Pathophysiology of the coronary circulation: role of FFR Giuseppe Biondi Zoccai University of Modena and Reggio Emilia, Modena, Italy [email protected]

Pathophysiology of Pathophysiology of the coronary the coronary

circulation: role of circulation: role of FFRFFR

Giuseppe Biondi ZoccaiGiuseppe Biondi Zoccai

University of Modena and Reggio Emilia, Modena, University of Modena and Reggio Emilia, Modena, ItalyItaly

[email protected]@gmail.com

Functional significance of Functional significance of coronary stenosiscoronary stenosis

• Past, present, future

• Pathophysiology

• Definitions and basics

• Other aspects

The original balloon from The original balloon from Andreas GruentzigAndreas Gruentzig

The first coronary angioplasty The first coronary angioplasty by Andreas Gruentzigby Andreas Gruentzig



• Pathophysiology


• Other aspects

• Coronary blood flow = 3-5% of CO

Basic coronary physiologyBasic coronary physiologyBasic coronary physiologyBasic coronary physiology

• Resting myocardial O2 demand is extremely high (20 x skeletal O2 demand)• Myocardium extracts maximum O2 from

blood (80% versus 30-40% skeletal muscle)

• Therefore, only way to meet increasing demand is to increase blood flow

• Myocardium has high capillary density (3000-4000/mm2 versus 500-2000/mm2 skeletal muscle)

Maintaining coronary flowMaintaining coronary flow

Maintaining coronary flowMaintaining coronary flow

Coronary circulationCoronary circulation

Myocardial blood flow =

coronary flow (Qs) + collateral flow (Qc)


Blood flow (Q) = Blood flow (Q) =

Pressure (PPressure (Pmeanmean))

Resistance (R)Resistance (R)

Pressure derived flow measurements


Resistance distribution in the coronary tree

Stenosis lead to drop in pressureStenosis lead to drop in pressure

Stenosis lead to drop in pressureStenosis lead to drop in pressure

Coronary blood flow vs % diameter stenosis:Coronary blood flow vs % diameter stenosis:Autoregulation of resting flowAutoregulation of resting flow

% Stenosis

Res

t C

BF

Ml/

gm

/min

0% 85%50%1.0

0 50 80

Coronary reserveCoronary reserve



• Pathophysiology


• Key aspects


What is FFR?What is FFR?

FFR is a ratio or % of two flows: Maximum hyperemic flow in the presence of a stenosisFFR = Normal maximum flow

FFR represents the extent to wich maximal myocardial blood flow is limited by the presence of epicardial stenosis

FFR is a segment by segment evaluation of the flow

Pressure derived flow Pressure derived flow measurementsmeasurements

Theoretical bases of FFRTheoretical bases of FFR

Pressure derived flow Pressure derived flow measurementsmeasurements

R = Myocardial resistance at maximum vasodilation

Pa = Mean aortic pressurePV = Mean central venous pressure

(Pa - Pv)

R

FFR =

QN

Q( Pd – Pv )

R= =

Pd

Pa

(Pd – Pv)

(Pa - Pv)myo

=

Pd = Hyperemic distal coronary pressure

•Because the myocardial vascular bed is maximally vasodilated its resistance is minimal and constant.

•Because, generally, central venous pressure is close to 0

Relative pressure and relative flowRelative pressure and relative flow

Pijls et al, Circulation 1993;87:1354-67

QS = Flow in stenotic vessel

QN = Flow in normal vessel

Rationale of FFRRationale of FFR

ΔP = 30 mm Hg in all 3 cases

but

Driving pressure over the myocardium(wich determines myocardial perfusion at maximum vasodilatation) varies from

25 to 70 mm Hg

Hyperemic blood flow is not determined by ΔP but by (Pd-Pv)/(Pa-Pv)

=

FFR myo

Rationale of FFRRationale of FFR

Intermediate lesionsIntermediate lesions 54-y-o. man, PTCA prox LAD 8 years ago,54-y-o. man, PTCA prox LAD 8 years ago,

stable angina, occluded distal LCxstable angina, occluded distal LCx

• Intermediate stenosisIntermediate stenosis

• Mild-to-moderate stenosisMild-to-moderate stenosis

• Non flow limiting stenosisNon flow limiting stenosis

• Non significant stenosisNon significant stenosis

• Gross irregularityGross irregularity

• ......

Angiographist’s glossaryAngiographist’s glossary

FFR = 50 / 92 = 0.53FFR = 50 / 92 = 0.53FFR = 90 / 93 = 0.97FFR = 90 / 93 = 0.97

Adenosine 40 µg ICAdenosine 40 µg IC Adenosine 40 µg ICAdenosine 40 µg IC

48-y-o. man, aborted sudden death,48-y-o. man, aborted sudden death,no other stenosis at angiono other stenosis at angio


Myocardial blood flow =

coronary flow (Qs) + collateral flow (Qc)

• 26 col-schema fcf (figuur)26 col-schema fcf (figuur)

Poor collaterals low FFR = 0.50

100

Pd

50

An identical stenosis, but...An identical stenosis, but...

0

• 26 col-schema fcf (figuur)26 col-schema fcf (figuur)

Good collaterals higher FFR = 0.75

100

Pd

75 0

An identical stenosis, but...An identical stenosis, but...

Visible collaterals on the Visible collaterals on the coronary angiogram (Rentrop) coronary angiogram (Rentrop) and fractional collateral blood and fractional collateral blood

flow Qc/Qnflow Qc/Qn

Comparison with stress testingComparison with stress testing

Gould, Am J Cardiol 1974;33:87-94

Anatomic assesement of a stenosisAnatomic assesement of a stenosisAngiographic significance of coronary lesions

% d

iam

eter

st

enos

is

10 20 30 40 50 60 70 80 90 1000

Discrete non-ischemic

AmbiguousBorderline

IntermediateModerate

CriticalIschemicSevere

Significant

Physiologic lesion assessmentPhysiologic lesion assessment

Threshold value of FFR to detect significant stenosis

FFR Non-signif. Significant stenosis

1.0 0.80 0.75 0

Sensitivity : 90%Specificity : 100%

Pijls et al, New Engl J Med 1996; 334:1703-1708

Gray zone

Visual angiographic Visual angiographic assessment vs FFR in the FAME assessment vs FFR in the FAME

trialtrial

Tonino et al, J Am Coll Cardiol 2010;55:2816-21



• Pathophysiology


• Other aspects

Acute microvascular damage in Acute microvascular damage in myocardial infarctionmyocardial infarction

STEMI

Variable degree of reversible microvascular

stunning

Maximum achievable flow is less

Smaller gradient and higher FFR across any

given stenosis

With time, the microvasculature may recover, maximum achievable flow may increase, and a larger gradient with a

lower FFR may be measured across a given stenosis

Normal MyocardiumNormal Myocardium

Normal MyocardiumNormal Myocardium

Scar

Similar stenosis but different extent Similar stenosis but different extent of perfusion areaof perfusion area

FFR = degree of stenosis and extent of perfused miocardial mass

50 ml /min is too low

50 ml /min is sufficient

What about serial lesions?What about serial lesions?

Hyperemic stimulantsHyperemic stimulants


Jeremias et al, Am Heart J 2000;140:651-7


Casella et al, Am Heart J 2004;148:590-5

What about coffee?What about coffee?

What about severe left ventricular What about severe left ventricular hypertrophy?hypertrophy?

In severe left ventricular hypertrophy, there is an exaggerated increase of left ventricular mass in comparison to the vascular bed,

resulting in the potential for ischemia even in normal or almost normal coronary arteries

Thus, sensitivity may be reduced (cut-off >0.80?)However, specificity remains satisfactory

What about lesion length?What about lesion length?

Brosh et al, Am Heart J 2005;150:338-43

What about microcirculation?What about microcirculation?

Take home messagesTake home messages

Take home messagesTake home messages• Normal valueNormal value = 1.0 = 1.0 for every patient and every artery for every patient and every artery

• FFR is FFR is not not influenced influenced by changing by changing hemodynamic hemodynamic conditionsconditions (heart rate, blood pressure, contractility)(heart rate, blood pressure, contractility)

• FFR FFR specifically relates the influence of the specifically relates the influence of the epicardial epicardial stenosis tostenosis to viable myocardial perfusion area and viable myocardial perfusion area and blood flowblood flow

• FFR accounts for FFR accounts for collateralscollaterals

• FFR has FFR has a a circumscriptcircumscript threshold valuethreshold value (~ 0.75 – 0.80 ) to (~ 0.75 – 0.80 ) to indicate ischemiaindicate ischemia

• FFR is FFR is easeasyy to measure (success rate 99 %) and extremely to measure (success rate 99 %) and extremely reproduciblereproducible

• Pressure measurement has un Pressure measurement has un unequaled spatial resolutionunequaled spatial resolution (pressure pull-back curve)(pressure pull-back curve)

• Caution in Caution in acute myocardial infarction acute myocardial infarction and and LV hypertrophyLV hypertrophy

Interested in more?Interested in more?

Thank you for your attention

For any correspondence: [email protected]

For these and further slides on these topics feel free to visit the metcardio.org website:

http://www.metcardio.org/slides.html

mailto:[email protected]



Documents

Pathophysiology of the coronary circulation: role of FFR Giuseppe Biondi Zoccai University of Modena and Reggio Emilia, Modena, Italy [email protected]