Gerasimos Filippatos, MD, FESC, FHFA

President HFA

Heart Failure and Renal Failure

• Definition

• Epidemiology

• Pathophysiology

• Management (?)

Recommendations for NHLBI in cardio-

renal interactions related to heart failure

• “The result of interactions between the kidneys and

other circulatory compartments that increase

circulating volume and symptoms of heart failure

and disease progression are exacerbated. At its

extreme, cardio-renal dysregulation leads to what

is termed ‘cardio-renal syndrome’ in which

therapy to relieve congestive symptoms of heart

failure is limited by further decline in renal function”

NHLBI Working Group. Cardio-renal connections in heart failure and cardiovascular disease: executive summary .

Available at: http://www.nhlbi.nih.gov/meetings/workshops/cardiorenal-hf-hd.htm.

The New Definition of Cardiorenal Syndrome

Cardiorenal Syndrome (CRS) General Definition: A pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction

in one organ may induce acute or chronic dysfunction in the other organ

CRS Type I (Acute Cardiorenal Syndrome) Abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated

congestive heart failure) leading to acute kidney injury

CRS Type II (Chronic Cardiorenal Syndrome) Chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing

progressive and permanent chronic kidney disease

CRS Type III (Acute Renocardiac Syndrome) Abrupt worsening of renal function (e.g. acute kidney ischaemia or glomerulonephritis)

causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia)

CRS Type IV (Chronic Renocardiac Syndrome) Chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac

function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events

CRS Type V (Secondary Cardiorenal Syndrome) Systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal

dysfunction

Ronco C. et al, EHJ 2010

The Definition

What defines the above factors?

Any degree of

cardiac

dysfunction

Any degree of

anemia

Any degree of

kidney failure

Iron Deficiency

The interaction between heart failure, renal dysfunction, anaemia, and iron deficiency.

Macdougall I C et al. Eur J Heart Fail 2012;14:882-886

Stage Description CreatClearance

(ml/min/1.73m)

1 Early renal damage, ifother

Markers of this (proteinuria or

Structural abnormality)

>90

2 Early renal insufficiency 60-89

3 Moderate renal failure 30-59

4 Severe renal failure 15-29

5 End stage renal disease <15

Classification of CKD

US National Kidney Foundation Classification. Am J Kid Dis 2002; 39: S1-246

Filippatos G et al. Eur Heart J 2014

• Definition

• Epidemiology

• Pathophysiology

• Management (?)

From: Braunwald’s Heart Disease. 9th ed. Philadelphia, Elsevier, 2011

eGFR, ml/min/1.73 m2

60% of patients

with eGFR <60

ml/min

Prevalence of renal dysfunction

Heywood et al., J Card Fail 2007; 13:422

Renal Function as a Predictor of Outcome

in a Broad Spectrum of Patients With Heart

Failure. Results from CHARM

Low LVEF Preserved LVEF

Hillege et al., Circulation. 2006;113:671-678

BUN and Death or HF Rehospitalization

Log-Rank Test

P-Value = 0.0005

PR

OP

OR

TIO

N O

F R

EM

AIN

ING

IN

ST

UD

Y

0.5

0.6

0.7

0.8

0.9

1.0

DAYS IN STUDY

0 10 20 30 40 50 60 70

BUN > 40 mg/dL

BUN < 18 mg/dL

BUN 19-26 mg/dL

BUN 27-39 mg/dL

Filippatos G et al .J Cardiac Failure 2007

Determinants and forms of worsening renal function in heart failure.

Filippatos G et al. Eur Heart J 2013;eurheartj.eht515

• Definition

• Epidemiology

• Pathophysiology

• Management (?)

i.v. Furosemide

↑ systemic

venous

pressure

Renal

dysfunction

Neurohormonal

activation

Renal

hypoperfusion

Adenosine release

Tubuloglomerular

feedback

↓ cardiac

output

Hypotension

ACEi/

ARBs

Cardiac

dysfunction

Metra, Brutsaert, Dei Cas, Gheorghiade. IACC ESC Textbook, 2011

↑ Renal

venous

pressure

i.v. Furosemide

↑ systemic

venous

pressure

Renal

dysfunction

Neurohormonal

activation

Renal

hypoperfusion

Adenosine release

Tubuloglomerular

feedback

↓ cardiac

output

Hypotension

ACEi/

ARBs

Cardiac

dysfunction

Metra, Brutsaert, Dei Cas, Gheorghiade. IACC ESC Textbook, 2011

↑ Renal venous

pressure

Emerging Therapies in HF De Luca L, Mebazaa A, Filippatos G et al. Eur J Heart Fail 2008

Blocks adenosine mediated afferent arteriole vasoconstriction maintains GFR

Inhibits reabsorption of sodium and water in the proximal tubule diuresis

MECHANISMS OF DISEASE PROGRESSION

Cardiac and Renal Injury Cell death by necrosis and apoptosis

Tn Release

Fibrosis

Progression

of Heart and

Kidney Failure

Neurohormonal

Activation

Hemodynamic

Deterioration

Modified from Filippatos G et al. Am J Physiol 1999

RAAS

DRUG TOXICITY

Early drop in systolic blood pressure and worsening

renal function in AHF: renal results of Pre‐RELAX‐AHF

European Journal of Heart Failure vol 13, pages 961-967, 2014 DOI: 10.1093/eurjhf/hfr060

Early drop in systolic blood pressure and worsening

renal function in AHF: renal results of Pre‐RELAX‐AHF

European Journal of Heart Failure vol 13, pages 961-967, 2014 DOI: 10.1093/eurjhf/hfr060

Potential pathogenetic pathways linking heart failure with renal dysfunction.

Filippatos G et al. Eur Heart J 2014

• Definition

• Epidemiology

• Pathophysiology

• Management (?)

Heart Failure Drug Treatment Options

Symptom Relieving

• Diuretics

• Digoxin

Disease Modifying

• ACE inhibitors

/angiotensin II receptor

antagonists

• Beta-blockers

• Aldosterone receptor

antagonists

Shlipak, M. G. Ann Intern Med 2003;138:917-924

Selected Placebo-Controlled Trials in Patients with Heart Failure: Renal Function of Participants and Medication Efficacy

Shlipak, M. G. Ann Intern Med 2003;138:917-924

Treatment algorithm for patients with systolic heart failure, based on renal function

ACE-I associated creatinine elevations

Bakris GL et al. Arch Int Med 2000;160:685

ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

Decompensated chronic HF

• Consider higher dose of diuretics in

renal dysfunction or with chronic

diuretic use.

What to do next ?

1. Increase furosemide dose

2. Ιntravenous infusion rather than bolus therapy

3. Substitution of an ineffective loop diuretic for another one

4. Add metolazone and/ or potasium sparing diuretic

5. Add dopamine at 2-5 mcg/k/m

6. Withdraw b-blocker and/ or ACE inhibitor

7. Add dobutamine

8. Add levosimendan

9. Start ultrafiltration

10. Start dialysis

11. Insert IABP

12. Insert another device

Maisel A, Filippatos G, Heart Failure. Publisher Jaypoor Brothers, 2014

Renal Replacement Therapy

Ultrafiltration may be considered for patients with

obvious volume overload to alleviate congestive

symptoms and fluid weight.

Ultrafiltration may be considered for patients with

refractory congestion not responding to medical

therapy.

I IIa IIb III

I IIa IIb III

Acute Kidney Injury Timeline

Cardiorenal Interaction: The Future

We need to use meaningful definitions and

validate them in different clinical settings.

We need to evaluate the impact of early

biomarkers on diagnosis and various therapeutic

approaches

We need to appraise current evidence and

generate wise recommendations for practice.

We need research to generate the missing

evidence.