Aortic Aneurysms: What s s New?

Transcription

1 25th Annual Advances in Heart Disease 12 December 2008 Aortic Aneurysms: What s s New? Melvin D. Cheitlin, M.D., MACC Emeritus Professor of Medicine UCSF 1

2 AAA in the U.S. 13th cause of death -16,000 deaths/yr Autopsy incidence %. tripled in incidence from 1951 to 1980 (8.7/100,000 in 1951to /100,000 person-yrs in ) Male dominance 3-8 :1 Genetic effects: Familial - 6 fold increase in first degree relatives markedly increased if mother is involved Reilley and Tilson. Surg Clinics N Amer 69:1989 2

3 Prevalence of AAA in Different Populations 24,000 consecutive autopsies - AAA in 2% Darling, Amer J Surg 1970 Unselected population 2 to 3% White males 4.2% White females, black males and females 1.5% With CAD 5% Peripheral art. or cerebrovasc. disease 10% Peripheral aneurysms 40% First order relatives 19.2% v s 2.4% 3

4 AAA - Etiology and Pathogenesis Three components to arterial wall Elastin -elasticity Collagen - wall integrity and strength Smooth muscle - synthesizes collagen and elastin Distending force = LaPlace s law T ~ P x r Stress ~ P x r / t t = 0.7 mm 4

5 AAA - Pathogenesis Why does the aneurysm form? This is a disease of increased load and material failure Abdominal aorta narrows - radius decreases Reflected waves increase systolic pressure Abdominal aorta has few vasa vasora Atherosclerosis - poor nutrition of wall decreases collagen increased elastin Oscillation of wall stretch is stimulus to smooth muscle -aorta stiff- decreased distention MMPs increased, tissue inhibitors of MMPs decreased* doxycycline, statins inhibit MMP activity Role of genetics * Kadoglou NP, Lapis CD. Curr Med Res Opin 2004; 20:419 5

6 AAA - Definition By ultrasound - ULN aorta = 2.5 cm. Crawford s definition diameter of infrarenal abdominal aorta > 1.5 x diameter of aorta at renal level If abdominal aorta is 2 x proximal uninvolved aorta there is threat of rupture Therefore AAA = aortic diameter of 3.0 cm. 6

7 Time to Expansion vs Pulse Pressure 7

8 AAA - Rupture Rupture of AAA - 1.2% deaths in men > age % deaths in women > age 65 Overall mortality of ruptured AAA die before getting to hospital - 27 to 50% die after arrival, before surgery - 24 to 58% die perioperatively - 42 to 80% Overall mortality - 78 to 94% Perioperative mortality - elective AAA repair - 4 to 11% in most series 5% Most AAA are asymptomatic before rupture Quill Surg Clinics N Amer 69;713:

9 AAA - How Fast Do They Grow? 50 patients with AAA 2.5 to 5.0 cm in A-P diameter mean 3.1 ± 0.1 cm. Median annual growth = 0.22 cm. 77.8% increased in size between 6 month echos For aneurysms < 4.0 cm, maximum 6 month increment in diameter was 0.7 cm. Collin. Eur J Vasc Surg 3; 15: patients with serial echos Increase in diameter 0.21 cm/ yr 24% increased 0.4 cm/yr Nevitt. NEJM 34; 1009: 1989 Echos should be done every 6 months 9

10 AAA - Prognosis Nevitt. NEJM 1989;34:1009 Rochester - population-based study aneurysms 181 diagnosed by ultrasound - 5 leaked within 48 hours 176 patients unruptured at first echo < 3.5 cm. Cumulative incidence of rupture 6% at 5 years 8% at 10 years Rupture at 5 years 130 patients < 5.0 cm 46 patients 5 cm (25%) However, small AAA can rupture 473 AAA, 118 (25%) ruptured and died < 4.0 cm 9. 5% died > 10 cm 60.5% died Darling. Am J Surg 1970 Quill Surg Clinics N Amer 69;713:

11 Screening for AAA Family Practice - Ultrasound screen 1195 men - age 65 to 74 years 906 patients done 71 (7.8%) aortic diameter > 2.5 cm 14 (1.5%) aortic diameter > 4.0 cm. O Kelly Brit J Surg 71: subjects (97% male) were screened by ultrasound 144 (1.4%) had aortic diameter 4.0 cm. The risk factor most strongly associated with AAA was smoking: O.R. for diameters 4.0 vs < 3.0 was 5.6 Lederle FA, et al. Ann Intern Med 1997; 126:441 The excess prevalence associated with smoking accounted for 78% of all AAA 4.0 cm or larger 11

12 Screening for AAA Literature search - randomized controlled trials Screening vs No screening 4 Studies - 127,891 men - 9,432 women 3 to 5 years after screening Men Odds ratio Women All cause mortality 0.95 p = 0.4 for both 1.06 AAA-related mortality Rupture AAA Surgery for AAA 0.60 p = men 1.99 p = 0.4 women 0.45 p = 0.05 men 1.49 p = 0.7 women 2.03 p = men - Coford PA, Leng GC. Cochrane Database of Systematic Reviews

13 AAA - Screening the High Risk Population Men 60 to 75 with HVD &/or CAD 201 patients - 18 (9%) (95% CI %) had unsuspected AAA 3.6 to 5.9 cm (mean 4.4 cm) Lederle FA, et al Arch Intern Med 1988;148:

14 AAA - Screening the High Risk Population Men 60 to 75 with HVD &/or CAD 201 patients - 18 (9%) (95% CI %) had unsuspected AAA Accuracy of Physical Exam to Detect AAA 200 men (age 51 to 88 yrs) 99 with without AAA ( 2 internists vs ultrasound) Sensitivity for detecting AAA 68% Specificity 75% Sensitivity Sensitivity 3.6 to 5.9 cm (mean 4.4 cm) Lederle FA, et al Arch Intern Med 1988;148: % Aortic diameter % Abd Girth < 40 in 91% % 40 in P< % % When abd girth < 40 in. and diameter 5.0 cm sensitivity 100% Lederle FA, et al. Arch Intern Med 2000; 160:833 14

15 AAA - Immediate Repair vs Surveillance Lederle FA, et al. NEJM 2002;346:1437 N = 1136 Ages Aneurysm Diameter cm Randomized Follow-up time (mean 4.9)yrs Immediate Surgery N=569 N=567 Operative mortality 2.7% Surveillance -CT/Ultrasound 2 patients Rupture of Aneurysm 11 patients (0.6%/yr) Death - Relative risk Surgery/Surveillance 1.21 (95% CI ) Death Due to Aneurysm 3.0% 2.6% 15

16 AAA - Immediate Repair vs Surveillance Lederle FA, et al. NEJM 2002;346:1437 N = 1136 Ages Aneurysm Diameter cm Randomized Follow-up time (mean 4.9)yrs Immediate Surgery N=569 N=567 Operative mortality 2.7% Surveillance -CT/Ultrasound 2 patients Rupture of Aneurysm 11 patients (0.6%/yr) Death - Relative risk Surgery/Surveillance 1.21 (95% CI ) Death Due to Aneurysm 3.0% 2.6% 16

17 Immediate Surgical Repair vs Surveillance of Small AAA UK Small Aneurysm Trial. NEJM 2002;346:1445 Cumulative Repair of AAA by Treatment Group Cumulative Survival by Treatment Group 92.6% Immediate Repair 61.6% Surveillance Immediate Repair Surveillance QuickTime and a decompressor are needed to see this picture. QuickTime and a decompressor are needed to see this picture. Lederle FA, et al. NEJM 2002; 346:

18 Doxycycline vs Atenolol in Preventing TAA in Marfan Disease Mouse model of Marfan disease 3 months * 1.41* 1.38 (mm) 6 months * 1.85* 1.62** (mm) 9 months * 2.12* 1.78** (mm) Control Marfan Atenolol Doxycycline (40) (40) (30) (30) * <0.05 vs control ** < 0.05 vs Atenolol Chung, A. W.Y. et al. Circ Res 2008;102:e73-e85 18

19 Integrity of Elastic Fibers Elastic Fiber Score 1= extensive Degradation + fragmentation * p=0.05 4=Intact with wavy elastic organization Chung, A. W.Y. et al. Circ Res 2008;102:e73-e85 19

20 Mouse Marfan model (under express fibrillin-1) - die aortic rupture 2-4 months of age MMP-2, -4 in Marfan Syn QuickTime and a decompressor are needed to see this picture. P = Xiong W, et al J Vasc Surg 2008; 47:

21 Results of Interventions on AAA Growth Intervention Effect on AAA Level of Evidence Class Growth Propranolol No inhibition A III Macrolides Inhibition B IIa Tetracycline* Inhibition B IIa Statins Inhibition B IIb ACE inhibitors No inhibition B and C IIb AR blockers Animal data C IIb *Inhibition at 6 and 12 months after 3 months of treatment. Baxter BT, et al. Circulation 2008; 117:

22 Efficacy of Drugs for Decreasing Expansion Rate of AAA Guessous I, et al. Plos One 2008;3:e

23 Deployment of the Gore TAG endoprosthesis.(a) Initial deployment involves the turning and pulling the deployment knob. (B) The endoprosthesis is fully constrained on delivery catheter. (C) The stent graft is deployed from the middle segment expanding outwards. (D) Fully deployed thoracic device.adapted from WL Gore & Associates, Flagstaff, Arizona. Lin PH, et al Vasc Endovasc Surg 25 June

24 Type B dissection - Endovascular With Unistent Wall Stent SMA RA RA Chang WT, et al. Catheter Cardiovasc Intervention 2001; 52:112 24

25 EVR vs Surgery for Thoracic and Thoracoabdominal Aneurysms Greenberg RK, et al Circulation 2008: 118 EVR 352 pts Surg 372 pts Spinal cord injury EVR 15 (4.3%) Surgery 28 (7.5%) P =

26 Computed CT Angiography A. Multibranch repair - thoracoabdominal aneurysm B. L carotid-subclavian bypass with stent distal Arch Aneurysm Chuter TA, et al. J Vasc Surg 2008; 47:6 26

27 Overall Survival and Freedom from Aneurysm-Related Death 22 patients 21 stent graphs 81 branches % patency 9 (41%) periop complications Late - 1 with branch graft stenosis Chuter TA, et al. J Vasc Surg 2008; 47:6 27

28 AAA- Perioperative Outcomes after Elective Surgery and Endovascular Repair (EVR) Lee WA, et al J Vasc Surg 2004; 39:491 The 2001 National Inpatient Sample Database (20% of all non-federal hospitals) 7,172 patients had surgery (64%) or EVR (36%) Despite higher number of octogenarians (23% vs 16%) in EVR and comparable comorbidities 28

29 AAA- Perioperative Outcomes after Elective Surgery and Endovascular Repair (EVR) Lee WA, et al J Vasc Surg 2004; 39:491 The 2001 National Inpatient Sample Database (20% of all non-federal hospitals) 7,172 patients had surgery (64%) or EVR (36%) Despite higher number of octogenarians (23% vs 16%) in EVR and comparable comorbidities Morbidity Mortality EVR 18% 1.3% Surgery 29% 3.8% Multivariate analysis Surgery and age > 80 years strong predictors of: Surgery vs EVR Age > 80 vs < 80 Death O.R Complications O.R Not DC to home O.R All p<

30 AAA - Coronary Artery Disease CAD increases the mortality of AAA surgery by a factor of 3 X 850 patients with prior CABG 4 deaths after subsequent vascular operations Crawford. Ann Thorac Surg 1978;26:215 Mccollom. Surg 1977; 81:302 Reul. J Vasc Surg 1986; 3:

31 AAA - Perioperative Mortality- Risk Factors & Dobutamine Echo Kertai MD,et al. NEJM 2002; 347:1113 Risk Score Pulmonary disease Angina Myocardial infarction Diabetes mellitus Heart failure Stroke Renal failure N = 661 patients with AAA Mean age 67 years Perioperative mortality 9.1% 31

32 AAA -Preoperative Evaluation 500 consecutive patients - urgent and elective Group I 260 (52%) Group II 212 (42%) Group III 28 (6%) No clinical or ECG signs of CAD Golden MA, et al. Ann Surg 1990; 212: 415 Clinical or ECG signs of CAD Severe or unstable angina No further evaluation Repair aneurysm Considered stable after evaluation - No CABG (myo perfusion, echo, coronary arteriogram) Cardiac Deaths 1 (0.4%) P< (2.4%) Revascularization Before AAA in 21 Both together in 7 No deaths 30 day mortality for all 500 patients - 8 (1.6%) 32

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35 AAA in the U.S. 13th cause of death -16,000 deaths/yr Autopsy incidence %. tripled in incidence from 1951 to 1980 (8.7/100,000 in 1951to /100,000 person-yrs in ) Male dominance 3-8 :1 Genetic effects: Familial - 6 fold increase in first degree relatives markedly increased if mother is involved Reilley and Tilson. Surg Clinics N Amer 69:

36 AAA - Etiology and Pathogenesis Three components to arterial wall Elastin -elasticity Collagen - wall integrity and strength Smooth muscle - synthesizes collagen and elastin Distending force = LaPlace s law T ~ P x r Stress ~ P x r / t t = 0.7 mm 36

37 AAA - Rupture Rupture of AAA - 1.2% deaths in men > age % deaths in women > age 65 Multivariate analysis for rupture* aortic tortuosity (O.R. 3.3 greater risk with least tortuosity) diameter asymmetry (O.R. 3.2 for 1 cm difference major-minor axis current smoking (O.R. 2.7) *Fillinger MF, t al J Vasc Surg 2004; 39:1243 Overall mortality of ruptured AAA die before getting to hospital - 27 to 50% die after arrival, before surgery - 24 to 58% die perioperatively - 42 to 80% Overall mortality - 78 to 94% Perioperative mortality - elective AAA repair - 4 to 11% in most series 5% Most AAA are asymptomatic before rupture Quill Surg Clinics N Amer 69;713:

38 AAA - Screening the High Risk Population Men 60 to 75 with HVD &/or CAD 201 patients - 18 (9%) (95% CI %) had unsuspected AAA Accuracy of Physical Exam to Detect AAA 200 men (age 51 to 88 yrs) 99 with without AAA ( 2 internists vs ultrasound) Sensitivity Sensitivity 3.6 to 5.9 cm (mean 4.4 cm) % Lederle FA, et al Arch Intern Med 1988;148:1753 Sensitivity for detecting AAA 68% Specificity 75% Aortic diameter % < 40 in 91% Abd Girth % 40 in P< % % When abd girth < 40 in. and diameter 5.0 cm sensitivity 100% Lederle FA, et al. Arch Intern Med 2000; 160:833 38

39 AAA - Immediate Repair vs Surveillance Lederle FA, et al. NEJM 2002;346:1437 N = 1136 Ages Aneurysm Diameter cm Randomized Follow-up time (mean 4.9)yrs Immediate Surgery N=569 N=567 Operative mortality 2.7% Surveillance -CT/Ultrasound 2 patients Rupture of Aneurysm 11 patients (0.6%/yr) Death - Relative risk Surgery/Surveillance 1.21 (95% CI ) Death Due to Aneurysm 3.0% 2.6% 39

40 Chung, A. W.Y. et al. Circ Res 2008;102:e73-e85 40

41 The proximal component of the Zenith TX2 thoracic endograft device, which has stainless steel barbs protruding through the graft fabric for secure aortic attachment.adapted from Cook Medical, Bloomington, Indiana. Lin PH, et al Vasc Endovasc Surg 25 June

42 Golledge J, Eagle K Lancet 2008; 372:55 42

43 AAA- Perioperative Outcomes after Elective Surgery and Endovascular Repair (EVR) The 2001 National Inpatient Sample Database (20% of all non-federal hospitals) 7,172 patients had surgery (64%) or EVR (36%) Despite higher number of octogenarians (23% vs 16%) in EVR and comparable comorbidities Morbidity Mortality Lee WA, et al J Vasc Surg 2004; 39:491 EVR 18% 1.3% Surgery 29% 3.8% Multivariate analysis Surgery and age > 80 years strong predictors of: Surgery vs EVR Age > 80 vs < 80 Death O.R Complications O.R Not DC to home O.R All p<

44 AAA - Preoperative Evaluation Operative mortality - Acute myocardial infarction and CHF account for 40 to 70% of all deaths DeBakey - Mortality at 5 years - 42% at 10 years - 70% Graor - Cleveland Clinic AAA resections - 3.6% mortality 37% of all deaths - acute myocardial infarction Mortality at 5 years - 31% at 11 years - 52% 44

45 AAA - Rupture Rupture of AAA - 1.2% deaths in men > age % deaths in women > age 65 Multivariate analysis for rupture* aortic tortuosity (O.R. 3.3 greater risk with least tortuosity) diameter asymmetry (O.R. 3.2 for 1 cm difference major-minor axis current smoking (O.R. 2.7) *Fillinger MF, t al J Vasc Surg 2004; 39:1243 Overall mortality of ruptured AAA die before getting to hospital - 27 to 50% die after arrival, before surgery - 24 to 58% die perioperatively - 42 to 80% Overall mortality - 78 to 94% Perioperative mortality - elective AAA repair - 4 to 11% in most series 5% Most AAA are asymptomatic before rupture Quill Surg Clinics N Amer 69;713:

46 Aortic Root (mm) Diameter of Aortic Root Control Marfan Atenolol Doxycycline Marfan Increase vs Control 3 months 9 months 27% * 33% * 0.5 Atenolol Doxycyc 13% * 22% * 0 ** 0 ** 3 months 6 months 9 months Chung, A. W.Y. et al. Circ Res 2008;102:e73-e85 * <0.05 vs control ** < 0.05 vs Atenolol 46

47 p <0.05 * vs WT # vs untreated Marfan QuickTime and a decompressor are needed to see this picture. Control Marfan Marfan - Doxy Aortic tissue trichrome-stained at 6 weeks of age Xiong W, et al J Vasc Surg 2008; 47:

48 Aneurysm Etiology Trauma Atherosclerotic Aortitis Connective tissue disease Marfan disease, Ehlers-Danlos, etc. Aortic dissection Classification False - rupture of the wall True - all layers of aorta Geometry Diffuse Cylindrical Saccular 48