99(4):450-6. Epub 2006 Dec 20.
- Corcoran D, Hennigan B, Berry C. Fractional flow reserve: a clinical perspective. Int J Cardiovasc Imaging. 2017 Jul;33(7):961-974. doi: 10.1007/s10554-017-1159-2. Epub 2017 Jun 2. Review.
- De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Möbius-Winkler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engström T, Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Jüni P, Fearon WF; FAME 2 Trial Investigators. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012 Sep 13;367(11):991-1001. doi: 10.1056/NEJMoa1205361. Epub 2012 Aug 27. Erratum in: N Engl J Med. 2012 Nov;367(18):1768. Mobius-Winckler, Sven [corrected to Möbius-Winkler, Sven].
- De Rosa R, Piccolo R, Cassese S, Petretta A, D'Andrea C, D'Anna C, Piscione F, Chiariello M. Coronary flow reserve evaluation: basics, techniques and clinical applications. Minerva Cardioangiol. 2011 Dec;59(6):569-80. Epub 2009 Nov 30. Review.
- Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation. 2003 Jun 17;107(23):2900-7. Epub 2003 May 27.
- Jung PH, Rieber J, Störk S, Hoyer C, Erhardt I, Nowotny A, Voelker W, Weidemann F, Ertl G, Klauss V, Angermann CE. Effect of contrast application on interpretability and diagnostic value of dobutamine stress echocardiography in patients with intermediate coronary lesions: comparison with myocardial fractional flow reserve. Eur Heart J. 2008 Oct;29(20):2536-43. doi: 10.1093/eurheartj/ehn204. Epub 2008 May 21.
- Rogers WJ, Bourassa MG, Andrews TC, Bertolet BD, Blumenthal RS, Chaitman BR, Forman SA, Geller NL, Goldberg AD, Habib GB, et al. Asymptomatic Cardiac Ischemia Pilot (ACIP) study: outcome at 1 year for patients with asymptomatic cardiac ischemia randomized to medical therapy or revascularization. The ACIP Investigators. J Am Coll Cardiol. 1995 Sep;26(3):594-605.
- Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, Weintraub WS, O'Rourke RA, Dada M, Spertus JA, Chaitman BR, Friedman J, Slomka P, Heller GV, Germano G, Gosselin G, Berger P, Kostuk WJ, Schwartz RG, Knudtson M, Veledar E, Bates ER, McCallister B, Teo KK, Boden WE; COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008 Mar 11;117(10):1283-91. doi: 10.1161/CIRCULATIONAHA.107.743963. Epub 2008 Feb 11.
- Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabaté M, Senior R, Taggart DP, van der Wall EE, Vrints CJ; ESC Committee for Practice Guidelines, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Rydén L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013 Oct;34(38):2949-3003. doi: 10.1093/eurheartj/eht296. Epub 2013 Aug 30. Erratum in: Eur Heart J. 2014 Sep 1;35(33):2260-1.
- Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611.
- Toth G, De Bruyne B, Casselman F, De Vroey F, Pyxaras S, Di Serafino L, Van Praet F, Van Mieghem C, Stockman B, Wijns W, Degrieck I, Barbato E. Fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery. Circulation. 2013 Sep 24;128(13):1405-11. doi: 10.1161/CIRCULATIONAHA.113.002740. Epub 2013 Aug 28.
- Toth G, Hamilos M, Pyxaras S, Mangiacapra F, Nelis O, De Vroey F, Di Serafino L, Muller O, Van Mieghem C, Wyffels E, Heyndrickx GR, Bartunek J, Vanderheyden M, Barbato E, Wijns W, De Bruyne B. Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses. Eur Heart J. 2014 Oct 21;35(40):2831-8. doi: 10.1093/eurheartj/ehu094. Epub 2014 Mar 18.
- Weidemann F, Jung P, Hoyer C, Broscheit J, Voelker W, Ertl G, Störk S, Angermann CE, Strotmann JM. Assessment of the contractile reserve in patients with intermediate coronary lesions: a strain rate imaging study validated by invasive myocardial fractional flow reserve. Eur Heart J. 2007 Jun;28(12):1425-32. Epub 2007 May 15.
- NON-CULPRIT