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Cardiology – Faculty of Medicine and Surgery University of Turin. Heart failure (3 of 3): treatment. Giuseppe Biondi Zoccai Division of Cardiology 1, Ospedale San Giovanni Battista “Molinette”, Turin, Italy gbiondizoccai@gmail.com – http://www.metcardio.org. Learning goals.

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heart failure 3 of 3 treatment

Cardiology – Faculty

of Medicine and Surgery

UniversityofTurin

Heart failure(3 of 3): treatment

Giuseppe Biondi Zoccai

Division of Cardiology 1, Ospedale San

Giovanni Battista “Molinette”, Turin, Italy

gbiondizoccai@gmail.com – http://www.metcardio.org

learning goals
Learning goals
  • Definition
  • Epidemiology
  • Pathophysiology
  • Diagnosis
  • Prognosis
  • Management
learning goals3
Learning goals
  • Management:
    • Prevention
    • Treatment with “ABCDE”:
      • Pharmacologic therapy
      • Non-pharmacologic therapy
learning goals4
Learning goals
  • Management:
    • Prevention
    • Treatment with “ABCDE”:
      • Pharmacologic therapy
      • Non-pharmacologic therapy
learning goals6
Learning goals
  • Management:
    • Prevention
    • Treatment with “ABCDE”:
      • Pharmacologic therapy
      • Non-pharmacologic therapy
prevention
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
learning goals8
Learning goals
  • Management:
    • Prevention
    • Treatment with “ABCDE”:
      • Pharmacologic therapy
      • Non-pharmacologic therapy
goals means of treatment
Goals/means of treatment
  • Prognostic benefits vssymptomatic benefitsvssurrogate benefits
  • Correction of reversible causes:
    • Ischemia, valvular disease, thyrotoxicosis and other high output status, shunts, arrhythmias, medications
  • Palliation for irreversible damage
slide10

Survival

Morbidity

Exercise capacity

Quality of life

Neurohormonal changes

Progression of CHF

Symptoms

Treatment objectives

(Cost)

slide11

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

learning goals12
Learning goals
  • Management:
    • Prevention
    • Treatment with “ABCDE”:
      • Pharmacologic therapy
      • Non-pharmacologic therapy
abcde approach for hf
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
abcde approach for hf14
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
angiotensin converting enzyme inhibitors ace inhibitors
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!

angiotensin converting enzyme inhibitors ace inhibitors16
Angiotensin Converting Enzyme Inhibitors (ACE-inhibitors)

30

Asymptomatic

ventricular

dysfunction post MI

Placebo

n=1116

Mortality

%

20

Captopril

n = 2231

3 - 16 days post AMI

EF < 40

12.5 - 150 mg / day

n=1115

10

SAVE

N Engl J Med 1992;327:669

p=0.019

0

0

3

4

1

2

Years

angiotensin ii antagonists
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!

aldosterone antagonists
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!

aldosterone antagonists20

1.0

0.9

0.8

0.7

0.6

0.5

0

6

12

24

30

36

18

Aldosterone antagonists

Annual Mortality

Aldactone 18%; Placebo 23%

Survival

N = 1663

NYHA III-IV

Mean follow-up 2 y

Aldactone

p < 0.0001

Placebo

months

RALES

NEJM 1999;341:709

antiarrhythmics
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 amiodaronehas 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!

aspirin oral anticoagulants
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!

abcde approach for hf23
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
beta blockers
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!

beta blockers25
Beta-blockers

100

90

80

Survival

%

Carvedilol

70

p=0.00014

35% RR

N = 2289

III-IV NYHA

60

Placebo

50

0

4

8

12

16

20

24

28

COPERNICUS

NEJM 2001;344:1651

Months

abcde approach for hf28
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
abcde approach for hf29
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
diuretics
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!

digitalis glycosides digoxin digitoxin
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!

digitalis glycosides digoxin digitoxin33
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)
vaso dilators nitrates hydralazine
(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!

vaso dilators nitrates hydralazine36
(vaso) Dilators: nitrates & hydralazine

A-HeFT

Trial

NEJM 2004;351:2049

abcde approach for hf37
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
positive inotropic agents
Positive inotropic agents
  • Improve myocardial contractility (β 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!

learning goals40
Learning goals
  • Management:
    • Prevention
    • Treatment with “ABCDE”:
      • Pharmacologic therapy
      • Non-pharmacologic therapy
slide41
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!

exercise training
Exercise training

ExTraMATCH Meta-analysis

N=801

BMJ 2004;328:189

PROGNOSTIC BENEFIT!

SYMPTOMATIC BENEFIT!

non invasive ventilatory assistance
Non-invasiveventilatoryassistance
  • 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!

non invasive ventilatory assistance44
Non-invasiveventilatoryassistance

Masip et al meta-analysis

N=783

JAMA 2004;294:3124

implantable cardioverter debribillators icd
Implantable cardioverter debribillators (ICD)
  • Patients with EF≤35% 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!

implantable cardioverter debribillators icd46
Implantable cardioverter debribillators (ICD)

DEFINITE Trial

NEJM 2004;350:2151

amiodarone vs icd scd heft
Amiodarone vs ICD – SCD-HeFT

SCD-HeFT Trial

NEJM 2005;352:225

cardiac resynchronization therapy crt
Cardiacresynchronizationtherapy (CRT)

PROGNOSTIC BENEFIT!

SYMPTOMATIC BENEFIT!

crt improves cardiac function 6 months
CRT improves cardiac function (6 Months)

LVEF

Avg. Change

(Absolute %)

MR Jet Area

Avg. Change

(cm2)

Not

Reported

 Control CRT

Data sources:

MIRACLE: Circulation 2003;107:1985-1990

MIRACLE ICD:JAMA 2003;289:2685-2694

Contak CD: J Am Coll Cardiol 2003;2003;42:1454-1459

cardiac transplant
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
stem cells for cardiac regeneration
Stem cells for cardiac regeneration

Orlic et al, Nature 2001

Lipinski et al, J Am Coll Cardiol 2007

impedence monitoring devices
Impedence monitoring devices

Bourge et al,

J Am Coll Cardiol 2008

recommended reading
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 2007;50:2344-51
take home messages66
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
slide67

Manythanks

for these and furtherslides, pleasevisit the www.metcardio.org website