Cardiovascular risk evaluation and management before renal transplantation slideshare

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Presentation focused on pre-operative evaluation of Major Adverse Cardiac Events prior to renal transplantation.

Modified from a presentation I gave in 2007; compared to the original there is a less enthusiastic endorsement of a peri-operative fixed dose beta blockade administration strategy given the discrepant results of the POISE and DECREASE-II studies

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  • Standard Care: 9/53 (17%) died of cardiac causes in perioperative period and 9/53 (17%) had non-fatal MI. Bisoprolol Group: 2/59 (3.3%) died of cardiac causes in perioperative period and 0/59 (0%) had non-fatal MI. Bisoprolol Group including Data from the 8 excluded: 4/67 (6.0%) died of cardiac causes in perioperative period and 1/67 (1.5%) had non-fatal MI.
  • Cardiovascular risk evaluation and management before renal transplantation slideshare

    1. 1. Cardiovascular Risk Evaluation and Management B efore Kidney Transplantation Christos Argyropoulos MD, PhD April 9 th 2007
    2. 2. Outline of the presentation <ul><li>Focus on MA jor perioperative C ardiac E vents (MACE) defined as cardiac death, nonfatal MI and nonfatal cardiac arrest </li></ul><ul><li>Discuss the disease burden of peri-operative and peri-transplant MACE </li></ul><ul><li>Pathophysiology of peri-operative MACE </li></ul><ul><li>Risk stratification and risk modification strategies </li></ul><ul><li>Will NOT cover management strategies for CAD in the CKD or the transplant patient unless they relate to the perioperative period </li></ul>
    3. 3. Goals of Non-Transplant Surgery Perioperative Cardiac Assessment <ul><li>Evaluate symptoms? </li></ul><ul><li>Help long-term mortality? </li></ul><ul><li>Help patient survive the immediate surgery only? </li></ul><ul><li>Make money? </li></ul><ul><li>Reduce risk of lawsuits? </li></ul><ul><li>Improve long-term quality of life, mortality, and cost-effectiveness of treatment (hence Medicare solvency)? Ideally. </li></ul>
    4. 4. Goals of Renal Transplant Surgery Perioperative Cardiac Assessment <ul><li>Additional goals may be pursued during the perioperative cardiac assessment of a patient prior to renal transplantation: </li></ul><ul><li>Reduce long – term cardiovascular risk for the individual patient by deeming him or her an acceptable candidate </li></ul><ul><li>Increase the systemic efficiency of utilization of scarce resources by rejecting high – risks patients for transplantation </li></ul>
    5. 5. Epidemiology <ul><li>Review the incidence of MACE in non-transplant non-cardiac v.s. renal transplant surgery </li></ul><ul><li>Review the clinical risk factors of MACE in non-transplant non-cardiac v.s. renal transplant surgery </li></ul>
    6. 6. Magnitude of risk of major perioperative cardiac events <ul><li>Patients experiencing an MI after noncardiac surgery have : </li></ul><ul><ul><li>a hospital mortality rate of 15%–25% </li></ul></ul><ul><ul><li>18-fold increased risk for cardiovascular death and nonfatal MI during the 6 months following surgery </li></ul></ul><ul><li>Patients who have a nonfatal cardiac arrest after noncardiac surgery have : </li></ul><ul><ul><li>a hospital mortality rate of 65%, </li></ul></ul><ul><ul><li>higher cardiac death during the 5 years following surgery </li></ul></ul>CMAJ • September 13, 2005; 173 (6)
    7. 7. Frequency of MACE in pts at cardiac risk (non-transplant Sx) CMAJ • September 13, 2005; 173 (6)
    8. 8. Frequency of MACE in pts at cardiac risk (non-transplant Sx) 3.9 % for ALL MACEs CI (3.3% - 4.6%) 3.1% for AMIs CMAJ • September 13, 2005; 173 (6)
    9. 9. Incidence of Perioperative MACE in Renal Transplantation I <ul><li>2694 transplants from 1/85-12/98 (51.5% DM) </li></ul><ul><li>ISP: ATG/ALG/OCT3 (Ind) CSA/AZA/P (Maint) </li></ul><ul><li>6.1% incidence of MACE (MI: 1.6%, Angina: 1.2%, Cardiac Arrest: 0.5%, CHF: 0.1%, Arrhythmia: 2.7%) </li></ul><ul><li>MACE affected patient but not death – censored graft survival </li></ul><ul><li>Screening program: Coronary angio for all diabetics , Stress Th for all pts > 50 (potential for selection bias) </li></ul>
    10. 10. Incidence of Perioperative MACE in Renal Transplantation II <ul><li>Pooled results from all Medicare Beneficiaries (n=53297) either listed for DDRT or who received kidney without being listed during 1995 - 2002 </li></ul><ul><li>3- month incidence of fatal and nonfatal AMI was: </li></ul><ul><ul><li>2.27% (DDRT, n=1118, total at risk =49288) </li></ul></ul><ul><ul><li>1.54% (living-donor transplantation, n=61, total at risk = 4009) </li></ul></ul><ul><li>The risk is actually less than the risk for other non-cardiac surgeries in high risk populations (store this fact in short term memory for a few minutes) </li></ul>
    11. 11. Defining “High – Risk” <ul><li>“ Renal patients” have a high cardiovascular disease burden: </li></ul><ul><ul><li>45% of ALL ESRD deaths and ~50% of all deaths after transplantation are due to cardiovascular disease </li></ul></ul><ul><ul><li>There is a high prevalence of angiographically significant CAD (35-60%) </li></ul></ul><ul><ul><li>Traditional and non-traditional risk factors are implicated in the high disease burden ( KI 2006, 70:757-764) </li></ul></ul><ul><ul><li>Management of CKD/Renal Transplant associated CKD is a moving target ( Exper Opin Pharmacother 2005, 6:929-943) </li></ul></ul>
    12. 12. Is “high CAD risk” = “high – perioperative” risk?
    13. 13. Is “high CAD risk” = “high – perioperative” risk? <ul><li>This position differs, and remarkably so, from AHA/ACC’s viewpoint … </li></ul><ul><li>but it will be instructive to let the data “speak for themselves” before I present their algorithm </li></ul>
    14. 14. “ Textbook” Risk Factors for MACEs in Noncardiac Surgery <ul><li>Congestive Heart Failure </li></ul><ul><li>Myocardial Infarction (<6 months) </li></ul><ul><li>Cardiac Arrhythmias </li></ul><ul><li>Age > 70 y/o </li></ul><ul><li>Emergency Operation </li></ul><ul><li>Aortic Stenosis </li></ul><ul><li>Pre-existing CAD </li></ul><ul><li>USA </li></ul><ul><li>Δ ST in resting EKG </li></ul><ul><li>DM </li></ul><ul><li>HTN </li></ul><ul><li>Cigarette Smoking </li></ul><ul><li>Renal Dysfunction! </li></ul>1. New England J Med 1977: 297: 845. 2. Eur Heart J 1987: 8: 179. 3. Ann Thorac Surg 1986: 41: 42. 4. Amer J Med Sci 1994: 308: 41. 5. Ann Vasc Surg 1995: 9: 155.
    15. 15. A Clinical Scoring System for MACEs in Noncardiac Surgery I <ul><li>4315 p atients aged > 50 years </li></ul><ul><li>Postop MACE: ↑ CK-MB i mmediately after surgery, at 8 PM on the evening of surgery, and on the next 2 mornings </li></ul><ul><li>2/3 of the patients assigned to “derivation” cohort (used to derive the scoring system) </li></ul><ul><li>1/3 of the patients assigned to “validation” cohort </li></ul>Circulation. 1999;100:1043-1049.
    16. 16. A Clinical Scoring System for MACEs in Noncardiac Surgery IIa <ul><li>In logistic regression analyses, 6 independent correlates of MACEs were identified in the derivation cohort: </li></ul><ul><ul><li>high-risk type of surgery (27/894; 3%), </li></ul></ul><ul><ul><li>ischemic heart disease (34/951; 4%), </li></ul></ul><ul><ul><li>congestive heart failure (23/434; 5%), </li></ul></ul><ul><ul><li>history of cerebrovascular disease (17/291; 6%), </li></ul></ul><ul><ul><li>insulin therapy for diabetes (7/112; 6%), </li></ul></ul><ul><ul><li>preoperative serum creatinine >2.0 mg/dL (9/103; 9%). </li></ul></ul><ul><li>In the validation cohort, DM and renal dysfunction were no longer significant </li></ul>Circulation. 1999;100:1043-1049. Statistical Trivia : A K-fold cross-validation rather than the holdout strategy utilized, would have clarified the role of DM and CKD in perioperative MACE somewhat better
    17. 17. A Clinical Scoring System for MACEs in Noncardiac Surgery IIb <ul><li>In logistic regression analyses, 6 independent correlates of MACEs were identified in the derivation cohort: </li></ul><ul><ul><li>high-risk type of surgery (27/894; 3%), </li></ul></ul><ul><ul><li>ischemic heart disease (34/951; 4%), </li></ul></ul><ul><ul><li>congestive heart failure (23/434; 5%), </li></ul></ul><ul><ul><li>history of cerebrovascular disease (17/291; 6%), </li></ul></ul><ul><ul><li>insulin therapy for diabetes (7/112; 6%), </li></ul></ul><ul><ul><li>preoperative serum creatinine >2.0 mg/dL (9/103; 9%). </li></ul></ul><ul><li>In the validation cohort, DM and renal dysfunction were no longer significant </li></ul>Circulation. 1999;100:1043-1049.
    18. 18. A Clinical Scoring System for MACEs in Noncardiac Surgery III Circulation. 1999;100:1043-1049.
    19. 19. Clinical Risk Factors for post-transplantation MACEs : Age <ul><li>Older individuals are more likely to have one </li></ul><ul><li>Older individuals are more likely to have an early MACE (in the first 3 months) than younger individuals </li></ul><ul><li>All age groups are likely to have a MACE in the early period </li></ul>Reference group: 18-34
    20. 20. Clinical Risk Factors for post-transplantation MACEs : Race <ul><li>Black and Asian patients experience fewer early events </li></ul><ul><li>Black patients experience less of a late risk reduction after transplantation </li></ul>Reference group: White patients
    21. 21. Clinical Risk Factors for post-txp MACEs : Primary Renal Dx <ul><li>Compared to GN: diabetics experience a relative risk reduction immediately after transplantation </li></ul><ul><li>“ Non-GN” causes of CKD less likely to be associated with AMI </li></ul>Reference group: GN C ystic K idney D isease
    22. 22. Clinical Risk Factors for post-transplantation MACEs : CAD <ul><li>The presence of CAD prior to listing increases the risk for AMI after listing by about 1.6 times </li></ul><ul><li>However, there is no interaction between pre-listing CAD and post-TxP AMI (in spite of OR because of screening?) </li></ul>Reference group: no CAD
    23. 23. Clinical Risk Factors for post-transplantation MACEs : Other
    24. 24. Clinical Risk Factors for post-transplant MACEs – more Cox PH fun <ul><li>Analysis of a subset of the same Medicare dataset limited to first renal allograft recipients uncovered the following clinical risk factors: </li></ul><ul><li>Increased Risk : Older age, male sex, diabetes, hyperlipidemia, increased donor age, DGF, deceased donor, CMV(+) donor, CMV(+) recipient, time on HD, smoking, acute rejection, steroid free protocols!, DM (weakly positive) </li></ul><ul><li>Decreased Risk : Female, Black/Hispanic Race, employment, GN </li></ul>
    25. 25. Clinical Risk Factors for post-transplantation MACEs: Summary <ul><li>Similar to non – transplantation non cardiac surgeries, database driven multivariate exercises suggest the importance of the following factors: </li></ul><ul><li>Age </li></ul><ul><li>Sex </li></ul><ul><li>Diabetes </li></ul><ul><li>History of Cardiovascular Disease (especially CAD) </li></ul><ul><li>Functional Status (employment as proxy) </li></ul><ul><li>Diabetes (weak predictor) </li></ul><ul><li>“ Uremia” i.e. high SCr vs duration of ESRD </li></ul>
    26. 26. Research about MACEs in Renal Transplant v.s. Non – Transplant Operations <ul><li>Data about specific laboratory pre-op correlates of kidney – transplant perioperative MACEs is very limited (in contrast to other types of operations) </li></ul><ul><li>Most of the studies actually rely on coronary events in the long period after transplantation to infer risk factors for CAD in the recipient prior to transplantation (this is no different from the non – transplant literature) . </li></ul><ul><li>Even though the events recorded are usually NOT in the immediate peri-operative period, they are translated into evidence for or against particular screening strategies to prevent early MACEs (this is no different from the non – transplant literature) </li></ul><ul><li>The underlying assumption is that laboratory evidence of ischemia -> MACE (this assumption is also implicit in the noncardiac surgery literature) </li></ul><ul><li>Statistical trivia : one could turn positive findings into negative and vice versa by swapping the log-rank test (emphasizes late events) with the Wilcoxon test (emphasizes early events) </li></ul>
    27. 27. Risk Factors for MACEs in High – Risk Vascular Procedures I <ul><li>Clinical Risk Factors </li></ul><ul><li>Age > 70 </li></ul><ul><li>Angina </li></ul><ul><li>Prior MI (historical or Q waves in EKG) </li></ul><ul><li>Compensated CHF </li></ul><ul><li>Drug Tx for DM </li></ul><ul><li>Renal Dysfunction (SCr > 1.8 mg/dl) </li></ul><ul><li>Prior stroke or TIA </li></ul><ul><li>Laboratory Evaluation </li></ul><ul><li>Regional Wall Motion Abnormalities (RWMA) scored a 5-point ordinal scale in the 16-segment Dobutamine Stress Echo (DSE) </li></ul><ul><li>Determination of the “ischemia – threshold” i.e. the HR threshold at which ischemia (  RWMA) occurred was added to the protocol during the DECREASE-II f/u study </li></ul>JAMA.  2001;285:1865-1873
    28. 28. Risk Factors for MACEs in High – Risk Vascular Procedures IIa JAMA.  2001;285:1865-1873
    29. 29. Risk Factors for MACEs in High – Risk Vascular Procedures IIb JAMA.  2001;285:1865-1873
    30. 30. Risk Factors for MACEs in High – Risk Vascular Procedures IIc JAMA.  2001;285:1865-1873
    31. 31. Risk Factors for MACEs in High – Risk Vascular Procedures IIIa JAMA.  2001;285:1865-1873
    32. 32. Risk Factors for MACEs in High – Risk Vascular Procedures IIIb JAMA.  2001;285:1865-1873
    33. 33. “ Objective” predictors of MACEs in Renal Transplantation <ul><li>One meta-analysis of early studies and multiple more recent small studies with the limitations outlined previously </li></ul><ul><li>The cardiologists in the audience (if any) are likely to have a “Déjà vu” experience – the studies generalize the merits of the same tests from rare events observed in small samples </li></ul><ul><li>Do such studies quantify the risk of CAD rather than the risk of a perioperative MACE? </li></ul>
    34. 34. Prognostic Value of Myocardial Perfusion Studies in Patients with End-Stage Renal Disease Assessed for Kidney or Kidney-Pancreas Transplantation: A Meta-Analysis
    35. 35. Prognostic Value of Myocardial Perfusion Studies in Patients with End-Stage Renal Disease Assessed for Kidney or Kidney-Pancreas Transplantation: A Meta-Analysis
    36. 36. Prognostic Value of Myocardial Perfusion Studies in Patients with End-Stage Renal Disease Assessed for Kidney or Kidney-Pancreas Transplantation: A Meta-Analysis Did these events occur before, immediately after, a long time after the transplant, or on dialysis, the cath table or a CTICU ? Toss a dice – they never told us
    37. 37. <ul><li>Quotes from the discussion of the article: </li></ul><ul><li>“ The results of our meta-analysis are based on univariate analysis and are not adjusted for other important factors such as age, diabetes, and known coronary artery disease” </li></ul><ul><li>“ The combined analysis of any MPS abnormality has adequate sensitivity for future MI or CD ( 0.7 and 0.8 ) respectively” </li></ul><ul><li>“ The specificity is 0.59 for both MI and CD” </li></ul>Prognostic Value of Myocardial Perfusion Studies in Patients with End-Stage Renal Disease Assessed for Kidney or Kidney-Pancreas Transplantation: A Meta-Analysis
    38. 38. Prognostic Value of Myocardial Perfusion Imaging in Predicting Outcome After Renal Transplantation DM, known CAD, multiple clinical RFs
    39. 39. Prognostic Value of Myocardial Perfusion Imaging in Predicting Outcome After Renal Transplantation <ul><li>Only 6/59 events occurred in the early perioperative period (the other 53 were observed over 42 months of f/u); only four early cardiac deaths were observed </li></ul><ul><li>42 (7%) patients were forced to seek pre-transplant revascularization </li></ul><ul><li>Average risk for MACE was 1.4%/yr cardiac event rate post transplant </li></ul><ul><li>Multivariate Predictors of death: age, diabetes (pts w/o SPECT imaging) vs abn SPECT (the paper hints why) </li></ul>
    40. 40. Prognostic Value of Myocardial Perfusion Imaging in Predicting Outcome After Renal Transplantation Similar to previous studies, no conclusion could be drawn apropos early perioperative MACEs
    41. 41. Noninvasive assessment of cardiac risk in type I diabetic patients being evaluated for combined pancreas-kidney transplantation using dipyridamole – MIBI perfusion tomographic scintigraphy <ul><li>Sample of n = 77, evaluated by SPECT </li></ul><ul><li>Perfusion defects (12) evaluated by angio: normal cors (2), no stenosis (4), tight lesion (>70% in 6) </li></ul><ul><li>No coronary events in the early-immediate post-op period (< 6 mos) </li></ul><ul><li>7 events in the late post-op period (4 in pts with the tight lesions, 3 in the others) all seen in pts with abnormal scans </li></ul>
    42. 42. Clinical, resting echo and dipyridamole stress echocardiography findings for the screening of renal transplant candidates <ul><li>Cohort of 313 consecutive HD outpts in Northern Italy. 89 were considered acceptable candidates for TxP </li></ul><ul><li>Two tier clinical system: </li></ul><ul><ul><li>Clinical Tier: H/o CAD, RWMA, On dialysis > 5 years (17% of all pts), ≥2 Framingham Risk Factors </li></ul></ul><ul><ul><li>CST Tier : Pts ≥ 1 point in clinical screening were selected for Dipyridamole+Atropine echo. Images were scored using a 16 region, 4-point scale model </li></ul></ul>
    43. 43. Clinical, resting echo and dipyridamole stress echocardiography findings for the screening of renal transplant candidates <ul><li>The analysis is based on 8 events over a period of 4 years (average f/u was 3 years)-> event rate of 3.3%/pt – year </li></ul><ul><li>Diabetes – age, resting LVMI, RWMA independent “significant” predictors </li></ul><ul><li>A careful reading of the statistics showed that the CIs for most of the factors except age (and possibly RWMA), cross 1 </li></ul>
    44. 44. Coronary Angiography Is the Best Predictor of Events in Renal T ransplant Candidates Compared With Noninvasive Testing <ul><li>Applied a clinical screening algorithm to classify patients as high-cardiac risk if they had ≥ 1 of the following: age ≥ 50,DM, AP, previous AMI/stroke, LVH, PVD vs low risk </li></ul><ul><li>High risk patients had ≥ 1 of the following: Coronary Angiogram, DSE, SPECT </li></ul><ul><li>Total sample size : 165 patients </li></ul>
    45. 45. Coronary Angiography Is the Best Predictor of Events in Renal T ransplant Candidates Compared With Noninvasive Testing <ul><li>42% of the 106 patients that underwent angio had tight lesions (“CAD”) </li></ul><ul><li>CAD associated with DM, PVD, AMI, stroke </li></ul><ul><li>In spite of the title of the paper check out Tables 4 and 6 of the publication </li></ul>
    46. 46. Coronary Angiography Is the Best Predictor of Events in Renal T ransplant Candidates Compared With Noninvasive Testing
    47. 47. Is Coronary Angiography a much better p redictor of Events in Renal T ransplant Candidates when c ompared to Clinical Risk Stratification ?
    48. 48. Is Coronary Angiography a much better p redictor of MACEs after Renal T ransplant ation when c ompared to Clinical Risk Stratification ? <ul><li>Probabilities of event-free survival at 6, 12, 24, 36, and 48 months were </li></ul><ul><ul><li>100%, 98%, 87%, 87%, 87% </li></ul></ul><ul><ul><li>(moderate-risk patients) </li></ul></ul><ul><ul><li>95%, 83%, 71%, 71%, 67% (high-risk patients) </li></ul></ul><ul><ul><li>98%, 98%, 94%, 94%, 94% (CA < 70% stenosis) </li></ul></ul><ul><ul><li>97%, 87%, 61%, 56%, 54% (CA > 70% stenosis) </li></ul></ul><ul><li>Predictably the log-rank P value was smaller for CA compared to the Risk Stratification P-value </li></ul>Coronary angiogram answers a different question than the one generally asked in the preop period That’s ok .. We have fallen into this trap before
    49. 49. Routine Coronary Angiography in Diabetic N ephropathy Patients Before Transplantation <ul><li>Tight lesions are found in 45% of diabetics considered for transplantation </li></ul><ul><li>Age (>35) was the only significant predictor of coronary stenosis in multivariate models </li></ul><ul><li>Only 2 patients were rejected for transplantation </li></ul><ul><li>There was no mention of how well the two groups of patients did after transplant </li></ul><ul><li>All Norwegian diabetic patients screened for PKT/KT between 1999-2004 </li></ul>
    50. 50. Routine Coronary Angiography in Diabetic N ephropathy Patients Before Transplantation 6% of predialytic patients required dialysis after they had their coronary angiogram !! SAFETY WARNING !
    51. 51. Pretransplant Cardiac Investigations in the Irish Renal Transplant P opulation <ul><li>All 190 Irish patients receiving a CRT from 1/92 – 12/97, using </li></ul><ul><ul><li>EKG for all patients </li></ul></ul><ul><ul><li>coronary angiogram for all diabetics, pts > 40 y/o, and everyone perceived to be “a high – cardiac risk” </li></ul></ul><ul><ul><li>Stress testing and echo at the discretion of the attending physician </li></ul></ul><ul><li>Multivariate predictors of risk were: age, CVA, Q waves on the EKG </li></ul>
    52. 52. Validation of an Algorithm for Predicting Cardiac Events in Renal Transplant Candidates (“Portland Score”) <ul><li>A prospective evaluation of 2- tier noninvasive cardiac risk stratification algorithm: </li></ul><ul><ul><li>Clinical Tier : age>50, IDDM, abnormal EKG, personal history AMI/CHF </li></ul></ul><ul><ul><li>Noninvasive assessment: planar or SPECT Thallium Cardiac Stress Imaging for pts with ≥ 1 risk factors </li></ul></ul><ul><li>Two populations: test and validation c/o consecutive renal transplant candidates </li></ul>
    53. 53. Validation of an Algorithm for Predicting Cardiac Events in Renal Transplant Candidates (“Portland Score”) <ul><li>56% of patients received a kidney transplant after a mean of 15.3 months </li></ul><ul><li>39, (54%) of high risk patients underwent angio but only 3/29 pts received a revascularization procedure </li></ul><ul><li>Abnormal Thallium predicted overall cardiac mortality but NOT early perioperative cardiac mortality </li></ul>Which question did this study answer?
    54. 54. Derivation and validation of a disease-specific risk score for cardiac r isk stratification in chronic kidney disease (“Brisbane Score”) <ul><li>Prospective evaluation of a 2-tier system in (predominantly white) Australian CKD pts </li></ul><ul><li>Derivation population : 167 pts with CKD 4/5 </li></ul><ul><li>Validation population : 99 pts with CKD 4/5 </li></ul>
    55. 55. Derivation and validation of a disease-specific risk score for cardiac r isk stratification in chronic kidney disease (“Brisbane Score”) <ul><li>Role of DM : Significant only if the pt had no previous event AND was not obese .. </li></ul>
    56. 56. Derivation and validation of a disease-specific risk score for cardiac r isk stratification in chronic kidney disease (“Brisbane Score”) Derivation Population Validation Population
    57. 57. Derivation and validation of a disease-specific risk score for cardiac r isk stratification in chronic kidney disease (“Brisbane Score”) Validation Population Derivation Population AUC 0.61 0.80 0.58 0.67 AUC 0.60 0.77 0.64 0.67
    58. 58. Risk stratification of patients with chronic kidney d isease: Results of screening strategies incorporating clinical risk scoring and dobutamine stress echo <ul><li>Prospective evaluation of 3 different clinical scoring systems ( Brisbane , Portland , Framingham ) for a two tier risk stratification algorithm </li></ul><ul><li>All patients underwent DSE (with atropine augmentation if necessary) </li></ul><ul><li>Sample size n=244 (169 were on RRT) </li></ul><ul><li>Patients were censored for events at the time of transplantation </li></ul>
    59. 59. Risk stratification of patients with chronic kidney d isease: Results of screening strategies incorporating clinical risk scoring and dobutamine stress echo <ul><li>DSE related trivia </li></ul><ul><li>Atropine infused to 102 pts </li></ul><ul><li>35 pts developed SEs </li></ul><ul><li>In 21 pts the test had to be stopped (CP, arrhythmia, hypotension) </li></ul><ul><li>75% had no RWMA </li></ul><ul><li>10% had resting LV dz </li></ul><ul><li>15% had RWMA </li></ul>
    60. 60. Risk stratification of patients with chronic kidney d isease: Results of screening strategies incorporating clinical risk scoring and dobutamine stress echo <ul><li>DSE related Predictors </li></ul><ul><li>Ischemia + scar had the higher HR: 4.3 (CI 3-15.2) </li></ul><ul><li>Angina on testing had HR 2.9 (CI: 1.2-6.7) </li></ul><ul><li>Lower diastolic BP at rest was protective, HR: 0.98 (CI: 0.95-1.0) </li></ul><ul><li>Clinical Scoring systems </li></ul><ul><li>Brisbane ≥ Portland </li></ul><ul><li>> Framingham </li></ul>Remember CHOICE ?
    61. 61. What about pre-emptive revascularization? <ul><li>Manske et al screened 151 consecutive diabetic patients and found 31 with tight lesions (>75%) </li></ul><ul><li>26 agreed to be randomized to standard medical therapy (CaB+ASA) v.s. PTCA/CABG </li></ul><ul><li>Over a period of 8.4 months, 10/13 (medical management) v.s. 2/13 (revascularization) had developed an end-point (p<0.01) </li></ul><ul><li>Data Safety Board stopped the study early … </li></ul><ul><li>Is this study still relevant in the age of modern medical CAD management? </li></ul>Lancet. 1992 Oct 24;340(8826):998-1002.
    62. 62. Is Preoperative Cardiac Evaluation Revascularization Ever Necessary?  <ul><li>“ Confirmed a high incidence of significant coronary artery disease in patients undergoing aortic reconstruction, but prophylactic cardiac intervention does not reduce operative or long-term mortality.” </li></ul><ul><li>“ And it’s interesting to see now for the practicing vascular surgeon that we may have been led down the primrose path . </li></ul>Certainly, cardiac complications are the most frequent cause of perioperative and late mortality in the patients with PVD. Despite this fact, coronary revascularization has never been prospectively shown to decrease mortality…”
    63. 63. Coronary-Artery Revascularization before Elective Major Vascular Surgery (CARP) <ul><li>C oronary A rtery R evascularization P rophylaxis. </li></ul><ul><li>McFalls et al, NEJM, V. 351, No. 27 (December 30, 2004), pp. 2795-2804. </li></ul><ul><li>Conclusions : Coronary-artery revascularization before elective vascular surgery does not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended. </li></ul>
    64. 64. Coronary Angiography for the Study Patients <ul><li>Recommended for eligible patients if the patient was considered by a cardiology consultant to be at increased risk for a perioperative cardiac complication. </li></ul><ul><ul><li>Considered risk factors and noninvasive evaluation. </li></ul></ul><ul><li>Eligible: If >= 1 major coronary arteries had a stenosis of at least 70%. </li></ul><ul><ul><li>Local investigators decided which revascularization procedure to use. </li></ul></ul><ul><ul><li>PTCA and CABG considered equivalent but potential long-term advantage of CABG among patients with DM2 and multivessel CAD was recognized. </li></ul></ul><ul><li>Anatomic Exclusion: L main stenosis > 50%, EF<20%, or Severe aortic stenosis. </li></ul>
    65. 65. Outcomes <ul><li>Primary End-Point: Long-Term Mortality </li></ul><ul><li>Secondary End-Points: </li></ul><ul><ul><li>MI: Elevated levels of enzymes and ischemic changes on electrocardiogram. </li></ul></ul><ul><ul><li>Stroke </li></ul></ul><ul><ul><li>Limb Loss </li></ul></ul><ul><ul><li>Dialysis </li></ul></ul>
    66. 66. Results: Prior to Vascular Surgery <ul><li>10 deaths in the revascularization group. </li></ul><ul><li>1 death in the no revascularization group. </li></ul><ul><li>Please note: </li></ul><ul><ul><li>PCI Death Rate: 1.4% </li></ul></ul><ul><ul><li>CABG Death Rate: 2% </li></ul></ul><ul><ul><li>“ Sir, cardiac cath is very safe these days. Maybe 1 in a 1000 have problems.” </li></ul></ul>
    67. 67. Results: After Vascular Surgery
    68. 68. Results: Final Analysis <ul><li>If you have coronary revascularization before vascular surgery, you have increased your rate of death by 1.4-2.0% with no more chance of surviving the vascular surgery. </li></ul>
    69. 69. What about Left Main Disease? <ul><li>Analysis of outcomes of patients with LMD who were screened but not randomized to CARP </li></ul><ul><li>Censored at 2.5 years </li></ul>Am J Cardiol. 2008 Oct 1;102(7):809-13 <ul><li>High-risk coronary anatomy: </li></ul><ul><li>2-vessel disease (n = 204 [19.5%]) </li></ul><ul><li>3-vessel disease (n = 130 [12.4%]), </li></ul><ul><li>left main coronary artery stenosis > or = 50% (n = 48 [4.6%]). </li></ul><ul><li>Improved survival in </li></ul><ul><li>Patients with a left main coronary artery stenoses (0.84 vs 0.52, p <0.01) </li></ul><ul><li>No effect on: </li></ul><ul><ul><li>2-vessel (0.80 vs 0.79, p = 0.83) </li></ul></ul><ul><ul><li>3-vessel (0.79 vs 0.71, p = 0.15) disease. </li></ul></ul>
    70. 70. Translating CARP to Renal Transplantation <ul><li>In a group of patients with angiographically documented CAD, scheduled to undergo a much riskier operation than renal transplant, revascularization was not associated with improved outcomes (in fact there was a tendency towards worse outcomes) </li></ul><ul><li>Revascularization is also a much trickier business in patients with CKD (especially the ones on dialysis). </li></ul>
    71. 71. Detour: What about revascularization? <ul><li>A database driven multivariate analysis focusing on transplant recipients hospitalized from 1995 to 1999 for first coronary revascularization was undertaken by Herzog et al in 2004 </li></ul><ul><li>The purpose of this paper was: “ to compare the long-term outcome of renal transplant recipients after stent, PTCA, or CAB with or without internal mammary grafting ” </li></ul>
    72. 72. Detour: What about revascularization? <ul><li>“ In the present study of renal transplant recipients (without prior coronary revascularization),we found no difference in long-term survival related to type of coronary revascularization ” </li></ul><ul><li>“ Our findings confirm the importance of internal mammary graft utilization in patients undergoing CAB surgery, as the 812 patients in this group had a 43% reduction in the risk of cardiac death or AMI. ” </li></ul><ul><li>In the present study, the estimated 2-year all-cause survival of renal transplant recipients after coronary revascularization (except for CAB[ - IMG] patients) was 82%, compared with 57% after CAB surgery and 53% after PTCA in dialysis patients , as we found in a previous study. Thus, it should not be assumed that all patients with ESRD have common cardiovascular fates, particularly after coronary revascularization </li></ul>
    73. 73. Devereaux, P.J. et al. CMAJ 2005;173:627-634 Potential triggers of states associated with perioperative elevations in troponin levels, arterial thrombosis and fatal myocardial infarction
    74. 74. What Is Perioperative Myocardial Ischemia? <ul><li>Mangano et al Characterized ECG changes consistent with ischemia in 100 patients with or at risk for CAD undergoing non-cardiac surgery. ECG ischemic episodes defined by ST depression  1mm or elevation  2mm. </li></ul>Mangano DT, Hollenberg M, et al, “Perioperative Myocardial Ischemia in Patients Undergoing Noncardiac Surgery- I. Incidence and Severity During the 4 Day Perioperative Period,” JACC, Vol. 17, No. 4 (1991), pp. 843-850.
    75. 75. Perioperative Ischemia <ul><li>Incidence of preoperative ischemia did not differ in patients with CAD versus those at risk for CAD. </li></ul><ul><li>Incidence of intraoperative ischemia is similar to that of preoperative ischemia. </li></ul><ul><ul><li>Anesthesia and surgery were not associated with an increased incidence or severity of ischemia. </li></ul></ul><ul><li>Ischemia is most frequent and most severe during the post-operative period. </li></ul><ul><li>Postoperative ischemia is usually silent (no Chest pain/edema/syncope) and may be related to HR. </li></ul>
    76. 76. Perioperative Ischemia
    77. 77. Why Should We Care About Perioperative Myocardial Ischemia? <ul><li>Association of Perioperative Ischemia with Adverse Outcomes </li></ul><ul><li>Prospective analysis of 474 men with CAD or at high risk for it who were undergoing elective non-cardiac surgery. </li></ul><ul><li>- “…postoperative myocardial ischemia during the first 48 hours after surgery confers a nearly threefold increase in the odds of having an adverse cardiac outcome and, more important, a ninefold increase in the odds of having an ischemic event (cardiac death, nonfatal myocardial infarction, or unstable angina) in patients undergoing noncardiac surgery.” </li></ul>
    78. 78. Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery. Poldermans D, Boersma E, et al, “Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery,” NEJM, Vol. 341, No. 24 (1999), pp. 1789-1794.
    79. 79. Let’s call a path consult (for an autopsy)
    80. 80. Let’s call a path consult (for an autopsy)
    81. 81. Let’s call a path consult (for an autopsy)
    82. 82. Let’s call a path consult (for an autopsy)
    83. 83. Autopsy Report Question: has revascularization been shown to prevent acute coronary events in stable CAD? Answer: The lesions that rupture are different from the ones that get stented i.e. a full metal jacket strategy is unlikely to work
    84. 84. Where do we go from here? <ul><li>How about the ACC/AHA algorithm? </li></ul>Renal Transplantation does NOT qualify as such
    85. 85. Where do we go from here? <ul><li>How about the ACC/AHA algorithm? </li></ul>Captures the clinical characteristics of the transplant candidate Captures the risk profile of transplant surgery
    86. 86. My personal approach I <ul><li>Lobby for a prospective study (similar to CARP/DECREASE-II) </li></ul><ul><li>In the absence of such a study … the things I do at 3 am in the morning when they call me to “preop” a transplant candidate is to follow the AHA/ACC algo: </li></ul><ul><ul><ul><li>Make sure the patient is not actively infarcting (hint: ask for chest pain, look at EKG) </li></ul></ul></ul><ul><ul><ul><li>Make sure the patient is not in florid heart failure (hint: ask for DOE/PND, listen to chest/lungs) </li></ul></ul></ul><ul><ul><ul><li>If 1, suggest that the surgery be cancelled (irrespective of the recent cath/DSE/Thallium). </li></ul></ul></ul><ul><ul><ul><li>If 2, suggest that the patient is dialyzed first; if no improvement wake up cardiologist for an echo (but if cold ischemia time is a prime concern, may have to call another candidate) </li></ul></ul></ul>
    87. 87. My personal approach II <ul><ul><ul><li>If not 1 OR 2, tease out past medical history, functional capacity and exercise tolerance (FC/ET) </li></ul></ul></ul><ul><ul><ul><li>If FC/ET are OK, glance at EKG/CXR and do not worry too much about the functional test in chart (unless there are high risk findings and no one has done something about them!!) </li></ul></ul></ul><ul><ul><ul><li>If FC/ET are not OK, show real interest at the result of the functional study in chart </li></ul></ul></ul><ul><ul><ul><li>Select post-op battlefield based on the expected extent of damage control that will be required after the operation (floor, tele, TICU) </li></ul></ul></ul>
    88. 88. My personal approach III <ul><ul><ul><li>Recommend (dose-adjusted to HR and Blood Pressure) beta blockers (best done in the pre-op clinic, not the day of the surgery given the POISE study results), low dose ASA (AND ? Statins) as a pre-operative risk reduction strategy (no time to go over these studies today) </li></ul></ul></ul><ul><ul><ul><li>Sign consult note, call attending … and move on </li></ul></ul></ul><ul><ul><ul><li>In order to apply the strategy though, surgeons, cardiologists, anesthesiologists, the nephrologists AND the human monitors monitoring the tele- monitors should be on the same page … </li></ul></ul></ul>
    89. 89. EPILOGUE Cardiovascular Risk Evaluation and Management B efore Kidney Transplantation
    90. 90. Goals of Renal Transplant Surgery Perioperative Cardiac Assessment <ul><li>Improve long-term quality of life, mortality, and cost-effectiveness of treatment: </li></ul><ul><ul><li>Help patient survive the immediate surgery </li></ul></ul><ul><ul><li>Reduce long – term cardiovascular risk for the individual patient by deeming him or her an acceptable candidate </li></ul></ul><ul><ul><li>Increase the systemic efficiency of utilization of scarce resources by rejecting high – risks patients for transplantation </li></ul></ul>
    91. 91. Deciding About Strategies for PTCRA & Interpreting the Literature <ul><li>Who is asking the question? </li></ul><ul><ul><li>Patient : dislikes MACEs over one’s lifetime </li></ul></ul><ul><ul><li>Transplant Physician (Surgeon & Nephrologist) : dislike MACEs in the first 90 days </li></ul></ul><ul><ul><li>Transplant Program : Make the numbers look good by doing the low risk cases v.s. make headlines by doing the riskier cases </li></ul></ul><ul><ul><li>Hospital System : Maximize the number of procedures performed </li></ul></ul><ul><ul><li>UNOS (depending on the allocation policy): does not want any MACEs that lead to graft loss v.s. early MACEs </li></ul></ul><ul><ul><li>Medicare Administrators : Pay as little as possible </li></ul></ul>
    92. 92. Pre-transplant Cardiac Risk Assessment (PTCRA) may : <ul><li>Estimate the lifetime risk for MACE </li></ul><ul><li>Estimate the peri-operative (peritransplant) risk for MACE </li></ul><ul><li>Select a revascularization strategy prior to transplant (including no revascularization) </li></ul><ul><li>Deny transplant eligibility </li></ul><ul><li>Common denominator: Estimate the CAD disease burden AND decide on a strategy to cope with it over a varying event horizon </li></ul>
    93. 93. Is Renal Transplantation a Surgical Therapy for CAD?
    94. 94. Is Renal Transplantation a Surgical Therapy for CAD? <ul><li>Overall RT is associated with a 17% lower risk for AMI (11% in DDKT but 31% in LRT) </li></ul><ul><li>However the risk is increased in the early (<3mo) vs late post-transplantation period compared to the waiting list </li></ul>
    95. 95. Time for a new conceptual framework? <ul><li>The AST guidelines, the existing literature, and my presentation examine renal transplantation from the viewpoint of someone concerned about the cardiac risks of a non-cardiac surgery. </li></ul><ul><li>If renal transplantation modifies cardiac risk , then this mindset may be misguided </li></ul><ul><li>Should we be approaching renal transplantation from a CABG rather than a AAA repair perspective? </li></ul>
    96. 96. Time for a new conceptual framework? Think not what a stress test can’t do preoperatively, think what you can do for the patient perioperatively.
    97. 97. Time for a new conceptual framework? <ul><li>Elements of a new approach: </li></ul><ul><li>Pre-operative risk stratification should be limited to predicting who will die on the table AND/OR end up in a nursing home </li></ul><ul><li>A “ASA/statin standing order” with a risk-stratified “beta-blocker”approach may be more cost effective or even safer than stress testing </li></ul><ul><li>A shift of focus from peri-op to pre-op/post-operative management is recommended in order to manage the cardio-vascular disease burden of the CKD patients over the long term </li></ul>
    98. 98. Time for a new conceptual framework? <ul><ul><li>“ Revascularize” a CKD patient </li></ul></ul><ul><ul><li>with a transplant first, </li></ul></ul><ul><ul><li>and reserve CABG/PCI for </li></ul></ul><ul><ul><li>when it is truly needed </li></ul></ul>Organ allocation policies will determine who will be “renally” revascularized though
    99. 99. Many thanks go to … <ul><li>Jeff Williams MD, M.Sc (Division of Cardiology, UPMC) for suggesting non transplant pre-op papers (and providing me with Power Point slides about them) </li></ul><ul><li>My cardiologist friends: Jeff (again), Chris Wright MD, Nauman Mustaq MD for the lively debates about the subject dating back to our intern year in Cincinnati </li></ul>
    100. 100. ECG evidence of “high troponin” syndrome or normal variant?

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