Heart failure

Trương Thanh Hương, PhD.

Hanoi Medical University

Definition

•

Heart failure is a condition in which the cardiac output is insufficient in meeting the needs of oxygen of the body in any situation. Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. The term "heart failure" is more accurate than "congestive heart failure" because fluid accumulation may not occur in all patients.

Heart failure classification

failure, right-sided heart failure.

• The side of the heart involved: left-sided heart

• Progress of heart failure: acute heart failure,

chronic heart failure.

• The change in the cardiac output: low-output

heart failure, high-output heart failure.

• Systolic heart failure and diastolic heart failure

Causes

Left-sided heart failure

• Hypertension • Valvular heart diseases: aortic valve stenosis, aortic

regurgitation (pured or combined), mitral regurgitation • Myocardial injury: MI, rheumatic myocarditis, intoxication,

bacterial contamination, myocardial diseasesthmias

• Congenital heareases: coarctation of the aorta, patent ductus

arteriosus • Arrhythmias • Be noticed of mitral stenosis

causes

Right-sided heart failure • Left-sided heart failure • Pulmoray diseases, deformity of thorax-spine • Cardiovascular causes:

– Mitral stenosis is a common cause – Tricupid and aortic valvular diseases – Congenital heart diseases (Pulmonary valve stenosis, tetralogy of Fallot): congenital heart diseases with reversed shunt, ruptured sinus of valsalva into right heart chambers, left atrial myoxoma...

• Be noticed of pericardial effusions and compressive

syndromes

causes

Two-sided heart failure • Left-sided heart failure often leads to two-sided

heart failure in the longer term.

• Dilated cardiomyopathy, carditis caused by

rheumatic fever, myocarditis

• Two-sided heart failure with high cardiac output: severve anaemia, hyperthyroidism, vitamin B1 deficiency, arteriovenous fistula...

Left-sided heart failure symptoms

Clinical symptoms

Presenting symptoms • Dyspnea on exertion -> dyspnea at rest, orthopnea,

cardiac asthma or acute pulmonary edema • Dry/loose cough or coughing up blood, cough

nocturnally/on exertion

Left-sided heart failure symptoms

Signs • Left-laterally displaced apex, tachypnea, a gallop rhythm. • A faint apical systolic murmur indicates secondary mitral regurgitation (due to the dilatation of the left ventricle).

• Signs of left-sided heart failure causes. • Wet rales heard initially in the bottom of the lung bases.

Cardiac asthma: wheezing, snoring. Pulmonary edema: rales extend from the base upward.

• Decreased systolic blood pressure, normal diastolic blood pressure leading to decreased hypertension difference.

Left-sided heart failure symptoms

NONCLINICAL SYSTOMS • Chest X-ray: cardiomegaly, bulging and prolonged left heart border caused by dialated left ventricle. Bilateral increased lung markings especially in the centre, Kerley B lines caused by edema in the interstitial of lung lymphatic system, shaped like bats wings in the centre when pulmonary edema presents.

• ECG:

left heart axis,

left atrial hypertrophy,

left ventricular

hypertrophy.

• Echocardiagraphy: dialated left atrium and ventricle, decreased contraction of heart walls, decreased left ventricular systolic funtion, finding out causes of left-sided heart failure.

• Haemodynamic study: decreased cardiac index (normal value 2- left-ventricular end-diastolic pressure,

increased

3.5l/min/m2), grading the severity of mitral regurgitation, aortic regurgitation...

right-sided heart failure symptoms

Clinical symptoms

–

Presenting symptoms – Dyspnea: increasing dyspnea without paroxysmal nocturnal dyspnea as left-sided heart failure. Pain in the right upper quadrant caused by painful hepatomegaly.

Signs – Hepatomegaly with "accordion effect". –

Jugular venous distension, positive hepatojugular reflex

right-sided heart failure symptoms

• Signs

Peripheral blood stagnant -> increased deoxyhemoglobin -> light blue of the skin and mucous membranes -> cyanosis – The excess fluid accumulation in the lower limbs -> in the

– Increased peripheral and central venous pressure. – A blue coloration of the skin and mucous membranes:

– Oliguria, dark urine (200-300ml/day) – Hartzer sign: dilated displaced right ventricular apex. – Tachypnea, a right-sided gallop rhythm. – A faint systolic murmur heard low on the lower left sternal border indicates tricuspid regurgitation. It becomes louder during inspiration (Rivero Carvanlho's sign).

whole body.

pressure.

– Normal systolic blood pressure, increased diastolic blood

right-sided heart failure symptoms

NONCLINICAL SYMSTOMS • Chest X-ray: bulging right heart border, upward heart apex caused by dilated right ventricle. Distended pulmonary vascular bed, lung markings caused by blood stagnant. Enlarged right ventricle causes narrow light gap behind the sternum.

• ECG: right heart axis, right atrial hypertrophy, right

ventricular hypertrophy.

• Echocardiography: enlarged right ventricle, signs of

pulmonary arterial hypertension.

• Haemodynamic study: increased right ventricular end-diastolic pressure (>12mmHg), pulmonary arterial hypertension.

Biventricular heart failure

• Constant dyspnea, the excess fluid accumulation

in the whole body.

• Jugular venous distension. • Increased venous pressure. • Hepatomegaly. • Pericardial effusion, pleural effusion, ascites. • Decreased systolic blood pressure, increased

diastolic blood pressure. • Chest X-ray: cardiomegaly. • ECG: biventricular hypertrophy.

X-Ray Image

Right-sided heart failure

Left-sided heart failure

Electrocardiography

LEFT-SIDED HEART FAILURE ECG: Left heart axis, left atrial hypertrophy, left ventricular hypertrophy

RIGHT-SIDED HEART FAILURE ECG: Right heart axis, right atrial hypertrophy, right ventricular hypertrophy

Echocardiography

LEFT-SIDED HEART FAILURE

RIGHT-SIDED HEART FAILURE

Heart failure classification The ACC/AHA staging system NYHA classification for heart failure

A A

Patients are at high risk for heart Có Nguy cơ cao ST song không có bệnh failure but have no structural heart tim thực tổn hoặc không có biểu hiện suy tim disease or symptoms of heart failure

I I

B B

Patients have no limitation of Patients have no limitation of physical activity physical activity

Patients have structural heart disease Có bệnh tim thực tổn nhưng không có biểu but have no symptoms of heart hiện suy tim failure

C C

Patients have structural heart disease Bệnh tim thực tổn đã hoặc đang có biểu and have symptoms of heart failure hiện suy tim

II II III III

Patients have slight limitation of physical Patients have slight limitation of activity physical activity Patients have marked limitation of Có triệu chứng khi gắng sức nhẹ physical activity

IV IV

D D

Patients have refractory heart failure Suy tim trơ, đòi hỏi phải các biện pháp điều trị đặc biệt requiring specialized interventions

Patients have symptoms even at rest and are unable to carry on any Có triệu chứng ngay cả lúc nghỉ physical activity without discomfort

TREATMENT

Schematic therapy of progressive chronic heart failure

The role of drugs in the treatment of heart failure

• Reduce Mortality:

– ACE inhibitors or ARBs – Beta blockers – Spironolactone; Eplerenone Improve symptoms: – Diuretics – Digoxin (low dose) – Nitrates

•

• May be harmful: use cautiously after due

consideration: – Inotropes and inotropic dilators – Antiarrhythmics, expect Beta blockers and amiodarone – Calcium channel blockers – Digoxin (high dose)

Nonpharmacologic Therapy

•

Sodium restriction:

• Salts cause increased osmotic pressure, increased circulatory

volume and increase the burden on the heart

• Normal: 6-18g NaCl/day=2,4-7,2g (100-300 mmol) Natri/day.

• Sodium restriction : <3g NaCl/day  <1,2g (50  mmol)

Natri/day.

• Completed sodium restriction : <1,2g NaCl/day  0,48g (20

mmol) Natri/day.

• Rest: reduce cardiac load. Severe heart failure: bed rest, down in Fowler's position, massage legs to prevent venous thrombosis.

Nonpharmacologic Therapy

– Fluid and free water restriction reduce circulatory volume and

decrease the burden on the heart: 500-100ml/day

– Administration of supplemental oxygen may relieve dyspnea,

improve oxygen delivery, reduce the work of breathing and limit pulmonary vasoconstriction – Lifestyle/Risk modification

Reducing Alcohol intake, cessation of smoking, cafe...

Weight loss in obesity patient

Avoid stress

Stop inotropic: Verapamil, Disopyramide, Flecainide.

• • • • •

Identify precipitating and exacarbating factors and any concomitant factors relevant to HF: sepsis, Arrhythmias

Pharmacologic Therapy

Glucoside (Digoxin).

•

Increase myocardial contractility (Inhibition of Na, K ATPase  Altered balance of Na/Ca exchange  Enhanced Ca storage/release). Enhanced vagal tone (reduce heart rate). Digoxin may attenuate the neuro-hormonal activation associated with HF.

• The serum haft-life of digoxin is 36 h; the usual daily dose is

• Therapeutic dose: 0,5-0,8-2,0 ng/ml serum. The toxic –

0.125-0.375mg

therapeutic ration is narrow

Verapamil, Spironolacton, Amiodarone...

• Drug interactions which decrease digoxin release: Quinidin,

Pharmacologic Therapy

Glucoside (Digoxin)

•

Indication:

– Low-output cardiac failure, especially rapid atrial fibrillation

– No indication in High output cardiac failure: anemia, thyrotoxicosis,

fistula arteriovenous, Chronic cor-pulmonale.

– Bradycardiac, Block A-V II, III, ventricular fibrillation, ventricular

tachycardiac, WPW symdrome

• Contraindication:

– Acute myocardial infarction: increase oxygen demand.

– Electrolyte abnormalities:  K+ vµ / Mg++

• Caution:

Pharmacologic Therapy

Glucoside (Digoxin)

– Risk factors

– Clinical signs and symptoms

• Loss of appetide, nausea/vomiting, diarrhea.

• Visual disturbances, confusion, dizziness, nightmares.

•

Increased automaticity and depressed conduction

• Treatment:

– Stop the drug, control Electrolyte abnormalitie, kalemia.

– 20-50ml KCl 10%, oral or IV 13-15 mmol/h.

– Atropin 0,5-1 mg IV: sinus bradycardiac, bloc AV.

– Lidocain IV1-4mg/phót: ventricular arrhythmia.

– Antidotal therapy with antibody (Fab) fragments.

• Digoxin toxicity

dig study (Digitalis Investigators Group)

N Eng J Med 1997, 336: 525-33.

n NYHA II (%) NYHA III NYHA IV CAD ACE (%) Death after 3,5 years Severe heart failure Placebo 4303 55 31 2 70(%) 95 30 (%) 34,7 Digoxin 3397 53 31 2 71(%) 94 30 (%) 26,8 **

drugs in treatment hf

Diuretics • Mechanism: Removal of excess extracellular fluid with diuretics

• Classification:

to treat peripheral and/or pulmonary edema is one of the mainstays of volume management. Diuretics reduce magnesium absorption and hypomagnesaemia may occur with prolonged use

• Indication with normal renal function.

• Inhibit sodium transport in the distal tubule.

• Hydrochlorothiazide (Thiazide): The potential adverse metabolic effects of thiazide therapy include hypokalemia, hyponatremia, hyperuricemia, elevations in the plasma glucose and cholesterol concentrations, and magnesium depletion

• Indapamide little effect on lipid

– Thiazides

drugs in treatment hf

• Loop diuretics: Furosemide, Bumetanide.

– Inhibit sodium and chloride reabsorption. Side effect: Electrolyte imbalances (particularly hypokalemia and hypomagnesemia)

– Use in renal impairment. Direct intravenous vasodilators

– Act in the thick ascending limb of the loop of Henle.

Amiloride.

– Act in the principal cells in the cortical collecting tubule.

– Have relatively weak natriuretic activity

– ThËn träng khi dïng kÌm IEC, gi¶m viªm kh«ng steroide ( K+)

– Increase BUN, Nephrolithiasis (Triamterene); gynecomastia

(Spironolactone).

• Potassium-sparing diuretics: Spironolacton, Triamterene,

Diuretics aldosterone antagonist has obvious benefits in the treatment of heart failure because it does not merely diuretic

• Often used in combination with other diuretics

(Loop, thiazides) – Increase the diuretic effect – Reduce drug effect – Reduce the side effects

• Improve turns vicious circle in chronic

congestive heart failure:

• Reduce the harmful effects of aldosterone

Aldosterone for heart failure treatment

Aldosterone

 Na+

 LV mass & fibrosis

 Arterial compliance  Baroreceptor function  Norepinephrine uptake  Endothelial function  PAI-1

 K+  Mg++  Fibrosis  Norepinephrine Uptake  Heart rate variability

 Arrhythmia

 Edema  Remodeling

 Ischemic Events

Sudden cardiac death

Progression of HF

RALES: Study design

Suy tim NYHA III, IV LVEF ≤ 35% ACEI + Loop diuretics ± digoxin

3 n¨m

Placebo (n = 841)

Spironolactone 25 – 50 mg/day* (n = 822)

Primary Endpoint • Total mortality

Secondary Endpoints • Total mortality • Cardiac hospitalization • Cardiac mortality or cardiac hospitalization

Pitt B, Zannad F, Remme WJ, et al. N Engl J Med. 1999;341:709-717. *Protocol used a starting dose of 25 mg/day whereas the mean daily dose was 25 mg.

RALES: All - cause mortality

1.00

0.95

0.90 Reduce the risk of death 30% 95% Cl (18%-40%) P<0.001

0.85

0.80

0.75 Spironolactone + Standard therapy

0.70 Probability of survival

0.65

0.60

0.55

0.50 Standard therapy (ACE + Loop diuretic + digoxin)

0.45 0 3 6 9 12 15 18 21 24 27 30 33 36 Months

Pitt B, Zannad F, Remme WJ, et al. N Engl J Med, 1999;341:709-717.

drugs in treatment hf

Vasodilators.

• Compensatory mechanism in heart failure  artery

and veins spasm   preload and afterload.

– Pulmonary vasoconstriction because of Hypoxic blood, increasing blood flow through the lungs for a long time (shunt left - right),  left atrial pressure (mitral stenosis, heart failure).

Hypertrophic cardiomyopathy, Restrictive cardiomyopathy.

– Side effects: lowering BP. Caution in aortic stenosis,

drugs in treatment hf

Vasodilators.

• ACEs

–  Angiotensine II (vasoconstriction),  Bradikinine

– Vasoconstriction   preload and afterload.

– Contraindicationi: Renal artery stenosis (bilateral).

– Side effect: hypotension, cough, hyperkalemia.

– ACE inhibitors should be used with caution in hypotension patients treated

with Potassium-sparing diuretics

– Benazepril (Cibacene 10 mg), Enalapril (Renitec, Ednyt), Captopril

(Capoten, Lopril).

• Angiotensin II receptor antagonists

(vasodilation)

ACEs

the role of ACE in the treatment of heart failure

CONSENSUS I (1) SOLVD (2)

Placebo Enalapril Placebo Enalapril

35.2

n 126 NYHA II (%) 0 NYHA III 0 NYHA IV 100 74 CAD(%) Death (%) 44 127 0 0 100 72 26 1284 1285 57 57 31 30 2 79 72 39.7

(1) N Eng J Med 1987, 316:1429-35. (2) N Eng J Med 1991, 325:293-302.

Charm trial

candesartan or placebo in clinical HF patients

Primary end-point: cardiovascular mortality and rehospitalization due to HF

charm trial

intolerant : reduced CV mortality and

• rehospitalization 23% (p=0,0004) by candesartan.

• Candesartan added standard treatment (ACEI and betablocker) reduced CV mortality and rehospitalization 15% (p=0,011).

Nitrates

•

Nhóm Nitrates: – Vasodilator of the venous system and reduction of preload; while reducing myocardial ischemia, decreased cardiac filling pressure and directly vasodilator of coronary arteries. Nitrates are mainly used in patients with heart failure in CAD patients, or can not use ACE/ARB

– Side effects: headache, hypotension, rash, etc. Do not use along

with sinadefil.

– Administration: oral, topical patch, transdermal, Translingual spray or

IV.

Isosorbide dinitrate (1)

A-HeFT (African American Heart Failure Trial)

• 1050 African-American patients with NYHA III-IV and EF <35%.

• Random. isosorbide dinitrate 20 mg + hydralazine 37,5 mg hoÆc gi¶ dîc.

• General Mortality :6,2 % so víi 10,2 % (p=0,02)

• Rehospitalization due to HF: 16,4% so víi 24,4%

(p= 0,001).

Isosorbide dinitrate (2)

Thö nghiÖm A-HeFT (African American Heart Failure Trial)

Beta blockers

•

Indication in patients with HF due to systolic dysfunction of left ventricle, event with Diabetes Type 2 or Peripheral vascular disease. – LVEF≤ 40% (IA). – Heart Failure with Preserved Systolic Function due to old MI (IA), Hypertension (IB), atrial fibrillation need to control of ventricular rate (IB).

Caution:

asthma.

(1)

•

– Old patients with HF due to systolic dysfunction of left ventricle (IB). Recurrent Contraindication: Hypoglycemia in Diabetes; (2) Asthma; (3) Limbs ischemic rest pain , (4) Bradycardiac (<55 b/m) or (5) Hypotension (Systolic BP < 80 mmHg).

Activation of the Sympathetic Nervous System in Heart Failure

Increased central sympathetic tone

2 receptors

1 receptors

1 receptors

Increased renal and blood vessels sympathetic activation Increased cardiac sympathetic activation

Vasoconstriction Increased reabsorption of water Hypertrophy and dead myocardial cell Dilated cardiomyopathy, cardiac ischemia, arrhythmias

Beta blockers

•

indicated in the treatment of severe chronic heart failure when other routine full of drugs. The beta-blocker used to treat heart failure include: carvedilol (Dilatrend); Metoprolol (Betaloc) and Bisoprolol (Concor).

• Mechanism is to prevent the effects of excessive stimulation of the sympathetic nervous system in chronic congestive heart failure, improve prognosis, but the actual benefits only appear slow and long-termi.

low dose (prior

•

Start with a to discharge), monitored, increasing the dose very slowly (no earlier than two weeks / time) to achieve therapeutic doses within 8-12 weeks, and then maintained the highest dose which can be tolerated.

•

If it is difficult to increase the dose, we will increased the dose slowly, reduce the target dose.If side effects develop or worsening heart failure, add / adjust the dose of diuretics or inotropic

US-Carvedilol Study

CIBIS-II Study

Drugs increasing cardiac contractility

Inotropes agents: indicated in acute/severve/decompensated heart failure. • • Side effects: Increased cardiac ischemic, heart rate, peripheral vasocontriction. • Dopamine: advocated in heart failure with hypotension but increasing heart rate.

–

1-3μg/kg/min: mesenteric and renal vasodilation, increased blood flow to the kidneys and urine output. – 2-5μg/kg/min: increase the contractility of the heart muscle (beta-receptor stimulation) – >5-10 μg/mg/min: peripheral vasoconstriction, increased vascular resistance adversely

affecting cardiac output (alpha receptor stimulation).

• Dobutamine:

– Selective β1 stimulation (weakly on β2 and α): improve haemodynamic, directly

myocardiac contracity, dilate arteries for reflectance -> reduce afterload and increase cardiac output, create little change in heart rate and BP. – The initial dose: 1-2 g / kg / min IV, adjust to be effective. – Using 2-4 day course by course to reduce the symptoms of heart failure. – Not recommended for the treatment in diastolic dysfunctional heart failure patients (eg:

hypertrophic cardiomyopathy) or heart failure with increased cardiac out.

Drugs increasing cardiac contractility

– The phosphodiesterase inhibitors: increase the contractility of the heart

muscle and vasodilation by increasing AMPc.

– Two drugs used in clinical are Amrinone and Milrinone, indicated for acute

or short-term treatment in severe heart failure patients. • Amrinone has effects as Dobutamin but makes stronger vasodilation,

hypotension if used with other vasodilators.

• Dose: • Amrinone IV 750 μg/kg/2-3 minutes then 2.5 to 10.0

micrograms/kg/min.

• Milrinone: Initial dose 50 μg/kg/10 mins IV then 0.375 - 0.75 microg/kg

/min

– Side effects: May cause atrial fibrillation or ventricular arrhythmias and

sometimes embolism.

– Vesnarinone: (quinoline derivative) increases myocardial contractility.

When combined with Digoxin and angiotensin-converting enzyme inhibitors in the treatment of heart failure, it can improve heart failure condition better. The average dose is 60mg/day, prolonged use. Possible side effects are neutropenia. The benefit of this drug is not yet clear.

Role of drugs increasing cardiac contractility in treatment of end-stage heart failure

• PRIME-II trial on Dopamine (N Eng J Med 1983) • Unverferth on Dobutammine used uncontiniously/continiously in

treatment of end-stage heart failure • PROMISE on Milrinone (N Eng J Med 1986) • VEST on Vesnarinone (J Am Coll Cardiol 1993)

Increasing markedly mortality rate and the studies were stopped early

ROLE OF DRUGS INCREASING CARDIAC CONTRACTILITY IN TREATMENT OF HEART FAILURE

• Drugs increasing cardiac contractility play an

necessary and determinant in treatment of acute situation (shock).

• Less meaningful, even harmful if used for long in chronic heart failure, end-stage heart failure (except Digitalis).

NEW THERAPIES

Cardiac resynchronization therapy

•

Cardiac resynchronization therapy (CRT) uses dual-chamber pacemaker, programmed to optimize their systolic/diastolic time reasonably, helps the ... Can be combined with automatic heart to contract effectively deforestation (AICD)

•

Indication: (IIa-A) Sinus rhythm • QRS width ≥ 120 ms • Severe left ventricular systolic dysfuntion (EF <35% and LV stretching > • 55mm) Moderate-severe heart failure (NYHA ≥ 3) despite optimal treatment with drugs (Heart Failure Guideline. J Card Fail 2006;12:e1-e122)

Implantable cardioverter defibrillators

Indications: Patients with heart failure have optimal drug therapy (3-6 months), with or without accompanied CAD (including old myocardial infarction > 1 month). • Patients with moderate-severe heart failure (NYHA 2-3), LVEF ≤ 30% (IIa A). • Patients with moderate-severe heart failure (NYHA 2-3), LVEF 31-35% (IIb A). • Combined with the two-chamber pacemakers in patients with severe heart failure (NYHA 3-4) (IIb B)

Left ventricular assist devices

MicroMed DeBakey

HeartMate II

HeartMate XVE

Jarvik 2000

Novacor LVAD

Surgery for heart failure treatment

Potential Cells

Unresolved Issues: 1. Long term fate of cells 2. Ability of cell to find optimum “niche”

3. Transdifferentiation

potential

4. Optimal angiogenic milieu 5. Manipulation of heart

tissue to “accept” cells

6. Detection of cells by labeling techniques 7. Optimal time course 8. Arrhythmogenesis 9. Characterization of

progenitor cells to predict effect

10. Development of delivery

system

Circulation 2003;107;929-934

Combination therapy and treatment of causes

• Anticoagulation therapy

• Treatment of causes

– Intra-aortic balloon pump

– Surgeries: valvular diseases, congenital heart diseases, CAD

– Transcatheter interventions: percutaneous mitral balloon

valvuloplasty, angioplasty, percutaneous transcatheter closure of defects...

• Heart transplantation

– Specific drugs for other causes

Health education

Health education is important to improve treatment efficiency to chronic heart failure patients especially severve heart failure ones (NYHA Class III-IV). Health education before discharge may improve patient compliance.

Content of patient education and administration: • Dietary and life-style (avoid excessive alcohol intake, smoking

cessation), daily physical activities.

• Avoid drugs worsening heart failure (corticoid, NSAIDs....) • Control other heart failure risk factors such as hypertension, diabetes,

lipid disorders...

• Self-management of systoms, adverse events to make a timely doctor's

visit.

• Habit build-up and skill training: daily weighing, understanding benefit of medicines, behaviors when getting worse, forgetting to take drugs, measurement of salt in fast food, targets of blood pressure and glucose levels.

Thank you !