1. Impact of Risk Factors on Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Class 5 1 st Year Mestrado Integrado em Medicina

2. IntroductionResearch Question and AimsParticipants and MethodsResultsDiscussion Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

3. Abdominal Aortic Aneurysm (AAA) 13 th cause of death in the US: 200,000 new diagnosis each year; 40,000 surgical repairs each year; 9,000 die from rupture each year. Risk Factors: Age>50 y.o. and male gender Hypertension Atherosclerosis Chronic obstructive pulmonary disease Smoking Family history of AAA Previous vascular surgery Introduction Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

4. Elective Open Repair (EOR) “Gold Standard” procedure for AAA repair; Peri and Postoperative complications Venous Bleeding/Haemorrhage Gastrointestinal ischemia and/or dysfunction Cardiac events (including Myocardial Infarction) Pulmonary insufficiency Organ Failure (including Renal failure) Graft infection Operative mortality rounds 1% to 5%; Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Introduction

5. Petr Utikala (2004), Biomed Papers 148(2), 183–187 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Introduction

6. IntroductionResearch Question and AimsParticipants and MethodsResultsDiscussion Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

7. Research Questions Which risk factors mostly contribute to mortality after EOR? Is it possible to improve the prediction of patients’ outcome after EOR? Aims Summarize risk factors, postoperative complications and mortality rates of patients with AAA undergoing EOR; Analyze the impact of risk factors on patients’ outcome after EOR; Research Question and Aims Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

8. IntroductionResearch Question and AimsParticipants and MethodsResultsDiscussion Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

9. Participants and Methods Type of Study Systematic Review followed by Meta-Analysis Study Participants All papers (n=203) published on PubMed Database considering: "abdominal aortic aneurysm"[Text Word] OR "aortic aneurysm, abdominal"[MeSH Terms] OR aaa[Text Word] AND elective[All Fields] AND open[All Fields] AND ((("wound healing"[TIAB] NOT Medline[SB]) OR "wound healing“[MeSH Terms] OR repair[Text Word]) OR ("surgery"[Subheading] OR "operative surgical procedures"[Text Word] OR "surgical procedures, operative"[MeSH Terms] OR "surgery"[MeSH Terms] OR surgery[Text Word])) AND mortality[Text Word] Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

10. Participants and Methods 1 st Triage Step (n=80) Inclusion Criteria Abdominal aortic aneurysms (AAA) Elective open repair/surgery (EOR) Mortality rates after elective open repair Postoperative complications Patient’s outcome Exclusion Criteria Other types or “mixed” aortic aneurysms (n=10) Emergency repair of ruptured AAA (n=13) Patients submitted to endovascular repair (EVAR) (n=51) Other papers as reviews, systematic reviews, meta-analysis, letters or editorials (n=20) Papers in other languages rather than English, French, Spanish or Portuguese (n=16) Not related studies (n=26) Participants and Methods

11. 2 nd Triage Step (n=29+17) Inclusion Criteria Full paper available Provide data about preoperative clinical variables and risk factors Provide data about postoperative complications Provide data about patients’ mortality/outcome Exclusion Criteria Impossibility to obtain full article by on line request, library acquisition or e-mail request to authors (n=13) Other types of articles such as, review (n=1) or meeting abstract (n=1) Not related to the study (n=5) Absence of data about risk factors (n=10) Absence of data about mortality (n=4) Absence of data combining mortality associated to risk factors (n=29) Participants and Methods

12. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors 46 papers (50 individual studies) provided information for Systematic Review: Clinical variables; Risk factor exposition; Postoperative complications; Outcome. 17 papers provided Statistical Data for Meta-Analysis: Risk factor associated Odds Ratio Risk factor associated Confidence Interval Study Participants Participants and Methods

13. Preoperative clinical variables Age (mean) Aneurysm Diameter (mean) Gender (male and female %) Risk Factors exposition Smoking Habits (%) Diabetes Mellitus, DM (%) History of Cardiac Disease, CDH (%) Myocardial Infarction or coronary disease Hypertension, HT (%) History of Pulmonary Disease, PDH (%) COPD or pulmonary embolism Chronic Renal Failure, CRF (%) Increased Creatinine levels (>1.5 or 2.0mg/dL) Postoperative Complications Gastrointestinal Ischemia, GIsch (%) MultiOrgan Failure, MOF (%) Renal Failure, RF (%) Cardiac Complications, CardiacC (%) Myocardial Infarction, MI (%) Respiratory Complications, RespC (%) Total Morbidity Events, (%) Patients Outcome Mortality (%) Risk factor associated outcome Number of deaths Number of livings Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Variables Selection Participants and Methods

14. Statistical Analysis Data input on Database using Statistical Package for Social Sciences (SPSS) Version 16.0 used to summarize the mean frequencies, confidence intervals and standard deviations of all clinical variables, risk factors exposition, postoperative complications, and mortality rates; Epi Info™, Version 6 to perform a χ 2 analysis to determine the Odds Ratio (OR) and 95% confidence interval for the association of risk factors influence on patients’ outcome; R Version 2.6.2 to elaborate the Forest Plot graphics in order to combine the information about the influence of risk factors on patients’ outcome. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Participants and Methods

15. IntroductionResearch Question and AimsParticipants and MethodsResultsDiscussion Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

16. Systematic Review Summarize data from 50 individual studies regarding: Risk Factors Postoperative complications Morbidity rates Mortality rates Results Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

17. Number of Studies MinimumPercentil 25MedianPercentil 75Maximum Mean Age (y.o.)4565,8 69,5 71,072,283,0 Mean Aneurysm Diameter (cm)294,7 5,6 5,96,36,5 Males in Patients Group (%)4667,0 78,0 86,990,399,2 Patients with HT (%)3630,0 46,1 60,072,588,6 Patients with Smoking (%)304,0 32,8 54,275,897,1 Patients with CDH (%)382,4 27,2 44,350,476,0 Patients with PDH (%)336,7 14,0 23,037,058,8 Patients with CRF (%)301,5 6,0 9,517,226,0 Patients with DM (%)372,9 7,0 9,512,036,0 Total Morbidity events (%)170,3 14,8 31,947,668,1 RespC events (%)230,5 5,0 7,513,940,0 CardiacC events (%)251,0 2,6 5,79,825,7 MOFailure events (%)80,8 1,2 3,66,88,0 MI events (%)170,6 1,2 2,26,410,9 GIsch events (%)140,2 0,9 1,73,828,6 RFailure events (%)180,2 1,0 1,56,217,1 <30 day Mortality (%)500,0 2,7 4,45,517,1 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

18. Systematic Review Major Findings Median % of Male Gender is 86.9% Median % of patients with HT is 60.0% Median % of patients with Smoking habits is 54.2% Median % of patients with CDH is 44.3% Median % of Respiratory Complications is 7.5% Median % of Cardiac Complications is 5.3% Median occurrence of Morbidity events of 31.0% Median frequency of Mortality was 4.0% Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

19. Meta-Analysis Determine the Odds Ratio (OR) and 95% confidence interval for the influence of risk factors on patients’ outcome: Mean Age (y.o.) Mean Aneurysm Diameter (cm) Gender Diabetes Mellitus, DM History of Cardiac Disease, CDH Hypertension, HT History of Pulmonary Disease, PDH Chronic Renal Failure, CRF Smoking Habits Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

20. Mean Age (per y.o.) Rigberg DA (2006) Hertzer NR (2005) Hua HT (2005) Leon LR (2005) Zeebregts CJ (2004) Kruger A (2002) Lederle FA (2002) Brady AR (2000) Adjusted OR OR=1.07 95% CI (1.05 – 1.09) p<0.001 Test of heterogeneity: Q: 21.35 d.f.: 7 p.value: 0.003 1.0 2.0 5.010.0 0.5 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

21. Mean Aneurysm Diameter (per cm) Test of heterogeneity: Q: 0.19 d.f.: 2 p.value: 0.910 Hertzer NR (2005) Lederle FA (2002) Brady AR (2000) Adjusted OR OR=1.58 95% CI (1.11 – 2.25) p=0.011 0.5 1.0 2.0 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

22. Female Gender Test of heterogeneity Q: 4.87 d.f.: 7 p.value: 0.676 0.2 1.0 10.00.52.05.020.0 OR=1.58 95% CI (1.39 – 1.80) p<0.001 Rigberg DA (2006) Hertzer NR (2005) Leon LR (2005) Nesi F (2004) Bianchari F (2003) #1 Bianchari F (2003) #2 Rayan SS (2002) Brady AR (2000) Adjusted OR Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

23. Diabetes Mellitus 1.0 2.0 5.010.0 20.0 0.5 Hua HT (2005)Ari Bianchari F (2003) #1 Bianchari F (2003) #2 Rayan SS (2002) Adjusted OR OR=1.28 95% CI (0.80 – 2.06) p=0.309 Test of heterogeneity Q: 1.24 d.f.: 3 p.value: 0.744 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

24. Cardiac Disease History (CDH) 0.2 1.0 0.52.05.020.0 50.0 0.10.05 OR=1.93 95% CI (1.42 – 2.62) p<0.001 Test of heterogeneity Q: 20 d.f.: 6 p.value: 0.003 Conrad MF (2007) Hirzalla O (2006) Hua HT (2005) Nesi F (2004) Bianchari F (2003) #1 Bianchari F (2003) #2 Hertzer NR (2002) Adjusted OR Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

25. Hypertension (HT) 0.2 1.0 10.00.52.05.020.0 50.0 0.10.05 Test of heterogeneity Q: 51.04 d.f.: 5 p.value: <0.001 OR=2.95 95% CI (2.14 – 4.05) p<0.001 Bonardelli S (2007) Hua HT (2005) Nesi F (2004) Bianchari F (2003) #1 Bianchari F (2003) #2 Liapis CD (2003) Adjusted OR Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

26. Pulmonary Disease History (PDH) 0.2 1.0 10.00.52.05.0 0.1 Bonardelli S (2007) Hertzer NR (2005) Hua HT (2005) Nesi F (2004) Bianchari F (2003) #1 Bianchari F (2003) #2 Hertzer NR (2002) Adjusted OR Test of heterogeneity Q: 6.26 d.f.: 6 p.value: 0.394 OR=1.32 95% CI (0.94 – 1.87) p=0.112 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

27. Chronic Renal Failure (CRF) Bonardelli S (2007) Conrad MF (2007) Hirzalla O (2006) Hertzer NR (2005) Hua HT (2005) Bianchari F (2003) #1 Bianchari F (2003) #2 Hertzer NR (2002) Adjusted OR Test of heterogeneity Q: 9.29 d.f.: 7 p.value: 0.232 OR=2.78 95% CI (2.21 – 3.47) p<0.001 1.05.0100.02.010.050.00.5 20.0 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

28. Smoking Habits (current smoker) 0.1 0.5 5.00.21.0 2.00.05 Hirzalla O (2006) Hua HT (2005) Nesi F (2004) Bianchari F (2003) #1 Bianchari F (2003) #2 Adjusted OR OR=1.00 95% CI (0.99 – 1.01) p=0.987 Test of heterogeneity Q: 4.29 d.f.: 4 p.value: 0.368 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

29. Meta-Analysis Influence of risk factor in patient’s outcome after EOR: Hypertension (OR=2.95; p<0.001) Chronic Renal Failure (OR=2.78; p<0.001) Cardiac Disease History (OR=1.93; p<0.001) Female Gender (OR=1.58; p<0.001) Aneurysm Diameter (OR=1.58; p=0.011) Pulmonary Disease History (OR=1.32; p=0.112) Diabetes Mellitus (OR=1.28; p=0.309) Mean Age (OR=1.07; p<0.001) Smoking (OR=1.00; p=0.987) Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Results

30. IntroductionResearch Question and AimsParticipants and MethodsResultsDiscussion Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors

31. Limitations related to study design: Search only in ONE online Database (PubMed). Limitations related to the query: Absence of a unique MeSh term to define “elective open repair”; The “huge” number of risk factors and postoperative complications; Difficulty to define the outcome as <30 days after surgery. Limitations related to studies: Heterogeneity of the studies; Absence of data relative to the most common risk factors; Absence of data relative to risk factors associated outcome. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

32. Epidemiological Data Systematic review revealed: Increased frequency of Male Gender (median 86.9%); Patients are diagnosed with advanced age (median 71.0 y.o); Increased Aneurism Diameter (median 5.9 cm); Our results show similar distribution to those shown in literature referring that AAA are more common in men with age ranging 65-75 y.o. and diagnosed with a diameter of the aorta below the renal arteries of >3.0 cm. Moreover, only patients with AAA >5.0cm are usually indicated for surgical repair. Gillum RF. J Clin Epidemiol. 1995 Nov;48(11):1289-98. Flemming C, et al. Ann. Intern. Med. 142 (3): 203-11. Lederle FA, et al. Arch Intern Med. 2000;160:1425-30. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

33. Risk Factors The most common risk factors found were: Male Gender (median 86.9%); Advanced age (median 71.0 y.o); History of Hypertension, HT (median 60.0%) Smoking Habits (median 54.1%) History of Cardiac Diseases, CDH (median 44.3%) The great majority of studies, including the “ ACC/AHA 2005 guidelines” refer age, smoking, and gender as the most significant AAA risk factors, although, hypertension and history of cardiac disease are also considered Cornuz J, et al. Eur J Public Health 2004; 14(4):343-349. Lederle FA, et al. Arch Intern Med 2000;160:1425-30. Hirsch AT, et al. J Am Coll Cardiol 2006 Mar 21;47(6):1239-312 Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

34. Morbidity/Postoperative Complications The median occurrence of Morbidity events was of 31.0%, and the most frequent postoperative complications found were: Respiratory Complications (median 7.5%) Cardiac Complications (median 5.7%) There is a wide variety of postoperative complications, and most of them are correlated with the healthy condition of the patient prior to the surgery, or also to the experience of the surgical team. Nevertheless, it is accepted that between 5-25% of all patients will at least suffer one complication. Hirsch AT, et al. J Am Coll Cardiol 2006 Mar 21;47(6):1239-312 Wilt TJ, et al. Evid Rep Technol Assess (Full Rep). 2006 Aug;(144):1-113. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

35. Mortality The median frequency of Mortality found was 4.0%. Mortality rates <30days after surgery for patients undergoing EOR ranges between 1-5%, although in some surgical teams this can be 0%. Despite the differential conditions of patients, in-hospital care conditions are extremely important to prevent higher mortality rates. Hirsch AT, et al. J Am Coll Cardiol 2006 Mar 21;47(6):1239-312 Moreover, mortality rates seem to be influenced by patients’ risk factor exposition and therefore can vary within studies. Lederle FA, et al. Arch Intern Med. 2000;160:1425-30. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

36. Influence of risk factor in patient’s outcome after EOR 1.Smoking is considered a significant risk marker for AAA development, although, statistical analysis revealed that it did not influence patient’s outcome. 2.Despite statistical analysis did not provide significant data, Pulmonary Disease History and Diabetes Mellitus may influence the outcome since they represent an increase of 32% and 28%, respectively, in the risk for death after EOR. Nevertheless, these two risk factors require more studies to clarify its effect on patients’ outcome. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

37. Influence of risk factor in patient’s outcome after EOR 3.Statistical analysis revealed that Hypertension or Chronic Renal Failure represent an almost 3-folds increased risk for death after EOR. These risk factors are strictly correlated with patients’ health condition and are extremely important in the recovery after any surgical procedure. 4.As expected Cardiac Disease represent an increased risk factor for death after EOR (almost 2-folds), since it is common that people who suffered cardiac events may have repetitions shortly in time. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

38. Influence of risk factor in patient’s outcome after EOR 5.Remarkably interesting is the fact that Female Gender revealed a 58% increase risk of death after EOR. Although, male gender is a risk factor, when a female develop AAA it has, usually, more severe consequences and death can occur shortly after surgery. 6.Statistical analysis also revealed that an increment of 1cm of the Aneurysm Diameter represents a 58% increase risk of death after EOR. 7.Age has also proved to influence the risk of death after EOR, with an increment of 7% per year. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

39. Despite the fact that EOR has been substituted by Endovascular Repair, EOR has proven to have good results in AAA management, but may require experienced surgeons and good in-hospital intensive care units in order to contribute for the improvement of AAA management. El SK, et al. Interact Cardiovasc Thorac Surg 2008; 7(1):121-124. Our study revealed important findings that contribute to the prediction of patient’s outcome after EOR, by simple analysis of risk factor exposition. Moreover, it may allow the development of a decision tree for the selection of patients that can be submitted to EOR and expect a good outcome. Morbidity and Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA): Impact of Risk Factors Discussion

40. Class 5 1 st Year Mestrado Integrado em Medicina Impact of Risk Factors on Mortality after Elective Open Repair of Abdominal Aortic Aneurysms (AAA):