充血性心衰的治疗，2004长城会演讲幻灯
Current Management of Congestive Heart Failure: 2004 Update
Hisham Dokainish, MD, FACC
Assistant Professor of Medicine
Baylor College of Medicine,
Director, Non-Invasive Cardiology,
Ben Taub General Hospital
Houston, Texas, USA
The Problem (USA)
? 5,000,000 patients
? 6,500,000 hospital days / year
? 300,000 deaths / year
? 6% - 10% of people > 65 years
? 5.4% of health care budget (38 billion)
? Incidence x 2 in last ten years
Gottdiener J et al. JACC 2000;35:1628
Haldeman GA et al. Am Heart J 1999;137:352
Kannel WB et al. Am Heart J 1991;121:951
O’Connell JB et al. J Heart Lung Transplant 1993;13:S107
Definition of heart failure
Suspected Heart Failure
because of SYMPTOMS and/or SIGNS
Assess presence of CARDIAC DISEASE
by ECG, X-Ray or BNP
Tests abnormal
VENTRICULAR FUNCTION
Imaging by Echo-Doppler,
Nuclear angiography or MRI if available
Tests abnormal
NORMAL
No Heart Failure
NORMAL
No Heart Failure
Heart Failure: Systolic / Diastolic
Identify etiology, evaluate severity, choose therapy
ESC HF guidelines 2001
Heart disease
No symptoms
HF Risk Factors
No Heart disease
No symptoms
Asymptomatic
LV dysfunction
Refractory
HF symptoms
Prior or current
HF Symptoms
Stages in the evolution
of Heart Failure
A
B
C
D
AHA / ACC HF guidelines 2001
ACE-i
? blockers
Treat risk factors
Diet and exercise
Avoid toxics
ACE-i in selected p.
In selected
patients
Palliative therapy
Mech. Assist device
Heart Transplant
ACE-i
? blockers
Diuretics / Digitalis
Stages in the Evolution
of Heart Failure
Treatment
A
B
C
D
AHA / ACC HF guidelines 2001
Aggravating Factors
Medications
New heart disease
Myocardial ischemia
Endocarditis
Obesity
Hypertension
Physical activity
Dietary excess
Pregnancy
Arrhythmias (AF)
Infections
Thromboembolism
Hyper/hypothyroidism
Initial / Ongoing Evaluation
Identify heart disease
Assess functional capacity (NYHA, 6 min walk, …)
Assess volume status: (edema, rales, jugular, hepatomegaly, body weight)
Lab assessment: routine: electrolytes, renal funct. Repeat Echo, RX only if significant changes in functional status
Assess prognosis
54-60
>60
50
40
30
20
10
0
Post MI
n=196
<30
31-35
36-45
46-53
Cardiac Mortality
%
LVEF
Brodie B. et al
Am J Cardiol 1992;69:1113
Prognosis
Treatment Objectives
(Cost)
Pharmacologic Therapy
Diuretics
ACE inhibitors
Beta Blockers
Digitalis
Spironolactone (Eplerenone)
Angiotensin II Blockers (Candesartan)
HMG-CoA Reductase Inhibitors (“Statins”)
Diuretics
? Essential to control symptoms
secondary to fluid retention
? Prevent progression from HTN to HF
Diuretics. Indications
1. Symptomatic HF, with fluid retention
Edema
Dyspnea
Lung Rales
Jugular distension
Hepatomegaly
Pulmonary edema (Xray)
AHA / ACC HF guidelines 2001
ESC HF guidelines 2001
VASOCONSTRICTION
VASODILATATION
Kininogen
Kallikrein
Inactive Fragments
Angiotensinogen
Angiotensin I
RENIN
Kininase II
Inhibitor
ALDOSTERONE
SYMPATHETIC
VASOPRESSIN
PROSTAGLANDINS
tPA
ANGIOTENSIN II
BRADYKININ
ACE-i. Mechanism of Action
A.C.E.
ACE-I: Clinical Effects
Improve symptoms
Reduce remodelling / progression
Reduce hospitalization
Improve survival
Mortality Reduction with ACE-i
Study ACE-i Clinical Setting
CONSENSUS Enalapril CHF
SOLVD treatment Enalapril CHF
AIRE Ramipril CHF
VHeft-II Enalapril CHF
TRACE Trandolapril CHF / LVD
SAVE Captopril LVD
SMILE Zofenopril High risk
HOPE Ramipril High risk
ACE-i. Dose (mg)
Initial Maximum
Captopril 6.25 / 8h 50 / 8h
Enalapril 2.5 / 12 h 10 to 20 / 12h
Fosinopril 5 to 10 / day 40 / day
Lisinopril 2.5 to 5.0 / day 20 to 40 / day
Quinapril 10 / 12 h 40 / 12 h
Ramipril 1.25 to 2.5 / day 10 / day
AHA / ACC HF guidelines 2001
ACE-I. Contraindications
Intolerance (angioedema, anuric renal fail.)
Bilateral renal artery stenosis
Pregnancy
Renal insufficiency (creatinine > 3 mg/dl)
Hyperkalemia (> 5,5 mmol/l)
Severe hypotension
?-Adrenergic Blockers
Mechanism of action
Density of ?1 receptors
Inhibit cardiotoxicity of catecholamines
Neurohormonal activation
HR
Antiischemic
Antihypertensive
Antiarrhythmic
Antioxidant, Antiproliferative
?-Adrenergic Blockers
Clinical Effects
Improve symptoms (only long term)
Reduce remodelling / progression
Reduce hospitalization
Reduce sudden death
Improve survival
US Carvedilol HF
NEJM 1996; 334: 1349-55
Carvedilol
(n=696)
Placebo
(n=398)
Risk reduction = 65%
p<0.001
0
50
100
150
200
250
300
350
400
1.0
0.9
0.8
0.7
0.6
?-Adrenergic Blockers
0.7
0.8
0.9
1.0
Survival
%
Days
I-II HF
Symptomatic heart failure
Asymptomatic ventricular dysfunction
- LVEF < 35 - 40 %
After AMI
AHA / ACC HF guidelines 2001
ESC HF guidelines 2001
?-Adrenergic Blockers:
Indications
Patient stable
No physical evidence of fluid retention
No need for i.v. inotropic drugs
Start ACE-I / diuretic first
No contraindications
In hospital or not
?-Adrenergic Blockers
When to start
Initial Target
Bisoprolol 1.25 / 24h 10 / 24h
Carvedilol 3.125 / 12h 25 / 12h
Metoprolol tartrate 6.25 / 12h 75 / 12h
Metoprolol succinnate 12,5-25 / 24h 200 / 24h
Start Low, Increase Slowly
Increase the dose every 2 - 4 weeks
?-Adrenergic Blockers
Dose (mg)
Hypotension
Fluid retention / worsening heart failure
Fatigue
Bradycardia / heart block
?-Adrenergic Blockers
Adverse Effects
Review treatment (+/-diuretics, other drugs)
Reduce dose
Consider cardiac pacing
Discontinue beta blocker only in severe cases
Digitalis: Mechanism of Action
Blocks Na+ / K+ ATPase => Ca+ +
? Inotropic effect
? Natriuresis
? Neurohormonal control
NEJM 1988;318:358
Digitalis. Clinical Effects
Improve symptoms
Modest reduction in hospitalization
Does not improve survival
Digoxin toxicity
Advanced A-V block without pacemaker
Bradycardia or sick sinus without PM
PVC’s and VT
Marked hypokalemia
W-P-W with atrial fibrillation
Digoxin. Contraindications
RENIN
Angiotensinogen
Angiotensin I ANGIOTENSIN II
ACE
Other pathways
Vasoconstriction
Proliferative
Action
Vasodilatation
Antiproliferative
Action
AT1
AT2
AT1