new heart failure-2

7/29/2019 New Heart Failure-2

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Outline

Management of Heart Failure Diuretics

VASODILATOR THERAPY IN HEART FAILURE

Angiotensin Converting EnzymeInhibitors

1. VASODILATION

2.

DIURESIS3. REMODELING REGRESSION

B- blockers

Digoxin


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Diuretics can relieve peripheral & pulmonaryedema within hours or days unlike other

agents (ACEIs/-blockers) that requireweeks to months

DIURETIC MONOTHERAPY

IS NOT ALLOWED as they offer ineffectivemaintenance alone.


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Diuretics are recommended when clinical evidenceexists for volume overload

Patients without peripheral/pulmonary edema canbe treated WITHOUT OR INTERMITTANTdiuretics

As-needed diuretic depends on wt gain

changes, neck vein distention (>0.5-1 kg/day or 2kg/week wt gain/swollen legs)

Otherwise, diuretic-free periods or week ends areapplied


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EFFICAY of diuretics depend on sodium load deliveredto their site of action

In HF, compromised GFR increases Na+ re-absorption,leading to minimal efficacy for thiazide & K+-sparingdiuretics.

Loop diuretics (furosemide, bumetanide & torsemide)are the preferred diuretics in HF

They are effective even at creatinine Clcr is less than 5mL/min

Furosemide has addition vasodilating properties decreasingrenal vascular resistance even before diuresis starts


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Diuretics Adverse Effects

1-Azotemia

Normal BUN/creatinine=10-20

Increased both values: progressive renal damage

Increased BUN/creatinine ratio above 20 denotes prerenalazotemia caused by poor renal perfusion &/or overdiuresis

Proper diuretic therapy would improve HF, renal perfusion &helps lower BUN

Prolonged over-diuresis & dehydration may cause decreased

renal perfusion & renal damage, where creatinine will rise aswell


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2- Hypokalemia

Definition: less than 3.5 mEq/L, HCTZ (50-100 mg/day),incidence is 15-40%

At lower-dose HCTZ & accepting serum levels of


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3- Hypomagnesemia

Severe hypomagnesemia can lead to muscle

spasms, decreased seizure threshold &cardiac arrythmias

Concurrent hypokalemia & hypomagnesemia

can be seriously dangerous IV MgSO4 is administered to restore serum

Mg2+


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4- Hyperuricemia

Usual increments in uric acid levels are1-2 mg/dL

Asymptomatic hyperuricemic patients usually do

not require treatments Persistent hyperuricemia >10 mg/dL, or history of

gout, consider urate-lowering agents

5- Hyperglycemia Hyperglycemia & glucose intolerance are side

effects to thiazide & loop diuretics

Family history & other risk factors are evaluated


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Potassium

Supplementation

Serum K+ must be monitored frequently

Hypokalemia can occur few hrs after first dose, & reaches

max after a week Hypokalemia takes several weeks to go to normal after

diuretic withdrawal

K+ replacement: Only KCl should be used because all

hypokalemic diuretics can cause hypochloremic alkalosis If hypochloremia was not corrected, hypokalemia &

alkalosis persist

K+-sparing diuretic or K+-containing food


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Diuretic Therapy

Monitoring

CHF symptoms

Wt Loss (0.5-1 kg/day) and decreasededema

Signs of volume depletion: hypotension,dizziness, weakness, decreased urine output

& raised BUN

Check serum K+, Mg2+, uric acid & glucose


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Diuretic-Independent

Effects of Spironolactone

Both ANGII & aldosterone have direct CV detrimentaleffects:

o Vascular & myocardial hypertrophy & fibrosis,o direct vascular & endothelial damage,

o increased oxidative stress

o

Inhibition of NE uptake by the myocardium Spironolactone addition to maintenance HF therapy,

significantly reduced mortality in severe HF (stage IV)


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VASODILATOR THERAPY IN

HEART FAILURE

Arterial vasodilation decreases afterload &venodilation lowers preload.

Hydralazine (arterial dilator) & nitrates (venousdilator) combination reduces HF symptoms & havemodest reduction of mortality.

ACEIs reduce both preload & afterload and suppress

cardiac remodelling.

It was recommended the use of ACEIs to all systolicHF patients unless contraindicated or intolerated.


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Angiotensin Converting Enzyme

Inhibitors (ACEIs)

VASODILATION, DIURESIS & REMODELINGREGRESSION are the beneficial triad for ACE

inhibition

Vasodilation: decreased ANG II & NE and increasedbradykinin (BK) & substance P

Bradykinin stimulates B1 receptors leading toincreased PGI2, NO & EDRF

BK increases natriuresis via direct tubular effect


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Inhibitors (ACEIs)

Mild diuresis:

Reduction of aldosterone & vasopressin secretion

Enhanced renal blood flow, via increased CO & locallythrough efferent arteriolar vasodialtion

Cardiac & Vascular Remdelling inhibitionby lowering

ANGII type-1 R - hypertrophic effects


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Inhibitors (ACEIs)

FDA-labeled ACEIs for HF: captopril, enalpril,fosinopril, lisinopril, quinapril, ramipril.

No drug is preferred to another Efficacy: ACEIs are effective in ischemic/non-

ischemic HF & all HF stages (I-IV)

Produce relative reduction of 20-30% HF mortality,superior to hydralazine-nitrate or ARBs

ACEIs showed better cardiac remodeling inhibitoryeffect over ARBs


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Various ACEIs

It was recommended captopril, enalpril, lisinopril &ramipril

Captopril & lisinopril have no active metabolites All other agents are PRODRUGS requiring enzymatic

conversion to active metabolites

Captopril has shorter onset and duration of action,administered frequently/day

Captopril is better for initiating ACEI therapy for 2days followed by longer-acting ones in good

responders


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ACE Inhibitors-Induced

Cough

ALL ACEIs can induce cough in 3-15% of patients

It occurs within few weeks to months of treatment &

persist 1-2 weeks after drug withdrawal Changing an ACEI to another or dose reduction do

not stop cough because of the Pharmacologicmechanism (increased Bradykinin & substance P)

Withdrawal of the ACEI drug is the only way to stopACEI-induced cough

If cough persists, shift to another vasodilator: ARB or

hydralazine-nitrate combination


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Angiotensin II Type-1 (AT1)

Receptor Antagonists (ARBs)

They preferentially block AT-1 receptors

They improve HF symptoms: increased

exercise tolerance & ejection fraction

ARBs were not superior to ACEIs in reductionof all-cause mortality, but cough-free

FDA approved valsartan for HF

Triple combination:

ACEI-ARB--blocker should not be used


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Adverse Effects of ACEIs & ARBs

1- Hyperkalemia

ANG II-induced aldosterone secretion is decreased

by ACEI/ARB leading to K+ retention Significant hyperkalemia occurs in

o Renal compromised patients

o K+ supplementation & K+-sparing diuretics K+-losing (thiazide & loop) diuretics concurrent use

leads to either normokalemia or hypokalemia


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Adverse Effects of ACEIs & ARBs

Angioedema (Angioneurotic edema)

It consists of facial/neck edema with airway obstruction(laryngeal& bronchial edema)

Mechanism is unknown but thought to be related to kinins

accumulation Though kinin-related, case reports exist for angioedema

induced by losartan & valsartan

ARBs are an option whenever ACE-induced angioedema occurs

Hydralazine-nitrate combination is another alternative African Americans & females are more vulnerable


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Effects of ACEIs & ARBs

on Kidney Function

HF Patients Beneficial Effect: ACEI/ARB decrease pre- &

afterload increase CO improve renal blood flow.

Non-beneficial Effect: Initial therapy rapid BP fall slow CO response worsening of renal function

Prediction of which event to occur is impossible

ACEI/ARB therapy initiated with low dose, slowincrease in dose/careful BP & renal function monitor

Diuretic dose is adjusted to avoid volume depletion& hypotension


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ACEIs in Asymptomatic Patients

HF patients in Stage A-B, with LVH ordecreased EF but NO signs benefits from

ACEI therapy.

Possibly ACEI retards cardiac remodelling

-blockers may be added to ACEI forasymptomatic HF patients whenevercompelling indication exists (e.g., MI)


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-Blockers in Systolic Heart

Failure

EVIDENCE: -blockers reduce mortality (30%) &hospitalization (40%)

Metoprolol & carvedilol reduce HF symptoms &mortality

They are added to diuretic-ACEI & often digoxin

They should not be delayed till refractoriness toHF therapy occurs

Addition to low-dose ACEI produces betterimprovement of symptoms & mortality


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-Blockers in Systolic Heart

Failure

Contraindication: Unstable HF hospialized patients,symptomatic bradycardia/heart block, resistant asthma

DOSE: Initial low dose, gradual increase every 1-2 weeksaccording to patient tolerance

Transient bradycardia, heart block, hypotension often areasymptomatic, no treatment, but patients advised to standslowly from lying position

If symptoms (dizziness, blurred vision) occur dosereduction &/or lower dose titration


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Metoprolol, Bisoprolol &

Carvedilol

They are FDA approved for HF

Metporolol & bisoprolol are cardioselective

showing myocardial 2-receptor upregulation Carvedilol is mixed ,-blocker with additional

antioxidant activity

Approved for stages II & III and now IV HF

Carvedilol is possibly associated with morehypotension & dizziness


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DIGOXIN

Digoxin Intervention Group (DIG) trial

HF patients Class II/III on digoxin (2-5 years) moderate

decrease of combined mortality/hospitalization but little effecton survival

Digoxin started early to reduce symptoms of HF patients onACEI or -blocker but not yet with improved symptoms

Digoxin is routinely advised for HF patients with chronic atrialfibrilation

Digoxin is avoided in patients with appreciable sinus/AV block

It is not indicated as 1ry therapy for acute decompensated HF


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Digoxin

Digoxin therapy can be delayed till responseto ACEI or -blocker is evident and given to

the still symptomatic patients Digoxin monotherapy or digoxin-diuretic

therapy is no longer recommended

Usual maintenace dose is 0.125-0.25 mg/day

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