Heart failure (3 of 3): treatment

1
Heart failure (3 of 3) treatment
Cardiology Faculty of Medicine and
Surgery University of Turin

• Giuseppe Biondi Zoccai
• Division of Cardiology 1, Ospedale San
• Giovanni Battista Molinette, Turin, Italy
• gbiondizoccai_at_gmail.com http//www.metcardio.org

2
Learning goals

• Definition
• Epidemiology
• Pathophysiology
• Diagnosis
• Prognosis
• Management

3
Learning goals

• Management
• Prevention
• Treatment with ABCDE
• Pharmacologic therapy
• Non-pharmacologic therapy

4
Learning goals

• Management
• Prevention
• Treatment with ABCDE
• Pharmacologic therapy
• Non-pharmacologic therapy

5
Management
6
Learning goals

• Management
• Prevention
• Treatment with ABCDE
• Pharmacologic therapy
• Non-pharmacologic therapy

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Prevention

• Addressing all primary causes of cardiac disease
  eventually leading to HF
• Hypertension
• Coronary heart disease
• Valvular heart disease
• Metabolic, toxic, or immunological heart disease

8
Learning goals

• Management
• Prevention
• Treatment with ABCDE
• Pharmacologic therapy
• Non-pharmacologic therapy

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Goals/means of treatment

• Prognostic benefits vs symptomatic benefits vs
  surrogate benefits
• Correction of reversible causes
• Ischemia, valvular disease, thyrotoxicosis and
  other high output status, shunts, arrhythmias,
  medications
• Palliation for irreversible damage

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Treatment objectives
(Cost)
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• Prevention/Control of risk factors
• Life style
• Treat etiologic cause / aggravating factors
• Drug therapy
• Personal care. Team work
• Revascularization if ischemia causes HF
• ICD (Implantable Cardiac Defibrillator)
• Ventricular resyncronization
• Ventricular assist devices
• Heart transplant
• Artificial heart
• Neoangiogenesis, Gene therapy

Treatment strategies
All
Selected patients
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Learning goals

• Management
• Prevention
• Treatment with ABCDE
• Pharmacologic therapy
• Non-pharmacologic therapy

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ABCDE approach for HF

• A ? ACE-inhibitors, AII-antagonists,
  aldosterone-antagonists, anti-arrhythmics,
  anti- hypertensives, aspirin/anticoagulants
• B ? beta-blockers
• C ? cholesterol (statins), cardiac
  resynchronization (CRT), coronary PTCA/CABG,
  cardiac restoration, cardiac transplant
• D ? daily weight, diet, diuretics, digoxin,
  defibrillators, (vaso)dilators
• E ? exercise, (anything) else

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ABCDE approach for HF

• A ? ACE-inhibitors, AII-antagonists,
  aldosterone-antagonists, anti-arrhythmics,
  anti- hypertensives, aspirin/anticoagulants
• B ? beta-blockers
• C ? cholesterol (statins), cardiac
  resynchronization (CRT), coronary PTCA/CABG,
  cardiac restoration, cardiac transplant
• D ? daily weight, diet, diuretics, digoxin,
  defibrillators, (vaso)dilators
• E ? exercise, (anything) else

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Angiotensin Converting Enzyme Inhibitors
(ACE-inhibitors)

• Block the renin-aldosterone-angiotensin system by
  inhibiting the conversion of angiotensin I to
  angiotensin II ? ?vasodilation and ?Na retention
• ?bradykinin degradation ?its level ? ?PG
  secretion NO
• Major anti-remodeling effects on myocardium and
  vessels
• Mainstay in HF they improve cardiac function,
  symptoms, and survival
• Several agents captopril, enalapril, lisinopril,
  perindopril, ramipril, zofenopril,

PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
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Angiotensin Converting Enzyme Inhibitors
(ACE-inhibitors)
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Asymptomatic ventricular dysfunction post MI
Placebo
n1116
Mortality
20
Captopril
n 2231 3 - 16 days post AMI EF lt 40 12.5 - 150
mg / day
n1115
10
SAVE N Engl J Med 1992327669
p0.019
0
4
3
0
1
2
Years
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Angiotensin Converting Enzyme Inhibitors
(ACE-inhibitors)
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Angiotensin II antagonists

• Comparable effect to ACE-inhibitors
• Fewer side effects than ACE-inhibitors
• Can be used in certain conditions when
  ACE-inhibitors are contraindicated (angioneurotic
  edema, cough)
• May be combined with ACE-inhibitors, provided BP
  is ok, to possibly improve survival and
  definitely reduce hospitalizations
• Commonly used agents candesartan,
• losartan, valsartan

PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
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Aldosterone antagonists

• Block aldosterone receptors
• Can be used in advanced HF, to further inhibit
  the R-A-A system after complete uptitration of
  ACE-inhibitors
• Check often for risk of hyperkalemia
• Available agents spironolactone, potassium
  canrenoate, eplerenone

PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
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Aldosterone antagonists
Annual Mortality Aldactone 18 Placebo 23
Survival
N 1663 NYHA III-IV Mean follow-up 2 y
Aldactone
p lt 0.0001
Placebo
months
RALES NEJM 1999341709
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Antiarrhythmics

• Most common cause of sudden cardiac death in HF
  is ventricular tachyarrhythmia
• Antiarrhythmic drugs may suppress PVC but may
  induce VT or VF!!!
• Only amiodarone has a reasonably safe profile in
  HF, but landmark SCD-HeFT Study has demonstrated
  no impact of amiodarone on prognosis
• Remember the many toxic effects of amiodarone
• lung, thyroid, eye, liver

SYMPTOMATIC BENEFIT!
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Aspirin/oral anticoagulants

• Aspirin is recommended in all patients with
  coronary heart disease, diabetes or any other
  established form of atherosclerotic disease,
  unless contraindicated by bleeding diathesis
• Oral anticoagulants are recommended in patients
  with paroxysmal/permanent atrial fibrillation, or
  those with previous embolic events (eg in LV
  dysfunction)
  despite aspirin treatment

PROGNOSTIC BENEFIT!
23
ABCDE approach for HF

• A ? ACE-inhibitors, AII-antagonists,
  aldosterone-antagonists, anti-arrhythmics,
  anti- hypertensives, aspirin/anticoagulants
• B ? beta-blockers
• C ? cholesterol (statins), cardiac
  resynchronization (CRT), coronary PTCA/CABG,
  cardiac restoration, cardiac transplant
• D ? daily weight, diet, diuretics, digoxin,
  defibrillators, (vaso)dilators
• E ? exercise, (anything) else

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Beta-blockers

• Traditionally were contraindicated in HF
• Now another mainstay in HF
• improved LV function and symptoms
• Improved survival
• The only contraindication is severe and truly
  decompensated HF
• Agents approved for HF bisoprolol, metoprolol,
  carvedilol

PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
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Beta-blockers
100
90
80
Survival
Carvedilol
70
p0.00014 35 RR
N 2289 III-IV NYHA
60
Placebo
50
24
0
20
16
12
8
4
28
Months
COPERNICUS NEJM 20013441651
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The best beta-blocker? Probably carvedilol
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Use of best beta-blocker invarious settings
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ABCDE approach for HF

• A ? ACE-inhibitors, AII-antagonists,
  aldosterone-antagonists, anti-arrhythmics,
  anti- hypertensives, aspirin/anticoagulants
• B ? beta-blockers
• C ? cholesterol (statins), cardiac
  resynchronization (CRT), coronary PTCA/CABG,
  cardiac restoration, cardiac transplant
• D ? daily weight, diet, diuretics, digoxin,
  defibrillators, (vaso)dilators
• E ? exercise, (anything) else

29
ABCDE approach for HF

• A ? ACE-inhibitors, AII-antagonists,
  aldosterone-antagonists, anti-arrhythmics,
  anti- hypertensives, aspirin/anticoagulants
• B ? beta-blockers
• C ? cholesterol (statins), cardiac
  resynchronization (CRT), coronary PTCA/CABG,
  cardiac restoration, cardiac transplant
• D ? daily weight, diet, diuretics, digoxin,
  defibrillators, (vaso)dilators
• E ? exercise, (anything) else

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Diuretics

• The most effective symptomatic relief
• Usually short-term IV therapy followed by
  long-term PO therapy
• Thiazides
• HCTZ, chlorthalidone
• Loop diuretics
• Furosemide, torasemide, bumetanide, etacrynic
  acid
• Mixed agents
• Metolazone, nesiritide

SYMPTOMATIC BENEFIT!
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Diuretics
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Digitalis glycosides (digoxin, digitoxin)

• Their role has declined in recent years (s/p DIG
  Study)
• Digitals does not affect mortality in CHF
  patients but causes significant
• Reduction in hospitalization
• Reduction in symptoms of HF
• Actions
• Positive inotropic effect
• Arrhythmogenic effect
• Vagotonic effect

USEFUL IN CASE OF CHF AF!
SYMPTOMATIC BENEFIT!
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Digitalis glycosides (digoxin, digitoxin)

• Digoxin levels should be 1.0 2.0 ng/dL, but
  narrow variable therapeutic window (check
  serum!)
• Toxicity - non cardiac manifestations
• Anorexia, nausea, vomiting, headache, xanthopsia
  sotoma, disorientation
• Toxicity - cardiac manifestations
• Sinus bradycardia and arrest, A/V block (usually
  2nd degree), atrial tachycardia with A/V block,
  development of junctional rhythm in patients with
  AF, PVC, VT/ VF (bi-directional VT)

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Daily doses of digoxin
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(vaso) Dilators nitrates hydralazine

• Reduction of afterload by arteriolar
  vasodilatation (hydralazin) ? ?LVEDP, O2
  consumption, ?myocardial perfusion, ?stroke
  volume and CO
• Reduction of preload by venous dilation
• (nitrates) ? ?venous return ? ?load on both
  ventricles
• Usually maximum benefit achieved by using both
  agents, but currently approved (in US) only for
  African Americans
• Other drugs (eg nesiritide) have still very
  limited
  clinical role

PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
36
(vaso) Dilators nitrates hydralazine
A-HeFT Trial NEJM 20043512049
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ABCDE approach for HF

• A ? ACE-inhibitors, AII-antagonists,
  aldosterone-antagonists, anti-arrhythmics,
  anti- hypertensives, aspirin/anticoagulants
• B ? beta-blockers
• C ? cholesterol (statins), cardiac
  resynchronization (CRT), coronary PTCA/CABG,
  cardiac restoration, cardiac transplant
• D ? daily weight, diet, diuretics, digoxin,
  defibrillators, (vaso)dilators
• E ? exercise, (anything) else

38
Positive inotropic agents

• Improve myocardial contractility (ß adrenergic
  agonists, dopaminergic agents, phosphodiesterase
  inhibitors, calcium-channel sensitizers)
  dopamine, dobutamine, milrinone, amrinone,
  levosimendan
• Most studies showed ? long-term mortality with
  inotropic agents
• Yet beneficial at short-term use for peripheral
  hypoperfusion /- pulmonary edema refractory to
  diuretics and vasodilators
• Only use them is in acute conditions such as
  cardiogenic shock, as bridge to another lasting
  intervention
  (eg transplant) or cardiac injury should be
  temporary

SYMPTOMATIC BENEFIT!
39
Positive inotropic agents
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Learning goals

• Management
• Prevention
• Treatment with ABCDE
• Pharmacologic therapy
• Non-pharmacologic therapy

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Diet

• Salt restriction
• Fluid restriction
• Low fat diet in patients at risk or with coronary
  artery disease
• Plus daily weight and, if needed, monitoring of
  urine output (to tailor therapy)

SYMPTOMATIC BENEFIT!
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Exercise training
ExTraMATCH Meta-analysis N801 BMJ 2004328189
PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
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Non-invasive ventilatory assistance

• CPAP and NIPPV in cardiogenic pulmonary edema
  reduce the need for tracheal intubation and
  mechanical ventilation
• Moreover, they reduce mortality in acutely
  decompensated patients
• However, there are logistic and compliance issues
  inherent to these treatment
  means, especially as long-term
  regimens

PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
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Non-invasive ventilatory assistance
Masip et al meta-analysis N783 JAMA
20042943124
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Implantable cardioverter debribillators (ICD)

• Patients with EF35 and CHF ? benefit from ICD
  (primary prevention)
• Patients with history of sustained VT or SCD ?
  benefit from ICD (secondary prevention)
• Patients with history of non-sustained VT and EF
  between 30-40 ? electrophysiological testing
  ICD (primary prevention)

PROGNOSTIC BENEFIT!
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Implantable cardioverter debribillators (ICD)
DEFINITE Trial NEJM 20043502151
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Amiodarone vs ICD SCD-HeFT
SCD-HeFT Trial NEJM 2005352225
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Cardiac resynchronization therapy (CRT)
PROGNOSTIC BENEFIT!
SYMPTOMATIC BENEFIT!
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Cardiac resynchronization therapy (CRT)
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CRT improves cardiac function (6 Months)
LVEF Avg. Change (Absolute )
MR Jet Area Avg. Change (cm2)
Not Reported
? Control ? CRT
Data sources MIRACLE Circulation
20031071985-1990 MIRACLE ICDJAMA
20032892685-2694 Contak CD J Am Coll Cardiol
20032003421454-1459
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Left ventricular assist devices (LVAD)
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Cardiac transplant

• It has become more widely used since the advances
  in immunosuppressive treatment
• Survival rate
• 1 year 80 - 90
• 5 years 70
• 10 years 50
• At Molinette Hospital no more than 20-30 cardiac
  transplants are done per year, thus it can be
  offered to very few people

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Stem cells for cardiac regeneration
Orlic et al, Nature 2001
Lipinski et al, J Am Coll Cardiol 2007
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Impedence monitoring devices
Bourge et al, J Am Coll Cardiol 2008
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Comprehensive management
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Nurse-lead clinics
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Everything is clear?
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The donkeys analogy
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The donkeys analogy beta-blockers
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The donkeys analogy diuretics and
ACE-inhibitors
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The donkeys analogy digoxin
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The donkeys analogy CRT
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Recommended reading

• Baker et al. ACC/AHA guidelines for the
  evaluation and management of chronic heart
  failure in the adult. J Am Coll Cardiol
• Swedberg et al. Guidelines for the diagnosis and
  treatment of chronic heart failure. Eur Heart J
  2005
• Tang et al. The year in heart failure. J Am Coll
  Cardiol 2007502344-51

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Take home messages
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Take home messages
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Take home messages

• The management of HF should maximize benefits and
  minimize adverse effects and resources
• Pharmacologic therapy can be summarized with an
  ABCDE approach
• Non-pharmacologic treatments should complement
  drug therapy in all cases
• Ultimately prevention will be key to achieve
  major results at the population level

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Many thanks for these and further slides, please
visit the www.metcardio.org website