all about cardiorenal syndrome defination ,riskfactors,etiology,treatment

1. The Cardiorenal Syndrome
A Cardiologist’s Perspective
J Thomas Heywood
Director, Heart Failure Program
Scripps Clinic,
La Jolla, California

2. Disclosures
Consulting: Medtronic
Research: St Jude, Medtronic,
Speakers Bureau: Otsuka, Actelion, Medtronic

3. High Prevalence of Renal Dysfunction and Its Impact on
Outcome in 118,465 Patients Hospitalized With Acute
Decompensated Heart Failure: A Report From the
ADHERE Database
J. Thomas Heywood MD et al J Card Failure Sept 2007
65%
Have at least
Moderate renal
dysfunction

4. 

BUN 43
(n=32220)
Inpatient mortality from ADHERE Registry
Based on admission BUN, creatinine and BP


8.35%
(n=67640)
SBP 115
(n=6697)
15.30%
(n-1863)
5.63%
(n-4834)
Cr 2.75
(n-1862)
13.23%
(n-1270)
19.76%
(n-592)
2.88%
(n=24469)
SBP 115
(n=2,702)
5.67%
(n=3882)
2.31%
(n=20820)
<
<
<
<
Analysis of patients in the National Acute Decompensated Heart Failure National Registry (ADHERE)
BUN=blood urea nitrogen, Cr=serum creatinine, SBP-systolic blood pressure
Fonarow GC et al. J Cardiac Fail 2003;9(suppl 1):S79.

6. Why is renal function abnormal
in patients with heart failure?

7. The cardiorenal syndrome (CRS)
Definition
• Worsening renal function (> 25% increase in creatinine or
BUN during treatment for acute decompensation)
• Difficulty in diuresis without worsening renal function
• ACE intolerance due to hypotension or hyperkalemia in
severe heart failure
• Chronic renal insufficiency complicating HF therapy
Heart failure with…

8. Role of the kidney in congestive heart failure:
Relationship of CI to kidney function
Group A
n=12
Group B
n=13
Group C
n=9
P
value
Car. Index 2.4±.15 1.78±.17* 1.35±.14* * <.001
SVR 1313±296 1866±455* 2464±956** * <.01
** <.001
RA 7±8 10±5 14±8 ns
Wedge 19±11 29±7* 30±8* * <.01
Ljungman, Cody Drugs 1990;39 Suppl 4:10-21

9. Role of the kidney in congestive heart
failure: Relationship of CI to kidney function
Ljungman, Cody Drugs 1990;39 Suppl 4:10-21
0
100
200
300
400
500
A, CI> 2 B, CI>1.5
<2.0
C, CI <1.5
Renal BF
RV Resistance
Renal
Blood
Flow
Renovascular
Resistance
RBF, p<.05 with Group A
RVR, p<.01 with Group A

10. Role of the kidney in congestive heart
failure: Relationship of CI to kidney function
Ljungman, Cody Drugs 1990;39 Suppl 4:10-21
0
10
20
30
40
50
60
70
A, CI> 2 B, CI>1.5 <2.0 C, CI <1.5
GFR
BUN
GFR/BUN
CI, p<.001 with Group A
BUN, p<.01 with Group A
Creatinine was not different between the groups. BUN better indicated
low CI and GFR than creatinine

11. `
Am J Cardiol 2006:97:1759

12. Effect of increasing central venous pressure
on GFR in dogs, constant BP
0.5
0.8
1.1
1.4
0 6.25 12 18.75 25 0 Central Venous Pressure
GFR
ml/min
P< .05
P< .05 Raised Venous
Pressure: A
direct cause of
renal sodium
retention
Firth et al Lancet
5/7/88
mm Hg
High CVP significantly
impairs GFR

13. Effect of Increased Renal Venous Pressure
on Renal Function
• Swine where anesthetized, instrumented and a unilateral nephrectomy
preformed.
• In the remaining kidney the renal vein was constricted in half the animals to
obtain a renal venous pressure of 30, the other animals served as controls
Doty J et al J of Trauma: Injury, Infection and Critical Care 1999 47:1000-1005
0
5
10
15
20
25
30
RA Blood
flow Index
GFR Aldosterone Renin
Activity
Control
RV Constric
P <.05 between groups

14. Renal Decapsulation in the Prevention of
Post-Ischemic Oliguria
• 15 rhesus monkeys, 1 hour suprarenal aortic clamping to produce ATN, after
which the renal capsule was stripped from one kidney. The ureters of each
kidneys were catheterized to collect urine for creatinine, urea and free water.
Stone HJ Annals of Surgery 1977:343-355
0
1
2
3
4
5
6
7
Cr Cl Urea Cl Free Water
Decapsuled
Control
P <.01

16. Mullens, W. et al. J Am Coll Cardiol 2009;53:589-596
Prevalence of Worsening Renal Function During Hospitalization
According to Categories of Admission CVP, CI, SBP, and PCWP

18. Treatment of the Cardiorenal Syndrome
5 important questions…
• What is the fluid status?
• Is the blood pressure adequate for renal perfusion?
• What is the cardiac output?
• Is there evidence of high central venous pressure?
• Is there intrinsic renal disease?

19. Hypovolemic Cardiorenal Syndrome
• Overdiuresed or intercurrent illness results in
volume loss and renal dysfunction
• Give fluids, stop diuretics and IV vasodilators
• Often a reluctance to give fluids to HF patients
but it may be critical in this situation and time is
of the essence to avoid irreversible renal damage
Too Dry!!!

20. CRS due to high central venous pressure
• Poor renal perfusion due to high central venous pressure
• Usually CVP > 15-20 mm Hg coupled with reduced blood
pressure
• Diuretics often held because of worsening renal function
and misguided idea of “ intravascular volume depletion”
• Continue diuretics to reduce central venous pressure
• Ultrafiltration
Too Wet!!!

21. CRS with vasoconstriction
• Low CO and hence renal hypoperfusion due to HF
mediated vasoconstriction (Ang II, endothelin induced
increased afterload)
• CO is low and SVR high, often over 1800-2000
• ACEI and vasodilators very useful since CO can increase
significantly if afterload normalized. Actual improvement
in renal function may be seen
• May need temporary inotropic support if systolic BP <80
as vasodilators are added
Clamped
Down!!!

22. ACEI play a complex role in renal function
in HF
• May improve CO in some patient and hence increase
effective renal perfusion
• ACEI may lower BP to the point where effective renal
perfusion is impaired
• With chronic renal disease, there is hyperfiltration in the
remaining nephrons. ACEI decreases efferent arteriole
constriction and hence decreases glomerular capillary
pressure which may preserve renal function longterm
• This may result in a 10-20% increase in creatinine, but
over the long term renal function is preserved

23. Circulation 2001:104:1985-1991

25. ACEI intolerance in low CO, low SVR states
GFR
Maintained
GFR
Declines

26. CRS with normal SVR but low CO or BP
“ No
Pump!!!”
• CRS due to inadequate renal
perfusion because of low CO
and/or BP, Nml SVR!!!
• Inotropes, Pressors, Temporary
circulatory support
• LVAD

27. “Although there is no serum creatinine level per se that
contraindicates ACE inhibitor therapy, greater increases in serum
creatinine occur more frequently when ACE inhibitors are used in
patients with underlying
chronic renal insufficiency.”

31. Heart Mate 2

32. Severe Renal Dysfunction Complicating
Cardiogenic Shock is not a contraindication to
Mechanical Support as a Bridge to Transplant
Khot UN et al JACC 2003

33. CRS
with vasodilation
• Renal hypoperfusion due to low perfusion; CO may be
normal but SVR and BP low
• Vasodilators worsen BP and hence renal perfusion
• Stop of ACEI, especially if SVR is low
• Rule out sepsis
• Pressors, Inotropes, ? Vasopressin
• Consider transplant or ventricular assist device if renal
dysfunction is felt to be reversible
“Vasodilated!!”

35. A Prospective Randomized Trial of Arginine
Vasopressin in the Treatment of Vasodilatory
Shock after Assist Device Placement
• 10/23 VAD patients with low blood pressure and
increased cardiac index
• Despite pressors, SVR still decreased
• 5 received saline placebo for 15 minutes and 5
vasopressin (.1 Units/min, 3 patients in placebo group
were blindly crossed over
• No change in BP in placebo group
• MAP increased from 61 to 87 in the Vaso group with
increase in SVR from 729 to 1374, with significant
reduction in NE dose
• NE was able to be weaned off in 4/5 patients within 15
minutes
Argenziano et al Circ 1997 Suppl II 290

36. CRS with normal CO and SVR
• Consider intrinsic renal disease (IRD) or diuretic
resistance syndrome, renal artery stenosis
• Probable IRD when long hx of HTN and/or diabetes,
look for proteinuria, renal artery stenosis
• Trial of loop diuretic infusion, combination with distal
tubular diuretic
• Add nesiritide
• Consider ultrafiltration
“It’s the
Kidneys,
Not the
Heart!!!!””

37. Renal Adaptation to Diuretics
Ellison DH. Am J Kidney Dis. 1994;5:623.
Stanton and Kaissling Am J Physiol 1988 255:F1269

38. Invasive hemodynamic monitoring
should be considered in a patient:
• who is refractory to initial therapy,
• whose volume status and cardiac filling pressures are unclear,
• who has clinically significant hypotension (typically SBP !80 mm Hg) or
worsening renal function during therapy,
Or
• who is being considered for cardiac transplant
and needs assessment of degree and reversibility of pulmonary
hypertension,
Or
in whom documentation of an adequate hemodynamic response to the
inotropic agent is necessary when chronic outpatient infusion is being
considered. (Strength of Evidence 5 C)
HFSA Guildelines 2010

40. Cardiac Output = VTI x Area of Outflow Tract x Heart Rate
8cm/sec x 3cm x 80 beats/min = 1920 ml/min, 1.9 L/min

41. Hemodynamic Echo-The Noninvasive swan
• Right Atrial pressure (Inferior Vena Cava)
• Pulmonary Artery Pressure (TR Velo + RA)
• Estimated mean left atrial pressure (E/Eʹ)
• Cardiac Output (VTI x Area x HR)
• Systemic Vascular Resistance
(MAP-RA)x80/CO
130/70 = Mean 130+140/3= 90
(90-20) x 80/1.9= 5600/1.9 =
SVR approx 2800 i.e. vasoconstricted

43. Case Study
• 56 yo male with ICM, CABG 1998, ICD 2001 EF 10%
• Dec 2011 admitted with AF another hospital
• Dec 19 Admitted Scripps for dyspnea, angioplasty of OM2,
Diagonal and PDA grafts, RA 15, PA 64/34, Wedge 20,
Fick 2.5 L/min, PA Sat 54%
• Discharge Furo 20, Carvedilol 3.125 bid, Lis 2.5
• wt 77.4 Kg

44. Mr CB
Did well for one week, admitted another hospital
for pneumonia
• Seen post discharge and digoxin was started for
Afib, EF 7% referred back to Scripps
• On Admission, Dyspneic, weight 75 KG
• Gen- A/Ox3 but very fatigued
• Neck- JVD to jawline, (+)AJR
• Heart- Irreg, tachy, 105bpm, 2/6 systolic murmur
• Lungs- CTAB
• Ext- no edema, cool to touch

45. Mr CB
1/12 creatinine 1.8
• 1/13 Echo EF 14%, PA sys 48, RA 10, Ascited, LVOT 6
cm
• 1/13-14 attempted to diuresis, poor UO, Creat 2.2
• 1/16 Cardioverted, CRT placed
• 1/17 Creat 2.9, 350 cc urine/24hr HF consult
• BP 80-90 systolic, cold extremities-Cardiogenic Shock

46. Initial Swan results in ICU
• RA = 22
• RV = 43/22
• PAP = 41/26(30)
• PCWP = 22
• CO/CI = 1.87/1.0 by Fick
• PA sat 33%,

47. What to do?

48. Intervention
• Dobutamine IV 5 mcg/kg/min
– Titrate to SBP>90
• Dopamine IV 3 mcg/kg/min
• Nitroprusside IV 0.5 mcg/kg/min
– maintain SVR 1200-1500
– Hold for SBP<90
• Lasix and Zaroxolyn for diuresis

50. PA
CVP
CO/CI
SVR

52. PA
CVP
CO/CI
SVR

53. 24 hours later…
• CO = 6 L/min
• UOP = 6 L overnight (325 mL over the
prior 24 hours)
• Inotropes weaned
• Captopril initiated, uptitrated over next 24
hours

55. Mr TW
• 62 yo male with severe nonischemic cardiomyopathy
(alcohol abuse and long standing insulin dependant
diabetes)
• Seen in HF Clinic first time 8/25/08 following BIV pacer
• Feeling terrible, dizzy BP 70/50
• neck veins to the jaw, Very Loud, palpable S3
• Intermittent capture of LV and RV by device
• Paced beats are very wide, wider than prior to device

56. • Readmitted 12 days later for confusion, possible
stroke
• BP 100/70 JVP 8,
• Creatinine 2.6
• Given fluids and placed on milrinone

57. Very difficult to titrate meds because of
combination of low blood pressure, renal
dysfunction and high serum potassium,
Could not tolerate spironolactone due to
hyperkalemia
Not a transplant candidate-poor social support,
advanced diabetesd, BKA
Left atrial pressure monitor inserted 12/08

58. 60
Implantable Components
HeartPOD® (Physiologically Optimized Dosimeter) ISL
Implantable
Communications
Module (ICM)
Lead
Sensor
Module
Proximal
Anchor
Distal
Anchor
Sensor
Diaphragm
~ 3 mm
Measures
•LAP
•IEGM
•Core Temp
Implantable
Sensor
Lead (ISL)

59. HeartPOD® System
Patient Advisory Module (PAM)
LARA
SAVACOR, INC
Modified PDA
•Powers implant through
clothing
•Atmospheric reference
•Stores telemetry
•Alerts patient to monitor
•‘DynamicRX®’ instructs
• Meds
• Activity
• Clinician contact
based on LAP values and
physician’s prescription

61. Very Low Low Optimal High Very High
LAP 0-8 9-17 18-30 31-39 40-50
Torsemide Hold 10 bid 20 bid 30 bid 30 bid call
Mean LAP
31 mm

62. Very Low Low Optimal High Very High
LAP 0-8 9-17 18-30 31-39 40-50
Torsemide Hold 10 bid 20 bid 30 bid 30 bid call
Mean LAP
31 mm
Very Low Low Optimal High Very High
LAP 0-4 5-12 13-23 24-39 40-50
Torsemide Hold 10 bid 20 bid 30 bid 30 bid call
Mean LAP
20.7

64. Very Low Low Optimal High Very High
LAP 0-4 5-12 13-23 24-39 40-50
Torsemide Hold 10 bid 20 bid 30 bid 30 bid call
Mean LAP
28 mm
Very Low Low Optimal High Very High
LAP 0-4 5-12 13-19 20-39 40-50
Torsemide Hold 10 bid 20 bid 30 bid 30 bid call
Mean LAP
16.5

66. 12/14/09 1/26/10 4/19/10 6/16/10 8/19/10
Weight 155 159 158 160 157
Creatinine 3.8 2.2 2.0 1.8 1.9
BUN 100 46 47 42 42

68. Profiles of the Cardiorenal Syndrome
CRS due to: Fluid
Status
CO
CI
SVR Proteinuria Treatment
Too Dry!!! Dry Low Nml or high None Fluids, stop diuretics
Too Wet!!!
(high CVP)
Wet Nml Nml None Continuous diuretic
infusion, distal tubular
diuretic, ultrafiltration
Too Clamped
Down!!!
Wet or
Nml
Low High None ACEI, Nitroprusside,
Nesiritide, Relaxin
Vasodilated!!!
Nml or
wet
Nml or
high
Low None Stop ACEI,
Pressors, Vasopressin
Inotropes, VAD
No Pump!!!
Wet or
Nml
Low Nml None Inotropes,
Vasopressors
Balloon Pump
LVAD
Intrinsic Renal
Disease/Diureti
c Resistance
Wet Nml Nml None Continuous diuretic
infusion, distal tubular
diuretic, ultrafiltration

70. Volume Management

71. Diuretics to increase
sodium loss and decrease
venous pressures
Concept of Plasma Refill Rate in ADHF
Redefining the Therapeutic Objective in
Decompensated Heart Failure: Hemoconcentration
as a Surrogate for Plasma Refill Rate Boyle and Sbotka J Card Failure May 2006

72. Diuretics to increase
sodium loss and decrease
venous pressures
Concept of Plasma Refill Rate in ADHF

73. The prognostic importance of different definitions
of worsening renal function in CHF
Risk of death
or
Hospitalization
>
10 days
S Gottlieb et al J Card Failure 6/02
100
80
60
40
20
0
> 0.1 > 0.2 > 0.3 > 0.4 > 0.5
Increase in Creatinine
Sensitivity
Specificity

75. Hemodynamic
Changes
No
Hemoconcentration Hemoconcentration P value
RA pressure -2.8±5.6 -5.4± 0.031
Pulm Art Sys Pres -9.0±12.4 -14.4±10.8 0.124
Wedge Pressure -6.2±8.3 -12.6±9.6 0.015

77. No Hemoconcentration
Hemoconcentration

78. Diuretic Optimization
Strategies Evaluation in Acute
Heart Failure (DOSE)
G. Michael Felker, MD, MHS, FACC
Christopher M. O’Connor, MD, FACC
on behalf of the
NHLBI Heart Failure Clinical Research Network

79. Secondary Endpoints:
Low vs. High Intensification
Low High P value
Dyspnea VAS AUC at 72 hours 4478 4668 0.041
% free from congestion at 72 hrs 11% 18% 0.091
Change in weight at 72 hrs -5.3 lbs -8.2 lbs 0.011
Net volume loss at 72 hrs 3575 mL 4899 mL <0.001
% Treatment failure 37% 40% 0.56
% with Cr increase > 0.3 mg/dL
at 72 hrs
14% 23% 0.041
Length of stay, days (median) 6 5 0.55

80. Changes in Creatinine over Time*:
High vs. Low
1.45
1.5
1.55
1.6
1.65
1.7
1.75
1.8
0 1 2 3 4 7 60
Time (days)
Low High
Creatinine(mg/dL)
p = 0.85
p = 0.07
p = 0.28
p = 0.59
p = 0.34
p = 0.81
*P values are for change in creatinine from baseline

81. Changes in Creatinine over Time*:
High vs. Low
1.45
1.5
1.55
1.6
1.65
1.7
1.75
1.8
0 1 2 3 4 7 60
Time (days)
Low High
Creatinine(mg/dL)
p = 0.85
p = 0.07
p = 0.28
p = 0.59
p = 0.34
p = 0.81
*P values are for change in creatinine from baseline

82. Proportion with Worsening Renal Function:
High vs. Low
0%
5%
10%
15%
20%
25%
0 1 2 3 4 7 60
Time (days)
Low High
%withΔCr>0.3mg/dL

83. Death, Rehospitalization, or ED Visit
HR for Continuous vs. Q12 = 1.19
95% CI 0.86, 1.66, p = 0.30
HR for High vs. Low = 0.83
95% CI 0.60, 1.16, p = 0.28
0
0.1
0.2
0.3
0.4
0.5
0.6
0 10 20 30 40 50 60
Days
ProportionwithDeath,Rehosp,orEDvisit
High Low
0
0.1
0.2
0.3
0.4
0.5
0.6
0 10 20 30 40 50 60
Days
ProportionwithDeath,Rehosp,orEDVisit
Continuous Q12

84. Original Article
Ultrafiltration in Decompensated Heart Failure with
Cardiorenal Syndrome
Bradley A. Bart, M.D., Steven R. Goldsmith, M.D., Kerry L. Lee, Ph.D., Michael M.
Givertz, M.D., Christopher M. O'Connor, M.D., David A. Bull, M.D., Margaret M.
Redfield, M.D., Anita Deswal, M.D., M.P.H., Jean L. Rouleau, M.D., Martin M.
LeWinter, M.D., Elizabeth O. Ofili, M.D., M.P.H., Lynne W. Stevenson, M.D., Marc J.
Semigran, M.D., G. Michael Felker, M.D., Horng H. Chen, M.D., Adrian F.
Hernandez, M.D., Kevin J. Anstrom, Ph.D., Steven E. McNulty, M.S., Eric J.
Velazquez, M.D., Jenny C. Ibarra, R.N., M.S.N., Alice M. Mascette, M.D., Eugene
Braunwald, M.D., for the Heart Failure Clinical Research Network
N Engl J Med
Volume 367(24):2296-2304
December 13, 2012

90. Literary Last Note
• “All happy families are all alike, all unhappy families are unhappy in
their own way.” Anna Karenina Leo Tolstoy
All patients compensated HF patients are alike,
all patients with cardiorenal syndrome are unhappy in their own way.