Angiographic V/s Functional Severity of Cor A Stenoses in the FAME Study

FFR v/s CAG in Multivessel Evaluation

JAmCollCardiol2010;55:2816–21Tonino, Fearon et al.

Frijo Jose A

Objectives

• To investigate the relationship between angiographic and functional severity of cor A stenoses in the FAME study

Background

• CAG may result in both underestimation & overestimation of a lesion’s severity & is often inaccurate in predicting which lesions cause ischemia

Principle

• FFR valueof <0.80 identifies ischemia-causing coronary stenoses with an accuracy of >90%

Fractional flow reserve

– During maximum vasodilation– Mean cor pressure/mean Ao pressure– Unaffected by alteration in resting flow– Can immediately assess importance of a lesion for

guiding intervention– Considerable prognostic information– FFR more than 0.8- excellent outcome with deferred

rather than prophylactic intervention– Most direct way to assess physiological significance of

a lesion

Clinical uses of FFR

1. Determining the hemodynamic significance of CAG intermediate lesions:

• Pijls et al - cutoff 0.75 detected ischemia – sensitivity- 88%, specificity- 100%, diagnostic accuracy- 93%

• DEFER - moderate CAD + FFR>0.75 - PCI v/s medical – PCI event rate > medical event rate

Clinical uses of FFR

2. Determining success of PCI: • Multicenter registry - FFR determined

immediately after stenting – most signi independent variable related to future events

Clinical uses of FFR

3. Determining significance of LMCA lesions: • Bech et al- 54pts (29/12)- equivocal LMCA• Medical - 24 pts with FFRs >0.75• CABG - 30 pts with FFR <0.75 • Survival – medical- 100%, CABG- 97%

Clinical uses of FFR

4. Determining the significance of multiple stenoses in the same coronary artery:

• FFR can be used to “map” the hemodynamic effects of multiple stenoses in the same vessel

• FAME

Recommendations for Use of Fractional Flow Reserve

Class IIa• Can be useful to determine whether PCI of a specific

cor lesion is warranted• Can be useful as an alternative to performing

noninvasive functional testing (eg, when the functional study is absent or ambiguous) to determine whether an intervention is warranted

• In the assessment of the effects of intermediate cor stenoses (30% to 70% luminal narrowing) in pts with anginal symptoms

Inclusion

• Mul-tivessel CAD, defined as cor A stenoses of ≥50% of vessel diameter in ≥2 of 3 major epicardial cor A, & if PCI was indicated

Exclusion

• Left main coronary disease• Previous CABG• Recent STEMI(<5days)• Recent N-STEMI(<5days) if peak CK is >1000IU• Cardiogenic shock• Extremely tortuous/calcified cor• Lifeexpectancy <2y• Pregnancy• Contraindication for DES placement

• In this subanalysis of the FAME study, the relationship between CAG & FFR in all pts in the FFR-guided arm ( 509) was analyzed

• 1,005 pts with multi vessel disease were randomly assigned to CAG –guided PCI ( 496) or FFR-guided PCI ( 509)

• Categorized the lesions according to visual CAG stenosis severity into 50%to70%, 71%to90%, & 91%to100% diameter stenosis

• In those randomized to FFR guidance, if the FFR of a particular stenosis was >0.80, -was considered as functionally nonsignificant & no stent was placed

• The definition of functional 0-,1-,2-,or3-VD was made on basis of no of main arteries with an FFR <0.80

• So, a pt with CAG 3- VD could be classified as having functional 0-,1-,2-,or3-VD, after FFR

Serial stenoses• Stenting is only performed if FFR beyond all narrowings

is≤0.80• Investigator then stents the narrowing that appears most

signi or is responsible for largest P gradient during pullback of P sensor

• After stenting 1st lesion, FFR is measured again & any residual narrowing causing an FFR ≤0.80 is stented

• IV adenosine as opposed to intra-coronary adenosine because IV adenosine provides prolonged hyperemia, which allows adequate time to perform a pullback of the pressure wire and localize pressure gradients

• In all FFR-guided pts, investigator is encouraged to measure a final FFR aft PCI

• Although the final FFR measurement can be quite useful for assessing PCI result, it is not mandated in protocol in an attempt to keep the procedure as simple as possible

primary end point (1yr)

• Rate of death• Nonfatal myocardial infarction • Repeat revascularization

• In pts presenting with a NSTEMI & ↑CK-MB before PCI, if peak CK-MB has not occurred, a periprocedural MI will be defined as – Recurrent chest pain lasting for ≥30 m OR new ECG

changes consistent with a 2nd MI – & an ↑ in CK-MB by ≥50% of the preprocedure CK-

MB level• If the pre-PCI CK-MB is falling or already N, then

a periprocedural MI will be defined as a CK-MB ↑ ≥3 times upperlimit of N & a 50% ↑from pre-PCI CK-MB level

Results

• FFR-guided arm of the FAME study -509 pts• 1,414 lesions –indicated before randomization

–FFR was measured successfully in 1,329(94%) of the 1,414 lesions

• 620(47%) - 50%to70%category• 513(39%) - 71%to90%category• 196(15%) - 91%to99%category

• Of all 1,329 lesions, 816(61%) were below ischemic threshold (FFR ≤0.80)

• Of 50%to70% category, in 402(65%), FFR was >0.80 and in 218(35%), FFR was ≤0.80

• Of 71%to90% category, in104(20%), FFR was >0.80 and in 409(80%), FFR was ≤0.80

• In 91%to99% category,7(4%) FFR >0.80 and 189(96%) had FFR ≤0.80

Discussion

• All stenoses with CAG severity 50%to70%, 65% - functionally nonsigni & 35% - functionally signi by FFR

• In more severe stenoses 71%-90% CAG severity- 20% did not induce reversible myo ischemia as established by FFR

• In pts with multivessel CAD, routine measurement of FFR during PCI, as compared with the standard strategy of PCI guided by CAG, signi ↓ rate of 1˚composite end point of death, MI, & repeat revasc at 1 year

• The combined of death & MI was also signi ↓• Without prolonging the procedure, the FFR-

guided strategy ↓the no of stents used, ↓ the amount of contrast agent used

Diabetic Atherosclerosis Preventionby Cilostazol (DAPC) Study

Katakami, Young-SeolKim et al.Circulation.2010;121:2584-2591

Background

• Anti-platelet drugs are effective in preventing recurrence of atherosclerosis in T2 DM.

• However, the efficacy & usefulness of 2 different antiplatelet drugs, aspirin and cilostazol, in the progression of carotid intima-media thickening are unknown.

Aim

• To compare cilostazol and aspirin in prevention of progression of atherosclerosis

• T2-DM aged 40-85years at the time of enrollment who were suspected of having PAD on the basis of an ABI of <1.0, poor pulsation bilaterally or substantially weaker pulsation on either side in the case of the popliteal artery or dorsalis pedis artery, and/or clinical symptoms of PAD

• 329 type2 DM suspected of PAD were allocated to either

• Aspirin-treated(81to100mg/d)group - 152• Cilostazol-treated(100to200mg/d)gp-145

• The changes in intima-media thickness of the common carotid artery during a 2-year observation period were examined as the primary endpoint

Results

• In pts in cilostazol gp, there was signi improvement in max & mean left CCA-IMT during treatment compared with baseline; max & mean right CCA-IMT also exhibited a tendency toward improvement

• In pts in the aspirin gp- there was signi ↑in max left, max right, and mean right CCA-IMT from baseline

Conclusions

• Compared with ASA, cilostazol potently inhibited progression of carotid IMT, an established surrogate marker of CV events, in pts with type2 DM

Effects of Intensive BP Control in T-2 DM

ACCORD-BP

Cushman, Evans et al.N Engl J Med 2010;362:1575-85.

Background

• There is no evidence from randomized trials to support a strategy of lowering SBP <135 to 140 mm Hg in persons with T2DM

Aim

• Whether therapy targeting normal SBP (i.e., <120 mm Hg) ↓ major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events

• 4733 type 2 DM• Intensive therapy- SBP-< 120 mm Hg• Standard therapy- SBP-< 140 mm Hg

• The ACCORD BP trial was a study of a treatment strategy to achieve specific SBP goals, rather than an evaluation of any specific drug regimen

• Type 2 diabetes mellitus and a glycated hemoglobin level of 7.5% or more

• And were ≥40 yrs with CV disease or ≥55 yrs with anatomical evidence of a substantial amount of atherosclerosis, albuminuria, LVH, or at least two additional risk factors for CVD (DLP, HTN, smoking, or obesity)

Primary composite outcome• nonfatal MI, nonfatal stroke, or death from CV

causesThe mean follow-up - 4.7 years

Results

• Mean SBP- 119.3 mm Hg intensive & 133.5 mm Hg standard

• Annual rate of primary outcome - 1.87% (intensive) & 2.09% (standard), P = 0.20)

• Annual rates of death from any cause -1.28% and 1.19% ; P = 0.55

• Annual rates of stroke- 0.32% and 0.53% ; P = 0.01• Serious adverse events attributed to anti-HTN

treatment -77 of 2362 (intensive-3.3%) and 30 of 2371 (standard-1.3%)- P<0.001

Conclusions

• In pts with T2 DM at high risk for CV events, targeting a SBP of <120 mm Hg, as compared with <140 mm Hg, did not reduce rate of a composite outcome of fatal & nonfatal major cardio-vascular events.

THANKS..