HEART FAILUREHEART FAILUREHEART FAILURE

黃雅華 藥師馬偕紀念醫院

2006.06.15

壹、Introduction貳、Definition of HF參、Diagnosis of HF一）Symptoms and signs二）NYHA Fc

　三） Diagnostic tests

肆、Treatment of HF

Content

Heart failure• HF is the inability of the heart to maintain

an output adequate to meet metabolic demand of the body

• Syndrome of hemodynamic abnormalitis：↓Preload↓afterload ↑cardiac output

Epidemiology• Heart failure is a long-term complication of

other cardiovascular disease• Heart failure:

– Incidence (10 new cases/1000 >65yrs)↑– Prevalence (4.6 million in the U.S.) ↑

• Age ↑, post MI survival ↑• Coronary heart disease 12 million in U.S.

– 28%↓death (1987-1997)• Hypertension 50 million in U.S.

– 27.4% blood pressure adequately controlled– 75% heart failure cases have hypertension

• Heart failure is the most common cause for hospitalizations among patients >65yrs

Etiology•Systolic failure

Coronary arterial diseaseHypertensionDilated cardiomyopathy

• Diastolic failureHypertensionHypertrophic cardiomyopathyRestrictive cardiomyopathyConstrictive pericarditis

•High-output failureChronic anemiaAtrioventricular shuntsThyotoxicosis

Prognosis• 22-46% of patients who had an MI

will develop heart failure within 6 years

• 5-year mortality rate of 50%• Median survival after onset of heart

failure is 1.7 yrs for men and 3.2 yrs for women

Palliative Care for Patients With Heart Failure JAMA Vol. 291 No. 20, May 26, 2004

Problem- Very Subjective

Definitions• Strength of the Recommendations:• Class I:• Conditions for which there is evidence and/or general agreement

that a given procedure/therapy is useful and effective.• Class II:• Conditions for which there is conflicting evidence and/or a

divergence of opinion about the usefulness/efficacy of performing the procedure/therapy.

• Class IIa:• Weight of evidence/opinion is in favor of usefulness/efficacy.• Class IIb:• Usefulness/efficacy is less well established by evidence/opinion.• Class III:• Conditions for which there is evidence and/or general agreement

that a procedure/therapy is not useful/effective and in some cases may be harmful.

Levels of Evidence

A. Data were derived from multiple randomized clinical trials

B. Data were derived from a single randomized trial or non-randomized studies

C. Consensus opinion of experts was the primary source of recommendations

What drugs may induce CHF?

•Negative Inotropic Agent：ß-Blocke、CCB、Antiarrhythmics (class 1)

•Direct Cardiotoxins：Anthracycline cancer chemotherapeutic drugs– Daunomycin and daunorubicin(Adriamycin);dose related ;Keep

total cumulative dose

Diagnosis of HF1)Symptoms of HF (at rest or during exercise)

Dyspnea、Leg edema、hepatomegaly、S3、engorgement、tachycardia、lung rhonchus

And2)Object evidence (by echocardiography) or cardiac dysfuntion

and3)Response to treatment directed towards HF

☞Signs and symptoms of systolic symptomLV failure RV failure

Subjective DOE ，SOBOrthopnea(2-3 pillows) PND，CoughWeakness，fatigue confusion

Peripheral edemaWeaknessfatigue

Objective LVH，↓BPEF‹40%Rales,S3 gallop rhythm ，Reflex tachycardia↑BUN (poor renal perfusion)

Weight gain(fulidretention)

Neck vein distentionHepatomegalyHepatojugular

reflex

Table . Staging and classification schemes for HF

ACC/AHA staging system

NYHA Fc

A At high risk for HF without structural heart disease or symptoms of HF.

I No symptoms with ordinary physical activity

B Structural heart disease without symptoms of HF

II Symptoms with ordinary activity

C Structural heart disease with prior or current symptoms of HF

III Symptoms with less than ordinary activity. Marked limitation of activity

D Refractory HF requiring specialized interventions

IV Symptoms with any physical activity or at rest.

Laboratory testing–CBC, urinalysis–serum electrolytes (including Ca, Mg)–blood lipids– renal and hepatic function tests–Thyroid function tests (TSH)

Diagnosis test• Electrocardiogram• 正常時,可排除左心室異常之negative predictive value超過90%以上• 可提供陳舊性心肌梗塞,左心室肥厚,心房纖維顫動,心房撲動等重要資訊

• chest radiography– the degree of cardiac enlargement, pulmonary congestion,

pulmonary disease.

• Echocardiography• Image scopy• Others---B-type Natriuretic peptide(BNP)---Hf patients BNP ＞400pg/ml

---BNP ＜100pg/ml有相當高的陰性測驗值---BNP 100~400pg/ml,考慮是否其他因素引起之非心因性呼吸困難

Stage AAt high risk for HF

but withiut structural heart dieaseor symptoms of HF

.patients with:-hypertension-coronary artery disease-DM-using cardiotoxins-with FHx CM

StructuralHeart

disease

Stage Bstructural heart diease

but without symptoms HF

.patients with:-previous MI-LV systolic dysfunction-asymptomatic Vavulardisease

DevelopmentOf symptoms

Of HF

Therapy-All measures under stage A-ACEI in appropriate p’t-ß-Blocker in appropriate p’t

Therapy-treat hypertension-encourage smoking cessation-treat lipid disorder-Encourage regular exercise-Discourage alchol intake,illicit drug use-ACEI in appropriate P’t

Stage Cstructural heart diease

with prior or current symptoms of HF

Stage DRefractory HF requiring specialized interventions

patients who have marked symptoms at rest despite maximal medical therapy

(eg,those who are recurrently hospitalized orcan’t be safely discharged from the

hospital without specialized interventions

RefractorySymptoms of

HF at rest

.patients with:-Known structural heart

Disease-shortuess of breath and fatigue

,reduced exereise tolerance

Therapy--All measures under stage A

-,B and C--Mechanical assist devices

--Heart transplantation--Continuous(not inotropic

-infusions for palliation--Hospice care

Therapy-All measures under stage A

-Drug for routine use:Diuretics

ACEIß-BlockerDigitalis

-Dietary salt restriction

Treatment Approach for the Patient with Heart Failure

Stage AStage A Stage BStage B Stage DStage D

•• Treat HTN (IA)Treat HTN (IA)

•• Treat lipid Treat lipid disorders (IB)disorders (IB)

•• Discourage Discourage alcohol , smoking, alcohol , smoking, illicit drug use (IC)illicit drug use (IC)

•• ACEI in ACEI in atherosclerotic Dxatherosclerotic Dx, , DM, HTN (IB)DM, HTN (IB)

•• Control VR in pts Control VR in pts with SVT (IB)with SVT (IB)

•• Tx Tx thyroid (IC)thyroid (IC)

•• Evaluate sign (IC)Evaluate sign (IC)

•• Noninvasive Noninvasive evaeva. . LV function (IIA)LV function (IIA)

•• All measures All measures under stage Aunder stage A

•• ACEI in MI pts (IA)ACEI in MI pts (IA)

•• ACEI in low EF ptsACEI in low EF pts(IB)(IB)

•• BB in MI pts (IA) BB in MI pts (IA)

•• BB in low EF ptsBB in low EF pts(IB)(IB)

•• Valve replacement Valve replacement (IB)(IB)

•• LongLong--term term Tx Tx withwithsystemic systemic vasodilators (IIB)vasodilators (IIB)

•• All measures All measures under stage Aunder stage A

•• Diuretics (IA)Diuretics (IA)

•• ACEI for all pts, ACEI for all pts, unless contra. (IA)unless contra. (IA)

•• BetaBeta--blockers in all blockers in all stable pts, unless stable pts, unless contra. X fluid contra. X fluid retention, x IV retention, x IV inotropic inotropic agent (IA)agent (IA)

•• Digitalis unless Digitalis unless contra. (IA)contra. (IA)

•• x NSAID, CCBx NSAID, CCBantiarrhythmic antiarrhythmic (IB)(IB)

•• Adactone (IIaBAdactone (IIaB))

•• ARB ARB (IIaA(IIaA))

•• Hydralazine Hydralazine + + nitrate nitrate (IIaB(IIaB))

•• All measures All measures under stages A,B, under stages A,B, and Cand C

•• Mechanical assist Mechanical assist devicesdevices

•• Heart Heart transplantation IB)transplantation IB)

•• PulPul. Artery catheter. Artery catheterplacement placement (IIbC(IIbC))

•• Mitral Mitral valve repair valve repair (IIbC(IIbC))

•• Continuous (not Continuous (not intermittent) IV intermittent) IV inotropicinotropic infusions infusions for palliation for palliation (IIbC(IIbC))

•• Hospice careHospice care

Stage CStage C

Medical therapy 3 main goals: (1) preload reduction→ results in increased cardiac output and improved renal

perfusion

(2) afterload reduction(reduction of systemic vascular resistance)

→results in increased cardiac output and improved renal perfusion

(3) inhibition of both the RAAS systems and vasoconstrictor neurohumoral factors

→ results in favored vasodilation and reduction of neurohumoral vasoconstrictors

→ thereby increasing cardiac output and reducing blood volume and myocardial oxygen demand

☞↓Preload drug：Nitrate Diuretics☞Combined ↓Preload & afterload(Vasodilators) ：

ACEIARBHydralazineNitroprusside☞ Inotropic support：

DigoxinPDE inhibitorsDobutamineDoPamineβ-Blocker

Drug therapy•12.02 Cardiotonic agent (Intropic Agents)

1202A Digoxin1202B PDE inhibtors1202C Adrenergic agent

•1208A Renin-Angiotensin systen inhibotor1208A1 ACEI1208A2 Angiotensin Receptor Blockers(ARB)

•1208F ß-Blockers•1806 Diuretic

12.02A Digoxin • Na pump inhibition

– ↑cytosolic Ca conc– Enhance myocardial contractility

• Autonomic and renin-angiotensin effects– Parasympatheti activation

• Sinus slowing &AV nodal inh– Symptathetic inhibition– Renin release inh:

• Decreased activity of renal Na pump with natriureticeffect

– →offset direct vasoconstriction• Increase EF and CO• primacy in the treatment of HF with atrial

fibrillation

• 據PROVED 及RADIANCE trial，心臟衰竭症狀惡化之情形，因 Digoxin使用而減少。

• 據DIG trial。在Ejection fraction

Digoxin Pharmacokinetcis•T1/2 : Normal:1.6-2 days

Renal failure: >4.4 daysChildren:0.7-1.5 days

•Therapeutic serum level 0.8-2 ng/mlPeak:8-12hrs after oral or IV doseTrough:immediately before next dose

•Steady state:5-7days•Resampling time:5-7daysUsual Digitalizing dose 0.5-1mg

or 0.01-0.02mg/kgUsual maintenance dose 0.125-0.5 mg/day

Dose:Loading Dose: VD*Cp/S*F

8-12µg/kg–LD is administered in divided dose, 50% of the total dose given at the first dose, additional 25% fraction is administered at 4-6hr interval IV or 6-8hr intervals orally until total digitalizing dose.

Maintenance dose:–Adult:25-35% of LD.–Pediatric:10 µg/kg/d(elixir:0.5mg/ml)

CLcr Digoxin (with CHF)=(0.33ml/min)*Wt + 0.9CLcr

Vd Digoxin=(3.8L/kg)*Wt + 3.1CLcrKd=CL/VdT 1/2 = 0.693/Kd =2.53d達S-S的時間: 4 x T ½Clcr = (140-age) × BW / (72 × Scr) ml/minCss = F×D / Cl×t)

•Factors That May Predispose Patients to the Development of Digoxin Intoxication:

Electrolyte abnormalitiesHypokaelemiaHypomagnesiumHypercalemia

Advanced age AlkalosisHypoxiaRenal dysfunctionHypothyroidismDrug interactions

• Side effect一)Noncardiac1.Gastrointestinal: anorexia, N/V2.Neurologic : fatigue, malaise, delirium acute

psychosis, neuralgic pain3.Ocular : halo vision, green or yellow vision4.Miscellaneous : gynecomastia, sexual

dysfunction (male)二)Common cardiac arrhythmias

Ventricular premature depolarizations (VPD), VPCs, bigeminy or trigeminyFirst-degree AV block multifocal Nonparoxysmal junctional tachycardiaSupraventricular tachycardia with blockVentricular tachycardia

◎Digoxin drug Interaction•Drugs lowering serum digoxin conc

antiacids、questran、kaopectin、neomycin、 metoclopramide、rifampin、sulfasalazine

•Drugs raising serum digoxin concalprazolam、amiodarone、captopril、

CCB、Clarithromycin、cyclosporine、EM、itraconazole、omeprazole、quinidine、telmisartan

Contraindications：• Bradycardia• 2-3。AV block• Sick sinus syndrome• Carotid sinus syndrome• Hypo-kalaemia and hyper- kalaemia

12.02B PDE inhibitorsPhosphodiesterase inhibitor

• PDE inhibitor that has direct positive inotropic and vasodilatory actions•Higher incidence of treatment-related new AF and sustained hypotension•Trend toward more MIs and ventricular tachyarrhymias

Milrinone (Primacor 派明克注射劑 )10mg/10mL Vial

• Adult CFH IV infusioninitial loading dose, 50 mcg/kg IV over 10min,MD 0.375- 0.75 mcg/kg/min,

Max. total dose 1.13 mg/kg daily•PediatricLD, IV, 75mcg/kg; MD 0.75-1 mcg/kg/min •Dosing adjustments in renal impairmeny

Clcr 50mL/min: 0.43 mcg/kg/minClcr 40mL/min: 0.38 mcg/kg/minClcr 30mL/min: 0.33 mcg/kg/minClcr 20mL/min: 0.28 mcg/kg/minClcr 10mL/min: 0.23 mcg/kg/minClcr 5mL/min: 0.2 mcg/kg/min

Side effect• Chest pain, hypotension, headache,

hepatotoxicity, • proarrhythmic events, thrombocytopenia• Cardiac monitor, BP, serum potassiumNote• Continuous infusion 0.25-1

mcg/kg/min to maintain beneficial hemodynamic effects for 24h period in severe heart failure.

Contraindication• AMI• Tight aortic stenosis• obstructive hypertrophic cariomyopathy

12.02C Adrenergic agentinotropic agent

•Dopamine,Dobutamine–Acute cardiac emergencies

•β2 receptor effect–Dobutamine > Dopamine

•IF shock、hypotension、pulmonary edema•systolic BP < 70mmHg (clinical shock) ⇒Norepinephrine 0.5-30μg/min

Or Dopamine 5-20 μg/kg/min•systolic BP 70-100 mmHg (clinical shock) ⇒Dopamine 2.5-20μg/kg/min, then add

Norepinephrine•systolic BP 70-100 mmHg (no clinical shock) ⇒Dobutamine 2.5-20μg/kg/min•systolic BP > 100mmHg •⇒Nitroglycerin start 10-20μg/min

And/Or Nitropresside 0.-0.5μg/kg/min

Dopamine Dobutamine mechanism α1，β1，β2，D1 β1 >β2 >α1 Dose Congestive heart failure:

IV infusion, Initial 0.5-2mcg/kg/min. Most p't respond adequatley to dose of 1-3mcg/kg/min.

Inotropic support: IV, initial, 0.5-1 mcg/kg/min, MD 2.5-20 mcg/kg/min ; titrate according to response, Max.40 mcg/kg/min.

COMMON

anxiety,headache,chest pain, hypertension, palpitations, tachycardia, dyspnea,

chestpain, hypertension, palpitations, tachycardia, dyspnea, headache, hypokalemia,

SERIOUS

ectopic heartbeats, gangrene of extremities, widened QRS complex, ventricular arrhythmias

arrhythmias, eosinophilic myocarditis, thrombocytopenia

Contraindications

pheochromocytoma, tachyarrhythmias/ventricular fibrillation

hypersensitivity to dobutamine idiopathic hypertrophic subaortic stenosis

note 1.correct hypovolemia before initiation, monitor ECG and BP

•DopamineA endogenous precursor of norepinephrineMechanism•Congestive heart failure:IV infusion, Initial 0.5-2mcg/kg/min. Most p't respond adequatley to dose of 1-3mcg/kg/min.

Hemodynamic effect :• Low-dose : IV infusion,1-3mcg/kg/min,

increased renal blood flow and urine output

• Intermediate-dose : IV infusion,3-10mcg/kg/min, increased renal blood flow, heart rate, cardiaccontractility, and cardiac output.

• High-dose :IV infusion, >10mcg/kg/min, alph-adrenergic effects begin to predominate, vasoconstriction, increased blood pressure.

CLINICAL APPLICATIONS: •The overall hemodynamic ffect are a potent inotropic agent with vasodilation•IndicationSeverely depressed LV function with a low cardiac index and elevated LV filling pressure，but mean arterial BP not <70mmHg

Dobutemine (Dobutrex)• Peoduces vasodilation and increasea

inotropis state• At higher dosage may cause ↑ heart

rate , exacerbating myocardial ischemia• Inotropic support:

IV, initial, 0.5-1 mcg/kg/min,MD 2.5-20 mcg/kg/min ; titrate

according to response, Max.40 mcg/kg/min

12.08A1 ACEI•Decrease preloag & afterload and blood volume

•根據CONSENSUS、V-HeFT II、SOLVD、SAVE、AIRE、TRACE 等clinical trials， preference to ACEI that have been shown to reduce morbidity and mortality

•FDA approval for use in HF:Captopril (capoten) 、 enalapril (Renitec) 、fosinopril (monopril) 、ramipril (tritace)

•Prevents ischemia— Stimulates endothelial NO production— Reduces myocardial oxygen consumption• Opposes atherogenesis • Lowers systemic vascular resistance and mean blood pressure • Reduces cardiac afterload and systolic ventricular wall stress • Attenuates remodeling in heartfailure

Renal insufficiency: • If SCr continues to rise, patient

should discontinue the ACE inhibitor• Even patient with baseline renal

insufficiency (SCr

學名 Captopril Enalopril Ramipril Fosinopril 商品名 Capoten Renitec Tritace Monopril 劑型 25mg/tab 20mg/tab 2.5 mg/tab 10 mg/tab 劑量 initial 6.25-12.5 mg

tid; MD 12.5-25 mg tid; may be increased to 50-100 mg tid,

Max. 450 mg/day

initial 2.5 mg qd or bid; MD 5-20 mg/day div. 2 doses; Max. 40 mg/day

CHF (post MI): initial 1.25-2.5 mg bid; titrated as tolerated to 5 mg bid

initial 10 mg qd; MD 20-40mg/day; Max. 40mg/day

劑量 調整

Clcr 10-15 mL/min: 75% of normal dose or q12-18 hr Clcr < 10 mL/min: 50% of normal dose or q24h

(Clcr about 16 mL/min) or hyponatremia: starting dose 2.5 mg qd; titrate at 4-day intervals to 2.5 mg bid, then 5 mg bid Max. 40 mg/day

Clcr < 40mL/min, initial 1.25 mg qd, then 1.25 mg bid, Max. 2.5 mg bid

Initial dose of 5 mg is preferred in patients with CHF and moderate to severe renal impairment.

Note reduce dose if used with diuretics

reduce dose if used with diuretics

reduce dose if used with diuretics

NOT NECESSARY

健保價 9.4 14.3 19.4 17.4

Side effectCOMMON–cough, headache– dizziness, fatigue,, hyperkalemia,–hypotension, N/VSERIOUS–angioedema,– hepatic failure

•Contraindicant＊Absolute: History of angioedema,

bilateral renal artey stenosis, pregnancy＊Relative: Unilateral renal artery stenosis,

renal insufficiency, hyperkalemia,hypotension, cough

•Caution– SBP < 80 mmHg– Cr > 3mg/dL– Bilateral renal artery stenosis– K > 5.5 mmol/L

12.08A2 ARBs

• Mimic ACEI• Arterial vasodilators• 據ELITE II trial， Losartan用於治療有症狀心衰竭，與Captopril 比較，無明顯差異，俱可以減少死亡率。據VAL-HeFT trial，Valsartan 可以減少因心衰竭所致死亡率

12.08F ß-Blocker•Reverses cardiac remodeling

Prevents sudden death Prevents ischemia

•Decreases heart rate and blood pressure- Prolongs diastole (filling of coronary arteries

• 據MCD , CIBIS-II 及U.S. trials 此類藥物如Metoprolol，Bisoprolol，Carvedilol可減少擴大型及缺血性心肌病變之死亡率。

◎Patient selection• The safety and efficacy in the patient

with active volume overload or acute exacerbations of chronic heart failure is unknown

• Used in all patients with stable NYHA class II-III ischemic and non-ischemicheart failure without contraindications

學名 Metoprolol

Bisoprolol Carvediol

商品名 Concor Dilatrend form 5mg 6.25mg/25mg dose initial 1.25 mg qd; titrate

to Max. 10 mg/day 3.125mg bid for 2 wks, then doubled every 2 wks if necessary, Max. 50mg/day

劑量 調整

Clcr < 40 mL/min: initial 2.5 mg daily

Use is contraindicated in liver dysfunction

Side

effec bradycardia,hypotension,

dizziness, diarrhea sleep disturbances

dizziness hypotension hyperglycemia diarrhea bradycardia

Contraindications cardiogenic shock, overt cardiac failure, 2-3 degree AV block, severe sinus bradycardia

bronchial asthma,COPD, cardiogenic shock, overt cardiac failure, 2-3 degree AV block, severe liver failure, severe sinus bradycardia, sick sinus syndrome

• Carvedilol: 35% mortality reduction, 1996

• Carvedilol (FDA), metoprolol and bisoprolol are the only β-Blockers which should be used in treating heart failure

• Hypertensive cardiomyopathy or persistent hypertension →Carvedilol

• Borderline hypotension, reactive airway disease →metoprolol

12.08F ß-Blocker-2•Side effect

–Hypotension,worsen HF,Fluid restension

• Contraindicant：–Asthma –Severe bronchial disease–Symptomatic bradycardia or hypotension–Heart rate ＜50下/min (使用心節律器者除外) –BP ＜ 85mmHg

1806 Diuretic-1

• Decrease Vascular volume• Relieving ventricular and pulmonary

congestion and decrease peripheral edema• 主要用於減輕肺鬱血及周邊水腫。開始時可用

Thiazides 或Loop diuretics，合併ACEI使用。• 若GFR ≤30ml/min，則使用Loop diuretics，若效果不彰，可合併 Loop diuretics + Thiazides或增加Loop diuretics 之Dose。

thiazide loop spironolactone Site of action Distal convoluted tubule Ascending loop of Henle Distal convoluted tubule

Aldosterone antagonism

↑Na excretion 5-8 % 25-30% 2-3%

Side effect dizziness, hypotension

↓Na, K, Mg

↑uric acid ,glucose

Hypokalemia,

hyperuricemia,

dizziness, headache

Gynecomastia

Hyperkalemina

diarrhea, rash

precaution anuria anuria anuria, hyperkalemia, acute

renal insufficiency

• Signs of volume depletion：WeaknessHypotension ，diazzinessOrthostatic change in BP↓urin output↑BUN

• Insufficient response：---increase dose of diuretic---combine loop diuretics and thiazides---with persistent fluid retention；

adminster loop diuretics twice daily---in severe HF add spironolactone with

frequent measurement of creatinine和 electrolytes

Spironolactone• RALES:

– 40% mortality reduction among patients with advanced heart failure (NYHA III-IV)

– Background therapy : ACE inhibitors, β-Blockers, digoxin, diuretics

• Drug interactiondrug diuretic Effectß-Blocker thiazide glucose, uric acid, lipid

Digoxin ThiazideLoop D

K (digoxin toxicity)

ACEI K-sparing D K (arrhythmia)

Aminoglycoside Loop D ototoxicity, nephrotoxicity

Adrenal steroidAmphotericin B

ThiazideLoop D

Enhanced hypokalemia

Chloropamide thiazide hyponatremia

Lithium thiazide lithium clearance

血管擴張劑

• 據V-HeFT I trial，Nitrate-Hydralazine 合併使用可減少心衰竭之死亡率。

– V-HeFT II study： Mortality ↓, norepinephrine↑, compliance, neurohormone ↑

• Used in patients with ACE inhibitor intolerance secondary to renal insufficiency, angioedema, or hyperkalemia

ConclusionDrug treatments should be initiated in the following order：•ACE inhibitor - with diuretic if needed -

for NYHA Grades I-IV•ARB - if intolerant of ACE inhibitor•Beta-blocker - for NYHA Grades I-IV.•Spironolactone - for NYHA Grades III-IV.•Digoxin - for NYHA Grades II-IV

THE ENDTHE ENDTHE END

Thanks !!!Thanks !!!

HEART FAILUREHeart failureEpidemiologyEtiologyPrognosisDefinitionsLevels of EvidenceWhat drugs may induce CHF?Diagnosis of HF☞Signs and symptoms of systolic symptomTable . Staging and classification schemes for HF Laboratory testingDiagnosis testMedical therapy 3 main goals:Drug therapy12.02A Digoxin12.02B PDE inhibitors Phosphodiesterase inhibitor12.02C Adrenergic agentinotropic agent12.08A1 ACEI12.08A2 ARBs12.08F ß-Blocker12.08F ß-Blocker-21806 Diuretic-1Spironolactone血管擴張劑ConclusionTHE END