Chronic Kidney DiseaseIn

Acute Coronary Syndrome

Prof. Dr. Alia Abd El-Fattah, MDProf. Dr. Alia Abd El-Fattah, MDProfessor of Critical Care Medicine,

Critical Care Department ,Cairo University

20102010

ST-segment Elevation

No ST-segment Elevation

ST-Elevation MI Non-ST-Elevation Unstable Angina

Q-Wave MI Non-Q-Wave MI

Initial ECG

Cardiac Markers

ECG Evolution

Acute Coronary Syndrome

Invasive Reperfusion Available Yes PCI

No

Rapid Transfer to Facility With PCI Capability Possible Yes Transfer Within 30 Minutes

No

Candidate for Thrombolysis

Yes

Thrombolytic Agent Given

The higher the patient's mortality risk:

Large infarctions,

Heart failure or

Hemodynamic instability,

Previous infarctions, or

Acute LBBB,

The more primary PCI is preferred.

The higher the risk of thrombolysis, also the more primary PCI is preferred.

Choice of reperfusion strategy:Choice of reperfusion strategy:

ACS

CKD

Chronic Kidney Disease

www.usrds.org

Stages based on GFR (ml/min/1.73 m2 )

Stage 1: normal (proteinuria, abnormal markers)

Stage 2: 60-89

Stage 3: 30-59

Stage 4: 15-29

Stage 5: < 15 (dialysis or renal failure)

Age-Standardized Rates of Death from Any Cause According to the Estimated GFR

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Age

-Sta

ndar

dize

d R

ate

of D

eath

from

Any

Cau

se (p

er 1

00 p

erso

n-yr

)

Estimated GFR (ml/min/1.73 m2)

> 60 45 - 59 30 - 44 15 - 29 < 15

0.76 1.08

4.76

11.36

14.14

Go, A. et al., N Engl J Med 2004;351:1296-305.

Age-Standardized Rates of Death from CV Events According to the Estimated GFR

0

5

10

15

20

25

30

35

40

Age

-Sta

ndar

dize

d R

ate

of C

ardi

o.Ev

ents

(per

100

per

son-

yr)

Estimated GFR (ml/min/1.73 m2)

> 60 45 - 59 30 - 44 15 - 29 < 15

2.113.65

11.29

21.80

36.60

Go, A. et al., N Engl J Med 2004;351:1296-305.

Age-Standardized Rates of Hospitalization According to the Estimated GFR

0

10

20

30

40

50

60

70

80

90

100

110

120

130

140

150

Age

-Sta

ndar

dize

d R

ate

of

Hos

pita

lizat

ion

(per

100

per

son-

yr)

Estimated GFR (ml/min/1.73 m2)

> 60 45 - 59 30 - 44 15 - 29 < 15

13.54 17.22

45.26

86.75

144.61

Go, A. et al., N Engl J Med 2004;351:1296-305.

Kidney Int 2008; 74: 1335-42J Am Coll Cardiol, 2003; 41:725-728

Coronary Heart Disease in CKD

CRP levels are increased (1/3-1/2 have high levels) esp. in stage 5 where it may be X10 as high

IL-6, produced in abdominal adipocytes, is elevated which stimulates the hepatocytes to produce CRP

CRP falls with treatment of risk factors and may not be pathogenic in itself

CRP is related to anemia, calcification and progression of CKD

Systemic inflammation:

Coronary Heart Disease in CKD

• Structural and physiological changes in myocardium: LVH. LV/RV dilation. Fibrosis. Ischemia.

• Imaging: Nuclear 2DE. MRI: There is a small risk of nephrogenic systemic

fibrosis with use of gadolinium. CT/ EBCT.

Circulation 2007; 116: 85-97

Endothelial dysfunction

Nitric oxide availability

Dyslipidemia

Inflammation

Oxidative stress

Renin-Angiotensin System

Vascular calcification

CKD: Mechanisms of CV Complications

Risk of contrast nephrotoxicity due to contrast agents before stage 5

Rates of morbidity, mortality and in-stent stenosis are higher in CKD than non- CKD patients

DES is superior to BMS, though still not as good as in patients with no CKD

Based on non-randomized trials, there is evidence that PCI and CABG are superior to medical therapy

in select patients

Coronary Heart Disease in CKD:Coronary revascularization (based on review of

>80 published reports)

after CABG 1998-2000 after PCI 1998-2000

Survival

Foley RN et al Kidney Int 1995; 47(1): 186-92

Echo findings at onset dialysis (n=443)Echo finding (prevalence)

Systolic dysfunction 15%

LV Dilation

32%

LV Hypertrophy

74%

Clinical correlates

AgeCAD

Age MaleAnemiaLow CaHigh PO4

AgeFemaleWide Pulse PressureLow BUNLow albumin

Uremic CardiomyopathySt. John's, Newfoundland, Canada

LVEF by MIBI

Normal(--> 50%)

1,598 / 63%

Decreased (< 40%)

402 / 16%

Borderline (40-49%)521 / 21%

Systolic Function

0

0.5

1

1.5

2

2.5

<= 30% 31 - 40% 41 - 50% 51 - 60% => 71%

adj-RR for All-causes Mortality

Relative- risk

LVEF and Mortality on the Wait-List

Survival on waitlist (months)

847260483624120

Pro

po

rtio

n S

urv

iva

l1.0

.8

.6

.4

.2

0.0

<=30%

31- 40%

41- 50%

51- 60%

> 60%

Adjusted Survival Curvesby Categories of LVEF

J Am Coll Cardiol 2005;45:1051-1060

0

10

20

30

40

50

60

All No CAD CAD No CABG CABG No PTCA PTCA No DM DM

Pre LVEF Post LVEF

LVEF%

Pre-transplant (while on dialysis) & post-transplant LVEF

in different subgroups of patients

Relation Between Perfusion Defect Size and Survival

Circulation 2008;118:2540-2549

Annual CD stratified by presence of ischemia and scar

4.7%

2.2%

0.9%0.4%0%

5.5%

2.2%3.3%

9.6%

11%

3.8%3.4%

0

2

4

6

8

10

12

> 90 (N = 176) 60-89 (N=875) 59-30 (N=511) <30 (N=90)

Normal Scar Ischemia

Card

iac d

eath

/yea

r

Estimated GFR

Outcome TotalAnnual

RateTotal

Annual Rate

P value

Cardiac Death 11(1.6%) 0.8% 16 (5.3%) 2.7% 0.001

All Cause Mortality 56 (8.1%) 4% 37 (12.3%) 6.2% 0.04

MI 15 (2.2%) 1% 11 (3.6%) 1.9% 0.15

Circulation 2008;118:2540-2549

GFR>60(n=684) GFR<60(n=304)

Unadjusted event rates for Patients With No Defects on MPI (n=664)

Outcome Total Annual Rate Total Annual Rate P value

Cardiac Death 29(8%) 4% 58 (19.3%) 9.5% <0.001

All Cause Mortality

48 (13%) 6.5% 76 (25.3%) 12.5% <0.001

MI 24 (6.6%) 3.3% 23 (7.6%) 3.8% 0.59

Circulation 2008;118:2540-2549

GFR > 60 (n=364) GFR < 60 (n=300)

Unadjusted event rates for Patients With Defects on MPI (n=988)

Autonomic Dysfunction

Renalase is excreted in an inactive form by the

kidneys

It is activated in the presence of catecholamine

surges and hypertension to inactivate the

excess catecholamines

It is deficient in CKD

Also, DM is common in CKD

318 pts had dual imaging, None had prior MI, PCI or CABG, 50 died at 31/2 years, Age: >70 (HR 2.3), BMIPP > 12 (HR 21.8)

JACC 2008, 51: 139-145

BMIPP Imaging in ESRD

Sasano, T. et al. J Am Coll Cardiol 2008;51:2266-2275

Perfusion-Innervation Mismatch in a Pig with Inducible VT after LAD Occlusion

0. 00

0. 25

0. 50

0. 75

1. 00

sur v_ year s

0 1 2 3 4 5 6 7

STRATA: hr r at i o=0 Censor ed hr r at i o=0 hr r at i o=1 Censor ed hr r at i o=1Time after myocardial perfusion imaging (years)

Su

rviv

al

Pro

po

rtio

n

%ΔHR>15

%ΔHR≤15

Relationship between HR response and survival in ESRD

Excludes patients whose cause of death was unknownSource: US Renal Data System: 1999 Annual Data Report

Total CVD45.7%

Malignancy, 13%

Other, 21%

Cerebral-vascular, 7.4%

Myocardial infarct, 13% Other

cardiovascular, 25.3%

Infection,20.4%

Cause of Death in Renal Transplant Recipients with functioning grafts (1995–97)

Circulation 2008;118:2540-2549

Risk-adjusted Kaplan-Meier survival plot for CD combining SSS and GFR

>20%5-20%

<5%

0

10

20

30

40

50

60

Total defect size

Mo

rtal

ity

%ΔHR>15

%ΔHR≤151

1

12

5

24

7

Interaction between perfusion defect size and HR response in ESRD

Post Renal Transplant

Immuno-suppression

HT.

HL: Fluvastatin decreased the rates of death and MI but not the primary endpoint of death,

MI, revascularization, (Lancet 2003; 361: 2024-31).

DM

• Risk for death, MI and HF remains high:

Post Renal Transplant

Smoking

Obesity

Pre-transplant dialysis duration

Chronic infection

Hypercoagulable state

Allograft rejection

Type of donor: living vs. deceased

Anemia

J Am Coll Cardiol 2005;45:1051-1060

Kaplan-Meier analysis of survival plots for death in the post-transplant period

(after first six months after transplantation)

Survivors (n=97) Non-Survivors (n=53)

Abnormal Perfusion 80% 94%*

PD size 20+16% 26+16%*

EF 40+12% 44+13%*

EDV (ml) 111+48 131+ 64*

LV mass (gm) 192+46 203+58

# diseased vessels 1.5+1.2 2.0+1.2*

PCI/CABG 47% 40%

Renal Transplant 44% 9%*

* P < 0.05

Comparison of survivors and non-survivors with ESRD

Ref N Age men Technique Abnormal (%) End-point F/U (mons)Outcome

P-valueAbnormal Normal

Am J Surg 1983;146: 331-5

60 35 75 Ex-MPI 21 CV events 30 22% 4% P<0.05

Am J Kid Dis 1994; 24:65-71

95 40 NA Ex-MPI 56 Cardiac death 46 23% 5% P<0.05

AJC 1996; 77:175-9 53 36 64 DSE 38 Cardiac death 14 45% 6% P=0.003

J Inten Med 1998;244:155-61

193 63 62 DSE 37 Cardiac death 38 34% 16% P=0.006

Clin Transpl 2003;92:146-51

176 43 67 Dip MPI 43 Cardiac death 1.5 11% 0.9% P<0.05

AJC 2003; 92:146-151

174 48 61 Aden-MPI 31 Cardiac death 42 15% 3% P=0.006

Kid Intern 2004;66:1633-9

97 48± 66 Ex/Dip-MPI 10 CV events 4 years 25% 1.2% P<0.0001

Studies examining the outcome of ESRD patients in relation to non-invasive

assessment for myocardial ischemia

MPI: Special Considerations in ESRD

The septum is often brightest area in LV, which may lead to downscaling of other regions esp. the lateral wall. This

may lead to over diagnosis of “scar” even when quantitative programs are used.

The severe and disproportionate LV hypertrophy, may affect endocardial edge detection and under-estimation

of EF by gated SPECT. Review of slices cine without outlines is helpful.

LV and RV dilatation is common even with normal perfusion and EF.

Study timing in relation to last dialysis is important in serial images as it may change LV/RV size and EF.

Patient Management

Patient 1: ESRD, EF 25%, normal MIBI.

Does this patient move up or down on the waiting list for

renal transplant ?

Question

Patient Management

Patient 2: Stage 3 CKD with atypical CP that warranted ED visit

what is the line of W/U?

Question

Patient Management

Patient 3:

What is the risk in this patient and what is “best” treatment?

Stage 3 CKD, stable angina, ischemia on MIBI, normal EF

Question

CKD & CV Events

CKD is a common problem.

CV events are higher than in patients without

CKD.

The causes of high CV events are more

complex than in any other group of patients

and mechanisms of death and esp. sudden

death remain to be defined.

Conclusions

Roles of vascular stiffness, calcification, Ca, P,

inflammatory markers, homocysteine level and

the potential for their reversals need to be

better defined.

The role of coronary revascularization remains

to be determined

CKD & CV Events

Conclusions

• Imaging plays an important role in patient management, but not necessarily in the traditional

way:

MBF, fibrosis, ischemia.

LV EF, mass, function, LV dyssynchrony.

Neuro-imaging.

Autonomic dysfunction.

Metabolic imaging.

CKD & CV Events

Conclusions