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

Chronic HF
Cardiac function and quality of life

Acute
Increased risk of decompensation
decompensations

Hospitalizations Cardiac and renal

More rapid damage/ incomplete
decline in recovery
Time chronic HF

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
 Clinical classification of acute heart failure
reflects a spectrum of overlapping
presentations

• >50% incidence for ↑SBP1

• Mainly pulmonary rather than
systemic congestion1 • 70% incidence1

• Many patients have Hypertensive • Usually a history of

preserved ejection fraction1 AHF progressive worsening of
chronic HF on treatment and
Acutely
evidence of systemic and
decompensated
pulmonary congestion2
• <3% incidence1 chronic HF

• Clinical characteristics: Pulmonary

severe dyspnea, tachypnea, edema
tachycardia and hypoxemia, ACS and
which may require immediate HF
airway intervention1
Right HF • Unknown incidence1
Cardiogenic
shock • Low output syndrome in the
absence of pulmonary
• Unknown incidence1 congestion, increased JVP
• Many patients have signs and and low LV filling pressures2
• <1% incidence1
symptoms of ACS that
resolve after initial therapy or • Primarily complicating acute MI,
resolution of ischemia1 fulminant myocarditis1
• Acute HF frequently • Tissue hypoperfusion after
precipitated by or associated adequate correction of preload
with an arrhythmia2 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
 The Short-term and long-term
Pathophysiogical consequences of AHF‡

Processes mediating short-term effects Processes mediating long-term effects

Initiation phase Amplification phase

O2 supply-demand
mismatch
Vaso- Decreased Fluid
constriction cardiac function overload Hemodynamic Neurohormonal Oxidative Inflammation
abnormalities activation stress

INCREASE INCREASE INCREASE INCREASE

Myocardial Myocardial
Renal
overload and Myocardial fibrosis and Renal dysfunction
renal damage remodelling damage as shown by
dysfunction as shown by
as shown by as shown by ↑Cystatin C,
↑fibroblast
↑hs-cTnT ↑uric acid ↑Creatinine,
proliferation
↑BUN
and activation

INCREASE
INCREASE

Preload
NT- Afterload
proBNP
NT-p r
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 HFpEF – a condition of

volume overload pressure overload
Left ventricle
• characterized by HFrEF normal
HFpEF • characterized by
eccentric hypertrophy concentric hypertrophic
• results in globular heart Volume Pressure growth
with thinning of the LV overload overload • results in normal sized LV
walls, decreased systolic cavity with thickened
function and enlarged Increased Increased walls and preserved
left ventricular volume diastolic pressure systolic pressure systolic function

Increased Increased
systolic wall stress systolic wall stress

Series addition of Parallel addition

new sarcomeres of new myofibrils

Chamber Wall
enlargement thickening

Eccentric Concentric
Left ventricle hypertrophy hypertrophy Left ventricle
volume pressure
overload overload

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
 Long-term Consequences of AHF: Higher NT-
proBNP 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
Quartile of Hazard p
levels NT-proBNP Ratio 95% CI value

increase
1st 1.0 Reference

2nd 1.7 0.7–4.4 0.247

During
episodes 3rd 2.5 1.0–6.0 0.043
of AHF1
4th 4.3 1.9–9.9 <0.001

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
 Long-term Consequences of AHF: Cardiac
troponin, a marker of myocyte injury/death, is
commonly elevated in AHF and is associated
with increased mortality

Higher levels of troponin T predict

Troponin is greater mortality in patients with AHF‡2
often released
in patients All-cause mortality at 6 months (%)
with AHF1 P=0.002
P=0.007

Elevated
troponin
is associated with
poor outcomes
in AHF1

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

An increase in cystatin C in the

first 48 hours following hospitalization for
~30–40% AHF is associated with poor prognosis‡5
of patients
hospitalized for 0.5
>0.5 mg/L increase
AHF have renal in cystatin C
impairment†1,2 0.4

Cumulative mortality
0.3 ≤0.5 mg/L increase
in cystatin C

Further 0.2

worsening of
0.1
renal function
occurs in ~25%
0
of patients
0 100 200 300 400
hospitalized Days
for AHF#3,4
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;
1. Maggioni et al. Eur J Heart Fail 2010;12:1076–84; #Worsening of renal function defined as an increase in serum creatinine of >0.3 mg/dL or >0.5 mg/dL;
2. Rudiger et al. Eur J Heart Fail 2005;7:662–70; ‡Analysis of data from 292 patients hospitalized for AHF from the Finnish Acute Heart Failure (FINN-AKVA) study
3. Forman et al. J Am Coll Cardiol 2004;43:61–7;
4. Akhter et al. Am J Cardiol 2004;94:957–60;
5. Lassus et al. Eur Heart J 2010;31:2791–98 Item Code: 153049 Copyright © Novartis Pharma AG.