עדי ר. בכר כלי דם שערי - צדק

 Aneurysms are focal dilatations of a 50% larger than the expected normal arterial diameter.  Normal aortic diameter is 1-2 cm.  Typically diagnosed if aortic diameter is ≥ 3.0 cm  Nearly all AAAs involve the infrarenal aorta, 25% of AAAs also involve the iliac arteries.

 In the US, AAA causes almost deaths each year and accounts for hospital discharges

 Abdominal aortic aneurysm (AAA) is diagnosed in 5%–10% of men above the age of 65.  There is mounting evidence that the population aged above 80 years will significantly increase over the next 20 years.

Age (per 7-year intervaD^: Female se;< Black race (compared with white) Other race (compared with white) Height (per 7-cm intervai)* Weight (per 16-kg interval)-t Waist circumference (per 11 -cm tnterval)1 Family history of abdominal aortic aneurysm History of smoking§ Hypertension High cholesterol levels Coronary artery disease Claudication Cerebral vascular disease Deep venous thrombosis Diabetes mellitus Chronic obstructive pulmonary disease Cancer at site other than skin Abdominal imaging in past 5 years 1.52(1.45-1,60) 0,62(0, ) 0.72 ( ) 0,85(0, ) 1.20( ) 0 97(0,89-1,06) 1 06(0,98-1,14) 1.96(1,68-2,28) 2. 72(2,37-3,11) 1.25(1,14-1,37) 1,33(1,20-1,48) 1.42(1,30-1,55) 1.39(1 20-1,62) 1-22(1,09-1,37) 0 90(0 76-1,06) 0.68(0, ) 1.04(0, ) 0.90(0,80-1,03) 1.06(0,96-1,18) Aortic Diameter 3,0-3,9 cm Compared vi/ith < 3.0 cm 1.65(1, ) 0.22(0,07-0,68) 0 49(0,35-0,69) 0 91 (0,63-1,33) 1,21 (1, ) 1.08(0, ) 1.15(1,03-1,29) 1.95( ) 5.57(4,24-7,31) 1,16(1,01-1,32) 1,54(1, ) 1-62(1, ) 0,96(0,74-1,25) 1 19(0, ) 0,67( ,54(0, ) 1-28(1,09-1,50) 0,90(0,74-1,09) 0,80(0,67-0,94) Aortic Diameter -- 4,0 cm Compared with < 3 0 cm Multivariabie Models of Factors Associated with Abdominal Aortic Aneurysm as Defined by Infrarenal Aortic Diameter March 1997 Annals of Intenud Medicine Volume 126 Number 6

Prevalence of AAA Patients Who Smoked Prevalence of AAA Patients Who Never Smoked Age %n%ny March 1997 Annals of Internal Medicine Volume I2. Number 6 Prevalence of Abdominal Aortic Aneurysm 4.0 cm or Larger Detected by Screening in Men

Destruction of the structural and cellular components of the aortic wall Proteolitic degradation of the elstin lead to weakening dilatation. Progressive irreversible degeneration of the elastic media

Degradation in the aneurysm wall is contributed by the matrix metalloproteinase family (MMP) Several studies suggested an imbalance between MMP and TIMPs (tissue inhibitor of metalloproteinase)

Circulation Journal Vol.77, December 2013

A promising potential molecular target of pharmacological treatment for AAA is MMPs Other potential medical treatments include anti-hypertensives, statins, and antibiotics. (some of which might work as MMP inhibitors)

Hypothesis: Propranolol might affect the growth of an aneurysm by lowering blood pressure and its biochemical effects on matrix proteins. Several animal studies have indicated that propranolol reduces the growth of an aneurysm and rupture risk. Propranolol for small abdominal aortic aneurysms: results of a randomized trial.(JVS 2002 Jan;35(1):72-9) Patients with AAAs do not tolerate propranolol well, and the drug did not significantly affect the growth rate of small AAAs

ACE inhibitors have found to both stimulate and inhibit MMPs depending on cell types and animal models Transforming growth factor-β (TGF-β) plays an important role in the pathogenesis of Marfan syndrome- Losartan, an ARB and also TGF-β antagonism suppressed the progressive matrix degradation in the mouse model of Marfan syndrome. Results are inconsistent yet

It has pleiotropic effects such as anti-inflammatory activities and has the ability to stabilize plaque as well as to control serum lipid levels. Although statins are expected to be one of the promising drugs for the medical treatment of AAA, further studies are still needed to establish the evidence of their beneficial effects

Several studies have reported that Chlamydia pneumoniae (C. pneumoniae) has been associated with the atherosclerotic lesions of arteries. Few discrepant studies that do not clarify the pharmacological mechanism in respect to the development of AAA, and no clear beneficial effect on AAA expansion

There are numerous reports with respect to the suppressive effects on MMP by tetracycline. There is some limited evidence that Doxycylin may have a slight protective effect in retarding the expansion rates of small AAAs. Further investigation is required.

WeaklowStatin WeaklowDoxycycline WeaklowRoxithromysin WeaklowACE inhibitors WeaklowAngiotensin receptor blockers SVS Guideline Recommendation in the Medical Management of AAA During the Surveillance Period Quality of Evidence Level of Recommendation

Initial size (cm) Mean growth rate (cm/yr)95% CI

 Risk of rupture for untreated aneurysm within 5 years (%) % 35% 75% Aneurysm size 5-5.9cm6-6.9cm≥7cm

 Mortality rate can be as high as 80%  More than one third of rupture cases die outside the hospital Ruptured AAA

Infrarenal AAA ≥ 5.5 cm should undergo repair Infrarenal AAA size cm, ultrasound/CT scans every 6-12 mo AAA <4.0cm, ultrasound every 1-2 years is reasonable Intervention not recommended asymptomatic infrarenal/ juxtarenal AAAs <5.0 cm (men) or <4.5 cm (women)

 Female gender  Rapid expansion- aneurysm growth of >5 mm in six months or 10 mm per year  Coexistent aneurysm or PAD  Symptomatic patient

 Abdominal/back/flank pain — Patients presenting with abdominal/back/flank pain in association with AAA should be admitted for further evaluation and monitoring  Thromboembolism  Aortic infection  Inflammatory aneurysm

Open surgery Endovascular stent grafting

Open surgery

Aneurysm content

 Established procedure more than 40 years of clinical experience  Excludes aneurysm and prevents sac growth  Proven, long-term results

Significant incision in the abdomen 30–90 minute cross-clamp Up to 4-hour procedure 1–2 days intensive care 7–14 days hospitalization 4–6 weeks recovery time

Prolonged convalescence Complications Patients Don’t Want a Big Operation

Endovascular aneurysm repair (EVAR) Benefits minimally invasive reduced risk of perioperative death faster recovery

Arterial Puncture

Arteriotomy devise insertion

Flexible tip Sheath marker Distal radio-opaques markers FreeFlo Fluoroscopy of Talent Stent graft Inside delivery system catheter

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Complete lining of the arterial wall, exclusion of the aneurysm sac with no residual blood flow (endoleak) Final Angiogram

AAA Repair: Closure of Incisions

Aortic neck diameter Aortic neck length Aortic neck angulation Iliac artery and access vessel morphology

 Postprocedural Renal Impairment observed a 10% decrease in creatinine clearance over the first year Life table analysis suggests that between 25% and 36% of EVAR patients have developed renal impairment by 3 years after the procedure, which compares to a 19% rate of renal impairment at 3 years following open repair. EVAR produces a steady deterioration in renal function over time

Device migration after endovascular aneurysm repair

TrialEndpointEVAROPENP EVAR [1] N=1082 ≥ 5.5 cm Mortality1.7 %4.7 %0.009 Secondary interventions 9.8 %5.8 %0.02 DREAM [2] N=345 ≥ 5.0 cm Mortality1.2 %4.6 %0.1 Mortality & severe complications 4.7 %9.8 %0.1

EndpointEVAROPENP Survival89.7%89.6%0.86 Survival free of moderate- severe complications 65.6%65.9%0.88 Aneurysm-related death2.1%5.7%0.05

 An aneurysm is an increase in the diameter of the aorta to more than 3 cm  Prevalence of AAA is 5%–10% of men above the age of 65.  The risk of rupture depends on the axial diameter of the aneurysm  The current available treatments of AAA is either open surgical repair or endovascular aneurysm repair.  Since first described by Parodi in 1991, endovascular aortic repair (EVAR) has progressively and dramatically changed the approach to treating abdominal aortic aneurysm (AAA) disease

 יש לי דמיון שעוזר לפעמים לשכוח חשיבה לוגית תוביל אותך מנקודה A לנקודה B, הדימיון יוביל אותך לכל מקום."