Frank Enseleit

Kardiologie, Universitätsspital Zürich

E-mail: frank.enseleit@usz.ch

Niere und Herz

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)

Vielen Dank

Kardiologie

Universitätsspital Zürich

E-mail: frank.enseleit@usz.ch