WO2003022122A2

WO2003022122A2 - Individual ffr determination for lesions of a multi-lesioned blood vessel

Info

Publication number: WO2003022122A2
Application number: PCT/IL2002/000694
Authority: WO
Inventors: Evgeny Shalman; Chen Barak; Michael Ortenberg
Original assignee: Florence Medical Ltd.
Priority date: 2001-09-10
Filing date: 2002-08-22
Publication date: 2003-03-20
Also published as: AU2002326135A1; WO2003022122A3

Abstract

A system determines the individual Fractional Flow Reserve (FFR) values for the lesion of a multi-lesioned blood vessel during continuous blood flow therethrough, using a multi-lesion FFR processor (8). The individual FFR value for a lesion of interest can be determined by one of two different approaches. Both approaches require a hyperemic pressure measurement distal to the last lesion. However, one approach requires additional pressure measurements at rest, while the other requires additional hyperemic pressure measurements.

Description

A SYSTEM FOR DETERMINING INDIVIDUAL FFR VALUES FOR THE LESIONS OF A MULTI-LESIONED BLOOD VESSEL, MULTI- LESION FFR PROCESSOR THEREFOR, AND METHOD

THEREFOR

Field of the Invention

The invention relates to determining the values of intravascular hemodynamic parameters in general, and the individual Fractional Flow Reserve (FFR) values for the lesions of a multi-lesioned blood vessel in particular.

Background of the Invention

Vascular diseases are often manifested by reduced blood flow due to atherosclerotic occlusion of blood vessels due to the isolated lesion of a single- lesioned blood vessel or the multiple typically either two or three lesions of a multi-lesioned blood vessel. For single-lesioned blood vessels, clinical studies have shown that angioplasty may be avoided in most cases in which Fractional Flow Reserve (FFR) >0.75, and conversely should be considered for cases in which FFR<0.75 as described in "Pressure-based simultaneous CFR and FFR measurements: understanding the physiology of a stenosed vessel", Shalman, E. et al., Comput. Biol. and Med. 31 (2001) 353-363.

However, it has been found that the technique for deteπnining the FFR value for the isolated lesion of a single-lesioned blood vessel is not applicable for determining the individual FFR value of a lesion of a multi-lesioned blood vessel due to hemodynamic interaction between its lesions as described in "Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery. Validation in humans.^'" by Pijls NJH, et al., Circulation, 2000; 102:2371 :2377, and "Pressure derived fractional flow reserve to assess serial epicardial stenoses: theoretical model and animal validation.^'" by De Bruyne B, et al., Circulation, 2000; 101:1840:1847. To overcome this problem, the articles describe a technique requiring complete obstruction of a tandem-lesioned blood vessel with two lesions for obtaining a so-called wedge pressure denoted P_w for determining the individual FFR values of the two lesions, thereby limiting the analysis to after at least partial treatment of the lesioned blood vessel.

Summary of the Invention

Generally speaking, the present invention enables the determination of the individual FFR values for the lesions of a multi-lesioned blood vessel during the diagnostic stage prior to intervention by virtue of the determination being based on pressure measurements acquired during continuous blood flow therethrough. The pressure measurements include an aortic pressure measurement acquired proximal to the first lesion of a multi-lesioned blood vessel, pressure measurements proximal and distal to the k^th lesion of interest, and at least a hyperemic pressure measurement distal to the last lesion of the lesioned blood vessel. The pressure measurements proximal and distal to the k¹¹ lesion of interest, and distal to the last lesion of a multi-lesioned blood vessel can be acquired with a pressure transducer of a pressure guide wire being deployed stationary at different positions therealong or alternatively they can be obtained during a so-called "pullback" procedure as described in "Practice and Potential Pitfalls of Coronary Pressure Measurement", Pijs, N. H. J., et al., Catherterization and Cardiovascular Interventions 49:1-16 (2000).

Determining the individual FFR values of the lesions of a multi-lesioned blood vessel is preferably achieved by means of an intermediate parameter termed the partial FFR value (hereinafter denoted "pFFR_k") for the first k lesions of a multi-lesioned blood vessel defined as the ratio of the maximal hyperemic pressure P_k distal to the k^lh lesion divided by the maximal hyperemic aortic pressure P₀, namely, pFFR_Ic = Pi/Po_, whereupon the desired individual FFR_k value of a k^th lesion of a multi-lesioned blood vessel is calculated from the following FFR relationship developed hereinbelow: ' -^FFRk _α.P^FFRk-ι -P^FFR

FFR^ pFFR²

where pFFR_k is its partial FFR value, and pFFR_k-] and pFFR_n are respectively the partial FFR values of the k-l^lh and the last lesions of the multi-lesioned blood vessel. The hyperemic aortic pressure P₀ can be equally and is preferably acquired at rest since aortic pressure is substantially equal both at rest and during hyperemia.

It is well known that the pressure gradient Δp across a k^lh lesion of a multi-lesioned blood vessel is proportional to the square of the flow therethrough: Δρ_k= p_k-ι - ρ_k = α_k Q² Eqn. (1) where the constant α_k is a function of its geometry, and Q is the flow through the blood vessel as discussed in articles: "Simultaneous assessment of coronary flow reserve and fractional flow reserve with a novel pressure-based method", Graberg, L., et al., Journal of Interventional Cardiology, 2000; 13:323-329, and the aforementioned "Pressure-based simultaneous CFR and FFR measurements: understanding the physiology) of a stenosed vessel", Shalman, E., et al., Comput. Biol. Med. 31 (2001) 353-364.

Substituting Q = Q_max pFFR_n into Δp_k = P_k-] - P_k = α_k Q², the following equation for the k^th lesion of a multi-lesioned blood vessel is obtained: ΔP_k = P_k__r P_k = α_k Q_max ² pFFR_n ²

Dividing this equation by the hyperemic aortic pressure P₀, substituting pFFR_k-] for P_k-]/Po and pFFR_k for P_k/P₀, and dividing both sides by the term pFFR„² renders the following equation: ρFFR_k_, -pFFR_{k =} α_k Q _1ιax pFFRj P₀ For the case of a single lesioned blood vessel, k=n=l such that pFFR_k-ι=P₀/Po=l, and pFFR_k= pFFR_n=FFR_k which on substitution into Eqn. (1) leads to

Equating the left hand sides of the Eqns. (2) and (3), leads to the following FFR quadratic equation for determining the individual FFR value for a k^lh lesion of a multi-lesioned blood vessel: l -FFR_{k =} p iFTrFπRt? _k_, _- 1p-ιTFττFrτR?

Eqn. (4) FFR_k pFVRl

Eqn. (4) requires at least two hyperemic pressure measurements for determining the individual FFR value for a k^th lesion of a multi-lesioned blood vessel depending on its location i.e. k=l, 2, .., n, and the number of lesions n. Since obtaining hyperemic pressure measurements is complicated and time consuming, an alternative approach for solving the FFR quadratic equation is preferable dependent on finding a suitable term to replace the righthand nominator, namely, ρFFR_k-rpFFR_k. From Eqn. (1),

Q_rest ² such that on re-arranging terms ΔP_k= Δp_k (Po-P_n)/(Po-p_n) where capital case P and small case p respectively denote hyperemic pressure measurements, and pressure measurements at rest. Also, since Δp_k=p_k- p , and pFFR_k- pFFR_k = P_k-]/Po - P_k/P₀ = ΔP_k/ P₀, then _PFFR_k-rpFFR_k = ΔP_k/ P₀ where ΔP_k= (p_k_,-p_k) (P₀-P„)/(p₀- P. -

Brief Description of the Drawings

In order to understand the invention and to see how it can be carried out in practice, preferred embodiments will now be described, by way of non-limiting examples only, with reference to the accompanying drawings, in which similar parts are likewise numbered, and in which:

Fig. 1 is a block diagram of a system for determining the individual FFR values for the lesions of a multi-lesioned blood vessel; Fig. 2 is a graph showing exemplary pressure waveforms of distal pressure measurements simultaneously acquired by a fluid filled pressure transducer and a pressure guide wire; Fig. 3 is a flow diagram showing the steps of a method for determining the individual FFR value for a k^lb lesion of a multi-lesioned blood vessel;

Fig. 4 is a graph showing a mean pressure pulse acquired distal to a lesion at rest before synchronization; Fig. 5 is a graph showing the pressure pulse of Figure 4 after synchronization;

Fig. 6 is a graph comparing the individual FFR values for the lesions of tandem-lesioned blood vessels in nine human patients obtained using the single vasodilatation induction approach of the present invention with the individual FFR values obtained for the same nine patients using the aforementioned Pijls &

DeBrayne technique; and

Fig. 7 is a graph comparing the individual FFR values for the lesions of the tandem-lesioned blood vessels in nine human patients obtained using the multi-vasodilatation induction approach of the present invention and the individual FFR values obtained for the same nine patients using the aforementioned Pijls & DeBruyne technique.

Detailed Description of the Preferred Embodiments

Figure 1 shows a system 1 for detemiining the individual FFR values for the lesions 2 A, ... , 2K- 1 , 2K, 2K+ 1 , ...., and 2N of a multi-lesioned blood vessel 3 for enabling the determination of the necessity of medical treatment of each lesion, and the type. The system 1 is under the control of a user console 4 including a display 6, and includes intravascular pressure measurement apparatus 7 for acquiring pressure waveforms both proximal to the lesions, and distal thereto. The system 1 further includes a multi-lesion FFR processor 8 programmed for calculating the individual FFR values for each k^th lesion where k=l, 2, ..., n. In a preferred embodiment of the present invention, the user console 4, the display 6 and the multi-lesion FFR processor 8 are embodied as a general puipose digital computer. The intravascular pressure measurement apparatus 7 includes a guiding catheter 9 connected to a fluid filled pressure transducer 11 for acquiring pressure measurements outside of patient's body at position A for use as a reference signal. An exemplary guiding catheter 9 is the Ascent JL4 catheter commercially available from Medtronic, USA whilst an exemplary fluid filled pressure transducer 11 is commercially available from Biometrix, Jerusalem, Israel. The intravascular pressure measurement apparatus 7 also includes a pressure guide wire 12 with a pressure transducer 13 at its tip connected to a signal conditioning device 14 for acquiring hyperemic and non hyperemic pressure measurements along the blood vessel proximal and distal to the lesions 2. An exemplary pressure guide wire 12 is the PressureWire™ pressure guide wire commercially available from Radi Medical Systems, Uppsala, Sweden whilst an exemplary signal conditioning device 14 is also commercially available from Radi Medical Systems. With reference to Figures 2-5, the use of the system 1 for determining the

FFR value for a k^lh lesion of a multi-lesioned blood vessel is now described in connection with the single vasodilatation induction approach using the same notation as before, namely, capital case P denotes hyperemic pressure measurements and small case p denotes pressure measurements at rest: The guiding catheter 9 is introduced into the multi-lesioned blood vessel 3 to location A proximal to the lesion 2 A. The pressure guide wire 12 is introduced into the guiding catheter 9 such that its pressure transducer 13 is also proximal to the lesion 2A. The fluid filled pressure transducer 11 continuously acquires the aortic pressure for use as a baseline for correcting pressure measurements acquired by the pressure transducer 13 to compensate for various factors, for example, breathing, patient movement, and the like, which may influence the pressure measurements since they are not acquired simultaneously. The pressure guide wire 12 is advanced to positions proximal to the intermediate lesions, 2K- 1, 2K, and 2K+1, and distal to the lesion 2N for acquiring pressure measurements thereat. Figure 2 illustrates pressure measurements simultaneously acquired by the fluid filled pressure transducer 11 and the pressure transducer 13. The pressure measurement distal to the last lesion 2N is repeated after induction of vasodilatation by administration of a suitable vasodilatation medicament, for example, adenosin. Upon acquiring the pressure measurements, the multi-lesion FFR processor 8 executes the following steps to determine the individual FFR value for a k^lh lesion of interest:

Step 1 : Calculate four amplification factors A _-], A_k) A_n(rest), and _n(hyperemi_c) from the pressure measurement acquired by the pressure transducer 11 for nomialization purposes. The subscripts of the amplification factors correspond to the location of the pressure transducer 13 along the blood vessel, namely, proximal and distal to the k^tb lesion of interest, and distal to the last lesion at rest and at hyperemia. Each amplification factor is the ratio between the mean pressure measurement corresponding to the location of the pressure transducer 13 with respect to the aortic mean pressure.

Step 2: Separate the pressure measurement acquired by the pressure transducer 13 into four sets of discrete pulses, namely, each starting and ending with a local minimum, respectively proximal and distal to the k^th lesion of interest, and distal to the last lesion at rest and at hyperemia. Step 3: Amplify the discrete pulses using the factors A_k-1, A_k, A_n(rest), and _n(hyperemi_c)j respectively, and synchronize them such that each pulse has the same period between its local minimum values using a technique known as Automatic Synchronization Transformation (AST). Figures 4 and 5 illustrate the same pressure pulse before and after synchronization, respectively. Step 4: Calculate four series of mean pressure measurements p_k-ι, p_k, p_n and P„ from the synchronized amplified pulses.

Step 5: Calculate values of pFFR_k-1-pFFR_k where pFFR_k- pFFR_k=ΔP_k/P₀ and ΔP_k=(pk-rpk) (Po-Pn)/(po-Pn) on the assumption that Po^o, and pFFR_n values where pFFR_n=P„/Po also on the assumption that Po=po- Step 6: Calculate the FFR value for the k^th lesion of interest by solving the FFR quadratic equation: l - FFR_{k =} pFFR_k_, - pFFR_k FFR_k ^~ pFFR* using the third largest values for each of pFFR_k-rpFFR _ι and pFFR_n from Step 6. Figure 6 shows that the individual FFR values obtained using the above approach have a high correlation of about 0.92 with those obtained using the Pijls & DeBrayne technique for the same nine human patients.

The system 1 may alternatively be employed for determining the individual FFR values for the lesions of a multi-lesioned blood vessel by solving the FFR quadratic equation using multiple hyperemic pressure measurements. In this case, vasodilatation is repeatedly induced prior to pressure measurements taken proximal and distal to a k^lh lesion of interest, and distal to the last lesion. The pressure measurements using the fluid filled pressure transducer 11 are also taken to use for baseline purposes as described hereinabove. Figure 7 shows that the individual FFR values obtained using the multiple vasodilatation induction approach of the present invention also have a high con-elation of about 0.9 with those obtained using the Pijls & DeBrayne technique for the same nine human patients.

While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications, and other applications of the invention can be made within the scope of the appended claims. For example, pressure data may be mean pressures over a heartbeat, maximal diastolic pressures, and the like.

Claims

Claims:

1. A system for detennining the individual Fractional Flow Reserve (FFR) value for a lesion of interest of a multi-lesioned blood vessel, the system comprising: (a) intravascular pressure measurement apparatus for acquiring pressure measurements in the multi-lesioned blood vessel during continuous blood flow therethrough; and

(b) a multi-lesion FFR processor for determining the FFR_k value for a k^th lesion of the multi-lesioned blood vessel where k=l, 2, ..., n based on an aortic pressure measurement acquired proximal to the first lesion of the multi-lesioned blood vessel, pressure measurements proximal and distal to the k^th lesion, and at least a hyperemic pressure measurement distal to the last lesion of the multi- lesioned blood vessel.

2. The system according to claim 1 wherein said multi-lesion FFR processor ddeetteerrmmiinneess the FFRv value for the k^th lesion in accordance with the FFR relationship

where pFFR is its partial FFR value, and pFFR_k-] and pFFR are respectively the partial FFR values of the k- 1 ^th and the last lesions.

3. 'The system according to claim 2 wherein pFFR_k- pFFR_k=ΔP_k/P₀ and

Λ p_k = £..=! — F^j (p_o _ p_n) where p_k-1 and p_k are respectively pressure

measurements proximal and distal to the k^th lesion at rest, P₀ and p₀ are aortic pressure measurements, and p_n and P_n are pressure measurements distal to the last lesion at rest and at hyperemia, respectively.

4. The system according to claim 2 wherein pFFR_k.ι=P_k.ι/P_0% pFFR_k=P_k/P₀ and pFFR^P Po where P_k-! and P_k are respectively hyperemic pressure measurements proximal and distal to the k¹'¹ lesion, Po is an aortic pressure measurement, and P_n is a hyperemic pressure measurement distal to the last lesion.

5. The system according to claim 2 wherein the FFR relationship is as follows:

1 - FFR, pFFR -pFFR k- 1 k

FFR pFFR; k n

6. For use with intravascular pressure measurement apparatus capable of acquiring pressure measurements in a multi-lesioned blood vessel, a multi-lesion FFR processor for determining the individual Fractional Flow Reserve (FFR) value for a lesion of interest of a multi-lesioned blood vessel, the multi-lesion FFR processor operable to :

(a) receive pressure measurements acquired in the multi-lesioned blood vessel during continuous blood flow therethrough; and

(b) deteπnine the FFR_k value for a k^th lesion of the multi-lesioned blood vessel where k=l, 2, ..., n based on an aortic pressure measurement acquired proximal to the first lesion of the multi-lesioned blood vessel, pressure measurements proximal and distal to the k^lh lesion, and at least a hyperemic pressure measurement distal to the last lesion of the multi-lesioned blood vessel.

7. The multi-lesion FFR processor according to claim 6 and operable to deteπnine the FFR value for the k^lh lesion in accordance with the FFR relationship:

where pFFR_k is its partial FFR value, and pFFR_k-] and pFFR_n are respectively the partial FFR values of the k-l^lh and the last lesions.

8. The multi-lesion FFR processor according to claim 7 wherein pFFR _-1-

pFFR =ΔP_k/P₀ and ΔP_k = ■£-*--! — £- (p_o _ p where p -ι and p_k are respectively

Po -P„ pressure measurements proximal and distal to the k^lh lesion at rest, P₀ and p₀ are the aortic pressure measurements, and p_n and P„ are pressure measurements distal to the last lesion at rest and at hyperemia, respectively.

9. The multi-lesion FFR processor according to claim 7 wherein pFFR _-1=P_k_ ]/P_0, pFFR_k=P_k/P₀ and ρFFR„=P_n/P₀ where P_k-] and P_k are respectively hyperemic pressure measurements proximal and distal to the k^th lesion, P₀ is an aortic pressure measurement, and P_n is a hyperemic pressure measurement distal to the last lesion.

10. The multi-lesion FFR processor according to claim 7 wherein the FFR relationship is as follows:

1- - FFR_k _ pFFR_k _₁ -pFFR_k

FFR² pFFR² k n

11. A method for determining the individual Fractional Flow Reserve (FFR) value for a lesion of interest of a multi-lesioned blood vessel, the method comprising the steps of:

(a) deploying intravascular pressure measurement apparatus for acquiring pressure measurements in the multi-lesioned blood vessel during continuous blood flow therethrough; and

(b) determining the FFR_k value for a k^lh lesion of the multi-lesioned blood vessel where k=l, 2, ..., n based on an aortic pressure measurement acquired proximal to the first lesion of the multi-lesioned blood vessel, pressure measurements proximal and distal to the k^th lesion, and at least a hyperemic pressure measurement distal to the last lesion of the multi-lesioned blood vessel.

12. The method according to claim 11 wherein step (b) includes determining the FFR value for the k^th lesion in accordance with the FFR relationship:

13. The method according to claim 12 wherein pFFR_k-]-pFFR_k=ΔP_k/P₀ and

ΔP_k = ?_--=! — r (p_o._p_n) where p_k-] and p_k are respectively pressure

Po ^~P„ measurements proximal and distal to the k¹ lesion at rest, P₀ and p₀ are aortic pressure measurements, and p_n and P_n are pressure measurements distal to the last lesion at rest and at hyperemia, respectively.

14. The method according to claim 12 wherein pFFR _ι=P_k-ι/P₀, pFFR_k=P_k/P₀ and pFFR_n=P₁₁/T₀ where P_k-] and P_k are respectively hyperemic pressure measurements proximal and distal to the k¹¹ lesion, P₀ is an aortic pressure measurement, and P„ is a hyperemic pressure measurement distal to the last lesion.

15. The method according to claim 12 wherein the FFR relationship is as follows: 1-FFR- _PFFR_k__rpFFR_k k .

FFR² pFFR² k