Pathophysiology of acute decompensated heart failure.

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Transcript Pathophysiology of acute decompensated heart failure.

Congestive Heart
Failure VS Acute
Kidney Injury
Definition of Congestive heart failure and
acute kidney injury
 Epidemiology of AKI in heart failure
 Pathogenesis of AKI in heart failure
 Biomarker of AKI and CHF
 Treatment
Definition of heart failure
failure of pumping CO to peripheral tissues
and stasis of blood, fatigue, edema and
pulmonary congestion
 complex mechanical and neurohumoral
syndrome characterized by effort intolerance,
fluid retention
Acute kidney injury
AKI can result from
decreased renal blood
flow, a toxic insult to the
renal tubule, tubulointerstitial inflammation
or a primary reduction in
Criteria of acute kidney injury
Nephron Clin Pract 2009, 112, c222-229
Causes of Acute Kidney Injury
AKI effect on heart
Fluid overload pulmonary edema.
Hyperkalemia arrhythmias and cardiac arrest.
Untreated uremia affects myocardial
Acidemia pulmonary vasoconstriction , rightsided HF, negative inotropic effect and might
Renal ischemia activation of inflammation and
apoptosis at cardiac level
Cardiorenal syndrome (CRS)
Disorders of the heart and kidneys whereby
acute or chronic dysfunction in one organ
may induce acute or chronic dysfunction
of the other
Nephrol Dial Transplant 2011; 26: 62–74
Cardiorenal syndrome classification
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 acutely 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 potentially 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 or interstitial 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
up to 45% of patients hospitalized with
decompensated HF developing worsening renal
function (WRF) (Kimmenade et al, 2007)
an independent poor prognostic marker
poor clinical outcomes in patients who
develop AKI when hospitalized for
decompensated heart failure (Cowie et al, 2004)
small increases in SCr (50% increase or
absolute increase of 0.3 mg/dL from
baseline as in stage I AKI), independently
associated with both short-term and
long-term outcomes
 small changes in SCr are transient and
renal function ‘‘improves,’’prognosis
remains worse
Gottlieb et al., 2002
POSH trial (Prospective outcomes study in
heart failure)
299 patients aged >20 years, across eight
European countries admitted to hospital
with decompensated heart
 33% developed AKI (described as
‘worsening renal function’), defined by an
increase in SCr. > 0.3 mg/dl from
baseline during their hospital admission
with a mean time of of 4 days
ADHERE registry
more than 100 000 patients, heart failure, included
elderly patients and CKD
Impaired eGFR was a strong predictor of mortality,
more than ejection fraction in decompensated heart
Even a moderate rise in creatinine (>0.3 mg/dl) in
hospitalized patients predicted an increased risk of
death and prolonged hospitalization
pre-existing chronic kidney disease is also a predictor
of worse outcome and mortality
renal impairment and acute kidney injury
in heart failure are strong and
independent predictors of poor outcome
and prognosis.
 Even a relatively small decline in renal
Risk factors for development of
cardiorenal syndrome
Advanced age, diabetes, pulmonary edema on
chest X-ray on admission (Cowie et al, 2004)
co-morbid vascular disease, higher level of
baseline urea (Heywood, 2004)
HTN and lower SBP on admission (SOLVD
Investigators, 1991)
EF with studies such as SOLVD suggesting a
link between poor EF and increased risk of
AKI in decompensated cardiac failure, while
others have shown no association (Geisberg and Butler,
Cardio-Renal Axis: any increase in atrial
pressure diminishes the arginine
vasopressin release (AVP) through the
Henry-Gauer Reflex, decreases renal
sympathetic tone, and increases the atrial
natriuretic peptide, increase the urinary
sodium and water excretion rate
Pathophysiology of acute decompensated heart failure. [Reproduced with permission from
Schrier RW. Body fluid volume regulation in health and disease: A unifying hypothesis.
Sarraf M et al. CJASN 2009;4:2013-2026
©2009 by American Society of Nephrology
Role of decreased baroreceptor sensitivity, and activation of RAAS and SNS in expansion of
water and sodium retention as well as worsening HF. [Reprinted from J Am Coll Cardiol, vol.
47, Schrier RW, Role of diminished renal function in cardiovascular mortal...
Sarraf M et al. CJASN 2009;4:2013-2026
©2009 by American Society of Nephrology
Vasopressin stimulation of V2 and V1a receptors can contribute to events that worsen
cardiac function. [Reprinted from J Am Coll Cardiol, vol. 47, Schrier RW, Role of diminished
renal function in cardiovascular mortality: Marker or pathogenetic factor? pp. ...
Sarraf M et al. CJASN 2009;4:2013-2026
©2009 by American Society of Nephrology
Pathophysiological mechanisms
 Neurohormonal activation of RAAS, SNS,
 Inflammatory immune activation
CRS were more likely to be clinically
fluid overloaded than deplete on
admission to hospital While Forman et al (2004)
 venous congestion, increase in right
atrial pressure was a significant
independent predictor for the
development of renal dysfunction in
decompensated heart failure
renal perfusion : pressure gradient
across the kidney, reduced not only when
a reduction in mean arterial pressure but
also when renal venous pressure is
elevated (congestion and elevated right
atrial pressure)
Activation of renin–angiotensin–aldosterone
secondary to low renal perfusion pressure
or blood flow (Bongartz et al, 2005)
 sodium and water retention as a result
of the actions of angiotensin II and
prolonged activation leads to both
worsening renal function, with a
reduction in renal blood flow and eGFR
(Bongartz et al, 2005),
worsening cardiac function with increased
myocardial oxygen demand, myocardial
ischaemia, impaired contractility and
Pathophysiology of the relation between venous congestion and reduced glomerular filtration
rate (GFR).
Damman K et al. Eur J Heart Fail 2007;9:872-878
© 2007 European Society of Cardiology
Inflammatory immune activation
CHF and advanced CKD : neurohormonal and
inflammatory immune activation
CHF inflammatory cytokines :TNF and IL-6 independent
predictors of adverse outcome, progression (Anker et al, 2002)
in decompensated HF gut wall edema (secondary to
elevated RA pressure) facilitates translocation of
bacterial endotoxin (lipopolysaccharide) (Niebauer et al, 1999).
The net result of inflammatory cytokine activation,
adversely impact on cardiac and renal function.
Biomarker in kidney
and heart disease
AKI: Pathophysiology and markers
Heart Fail Rev (2011) 16:503–508
BNP and NT-proBNP
Mean BNP as it relates to GFR.
Nephrol Dial Transplant 2011; 26: 62–74
With a cut-point set at 300 pg/mL for
excluding acute HF, a negative predictive
value of 94 and 100% for patients with a
GFR < and ≥ 60 mL/min/1.73 m2,
Nephrol Dial Transplant 2011; 26: 62–74
Treatment options
Most heart failure trials excluded
patients with marked renal impairment,
resulting in a lack of evidence to guide
best practice in the management of
patients with renal impairment and heart
British Journal of Hospital Medicine, May 2010,
Vol 71, No 5
the mainstay of treatment in
decompensated HF.
 higher doses of diuretics were
independently associated with increased
risk of death, sicker patients receive the
highest doses of diuretic (Geisberg and Butler,
A number of studies shown aggressive
diuresis to be associated with worsening
renal function (Shlipak and Massie, 2004)
more effective when slow continuous infusions
than in bolus ( Geisberg and Butler, 2006)
gradual diuresis, allowing time for fluid to move
from the extravascular to intravascular space
and avoid significant drops in renal perfusion
co-administer a thiazide diuretic, provide
synergistic benefit, sodium reabsorption is
inhibited at multiple sites within the nephron (i.e.
loop of Henle and distal tubule)
Angiotensin-converting enzyme inhibitors
and/or angiotensin receptor blockers
ACEI has a survival benefit in patients with heart failure
(SOLVD Investigators, 1991; Cowie et al, 2004).
Cr. levels often rise after the initiation of ACEI in
decompensated heart failure, especially with preexisting renal impairment (Shlipak and Massie, 2004)
patients with renal impairment may derive greater
benefit from ACEI
a moderate deterioration of renal function, allowing up to
20% increase in creatinine, should be tolerated.
more likely to have a Cr. rise if they
had pre-existing renal impairment or
severe HF
 Most patients had a 10–15% increase in
Cr. within 3 weeks of starting enalapril,
irrespective of their baseline Cr., then
tended to settle at this or an improved
level over the subsequent months
intravascular volume optimized, nephrotoxic
drugs, NSAID should be avoided.
Initiation of ACEI in declining renal function and
decompensated heart failure is not
ACEI/ARB should be maintained wherever
possible, provided renal function does not
steadily decline or severe hyperkalaemia (K>6.0
very low BP may require temporary
reduction in beta-blockers or ACEI/ARB
(other anti-HTN agents, CCB should be
stopped first) during major exacerbations,
with the aim of increasing MAP and renal
 Once stabilized these should be reintroduced or uptitrated.
Other treatments
beta-blocker : improved the prognosis for
CHF, not be started in acute
decompensated heart failure.
Spirinolactone is of prognostic and symptomatic
benefit in advanced heart failure (Pitt et al, 1999)
hyperkalaemia in AKI and pre-existing CKD,
especially in conjunction with ACEI/ARB.
stopped in severe hyperkalaemia (K >6.0
mmol/liter), other diuretic therapy and
appropriate dietary modifications
ADHERE registry 5% of patients with
decompensated HF had severe hyponatraemia with
sodium <130 mmol/litre (a larger number had milder
degrees of hyponatraemia)
EVEREST study 4133 patients with decompensated HF
were randomized to conventional therapy and
tolvaptan (vasopressin antagonist) or placebo
no difference in mortality at 60 days, but tolvaptan
was associated with improved weight loss and
patient symptoms (Gheorghiade et al, 2005; Cavalcante et al, 2008).
Novel therapies
Arginine vasopressin secretion from the
pituitary gland increased by low BP in HF,
aquaporin 2 activity in the collecting duct of the
kidney, water permeability, decreased diuresis;
free water retention and hyponatraemia.
(Kalra et al, 2001).
Blocking the vasopressin receptor, increased
free-water diuresis and improving congestion
and hyponatraemia (Geisberg and Butler, 2006)
Adenosine receptor antagonists
high plasma adenosine levels in CHF
lower renal cortical blood flow, restricting the
diuretic response to traditional diuretic agents
Blocking the adenosine receptor improves
diuresis without adversely affecting the eGFR
(Cotter et al, 2008).
The results of large scale outcome studies are
alternative to diuretic therapy has many
theoretical advantages in patients with
severe decompensated HF
 removal of isotonic fluid directly from the
intravascular space and also cytokines
 Small scale clinical studies have not
demonstrated consistent improvement in
outcomes or renal function (Francis, 2006)
Costanzo et al (2007) comparing
ultrafiltration and standard intravenous
diuretic therapy for hypervolaemic heart
failure patients
 no significant difference in dyspnoea
scores, serum creatinine levels or death
Take home message
Traditionally AKI attributed to poor CO pre-renal
failure, accumulating evidence showed
mechanisms are much more complex.
a poor prognostic indicator associated with
increased mortality and longer hospital stay.
maintained, albeit with greater care, monitoring
and appropriate dose alterations
New therapeutic options provide a brighter
future for this high-risk group of patients
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