Small artery disease (SAD) and medial artery calcification ... · WIfI-WOUND 3 24 9% Mean FU 19 months (3-59) Preliminary analysis, preparing for publication Pts selection criteria

Vincenzo Foppa, 1462“The miracle of the salvaged foot” Cappella Portinari, S. Eustorgio Church Milan, Italy

Small artery disease (SAD) and medial artery calcification (MAC) are changing the fate of CLI patients

- SAD is a major cause of CLTI

- MAC is strongly associated with PAD

- Are SAD & MAC the same non-atherosclerotic disease?

- SAD-MAC is a leading actor in CLI pts

SAD: small artery diseaseMAC: medial artery calcification

Claudicants CLTI

0.51 (0.29 - 0.89)

0 artery ref.1 artery 1.7 (0.76 - 3.83)2 arteries 1.86 (0.72 - 4.83)3 arteries 4.84 (1.12 - 20.88)

0 artery ref.1 artery 1.69 (0.74 - 3.87)2 arteries 5.81 (1.91 - 17.62)3 arteries 5.71 (1.03 - 31.78)

Any of BTA and Arch

13.25 (1.69 - 104.16)

0.53 (0.26 - 1.1)

1.17 (0.68 – 2.01)

Prox

BTK

Dist

BTK

BTA

vessels

Arch

P-TPT

SFA

ATG

Aggregated segments

Risk factors for CLTIOdds Ratio (95% CI)

SAD is strongly and independently associated with CLTI, diabetes and dialysis and must be considered as a leading actor in CLTI

What is MAC?

MAC, also known as Mönckeberg's medial

sclerosis, occurs independently of

atherosclerosis and is strongly associated with

aging, DM and CKD. MAC tends to affect the

artery diffusely, appearing as a linear

contiguous rail-track pattern of calcification

on plain radiography.

MAC is a strong marker of future

cardiovascular events and death

P. Lanzer et al., “Medial vascular calcification revisited: review and

perspectives,” Eur. Heart J., vol. 35, no. 23, pp. 1515–1525, Jun. 2014

K. L. Jablonski and M. Chonchol, “Vascular calcification in end-stage

renal disease,” Hemodial. Int. Int. Symp. Home Hemodial., vol. 17 Suppl

1, pp. S17-21, Oct. 2013

K. J. Rocha-Singh, T. Zeller, and M. R. Jaff, “Peripheral arterial

calcification: prevalence, mechanism, detection, and clinical

implications,” Catheter. Cardiovasc. Interv. Off. J. Soc. Card. Angiogr.

Interv., vol. 83, no. 6, pp. E212-220, May 2014

W. L. Lau and J. H. Ix, “Clinical detection, risk factors, and

cardiovascular consequences of medial arterial calcification: a pattern

of vascular injury associated with aberrant mineral metabolism,”

Semin. Nephrol., vol. 33, no. 2, pp. 93–105, Mar. 2013

S. Lehto et al. “Medial artery calcification. A neglected harbinger of

cardiovascular complications in non-insulin-dependent diabetes

mellitus,” Arterioscler. Thromb. Vasc. Biol., vol. 16, no. 8, pp. 978–983,

Aug. 1996

L. Niskanen et al. “Medial artery calcification predicts cardiovascular

mortality in patients with NIDDM,” Diabetes Care, vol. 17, no. 11, pp.

1252–1256, Nov. 1994

G. M. London et al. “Arterial media calcification in end-stage renal

disease: impact on all-cause and cardiovascular mortality,” Nephrol.

Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. - Eur. Ren. Assoc.,

vol. 18, no. 9, pp. 1731–1740, Sep. 2003

MAC & PAD are strongly associated

Histopathological studies on amputated limbs

of patients with PAD demonstrated that MAC

is highly prevalent, suggesting MAC as one of

the main determinants of PAD, in

combination or not with atherosclerosis

MAC and elevated ABI are associated with

foot ulcer, occlusive PAD and amputation

G. S. Soor et al. “Peripheral vascular disease: who gets it and why? A

histomorphological analysis of 261 arterial segments from 58 cases,” Pathology

(Phila.), vol. 40, no. 4, pp. 385–391, Jun. 2008

N. Narula et al., “Pathology of Peripheral Artery Disease in Patients With Critical Limb

Ischemia,” J. Am. Coll. Cardiol., vol. 72, no. 18, pp. 2152–2163, 30 2018

W. C. O’Neill et al. “Prevalence of nonatheromatous lesions in peripheral arterial

disease,” Arterioscler. Thromb. Vasc. Biol., vol. 35, no. 2, pp. 439–447, Feb. 2015

J. A. Mustapha et al. “Infrapopliteal calcification patterns in critical limb ischemia:

diagnostic, pathologic and therapeutic implications in the search for the endovascular

holy grail,” J. Cardiovasc. Surg. (Torino), vol. 58, no. 3, pp. 383–401, Jun. 2017

C. David Smith et al. “Medial artery calcification as an indicator of diabetic peripheral

vascular disease,” Foot Ankle Int., vol. 29, no. 2, pp. 185–190, Feb. 2008, doi:

10.3113/FAI.2008.0185.

N. Abou-Hassan et al. “The clinical significance of medial arterial calcification in end-

stage renal disease in women,” Kidney Int., vol. 87, no. 1, pp. 195–199, Jan. 2015

W. S. An et al., “Vascular calcification score on plain radiographs of the feet as a

predictor of peripheral arterial disease in patients with chronic kidney disease,” Int.

Urol. Nephrol., vol. 42, no. 3, pp. 773–780, Sep. 2010

M. S. Randhawa et al. “Prevalence of Tibial Artery and Pedal Arch Patency by

Angiography in Patients With Critical Limb Ischemia and Noncompressible Ankle

Brachial Index,” Circ. Cardiovasc. Interv., vol. 10, no. 5, May 2017

V. Aboyans et al. “The association between elevated ankle systolic pressures and

peripheral occlusive arterial disease in diabetic and nondiabetic subjects,” J. Vasc.

Surg., vol. 48, no. 5, pp. 1197–1203, Nov. 2008

E. Lew et al. “Lower extremity amputation risk factors associated with elevated ankle

brachial indices and radiographic arterial calcification,” J. Foot Ankle Surg. Off. Publ.

Am. Coll. Foot Ankle Surg., vol. 54, no. 3, pp. 473–477, Jun. 2015

The wrong concept:MAC as a non-obstructive disease

Despite this strong association between MAC

and PAD, the interaction in determining the

clinical manifestations of the disease is still

unknown, essentially because MAC is

considered by most authors a “non-

obstructive” disease.

Due to this concept, the hypothetic

“mechanisms of action” are supposed to be

indirect effects of the arterial wall stiffening:

loss of vasomotion and adverse remodeling

predisposing to an accelerated vascular aging,

atherosclerosis and plaque rupture

P. Lanzer et al., “Medial vascular calcification revisited: review and

perspectives,” Eur. Heart J., vol. 35, no. 23, pp. 1515–1525, Jun. 2014

K. J. Rocha-Singh, T. Zeller, and M. R. Jaff, “Peripheral arterial

calcification: prevalence, mechanism, detection, and clinical

implications,” Catheter. Cardiovasc. Interv. Off. J. Soc. Card. Angiogr.

Interv., vol. 83, no. 6, pp. E212-220, May 2014

J. A. Mustapha, L. J. Diaz-Sandoval, and F. Saab, “Infrapopliteal

calcification patterns in critical limb ischemia: diagnostic, pathologic

and therapeutic implications in the search for the endovascular holy

grail,” J. Cardiovasc. Surg. (Torino), vol. 58, no. 3, pp. 383–401, Jun.

2017

C. Y. Ho and C. M. Shanahan, “Medial Arterial Calcification: An

Overlooked Player in Peripheral Arterial Disease,” Arterioscler.

Thromb. Vasc. Biol., vol. 36, no. 8, pp. 1475–1482, 2016, doi:

10.1161/ATVBAHA.116.306717.

P.-W. Fok and P. Lanzer, “Media sclerosis drives and localizes

atherosclerosis in peripheral arteries,” PloS One, vol. 13, no. 10, p.

e0205599, 2018

At the best of our knowledge, SAD and MAC were

never considered directly correlated

However, in our daily practice in treating CLTI patients,

we very often observe their coexistence, raising the

question if they could be expression of different

pathophysiological conditions or of the same

underlying non-atherosclerotic disease, leading to

common clinical symptoms

In our daily practice we

observe a strong association

between SAD & MAC

N

Patients 221 100%

Mean age 74 yy

Male 194 76%

DM 191 86%

ESRD-HD 53 24%

Limbs 259 100%

WIfI-WOUND 1 37 14%

WIfI-WOUND 2 198 77%

WIfI-WOUND 3 24 9%

Mean FU19 months

(3-59)

Preliminary analysis, preparing for publication

Pts selection criteria

- 2014-2018

- Consecutive CLTI pts →WIfI Ischemia grade 3

- Tissue loss → RTF 5-6 = WIfI Wound 1-2-3

- Pts with a detailed angiographic imaging of the foot vessels in 2 projections

- Patients living in our region followed in our outpatient clinic

Study on MAC-score & SAD-score

No SADAbsence of disease or mild disease with a well-represented network of forefoot and calcaneal arteries

Moderate SADDiffuse disease with narrowing and poverty of arch, metatarsal, digital and calcaneal arteries

Severe SAD Occlusion or severe disease with extreme poverty of arch, metatarsal, digital and calcaneal arteries

SAD-score

- 5-steps MAC-score- Simple foot X-ray: latero-lateral and antero-posterior- Look for “rail-tracking” calcification length

0-1 ≥20 mm

0-1≥10 mm

0-1 ≥20 mm

0-1 ≥20 mm

0-1 ≥10 mm

0-1 ≥10 mm

0-1 ≥10 mm

MAC-score


MAC-scoreNo MAC

21%

Moderate MAC35%

Severe MAC44%

0-1 = no-MAC

2-3 = moderate MAC

4-5 = severe MAC

Distribution in 259 CLTI-limbs

SAD-score

No-SAD26%

Moderate SAD29%

Severe SAD45%

MAC-score versus SAD-score

MAC-score sensitivity specificity

0-1 no-MAC 100 % 98.1 %

2-3 moderate MAC 99.1 % 92.7 %

4-5 severe MAC 100 % 98.1 %


MAC-score versus SAD-score

SAD & MAC are the same disease! From now on I will talk about SAD-MAC


Healing rate

Global population MAC-score groups SAD-score groups


Limb salvage



Survival



Amputation-free survival



Freedom from foot surgical reintervention



Freedom from redo-PTA



SAD-MAC is a single non-atherosclerotic disease and must be considered the leading actor in CLTI

CLTI-pts with high SAD-MAC scores present at 2yy:- only 30% healing rate without reulceration- double risk of major amputation and death- higher rate of foot and vascular reinterventions

These no-option CLTI pts should be considered for alternative therapies such as:

- primary major amputation

- palliative care

- foot vein arterialization

In the last 50 yy our attention was focalized on pure atherosclerotic BAD-PAD, for which we developed wonderful weapons: bypass, PTA, drugs. Now we are facing a worldwide epidemic of old/DM/CKD CLTI pts that are not pure-BAD-PAD

Vincenzo Foppa, 1462“The miracle of the salvaged foot” Cappella Portinari, S. Eustorgio Church Milan, Italy

Small artery disease (SAD) and medial artery calcification (MAC) are changing the fate of CLI patients

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Small artery disease (SAD) and medial artery calcification ... · WIfI-WOUND 3 24 9% Mean FU 19 months (3-59) Preliminary analysis, preparing for publication Pts selection criteria