An Evidence-Based Review:
Congestive Heart Failure
Mike Mendoza, MD, MPH
Chief Resident
Department of Family and Community Medicine
September 2004
Overview
• Pathophysiology
• Diagnosis of CHF
• ACC / AHA Reclassification of CHF
• Pharmacologic Treatments
• Diastolic Heart Failure
The Syndrome of Heart Failure
Circulation. 1999;100:999-1008
It’s Not Just About Diuresis and
Digoxin Anymore, Toto!
• Long-term reduction of
circulating volume and
improvement of cardiac
function alone do not
prevent progression of
disease.
• Treatment focused only
on diuresis and inotropy
is insufficient.
The “Neurohumoral” Effect
• Plays a role in compensatory
mechanisms resulting from
the initial cardiac insult.
– Sympathetic Nervous System
– Renin-Angiotensin System
• Successful treatment of heart
failure must account for these
neurohumoral processes.
Jessup M, NEJM 2003; 348:2007-18.
Sympathetic Nervous System
• Adaptive mechanism if you
are being consumed by a
dinosaur.
• Counterproductive in heart
failure.
– Sodium (i.e., volume)
retention
– Increased peripheral
resistance through
vasoconstriction
– Increased release and
decreased reuptake of NE
Circulating Evil Humours
• In a series of patients with stable CHF
treated with digoxin but NOT diuretics,
ACE-Is or beta-blockers…
Francis, GS et al Ann Intern Med 1984; 101:370
Increases in NE are Bad
• Increases in circulating norepinephrine
confer worse prognosis.
• ValHeFT Study
Renin-Angiotensin-Aldosterone
The Role of Remodeling
• Ventricular
remodeling results
in decline of overall
pump function of
the heart
• Trials aimed at
reducing remodeling
showed a return
normal ventricular
size and shape.
Jessup M, NEJM 2003; 348:2007-18.
Remodeling
• The SOLVD study demonstrated
that enalapril significantly
improved clinical course of
patients with LVSD.
• The SOLVD-Echo Substudy
sought to determine the basis
for this improvement.
• A subset of the original patients
in the treatment and placebo
groups underwent TTE.
SOLVD Study. Circulation 1995;91:2573-2581.
Clinical Diagnosis of CHF
• Can be difficult based on history and exam alone.
• Cross-sectional study of 259 patients thought to have
CHF by conventional clinical criteria underwent TTE.
• Clinical findings then correlated to presence of LVSD
(LVEF < 25%) on echo.
• Only 16% of patients suspected to have CHF had
LVSD on echo.
• Addition of electrocardiogram (ECG) assists in making
diagnosis.
Davie et al. QJM 1997; 90:335-339.
Clinical Diagnosis of CHF
Exam Finding Likelihood Ratio PPV
S3 gallop + 24.0 77%
Displaced Cardiac Apex + 16.5 75%
JVD + 8.5 64%
Hx of DM2 + 6.0
Hx of MI + 4.2
Absence of DOE - 0.03
Displaced Apex + Hx of MI 89%
Davie et al. QJM 1997; 90:335-339.
New York Heart Association
Class 1 No limitation of activities;
asymptomatic from ordinary
activities.
Class 2 Slight, mild limitation of activities;
comfortable with rest or with mild
exertion.
Class 3 Marked limitation of activity;
comfortable only at rest.
Class 4 Symptoms at rest.
ACC/AHA Classification of CHF
Stage A At high risk for the development of
heart failure but have no apparent
structural abnormality of the heart
Stage B Structural heart disease, asymptomatic
Stage C Structural heart disease, previous or
currently symptomatic
Stage D Refractory symptoms requiring special
intervention
Why the Reclassification?
• NYHA classification
– A functional classification only; you could be
reclassified based on your response to medication
– No emphasis on risk factors and modification
• ACC/AHA classification
– Underscores progressive nature of CHF
– Emphasizes identification of risk factors and risk
factor modification
– Link Stage of CHF to Treatment Recommendations
ACC/AHA Treatment
Recommendations
STAGE A
• Treating hypertension reduces the prevalence of LVH and
CHF.
• A retrospective cohort study of 10,333 participants in the
Framingham study, aged 45 to 74 years old, conducted from
1950-1989
– Age-adjusted prevalence of SBP > 160 or DBP > 100 declined
from
• 18.5% to 9.2% in men and
• 28.0% to 7.7% among women
– Age-adjusted prevalence of LVH (on ECG) declined from
• 4.5 percent to 2.5% among men and
• 3.6% to 1.1% among women
• Over this period, incidence of heart failure has decreased 30
to 50%
Mosterd A, NEJM 1999; 340:1279-80. & Deedwania. Arch Int Med 2000;160:1585-94.
Anti-Hypertensive Therapy
• Goal diastolic BP in patients with DM2 < 80.
• Treatment with ACE-inhibitor even in absence of
symptoms reduces rates of death, MI and stroke.
– Type 2 Diabetics especially at risk.
– UKPDS: an RCT of 1148 patients randomized to tight or
less tight BP control
– Significant reduction in the risk of death related to
diabetes, diabetic nephropathy, diabetic retinopathy.
– ACE-I or beta-blocker equally effective for these
endpoints.
• Prevent remodeling.
UKPDS 38. BMJ 1998; 317:703-13.
STAGE B
• Structural heart disease is present, but
asymptomatic
• Continue to address risk factors
– Moderate sodium restriction
– Weight monitoring
– Moderation of EtOH, avoidance of NSAIDs
• ACE-inhibitors or ARBs in all patients; beta-
blockers in selected patients
ACE Inhibitors
• Decrease the conversion of angiotensin I to angiotensin II,
thus minimizing the physiologic effects of angiotensin II on
the heart, vasculature, and renal blood flow.
• A meta-analysis of all RCTs of ACE-inhibitors showed a
statistically significant reduction in total mortality (OR, 0.77)
and in combined endpoint of mortality or hospitalization (OR,
0.65).
– Similar effects for all ACE-Is studied.
– Patients with the lowest EF had the greatest benefit, usually in
the first 3 months of treatment.
• CONSENSUS trial showed that one-year mortality reduced
from 52% to 36% for NYHA Class IV patients.
Garg R. JAMA. 1995;273:1450-6.
Beta Blockers
• Blunt the sympathetic nervous system, slow
HR, decrease blood pressure. Also thought to
have a direct effect on reversing remodeling.
• Reported reduction in mortality is 34 to 65%
with NNT 14 to 26.
• Most widely studied: metoprolol, carvedilol,
and bisoprolol.
• Most patients enrolled in these studies had
NYHA Class II or worse CHF.
Beta Blockers (cont’d)
• Metoprolol
– MERIT-HF
– 3991 patients with NYHA Class II – IV CHF and
EF < 40% randomized to metoprolol or placebo,
with target metoprolol dose of 200mg daily.
– Study stopped early after one year when all-cause
mortality was lower in the metoprolol group vs.
placebo group.
– Overall reduction in mortality (RR 0.66).
MERIT-HF. Lancet 1999;353:2001-2007.
Beta Blockers (cont’d)
• Carvedilol
– COPERNICUS Trial
– A study of 2289 patients
with severe HF, EF < 25%,
randomized to carvedilol or
placebo in addition to usual
care.
– 35% decrease in the risk
of death in carvedilol group
– 24% decrease in the
combined risk of death or
hospitalization
Packer M. NEJM 2001;344:1651-8.
Angiotensin Receptor Blockers
• ARBs also interfere with the renin-angiogensin-
aldosterone system
• A Cochrane meta-analysis of 17 RCTs comparing ARBs
to ACE-Is in patients with NYHA Class II – IV CHF
– ARBs and ACE-Is are equivalent for all-cause mortality
– Small reduction in rate of hospitalization for the
combination of ARB + ACE over ACE alone (OR, 0.74)
– A good option for people who cannot tolerate
ACE-Is
Jong P, JACC 2002;39:463-70.
Angiotensin Receptor Blockers
Jong P, JACC 2002;39:463-70.
STAGE C
• Symptomatic from
structural heart
disease.
• ACE-Is and beta-
blockers in all
patients
• Consider digoxin,
diuretics and
revascularization.
Digoxin
• Digitalis Investigation Group (“DIG”)
– Overall survival is not improved with digoxin.
– Rate of hospitalization is improved, particularly
those with EF < 25%, dilated cardiomyopathy, and
NYHA III or IV.
– Improves exercise tolerance and decreases
symptoms.
• Cochrane review of 20 RCTs in 2004 agreed
with the above.
DIG. NEJM 1997;336:525-533. & Hood et al. Cochrane Library, Issue 2, 2004.
Spironolactone
• A potassium-sparing diuretic that
antagonizes aldosterone at the
DCT and causes water excretion
and potassium retention.
• RALES Trial
– 1663 NYHA Class IV patients
already on ACE-I and loop diuretic.
70% of patients also on digoxin.
Only 10% taking beta-blockers.
– Randomized to addition of placebo
or spironolactone 25 titrated
upward.
– 30% reduction in death in
treatment group. NNT=9.
RALES. Am J Cardiol [Link]-7. & Pitt NEJM 1999;341:709-17.
Diuretics
• Loop diuretics (e.g.,
furosemide) relieve
symptoms but do not
slow progression of
underlying disease.
• Loop diuretics
preferable to
thiazides.
Lonn E, BMJ 2000;320:1188.
Diastolic Heart Failure
• Refers to an abnormality of diastolic
distensibility, filling or relaxing of
the LV.
• One-third of all patients with CHF.
• Etiologies: hypertrophic, scarring
from ischemic disease, infiltrative
diseases
• Diagnosis requires Echo with
EF > 40% and no evidence of acute
valvular disease or pericarditis.
Aurigemma, G. P. et al. N Engl J Med 2004;351:1097-1105
Diastolic Heart Failure
Aurigemma, G. P. et al. N Engl J Med 2004;351:1097-1105
Management of Diastolic HF
• Initial Management
– Diuretics
– Rate control
• Long-term Management
– RCTs of any one agent are generally lacking.
– In one RCT of NYHA II, III or IV comparing
candesartan (ARB) to placebo, treatment was
associated with fewer hospitalizations, and a non-
significant trend toward reducing death.
