Catheterization and Cardiovascular Interventions 86:19–20 (2015)
Editorial Comment Is the Left Main Just Another Artery to FFR? Arnold H. Seto,* MD, and Morton J. Kern, MD Long Beach Veterans Affairs Medical Center, Long Beach, California
Key Points
This meta-analysis includes all prospective FFR studies of the left main artery with outcomes. Patients who had deferral of revascularization in FFR-negative stenoses had no difference in cardiovascular events compared with patients who underwent revascularization. FFR-guided revascularization of left main stenosis is safe and effective.
Discovery of a left main artery (LM) stenosis justifiably creates a sense of impending doom in the cardiologist (and potentially the patient). Due to a large area of myocardium subtended by the LM, hemodynamically significant LM stenoses can cause rapid decompensation and sudden cardiac arrest in otherwise stable-appearing patients. From the clinical consequences of untreated LM patients reported in the decadesold CASS study, coupled with early angioplasty outcomes, LM stenoses are traditionally accorded great respect in practice and in guidelines. Before 2011, the AHA/ACC/SCAI PCI guidelines classified unprotected LM PCI as a class III intervention. In clinical practice, respect for LM stenoses is seen in the lower angiographic threshold of 50% for the definition of a significant lesion. After more than two decades of physiologic– anatomic comparisons, it should be well recognized that two-dimensional angiography may underestimate or overestimate the hemodynamic significance of a lesion due to angulation, lesion eccentricity, foreshortening, and bifurcation anatomy. The LM is at a higher risk of such visual-functional mismatch compared with other arteries, with an angiographic >50% stenosis only having a 33% sensitivity, 91% specificity, and 71% accuracy in physiologic significance (i.e., a fractional flow reserve [FFR] 0.75 or >0.80, depending on the study. In their meta-analysis of all 525 patients, Mallidi et al. [4] found that the primary composite endpoint of death, myocardial infarction, or subsequent revascularization occurred in 60 (19.4%) of the deferred patients compared with 31 (14.2%) of the revascularized patients, a nonsignificant difference (P ¼ 0.15). There was a trend toward reduced all-cause mortality in the deferred group compared with the revascularized patients (4.5% vs. 8.8%, P ¼ 0.06), reflecting either the consequences of more severe disease or the upfront risks of bypass surgery. Over an average follow-up of 26.5 months, the deferred group had an increased rate of subsequent revascularization (OR 3.28, 95% CI
Conflict of interest: Dr. Seto is a speaker for Volcano Corp, St Jude Medical, and consultant to Acist Inc. Dr. Kern is a speaker and consultant for Volcano Corp, St Jude Medical, and consultant to Acist Inc and Opsens Inc. *Correspondence to: Arnold Hoo Seto, Long Beach Veterans Affairs Medical Center, 5901 East 7th Street, 111C, Long Beach, CA 90822. E-mail: [email protected] Received 7 May 2015; Revision accepted 11 May 2015 DOI: 10.1002/ccd.26050 Published online 18 June 2015 in Wiley Online Library (wileyonlinelibrary.com)
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1.51–6.93), which is understandable given the natural progression of coronary disease. The strength of this study was that the trials were relatively homogeneous in their design, making combining them in a meta-analysis appropriate. Although the included trials used either a FFR 0.75 or 0.80 as the cutoff for revascularization, FFR 0.80 was used in the largest LM FFR study [1] and has been validated in non-LM stenoses in the FAME studies. Considering the greater concern associated with deferral of LM stenoses, the use of this higher cutoff value for LM FFR gives the benefit of doubt to the patient and clinician. The weakness of this meta-analysis is that its power was limited by the small sample sizes and small numbers of trials available to be included— with more trials it is conceivable that a mortality benefit might have emerged. Lastly, none of the trials were randomized, leading to a risk of selection bias. This meta-analysis cogently summarizes what each of the relatively small trials individually suggested: that LM FFR safely identifies which LM stenoses require revascularization, and which can be safely deferred. Deferring revascularization is not associated with an increased risk of myocardial infarction or death, and may be associated with decreased mortality, at the cost of some patients needing revascularization at a later date. Respecting LM disease should not mean
sending more patients to surgery based on angiography alone, but should rather drive the operator to be more objective and measure the functional significance of the stenosis. In this regard, the LM artery may be like any other coronary artery. It’s just another vessel that needs FFR. REFERENCES 1. Hamilos M, Muller O, Cuisset T, Ntalianis A, Chlouverakis G, Sarno G, Nelis O, Bartunek J, Vanderheyden M, Wyffels E, Barbato E, Heyndrickx GR, Wijns W, De Bruyne B. Long-term clinical outcome after fractional flow reserve-guided treatment in patients with angiographically equivocal left main coronary artery stenosis. Circulation 2009;120:1505–1512. 2. Park SJ, Kang SJ, Ahn JM, Shim EB, Kim YT, Yun SC, Song H, Lee JY, Kim WJ, Park DW, Lee SW, Kim YH, Lee CW, Mintz GS, Park SW. Visual-functional mismatch between coronary angiography and fractional flow reserve. JACC Cardiovasc Interv 2012;5:1029–1036. 3. Fearon WF, Yong AS, Lenders G, Toth GG, Dao C, Daniels DV, Pijls NH, De Bruyne B. The impact of downstream coronary stenosis on fractional flow reserve assessment of intermediate left main coronary artery disease: Human validation. JACC Cardiovasc Interv 2015;8:398–403. 4. Mallidi J, Atreya AR, Cook J, Garb J, Jeremias A, Klein LW, Lotfi A. Long term outcomes following fractional flow reserve guided treatment of angiographically ambiguous left main coronary artery disease: A meta-analysis of prospective cohort studies. Catheter Cardiovasc Interv 2015;86:12–18.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Editorial Comment Is the Left Main Just Another Artery to FFR? Arnold H. Seto,* MD, and Morton J. Kern, MD Long Beach Veterans Affairs Medical Center, Long Beach, California
Key Points
This meta-analysis includes all prospective FFR studies of the left main artery with outcomes. Patients who had deferral of revascularization in FFR-negative stenoses had no difference in cardiovascular events compared with patients who underwent revascularization. FFR-guided revascularization of left main stenosis is safe and effective.
Discovery of a left main artery (LM) stenosis justifiably creates a sense of impending doom in the cardiologist (and potentially the patient). Due to a large area of myocardium subtended by the LM, hemodynamically significant LM stenoses can cause rapid decompensation and sudden cardiac arrest in otherwise stable-appearing patients. From the clinical consequences of untreated LM patients reported in the decadesold CASS study, coupled with early angioplasty outcomes, LM stenoses are traditionally accorded great respect in practice and in guidelines. Before 2011, the AHA/ACC/SCAI PCI guidelines classified unprotected LM PCI as a class III intervention. In clinical practice, respect for LM stenoses is seen in the lower angiographic threshold of 50% for the definition of a significant lesion. After more than two decades of physiologic– anatomic comparisons, it should be well recognized that two-dimensional angiography may underestimate or overestimate the hemodynamic significance of a lesion due to angulation, lesion eccentricity, foreshortening, and bifurcation anatomy. The LM is at a higher risk of such visual-functional mismatch compared with other arteries, with an angiographic >50% stenosis only having a 33% sensitivity, 91% specificity, and 71% accuracy in physiologic significance (i.e., a fractional flow reserve [FFR] 0.75 or >0.80, depending on the study. In their meta-analysis of all 525 patients, Mallidi et al. [4] found that the primary composite endpoint of death, myocardial infarction, or subsequent revascularization occurred in 60 (19.4%) of the deferred patients compared with 31 (14.2%) of the revascularized patients, a nonsignificant difference (P ¼ 0.15). There was a trend toward reduced all-cause mortality in the deferred group compared with the revascularized patients (4.5% vs. 8.8%, P ¼ 0.06), reflecting either the consequences of more severe disease or the upfront risks of bypass surgery. Over an average follow-up of 26.5 months, the deferred group had an increased rate of subsequent revascularization (OR 3.28, 95% CI
Conflict of interest: Dr. Seto is a speaker for Volcano Corp, St Jude Medical, and consultant to Acist Inc. Dr. Kern is a speaker and consultant for Volcano Corp, St Jude Medical, and consultant to Acist Inc and Opsens Inc. *Correspondence to: Arnold Hoo Seto, Long Beach Veterans Affairs Medical Center, 5901 East 7th Street, 111C, Long Beach, CA 90822. E-mail: [email protected] Received 7 May 2015; Revision accepted 11 May 2015 DOI: 10.1002/ccd.26050 Published online 18 June 2015 in Wiley Online Library (wileyonlinelibrary.com)
20
Seto and Kern
1.51–6.93), which is understandable given the natural progression of coronary disease. The strength of this study was that the trials were relatively homogeneous in their design, making combining them in a meta-analysis appropriate. Although the included trials used either a FFR 0.75 or 0.80 as the cutoff for revascularization, FFR 0.80 was used in the largest LM FFR study [1] and has been validated in non-LM stenoses in the FAME studies. Considering the greater concern associated with deferral of LM stenoses, the use of this higher cutoff value for LM FFR gives the benefit of doubt to the patient and clinician. The weakness of this meta-analysis is that its power was limited by the small sample sizes and small numbers of trials available to be included— with more trials it is conceivable that a mortality benefit might have emerged. Lastly, none of the trials were randomized, leading to a risk of selection bias. This meta-analysis cogently summarizes what each of the relatively small trials individually suggested: that LM FFR safely identifies which LM stenoses require revascularization, and which can be safely deferred. Deferring revascularization is not associated with an increased risk of myocardial infarction or death, and may be associated with decreased mortality, at the cost of some patients needing revascularization at a later date. Respecting LM disease should not mean
sending more patients to surgery based on angiography alone, but should rather drive the operator to be more objective and measure the functional significance of the stenosis. In this regard, the LM artery may be like any other coronary artery. It’s just another vessel that needs FFR. REFERENCES 1. Hamilos M, Muller O, Cuisset T, Ntalianis A, Chlouverakis G, Sarno G, Nelis O, Bartunek J, Vanderheyden M, Wyffels E, Barbato E, Heyndrickx GR, Wijns W, De Bruyne B. Long-term clinical outcome after fractional flow reserve-guided treatment in patients with angiographically equivocal left main coronary artery stenosis. Circulation 2009;120:1505–1512. 2. Park SJ, Kang SJ, Ahn JM, Shim EB, Kim YT, Yun SC, Song H, Lee JY, Kim WJ, Park DW, Lee SW, Kim YH, Lee CW, Mintz GS, Park SW. Visual-functional mismatch between coronary angiography and fractional flow reserve. JACC Cardiovasc Interv 2012;5:1029–1036. 3. Fearon WF, Yong AS, Lenders G, Toth GG, Dao C, Daniels DV, Pijls NH, De Bruyne B. The impact of downstream coronary stenosis on fractional flow reserve assessment of intermediate left main coronary artery disease: Human validation. JACC Cardiovasc Interv 2015;8:398–403. 4. Mallidi J, Atreya AR, Cook J, Garb J, Jeremias A, Klein LW, Lotfi A. Long term outcomes following fractional flow reserve guided treatment of angiographically ambiguous left main coronary artery disease: A meta-analysis of prospective cohort studies. Catheter Cardiovasc Interv 2015;86:12–18.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
