1. Pathophysiology of the coronary circulation: role of FFR Giuseppe Biondi Zoccai University of Modena and Reggio Emilia, Modena, Italy gbiondizoccai@gmail.com

2. Functional significance of coronary stenosis Past, present, future Pathophysiology Definitions and basics Other aspects

3. The original balloon from Andreas Gruentzig

4. The first coronary angioplasty by Andreas Gruentzig

5. Functional significance of coronary stenosis Past, present, future Pathophysiology Definitions and basics Other aspects

6. Coronary blood flow = 3-5% of CO Basic coronary physiology Resting myocardial O 2 demand is extremely high (20 x skeletal O 2 demand) Myocardium extracts maximum O 2 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/mm 2 versus 500-2000/mm 2 skeletal muscle)

7. Maintaining coronary flow

9. Coronary circulation Myocardial blood flow = coronary flow (Qs) + collateral flow (Qc)

10. Coronary circulation Blood flow (Q) = Pressure (P mean ) Resistance (R) Pressure derived flow measurements

11. Coronary circulation Resistance distribution in the coronary tree

12. Stenosis lead to drop in pressure

14. Coronary blood flow vs % diameter stenosis: Autoregulation of resting flow % Stenosis Rest CBF Ml/gm/min 0% 85% 50% 1.0 05080

15. Coronary reserve

16. Functional significance of coronary stenosis Past, present, future Pathophysiology Definitions and basics Key aspects

17. Coronary circulation

18. What is FFR? FFR is a ratio or % of two flows: Maximum hyperemic flow in the presence of a stenosis FFR = 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

19. Pressure derived flow measurements

20. Theoretical bases of FFR

21. Pressure derived flow measurements R = Myocardial resistance at maximum vasodilation P a = Mean aortic pressure P V = Mean central venous pressure (P a - P v ) R FFR = QNQN Q ( P d – P v ) R = = PdPd PaPa (P a - P v ) myo = P d = 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

22. Relative pressure and relative flow Pijls et al, Circulation 1993;87:1354-67 Q S = Flow in stenotic vessel Q N = Flow in normal vessel

23. Rationale of FFR

24. 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 FFR

25. Intermediate lesions 54-y-o. man, PTCA prox LAD 8 years ago, stable angina, occluded distal LCx Intermediate stenosis Intermediate stenosis Mild-to-moderate stenosis Mild-to-moderate stenosis Non flow limiting stenosis Non flow limiting stenosis Non significant stenosis Non significant stenosis Gross irregularity Gross irregularity...... Angiographist’s glossary FFR = 50 / 92 = 0.53 FFR = 90 / 93 = 0.97 Adenosine 40 µg IC 48-y-o. man, aborted sudden death, no other stenosis at angio

26. Coronary circulation Myocardial blood flow = coronary flow (Qs) + collateral flow (Qc)

27. 26 col-schema fcf (figuur) 26 col-schema fcf (figuur) Poor collaterals low FFR = 0.50 100 Pd 50 An identical stenosis, but... 0

28. 26 col-schema fcf (figuur) 26 col-schema fcf (figuur) Good collaterals higher FFR = 0.75 100 Pd 750 An identical stenosis, but...

29. Visible collaterals on the coronary angiogram (Rentrop) and fractional collateral blood flow Qc/Qn

30. Comparison with stress testing

31. Gould, Am J Cardiol 1974;33:87-94 Anatomic assesement of a stenosis Angiographic significance of coronary lesions % diameter stenosis 102030405060708090100 0 Discrete non- ischemic Ambiguous Borderline Intermediate Moderate Critical Ischemic Severe Significant

32. Physiologic lesion assessment Physiologic lesion assessment Threshold value of FFR to detect significant stenosis FFR Non-signif.Significant stenosis 1.00.800.750 Sensitivity : 90% Specificity : 100% Pijls et al, New Engl J Med 1996; 334:1703-1708 Gray zone

33. Visual angiographic assessment vs FFR in the FAME trial Tonino et al, J Am Coll Cardiol 2010;55:2816-21

34. Functional significance of coronary stenosis Past, present, future Pathophysiology Definitions and basics Other aspects

35. Acute microvascular damage in myocardial 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

36. Normal Myocardium Scar Similar stenosis but different extent of perfusion area FFR = degree of stenosis and extent of perfused miocardial mass 50 ml /min is too low 50 ml /min is sufficient

37. What about serial lesions?

38. Hyperemic stimulants

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

40. Hyperemic stimulants Casella et al, Am Heart J 2004;148:590-5

41. What about coffee?

42. What about severe left ventricular 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

43. What about lesion length? Brosh et al, Am Heart J 2005;150:338-43

44. What about microcirculation?

45. Take home messages

46. Normal value = 1.0 for every patient and every artery Normal value = 1.0 for every patient and every artery FFR is not influenced by changing hemodynamic conditions (heart rate, blood pressure, contractility) FFR is not influenced by changing hemodynamic conditions (heart rate, blood pressure, contractility) FFR specifically relates the influence of the epicardial stenosis to viable myocardial perfusion area and blood flow FFR specifically relates the influence of the epicardial stenosis to viable myocardial perfusion area and blood flow FFR accounts for collaterals FFR accounts for collaterals FFR has a circumscript threshold value (~ 0.75 – 0.80 ) to indicate ischemia FFR has a circumscript threshold value (~ 0.75 – 0.80 ) to indicate ischemia FFR is easy to measure (success rate 99 %) and extremely reproducible FFR is easy to measure (success rate 99 %) and extremely reproducible Pressure measurement has un unequaled spatial resolution (pressure pull-back curve) Pressure measurement has un unequaled spatial resolution (pressure pull-back curve) Caution in acute myocardial infarction and LV hypertrophy Caution in acute myocardial infarction and LV hypertrophy

47. Interested in more?

48. Thank you for your attention For any correspondence: gbiondizoccai@gmail.com For these and further slides on these topics feel free to visit the metcardio.org website: http://www.metcardio.org/slides.html gbiondizoccai@gmail.com http://www.metcardio.org/slides.html