Heart Failure

1
Heart Failure

• J.B. Handler, M.D.
• Physician Assistant Program
• University of New England

2
Abbreviations

• CO- cardiac output
• PCW- pulmonary capillary wedge
• SVR- systemic vascular resistance
• SVR ? PVR (peripheral vascular resistance)
• HR- heart rate
• JVD- jugular venous distension
• AV- arterial and venous
• C- cardiac
• EF- ejection fraction
• ED- emergency department
• LHF- left heart failure
• BVF- biventricular failure

• P- Pulmonary
• ACEI- angiotensin converting enzyme inhibitor
• ARB- angiotensin receptor blocker
• NYHA- New York Heart Association criterion
• BNP- beta natiuretic peptide
• MVO2- myocardial oxygen consumption
• ICD- implantable cardioverter defibrillator
• RHF- right heart failure
• CRT- cardiac resynchronization therapy

3
Heart Failure Definition

• A pathophysiologic state in which an abnormality
  of cardiac function is responsible for failure of
  the heart to pump blood at a rate commensurate
  with the requirements of the metabolizing tissues
  and/or can do so only from an abnormally elevated
  diastolic volume/pressure.

4
Heart Failure Basics

• Over 5 million patients in U.S. with HF
• 550,000 patients newly diagnosed each year
• gt 1 million hospitalizations/yr- HF as 1st Dx
  gt2.5 hospitalizations- HF among Dx.
• ? number of HF deaths in spite of advances in Rx
• Increased salvage of patients with acute MI
• Numbers are rising as baby boomers age
• Management must be individualized

5
Etiologies of Heart Failure (HF)

• Coronary Heart Disease MI(s) or ischemia
  superimposed on prior infarction(s)? 75 of all
  cases.
• Primary pump failure - Cardiomyopathy, viral
  myocarditis
• Valvular heart disease
• Congenital heart disease
• Long standing, uncontrolled hypertension

6
Precipating Causes

• Progressive weakening of the myocardium and
  consequences? heart failure
• Infection
• Anemia
• Thyrotoxicosis
• Arrhythmias
• Aggravation of hypertension
• Myocardial ischemia or infarction
• Physical, dietary (Na/fluid) or emotional
  excesses

7
HF Systolic or Diastolic?

• Systolic Failure (or dysfunction) Primary
  contraction abnormality inadequate delivery of
  O2 to tissues and associated symptoms e.g
  large or multiple MI(s), dilated cardiomyopathy,
  chronic AR, MR.
• Diastolic Failure (or dysfunction) - Impaired
  ventricular relaxation- elevation of ventricular
  filling pressures and associated symptoms e.g
  long standing hypertension (with LVH),
  hypertrophic cardiomyopathy, acute ischemia,
  prior infarcts, restrictive cardiomyopathy.
• Systolic and diastolic failure often occur
  together.

8
HF Acute or Chronic?

• Acute - Large MI? sudden onset of symptoms,
  systolic failure, hypotension, pulmonary edema.
• Chronic - pathophysiology and symptoms develop
  slowly, BP usually maintained until late in
  course peripheral edema common e.g dilated
  cardiomyopathy, chronic valvular insufficiency,
  large or multiple infarcts.
• Acute episodes may be superimposed on chronic HF?
  development of pulmonary edema in patient with
  previously compensated (treated) HF.

9
HF Rt Sided or Lt Sided?

• Lt sided failure e.g post MI, aortic/mitral
  valve disease. Inadequate CO with pulmonary
  congestion and related symptoms.
• Rt. sided failure e.g COPD/pulmonary
  hypertension, pulmonic stenosis associated with
  peripheral edema, hepatic congestion, etc.
• Most common cause of right sided failure is
  left sided failure/dysfunction!

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Cardiac Pressures
4-12
4-12
4-12
4-12
4-12
4-12
8-15
Images.google.com
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HF Backward or Forward?

• Backward failure Inadequate ventricular
  emptying pressures in the atrium and venous
  system behind the failing ventricle rise
  resulting in transudation of fluid into
  interstitial spaces.
• Forward failure Inadequate forward CO Na and
  water retention result from diminished renal
  perfusion and activation of renin-angiotensin-aldo
  sterone system.

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Compensatory Mechanisms

• Redistribution of CO Blood flow redistributed to
  vital organs- brain and myocardium with reduced
  blood flow to skin and muscle? mediated via
  activation of the adrenergic nervous system and
  vasoconstriction to less vital tissues.
• Na and water retention Complex sequence of
  adjustments occurs resulting in accumulation of
  fluid and increasing SVR
• Helps maintain CO via Starling mechanism
• Cost is volume overload and ?afterload.

13
Adrenergic Nervous System

• Activated in CHF-beneficial and harmful.
• Increase levels of norepinephrine result in
  increase HR, contractility and SVR- helps
  maintain arterial perfusion pressure (BP) in
  presence of decreased CO.
• Elevation of SVR results in increased hemodynamic
  burden (afterload) and O2 requirement of the
  failing ventricle. Long term elevation of
  catecholamines lead to progressive myocardial
  damage and fibrosis.

BP CO x SVR
CO BP/SVR
14
Renin-Angiotensin System

• Renin enzyme released by kidneys if ?perfusion
  or ?BP.
• Angiotensinogen (renin substrate) converted to
  Angiotensin I by renin.
• Angiotensin I converted to Angiotensin II in
  lungs by angiotensin converting enzyme.
• Angiotensin II extremely potent
  vasoconstrictor- leads to arteriolar constriction
  and increase in SVR, raising BP.

15
Renin-Angiotensin System

• Angiotensin II stimulates adrenal gland to
  secrete Aldosterone.
• Aldosterone a mineralocorticoid hormone increases
  renal Na and H2O reabsorption.
• Renin-angiotensin-aldosterone activation (by
  decreased cardiac output) in heart failure is a
  major factor in edema formation and increased
  SVR.
• Long term activation of angiotensin II and
  aldosterone lead to myocardial thinning and
  fibrosis (remodeling).

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Functional Classification of Heart Disease NYHA
Criterion

• I No limitation of physical activity. No
  symptoms of SOB, CP dizzyness, etc.
• II Slight limitation of physical activity. Some
  (ordinary) activities (exercise, exertion, etc)
  cause symptoms.
• III Marked limitation of physical activity. Less
  than ordinary activities (walking, dressing,
  etc.) cause symptoms.
• IV Symptomatic at rest or minimal activity
  unable to engage in any physical activity.

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Clinical Manifestation of HF

• Dyspnea Initially with activity, then at rest
  due to elevation of pulmonary venous pressure.
• Orthopnea Dyspnea in recumbent position
  redistribution of fluid from abdomen and lower
  extremities into chest.
• Paroxysmal Nocturnal Dyspnea Attacks of severe
  SOB, coughing and wheezing awakening patient from
  sleep.
• Unexplained weight gain Sodium and water
  retention. Patients may note swelling of the
  legs.
• Nocturia commonly occurs

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• Fatigue, weakness, abdominal symptoms, decreased
  exercise capacity reflects ?CO to muscles, GI
  tract and other organs.
• Cerebral symptoms (esp. in patients with
  co-existing cerebrovascular disease) Decreased
  perfusion to brain.
• Acute Pulmonary Edema Severe dyspnea at rest as
  pulmonary congestion progresses accompanied by
  marked elevation of pulmonary capillary pressure
  leading to alveolar edema PCW gt20 ?
  interstitial edema PCW gt 25 ? alveolar edema. A
  medical emergency usually addressed in ED.

PCW Pulmonary Capillary Wedge pressure
19
Physical Exam (LR sided HF)

• Symptoms vary depending on severity.
• Patient may be uncomfortable lying flat BP
  normal or low tachycardia common. Cyanosis of
  lips nailbeds reflects hypoxemia.
• Crackles (Rales- older term)- moist inspiratory
  crackles wheezes. Begin at bases and progress
  upwards through the lungs.
• S3 gallop- low pitched sound in early diastole.

20
Physical Exam (LR sided HF)

• Increased systemic venous pressure JVD reflects
  ?JVP.
• Hepato-Jugular Reflux.
• Congestive hepatomegaly- enlarged, tender,
  pulsatile liver.

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Physical Exam

• Peripheral edema develops with progressive HF.
• Hydrothorax and ascites- pleural effusions.
• Cardiac cachexia- Wasted appearance occurs with
  severe chronic heart failure?weight loss,
  anorexia, nausea correlates with increased
  levels of cytokines like circulating tumor
  necrosis factor.

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Additional Findings

• CxR Cardiomegaly distension of pulmonary veins
  venous redistribution to apices
  interstitial?alveolar edema pleural effusions.
• Echo-Doppler- findings unique to pathology
  responsible for HF best non-invasive tool.
  Identifies ventricular dysfunction and EF.
• ECG- may reflect underlying pathology i.e.
  infarct, LVH, arrhythmia, etc.

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CxR CHF
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?-type Natriuretic Peptide

• ?NP- hormone produced by heart (ventricle) in
  response to wall stress- marker of decompensated
  heart failure in blood.
• Blood test for acute ventricular dysfunction ?
  symptomatic heart failure
• Useful in diagnosis of HF in patients presenting
  with SOB of uncertain (C vs P) etiology and
  confirming HF when suspected clinically.
• Has vasodilator (av) and diuretic properties-
  new Rx for treating refractory heart failure
  (below).
• Normal is lt 100 pg/ml

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Pathophysiologic Basis of Therapy

• Taylor treatment to the manifestations of heart
  failure in each individual patient.
• Excessive increase in preload diuretics,
  venodilators (nitrates).
• Excess Na retention with edema diuretics.
• Increased afterload Vasodilator therapy
• ACE inhibitors, Angiotensin Receptor blockers
  and others.

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Pathophysiologic Basis of Therapy

• Myocardial systolic failure -Rx. to improve
  contractility- Digoxin sympathomimetics.
• Slow progression of cardiac deterioration- ACE
  inhibitorsBeta blockers Spironolactone
• Improve diastolic dysfunction if possible
  regression of LVH with treatment of co-existing
  HTN
• Treat arrhythmias as needed

Prevent Remodeling
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Mortality in Heart Failure

• Overall poor prognosis once symptomatic
• Severe failure (class IV)- 40-50 mortality in 12
  months
• Moderate failure (class III)- 40-50 mortality in
  3-4 yrs
• Ejection Fraction (EF) is predictive
• 30-40 die suddenly- arrhythmia.

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HF Goals of Therapy

• Removal of precipitating factors.
• Treatment of underlying cause? active ischemia,
  valvular disease, cardiomyopathy, etc.
• Control of the HF stateReduction of cardiac
  workloadControl of excessive Na/water
  retentionEnhancement of cardiac contractility
• Early initiation of ACEI therapy for most
  patients
• Hydralazine and nitrates in black populations
  added to ACEI if needed.

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Treatment of HF

• Reduction of cardiac workload decreased/limited
  activity elastic stockings, anxiolytic therapy
  anticoagulation for prolonged bed rest.
• Control excessive dietary sodium (4 gram Na diet
  or less).
• No added salt no salt in preparation of foods
  avoid foods with high sodium content.

30
Diuretics

• Early addition of diuretics beneficial in
  relieving symptoms (shortness of breath) and
  reducing preload- does not ?mortality.
• Loop diuretics Most potent diuretics and
  cornerstone of diuretic Rx in CHF- Furosemide,
  Bumetanide, Torsemide
• Metolazone - similar to thiazide diuretics added
  to and potentiate loop diuretics in severe,
  refractory heart failure caution ?K

31

Diuretics

• Loop diuretics remain effective in renal failure.
• Must monitor renal function (BUN, Cr.) serum
  electrolytes (esp. K), uric acid and glucose
  loop diuretics can cause hypokalemia, and
  hyperuricemia as well as metabolic alkalosis.
• Over aggressive diuresis can lead to pre-renal
  azotemia ?impaired renal fx from hypovolemia and
  ?perfusion.
• Triamterene and Amiloride are weak diuretics that
  are K sparing - elevate K levels may be used in
  combination with loop diuretics to offset K losses

32
Vasodilator Therapy in HF

• LV afterload always elevated in HF due to neural
  and humoral influences that act to constrict the
  peripheral vascular bed and elevate SVR preload
  also increased from Na/H20 retention.
• In presence of impaired cardiac function,
  increasing afterload will reduce cardiac output
  further and lead to elevation of pulmonary
  pressures and pulmonary congestion.
• In patients with acute and chronic HF, treatment
  with vasodilators results in decreasing SVR,
  increasing CO, decreasing PCW, and relief of
  symptoms also decreases mortality.

33
Angiotensin Converting Enzyme Inhibitors

• Activation of the Renin-Angiotensin-Aldosterone
  system in heart failure results in marked
  vasoconstriction via Angiotensin II and Na and
  H2O retention via Aldosterone.
• ACE Inhibitors dramatically reduce afterload, and
  to a lesser degree, preload in patients with HF
  by ?ing the production of Angiotensin II and
  aldosterone.
• CO BP/SVR

34
ACE Inhibitors

• Superior to all other treatment of HF in terms of
  long-term symptomatic improvement and outcome -
  Reduce mortality by gt25.
• Long term ACEI has significant natriuretic
  effects resulting in improved diuresis.
• Captopril, enalapril, lisinopril, ramipril,
  fosinopril, perindopril et al all equally
  beneficial.

35
ACE Inhibitors

• ACEI decrease remodeling of the LV post MI and in
  HF by reducing wall thinning, fibrosis and
  interfering with programmed cell death
  (apoptosis) result is ? mortality.
• Elevation of kinins from ACE inhibition may also
  have beneficial effects on hemodynamics
  (vasodilation) and remodeling increased levels
  of prostaglandins and nitric oxide vasodilation.

36
LV Remodeling
NYerRN
37
Limitations of ACEI

• Fall in systemic BP. ACEI usually well tolerated
  if initiate with low dose and gradually increase.
• Cough- Drug related persistent cough resulting
  from elevated bradykinin levels occurs in up to
  15-20 of patients, but only 5 need to DC the
  drug.
• Less effective in black populations. Hydralazine
  long acting nitrates are added to ACEI prn.
• BiDil Hydralazine isosorbide dinitrate
• Must monitor renal function Cr and BUN often
  increase mildly (and expectedly) with ACEI.

38
Angiotensin II Receptor Blockers

• Released and FDA approved for hypertension.
• Inhibit angiotensin II receptor - reduce SVR, BP
  and afterload.
• Similar hemodynamic effects to ACEI.
• Do not increase bradykinen- no cough but less
  protection against remodeling.
• Useful as an alternative to ACEI (if pt
  intolerant) sometimes added to ACEI for severe
  HF.
• Comparison studies ARB vs ACEI have demonstrated
  ACEI superiority in most large clinical trials.

39
Beta-Blocker Therapy

• Previously contraindicated in treating HF.
• Now proven that ?-blockers are not only useful in
  treating HF, but reduce mortality as well as
  improve cardiac function and symptoms.
• Multiple clinical trials using carvedilol,
  metoprolol and bisoprolol (MERIT et al).
• Begin once patient stable and euvolemic for
  chronic heart failure.

40
Beta-Blocker Therapy

• Likely that chronic elevations of catecholamines
  and sympathetic nervous system activity cause
  progressive myocardial damage, fibrosis and
  dysfunction?abnormal remodeling.
• Beneficial for all classes of heart failure with
  up to 30 decrease in mortality.
• Must begin with very low doses and gradually
  increase e.g carvedilol 3.125 mgs b.i.d.
• Unclear if all ?-blockers are alike for HF.
  Carvedilol may be drug of choice because of its
  combined ? and ? blocking effects.

41
Aldosterone Antagonists

• Spironolactone Competitive inhibitor of
  aldosterone has mild diuretic properties and
  elevates K (often used in combination with loop
  diuretics which can cause hypokalemia).
• In low dose (12.5-25 mgs/daily) spironolactone
  has been shown to decrease morbidity and
  mortality in patients with severe heart failure.
• Has anti-androgenic properties.
• Must monitor serum K to avoid hyperkalemia.

42
Actions of Spironolactone

• Aldosterone mediates some of the deleterious
  effects of renin-angiotensin-aldosterone system
  activation, such as myocardial remodeling and
  fibrosis.
• By blocking aldosterone, spironolactone should be
  considered as a neurohormonal antagonist rather
  than narrowly as a K sparing diuretic.
• Clinical trials (RALES et al) show 29 reduction
  in mortality in NYHA class III and IV patients.
• Eplerenone- released in 2003 aldosterone
  antagonist without anti-androgenic properties.

43
Aldosterone Blockade Post MI

• Spironolactone and eplerenone post MI reduce
  morbidity and mortality in patients with LV
  dysfunction/heart failure.
• Mineralocorticoid blockade prevents remodeling,
  blocks collagen production, improves EF and
  decreases LV dilatation.
• Adjunct Rx to ACEI. Should be considered early
  in Rx of patients with large MI/LV dysfunction
  and heart failure.
• Must monitor K closely

44
Enhancement of Contractility

• Digitalis Glycosides - Digoxin most commonly
  used only oral inotropic agent available
  improves cardiac contractility.
• Increases automaticity of cardiac electrical
  tissue - can induce arrhythmias.

45
Digoxin

• Prolongs refractory period of AV node (vagal tone
  increased) slows rate of Atrial fibrillation and
  flutter.
• Modest improvement in cardiac function in
  patients with LV dilatation and dysfunction.
• Falling out of favor for Rx of CHF improves
  symptom but not mortality.
• Low Therapeutic/Toxic index- toxicity includes N,
  V, arrhythmias (PVCs, atrial tachycardia) and
  2nd/3rd degree A-V block.

46
Sympathomimmetic Amines

• Indication refractory HF. Must be given (short
  term) by continuous IV infusion in a hospitalized
  setting, preferably with invasive hemodynamic
  monitoring (rt. heart catheter).
• Dobutamine Potent inotrope- stimulates Beta
  receptors, raises CO.
• Dopamine Low dose-dilates renal and mesenteric
  blood vessels via Dopaminergic receptors
  Moderate dose- Stimulates B receptorsHigh dose-
  Stimulates Alpha receptors.

47
Phosphodiesterase Inhibitors

• Indication refractory HF. Improve cardiac
  contractility by inhibiting myocardial
  phosphodiesterase.
• Potent inotropes administered IV for short term
  use.
• Amrinone, Milrinone.
• Trials using these and other newer inotropes
  orally for long term use have all demonstrated
  substantial increase in mortality.

48
Nesiritide

• New- recombinant form of beta natriuretic peptide
  (BNP). Indication refractory HF.
• Potent vasodilator (venousgtarteriolar) decreases
  LV filling pressures (pre-load) and SVR
  (afterload) improves cardiac output.
• Must monitor renal function- renal failure
  occurs.
• Continuous IV infusion following a bolus.
• May have diuretic effects in some individuals.

49
Biventricular Pacing and ICDs

• Abnormal IVCD results in dyssynchronous
  contraction.
• If QRS gt 120ms and severe refractory CHF,
  synchronized biventricular pacing (CRT) improves
  symptoms and quality of life may decrease
  mortality.
• ICD decrease mortality in patients with LV
  dysfunction and symptoms of HF.
• Indications for ICD
• Secondary Rescusitated cardiac arrest/Vfib or
  hemodynamically unstable Vtach
• Primary EF ? .35 mild to moderate HF symptoms
• CRT-Ds address resynchronization pacing ICD

CRT cardiac resynchronization therapy
50
End-Stage Heart Failure

• HF unresponsive to intensive medical Rx.
• LV assist devices Implantable assist device
  (pump) connected to external power supply.
  Decrease workload of native heart and buy time
  (bridge) to heart transplant.
• Allow mobility and discharge from hospital to
  await transplant. Heart may improve over time.
• Complications Bleeding, infections,
  thromboembolism.
• Very expensive 2-300,000 for up to 3 months.

51
Cardiac Transplantation

• Widely used. Problem Not enough donor hearts.
• Living donor heart replaces failing one.
• Improved immunosuppressive drugs yield 70 or
  greater 5 year survival with excellent quality of
  life.
• High cost- 200,000 initially
• Complications
• Rejection, infections, accelerated CHD in donor
  coronary arteries.
• Immunospuppressive related cancers

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Acute Pulmonary Edema

• Medical emergency
• Treatment modalities may include
• Morphine sulfate- reflex withdrawal of
  sympathetic tone decreases anxiety
• O2
• IV loop diuretics - promote diuresis and have
  direct venodilator activity.
• Afterload reduction IV Nitroprusside
• IV Inotropes -Dobutamine
• Preload reduction- Nitrates
• Invasive hemodynamic monitoring improves
  management.