Recommandation consensuelle du traitement du patient avec dysfonction ventriculaire

gauche asymptomatique.

Dr Serge Lepage cardiologue

CHUS

Dysfonction VG

Cardiomyopathie F R Post mi

Pré-angioplastie primaire

Post-angioplastie primaire

L ’insuffisance cardiaque (2)

Classification

Classes NYHA2

(New York Heart Association)

III : Symptômes pendant des activités moins qu’ordinaires

IV : Symptômes au repos

A : Avant

B : Émergence de l ’insuffisance cardiaque

Étapes de la maladie et (périodes critiques d ’organisation des services3)

I : Aucun symptôme

II : Symptômes pendant des activités ordinaires

C : Relative autonomie

D: Perte sévère d ’autonomie

E: Fin de vie

Pronostic de l’IC

Smith WM. Am J Cardiol 1985;55:3A-8A.NYHA = New York Heart Association

1 2 3 4 5 6

Période après inclusion (années)

Pas d’IC (n = 1728)Classe I NYHA (n = 36)Classe II NYHA (n = 79)Classe III NYHA (n = 62)Classe IV NYHA (n = 59)

Su

rvie

1,0

0,8

0,6

0,4

0,2

0

Diagnostic cliniqueCritères de Framingham1

Majeur

• DNP ou orthopnée

• DVC

• Râles

• Cardiomégalie

• Œdème pulmonaire aigu

• Bruits de galop

• PVC > 16 cm H2O

• Temps de circulation 25 sec.

• Reflux hépatojugulaire

Mineur

• Œdème bilatéral des chevilles

• Toux nocturne

• Dyspnée à l’effort ordinaire

• Hépatomégalie

• Épanchement pleural

• Baisse de la capacité vitale du ⅓ p/r aux valeurs maximales notées

• Tachycardie (≥ 120 battements/min.)

Majeur ou mineur

• Perte pondérale ≥ 4,5 kg en 5 jours en réponse au traitementPVC = pression veineuse centrale

PVJ = pression veineuse jugulaireDVC = distention des veines du couDNP = dyspnée nocture paroxystique

1. McKee PA, et al. N Engl J Med 1971;285:1441-1446.

2 symptômes majeurs OU 1 majeur + 2 mineurs = diagnostic

Screening studies using LVEF

• The prevalence in echocardiographic screening studies varies in part with the LVEF used to define LV systolic dysfunction and with age. The normal reference limit for LVEF by echocardiography is ≥55 percent [8]. The following observations illustrate the reported prevalence of asymptomatic LV systolic dysfunction in relation to LVEF; the mean age in these studies was 50 to 70 years [9]:

• LVEF ≤54 percent — 12.5 percent [10]

• LVEF ≤50 percent — 3.3 to 4.7 percent [11,12]

• LVEF ≤40 percent — 0.9 to 2.1 percent [10-13]

• LVEF ≤30 percent — 1.4 percent; almost all of these patients with severe LV dysfunction had evidence of coronary heart disease and/or hypertension [14 ]

First National Health and Nutrition Examination Survey (NHANES I)

• 13,643 men and women who were followed for 19 years found that the risk factors for HF and their population attributable risk (PAR) were as follows

• Coronary heart disease — relative risk 8.1; overall PAR 62 percent, 68 percent in men and 56 percent in women

• Cigarette smoking — relative risk 1.6, PAR 17 percent

• Hypertension — relative risk 1.4, PAR 10 percent

• Overweight — relative risk 1.3, PAR 8 percentDiabetes — relative risk 1.9, PAR 3 percent

• Valvular heart disease — relative risk 1.5, PAR 2 percent; however, valve disease is an increasingly common cause of HF at older ages, with calcific aortic stenosis being the most common disorder requiring surgery

Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population.

• BACKGROUND: In most previous epidemiological studies on the prevalence of chronic heart failure (CHF) the disorder has been defined on clinical criteria. In a cross-sectional survey of 2000 men and women aged 25-74, randomly sampled from one geographical area, we assessed left-ventricular systolic function by echocardiography.

• METHODS: 1640 (83%) of those invited took part. They completed a questionnaire on current medication, history, and symptoms of breathlessness. Blood pressure was measured and electrocardiography (ECG) and echocardiography were done. Left-ventricular ejection fraction was measurable in 1467 (89.5%) participants by the biplane Simpson's rate method.

• FINDINGS: The mean left-ventricular ejection fraction was 47.3%. The prevalence of definite left-ventricular systolic dysfunction (defined as a left-ventricular ejection fraction<or = 30%) was 2.9% overall (43 participants); it increased with age and was higher in men than in women (4.0 vs 2.0%). The left-ventricular systolic dysfunction was symptomatic in 1.5% of participants and asymptomatic in 1.4%, 83% of participants with left-ventricular systolic dysfunction had evidence of ischaemic heart disease (IHD) from history or ECG criteria compared with 21% of those without this abnormality (p<0.001). Hypertension was also more common in those with left-ventricular systolic dysfunction (72 vs 38%, p<0.001), but there was no difference between those with and without left-ventricular systolic dysfunction in the rate of hypertension without IHD.

• INTERPRETATION: Left-ventricular systolic dysfunction was at least twice as common as symptomatic heart failure defined by clinical criteria. The main risk factors are IHD and hypertension in the presence of IHD; screening of such high-risk groups for left-ventricular systolic dysfunction should be considered.

Lancet. 1997;350(9081):829.

McDonagh TA, Morrison CE, Lawrence A, Ford I, Tunstall-Pedoe H, McMurray JJ, Dargie HJ

Echocardiography has been used to diagnose LV dysfunction in community-based studies and clinical trials. However, echocardiography is

expensive and serial testing would be required if the initial test is negative. Furthermore, the yield is very low in patients with no risk factors (1 of

444 [0.2 percent] in one report) [15]. Thus, routine screening with echocardiography is not

recommended [7].

Copyright ©2010 American College of Cardiology Foundation. Restrictions may apply.

Atherton, J. J. J Am Coll Cardiol Img 2010;3:421-428

Kaplan-Meier Curves for Survival of Participants From the Framingham Study

Diagnostic d’IC

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

Principes de la pharmacothérapie

• Les médicaments dont les effets ont été prouvés lors d’essais cliniques à grande échelle sont recommandés, car ils ont des doses cibles efficaces reconnues

(Classe I, Niveau A)

• Il faut utiliser les doses issues d’essais cliniques à grande échelle ou une dose inférieure correspondant à la dose maximale tolérée (voir tableau de la diapositive suivante)

(Classe I, Niveau A)

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

* L’essai Healing and Early Afterload Reduced Therapy (HEART) a montré que la dose efficace pour atténuer le remodelage du ventricule gauche était de 10 mg od.

† Non disponible au Canada.

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

Quelle dose de médicament doit-on utiliser?

SOLVD(Studies of Left Ventricular Dysfunction)

• Enalapril vs placebo in 6,794 patients• Ejection fraction < 35%

– End points include : Delaying the progression of heart failure– Improving signs and symptoms– Reducing mortality

• Treatment arm - 2,568 symptomatic class II-III patients most on digitalis and diuretics

• Prevention arm - 4,226 asymptomatic class I-II patients, most on no concomitant therapy

N Engl J Med 1991:325:293-302

SOLVD Prevention Trial All Cause Mortality

0

5

10

15

20

25

0 6 12 18 24 30 36 42 48

Months

Mor

talit

y fro

m A

ll C

ause

s (%

) PlaceboEnalapril

Risk Reduction 8%Risk Reduction 8%

P=0.30P=0.30

N Engl J Med 1992;327:685-91

SOLVD Prevention TrialDeath or Development of CHF

05

101520253035404550

0 6 12 18 24 30 36 42 48Months of Follow-up

% E

vents

Placebo

Enalapril

Risk Reduction 29%Risk Reduction 29%

p<0.001p<0.001

N Engl J Med 1992;327:685-91

SOLVD Prevention TrialFirst Hospitalization for CHF

0

2

46

8

10

1214

16

18

0 6 12 18 24 30 36 42 48

Months of Follow-up

% E

vent

s

Placebo

Enalapril

Risk Reduction 36%Risk Reduction 36%

p<0.001p<0.001

N Engl J Med 1992;327:685-91

SOLVD Prevention Trial

13,2

8,3

27,8

22,3

0

5

10

15

20

25

30

35

Median length of time to first CHFhospitalization

Median length of time to develop CHF

months

placeboenalapril

N Engl J Med 1992;327:685-91

SOLVD Prevention- Enalapril Asymptomatic HF Patients w/ LVD (EF < 35%)

(NYHA Class I-II)

0

50

100

150

200

250

300

Placebo (n=2,177)

Enalapril (n=2,111)

32% Fewer FirstHospitalizations

p<0.001

Number of First Hospitalizations for Heart FailureNumber of First Hospitalizations for Heart Failure

The SOLVD Investigators, N Engl J Med, 1992.

273273 184184

SOLVD Prevention TrialMorbidity and Combined Outcomes

Endpoint Placebo %

Enalapril %

RR P value

Development of CHF 30.2 20.7 37% <0.001

Development of CHF and anti-CHF Rx

22.5 13.9 43% <0.001

First Hospitalization for CHF

12.9 8.7 36% <0.001

Multiple Hospitalization for CHF

4.8 2.7 44% <0.001

Death or Development of CHF

38.6 29.8 29% <0.001

Death or Hospitalization for CHF

24.5 20.6 20% <0.001

Par où commencer?

• Une pharmacothérapie combinée fondée sur des preuves scientifiques est recommandée pour la majorité des patients souffrant d’IC

(Classe I, Niveau A)

• Tous les patients souffrant d’IC avec une FEVG < 40 % doivent être traités avec un IECA et un bêta-bloquant, sauf dans le cas d’une contre-indication particulière

(Classe I, Niveau A)

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

Quand doit-on utiliser des inhibiteurs de l’ECA?

Tous les patients souffrant d’IC avec une FEVG < 40 % doivent être traités avec un IECA et un bêta-bloquant, sauf dans le cas d’une contre-indication particulière (Classe I, Niveau A)

CONSENSUS Trial. N Engl J Med 1987;316:1429-35. SOLVD Investigators. N Engl J Med 1991;325:293-302. Flather MD et al. Lancet 2000;355:1575-81.

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

Ces études constituent le fondement de l’utilisation des IECA chez les insuffisants cardiaques avec une FEVG < 40 % ou chez les patients post-IM présentant une FEVG réduite ou une IC.

Quand doit-on utiliser des inhibiteurs de l’ECA?

Les inhibiteurs de l’ECA préviennent la survenue de l’IC chez les patients à risque

Arnold JMO et al. Circulation 2003;107:1284-90. SOLVD Investigators. N Engl J Med 1992;327:685-91.

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

Hall AS et al. Lancet 1997;349:1493-7.Swedberg K et al. Eur Heart J 1999;20:136-9.

Jong P et al. Lancet 2003;361:1843-8.HOPE/HOPE-TOO Study Investigators. Circulation 2005;112:1339-46.

Des études additionnelles soulignent les avantages prolongés des inhibiteurs

des ECA

Traitement Ramipril Énalapril Énalapril Ramipril

Suivi 5-10 ans 10 ans 12 ans 7,2 ans

Caractéristique IC clinique, IC de classe IV IC, dysfonctionnement Risque CV élevépost-IM (NYHA) du VG sans dysfonctionnement

du VG, sans IC

Résultats RRR de mortalité Survie générale Survie prolongée Réduction du nombrede 36 % prolongée de 9,4 mois d’événements CV majeurs de 50 %

et de nouveaux cas de diabète

Résumé Importante réduction de Effets bénéfiques Meilleure survie Avantages CV etmortalité à long terme maintenus pendant à long terme métaboliques à longavec le traitement IECA au moins 4 ans terme chez les patients post-IM ne souffrant ni d’insuffisance

cardiaque ni d’un dysfonctionnement du VG

Jong P et al. Lancet 2003;361:1843-8.Hall AS et al. Lancet 1997;349:1493-7.

Les avantages à long terme des inhibiteurs d’ECA sur la mortalité

Les avantages à long terme des inhibiteurs d’ECA sur la mortalité

HOPE/HOPE-TOO Study Investigators. Circulation2005;112:1339-46. Swedberg K et al. Eur Heart J 1999;20:136-9.

Quand utiliser les bêta-bloquants?

• Chez tous les patients souffrant d’IC avec une FEVG ≤ 40 % (utiliser des bêta-

bloquants ayant fait l’objet de preuves scientifiques) (Classe I, Niveau A)

• Chez tous les patients stabilisés présentant des symptômes de classe IV NYHA

(Classe I, Niveau C)

MERIT-HF Study Group. Lancet 1999;353:2001-7.CIBIS II Investigators Lancet 1999;353:9-13.Packer M et al. Circulation 2002;106:2194-9.

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

Stratégies de traitement de l’IC

IECA/(ARA)

Ajustement des BB

Spironolactone

Digoxine/Dérivés nitrés

Aucun selajouté

2 gm Na

Suivi cliniquede l’IC

Programme de style de vie

personnalisé

CRT (LBBB), CPAP

Asymptomatique Légère/Mod. Grave Réfractaire

Risque de mort subit — AICD

Treatment Approach for the Patient with Heart Failure

Stage A

At high risk, no structural disease

Stage B

Structural heart disease,

asymptomatic

Stage D

Refractory HF requiring

specialized interventions

Therapy

• Treat Hypertension

• Treat lipid disorders

• Encourage regular exercise

• Discourage alcohol intake

• ACE inhibition

Therapy

• All measures under stage A

• ACE inhibitors in appropriate patients

• Beta-blockers in appropriate patients

Therapy

• All measures under stage A

Drugs:

• Diuretics

• ACE inhibitors

• Beta-blockers

• Digitalis

• Dietary salt restriction

Therapy

• All measures under stages A,B, and C

• Mechanical assist devices

• Heart transplantation

• Continuous (not intermittent) IV inotropic infusions for palliation

• Hospice care

Stage C

Structural heart disease with prior/current

symptoms of HF

Hunt, SA et al. ACC/AHA Guidelines CHF, 2001.

Treatment Approach for the Patient with Heart FailureStage A

At high risk, no structural disease

Stage B

Structural heart disease,

asymptomatic

Therapy

• Treat Hypertension

• Treat lipid disorders

• Encourage regular exercise

• Discourage alcohol intake

• ACE inhibition

Therapy

• All measures under stage A

• ACE inhibitors in appropriate patients

• Beta-blockers in appropriate patients

Hunt, SA et al. ACC/AHA Guidelines CHF, 2001.

Treatment Overview

Jessup and Brozena. Heart Failure; N Engl Med. 2003;348:2007-2018.

Mortality Trials in Systolic Heart Failure: 1986-2004

ACE inhibitors

CONSENSUS-IIV-HeFT-IISOLVD-TSOLVD-PSAVEAIRETRACEATLAS

-Blockers

MDCU.S. CarvedilolANZ CarvedilolMERIT-HFCIBIS-IIBESTCOPERNICUSCAPRICORN

Aldosterone antagonists

RALESEPHESUS

ARBs

ELITE-IIVal-HeFTOPTIMAALCHARMVALIANT

Inotropic agents

PROMISEVESTDIGOPTIME-II

Vasodilators

V-HeFTFIRSTPRAISE-I/-II

ACE/NEP Inhibitors

OVERTURE

Cytokine antagonists

RENAISSANCERECOVER

Endothelin antagonists

ENABLE-2

PositiveBorderline/NeutralNegative

Sympatholytic agents

MOXCON

Slide courtesy of G. Francis

Traitement de l’insuffisance cardiaque

Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

ACE inhibition, angiotensin receptor blockade and aldosterone antagonism

• Recommendations Consensus conference recommendations on heart failure 2006

• ACE inhibitors should be used in all patients as soon as safely possible after acute myocardial infarction, and should be continued indefinitely if LVEF is less than 40% or if AHF complicated the myocardial infarction

(class I, level A).

Can J Cardiol Vol 22 No 1 January 2006

• ACE inhibitors should be used in all asymptomatic patients with an LVEF less than 35% (class I, level A).

• ACE inhibitors should be used in all patients with symptoms of heart failure and an LVEF less than 40% (class I, level A).

ACE inhibition, angiotensin receptor blockade and aldosterone antagonism

Consensus conference recommendations on heart failure 2006

Beta-adrenoceptor blockade

Recommendations

All heart failure patients with an LVEF equal to or less than 40% should receive a beta-blocker

proven to be beneficial in large-scale clinical trials (class I, level A).

Consensus conference recommendations on heart failure 2006

Practical tips• Patients in NYHA class I or II can be safely initiated andtitrated with a beta-blocker by nonspecialist physicians.

New York Heart Association functional classificationClass DefinitionI No symptoms

Potential to Prevent HF Hospitalizations

17%Other

19%Failure to Seek

Care

16%Inappropriate Rx

Rx Noncompliance 24%

Diet Noncompliance24%