Transcript General Heart Failure

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SE1602441959
General Heart Failure
Deck for external distribution
Upon unsolicited requests
Created 2015-09-30
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Introduction to heart failure:
History
3
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Our understanding of HF has evolved over time
 The Ancient Egyptian text, Ebers papyrus, contains some of the earliest
documented observations of the syndrome of HF1,2
 The term “dropsy”, derived from the Greek word for water, was used to
describe a syndrome of fluid overload and the symptoms synonymous
with HF for many centuries2
Changing views of HF3
A clinical syndrome
Disordered fluid balance
A circulatory disorder
Altered architecture of the heart
Abnormal hemodynamics
Biochemical abnormalities
Maladaptive hypertrophy
Genomics
Epigenetics
4
*Century in which the view of HF was first described
BCE=before common era; CE=common era; HF=heart failure
Century*
th
5 BCE
th
16 CE
th
17 CE
th
18 CE
th
19 CE
th
20 CE
th
20 CE
Ebers papyrus, an
Egyptian medical papyrus
th
20 CE
st
21 CE
1. Saba et al. J Card Fail 2006;12:416–21
2. Ventura & Mehra. J Card Fail 2005;11:247–52
3. Katz. Circ: Heart Fail 2008;1:63–71
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Introduction to heart failure:
Definition
5
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HF – abnormality of cardiac structure and/or function
 Abnormality of cardiac structure or function leads to failure of the heart to adequately
perfuse organ systems1
 Weakening or stiffening of the heart muscle over time leads to pump failure and insufficient
delivery of blood around the body2
Normal heart
HF
Weakened heart
muscle
6
HF=heart failure
1. McMurray et al. Eur Heart J 2012;33:1787–847
2. Harrison’s ‘Principles of Internal Medicine’, Seventeenth Edition p1442–55
Images from: Wilde and Behr. Nat Rev Cardiol 2013;10:571–83
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A progressive condition with high mortality
Clinical manifestations
 Increasing frequency of acute events with disease progression leads to high rates of
hospitalization and increased risk of mortality
 With each acute event, myocardial injury may contribute to progressive LV dysfunction
Chronic decline
Function
& quality
of life
(QoL)
Mortality
Acute episodes
Disease progression
LV: left ventricular
Gheorghiade et al. Am J Cardiol 2005;96:11G–17G;
Gheorghiade & Pang. J Am Coll Cardiol 2009;53:557–73
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Chronic HF can be classified as HF with reduced or
preserved ejection fraction
HF with preserved ejection fraction
(HFpEF)1–4
HF with reduced ejection
fraction (HFrEF)1–4
Dysfunction
Diastolic
Systolic-diastolic
LVEF
>40–50%
≤35–40%
LV remodeling
Concentric
Eccentric
Characteristic
• Normal end-diastolic volume
• ↑ wall thickness and mass
• High ratio of mass:volume
Prognostic improvement with
current HF therapy
8
HF=heart failure; LV=left ventricular;
LVEF=left ventricular ejection fraction
No
• ↑ end-diastolic volume
• ↓ wall thickness
• Low ratio of mass:volume
Yes, but morbidity and mortality
remain high
1. Aurigemma. Circulation 2006;113;296–304
2. Paulus et al. Eur Heart J 2007;28:2539–50
3. Colucci (Ed.). Atlas of Heart Failure, 5th ed. Springer 2008
4. McMurray et al. Eur Heart J 2012;33:1787–847
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Terminology related to left ventricular ejection fraction
9
McMurray et al. Eur Heart J 2012;33:1787–847
Figure from: http://www.cardiachealth.org/heart-information/heart-failure
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HFrEF vs HFpEF
Systolic
dysfunction
Diastolic
dysfunction
HFrEF
EF≤35–40%
EF≤35–40%
HFpEF
HFpEF
EF>40–50%
EF>40–50%
 Echocardiography is a useful method for evaluating left ventricular ejection fraction
HFrEF: heart failure with reduced ejection fraction; HFpEF: heart failure with preserved ejection fraction
McMurray et al. Eur Heart J 2012;33:1787–847; Dickstein et al. Eur Heart J 2008;29:2388–442
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Determing ejection fraction
McMurray et al. Eur Heart J 2012;33:1787–847; Dickstein et al. Eur Heart J 2008;29:2388–442
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There is a lack of consensus regarding the definition of HFpEF
 In patients with HFpEF, the ventricles are unable to relax properly when the heart
contracts. Consequently, during filling, less blood enters the heart and the
ejection fraction may be considered normal1
 There is no consensus concerning the cut-off for preserved LVEF2
 Approximately half of patients presenting with symptoms of HF have HFpEF2
• patients with an LVEF in the range 40–50% represent a ‘grey area’ and may have
primarily mild systolic dysfunction3
Definite HFrEF
(LVEF <40%)4
Uncertain
(40% ≤LVEF <50%)4
50%
14%
Definite HFpEF
(LVEF ≥50%)4
36%
Proportion of patients
12
HF=heart failure; HFpEF=heart failure with
preserved ejection fraction; HFrEF=heart
failure with reduced ejection fraction;
LVEF=left ventricular ejection fraction
1. Hsich & Wilkoff. Clevelandclinic.org 2013. Available at:
http://my.clevelandclinic.org/services/heart/disorders/heart-failure-what-is/ejectionfraction. Last
accessed 9 Jan 2014; 2. Dickstein et al. Eur Heart J 2008;29:2388–442; 3. McMurray et al.
Eur Heart J 2012;33:1787–847; 4. Steinberg et al. Circulation 2012;126:65–75
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Pathophysiology:
Risk factors
Myocardial injury to the heart
Initial fall in left ventricle
performance
Activation of RAAS and SNS to
maintain cardiac output
RAAS: stimulates
vasoconstriction, salt and
water retention
SNS: stimulates
vasoconstriction, increases
heart rate and contractility
Systemic effects of neurohormonal activation
= pathophysiological ‘vicious cycle’
LV: left ventricular; RAAS: renin-angiotensin-aldosterone system, SNS: sympathetic nervous system
Krum, Abraham. Lancet 2009;373:941–55; Khan. Cardiac Drug Therapy, 6th ed. 2003; Philadelphia: Saunders WB
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Renin Angiotensin Aldosterone System
Pathophysiology
ACE: angiotensin-converting-enzyme; ADH: antidiuretic hormone
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Sympathetic (or adrenal) Nervous System
Pathophysiology
Heart
 The SNS exerts a wide
Postganglionic
ANS neurons
variety of cardiovascular
effects:
(-)
• Heart rate acceleration
• Increased cardiac
contractility
(+)
Vessels
- Arterial baroreflex
- Cardiopulmonary
reflex
- Arterial chemoreflex
- CSAR
Postganglionic
cholinergic neurons
Preganglionic
ANS neurons
• Peripheral
vasoconstriction
Spinal Cord
Adrenal
Preganglionic
ANS neurons
Prevertebral ganglia
Epinephrine
Paravertebral
ganglia
ANS: autonomic nervous system; CSAR: cardiac sympathetic afferent reflex; SNS: sympathetic nervous system
Lymperopoulos et al. Circ Res 2013;113:739–53
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Effects of the long term neurohormonal activation
Pathophysiology
Risk factors
Myocardial injury to the heart
Initial fall in LV performance
Activation of RAAS and SNS to
maintain cardiac output
Remodeling and
progressive worsening of
LV function
Fibrosis, apoptosis, hypertension,
hypertrophy, cellular and molecular
alterations, myotoxicity
Morbidity and mortality:
arrhythmias, pump failure
Hemodynamic alterations,
salt and water retention
HF symptoms: dyspnea,
edema, fatigue
LV: left ventricular; RAAS: renin-angiotensin-aldosterone system, SNS: sympathetic nervous system
Krum, Abraham. Lancet 2009;373:941–55; Khan. Cardiac Drug Therapy, 6th ed. 2003; Philadelphia: Saunders WB
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Initial diagnosis of HF can be complex
Initial
clinical
examination
Assess
cardiac
function
Evaluate
cause
17
Assessment of signs and symptoms, patient history and physical
examination
Tests include echocardiography, chest X-ray and ECG. Other tests
such as radionuclide ventriculography, MRI, computed tomography
may also be carried out to provide information on the nature and
severity of cardiac abnormality
Laboratory tests used to assist with the identification of etiology inlcude
complete blood count, urinalysis, serum electrolytes, glycohemoglobin,
blood lipids and tests of renal and hepatic function, as well as BNP (or NTproBNP levels) and Troponin I or T
BNP=B-type natriuretic peptide; ECG=electrocardiogram;
HF=heart failure; MRI=magnetic resonance imaging; NTproBNP=N-terminal pro-B-type natriuretic peptide
Dickstein et al. Eur Heart J 2008;29:2388–442
Hunt et al. J Am Coll Cardiol 2009;53:e1–90
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Signs and symptoms
Clinical manifestations
Tiredness
Shortness of breath
 Symptoms
• Breathlessness
• Orthopnea
Coughing
Pumping action
of the heart
grows weaker
Fluid retention
• Paroxysmal Nocturnal Dyspnea
• Reduced exercise tolerance
Pleural effusion
• Fatigue
• Ankle swelling
 Signs
Swelling of feet,
ankles, abdomen
and lower back
area
• Elevated jugular venous pressure
• Hepato-jugular reflux
• Third heart sound
• Laterally displaced apical impulse
• Cardiac murmur
Pulmonary edema
McMurray et al. Eur Heart J 2012;33:1787–847
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Frequency of signs and symptoms
Clinical manifestations of acute heart failure
100
Signs and symptoms in 4,537 residents of Worcester, Massachusetts, USA,
hospitalized for acute HF between 1995 and 2000
Patients (%)
80
60
40
20
0
Goldberg et al. Clin Cardiol 2010;33:e73–80
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Frequency of signs and symptoms
Clinical manifestations of chronic heart failure
Signs and symptoms in a small study conducted by two cardiac outpatient centers
from the US
Patients (%)
Frequency of signs and symptoms
70
60
50
40
30
20
10
0
Bekelman D et al. J Card fail 2007;13:643-648
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Symptomatic severity of heart failure
Clinical manifestations
New York Heart Association functional classification
based on severity of symptoms and physical activity
Class I
No limitation of physical activity. Ordinary
physical activity does not cause undue
breathlessness, fatigue, or palpitations.
Class II
Slight limitation of physical activity.
Comfortable at rest, but ordinary physical
activity results in undue breathlessness,
fatigue, or palpitations.
Class III
Marked limitation of physical activity.
Comfortable at rest, but less than
ordinary physical activity results in undue
breathlessness, fatigue, or palpitations.
Class IV
Unable to carry on any physical activity
without discomfort. Symptoms at rest can
be present. If any physical activity is
undertaken, discomfort is increased.
 Clear relationship between severity
of symptoms and survival
 Poor relationship between severity
of symptoms and ventricular
function
 Patients with mild symptoms may
still have a relatively high absolute
risk of hospitalization and death
McMurray et al. Eur Heart J 2012;33:1787–847
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NYHA class is related to prognosis in chronic HF
Clinical manifestations
 Among 411 outpatients with NYHA class II, III or IV HF, total mortality was 7.1%,
15.0% and 28.0%, respectively during a mean follow-up period of 1.4 years
Survival probability according
to NYHA class
1.0
NYHA II
0.9
NYHA III
0.8
NYHA IV
0.7
P<0.001
0.6
0
3
6
9
12
15
Time (months)
NYHA: New York Heart Association
Muntwyler et al. Eur Heart J 2002;23:1861–6
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A number of diagnostic assessments support the
presence of HF
23
Assessment of
symptoms
Compatible symptoms include breathlessness, fatigue, angina, palpitations or
syncope
Assessment
of signs
Compatible signs should include appearance, pulse, BP, fluid overload,
respiratory and heart rate
ECG
ECG changes are common (e.g. presence of new Q waves reflecting a MI;
wave abnormalities reflecting ischemia, or an arrhythmia). If the ECG is
completely normal, HF, especially with systolic dysfunction, is unlikely (<10%)
Laboratory
analyses
Elevated BNP/NT-proBNP, hyponatremia, renal dysfunction, mild elevations of
troponin
Chest X-ray
Permits assessment of pulmonary congestion and may demonstrate important
pulmonary or thoracic causes of dyspnea
Echocardiography
Provides extensive information on cardiac anatomy, wall motion and valvular
and ventricular function; used to confirm HF diagnosis
BNP=B-type natriuretic peptide; BP=blood pressure;
ECG=echocardiograph; HF=heart failure; MI=myocardial
infarction; NT-proBNP=N-terminal pro-B-type natriuretic
peptide
Dickstein et al. Eur Heart J 2008;29:2388–442
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BNP and NT-proBNP measurement is useful for the
diagnosis of HFrEF
Clinical examination, ECG,
chest X-ray, echocardiography
Natriuretic peptides
BNP <100 pg/mL
NT-proBNP <400 pg/mL
BNP 100–400 pg/mL
NT-proBNP 400–2,000 pg/mL
BNP >400 pg/mL
NT-proBNP >2,000 pg/mL
Chronic HF unlikely
Uncertain diagnosis
Chronic HF likely
 Clinical usefulness of BNP and NT-proBNP testing in patients with chronic HF:
• diagnosis of chronic HF in patients with dyspnea
• prognosis and risk stratification
• screening for chronic HF in high-risk populations
• monitoring and guiding treatment
• treatment with recombinant BNP
24
BNP=B-type natriuretic peptide; ECG=electrocardiograph;
HF=heart failure; HFrEF=heart failure with reduced ejection
fraction; NT-proBNP=N-terminal pro-B-type natriuretic peptide
Dickstein et al. Eur Heart J 2008;29:2388–442
Melanson, Lewandrowski. Am J Clin PathoI 2005;124:S122–
8
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Introduction to heart failure:
Epidemiology
25
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HF is a common clinical condition
Prevalence
Approximately 1–2% of the adult population in developed countries
has HF, with the prevalence rising to ≥10% among persons
70 years of age or older1
Incidence
Mortality
26
HF=heart failure
Over 650,000 new cases of HF are diagnosed annually in the
USA2 and more than 25,000 new cases are reported every year
in the UK3
The mortality rate for patients with chronic HF is as high as 50% at
5 years post-diagnosis4–5
1. McMurray et al. Eur Heart J 2012;33:1787–847; 2. Yancy et al. JACC 2013;62:e147–239
3. Townsend et al. 2012 Coronary heart disease statistics 2012 edition.
Available at: https://www.bhf.org.uk/publications/statistics/coronary-heart-disease-statistics-2012
4.Roger et al. JAMA 2004;292:344–50; 5. Levy et al. NEJM 2002;347:1397–402
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HF is increasing in prevalence
Hospital discharges for HF by gender (USA: 1979–2006)*
700
Discharges in thousands
Male
600
500
400
300
200
100
0
27
Female
79
80
85
*Hospital discharges include people discharged alive, dead and of unknown status
HF=heart failure
90
Years
95
00
05
Lloyd-Jones et al. Circulation 2010;121:e46–e215
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Prevalence of HFpEF is consistent worldwide
 Large European, USA and Asian registries have consistently demonstrated that 40–50% of
patients hospitalized for acute HF have a preserved LVEF1–3
 The ‘true’ overall prevalence of HFpEF in the general population has been estimated at
1.1–5.5%4
Registry
Region
Total patients
assessed
EuroHeart Failure Survey1
Europe
6,806
46%
USA
52,187
50.4%
Japan
1,692
42%*
ADHERE2
JCARE-CARD3
HFpEF
(LVEF ≥40%)
*26% with LVEF ≥50%, 16% with LVEF 40–50%
28
ADHERE=Acute Decompensated Heart Failure National Registry;
HF=heart failure; HFpEF=heart failure with preserved ejection fraction;
JCARE-CARD=Japanese Cardiac Registry of Heart Failure in
Cardiology; LVEF=left ventricular ejection fraction
1. Lenzen et al. Eur Heart J 2004;25:1214–20
2. Yancy et al. J Am Coll Cardiol 2006;47:76–84
3. Tsuchihashi-Makaya et al. Circ J 2009;73:1893–900
4. Owan, Redfield. Prog Cardiovasc Dis 2005;47:320–32
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Trends show that prevalence of HFpEF is increasing
 Prevalence of HFpEF among patients with a discharge diagnosis of HF increased from
38% to 54% from 1987–20011
 Increasing prevalence of HFpEF may be a consequence of growing recognition,
population aging and increases in hypertension and obesity2
Patients with preserved
ejection fraction (%)
70
60
50
40
30
20
0
1986
29
r=0.92, p<0.001
1990
1994
Data based on n=4,596 patients with LVEF measurements and a discharge diagnosis of HF from Mayo Clinic
Hospitals, Minnesota, USA over a 15-year period between 1987 and 2001. HFpEF was defined as LVEF ≥50%;
Solid lines represent the regression lines and the dashed line indicates 95 percent confidence intervals.
HF=heart failure; HFpEF=heart failure with preserved ejection fraction; LVEF=left ventricular ejection fraction
1998
2002
1. Owan et al. N Engl J Med 2006;355:251–9
2. Blanche et al. Swiss Med Wkly 2010;140:66–72
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HFpEF is more common in women than in men
 Distribution of LVEF amongst women (n=2,048) and men (n=3,249) enrolled in the
EuroHeart Failure survey
•
51% of men but only 28% of women had LVEF <40%
14.0
Women
Men
12.0
Patients (%)
10.0
8.0
6.0
4.0
2.0
0
<10
10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–80
LVEF (%)
30
HFpEF=heart failure with preserved ejection fraction;
LVEF=left ventricular ejection fraction
Cleland et al. Eur Heart J 2003;24:442–63
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Rates of initial hospital admission are similar in patients with
HFpEF and HFrEF
 In a retrospective study of 451 patients with HF in Sweden, time from diagnosis to first
post-diagnosis CV- or HF-related hospitalization was not significantly different between
HFpEF and HFrEF (p=0.49 and p=0.08, respectively)
Time to first CV hospitalization
Time to first HF hospitalization
1.00
Survival distribution function
Survival distribution function
1.00
0.75
0.50
0.25
0
0.75
0.50
0.25
0
0
31
HFpEF (LVEF >45%)
HFrEF (LVEF ≤45%)
200
400
600
Time (days)
800
CV=cardiovascular; HF=heart failure; HFpEF=heart failure with
preserved ejection fraction; HFrEF=heart failure with reduced
ejection fraction; LVEF=left ventricular ejection fraction
1,000
0
200
400
600
Time (days)
800
1,000
Wikstrom et al. ESC 2011 Gothenburg, Sweden, May 21–24, 2011
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Rates of hospital readmission are similar in patients with
HFpEF and HFrEF

In patients with new-onset HF, rates of readmission for HF and in-hospital complications
do not differ substantially between HFpEF and HFrEF1
p=0.09
Percentage of patients
18
16.1
16
13.5
14
12
HFpEF
10
8
6
HFrEF
p=0.66
4.5
4.9
4
2
0
30-day readmission
for HF*

32
1-year readmission
for HF*
Patients with HFpEF are as likely as those with HFrEF to be readmitted following hospital discharge, with a
re-hospitalization rate of 29% within 60–90 days,2 and a median time to re-hospitalization of 29 days3
*Readmission rates were calculated for the 2,339 patients who
survived the index admission: 1,493 with HFrEF and 846 with HFpEF
HF=heart failure; HFpEF=heart failure with preserved ejection fraction;
HFrEF=heart failure with reduced ejection fraction
1. Bhatia et al. N Engl J Med 2006;355:260–9
2. Fonarow et al. J Am Coll Cardiol 2007;50:768–77
3. Lenzen et al. Eur Heart J 2004;25:1214–20
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Mean length of hospital stay increases with each
rehospitalization for HF
Length of hospital stay following hospitalization for HF
Mean length of stay (days)
8.5
8.0
7.5
7.0
6.5
6.0
33
All HF
HFrEF
HFpEF
Acute HF
Chronic HF
First
Second
Third
Fourth
Hospitalization
278,307 patients in the USA with ≥1 hospitalization with a HF claim were followed from
first HF hospitalization for 24 months or until disenrollment or end of data availability
HF=heart failure; HFrEF=heart failure with reduced ejection fraction; HFpEF= heart
failure with preserved ejection fraction
Fifth
Korves et al. Presented at the American Heart Association
Quality of Care and Outcomes Research in Cardiovascular
Disease and Stroke 2010 Scientific Sessions,
Washington, D.C., May 19–21, 2010
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HFpEF and HFrEF are associated with similarly high levels
of mortality

Survival rate among patients with a discharge diagnosis of HF in the USA was slightly higher among
patients with HFpEF than those with HFrEF between 1987–20011
•
respective mortality rates were 29% and 32% at 1 year and 65% and 68% at 5 years
1.0
HFrEF (LVEF <50%)
HFpEF (LVEF ≥50%)
Survival
0.8
0.6
0.4
0.2
p=0.03
0
0

34
1
2
Year
3
4
5
HFpEF is associated with significant morbidity and mortality, despite having a slightly higher survival rate
compared with HFrEF2,3
HF=heart failure; HFpEF=heart failure with preserved ejection fraction;
HFrEF=heart failure with reduced ejection fraction;
LVEF=left ventricular ejection fraction
1. Owan et al. N Engl J Med 2006;355:251–9
2. Blanche et al. Swiss Med Wkly 2010;140:66–72
3. Meta-analysis Global Group in Chronic Heart Failure
(MAGGIC). Eur Heart J 2012;33:1750–7
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Unlike HFrEF, survival rates have not improved over time
for HFpEF
 Survival rate among patients with a discharge diagnosis of HFpEF has not changed
significantly over time
Patients with HFpEF (LVEF ≥50%)
1.0
1.0
1987–1991
1992–1996
1997–2001
0.6
0.4
1987–1991
1992–1996
1997–2001
0.8
Survival
0.8
Survival
Patients with HFrEF (LVEF <50%)
0.6
0.4
0.2
0.2
p=0.005
p=0.36
0
0
0
1
2
3
Year
35
HFpEF=heart failure with preserved ejection fraction;
HFrEF=heart failure with reduced ejection fraction;
LVEF=left ventricular ejection fraction
4
5
0
1
2
3
4
5
Year
Owan et al. N Engl J Med 2006;355:251–9
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HF has a detrimental effect on QoL
 Patients with HF commonly
report psychological distress,
including1
Concepts frequently reported as important
by patients with HF2
Impact of HF
Number of patients
reporting impact
(n=15)
Physical mobility
14/15
Physical activity
limitations
14/15
Daily activities
12/15
Emotional impacts
11/15
Lifestyle
11/15
Self-care
3/15
Sleep disturbance
3/15
• depression
• hostility and anxiety
• limitation in their activities of
daily living
• disruption of work roles and social
interaction with friends and family
• reduced sexual activity and
satisfaction
36
HF=heart failure; QoL=quality of life
1. Grady. Crit Care Nurs Clin North Am 1993;5:661–70
2. Gwaltney et al. Presented at the American Heart Association Quality of Care and Outcomes
Research in Cardiovascular Disease and Stroke 2010 Scientific Sessions,
Washington, D.C., May 19–21, 2010
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Health-related QoL is similar for patients with HFrEF and
HFpEF

Distribution of MLHF QoL scores reflects the wide range of health-related QoL among patients with
chronic HF1
•
patients with HFpEF and those with HFrEF have a similar distribution of MLHF QoL scores
16
HFpEF (LVEF >40%)
HFrEF (LVEF ≤40%)
Percent distribution
14
12
10
8
6
4
2
0
0–<10 10 –<20 20 –<30 30 –<40 40 –<50 50 –<60 60 –<70 70 –<80 80 –<90
Better QoL

37
MLHF summary score range
>90
Worse QoL
Patients with HFpEF may have greatly reduced general and symptom-specific QoL2
Distribution of the MLHF questionnaire responses in patients (n=2709) with HFpEF and
HFrEF. Scores range from 0 to 105 with a low score reflecting a better health-related QoL
HF=heart failure; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart
failure with reduced ejection fraction; LVEF=left ventricular ejection fraction;
MLHF=Minnesota Living with Heart Failure; QoL=quality of life
1. Lewis et al. Eur J Heart Fail 2007;9:83–91
2. Kitzman et al. JAMA 2002;288:2144-50
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HF imposes a significant burden on the carer
 Caregiving tasks related to feelings of burden include1
• personal care, such as assisting with washing and bathing and moving in and
around the house
 Caregiving burden in partners of patients with HF is similar to that in
partners of patients with cancer1
 HF caregivers report being socially isolated, physically exhausted and
unprepared for the stress of the caregiver role, with sleep and anxiety
issues over current and future needs, and worry over financial
concerns2
 Older caregivers experience decreased physiological functioning,
increased risk of health problems, and increased risk of mortality3
• caregivers experiencing heightened emotional strain from caregiving also
face a greatly increased mortality3
38
HF=heart failure
1. Luttik et al. Eur J Heart Fail 2007;9:695–701
2. Saunders. West J Nurs Res 2008;30:943–59
3. Schulz & Beach. JAMA 1999;282:2215–19
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