Pattern of calcification: intimal vs. medial, and difference below and above the knee. Aloke Finn, MD CVPath Institute Inc. Gaithersburg, MD.

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1 Pattern of calcification: intimal vs. medial, and difference below and above the knee Aloke Finn, MD CVPath Institute Inc. Gaithersburg, MD. USA

2 Conflict of Interest Declaration Institution grant/research support 480 Biomedical, Abbott Vascular, Atrium, BioSensors International, Biotronik, Boston Scientific, Cordis J&J, GSK, Kona, Medtronic, MicroPort Medical, CeloNova, OrbusNeich Medical, ReCore, SINO Medical Technology, Terumo Corporation, and W.L. Gore, Spectronics, CSI, Lutonix Bard, Surmodics, Microport, Meril Life Sciences Speaking Honoraria Abbott, Cook Medical

3 Talk Outline Intimal and Medial calcification in peripheral arteries Are patterns of calcification above and below the knee different and if so how? In diabetics is there excessive calcification and what type?

4 Intimal Calcification in commonly observed in SFA-POPLITIAL ARTERIES

5 Mönckeberg s Medial Calcification in Asymptomatic Individuals Ca ++ I Ca ++ M Kolodgie F, et al. ESVB 2007:49-70

6 Histologic Sections from Patients with CLI Undergoing a Lower Limb Amputation Dorsalis pedis segment with CTO neovascularization Posterior tibial artery with atheromatous thromboemboli recanalization fragmentation of elastin layer Posterior tibial artery with circumferential medial calcification Ca Ca Soor GS, et al. Pathology 2008;40:

7 Medial and Intimal calcification of the SFA PIT Intimal Calcification Medial Calcification

8 A B C D CV LEFT SFA E A B C D E F G H I J F J I H G

9 Popliteal artery Nodular calcification Ca2+ Plaque rupture with sheet calcification and propagated thrombus

10 Medial Calcification (Mönckeberg s) in dorsalis pedis artery

11 Study of Vascular calcification in human peripheral arteries Vascular calcification was assessed with five severely calcified peripheral arteries. Type of calcification: None, Microcalcification, Fragmented calcification, Sheet calcification, Nodular calcification Intimal vs. Medial calcification Bone formation 170 histologic sections (86 sections from superficial femoral artery [SFA] and 84 sections from popliteal artery) were evaluated.

12 Vascular calcification in human peripheral arteries, from 5 asymptomatic individuals Microcalcification Fragmented calcification Sheet calcification Nodular calcification

13 The relationship between % stenosis and plaque type 100% SFA+POP lesion (532 sections from 6 legs) 100% Below the knee lesion (1270 sections from 6 legs) 90% 90% 80% 80% 70% 60% 50% 40% 30% 20% 10% 0% 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 70% 60% 50% 40% 30% 20% 10% 0% n=16 n=64 0% n=76 n=73 n=59 n=60 n=66 n=42 n=25 n=51 n=502 n=68 n=68 n=73 n=56 n=59 n=69 n=88 n=106 n= % 10-20% 20-30% 30-40% 40-50% 50-60% 60-70% 70-80% 80-90% % AIT/Fibrous PIT Fibroatheroma Fibrocalcific plaque Nodular calcification TCFA Thrombus Total occlusion Fibrocalcific and nodular predominate (Rupture + Erosion) Fibrocalcific and fibroatheroma predominate

14 The relationship between % stenosis and intimal calcification pattern by histology SFA+POP lesion (369 sections from 6 legs) Below the knee lesion (1270 sections from 6 legs) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 100% 90% 80% 70% 60% 50% 40% 30% 20% 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 10% 0% 0-20% 20-40% 40-60% 60-80% % 0-20% 20-40% 40-60% 60-80% % 0% n=71 n=87 n=72 n=69 n=70 n=569 n=125 n=76 n=82 n= % 20-40% 40-60% 60-80% % none microcalcification Fragmented Nodular calcification sheet Microcalcification and fragmented predominate Nodular and sheet calcification predominate

15 Quadrant Calcification Grade Fanelli et al. Cardiovasc Intervent Radiol (2014) 37: Calcification in 10 asymptomatic legs. (preliminary data) AK 444 lesions BK 1126 lesions Intimal Medial 65.9% 24.4% 8.9% 0.8% 90.6% 7.2% 1.9% 0.2% Intimal 81.1% 10.0% 6.9% 0.2% Medial 98.2% 1.5% 0.3% 0%

16 Peripheral vascular disease: who gets it and why? 58 patients (33 men [57%] and 25 females [43%]), age 43 to 95 years (mean 68.7±12.5 years), who underwent a lower extremity amputation (33 [57%] below knee and the rest 25 [43%] above knee) over a 2 year period (Jan 2002 to Dec 2003). 50% had extensive non-healing ulcers and 71% had gangrene, which was more frequent in diabetics (n=34) versus non-diabetics (n=8, p=0.0032). The presence of medial calcification and concomitant atherosclerosis was observed in 168 (77%) of the 218 arterial segments with atherosclerotic plaques. However, the extent of atherosclerosis did not correlate with the extent of medial calcification. Soor GS, et al. Pathology 2008;40:

17 Diabetics have greater atherosclerosis, calcification and neovascularization than non-diabetics Characteristics Diabetic Non-diabetic P valve Number of Patients Medial calcification 40 (type II 80%) % (majority having >50% medial calcification) 28.6% P<0.001 Soor GS, et al. Pathology 2008;40:

18 Conclusion Intimal Atherosclerosis Calcification is frequently observed in both coronary and peripheral artery disease Coronary arteries do not show medial calcification but it is commonly observed in patients with peripheral vascular disease. Our data suggest atherosclerotic and medical calcification is more common above the knee. The most frequent type of calcification is fragmented but sheets of calcification is most frequent in the femoral than popliteal arteries Bone formation AK is seen in 10 to 15% of patients with peripheral vascular disease. Its significance is unknown. Medial calcification is common in peripheral arteries, especially in diabetes and CKD.

19 Funding CVPath Institute Inc. Acknowledgments CVPath Institute Sho Torii, MD Kazuyuki Yahagi, MD Hiroyoshi Mori, MD Emanuel Harari, MD Elena Ladich, MD Robert Kutz, MS Ed Acampado, DVM Youhui Liang, MD Abebe Atiso, HT Jinky Beyer Lila Adams, HT Frank D Kolodgie, PhD Liang Guo, PhD Renu Virmani, MD Washington DC My afinn@cvpath.org

20 Pattern of calcification: intimal vs. medial, and difference below and above the knee Aloke Finn, MD CVPath Institute Inc. Gaithersburg, MD. USA