CONGESTIVE HEART FAILURE

MA. LENY ALDA G. JUSAYAN, MD

HEART FAILURE
Inability of the heart to pump an adequate amount of blood to the bodys needs CONGESTIVE HEART FAILURE refers to the state in which abnormal circulatory congestion exists a result of heart failure

CAUSES OF HEART FAILURE:

Final common pathway of many kinds of heart diseases
Ischemic, alcoholic, restrictive, hypertrophic Optimal treatment requires identification of primary & secondary factors leading to CHF HELPFUL RESULT of dilatation: increases cardiac output HARMFUL RESULT of dilation: more wall tension, more oxygen is needed to produce any given stroke volume

CLASSIFICATION:
SYSTOLIC DYSFUNCTION:
Inadequate force is generated to eject blood normally Reduce cardiac output, ejection fraction (< 45%) Typical of acute heart failure Secondary to AMI Responsive to inotropics

CLASSIFICATION:
DIASTOLIC DYSFUNCTION
Inadequate relaxation to permit normal filling Hypertrophy and stiffening of myocardium Cardiac output may be reduced Ejection fraction is normal Do not respond optimally to inotropic agents

CLASSIFICATION:
HIGH OUTPUT FAILURE
Increase demand of the body with insufficient cardiac output Hyperthyroidism, beri-beri, anemia, AV shunts Treatment is correction of underlying cause

CLASSIFICATION:
ACUTE HEART FAILURE
Sudden development of a large myocardial infarction or rupture of a cardiac valve in a patient who previously was entirely well, usually predominant systolic dysfunction

CLASSIFICATION:
CHRONIC HEART FAILURE
Typically observed in patients with dilated cardiomyopathy or multivalvular heart diseases that develops or progresses slowly

PRECIPITATING CAUSES OF HEART FAILURE:

Infection Anemia Thyrotoxicosis & pregnancy Arrythmias Rheumatic, viral & other forms of myocarditis Infective endocarditis Systemic hypertension Myocardial infarction Physical, dietary, fluid, environmental & emotional excesses Pulmonary embolism

PULMONARY CONGESTION & RESPIRATORY SYMPTOMS:

Result of dilatation & increasing left ventricular end diastolic pressure, left atrial pressure & capillary pressures
Results to pulmonary vascular congestion & symptoms associated with cough with blood tinged sputum

Cont.
EDEMA OF THE BRONCHIAL MUCOSA
Increases resistance to airflow producing respiratory distress similar to asthma (cardiac asthma)

Cont:
DYSPNEA
Results from reflexes initiated by vascular distention Increased rigidity of lungs & impaired gas exchange resulting from interstitial edema Accumulation of fluid in ALVEOLARS SACS (pulmonary edema)

Cont.
TACHYCARDIA
An early compensatory response mediated by increased sympathetic tone EDEMA compensatory response mediated by the renin angiotensin aldosterone system & by increased sympathetic outflow CARDIOMEGALY a compensatory structural response

SYMPTOMS:
Due to inadequate perfusion of peripheral tissues (fatigue, dyspnea) Elevated intracardiac filling pressures (orthopnea, PND, peripheral edema)

PHYSICAL EXAM:
Jugular venous distention S3 Rales Pleural effusion Edema Hepatomegaly Ascites

All the signs of CHF are the consequences of inadequate force of contraction"

PATHOPHYSIOLOGY:
STARLINGS LAW
Within limits, the force of ventricular contraction is a function of the enddiastolic length of the cardiac muscle, which in turn is closely related to the ventricular end-diastolic volume.

PATHOPHYSIOLOGY:
Heart failure results in DEPRESSION of the ventricular function curve COMPENSATION in the form of stretching of myocardial fibers results Stretching leads to cardiac dilatation which occurs when the left ventricle fails to eject its normal end diastolic volume

CARDIAC FAILURE
VENOUS PRESSURE SYMPATHETIC ACTIVITY CARDIAC OUTPUT BLOOD PRESSURE

RENAL BLOOD FLOW

RENIN ANGIOTENSIN II

ALDOSTERONE
CAPILLARY FILTRATION SODIUM RETENTION EDEMA

NEUROHUMORAL ACTIVATION DURING MYOCARDIAL FAILURE

MYOCARDIAL FAILURE CARDIAC OUTPUT BLOOD PRESSURE/TISSUE PERFUSION

ACTIVATION OF ADRENERGIC SYSTEM

ARTERIOLAR CONSTRICTION INCREASED SYSTEMIC VASCULAR RESISTANCE INCREASED RESISTANCE TO EJECTION

COMPENSATORY RESPONSES DURING HEART FAILURE:

CARDIAC OUTPUT CAROTID SINUS FIRING RENAL BLOOD FLOW

SYMPATHETIC DISCHARGE FORCE RATE PRELOAD

RENIN RELEASE

AFTERLOAD

REMODELING

CARDIAC OUTPUT (VIA COMPENSATION)

Pathophysiology of Cardiac Performance

Factor Mechanism Therapeutic Strategy

1. Preload (work or stress the heart faces at the end of diastole)

increased blood volume and -salt restriction increased venous tone--->atrial -diuretic therapy filling pressure -venodilator drugs
- arteriolar vasodilators -decreased angiotensin II (ACE inhibitors)

2. Afterload (resistance against increased sympathetic which the heart must pump) stimulation & activation of renin-angiotensin system ---> vascular resistance ---> increased BP 3. Contractility

decreased myocardial -inotropic drugs (cardiac contractility ---> decreased CO glycosides) decreased contractility and decreased stroke volume ---> increased HR (via activation of b adrenoceptors)

4. Heart Rate

CLINICAL MANAGEMENT OF CONGESTIVE HEART FAILURE

OBJECTIVES:
Increase cardiac contractility Decrease preload ( left ventricular pressure) Decrease afterload (systemic vascular resistance) Normalize heart rate and rhythm

Approaches:
Reduce workload of heart 1.Limit activity level reduce weight control hypertension 2. Restrict sodium (low salt diet)

3. Give diuretics (removal of retained salt and water)

4. Give angiotensin-converting enzyme inhibitors (decreases afterload and retained salt and water) 5. Give digitalis (positive inotropic effect on depressed heart)

6. Give vasodilators (decreases preload & afterload)

DRUGS USED TO TREAT CONGESTIVE HEART DISEASE:

VASODILATORS
Reduce the preload (through venodilatation), or reduction in afterload (through arteriolar dilatation) or both Decrease the load of the myocardium

DIURETIC AGENTS:
Reduce salt & water retention, thereby reducing ventricular preload

INOTROPIC AGENTS: oIncrease the strength of contraction of cardiac muscles

DRUGS USED TO TREAT CONGESTIVE HEART FAILURE

VASODILATORS
-CAPTOPRIL -ENALAPRIL -FOSINOPRIL -LISINOPRIL -QUINAPRIL -HYDRALAZINE -ISOSORBIDE -MINOXIDIL -SODIUM NIITROPRUSSIDE -AMRINONE -MILRINONE -DOBUTAMINE

INOTROPIC AGENTS -DIGOXIN

-DIGITOXIN

DIURETICS

-BUMETANIDE -FUROSEMIDE -HYDROCHLOROTHIAZIDE -METALAZONE

BASIC PHARMACOLOGY OF DRUGS USED IN CONGESIVE HEART FAILURE: DIGITALIS PHARMACOKINETICS:

DIGOXIN
LIPID SOLUBILITY MEDIUM ORAL AVAILABILITY 75% HALF-LIFE 40 HRS PLASMA PROTEIN BINDING 20-40 HRS PERCENTAGE METABOLIZED <20 VOLUME OF DISTRIBUTION 6.3 L/KG

DIGITOXIN
HIGH >90% 168 HRS >90 HRS >80 0.6 L/KG

PHARMACOKINETICS:
-T1/2 is long (40 hrs) -Therapeutic plasma concentration: 0.5-2 ng/ml -Toxic plasma concentration: >2 ng/ml *digitalis must be present in the body in certain "saturating" amount before any effect on congestive failure is noted this is achieved by giving a large initial dose in a process called "digitalization" -after intial dosages, digitalis is given in "maintenance" amounts sufficient to replace that which is excreted to avoid exceeding therapeutic range during digitalization: - the loading dose should be adjusted according to the health of the patient - slow digitalization (over 1 week) is the safest technique - plasma digoxin levels should be monitored

METABOLISM & EXCRETION:

Digoxin not extensively metabolized, 2/3 excreted unchanged in the kidneys Digitoxin metabolized in the liver and excreted into the gut via the bile

MECHANISM OF ACTION:
Inhibit the monovalent cation transport enzyme coupled Na+, K+ ATPase & increased intracellular Na+ content increases intracellular Ca2+ through a Na+ - Ca2+ exchange carrier mechanism. Increased myocardial uptake of Ca2+ augments Ca2+ release to the myofilaments during excitation invokes a positive inotropic response

MECHANISM OF ACTION:
Produce alterations in the electrical properties of both contractile cells and the specialized automatic cells, leading to increased automaticity & ectopic impulse activity Prolong the effective refractory period of the AV node slow ventricular rate in atrial flutter & fibrillation

PROPERTIES OF CARDIAC GLYCOSIDES:

OUABAIN
Lipid solubility (oil/water coefficient) Oral availability (% absorbed) Half-life in the body (hrs) Plasma protein binding (% bound) Volume of distribution Low

DIGOXIN
Medium

DIGITOXIN
High

0 21 0

75 40 <20

> 90 168 >80

18

6.3

0.6

EFFECTS IN HEART FAILURE:

Stimulates myocardial contractility Improves ventricular emptying Increase cardiac output Augments ejection fraction Promotes diuresis Reduces elevated diastolic pressure & volume & end systolic volume Reduces symptoms resulting from pulmonary vascular congestion & elevated systemic venous pressure

DIGITALIS INTOXICATION:
Serious & potentially fatal complication Anorexia, nausea & vomiting = earliest signs of digitalis intoxication Arrythmias: ventricular premature beats, bigeminy, ventricular & atrial tachycardia w/ variable AV block Chronic digitalis intoxication = exacerbations of heart failure, weight loss, cachexia, neuralgias, gynecomastia, yellow vision, delirium

TREATMENT OF DIGITALIS INTOXICATION:

Tachyarrythmias: withdrawal of the drug, treatment with beta blocker or lidocaine Hypokalemia: potassium administration by the oral route

OTHER POSITIVE INOTROPIC DRUGS USED IN HEART FAILURE:

BIPYRIDINES
Amrinone & Milrinone Parenteral forms only Half-life: 2-3 hrs 10-40% excreted in the urine MOA: increase inward calcium influx in the heart during action potential & inhibits phosphodiesterase ADVERSE EFFECTS: nausea, vomiting, thrombocytopenia, liver enzyme changes

BETA ADRENOCEPTOR STIMULANTS:

DOBUTAMINE
Increases cardiac output Decrease in ventricular filling pressure Given parenterally CONTRAINDICATIONS: pheochromocytoma, tachyarrythmias ADVERSE EFFECTS: precipitation or exacerbation of arrythmia

DRUGS WITHOUT POSITIVE INOTROPIC EFFECTS USED IN HEART FAILURE:

DIURETICS
Reduce salt & water retention reduce ventricular preload Reduction in venous pressure reduction of edema & its symptoms, reduction of cardiac size improved efficiency of pump function

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS:

Reduce peripheral resistance reduce afterload Reduce salt & water retention ( by reducing aldosterone secretion) reduce preload Reduce the long term remodelling of the heart vessels ( maybe responsible for the observed reduction in the mortality & morbidity)

VASODILATORS:
HYDRALAZINE, ISDN Reduction in preload through venodilatation or reduction in afterload through arteriolar dilation or both

BETA-ADRENOCEPTOR BLOCKERS:
BISOPROLOL, CARVEDILOL, METOPROLOL
Reduction in mortality in patients with stable Class II & Class III heart failure

DIURETICS

RENAL TRANSPORT MECHANISM:

PROXIMAL CONVOLUTED TUBULE: Carries out isosmotic reabsorption of amino acids, glucose and cations Bicarbonate reabsorption 40-50% Na reabsorption

THICK PORTION OF ASCENDING LIMB OF THE LOOP OF HENLE: Pumps Na, K & Cl out of the lumen into the interstitium Provides the concentration gradient for the countercurrent concentrating mechanism Ca & Mg reabsorption

DISTAL CONVOLUTED TUBULE:

Actively pumps Na & Cl out of the lumen nephron 10 % Na reabsorbed Ca & Mg reabsorption

COLLECTING TUBULE:
Primary site of acidification of urine & aldosterone regulated reabsorption of Na 2-4 % reabsorbed filtered Na H2O reabsorption under ADH control

DIURETICS
Drugs that increase the rate of urine flow Increase the rate of Na & Cl excretion Decrease reabsorption of K, Ca & Mg

DIURETICS
CLASSIFICATION: SITE OF ACTION:
Proximal tubule Proimal tubule, Loop of Henle, Collecting tubule Ascending limb of the loop of Henle Distal convoluted tubule

1. CARBONIC ANHYDRASE INHIBITORS 2. OSMOTIC DIURETICS

3. LOOP DIURETICS 4. THIAZIDE DIURETICS

5. POTASSIUM SPARING Collecting ducts DIURETICS

CARBONIC ANHYDRASE INHIBITORS:

CLASSIFICATION & PROTOTYPES: ACETAZOLAMIDE (Diamox) a sulfonamide derivative MECHANISM OF ACTION:
Inhibits carbonic anhydrase w/c slows the ff. rxn: H + HCO3 H2O + CO2 Necessary for maximum reabsorption of HCO3 from the glomerular filtrate Drug effect occurs throughout the body

PHARMACOKINETICS:
Well absorbed after oral administration Onset of action: 30 minutes Duration: 12 hrs Excretion: proximal tubule

CLINICAL USES:
Treatment of glaucoma major application Urinary alkalinization Epilepsy Acute mountain sickness Correction of metabolic alkalosis

TOXICITY:
Hyperchloremic metabolic acidosis Renal stones Renal potassium wasting Drowsiness & paresthesias large doses

LOOP DIURETICS
CLASSIFICATION & PROTOTYPES: Furosemide prototype & sulfonamide derivative Bumetanide- sulfonamide Ethacrynic Acid phenoxyacetic acid

PHARMACOKINETICS:
Rapidly absorbed Diuretic response is extremely rapid following IV injection Duration of effect: 2-3 hrs Half life: dependent on renal function Excreted in the kidney

MECHANISM OF ACTION:
Inhibit the coupled Na+/K+/2Cl transport system in the luminal membrane of the thick asceding limb of the loop of henle reduce NaCl reabsorption Increase Mg & Ca+ excretion

CLINICAL USES:
Treatment of edematous states (CHF & ascites) Acute pulmonary edema in w/c a separate pulmonary vasodilating action may play a useful additive role Sometimes used in hypertension if response to thiazide is inadequate but their short duration of action is a disadvantage Treatment of severe hypercalcemia induced by a carcinoma less common Acute renal failure Hyperkalemia

TOXICITY:
Hypokalemic metabolic alkalosis Hyperuricemia Hypovolemia & cardiovascular complications Ototoxicity important toxic effect of the loop agents hypomagnesemia

THIAZIDE DIURETICS
CLASSIFICATION & PROTOTYPE:
HYDROCHLOROTHIAZIDE sulfonamide derivative INDAPAMIDE new thiazide like agent with a significant vasodilating effect than Na diuretic effect

MECHANISM OF ACTION:
Inhibit NaCl transport in the early segment of the distal convoluted tubule ( a site w/c significant dilution of urine takes place)

REDUCE THE DILUTING CAPACITY OF THE NEPHRON

EFFECTS:
Urinary excretion
Full doses produce a moderate Na & Cl diuresis hypokalemic metabolic alkalosis Reduced the blood pressure by reduction of the blood volume but with continued use these agents appear to reduce vascular resistance

CLINICAL USE:
Hypertension major application, for w/c their long duration of action & moderate intensity of action are useful Chronic therapy for edematous conditions (CHF) another common application Recurrent renal calcium stone formation can sometimes be controlled with thiazides

TOXICITY:
Hypokalemic metabolic alkalosis & hyperuricemia Chronic therapy is often associated with potassium wasting hyperlipidemia

POTASSIUM SPARING DIURETICS:

CLASSIFICATION & PROTOTYPES
o SPIRINOLACTONE antagonist of aldosterone in the collecting tubules
Has a slow onset & offset of action (24-72 hrs)

o TRIAMTERENE & AMILORIDE inhibitors of Na flux in this portion of the tubule

ADVERSE EFFECTS:
Decrease K & H ion excretion and may cause hyperchloremic metabolic acidosis Interfere with steroid biosynthesis

CLINICAL USE:
Hyperaldosteronism important indication Potassium wasting caused by chronic therapy with loop diuretic or thiazide if not controlled by dietary K supplements Most common use is in the form of products that combine a thiazide with a K sparing agent

TOXICITY:
Hyperkalemia most important toxic effect Metabolic acidosis in cirrhotic patients Gynecomastia & antiandrogenic effects

OSMOTIC DIURETICS
CLASSIFICATION & PROTOTYPE:
MANNITOL prototype osmotic diuretic given intravenously

MECHANISM OF ACTION:
Holds water in the lumen by virtue of its osmotic effect Major location for this action is the proximal convoluted tubule, where the bulk of isosmotic reabsorption takes place Reabsorption of H2O is also reduced in the descending limb of the loop of henle & the collecting tubule

EFFECTS:
Volume or urine is increased Most filtered solutes will be excreted in larger amounts unless they are actively reabsorbed

CLINICAL USES:
Maintain high urine flow (when renal blood flow is reduced & in conditions of solute overload from severe hemolysis or rhabdomyolysis) Useful in reducing intraocular pressure in acute glaucoma & increase intracranial pressure in neurologic conditions

TOXICITY:
Hyponatremia & pulmonary edema due to removal of water from the intracellular compartment Headache, nausea, vomiting dehydration

Asymptomatic Mild to LV Dysfubction moderate CHF ACE inhibitor Beta blocker Digoxin Diuretics ACE inhibitor

Moderate to severe CHF Digoxin Diuretics ACE inhibitor

Beta blocker
Spironolactone

Beta blocker