Heart failure is a a syndrome where the heart is not able to supply sufficient blood flow to meet the

metabolic needs of the body. It is a progressive syndrome caused by cardiac dysfunction generally
resulting from a myocardial muscle dysfunction or muscle loss and characterized by either left ventricle
dilatation and/or hypertrophy. Hypertension may cause heart failure coz the heart has to pump against a
high pressure. Other medical conditions that cause the heart to overwork are hyperthyroidism and
diabetics. CAD is a major cause of heart failure when disease result in a reduced blood flow to the heart
muscle. MI can also result in HF when a section pf the heart muscle is damaged from ischemia.
Congenital heart failure is rare. There are other less common causes including the use of cardiotoxic
drugs.

Pathophysiology

The heart has 4 chambers the right atrium and ventricle and a left atrium and ventricle. (I will spare the
anatomy where and how the blood circulates :) )
The heart's 4 valves which open and close keep the blood flowing in one direction – but sometimes the
valves “leak” and blood is allowed to flow back (regurgitate) the wrong way. If this occur the pt may
need valve replacement which may put him to risk of clots and requires long-term anticoagulation
therapy. Normal heart sounds make lub-dub, lub-dub sound. The normal S1 sound (lub) is the sound of
the tricuspid and mitral valves closing the right and left atrium. The S2 sound (dub) is the sound of the
polmunary valves and aortic valves closing in the right and left ventricle. The presence of sounds such
as S3 or S4 indicate abnormality.
Each time the ventricle contracts, a volume of blood is ejected. This is called the cardiac output (CO),
the CO is determined by the stroke volume x the number of beats per minute or the heart rate (HR).
CO=SV x HR
Cardiac output can also be individualized to a pt BSA and this value is known as the cardiac index (CI)
CI=CO/BSA

In early stages of HF the heart responds to the diminished output by stretching to hold more blood and
the walls grows thicker to pump more harder. This brings a short-term improvement but eventually the
chamber inside the left ventricle become smaller due to expanding muscle and the muscle walls are
weaken. This results in a decrease of CO. In attempt to compensate the body activates the SNS
bringing the activation of RAAS with increase of angiotensin II, vasopressin (ADH). This in turn
causes the increase of aldosterone release increasing the renal re-absorption of Na and water. Therefore
blood volume increase to help maintain CO but it is harmful coz it raises venous pressure and causes
pulmonary and systemic edema. The excess fluid cause the body to become congested and the classic
symptoms of congestive heart failure appear including dyspnea, SOB, fatigue, pulmonary congestion
and periferical edema. In severe cases the lack of perfusion in organs lead to organ failure, including
renal failure.

Non pharmacological therapy

Monitor weight daily, Instruct pt what to do if the body weight increases or the HF symptoms worsen,
Limit Na intake to < 2 grams/d. If the pt has also HTN limit Na intake to 1.5 g/d. Avoid NSAIDS,
including COX-2 inhibitors. Stop smoking, Pneummococcal vaccine and annual influenza. Encourage
weight reduction to BMI<30, exercise 30 minutes/day, 3-5 days per week as tolerated.

Drugs tha cause or worsen HF:

1. Chemiotherapic agents particularly anthraciclines and derivates (doxorubicin, daunorubicin etc.
) Also trasduzumab (Herceptin), Imatinib (Gleevec) and docetaxol (Taxotere) can cause fluid
 retention.
2. Amphetamines and sympathomimetics
3. Negative inotropic drugs (Verapamil and diltiazem ) can exacerbate HF and must be avoided,
also avoid itraconazole.
4. Antiarrhymic drugs ( lower the risk with amiodarone and dofetilide). Do not use class one
antiarrymic agents (mexiletine, tocainide , procainamide, quinidine, disopyramide, flecainide
and propafenone.
5. Heart failure disease can be caused by this drugs: fenfluramine (Pondimin), dexfenfluramine
(Redux), ergot derivates including ergotamine (Ergostat), dihydroergotamine (Migranal),
Methysergide (Sansert ) and others.
6. Immunomodulators, including interferons, etarnecept (TNF-blockers can worsen HF),
rituximab and others
7. NSAIDS, including selective COX2 inhibitor celecoxib. Use can cause renal dysfunction, fluid
retention and worsen HF.
8. Glucocorticoids can worsen HF
9. Triptan migraine drugs (controindicated with history of cardiovascolar disease or uncontrolled
HTN)
10. Thiozolidinediones in particular rosiglitazone (Avandia), Pioglitazione (Actos) due to increase
risk of edema, especially when used with insulin.
11. Excessive alcohol use: modest use may have mild cardiovascular benefit, but excessive uses
does not.

Pharmacotherapy

Two classes of agents have become the cornerstone of therapy to delay or halt the progression of
cardiac dysfunction and improve mortality. ACEi and BB – to be used with everyone with HF who
does not have a contraindication. Other agents with positive impact are: ARBs, aldosterone antagonits,
and the combination of hydralazine with nitrate. This drugs can be added to the standart therapy when
pt are still symptomatic.
Pt with congestive HF receive diuretics (primary loop diuretics) to reduce fluid retention. Diuretics are
use to treat overload manifested by signs of elevated filling pressures (jugular venous distention,
perpheral edema,rales etc) and by congestive symptoms (orthopnea, edema, shortness of breath).
Digoxin is a agent that can be used to treapt symptomatic HF in pt already controlled with standart
therapy.

HF classification:
ACC/AHA staging system NYHA funcional class
A. At high risk for development of HF, but have No corresponding category
no strictural heart disease or symptoms of HF ( pt
with HYN,CHD,DM,obesity,metabolic syndrome
B. Structural heart disease present, but no signs or 1. No limitations of physical activity. Ordinary
symptoms of HF (LVH, low EF, valvular disease, physical activity does not cause undue fatigue,
previous MI) palpitation or dispnea.
C. Structural heart disease with prior or current 2. Slight limitation of physical activity.
symptoms of HF (SOB, fatigue, reduced ex. Comfortable at rest but ordinary physical activity
Tolerance results in fatigue, palpitation or dispnea
3. Marked limitation of ph. Activity. Comfortable

D. Advanced structural heart disease with
symptoms of HF at rest despite max medical
therapy.
at rest but minimal exertion (bathing, dressing)
causes symptoms (fatigue, palpitation or dyspnea.
4. Unable to carry on any physical activity without
discomfort. Symptoms of HF present at rest.

RAASi
Titrate the drug to target dose, if possible. Titrate doses to reduce symptoms not BP
- Some pt may receive ACEi-ARBs together (not common) Both can increase K, so monitoring is
required. K should remain within the safe level of 3.5-5 mEq/L
- ARBs are given if pt is intolerant to ACEi or as a 1st line
- There is a increase of angioedema with Black Pt. Angioedema is more likely with ACEi. Counsel to
report any swelling or if the pt had any story of angioedema as it can be fatal.
- Pt. with this meds should not use salt suplements as it contains Kcl
- Captopril is more likely to couse ADRs because of dose (TID) others are BID

ACEi inhibit the ACE preventing the convertion of A1 to A2 a potent vasocostrictor, thereby
reducing BP.

Benazepril (Lotensin), Captopril (Capoten), Enalpril (Enalprilat IV, Vasotec), Fosinopril, Lisinopril (
Privinil, Zestril), Moexepril (Univasc), Peridopril (Aceon), Quinapril (Accupril), Ramipril (Altace),
Trandolapril (Mavik).

Black box warning: Same as ARBs

Contraindications: Same as ARBs

Side effects: Cough, hyperkalemia, angioedema, hypotension, headache, dizzines, and acute renal
failure, espetially if pt is dehydrated.

Monitor: Same as ARBs

Prengnancy category D.

ARBs block AII from binding to the AT-1 receptor on vascular smooth muscle.

Valsartan (Diovan), Losartan (Cozar),Irbesartan (Avapro), Candesartan (Atacand), Olmesartan

(Benicar), Telmisartan (Micardis), Eprosartan (Teveten), Azilsartan (Edarbi).

Black box warning Can cause injury and death to developing fetus; discontinue as soon the pregnancy
is detected.

Contraindications: Angioedema Do not use in bilateral stenosis, it can worsen the renal condition. Do
not co-administer with Aliskiren in pt with diabetes.
Side effects: Hyperkalemia, angioedema, headache dizzines,

Monitoring: BP, K, renal fx

Prengnancy category D.
Potassium sparing diuretics: Compete with aldosterone for receptor sites in the distal renal tubules,
reduce cardiac remodeling, increasing Na, Cl, and water excretion while conserving K and H ions.
Reduce morbidity and mortality. These agents are used in Class 3 and Class 4 HF, in addition of
standart therapy.
Spironolactone is non selective so also blocks androgen and progesterone receptors. Eplenerone is
selective therefore it has less side effects.

Amiloride (Midamor) Triamterene (Dyrenium) + HCTZ(Maxzide, Dyazide) Spironolactone

(Aldactone) Eplenorone (Inspra)

- Black box warning: Tumor risk with Spironolactone; Tumorogenic in chronic rat toxicity studies.
Only used in approved indications and avoid unnecessary use.
- Contraindications: Renal impairment (CrCl < 30 mL/min) Hyperkalemia, And concomitant use of
strong 3A4 inhibitors.
- Warnings: Do not initiate therapy in pt K> 5mEq/L, SCr>2 mg/dl (females) Scr > 2.5 mg?dL (males)
- Side effects: ↑K, ↑Scr, For spironolactone gynecomastia , breast tenderness, impotence , menstrual
changes, hirsutism. Rare ↑Cl acidosis.
- Monitor K before starting and frequently thereafter, BP, Scr.
- Pregnancy category C/B(eplenorone)

RAASi drug interactions

All RAASi can increase the risk of hyperkalemia, monitor frequently.

A triple therapy ACEi, ARBs, and aldosterone inhibitor is not recommended due to high risk of
hyperkalemia.
All RAASi can have additive effects on BP
Li should not be given with diuretics because it decreases Li renal clearance and increase tox.

Beta Blockers
These agents inhibit the SNS and reduce cardiac remodeling and mobility, mortality. BB are
recommended for Class 2-4 HF and are usually initiated when pt is euvolemic and asymptomatic. If pt
is already fluid-overloaded at initiation this may exacerbate HF symptoms. Avoid BB with ISA as these
agents may worsen survival.
BB mentioned in the guidelines: Bisoprolol (Zebeta) Metoprolol succinate ER ( Toprol XL), Non
selective, carvedilol (Coreg, Coreg CR)

Contraindications: Sinus bradycardia, 2nd or 3rd degree heartblock (unless pt has funcioning
pacemaker), cardiogenic shock, sick sinus syndrome. Do not initiate in pt with active asma or
brochospasm.

Side effects: Reduce HR, fatigue, dizziness. Less common: depression, reduce libido, impotence,
hyperglicemia with non-selective agents, hypertrigliceridemia, reduce HDL

Monitor: HR, BP, signs and symptoms of HF

- Avoid abrupt discontinuation, must taper.

Take carvedilol of all forms with food

BB drug interactions: Caution with diabetes: BB cover up symptoms of shakiness and anxiety with
hypoglicemia (occurs mostly with not-selectives). They do not cover up sweating and hunger.
BB can enhance the effects of insulin and oral hypoglicemics, monitor BG.
Use caution when admn other drugs that slow HR
Carvedilol is a substrate of CYP2D6, check interactions
Carvedilol can increase cyclosporine and digoxin levels.

Hydralazine / Nitrates

Hydralazine is a direct arterial vasodilatator which reduce afterload. Nitrates are venus vasodilatators
which and reduce preload. The combination product BiDil is indicated in black pt with Class 3 and
Class 4 HF who are symptomatic despite optimal therapy with ACEis and BB. BiDil also used with pt
who cannot take ACEi or ARBs due to poor renal fx, angioedema, hyperkalemia. Do not use nitrates
alone; hydralazine is used with nitrates to improve efficacy and reduce tolerance.

Isosorbide dinitrate/ Hydralazine ( BiDil )

Contraindications: CI with PDE-5 inhibitors

Side effects: LES-like syndrome, headache, dizziness, reflex tachycardia.
Monitor: HR, BP, signs and symptoms of HF

Hydralazine:
Side effects: LES-like syndrome (dose duration related, report fever, join/muscle aches, fatigue) reflex
tachycardia.
Monitor: HR, BP, signs and symptoms of HF

Isosorbide mononitrate (Monoket, Imdur), Isosorbide dinitrate ( Isordil, Dilatrate SR)

Contraindications: CI with PDE-5 Inhibitors
Side effects: Headache, dizziness, tachyphylaxis (need 10-12 hours of free nitrate interval)
Monitor: HR, BP, signs and symptoms of HF

Diuretics

Loopes are used to reduce congestive symptoms and restore euvolemia. These agents can fluid
retention, volume status, and venous pressure. Relief of congestive signns and effects ( orthopnea,
edema, SOB) must be achieved without causing side effects ( symptomatic hypotension, or worsening
of renal fx ). If more diuresis is needed may increase dose, switch to IV or add metozalone.

Loop diuretics Inhibit reabsorption of Na and Cl in the ascending loop of henle and distal renal tubule.
Intefering with the cloride binding co-trasport sustem thus causing increased excretion of water, Na, Cl,
Mg, and Ca ( difference with thiazides!)

Furosemide (Lasix, (most pt take it in divided doses, take 2nd in the early afternoon) Bumetanide,
Torsemide, (Demadex) Ethacrynic acid (Edecrin)
Black Box warning: Can lead to profound diuresis resulting in fluid and electrolyte depletion
Contraindication: Anuria
Side effects: ↓K, orthstatic hypotension, ↑UA ↑BG↓Ca↓Na↓Mg↓Cl photosensitivity, ototoxicity
Monitor renal fx, fluid status, BP, electrolytes, hearing with high doses or rapid IV adm
Furosemide IV:PO ratio is 1:2
Caution in pt with sulfa allergy except ethacrinic acid but this last is more associated with ototoxicity
Caution associating this drugs with aminoglycosides.
Pregnancy category B (torsemide/Eth. Acid)
Pregnancy category C ( furosemide/Bumetanide)

Loop Drug-Drug interactions

Additive effects with BP lowering particularly with diuresics.
Loop diuretics increase ototoxic potential of aminoglycosides
Avoid Li
Do not use NSAIDS in pt with HF. Also this drugs can cause Na and water retention

Digoxin:

Can be used in pt with symptomatic HF who are receiving standart therapy, including ACEi and BB. In
HF digoxin leads to symptom improvement, increase tolerance, and increase QOL. Dosing should be
based on renal fx, concomitant medications, and should be dosed 0.125 mg daily for most pt.

Digoxin (Lanoxin) inhibits Na/K/ATP-ase pump; acts as a positive inotrope ( increase contractility and
CO) and as a negative chronotrope ( decrease HR)
The therapeutic range for CHF = 0.5-0.9 ng/mL. Watch for renal impairment, decrease dose for CrCl<
50mL/min. Antidote: Digibind or DigiFab

Contraindication 2nd or 3rd degree heart block without a pacemaker, Wolf Parkinson-White syndrome
and A Fib

Side effects: Dizziness, headache, diarrhea, nausea, vomiting, anorexia, mental changes
Monitoring: HR, BP, electrolytes (K, Ca, Mg), renal fx. ECG
and drug level
Toxicity: First signs of toxicity are nausea/vomiting, and loss of appetite and bradycardia. Other signs
of toxicity include blurred/double vision, altered color perception, greenish-yellow halos around lights
or objects, abdominal pain, confusion, delirium, prolonged PR interval, accelerated junctional rhythm,
bidirectional ventricular tachycardia
Pregnancy category C

Digoxin drug interacions: BB and non-DHP CCB may have additive effects on the reducing the HR
Digoxin is mostly renally cleared and partially cleared hepatically. Decreased renal fx requires
reduction of Digoxin, or , in acute renal failure digoxin should be held.
Digoxin is a 3A4 substrate and its levels may increase with amiodarone, quinidine, verapamil,
erythromicin, clarithromycin, azole antifungals, cyclosporine, propafenone, Pis and a few others; a
dose reductions is required.
Hypokalemia ( K<3.5 mEq/L) may increase the risk of digoxin toxicity. Hyperkalemia may also
increse the risk of digoxin toxicity.