An EvidenceBased Review: Congestive Heart Failure

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An Evidence-Based ReviewCongestive Heart Failure

• Mike Mendoza, MD, MPHChief ResidentDepartment
  of Family and Community Medicine
• September 2004

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Overview

• Pathophysiology
• Diagnosis of CHF
• ACC / AHA Reclassification of CHF
• Pharmacologic Treatments
• Diastolic Heart Failure

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The Syndrome of Heart Failure
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Its 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.

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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.

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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

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Circulating Evil Humours

• In a series of patients with stable CHF treated
  with digoxin but NOT diuretics, ACE-Is or
  beta-blockers

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Increases in NE are Bad

• Increases in circulating norepinephrine confer
  worse prognosis.
• ValHeFT Study

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Renin-Angiotensin-Aldosterone
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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.

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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.

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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 lt 25) on echo.
• Only 16 of patients suspected to have CHF had
  LVSD on echo.
• Addition of electrocardiogram (ECG) assists in
  making diagnosis.

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Clinical Diagnosis of CHF
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New York Heart Association
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ACC/AHA Classification of CHF
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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

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ACC/AHA Treatment Recommendations
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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 gt 160 or DBP gt 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

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Anti-Hypertensive Therapy

• Goal diastolic BP in patients with DM2 lt 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.

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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

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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.

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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.

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Beta Blockers (contd)

• Metoprolol
• MERIT-HF
• 3991 patients with NYHA Class II IV CHF and EF
  lt 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).

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Beta Blockers (contd)

• Carvedilol
• COPERNICUS Trial
• A study of 2289 patients with severe HF, EF lt
  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

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Angiotensin Receptor Blockers

• ARBs also interfere with the renin-angiogensin-ald
  osterone 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

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Angiotensin Receptor Blockers
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STAGE C

• Symptomatic from structural heart disease.
• ACE-Is and beta-blockers in all patients
• Consider digoxin, diuretics and revascularization.

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Digoxin

• Digitalis Investigation Group (DIG)
• Overall survival is not improved with digoxin.
• Rate of hospitalization is improved, particularly
  those with EF lt 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.

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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. NNT9.

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Diuretics

• Loop diuretics (e.g., furosemide) relieve
  symptoms but do not slow progression of
  underlying disease.
• Loop diuretics preferable to thiazides.

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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 gt 40 and no
  evidence of acute valvular disease or
  pericarditis.

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Diastolic Heart Failure
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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.