PATHOPHYSIOLOGY
HF/AHF
Disease Awareness
The pathophysiology of heart failure results in
an increasingly downward spiral
•
Acute decompensated HF is associated with frequent hospitalizations1
•
With each hospitalization, there is likely myocardial and renal damage that
contributes to progressive LV or renal dysfunction, leading to an inevitable
downward spiral2
Cardiac function and quality of life
Chronic HF
Increased risk of
decompensations
Hospitalizations
Time
HF=heart failure; LV=left ventricular
1. Alla et al. Heart Fail Rev 2007;12:91–5; 2. Gheorghiade et al. Am J Cardiol
2005;96:11G–17G
More rapid
decline in
chronic HF
Acute
decompensation
Cardiac and renal
damage/ incomplete
recovery
Clinical classification of acute heart failure
reflects a spectrum of overlapping
presentations
• >50% incidence for ↑SBP1
• Mainly pulmonary rather than
systemic congestion1
• Many patients have
preserved ejection fraction1
• 70% incidence1
Hypertensive
AHF
Acutely
decompensated
chronic HF
• <3% incidence1
• Clinical characteristics:
severe dyspnea, tachypnea,
tachycardia and hypoxemia,
which may require immediate
airway intervention1
Pulmonary
edema
ACS and
HF
Cardiogenic
shock
Right HF
• Unknown incidence1
• Many patients have signs and
symptoms of ACS that
resolve after initial therapy or
resolution of ischemia1
• Acute HF frequently
precipitated by or associated
with an arrhythmia2
• Usually a history of
progressive worsening of
chronic HF on treatment and
evidence of systemic and
pulmonary congestion2
• <1% incidence1
• Primarily complicating acute MI,
fulminant myocarditis1
• Tissue hypoperfusion after
adequate correction of preload
and major arrhythmia2
ACS=acute coronary syndrome; AHF=acute HF; HF=heart failure;
JVP=jugular venous pressure; LV=left ventricular;
MI=myocardial infarction; SBP=systolic blood pressure
1. Gheorghiade et al. Circulation 2005;112:3958–68; 2. Dickstein et al. Eur Heart J 2008;29:2388–442
• Unknown incidence1
• Low output syndrome in the
absence of pulmonary
congestion, increased JVP
and low LV filling pressures2
The Short-term and long-term
Pathophysiogical consequences of AHF‡
Processes mediating short-term effects
Initiation phase
Vasoconstriction
Decreased
cardiac function
Processes mediating long-term effects
Amplification phase
O2 supply-demand
mismatch
Fluid
overload
Hemodynamic
abnormalities
INCREASE
Myocardial
overload and
renal
dysfunction
Myocardial
damage
as shown by
↑hs-cTnT
Neurohormonal
activation
Oxidative
stress
INCREASE
Inflammation
INCREASE
Myocardial
fibrosis and
remodelling
as shown by
↑fibroblast
proliferation
and activation
Renal
damage
as shown by
↑uric acid
INCREASE
Renal
dysfunction
as shown by
↑Cystatin C,
↑Creatinine,
↑BUN
INCREASE
INCREASE
NTNT-p r
proBNP
Preload
Afterload
Congestion
Organ damage and
dysfunction
‡Proposed schematic of acute heart failure pathophysiology
Biolo et al. Circ Heart Fail 2010;3:44–50; Bott-Flügel et al. Eur J Heart Fail 2008;10:129–32; Cotter et al. Am Heart J 2008;155:9–18; Cotter et al. Eur J Heart Fail 2008;10:165–69;
Feng & Wang. J Geriatr Cardiol 2008;5:1–6; Hunt et al. J Am Coll Cardiol 2009;53:e1–e90; Oikonomou et al. Hellenic J Cardiol 2011;52:30–40; Tsutsui et al. Am J Physiol Heart Circ
Physiol 2011;301:H2181–90
Patterns of ventricular remodelling are
different for HFrEF and HFpEF
HFrEF – a condition of
volume overload
• characterized by
eccentric hypertrophy
• results in globular heart
with thinning of the LV
walls, decreased systolic
function and enlarged
left ventricular volume
Left ventricle
volume
overload
HFrEF
Left ventricle
normal
HFpEF
Volume
overload
Pressure
overload
Increased
diastolic pressure
Increased
systolic pressure
Increased
systolic wall stress
Increased
systolic wall stress
Series addition of
new sarcomeres
Parallel addition
of new myofibrils
Chamber
enlargement
Wall
thickening
Eccentric
hypertrophy
Concentric
hypertrophy
HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction
Adapted from Colucci (Ed.). Atlas of Heart Failure, 5th ed. Springer 2008; Grossman et al. In: Perspectives
in Cardiovascular Research; Myocardial Hypertrophy and Failure. Vol 7. Edited by Alpert NR. New York:
Raven Press;1993:1–15
HFpEF – a condition of
pressure overload
• characterized by
concentric hypertrophic
growth
• results in normal sized LV
cavity with thickened
walls and preserved
systolic function
Left ventricle
pressure
overload
Long-term Consequences of AHF: Higher NTproBNP levels are associated with increased
risk of mortality in patients with AHF
Higher levels of NT-proBNP are associated
with increased risk of mortality by 90 days
in patients hospitalized for AHF‡2
NT-proBNP
levels
increase
During
episodes
of AHF1
Quartile of
NT-proBNP
Hazard
Ratio
95% CI
p
value
1st
1.0
2nd
1.7
0.7–4.4
0.247
3rd
2.5
1.0–6.0
0.043
4th
4.3
1.9–9.9
<0.001
0.1
1
Hazard ratio
AHF=acute heart failure; CI=confidence interval; NT-proBNP=N-terminal-pro-B-type natriuretic peptide
‡Analysis of data from 568 patients hospitalized for AHF in the Biomarkers in Acute Heart Failure (BACH) study
†The NT-proBNP cutoffs were 2,248, 5,017, and 10,455 pg/mL for the 25th, 50th and 75th percentiles, respectively
1. Biolo et al. Circ Heart Fail 2010;3:44–50; 2. Maisel et al. J Am Coll Cardiol 2010;55:2062–76
10
Reference
Long-term Consequences of AHF: Cardiac
troponin, a marker of myocyte injury/death, is
commonly elevated in AHF and is associated
with increased mortality
Troponin is
often released
in patients
with AHF1
Higher levels of troponin T predict
greater mortality in patients with AHF‡2
All-cause mortality at 6 months (%)
P=0.002
P=0.007
31.5
27.8
Elevated
troponin
14.1
is associated with
poor outcomes
in AHF1
<0.03
0.03–0.07
>0.07
Cardiac troponin T (g/L)
AHF=acute heart failure
‡Analysis of data from 364 patients hospitalized for AHF from the Finnish Acute Heart Failure (FINN-AKVA) study
1. Kociol et al. J Am Coll Cardiol 2010;56:1071–8; 2. Ilva et al. Eur J Heart Fail 2008;10:772–9
Long-term Consequences of AHF: Worsening
renal function in patients hospitalized for AHF
predicts poor outcomes
Further
worsening of
renal function
occurs in ~25%
of patients
hospitalized
for AHF#3,4
1.
2.
3.
4.
5.
Maggioni et al. Eur J Heart Fail 2010;12:1076–84;
Rudiger et al. Eur J Heart Fail 2005;7:662–70;
Forman et al. J Am Coll Cardiol 2004;43:61–7;
Akhter et al. Am J Cardiol 2004;94:957–60;
Lassus et al. Eur Heart J 2010;31:2791–98
0.5
>0.5 mg/L increase
in cystatin C
0.4
Cumulative mortality
~30–40%
of patients
hospitalized for
AHF have renal
impairment†1,2
An increase in cystatin C in the
first 48 hours following hospitalization for
AHF is associated with poor prognosis‡5
0.3
≤0.5 mg/L increase
in cystatin C
0.2
0.1
0
0
100
200
300
400
Days
AHF=acute heart failure
†Renal impairment defined as an estimated glomerular filtration rate <50 mL/min/1.73 m2 or creatinine clearance <50 mL/min;
#Worsening of renal function defined as an increase in serum creatinine of >0.3 mg/dL or >0.5 mg/dL;
‡Analysis of data from 292 patients hospitalized for AHF from the Finnish Acute Heart Failure (FINN-AKVA) study
Item Code: 153049 Copyright © Novartis Pharma AG.