Gagal jantung “Manajemen Iskemik Vs Non

Iskemik
dr.Tengku M Budiansyah, Sp.JP
Siloam Hospitals Bogor
Definition
Epidemiology
 Prevalence HF rise exponentially with age
 Relative incidence of HF lower in women than men
 Lifetime risk developing HF : 1 in 5 for 40 year old
 HfrEF (EF < 35%) : systolic failure
 HFPEF (EF > 50%) : diastolic failure : one half HF
 RF development HF : CAD, hypertension, diabetes,
obesity, smoking
 Hypertension play greater role in women
 CAD play greater role in men
• CAD : 60 – 75%
• Hypertension
• RHD in Asia & Africa
• Chagas : South
Amerika
• Nonischemic/
dilated/ idiopathic
cardiomyopathy : 20-
30%
• Viral infection
• Toxin exposure
• excess alcohol
consumption
• Chemotherapeutic
agent
• Familial : mutation
gen encoding
cytoskeleton (desmin,
myosin, vinculin), &
nuclear membran
(lamin)
• Duchenee, Becker,
Lim girdle muscular
Prognosis
 Framingham Heart Study : Median survival 1,7 y
for men, 3,2 y for women, 25% men and 38%
women surviving in 5 year
 Mortality HF in epidemiologi study higher than
in clinical trial  patient tend to younger,
more clinically stable, followed more closely
 Women with HF have overall better prognosis
than in men : greater degree functional
incapacity, higher prevalence HF with normal
EF
Biomarker & Prognosis
 Strong inverse survival correlation : norepinephrine, renin, arginin
vasopresin, aldosteron, ANP, BNP, NT proBNP, endotelin-1, TNF,
CRP, galactin 3, pentraxin3, soluble ST2
 Oxidized LDL & uric acid associated with worse clinical status in
HF
 Cardiac troponin I & Tpredicted adverse cardiac outcome in
noniscehmic chronic HF
 Low Hb & Ht associated with adverse outcome. Anemia  more HF
smptom, worse NYHA functional class, greater risk HF
hospitalization, reduced survival.
 Etiology anemia : reduced sensitivity hematopoietin receptor,
hematopoiesis inhibitor, defective iron supply
 Transfussion threshold : maintain Ht > 30%
 Fair HF Trial : correction iron deficiency in NYHA II, III, HF with
iron iv (ferric carboxymaltose) improved global assessment, NYHA
functional class, 6 minute walk distance & health related quality
of life
Renal Insufficiency
 Renal insufficiency associated with poor outcome : 50% increase mortality
risk compare with normal real function (ADHERE registry)
 Impair renal function was stronger predictor HF mortality than impair LV
function & NYHA functional class in patient with advance HF
 Renal hypoperfusion/ intrinsic renal disease show impair response to
diuretic & ACEI
Stage HF
Approach in HF
Patient high risk for developing HF
 ACE inhibitor useful in preventing HF in patient with atherosclerotic
vascular disease, diabetes mellitus or hypertension
 Patient high risk developing cardiomyopathy (strong family history/
receiving cardiotoxic) : 2D echocardiograpy screening
 Screen HF in population :
- Framingham criteria
- NHANES
Management transient LV dysfunction
 LV dysfunction may develop transiently not invariably lead to
development clinical syndrome HF
 LV dysfunction with pulmonary edema may develop acutely in patient wit
previously normal LV structure & function  postoperatively after cardiac
surgery, severe brain injury, after severe systemic infection
 Mechanism : 1) stunning functional myocardium, 2) activation pro-
infalmmatory cytokine capable supressing LV function
 Emotional stress can precipitate severe reversibel LV dysfunction,
accompanied by chest pain, pulmonary edema & cardiogenic shock 
takutsubo syndrome. LV dysfunction caused by detelerious effect
catecholamine after heightened sympatetic stimulation
 Exercise induced LV dysfunction usually caused by myocardial ischemia
may lead to symptom by rise in LV filling pressure and fall cardiac output
in absence LV dysfunction a rest
 LV dysfunction that persisted after initial cardiac injury  patient may
remain symptomatic for months to year
Goal treatment HF

 Reduce symptom
 Prolong survival
 Improve quality of life
 Prevent disease progression
 Alleviate fluid retention
 Lessen disability
 Reduce risk of death
General Measure
 Identification & correction condition responsible for cardiac structural &
functional abnormality
 Screen & treat comorbid illness
 Identify factor that provoke worsening HF
 Stop smoking
 Limit alcohol consumption : 2 drink/day in men, 1 drink/day in women
 Avoid excessive temperature & heavy physical exertion
 Avoid NSAID & COX-2 inhibitor
 Weight in regular basis  adjust diuretic dose in sudden unexpected
weight gain > 3-4 pound over 3 day
 Influenza & pneumococcal vaccine
 Educate family about importance of proper diet & compliance with
medical regiment
Activity
 Routine modest exercise beneficial in HF NYHA I-III
 HF-ACTION : no improvement in mortality / hospitalization in HF received
12 week (3x/week) exercise training program followed by 25-30 minute
home based self monitored exercise 5x/week  but quality of life
significantly improved
 Euvolemic patient reguler isotonic exercise (walking/ riding stationary
bicycle) can improve clinical status  exercise testing show no ischemia/
arrhytmia
 Exercise training not recommended in :
- HF with major cardiovascular event in past 6 week
- Patient with cardiac device
- Patient with baseline ischemia/ arrhytmia during baseline
cardiopulmonary exercise test
Diet
 Sodium restriction 2-3g/daily  <2g daily in moderate severe HF
 Fluid restriction (<2L/day) necessary in setting hyponatremia (Na <
130mEq/L) : because activation RAA system, excessive secretion AVP, loss
of salt in previous diuretic use
 Caloric supplementation in advance HF & unintentional weight loss/
muscle wasting (cardiac cahexia)
 Avoid dietary supplement because lack proven benefit & potential
significant interaction with HF therapeutic
Management fluid retention
Diuretic
 Diuretic : reduction JVP, pulmonary congestion, peripheral edema, body
weight, improve cardiac function, relieve symptom, increase exercise
tolerance, reduction mortality & worsening HF
 Classification diuretic :
- Loop diuretic : increase sodium excretion 20-25%, enhance free water
clearance
- Thiazide : increase sodium excretion 5-10%, decrease free water
clearance, lose effectiveness in impair renal function (creatinine
clearance < 40mL)
- Aquaretic/ diuretic induce free water diuresis : demeclocyline, lithium,
vasopresin V2 receptor antagonis
- Solute diuresis : divided into osmotic diuresis & ion transport inhibitor
Loop Diuretic
 Furosemide, bumetanide, torsemide
 Mechanism of Action :
a) inhibiting NaK2Cl sympoter on apical membran epithelial cell thick ascending
loop of henle  prevent salt transport
b) inhibit Ca & Mg resorption
c) reduce water resorption in collecting duct
d) enhance K excretion
e) venodilator : reduced RAP & PCWP
 bound extensively to plasma protein
 Efficacy depend on renal plasma blood flow & proximal tubular secretion
 Probenecid competitively inhibiting furosemid excretion by organic transport
system  reduced concentration response curve
 Bioavailability furosemide 40-70%, bumetanide & torsemide > 80%
 Ethacrynic acid  slower onset of action, delay & partial reversibility  safely
use in sulfa allergic patient
Thiazide Diuretic
 Benzothiaziadide, metolazone
 Mechanism of action :
a) Block NaCl transporter in cortical portion ascending loop of henle &
distal convoluted tubule
b) Decrease kidney ability to increase free water clearance  potentially
development hyponatremia
c) Increase ca resorption in distal nephron  hypercalcemia
d) Diminish Mg resorption
e) Increase NaCl delicery in collecting duct  enhance K & H secretion 
hypokalemia
 Efficacy depend on proximal tubular secretion
Mineralocorticoid Receptor Antagonis
 Spironolactone, eplerenone
 Act by :
a) inhibit aldosteron receptor in distal nephron that cause retention salt &
water, excretion of K & H
b) progesteron like  gynecomastia/ impotence in men, menstrual
irregularities in women
 Eplerenone has greater selectivity for mineralocorticoid receptor than
steroid receptor (fewer sex hormone effect), shorter half life, weak
diuretic
 Spironolactone competitively inhibit mineralocorticoid type I receptor in
distal convoluted tubule & collecting duct  ligan dependen transcription
factor  translocate to nucleus  bind to hormon response element in
promoter some genes involved in vascular & myocardial fibrosis,
inflammation, and calcification
Potassium Carbonic anhidrase
Sparing Diuretic inhibitor

 Triamterene, amiloride  Acetazolamide

 Act : block Na resorption  Act : Inhibit carbonic
in distal tubule & anhydrase  inhibit
collecting duct  mild NaHCO3 resorption in
incease NaCl excretion, proximal tubule
antikaliuretic but not  Use : correct metabolic
effective to achieve
alkalosis caused by
negative Na balance
other diuretic
because Na retention
occurs at proximal  Side effect : metabolic
nephron site acidosis & severe
hypokalemia
Vasopresin (AVP) antagonis/ vaptan
 MoA : reduced SVR & dilutional
hyponateremia  increase urine
volume, decrease urine osmolality
w/ no effect on na excretion
1) V1aR : block vasoconstrictor
effect AVP in peripehral vascular
smooth muscle cell
2) V2R : inhibit requirement
aquaporin water channel in apical
membrane collecting duct 
reducing ability to resorb water
 Tolvaptan, lixivaptan, satavaptan 
block V2 receptor
 Conivaptan  block V1 & V2
receptor
 Indication : treatment hypervolemic
& euvolemic hyponatremia (Na <
125) that is symptomatic & resistant
w/ fluid restriction therapy
Diuretic treatment of HF
 Indication : evidence of volume overload or history of fluid retention
 Loop diuretic : evidence moderte/ severe renal insufficiency
 Starting dose 40 mg in systolic HF with normal renal function  double
the dose until desire response/ maximal dose reached
 Short acting < 3 hours  given at least twice daily
 IV administration to relieve congestion acutely  after diuretic effect
achieved  increase administration frequency (more diuretic with less
physiologic pertubation)  congestion  diuretic continued to prevent
recurence of salt & water retention maintain patient ideal dry weight
Complication diuretic use
Electrolyte & metabolic disturbance
 potassium depletion caused by diuretic, increase
aldosteron, increase distal nephron na delivery
maintain kalium level 4-5 mEq/l : patient treat
pro-arrhytmic drug, treat : increase dietary K
intake & KCl supplementation, use aldosterone
antagonist
 hyperkalemia : use aldosteron antagonis combined
with ACE/ ARB
 hyponatremia : aggressive diuretic + HF with high
AVP level
 hypomagnesemia : combined use loop & thiazide
diuretic
Complication diuretic use
Hypotension & Azotemia
 Diuretic : decrease BP, decrease exercise tolerance, increase fatigue,
impair renal function  response after decrease dose/ frequency
 In chronic HF acceptance elevated BUN/ creatinin necessary to control
congestive symptom
Neurohormonal activation
 Diuretic increase activation endogenous neurohumoral that lead to disease
progression  treatment with concomitant neurohumoral agonis
Ototoxicity
 Ethacrynic acid caused tinnitus, hearing impairment, deafness
 Ototoxicity occurs more frequently with iv injection
Diuretic Resistance
 Braking phenomenon : time dependent decline in natriuresis for
a diuretic dose deped on reduction extracellular fluid volume 
stimulation efferen sympathetic  reduced renal blood flow 
stimulate renin – aldosterone relase  increase Na reabsorbtion
 reduced urinary na excretion
 Magnitude natriuretic potent diuretic decline with disease
progression in HF : delay rate absorbtion  peak drug level in
tubular lumen insufficient to induce maximal natriuresis  use
iv formulation
 Factor contributed to diuretic resistance :
a) most diuretic short acting : postdiuretic Na retention
overcome initial natriuresis
b) loss renal response to endogenous natriuretic peptide in
advance HF
c) diuretic increase solute delivery to distal nephron 
hypertrophy & hyperplasia epithelial cell
 Dose response curve loop diuretic

CRF impair diuretic secretion. HF Normal subject oral = iv, HF

diuretic resistant increase natriuretic threshold,
oral dose not effective
Diuretic resistance
Definition diuretic resistance : moderate dose diuretic doesn’t achieved
desire reduction extracellular fluid volume
Cause :
 decline cardiac/ renal function
 non-compliancee with diuretic regiment
 NSAID, COX2 inhibitor, trimetroprim, gentamicin (drug adversely
affect renal function)
 Thiazolidinedione  aktivasi PAR gamma di renal collecting duct 
enhance expression Na Channel
 Pioglitazone  stimulate renin plasma  increase Na retention
 Probenecid compate with organic ion transporter in proximal tubule
 Vasodilator use reduce renal perfussion in patient with renal artery
stenosis
 Cardiorenal syndrome  worsening renal function (pre- renal) that
limit diuresis in patient with obvious clinically volume overload
Management Diuretic Resistance
 Administer 2 class of drug : loop diuretic + distal collecting tubule diuretic
(Hct 50-100 mg or Metolazone 2,5 – 10 mg)  then decreasing dose distal
collecting tubule diuretic 3x weekly to avoid overdiuresis
- distal collecting tubule diuretic has longer half life : prevent post
diuretic NaCl retention
- potentiate loop diuretic by inhibiting Na transport in proximal
convoluted tubule, inhibiting carbonic anhidrase, inhibiting NaCl
transporter along distal renal tubule
 Administer parenteral dose loop diuretic  sustained natriuresis & avoid
postdiuretic rebound Na resoprtion. Dose : 20-40 mg iv loading dose
continued by 5-10 mg/ hour for patient already receiving oral dose 200
mg/day
 DOSE trial : no significance difference in symptom or renal function
patient ADHF treat with iv bolus compared with iv infusion
Device based therapy for management
fluid status
 Extracorporeal ultrafiltration : remove salt & water
isotonically by driving blood through highly permeable filter
in extracorporeal cicuid (arteriovenous or venovenous)
 Continuous hemofiltration, continuous hemodialysis or
continuous hemodiafiltration : slow continuous
ultrafiltration  reduced RAP & PCWP, increase CO,
natriuresis & diuresis without change in HR, SBP, renal
function, electrolyte/ intravascular volume
1) RAPID CHF trial : diuretic vs single 8 hour ultrafiltration in
ADHF  fluid removal after 24 h greater in ultrafiltration
2) UNLOAD trial : ultrafiltration vs IV diuretic  similar
dyspnea relief, but greater fluid loss in 48 h & lower rate
rehospitalization in ultrafiltration
3) CARRES trial : ultrafiltration result in similar weight loss
Prevention Disease
Progression
Angiotensin Converting Enzim Inhibitor
 Act : inhibit enzim responsible to convert angiotensin
I to angiotensin II, inhibit kinase II that upregulation
bradykinin
 Effect : stabilize RV remodelling, relive symptom,
prevent hospitalization, prolonged life
 Optimize dose diuretic before initiation ACE, slight
reduce diuretic dose during initiation to avoid
hypotension, initiated at low dose then slowly
increase if tolerable, double dose every 3-5 day
 Add therapy beta blocker before full target dose
achieved
 Evaluate : blood pressure, renal function & potassium
1-2 week after initiation

Angiotensin Converting Enzim Inhibitor
 SOLVD, SAVE, TRACE trial : asymptomatic LV
dysfunction less likely develop symptomatic HF & HF
requiring hospitalization when treated with ACE
Inhibitor
 CONSESUS I, SOLVD trial : ACE inhibitor for
symptomatic LV dysfunction, greatest benefit on
mortality on severe HF/ NYHA IV
 V-HeFT-II : ACE inhibitor improve natural history HF
through mechanism other than vasodilation
 Enalapril the only ACE inhibitor used in mortality
trial in chronic HF
 Patient with low BP (<90 mmHg) & impair renal
function (creatinine > 2,5 mg/mL) were not
Angiotensin Receptor Blocker
 Use in symptomatic & asymptomatic EF < 40% intolerance to ACEI because
reason other than hyperkalemia & renal insufficiency
 Act : Block angiotensin II on angiotensin type I receptor
 Losartan, valsartan, candesartan
 Start at low dose uptitrated every 3-5 day by doubling ARB dose
 Evaluation : BP, renal function & potassium 1-2 week after initiation or
change dose
Complication ACE Inhibitor/ ARB use
 Decrease BP & mild azotemia
 Hypotension + dizziness/ severe renal dysfunction  decrease diuretic
dose if no fluid retention or decrease ACE Inhibitor dose if there is fluid
retention
 Potassium retention in patient receiving potassium supplement/ potassium
sparing diuretic
 Kinin potentiation  non-productive cough (10-15%) & angioedema (1%) 
replace with ARB
 Hyperkalemia/ renal insufficiency  replace with hydralazine or oral
nitrate
Beta Blocker
 Act : competitively antagonizing adrenergic receptor (alpha 1, beta 1, beta2)
 Bisoprolol, metoprolol (block beta1), carvedilol (block beta1, beta2, alpha1)
 Effect : reverse RV remodelling, ameliorate symptom, prevent hospitalization,
prolonged life
 Use in symptomatic & asymtomatic HF with EF < 40%
 Initiated at low dose, optimize diuretic dose before initiation therapy  gradual
increase every 2 week
 Initiation & increasing dose may lead worsening of fluid retention because abrupt
withdrawal adrenergic support of heart & circulation  usually occur after 3-5
day manifested as increasing body weight worsening HF symptom  manage by
increase dose diuretic
 In patient taking low dose ACE Inhibitor, addition beta blocker produce greater
symptomatic improvemen & reduce risk of death than increasing dose of ACE
Inhibitor
 Beta blocker can safely initiated before discharge in stable patient who doesn’t
require iv diuretic therapy
 Intolerance beta bloker (10-15%) : worsening fluid retention, symptomatic
hypotension
Beta blocker
 MDC Trial : Metoprolol tartrate 3 x 50 mg in symptomatic idiopatic dilated
cardiomyopathy  reduced death & cardiac transplantation but not
significance  metoprolol succinate CR/XL reduced mortality
 CIBIS-I trial : bisoprolol in ischemic & nonischemic cardiomyopathy  non
significant reduction in mortality at 2 year follow up
 CIBIS-II trial : bisoprolol reduced mortality 32%, sudden death 45%, HF
hospitalization 30%, & all hospitalization 30%
 CIBIS III trial : bisoprolol non inferior to enalapril in newly diagnosed mild-
moderate HF
 ANZ-Carvedilol trial : carvediolol cause significant improvement LVEF &
LVEDV index at 12 months and reduction 26% death & hospitalization at 19
months
 COPERNICUS trial : carvedilol in advanced euvolemic HF EF < 25%  reduced
risk mortality at 12 month by 38% & reduced death & hospitalization by 31%
 CAPRICORN trial : carvediolol in LV dysfunction after MI  reduced mortality
by 23%, cardiovascular mortality by 25% & non fatal MI by 41%
 COMET trial : carvedilol 2 x 25 mg vs metoprolol 1 x 50 mg  carvedilol
associated with reduction 33% mortality
Side Effect Beta Bloker

 Fluid retention
 Fatigue/ weakness  resolves whithin weeks to months
 Bradycardia/ heart block  decrease dose if HR < 50
bpm / second-third degree heart block/ symptomatic
hypotension
 Continuation beta blocker during episode of acute
decompensation is safe with dose reduction
 Not recommended in asthma with active bronchospasm
Aldosterone Antagonis
 Use in NYHA II-IV with EF < 35% receiving ACEI, BB, & diuretic
 Spironolactone initiated at 1 x 12,5 - 25 mg  uptitrated to 1 x 25 – 50 mg
 Eplerenone initiated at 1 x 25 mg  uptitrated to 1 x 50 mg
 Stop potassium supplemetation at initiation, avoid high potassium food
 Check potassssium & renal function at 3 day and 1 week after initiation
then monthly up to 6 month
 Side effect : hyperkalemia & painful gynecomastia in 10-15%
 Not recommended in creatinin > 2,5 or potassium > 5,5
Aldosterone Antagonis
 RALES trial : spironolactone 25 – 50 mg for NYHA III-IV, EF < 35% already
received ACEI, loop diuretic & digoxin  reduction 30% mortality, 35%
hospitalization, gynecmastia reported in 10% men
 EMPHASIS-HF trial : eplerenone 50 mg in NYHA II HF, EF < 30% receive
ACE/ARB & BB  reduction 24% death, 23% hospitalization & 43% HF
hospitalization
 EPHESUS trial : eplerenone 50 mg in acute MI complicated by LV
dysfunction & HF  reduction 15% of death
Ivabradine
 Act : selectively block cardiac pacemaker (If) funny current that control
spontaneous depolarization SA node
 Magnitude If inhibition related to frequency of channel oppening 
effective in higher rate
 SHIFT trial : symptomatic HF, EF < 35%, sinus rhythm, HR > 70 bpm, on
beta blocker  ivabradine uptitrated to 2 x 7,5 mg reduced
cardiovascular death &HF hospitalization by 18%
 BEAUTIFUL trial : 2 x 7,5 mg ivabradine in CAD with EF < 40%  drug was
tolerated but not cause reduction in death, MI or HF hospitalization
Renin Inhibitor
 Aliskiren  direct renin inhibitor  prevention convertion
angiotensinogen to angiotensin I
 ALOFT trial : aliskiren decrease NT pro BNP in urinary aldosterone
secretion
 ASTRONAUT trial : LVEF < 40% with BNP > 400 ad NT pro BNP > 1400
discharge after ADHF  no significant difference in CV death/ HF
hospitalization with increase rate of hypotension, hyperkalemia & renal
impairment
 ATHMOSPHERE : aliskiren vs enalapril vs aliskiren-enalapril in NYHA II-IV -
ongoing
Management patient remain
symptomatic
Cardiac glycoside
 Act :
- inhibit Na K ATP ase pump in cell membrane &
sarcolemma cardiac myocyte  increase intracellular
calcium  increase cardiac contractility
- sensitize Na K ATP ase in vagal afferent fiber  inrease
vagal tone
- inhibit Na K ATP ase in kidney  blunt renal tubular
resorption of sodium
 Initiated at 1x 0,125 mg and maintain at 0,25 mg or 0,125
mg in elederly or impair renal function or lean body mass
 RADIANCE trial & PROVED trial  worsening HF &
increase HF hospitalization in patient withdrawal from
digoxin
 DIG trial : digoxin had neutral effect on HF mortality but
reduced hospitalization in HF, mortality related o serum
Complication of digoxin
1) Cardiac arrhytmia : heart bloc (in elderly), ectopic & reentrant cardiac
arrhytmia
2) Neurologic : visual disturbance, disorientation, confusion
3) GI symptom : anorexia, nausea, vomiting

 Goal maintan drug level 0,5 – 1 ng/mL

 Toxicity occur at serum drug level > 2 ng/mL, occur at lower drug level if
coexist with hypokalemia and hypomagnesemia
 Oral potassium supplementation useful for treatment atrial, av junctional
or ventricular ectopic rhythm even when normal serum potassium (unless
high grade av block present)
 Life threatening digoxin toxivity reverse by antidigoxin immunotherapy
 Concomittan use of quinideine, verapamil, spironolactone, flecainide,
propafenone, & amiodarone can increase serum digoxin level
 Not recomennded use in patient with advance heart block unless
pacemaker in place
N-3 polyunsaturated fatty acid
 N-3 PUFAs : effect on inflammation, reduction endothelial cell activation,
production cytokine, platelet aggregation, autonomic tone, BP, HR, & LV
function
 GISSI-HF : long term administration 1g/da omega n-3 PUFA  significant
reduction in mortality & hospital admission
Management Atherosclerotic Disease
 HFwith ischemic etiology : long term treatment
with aspirin 75-81 mg is recommended
 Favourable
outcome in HF has not been
demonstrated
 CABGhasn’t improved cardiac function,
symptom, prevent reinfarction or death in HF
without angina
 CABG ameliorate symptom & improve survival
in HF with modestly depressed EF and angina
 STICH trial : CABG didn’t reduced all cause of
death but reduced cardiovascular death and
hospitalization
Special population
Women
 Women poorly presented in trial
 Women HF likely to be older, preserved EF, nonischemic
etiology
 Women have survival advantage
 Women experience increase morbidity, worse quality of
life and increase depression
 Women increased risk developing HF after acute MI
Special Population
Race/ ethnicity
 SOLVD and V-HeFT trial : African american not benefit
from ACE Inhibitor
 A-HeFT trial : isosorbid dinitrate + hydralazine vs
standard HF in african american NYHA III-IV 
significant reduction rate of death & first
rehospitalization with HF
 Hydralazine imporved nitric oxide bioavailabilty
Special population
Elderly
 Elderly more likely to present with atypical symptom :
altered mental status, depression, poor executive
functioning
 Alteration pharmakokinetic & pharmacodynamic drug,
reduction dose may be necessary
 Blunt baroreceptor function, orthostatic dysregulation
blood pressure  difficult to use target dose
Anticaogulation & Antiplatelet
 HF increased risk atrial & venous thromboembolic event : stroke rates 1,4-
2,3%/ year
 Depresed EF  stasis blood in cardiac chamber  thrombus formation
 Recommended treatment with warfarin : INR target 2-3
1) Increased risk of stroke in HF REF assess by CHA2DS2VASc
2) History systemic/ pulmonary emboli : stroke/ TIA
3) Symptomatic/ asymptomatic ischemic cardiomyopathy with recent
large anterior MI with documented LV thrombus for 3 months after MI
 WARCEF trial : HF in sinus rhythm treat with anticoagulant didn’t reduced
time to ischemic stroke, intracerebral hemorrhage or death, Warfarin
significant decrease rate ischemic stroke but cause increase major
hemorrhage
Management Cardiac Arrhytmia
 Atrial fibrillation (15-30%) : lead to worsening HF & increased risk
thrombo-embolic complication
 In Chronic HF & AF : rhythm control was not superior to rate control
 Rhythm control for reversible secondary cause AF & Cannot tolerate
symptom AF after optimizatio rate control & AF therapy
 Rate control : 60-80 (resting), 90-115 (exercise)
- Beta-blocker prefer over digoxin (digoxin doesn’t control rate during
exercise, betablocker more favorable effect on mortality & morbidity)
- combination beta blocker with digoxin more efective
- amiodaron when beta adrenergic cant be used  risk thyroid disease &
lung toxicity in chronic use
- short term iv diltiazem or amiodarone for very rapid ventricular
response
Management cardiac arrhytmia
 AF-CHF trial : no difference clinical outcome berween strict rate control <
80 bpm at rest/ < 100 at 6 minute vs lenient rate control
 Amiodarone : anti-arrhytmia that has little negative inotropic & pro
arrhytmic  prefered drug to restore & maintain sinus rhythm
 increase drug level phenytoin & digoxin, prolonged INR in warfarin 
reduced dose by 50%
 SE : hopthyroid, hyperthyroid, pulmonary fibrosis, hepatitis
 Dronaderone : same pharmacological properties with amiodarone but not
contained iodine
 ANDROMEDA trial : 2x increase mortality in dronaderone treated patient
predominantly related to worsening HF
Device Therapy
 CRT in NYHA II-IV, EF < 30-35%, wide QRS, on optimal background therapy
 CRT add to optimal medical therapy in sinus rhythm  decrease mortality
& hospitalization, reversal LV remodelling, improve quality of life &
exercise capacity
 ICD in NYHA II-III, EF < 35%, on optimal background therapy, expectation
survival with good functional status > 1 year
 Prophylactic ICD in NYHA II-III reduced incidence sudden cardiac death in
ischemic & non ischemic cardiomyopathy
 CRT-D : NYHA – IV patients
Sleep disordered breathing
 HF EF < 40% : 40% have Central sleep apnea/ cheyne stokes
breathing, 10% obstructive sleep apnea
 CSA  periodic breathing in whith central apnea & hypopnea
alternate with periods of hyperventilation that exhibit
waxing & waning pattern of tidal volume
 RF : male, age > 60 yo, AF, hypocapnia
 CSA in HF associated with increase mortality, reflect
advance disease & poor LV function
 Optimize treatment aggressive diuresis
 Nocturnal oxygen & CPAP : allviate CSA, abolish apnea
related hypoxia, decrease nocturnal norepeinephrine level,
symptomatic & functional improvemen when use in HF up to
1 months
 CPAP  improve LV structure & function in CSA &
obstructive sleep apnea
Patophysiology CSA & Cheyne
stokes respiration in HF
Stages in development HF &
Recommended therapy
Initial patient evaluation
 Histrory : diabetes, rheumatic fever, chest irradiation, exposure to cardiotoxic drug,
use of alcohol, illicit drug, or alternative therapies,
 3 generation of family history in dilated cardiomyopathy
 Lab : CBC, urinalysis, serum electrolytes (calcium & magnesium), blood urea
nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests, &
thyroid-stimulating hormone
 a chest radiograph & a 12-lead electrocardiogram
 Two dimensional echocardiography with Doppler studies
 Screening for hemochromatosis, amyloidosis, HIV, sleep-disordered breathing, CT
diseases, amyloidosis, / pheochromocytoma may be reasonable
 Measurement of BNP / NTproBNP in ambulatory patients with dyspnea to support
clinical decision making & for establishing prognosis / disease severity in chronic HF
(IA)
 When ischemia may be contributing to HF  coronary arteriography (IIaC)
 Noninvasive imaging to detect myocardial ischemia & viability in patients presenting
with de novo HF, known CAD, & no angina (unless the patient not eligible for
revascularization), viability testing in select patients in planning revascularization
(IIa B-C)
 Endomyocardial biopsy in HF when a diagnosis would influence therapy is suspected
Treatment LV Dysfunction who
hasn’t developed symptom

 Beta blockers & ACE inhibitors (/ ARBs in those

intolerant) recommended for all patients with a history
of MI, regardless of EF and for all patients with
diminished EF, regardless of history of MI (I A-C)
 Discourage use of calcium channel blockers with
negative inotropic action I
 use of an ICD (IIbB) in patients with asymptomatic
ischemic cardiomyopathy who have had a recent (within
40 days) MI, with EF < 30%, on appropriate medical
therapy, & have a reasonable expectation of life > 1
year
Treatment LV dysfunction with
current/ previous symptom

 Physical activity & cardiac rehabilitation are recommended 

HF-ACTION trial
 Beta blockers (bisoprolol, carvedilol, sustained-release
metoprolol succinate) & ACE inhibitors (/ ARBs in patients who
cannot tolerate ACE inhibitors) for all stage C HF patients
 Diuretics for patients with fluid overload.
 EMPHASIS-HF :all NYHA patients class II - IV HF with an EF of
<35% aldosterone antagonists
 Hydralazine & isosorbide : African Americans who remain
symptomatic in NYHA class III - IV HF despite optimal therapy
& in patients who are intolerant of an ACE inhibitor or an ARB.
 Digitalis remains decrease hospitalizations in symptomatic
patients.
 WARCEF : anticoagulation is not recom- mended in patients
with chronic HF without atrial fibrillation, a previous embolic
event, or a recognized cardioembolic source (III)
Treatment refractory/ end stage HF
 Continuous intravenous inotropic support until definitive therapy
can be performed (MCS, heart transplantation), and/or to
maintain systemic perfusion and preserve end-organ performance
until the acute precipitating problem is resolved (IC)
 inotropic support as “bridge therapy”to GDMT and/or device
therapy (IIaB),
 short-term continuous intravenous inotropic agents in hospitalized
patients with documented severe systolic dysfunction who present
with low blood pressure and significantly depressed cardiac
output, to maintain systemic perfusion and preserve endorgan
performance, or as palliative therapy for symptom control (IIbB)
 MCS in carefully selected patients with stage D HFrEF, in whom
definitive management (cardiac transplantation) / cardiac
recovery is anticipated/ planned,
 Percutaneous & extracorporeal ventricular assist devices (VADs) :
“bridge to recovery” / “bridge to decision” for HFrEF with acute
profound hemodynamic compromise (IIbB)
Surgical/ Percutaneous/ Interventional
Treatment HF
 Coronary artery revascularization via CABG / percutaneous
intervention for patients on GDMT with angina and suitable coronary
artery anatomy, especially for a left main artery stenosis (>50%) or
left main equivalent disease (IC)
 CABG also was recommended to improve survival in mild to moderate
LV dysfunction (EF 35% - 50%) & significant (>70% diameter stenosis)
multivessel CAD or proximal left anterior descending coronary artery
stenosis when viable myocardium is present & to decrease morbidity &
CV mortality for patients with severe LV dysfunction (EF < 35%), HF, &
significant CAD (IIaB)
 CABG in patients with ischemic heart disease with severe LV systolic
dysfunction (EF < 35%) & operable coronary artery anatomy
irrespective of whether viable myocardium was present (IIbB)
 Surgical aortic valve replacement in patients with a predicted surgical
mortality of < 10% (IIaB)
 Transcatheter aortic valve replacement in inoperable patients with
critical aortic valve disease.