DSE vs. FFR in SCAD and BYSTANDER Lesions

Ischemic Heart Disease Clinical Trial

— DSE-vs-FFR  

Official title:

Comparison of Dobutamine Stress Echocardiography and Fractional Flow Reserve in Patients With Moderate Coronary Artery Disease: Stable and Non-culprit Lesions Investigation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03383718
• Other study ID #: 1.0
• Status: Completed
• Start date: December 1, 2014
• Est. completion date: December 1, 2019

Study information

• Verified date: December 2019
• Source: Bajcsy-Zsilinszky Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Enrollment:

• Patients with stable coronary artery disease (SCAD) and moderate coronary artery stenoses (30-70 %)

• Patients with acute myocardial infarction and moderate stenosis of non-culprit arteries (NCL; BYSTANDER LESION)

Aims:

• To assess the diagnostic accuracy of dobutamine stress echocardiography (DSE) and invasive fractional flow reserve (FFR) measurement

• To assess the prognostic impact of reclassification by a mismatching negative test

Hypothesis:

• DSE and FFR have similar prognostic value in both clinical settings (SCAD and NCL)

• Considering the strong negative predictive value of both DSE and FFR, one negative test is sufficiently enough to defer revascularisation, even in the case of mismatch

Description:

Easy accessibility made fractional flow reserve (FFR) a widely accepted method to evaluate myocardial ischaemia in patients with moderate coronary artery stenosis, although the prognostic value for "hard" endpoints such as myocardial infarction and cardiovascular death is equivocal.

Dobutamine stress echocardiography (DSE) is a useful and safe non-invasive functional test for myocardial ichaemia evaluation. There are robust data confirming the prognostic value of DSE regarding the same "hard" endpoints.

In patients with SCAD there are clear recommendations in the recent guidelines both for DSE guided or FFR guided revascularization but the data about prognosis is limited, especially in the case of FFR guidance. The outcome is also equivocal if there is a difference between the invasive and non-invasive test result.

In patients with acute myocardial infarction, more than 50% of patients have multivessel disease. There are clear recommendations for the management of infarct related artery, however controversy still exists for the management of angiographically moderate NCLs.

In DSE vs. FFR prospective trial, the Investigators plan to perform both the DSE and FFR tests in the above mentioned clinical settings, to investigate the correlation between them. The causes of differences between them would be investigated as well as the prognostic impact of reclassification by a second test (either DSE or FFR).

If both tests are positive, revascularisation is planned to be performed (PCI Group). In cases of either double negative or mismatching tests, optimal medical therapy will be chosen (OMT Group) with clinical follow up of at least 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age>18 years

• Moderate Coronary Stenosis (30-70 %)

• Stable coronary artery disease or patients with acute myocardial infarction and at least one moderate non-culprit vessel stenosis

Exclusion Criteria:

• Left Main Coronary artery stenosis

• Age>80 years

• Known non-cardiovascular disease with poor prognosis

• Patients for whom coronary angiography or stress echocardiography is contraindicated per institutional standard of care (e.g. History of severe and/or anaphylactic contrast reaction)

• Inability to provide informed consent;

• Inability to cooperate with the investigation

• Pregnancy

Related Conditions & MeSH terms

• Coronary Artery Disease
• Heart Diseases
• Ischemic Heart Disease
• Myocardial Ischemia

Intervention

Procedure:
• Revascularisation
Percutaneous coronary intervention or coronary artery bypass surgery

Other:
• Optimal Medical Treatment/OMT
Standard of care in stable coronary artery disease or after acute myocardial infarction.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bajcsy-Zsilinszky Hospital	Semmelweis University Heart and Vascular Center

References & Publications (22)

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. — View Citation

Cortigiani L, Bigi R, Sicari R, Landi P, Bovenzi F, Picano E. Prognostic value of pharmacological stress echocardiography in diabetic and nondiabetic patients with known or suspected coronary artery disease. J Am Coll Cardiol. 2006 Feb 7;47(3):605-10. Epub 2006 Jan 18. — View Citation

Cortigiani L, Rigo F, Gherardi S, Bovenzi F, Molinaro S, Picano E, Sicari R. Coronary flow reserve during dipyridamole stress echocardiography predicts mortality. JACC Cardiovasc Imaging. 2012 Nov;5(11):1079-85. doi: 10.1016/j.jcmg.2012.08.007. — View Citation

Dagdelen S, Yuce M, Emiroglu Y, Ergelen M, Pala S, Tanalp AC, Izgi A, Kirma C. Correlation between the tissue Doppler, strain rate, strain imaging during the dobutamine infusion and coronary fractional flow reserve during catheterization: a comparative study. Int J Cardiol. 2005 Jun 22;102(1):127-36. — View Citation

Danad I, Szymonifka J, Twisk JWR, Norgaard BL, Zarins CK, Knaapen P, Min JK. Diagnostic performance of cardiac imaging methods to diagnose ischaemia-causing coronary artery disease when directly compared with fractional flow reserve as a reference standard: a meta-analysis. Eur Heart J. 2017 Apr 1;38(13):991-998. doi: 10.1093/eurheartj/ehw095. Review. — View Citation

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]. — View Citation

Gaibazzi N, Rigo F, Lorenzoni V, Molinaro S, Bartolomucci F, Reverberi C, Marwick TH. Comparative prediction of cardiac events by wall motion, wall motion plus coronary flow reserve, or myocardial perfusion analysis: a multicenter study of contrast stress echocardiography. JACC Cardiovasc Imaging. 2013 Jan;6(1):1-12. doi: 10.1016/j.jcmg.2012.08.009. Epub 2012 Dec 5. — View Citation

Harb SC, Marwick TH. Prognostic value of stress imaging after revascularization: a systematic review of stress echocardiography and stress nuclear imaging. Am Heart J. 2014 Jan;167(1):77-85. doi: 10.1016/j.ahj.2013.07.035. Epub 2013 Nov 21. Review. — View Citation

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. — View Citation

Lachance P, Déry JP, Rodés-Cabau J, Potvin JM, Barbeau G, Bertrand OF, Gleeton O, Larose E, Nguyen CM, Noël B, Proulx G, Roy L, De Larochellière R. Impact of fractional flow reserve measurement on the clinical management of patients with coronary artery disease evaluated with noninvasive stress tests prior to cardiac catheterization. Cardiovasc Revasc Med. 2008 Oct-Dec;9(4):229-34. doi: 10.1016/j.carrev.2008.02.002. — View Citation

Neglia D, Rovai D, Caselli C, Pietila M, Teresinska A, Aguadé-Bruix S, Pizzi MN, Todiere G, Gimelli A, Schroeder S, Drosch T, Poddighe R, Casolo G, Anagnostopoulos C, Pugliese F, Rouzet F, Le Guludec D, Cappelli F, Valente S, Gensini GF, Zawaideh C, Capitanio S, Sambuceti G, Marsico F, Perrone Filardi P, Fernández-Golfín C, Rincón LM, Graner FP, de Graaf MA, Fiechter M, Stehli J, Gaemperli O, Reyes E, Nkomo S, Mäki M, Lorenzoni V, Turchetti G, Carpeggiani C, Marinelli M, Puzzuoli S, Mangione M, Marcheschi P, Mariani F, Giannessi D, Nekolla S, Lombardi M, Sicari R, Scholte AJ, Zamorano JL, Kaufmann PA, Underwood SR, Knuuti J; EVINCI Study Investigators. Detection of significant coronary artery disease by noninvasive anatomical and functional imaging. Circ Cardiovasc Imaging. 2015 Mar;8(3). pii: e002179. doi: 10.1161/CIRCIMAGING.114.002179. — View Citation

Ojaghi-Haghighi Z, Abtahi F, Fazlolah S, Moladoust H, Maleki M, Gholami S. Coronary flow reserve, strain and strain rate imaging during pharmacological stress before and after percutaneous coronary intervention: comparison and correlation. Echocardiography. 2011 May;28(5):570-4. doi: 10.1111/j.1540-8175.2011.01366.x. Epub 2011 May 4. — View Citation

Pattanshetty DJ, Bhat PK, Gandhi S, Pillai DP, Aneja A. Comparing stress testing and fractional flow reserve to evaluate presence, location and extent of ischemia in coronary artery disease. Indian Heart J. 2015 Jan-Feb;67(1):50-5. doi: 10.1016/j.ihj.2015.02.010. Epub 2015 Feb 25. — View Citation

Pijls NH, De Bruyne B, Peels K, Van Der Voort PH, Bonnier HJ, Bartunek J Koolen JJ, Koolen JJ. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996 Jun 27;334(26):1703-8. — View Citation

Pingitore A, Picano E, Varga A, Gigli G, Cortigiani L, Previtali M, Minardi G, Colosso MQ, Lowenstein J, Mathias W Jr, Landi P. Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. Echo-Persantine International Cooperative (EPIC) and Echo-Dobutamine International Cooperative (EDIC) Study Groups. J Am Coll Cardiol. 1999 Nov 15;34(6):1769-77. — View Citation

Samady H, Lepper W, Powers ER, Wei K, Ragosta M, Bishop GG, Sarembock IJ, Gimple L, Watson DD, Beller GA, Barringhaus KG. Fractional flow reserve of infarct-related arteries identifies reversible defects on noninvasive myocardial perfusion imaging early after myocardial infarction. J Am Coll Cardiol. 2006 Jun 6;47(11):2187-93. — View Citation

Steinberg EH, Madmon L, Patel CP, Sedlis SP, Kronzon I, Cohen JL. Long-term prognostic significance of dobutamine echocardiography in patients with suspected coronary artery disease: results of a 5-year follow-up study. J Am Coll Cardiol. 1997 Apr;29(5):969-73. — View Citation

Takx RA, Blomberg BA, El Aidi H, Habets J, de Jong PA, Nagel E, Hoffmann U, Leiner T. Diagnostic accuracy of stress myocardial perfusion imaging compared to invasive coronary angiography with fractional flow reserve meta-analysis. Circ Cardiovasc Imaging. 2015 Jan;8(1). pii: e002666. doi: 10.1161/CIRCIMAGING.114.002666. Review. — View Citation

Thomas D, Xie F, Smith LM, O'Leary E, Smith K, Olson J, Nalty K, Hess R, Graham M, Therrien S, Porter TR. Prospective randomized comparison of conventional stress echocardiography and real-time perfusion stress echocardiography in detecting significant coronary artery disease. J Am Soc Echocardiogr. 2012 Nov;25(11):1207-14. doi: 10.1016/j.echo.2012.08.016. Epub 2012 Sep 19. — View Citation

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. — View Citation

van der Sijde JN, Boiten HJ, van Domburg RT, Schinkel AF. Long-Term (>10 Years) Prognostic Value of Dobutamine Stress Echocardiography in a High-Risk Cohort. Am J Cardiol. 2016 Apr 1;117(7):1078-83. doi: 10.1016/j.amjcard.2016.01.002. Epub 2016 Jan 14. — View Citation

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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Myocardial Infarction	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).; Development of pathological Q waves in the ECG. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.; Identification of an intracoronary thrombus by angiography or autopsy	From baseline to at least 2 years
Primary	Target Vessel Revascularisation	The Investigated Vessel need Revascularisation because of at least Canadian Cardiology Society Angina Class III	From baseline to at least 2 years
Primary	Cardiovascular Death	Death occurs due to Cardiovascular cause	From baseline to at least 2 years
Secondary	Angina	Rehospitalisation due to Angina	From baseline to at least 2 years
Secondary	Heart failure	Rehospitalisation due to Heart Failure	From baseline to at least 2 years
Secondary	Non-Cardiac Death	Death occurs due to Non-Cardiovascular cause	From baseline to at least 2 years
Secondary	Non-Target Vessel Revascularisation	The Non-Investigated Vessel need Revascularisation	From baseline to at least 2 years