Fractional flow reserve the best tool for assessing intermediate stenoses

SNOWMASS, COLO. – Fractional flow reserve measurement has rapidly emerged as the tool of choice for deciding in the catheterization laboratory whether to revascularize an intermediate 50%-70% stenosis in a patient with stable ischemic heart disease, according to Dr. E. Murat *Tuzcu.

The evidence is now compelling that fractional flow reserve (FFR) calculated invasively from coronary pressure measurement is superior to angiographic assessment, intravascular ultrasound, or optical coherence tomography for this purpose.

"When the question is, ‘What should we do with the borderline lesion?’ the answer is fractional flow reserve, even in the left main coronary artery," Dr. Tuzcu, professor of medicine at the Cleveland Clinic, asserted at the Annual Cardiovascular Conference at Snowmass.

FFR is the method par excellence for determining if an intermediate stenosis is hemodynamically significant; that is, whether the lesion is responsible for reversible ischemia. If it is, then coronary stenting will improve the patient’s functional status and reduce the likelihood of acute MI and all-cause mortality down the road. If FFR indicates that the stenosis is not responsible for reversible ischemia, however, then PCI won’t improve the patient’s prognosis. FFR has the additional virtues of being fast and simple, and it enables immediate decision-making in the cath lab, he explained.

For Dr. Tuzcu, the game changer for FFR was the DEFER study, which he considers to be one of the most important clinical trials in the field of interventional cardiology in the past decade. It showed that, by using FFR, cardiologists could be more selective in their use of PCI in the setting of stable ischemic heart disease.

DEFER was a multicenter Dutch/Belgian study in which 325 patients underwent FFR measurement just prior to planned PCI for an intermediate stenosis. If the FFR value was less than 0.75 – indicative of reversible ischemia – then PCI was performed as planned. If it was 0.75 or greater, patients were randomized to PCI or to deferred PCI.

At 5 years of follow-up, the rate of cardiac death or acute MI was 3.3% in the 91 patients with an FFR of 0.75 or more in the deferred PCI group – less than 1% per year. That wasn’t significantly different from the 7.9% rate among the 90 patients with an FFR of at least 0.75 who underwent prompt PCI. In contrast, the combined endpoint occurred in 15.7% of the 144 PCI-treated patients with FFR evidence of reversible ischemia due to the target lesion (J. Am. Coll. Cardiol. 2007;49:2105-11.)

DEFER was conducted in the bare metal–stent era. The next major clinical trial advancing FFR was the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study, in which 1,005 patients with multivessel CAD were randomized to PCI with drug-eluting stents guided by FFR or by angiography alone. The FFR definition of reversible ischemia used in FAME and subsequent trials was a value of 0.80 or less.

The 2-year rate of death or MI was 8.4% in the FFR-guided group, significantly less than the 12.9% rate in the angiography-guided patients. For patients with stenotic lesions deferred from PCI on the basis of an FFR greater than 0.80, the 2-year rate of MI was just 0.2%, with a revascularization rate of 3.2% (J. Am. Coll. Cardiol. 2010;56:177-84).

Nearly half of all stenoses were categorized angiographically as intermediate, 50%-70% lesions. FFR classified 35% of such lesions as functionally significant, while 65% were not associated with reversible ischemia (J. Am. Coll. Cardiol. 2010;55:2816-21).

In the FAME-2 trial, 888 patients with stable CAD and at least one functionally significant stenosis with an FFR of 0.80 or less were randomized to PCI plus optimal medical therapy or to optimal medical therapy alone. Recruitment was halted prematurely by the data safety monitoring board because the combined endpoint of death, MI, or urgent revascularization had occurred in 4.3% of the PCI group versus 12.7% of those assigned to optimal medical management alone (N. Engl. J. Med. 2012;367:991-1001).

Dr. Tuzcu noted that optical coherence tomography (OCT) has drawn much interest as a tool for identifying hemodynamically severe coronary stenoses. "It provides great pictures with tremendous resolution. For looking at stent strut coverage, OCT is a star tool. It’s almost like histology," he said.

It can’t, however, hold a candle to FFR for hemodynamic assessment of stenoses, he added, pointing to a recent Spanish study comparing FFR, OCT, and intravascular ultrasound (IVUS) for this purpose. OCT and IVUS displayed moderate diagnostic efficiency, with no clinically meaningful difference between them, but Dr. Tuzcu concurred with the investigators that the low specificity of OCT and IVUS precludes their use in lieu of FFR for functional assessment (J. Am. Coll. Cardiol. 2012;59:1080-9).

The most recent significant development on the FFR front was Dr. Gregg W. Stone’s presentation of the pooled results of the VERDICT and FIRST trials at the Transcatheter Cardiovascular Therapeutics conference in Miami last October. VERDICT and FIRST included 516 patients with 544 intermediate coronary stenoses evaluated by both FFR and IVUS at 24 centers in nine countries. The bottom line was that IVUS-determined minimum luminal cross-sectional area was only modestly correlated with FFR, according to Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University Medical Center/New York Presbyterian Hospital.

"I think this clearly showed – and probably conclusively showed – that, while IVUS is useful in many, many settings, it’s probably not the best tool when FFR is available for deciding which lesion is significant and which is not," Dr. Tuzcu said.

"IVUS is a pretty good tool, sometimes, for morphologic assessment. I like it when there’s an issue with the left main coronary artery. I can size the artery, I can understand an ostial lesion, and I can certainly understand better a bifurcation or trifurcation of the left main coronary artery," he added.

The current American College of Cardiology/American Heart Association guidelines give IVUS a class IIa rating as "reasonable" to assess angiographically intermediate stenoses of the left main coronary artery. FFR gets the same relatively tepid IIa rating for assessment of intermediate stenoses in any coronary arteries. In contrast, the latest European Society of Cardiology guidelines on coronary revascularization have bumped up FFR to a class Ia rating, making it the standard for this assessment.

Dr. Tuzcu reported having no financial conflicts.

b.jancin@elsevier.com

*CORRECTION, 3/1/2013: In an earlier version of this story, the name of Dr. E. Murat Tuzcu was spelled incorrectly. This version has been updated.

SNOWMASS, COLO. – Fractional flow reserve measurement has rapidly emerged as the tool of choice for deciding in the catheterization laboratory whether to revascularize an intermediate 50%-70% stenosis in a patient with stable ischemic heart disease, according to Dr. E. Murat *Tuzcu.

The evidence is now compelling that fractional flow reserve (FFR) calculated invasively from coronary pressure measurement is superior to angiographic assessment, intravascular ultrasound, or optical coherence tomography for this purpose.

"When the question is, ‘What should we do with the borderline lesion?’ the answer is fractional flow reserve, even in the left main coronary artery," Dr. Tuzcu, professor of medicine at the Cleveland Clinic, asserted at the Annual Cardiovascular Conference at Snowmass.

FFR is the method par excellence for determining if an intermediate stenosis is hemodynamically significant; that is, whether the lesion is responsible for reversible ischemia. If it is, then coronary stenting will improve the patient’s functional status and reduce the likelihood of acute MI and all-cause mortality down the road. If FFR indicates that the stenosis is not responsible for reversible ischemia, however, then PCI won’t improve the patient’s prognosis. FFR has the additional virtues of being fast and simple, and it enables immediate decision-making in the cath lab, he explained.

For Dr. Tuzcu, the game changer for FFR was the DEFER study, which he considers to be one of the most important clinical trials in the field of interventional cardiology in the past decade. It showed that, by using FFR, cardiologists could be more selective in their use of PCI in the setting of stable ischemic heart disease.

DEFER was a multicenter Dutch/Belgian study in which 325 patients underwent FFR measurement just prior to planned PCI for an intermediate stenosis. If the FFR value was less than 0.75 – indicative of reversible ischemia – then PCI was performed as planned. If it was 0.75 or greater, patients were randomized to PCI or to deferred PCI.

At 5 years of follow-up, the rate of cardiac death or acute MI was 3.3% in the 91 patients with an FFR of 0.75 or more in the deferred PCI group – less than 1% per year. That wasn’t significantly different from the 7.9% rate among the 90 patients with an FFR of at least 0.75 who underwent prompt PCI. In contrast, the combined endpoint occurred in 15.7% of the 144 PCI-treated patients with FFR evidence of reversible ischemia due to the target lesion (J. Am. Coll. Cardiol. 2007;49:2105-11.)

DEFER was conducted in the bare metal–stent era. The next major clinical trial advancing FFR was the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study, in which 1,005 patients with multivessel CAD were randomized to PCI with drug-eluting stents guided by FFR or by angiography alone. The FFR definition of reversible ischemia used in FAME and subsequent trials was a value of 0.80 or less.

The 2-year rate of death or MI was 8.4% in the FFR-guided group, significantly less than the 12.9% rate in the angiography-guided patients. For patients with stenotic lesions deferred from PCI on the basis of an FFR greater than 0.80, the 2-year rate of MI was just 0.2%, with a revascularization rate of 3.2% (J. Am. Coll. Cardiol. 2010;56:177-84).

Nearly half of all stenoses were categorized angiographically as intermediate, 50%-70% lesions. FFR classified 35% of such lesions as functionally significant, while 65% were not associated with reversible ischemia (J. Am. Coll. Cardiol. 2010;55:2816-21).

In the FAME-2 trial, 888 patients with stable CAD and at least one functionally significant stenosis with an FFR of 0.80 or less were randomized to PCI plus optimal medical therapy or to optimal medical therapy alone. Recruitment was halted prematurely by the data safety monitoring board because the combined endpoint of death, MI, or urgent revascularization had occurred in 4.3% of the PCI group versus 12.7% of those assigned to optimal medical management alone (N. Engl. J. Med. 2012;367:991-1001).

Dr. Tuzcu noted that optical coherence tomography (OCT) has drawn much interest as a tool for identifying hemodynamically severe coronary stenoses. "It provides great pictures with tremendous resolution. For looking at stent strut coverage, OCT is a star tool. It’s almost like histology," he said.

It can’t, however, hold a candle to FFR for hemodynamic assessment of stenoses, he added, pointing to a recent Spanish study comparing FFR, OCT, and intravascular ultrasound (IVUS) for this purpose. OCT and IVUS displayed moderate diagnostic efficiency, with no clinically meaningful difference between them, but Dr. Tuzcu concurred with the investigators that the low specificity of OCT and IVUS precludes their use in lieu of FFR for functional assessment (J. Am. Coll. Cardiol. 2012;59:1080-9).

The most recent significant development on the FFR front was Dr. Gregg W. Stone’s presentation of the pooled results of the VERDICT and FIRST trials at the Transcatheter Cardiovascular Therapeutics conference in Miami last October. VERDICT and FIRST included 516 patients with 544 intermediate coronary stenoses evaluated by both FFR and IVUS at 24 centers in nine countries. The bottom line was that IVUS-determined minimum luminal cross-sectional area was only modestly correlated with FFR, according to Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University Medical Center/New York Presbyterian Hospital.

"I think this clearly showed – and probably conclusively showed – that, while IVUS is useful in many, many settings, it’s probably not the best tool when FFR is available for deciding which lesion is significant and which is not," Dr. Tuzcu said.

"IVUS is a pretty good tool, sometimes, for morphologic assessment. I like it when there’s an issue with the left main coronary artery. I can size the artery, I can understand an ostial lesion, and I can certainly understand better a bifurcation or trifurcation of the left main coronary artery," he added.

The current American College of Cardiology/American Heart Association guidelines give IVUS a class IIa rating as "reasonable" to assess angiographically intermediate stenoses of the left main coronary artery. FFR gets the same relatively tepid IIa rating for assessment of intermediate stenoses in any coronary arteries. In contrast, the latest European Society of Cardiology guidelines on coronary revascularization have bumped up FFR to a class Ia rating, making it the standard for this assessment.

Dr. Tuzcu reported having no financial conflicts.

b.jancin@elsevier.com

*CORRECTION, 3/1/2013: In an earlier version of this story, the name of Dr. E. Murat Tuzcu was spelled incorrectly. This version has been updated.

SNOWMASS, COLO. – Fractional flow reserve measurement has rapidly emerged as the tool of choice for deciding in the catheterization laboratory whether to revascularize an intermediate 50%-70% stenosis in a patient with stable ischemic heart disease, according to Dr. E. Murat *Tuzcu.

The evidence is now compelling that fractional flow reserve (FFR) calculated invasively from coronary pressure measurement is superior to angiographic assessment, intravascular ultrasound, or optical coherence tomography for this purpose.

"When the question is, ‘What should we do with the borderline lesion?’ the answer is fractional flow reserve, even in the left main coronary artery," Dr. Tuzcu, professor of medicine at the Cleveland Clinic, asserted at the Annual Cardiovascular Conference at Snowmass.

FFR is the method par excellence for determining if an intermediate stenosis is hemodynamically significant; that is, whether the lesion is responsible for reversible ischemia. If it is, then coronary stenting will improve the patient’s functional status and reduce the likelihood of acute MI and all-cause mortality down the road. If FFR indicates that the stenosis is not responsible for reversible ischemia, however, then PCI won’t improve the patient’s prognosis. FFR has the additional virtues of being fast and simple, and it enables immediate decision-making in the cath lab, he explained.

For Dr. Tuzcu, the game changer for FFR was the DEFER study, which he considers to be one of the most important clinical trials in the field of interventional cardiology in the past decade. It showed that, by using FFR, cardiologists could be more selective in their use of PCI in the setting of stable ischemic heart disease.

DEFER was a multicenter Dutch/Belgian study in which 325 patients underwent FFR measurement just prior to planned PCI for an intermediate stenosis. If the FFR value was less than 0.75 – indicative of reversible ischemia – then PCI was performed as planned. If it was 0.75 or greater, patients were randomized to PCI or to deferred PCI.

At 5 years of follow-up, the rate of cardiac death or acute MI was 3.3% in the 91 patients with an FFR of 0.75 or more in the deferred PCI group – less than 1% per year. That wasn’t significantly different from the 7.9% rate among the 90 patients with an FFR of at least 0.75 who underwent prompt PCI. In contrast, the combined endpoint occurred in 15.7% of the 144 PCI-treated patients with FFR evidence of reversible ischemia due to the target lesion (J. Am. Coll. Cardiol. 2007;49:2105-11.)

DEFER was conducted in the bare metal–stent era. The next major clinical trial advancing FFR was the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study, in which 1,005 patients with multivessel CAD were randomized to PCI with drug-eluting stents guided by FFR or by angiography alone. The FFR definition of reversible ischemia used in FAME and subsequent trials was a value of 0.80 or less.

The 2-year rate of death or MI was 8.4% in the FFR-guided group, significantly less than the 12.9% rate in the angiography-guided patients. For patients with stenotic lesions deferred from PCI on the basis of an FFR greater than 0.80, the 2-year rate of MI was just 0.2%, with a revascularization rate of 3.2% (J. Am. Coll. Cardiol. 2010;56:177-84).

Nearly half of all stenoses were categorized angiographically as intermediate, 50%-70% lesions. FFR classified 35% of such lesions as functionally significant, while 65% were not associated with reversible ischemia (J. Am. Coll. Cardiol. 2010;55:2816-21).

In the FAME-2 trial, 888 patients with stable CAD and at least one functionally significant stenosis with an FFR of 0.80 or less were randomized to PCI plus optimal medical therapy or to optimal medical therapy alone. Recruitment was halted prematurely by the data safety monitoring board because the combined endpoint of death, MI, or urgent revascularization had occurred in 4.3% of the PCI group versus 12.7% of those assigned to optimal medical management alone (N. Engl. J. Med. 2012;367:991-1001).

Dr. Tuzcu noted that optical coherence tomography (OCT) has drawn much interest as a tool for identifying hemodynamically severe coronary stenoses. "It provides great pictures with tremendous resolution. For looking at stent strut coverage, OCT is a star tool. It’s almost like histology," he said.

It can’t, however, hold a candle to FFR for hemodynamic assessment of stenoses, he added, pointing to a recent Spanish study comparing FFR, OCT, and intravascular ultrasound (IVUS) for this purpose. OCT and IVUS displayed moderate diagnostic efficiency, with no clinically meaningful difference between them, but Dr. Tuzcu concurred with the investigators that the low specificity of OCT and IVUS precludes their use in lieu of FFR for functional assessment (J. Am. Coll. Cardiol. 2012;59:1080-9).

The most recent significant development on the FFR front was Dr. Gregg W. Stone’s presentation of the pooled results of the VERDICT and FIRST trials at the Transcatheter Cardiovascular Therapeutics conference in Miami last October. VERDICT and FIRST included 516 patients with 544 intermediate coronary stenoses evaluated by both FFR and IVUS at 24 centers in nine countries. The bottom line was that IVUS-determined minimum luminal cross-sectional area was only modestly correlated with FFR, according to Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University Medical Center/New York Presbyterian Hospital.

"I think this clearly showed – and probably conclusively showed – that, while IVUS is useful in many, many settings, it’s probably not the best tool when FFR is available for deciding which lesion is significant and which is not," Dr. Tuzcu said.

"IVUS is a pretty good tool, sometimes, for morphologic assessment. I like it when there’s an issue with the left main coronary artery. I can size the artery, I can understand an ostial lesion, and I can certainly understand better a bifurcation or trifurcation of the left main coronary artery," he added.

The current American College of Cardiology/American Heart Association guidelines give IVUS a class IIa rating as "reasonable" to assess angiographically intermediate stenoses of the left main coronary artery. FFR gets the same relatively tepid IIa rating for assessment of intermediate stenoses in any coronary arteries. In contrast, the latest European Society of Cardiology guidelines on coronary revascularization have bumped up FFR to a class Ia rating, making it the standard for this assessment.

Dr. Tuzcu reported having no financial conflicts.

b.jancin@elsevier.com

*CORRECTION, 3/1/2013: In an earlier version of this story, the name of Dr. E. Murat Tuzcu was spelled incorrectly. This version has been updated.