comorbidities in AHF Kidney disease

Comorbidities in Acute Heart Failure

Kidney DiseaseHow to protect the kidney ?

Kevin Damman, MD, PhDUniversity Medical Center Groningen

Groningen, The Netherlands

k.damman@umcg.nl

Disclosures

Supported by the Netherlands Heart Institute (ICIN) and a HFA

Research Grant

Background

Chronic Kidney Disease (CKD) is one of the most prevalent

comorbidities in acute (and chronic) Heart Failure

Presence of an impaired renal function / reduced glomerular

filtration rate (GFR) is strongly associated with worse outcomes

Pathophysiology of impaired renal function multifactorial, and

probably slightly different form chronic HF

BackgroundEVEREST

(2007)VERITAS(2009)

PROTECT(2010)

ASCEND-HF(2011)

RELAX(2012)

N 4133 1448 2033 7141 1161

Age (years) 66 70 70 67 72

Male (%) 74 61 67 66 62

Creatinine (μmol/L) 124 118 124 106 NA

eGFR (mL/min/1.73m2) NA 57 50 62 53

CKD (%) 53 37 67 52 72

WRF (%) 14 20 18 13 NA

Background

EVEREST(2007)

VERITAS(2009)

PROTECT(2010)

ASCEND-HF(2011)

RELAX(2012)

CKD (%) 53 37 67 52 72

Hypertension (%) 71 80 79 72 87

Diabetes (%) 40 48 46 41 47

COPD (%) 10 NA 20 NA 15

AF (%) 43 37 56 38 52

CKD and prognosis

Smith et al Circulation 2005

CKD and prognosis

Heywood et al J Card Fail 2007, Blair et al Eur Heart J 2011

ADHERE EVEREST

CKD and Prognosis

Damman et al Eur Heart J 2014

Overall OR: 2.39 , 95% CI 2.25 to 2.54 (N=812139)

CKD and Prognosis

CKD present in 40 – 70% of (selected) AHF patients

Baseline CKD associated with strongly increased mortality

Cardiorenal Syndrome

Ronco et al JACC

“Cardiorenal Syndrome type I”

Classification based on epidemiology

Great for:- Creating Awareness- Popular term- Hype

However:- Does not help for

treatment- “CRS type I” very diverse

Pathophysiology

GFR ↓

RBF ↓Cardiac Output↓

CVP ↑

Salt and water retention ↑

• Interplay between: Comorbid organ dysfunction: Hypertension Diabetes CKD Peripheral artery disease

Hemodynamics: Reduced Cardiac Output Reduced Renal Blood Flow Increased Central Venous Pressure Increased Renal Venous Pressure

Intra-abdominal pressure

Therapy (Inotropes, vasodilators, diuretics)

Damman et al Progr Cardiovasc Dis 2011

Pathophysiology

Damman, Tang, Testani, McMurray Eur Heart J 2014

Renal Hemodynamics

Heart failure + ACEi/Diuretic

RVP ↑↑

RVP ↑↑RVP ↓

RVP ↑↑

Damman et al Progr Cardiovasc Dis 2011

Renal Hemodynamics

Mullens et al JACC 2011

Relative Importance CI/CVP

WRF and Prognosis

Damman et al Eur Heart J 2014

Overall OR: 1.75 , 95% CI 1.47to 2.08

Predictors of WRF

Damman et al Eur Heart J 2014

Predictors of WRF

Damman et al Eur Heart J 2014

Not all WRF equal

Testani et al AJC 2010, Metra et al Circ HF 2012

Any change (no) residual congestion

Not all WRF equal

Valente et al Eur Heart J 2014

Uncoupling between WRF,Diuretic Response and mortality

CKD and Diuretic Response

Singh J Card Fail 2014

AKI ≠ WRF

• Acute kidney injury is a condition in nephrology/intensive

care/shock

• Often intrinsic renal ‘hit’

• Very large increases in serum creatinine

• Associated with azotemia

• WRF can deteriorate in AKI

Terminology

Damman, Tang, Testani, McMurray Eur Heart J 2014

TerminologySuggested Definition

Serum Creatinine / eGFR Additional Criteria

Chronic HF (WRF)*

≥26.5 μmol/L and ≥ 25% increase in sCr#

OR

≥ 20% decrease in eGFR

over 1 to 26 weeks

Deterioration in HF status but

not leading to hospitalization

Acute HF (WRF/AKI)*

Increase 1.5 - 1.9 times baseline sCr within 1-7

days before or during hospitalization

OR

≥ 26.5 μmol/L increase in sCr# within 48 hours

OR

Urine output < 0.5 mL/kg/h for 6-12 hours

Deterioration in HF status or failure to

improve

OR

Need for inotropes, ultrafiltration or renal

replacement therapy

Damman, Tang, Testani, McMurray Eur Heart J 2014

Pseudo WRF

• ‘Unprovoked’ WRF associated with poor outcome

• WRF that occurs in patients with good Diuretic Response:

Often transient

No association with poor outcome

Could be called “Pseudo WRF”

Damman, Tang, Testani, McMurray Eur Heart J 2014

(Pseudo) WRF and AKI

Damman and Testani Eur Heart J 2015

Approach to (Pseudo) WRF

Damman and Testani Eur Heart J 2015

Dopamine

Chen JAMA 2013 ROSE-AHF study

Placebo Dopamine P-value

N 119 122

Urine volume (72h, mL) 8296 8524 0.59

Change in Cystatin C (mg/L) 0.11 0.12 0.72

Change in Creatinine (µmol/L) 1.8 0 0.78

WRF (%) 22 22 0.88

Sodium excretion (72h, mmol) 540 527 0.75

Weight change (72h, kg) -3.5 -3.3 0.82

Ultrafiltration

Bart et al NEJM 2012 CARRESS-HF study

Consider Paracentesis

Mullens et al JACC 2008 and J Card Fail 2008

Renal Spectrum in AHFDecreased Renal Blood Flow

Increased (Renal) Venous Pressure

Decreased GFR and renal reserve

Tubular and glomerular injury

Worsening Renal Function and Diuretic Resistance

Acute Kidney Injury / Azotemia

Renal Replacement Therapy / Ultrafiltration

Death

CKD/WRF in AHF• CKD at baseline strongly prevalent in AHF (50-70%)

• During admission, up to 20% experience WRF

However, WRF not always an omnious sign: Pseudo WRF

Risk stratify on WRF and diuretic response/efficiency

AKI is not the same as WRF

• Pathophysiology of both CKD and WRF is multifactorial

Decreased renal perfusion and increased renal venous pressure

Including abdominal hypertension (ascites)

• Treat the Heart – Don’t mind the Kidneys!*

(up to certain limits, and only if diuretic response is good)

* Ruggenenti et al Eur J Heart Fail 2011

Thank you for your attention!k.damman@umcg.nl