Aloke Finn, MDCVPath Institute Inc. Gaithersburg, MD.

USA

Vascular calcification in peripheral arteries: Implications for device design and

procedural success

Disclosure Statement of Financial Interest

Speaker's name : Aloke, Finn, Gaithersburg

☑ I have the following potential conflicts of interest to report:

Institutional Receipt of grants / research supports: Abbott, Biosensors, Biotronik, Boston Scientific, Celonova, Edwards Lifesciences, Medtronic, MicroPort, Mitralign, OrbusNeich, Sinomed

Receipt of honoraria or consultation fees: Abbott, Boston Scientific, Celonova, Sinomed, Cook, Bard, Amgen

Movat H&E

A Movat H&E

B

C

D

E

F

G

H

Movat H&E

Movat H&E

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Figure 1Atherosclerotic Plaque Progression in Peripheral Arteries

AIT

PIT

FA

TCFA

Rupture

Healed Rupture

Fibrous Plaque

CTO

Figure 2-A

A

B

C

D

E

F

G

Movat Von Kossa

Movat Von Kossa

H&E

H&E

H&E

Movat

Movat H&E

Sheet Ca2+

Intimal Calcification in Peripheral arteries

Figure 2-B

A

B

C

D

E

F

Movat Von Kossa

Movat Von Kossa

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Medial Calcification

Atherosclerosis and calcification

in human peripheral arteries

16 asymptomatic legs (3069 histologic sections) from 12 patients

Type of calcification

Intimal vs. Medial calcification

Mean age 82±4, Male 70% Torii S. JACC Imaging 2018 Dec 6.

AIT PIT Fibrous Plaque Fibroatheroma Fibrocalcific plaque TCFA

Rupture Calcified Nodule CTO

n=40 n=146 n=75 n=58n=142 n=45 n=45n=177 n=133 n=145 n=679 n=86 n=110 n=130n=87 n=123 n=283n=270 n=111 n=102

Above the knee lesion Below the knee lesion(%) (%)

0

10

20

30

40

50

60

70

80

90

100

0

10

20

30

40

50

60

70

80

90

100

Healed Rupture/Calcified Nodule/Erosion

n=1981n=1006

The relationship between % stenosis and plaque type

n=120 n=62n=151 n=170 n=86 n=485 n=209n=74 n=77 n=144

None Microcalcification Fragmented NodularSheet

Above the knee lesion Below the knee lesion

IntimalCalc

MedialCalc

(%) (%)

(%) (%)

Punctate

0

10

20

30

40

50

60

70

80

90

100

0-20% >20-40% >40-60% >60-80% >80-100%

0

10

20

30

40

50

60

70

80

90

100

1, 0-20% 2, <20-40% 3, <40-60% 4, <60-80% 5, <80-100%

0

10

20

30

40

50

60

70

80

90

100

1, 0-20% 2, <20-40% 3, <40-60% 4, <60-80% 5, <80-100%

0

10

20

30

40

50

60

70

80

90

100

1, 0-20% 2, <20-40% 3, <40-60% 4, <60-80% 5, <80-100%

n=989n=589

n=485 n=209n=74 n=77 n=144n=120 n=62n=151 n=170 n=86

The relationship between % stenosis and Calcification(non-decalcified arteries)

0-1

0%

>10-2

0%

>20-3

0%

>30-4

0%

>40-5

0%

>50-6

0%

>60-7

0%

>70-8

0%

>80-9

0%

>90-1

00%

0

2 0

4 0

6 0

8 0

1 0 0

in tim a l c a lc

m e d ia l c a lc

% stenosis

% s

ecti

on

s sh

ow

ing

calc

ific

atio

nCorrelation between calc and %stenosis

Medial Calcification

Intimal Calcification

Medial and Intimal calcification of the SFA

PIT

Medial calcification appears feathery

Dense calcium more likely to be intimal

SFA

POP

PTA

87 y.o. FemaleSmoker, COPD, CHF

Asymptomatic

ATA Peroneal

C D E

F G H I J

HI

J

B

CTO CTO CTOCTO

DA B C

ACalcifiedNodule

Mechanism of Calcifications of PAD not well understood

Calc

E GF

DA B C

EGF

H

CalcifiedNodule

Thr

Thr

CalcCalc

Calc

Calc

Calc

Calc

MedialMicrocalc

MedialMicrocalc

CT

X-ray

Histology (w/o decalcification)

PropogatedThr

CTOCTO

CTO CTO

OpenLumen

Above the knee (AK)vs.

Below the knee (BK)

A K B K

0

2 0

4 0

6 0

8 0

1 0 0

% stenosis

37.2 (21.6-52.6) 31.7 (9.5-44.7)

p=0.2752 A K B K

0

5

1 0

1 5

2 0

2 5

12.3 (2.9-16.4) 0.7 (0.2-8.0)

p=0.0164

A K B K

0

5

1 0

1 5

2 0

2 5

2.5 (0.7-4.6) 2.3 (1.1-4.4)

p=0.9826

% intimal calc

% medial calc

(%)

(%)

(%)

Calcification Grade

SFA

POP

IntimalMedial

70.7% 22.3% 6.7% 0.3%88.4% 9.5% 2.1% 0%

Medial 95.0% 5.0% 0% 0%Intimal 70.8% 20.8% 7.8% 0.6%

Fanelli et al. Cardiovasc Intervent Radiol (2014) 37:898-907

Ca2+

Ca2+

Ca2+

Ca2+

Calcification in10 asymptomaticlegs.

390 lesions

322 lesions

1a.(8.3%) 1b.(13.3%) 2a.(18.3%) 2b.(16.6%) 3a.(16.6%) 3b.(13.3%) 4a.(6.6%) 4b.(6.6%)

Prevalence of Calcification by CTAngiography in 60Symptomatic patients

None Microcalcification Fragmented NodularSheet

52.1%

63.4%

14.4%

6.4%0.2%

7.2%

23.5%

2.0%

DM: 6 legs from 4 Pts, n=1441

DM non-DM

Intimal calcification

69.0%66.2%

26.0%

0.5%0.1%

11.3%

7.7%2.1%

DM non-DM

15.3%

11.5%

9.9%

6.7%

Punctateor

Medial calcification

non-DM: 6 legs from 4 Pts, n=1546

Diabetes and degree of calcification in PAD

Why vessels below the knee occlude?

10 in 36 BK vessels (27.8%)

are CTO lesions

Atherosclerosis

Distal emboli

10 CTO

lesions

A th e ro sc le ro sis D ista l E m b o l i n o n C T O

0

5

1 0

1 5

2 0 p=0.0167% intimal calc

(%)

26

Patent

A th e ro sc le ro sis D ista l E m b o l i n o n C T O

0

5

1 0

1 5 p=0.4189% medial calc

(%)

5

5

CTO

CTO

SFA POP

ATAE

FG

H

I

B C

D

C D E

F G H I J

A B

Rupture

CTOCTO

A

Calc with Bone

J

Calc

Calc

CalcCalc

CTO secondary to distal emboli

85 y.o. MaleSmoker, HT, DM

Asymptomatic

CTO

Kamenskiy A et al. Arterioscler Thromb Vasc Biol. 2018 Apr;38(4):e48-e57.

Calcification is associated with age and disease stage

A B D E

A B D

F GC

C

E F G

E F

G

Intimal and medial calcification

in long SFA CTO lesion:MicroCT images

A B C D

ProxDist

Vein

VeinVein

Vein

Artery

77-yrs old Male died of CHF with pacemaker implantation, h/o DM, and a smoker.

Calcification worsen the outcome of both DCB and stent

Fanelli et al. Cardiovasc Intervent Radiol (2014) 37:898-907

(Late lumen loss)

a = <3cmb = >3cm

Calcification Grade

After revascularization of SFA lesion by DCB (In.PACT). 60 Symptomatic Pts, age 65±21, Lesion length 3cm-30cm

(n=5) (n=8) (n=11) (n=10) (n=10) (n=8) (n=4) (n=4)

Horimatsu T et al. Heart Vessels. 2017 May 2.

153 Symptomatic pts with SFA disease underwent IVUS followed by EVT

CalcifiedNodule

PlaqueRupture

0.58 0.80

% P

rim

ary

pat

ency

Late

lum

en

loss

Summary Intimal Atherosclerosis Calcification is frequently observed in both coronary

and lower extremities, and is more common in above the knee.

Medial calcification is observed in lower extremities, and calcification is especially high in diabetic and renal failure patients.

In patients with asymptomatic PAD, thrombotic events (calcified nodule and rupture) are exclusively seen in AK.

BK vessels with CTO lesions frequently occur secondary to both atherosclerosis and distal emboli.

Calcification medial and intimal does not allow good vessel preparation and the penetration of the drug, is hampered after DCB usage.

Calcified lesions need a dedicated device that either cracks or removes calcified areas in order to achieve adequate vessel expansion, probably such lesions need DES rather than DCBs.

Acknowledgments

CVPath Institute

Hiroyuki Jinnouchi, MDSho Torii, MDAtsushi Sakamoto, MDAnne Cornelissen, MDMaria Romero, MDAbebe Atiso, HTJinky BeyerLila Adams, HTFrank D Kolodgie, PhDLiang Guo, PhDRenu Virmani, MD

Washington DC

Funding

CVPath Institute Inc.

Calc

Influence of decalcification during sectioning

Non-decalcified Decalcified (paraffin embedded)

Movat HEEXACT

Medial Calcification (Mönckeberg’s) in Dorsalis pedis artery

CV32766 DPCV32766 ATACV32728 SFACV32728 SFA

Bone formation in AK and BK

Athero-Intimal Ca Athero-Intimal Ca Athero-Intimal Ca Medial Ca

7 in 12 Pts (58.3%)

Aloke Finn, MDCVPath Institute Inc. Gaithersburg, MD.

USA

Vascular calcification in peripheral arteries: Implications for device design and

procedural success