53y w/m
Ischemic CM
- LVEF 15%
07/2006:
- low output
Nierenfunktion vor und nach LVAD-
Implantation (2.8.2006)
Low output post-LVAD
Serum Creatinine is a Marker for Increased
Risk of Stroke
Wannamethee Stroke 1997
Str
ok
e ri
sk/1
000/p
erso
n y
ears
<109
Serum Creatinine mmol/l
1
3
5
7
9
109-116 116-130 >130
Follow-up: 14.8 years
7690 men
287 major stroke
(73 fatal and 214 nonfatal)
*
*
Serum Creatinine is a Marker for Increased
Risk of Ischemic Heart Disease
Wannamethee Stroke 1997
IHD
ris
k/1
00
0/p
erso
n y
ea
rs
<109
Serum Creatinine mmol/l
0
5
10
15
20
109-116 116-130 >130
Follow-up: 14.8 years
7690 men
967 IHD Events *
100
0
200
600
400
1200
1000
800
Seru
mkre
atinin
μm
ol/l
GFR schätzen (CG, MDRD) GFR messen (CrCl/Proteinurie)
Serumkreatinin wenig sensitiv für die Nierenfunktion
Kreatinin versus GFR
Schätzformel der Kreatininclearance Stadien chronische Niereninsuffizienz (CKD)
Cockcroft & Gault, 1976
Kreatinin-Cl (ml/min) = 1.2 x [140-Alter] x (Gewicht)
Serum Kreatinin
Frauen x 0.85
Stage Beschreibung GFR ml/min/1.73m2
1 Kidney damage with normal GFR
>90
2 mild GFR 60-89
3 moderate GFR 30-59
4 severe GFR 15-29
5 Kidney failure <15 or dialysis
GFR is the most powerful predictor of
mortality in CHF
Second Prospective Randomized study of Ibopamine on Mortality and Efficacy. Hillege Circ 2000
n=372/1906 patients
GFR is the more powerful predictor of mortality on
CHF than LVEF
PRIME II: Hillege Circ 2000
Schrier JACC 2006
Mechanisms by Which Heart Failure Leads to the Activation of
Neurohormonal Vasoconstrictor Systems and Renal Sodium and
Water Retention
Cardiorenal Axis
Ang II, Aldo, ET-1 • Vasoconstriction
• Growth stimulation
• Sodium retention
ANP, BNP, CNP • Vasodilation
• Growth inhibition
• Natriuresis
EPO • Erythropoiesis
• Neuroprotection
• Cardioprotection?
SNS • Vasoconstriction
• Sodium retention
• Growth stimulation
Vasopressin • antidiuretic
• Water reabsorption
• Hyponatremic
NO, Prostaglandins • Vasodilation
• Growth inhibition
• Natriuresis
Classification of Cardio-renal
Syndrome
Ronco, C. et al. J Am Coll Cardiol 2008;52:1527-1539
„disorders of the heart and kidneys whereby acute or chronic
dysfunction in one organ may induce acute or chronic
dysfunction of the other“
Ronco, C. et al. J Am Coll Cardiol 2008;52:1527-1539
Cardio-renal Syndrome Type 1
Navar 2000
Renal Effects of Angiotensin II
Pathophysiology of Angiotensin II
Shah, Int. J. Nephrology, 2011
Angiotensin II causes cardiac
dysfunction in CHF by:
• direct myocardial effects on remodeling/fibrosis
• increasing prox. sodium reabsorption
• impairing aldosterone escape
• perpetuating volume overload
•cardiac dilation
•(Worsening of) MR
•LVH
•blunting atrial-renal reflexes •CAVE: Excessive arterial vasodilation will cause
arterial underfilling
BL Aa BL Aa BL Aa
Renal Hemodynamic Reserve in Mild Heart Failure
is Restored by Angiotensin II Antagonism
Bl Aa
Ctl Ena Los Magri Circ 1998
Bl Aa Bl Aa Bl Aa
Schrier JACC 2006
Mechanisms by Which Heart Failure Leads to the Activation of
Neurohormonal Vasoconstrictor Systems and Renal Sodium and
Water Retention
Ligtenberg et al, NEJM 1999
Rump NDT 2000
The Kidney: A Nervous Organ
Carvedilol Improves Renal Blood Flow in
Heart Failure Patients
0
100
200
300
400
500
600
700
800
900
Placebo Metoprolol Carvedilol
Baseline
6 months
Renal blood flow (ml/min)
(n=4) (n=4) (n=6)
*p=0.02 vs placebo and metoprolol (6 months) †p=0.03 vs baseline
* †
Abraham et al (1998)
Angiotensin II and Natriuretic
Peptides: sworn enemies
Angiotensin II • Vasoconstriction
• Systemic and renal
• Vas efferens >afferens
• Oxidative Stress
• Vascular Inflammation
Aldosterone
• Na/H2O retention
• Preload
ANP, BNP, CNP
• Vasodilatation
• Systemic and renal
• Vas aff.>efferens
• Growth inhibition
• Natriuresis
rhBNP
D R I
M
K
R
G
S S
S
S
G
L
G F
C C
S S
G S G Q V M
K V L R
R H
K P S
Effects of Nesiritide
Venous, arterial, coronary
VASODILATION
CARDIAC
INDEX
Preload
Afterload
PCWP
Dyspnea
HEMODYNAMIC
CARDIAC
No increase in HR
Not proarrhythmic
Aldosterone
Endothelin
Norepinephrine
SYMPATHETIC AND
NEUROHORMONAL SYSTEMS
NATRIURESIS
DIURESIS
Fluid volume
Preload
Diuretic
usage
RENAL
Hemodynamic Effects of Nesiritide
in Heart Failure Patients
16 patients received a 4-hour continuous infusion of rhBNP (0.025 and 0.05 mg/kg/min) or placebo
Abraham WT, et al. J Card Fail 1998;4:37–44
Change from
baseline (%)
-60
-40
-20
0
20
40
60
HR RAP PCWP SVR CI SVI
Placebo
Nesiritide
* *
+
+
* p <0.01 vs placebo
+ p <0.05 vs placebo
Urinary Excretion with Nesiritide
Marcus LS, et al. Circulation
Urinary
sodium
excretion
(mEq/h)
Urinary volume
(mL/h)
0
25
50
75
100
Placebo Nesiritide
p<0.01 B
Creatinine
clearance
(mL/min)
0
25
50
75
100
125
Placebo Nesiritide
D
Placebo Nesiritide
p<0.05 A
0
1
2
3
4
Urinary
potassium
excretion
(mEq/h)
0
1
2
3
4
Placebo
C
Nesiritide
Possible Mortality Hazard Associated with
Nesiritide
JAMA 2005; 293:1900-1905
ADHERE: Acute Decompensated HEart Failure
National REgistry
• ADHERE is a prospective, observational database of patients hospitalized
with acutely decompensated
heart failure
• Over 250 US hospitals, including community, tertiary, and academic medical
centers
• Data from the first 33,046 patients enrolled in ADHERE were analyzed
• Treatment based on clinician judgement (not by a study protocol)
• Imbalances between groups in baseline characteristics were adjusted using
multivariable regression and propensity analysis
Abraham WT et al. J Card Fail 2003
ADHERE: In-Hospital Mortality and Use of
Parenteral Vasoactive Medications
ADHERE: Acute Decompensated HEart Failure National REgistry
ASCEND-HF - Results
NEJM 2011
Ronco, C. et al. J Am Coll Cardiol 2008;52:1527-1539
Cardio-renal Syndrome Type 2
Prevalence of Anemia in CHF
N=2281
Kosiborod M et al: Am J Med 2003
Mechanisms of Anemia in heart Failure
Jalal K. Ghali
Curr Opin Cardiol
2009
Hematocrit and Survival in CHF
Kosiborod M et al: Am J Med 2003
Outcome in FAIR-HF
Anker, SD, NEJM 2009
Auftreten von Komplikationen
Metabolische Azidose
Zeit
GRR
Renale Anämie
Calcium-Phosphat-Störungen
Hyperparathyreoidismus
Hyperkaliämie
30
60
15
Dialysepflicht
Kardiopathie
90
CKD Stadium I
CKD Stadium II
CKD Stadium III
CKD Stadium IV
CKD Stadium V
chronische Entzündung
Niereninsuffizienz - Herzkrankheit
Renal Dysfunction in Heart Failure
• Optimize hemodynamics to reverse mechanisms
responsible for salt and water retention
• Avoid volume overload (dietary recommendation)
• Avoid volume depletion (i.e. overzealous diuretic therapy)
• Avoid NSAIDs
• Prefer ACEI, ARB, Betablockers
• ANP negative, BNP controversial, Urodilatin promising
• AVP experimental
• Ibopamine, Flolan increase mortality
• Ultrafiltration (no difference compared to diruetics)