HEART FAILURE Sue-Ann R. Locnen, MD.

November 19, 2010

LEGEND Normal text : lecture and recording Italics : Harrisons 17th ed.(plus some other reliable books and websites) MYOCARDIAL MECHANICS AND CARDIAC FUNCTION A. THE FORCE-VELOCITY CURVE The mechanical activity of cardiac muscle may be expressed externally in 2 ways: shortening and tension development Velocity of shortening of cardiac muscle is inversely related to the level of tension The higher the tension of the LV the lower the velocity, vice versa The greater the load the muscle is called upon to lift, the lower its velocity of shortening of muscle fibers Contractility of the heart muscle is altered by changes in resting fiber length and by changes in the contractility B. VENTRICULAR EJECTION Analysis of the heart as a pump has classically centered on the relation between the EDV and its SV. Stroke volume (SV) varies directly with diastolic fiber length (preload) and inversely with the arterial resistance (afterload) As the heart fails, it delivers a progressively smaller SV from a normal or even elevated end-diastolic volume Ventricular function curve provides a useful definition of the level of contractility of the heart It is also dictated by adrenergic stimulation: cardiac adrenergic stimulationrelease of NE ventricular function NE activates beta receptors activating adenylate cyclasecAMPprotein kinase activationinflux of 2+ Ca contractile apparatus cAMP phosphorylates phospholamban Ca2+ uptake by sarcoplasmic reticulum rate of relaxation Effects of Adrenergic Activation: 1. Tachycardia 2. Increased rates of ejection and filling 3. Reduction in cardiac dimensions ASSESSMENT OF CARDIAC FUNCTION Stroke Volume the amount of blood that the heart pump in one cardiac cycle/heartbeat EDV ESV = SV Cardiac Output amount of blood that the heart pump in one minute SV x HR = CO Ejection Fraction ration of the volume of blood ejected from the left ventricle per beat (SV) to the volume of blood in the left ventricle at the end of diastole (EDV) EDV - ESV/EDV = EF LV End Systolic and Diastolic Volumes - in HF Diastolic Function ability of the heart to receive the blood

Length of muscle at onset of contraction Influenced by end diastolic fiber length and by diastolic ventricular volume Amount of myocardial stretch just before systole caused by the pressure created by the volume of blood with the ventricle Determinants of Preload: 1. Total blood volume 2. Distribution of blood volume 3. Atrial contraction

B. MYOCARDIAL CONTRACTILITY Affected by adrenergic activity adrenergic activity contractility Circulating cathecolamines contractility Force-frequency relation - rate and rhythm of myocardial contraction Exogenously administered inotropic agents contractility Physiologic depressants of contractility - Eg. Hypoxia, Ischemia, Acidosis, Infection - myocardial fiber shortening afterload CO Pharmacologic depressants of contractility - Eg. Sedatives, Anaesthesia Myocardial depression C. VENTRICULAR AFTERLOAD Tension developed in the ventricular wall during ejection Determined by: 1. Aortic pressure 2. Volume and thickness of the ventricular cavity
(Laplaces Law)

Laplace's Law- indicates that the tension of the myocardial fiber is a function of the product of the intracavitary ventricular pressure and ventricular radius divided by the wall thickness. Inversely related to preload and myocardial contractility preload and contractility myocardial fiber shortening afterload CO myocardial fiber shortening afterload CO
INTERACTIONS IN THE INTACT CIRCULATION OF PRELOAD, CONTRACTILITY & AFTERLOAD IN PRODUCING STROKE VOLUME

CONTROL OF CARDIAC PERFORMANCE AND OUTPUT A. VENTRICULAR END DIASTOLIC VOLUME Aka. Preload

Fig. 1 Stroke volume combined with heart rate determines cardiac output, which, when combined with peripheral vascular

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resistance, determines arterial pressure for tissue perfusion. The characteristics of the arterial system also contribute to afterload, an increase of which reduces stroke volume. The interaction of these components with carotid and aortic arch baroreceptors provides a feedback mechanism to higher medullary and vasomotor cardiac centers and to higher levels in the central nervous system to affect a modulating influence on heart rate, peripheral vascular resistance, venous return, and contractility.

PATHOGENESIS OF HEART FAILURE

Sudden Onset (eg.MI) Gradual Onset (eg. Hereditary, volume overload)

Index Event

HEART FAILURE 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 at a rate commensurate to the needs of the body. The problem is mainly on the ability of the heart to fill and to pump Inherited or acquired abnormality of cardiac structure and/or function inability of the heart to pump blood to meet the needs of the tissues for O2 and nutrients HF patients are now broadly categorized into one of two groups: HF with a depressed Ejection Fraction (aka Systolic HF) HF with a preserved Ejection Fraction (aka Diastolic HF) EPIDEMIOLOGY Leading problem in industrialized/western countries >5,000,000 patients 6,500,000 hospital days/year 300,000 deaths/year 6% - 10% of people >65 years Incidence rises with age 5.4% of health care budget (38 billion) Incidence x2 in last ten years Incidence is in women than in men ETIOLOGY AND CLINICAL CHARACTERISTICS OF HF Most common etiology: Coronary Artery Disease (CAD) 75% of CHF cases have antecedent hypertension Signs and symptoms of congestion (eg. rales, crackles, dyspnea, etc) are not always evident in HF patients CAD, Hypertension and Diabetes Mellitus interact to augment the risk of HF FORMS OF HEART FAILURE Systolic vs Diastolic HF Systolic HF - alteration in ventricular contraction Diastolic HF alteration in ventricular filling Low-Output vs High-Output HF Low-Output HF the CO is decreased High-Output HF the CO remains high or normal Right-Sided vs Left-Sided HF Right-sided HF when the right side of the heart cannot eject blood and cannot accommodate all the that normally returns to it from the venous circulation Left sided HF when the left side of the heart cannot pump the blood out of the ventricle to the systemic circulation Acute vs Chronic HF Backward vs Forward HF

Heart muscle damage

Disruption of the ability of the myocardium to generate force

Loss of functioning cardiac myocytes

Heart will not contract normally

Decline in the pumping capacity of the heart

Compensatory Mechanism Activation

RAAS

Adrenergic NS

Cytokine System

Asymptomatic HF

Sustained activation of compensatory mechanisms

Left Ventricular Remodeling

Cardiac decompensation

Symptomatic HF

A.

B.

C.

LEFT VENTRICULAR REMODELING Refers to the changes in LV mass, volume, shape, and composition of the heart that occur following cardiac injury and/or abnormal hemodynamic loading conditions May contribute independently to the progression of HF by virtue of the mechanical burdens that are engendered by the changes in the geometry of the remodelled LV. LV Remodelling Outcome: forward cardiac output LV dilation (stretch) hemodynamic overloading LV dilation LV wall thinning afterload functional afterload mismatch stroke volume CO LV dilation papillary muscles are pulled apart incompetence of the mitral valve functional mitral regurgitation hemodynamic overloading of the ventricle CHANGES IN LV-REMODELLING Myocyte hypertrophy Alterations in the contractile properties of the myocyte Progressive loss of myocytes through necrosis, apoptosis, and autophagic cell death -adrenergic desensitization Abnormal myocardial energetics and metabolism Reorganization of the extracellular matrix with dissolution of the organized structural collagen weave surrounding myocytes and subsequent replacement by an interstitial collagen matrix that does not provide structural support to the myocytes

1. 2. 3. 4. 5. 6.

D. E.

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CAUSES OF HEART FAILURE A. UNDERLYING CAUSES Ischemic Heart Disease most common, of all cases. Ischemia myocardium cell death contractility systolic HF Cardiomyopathies 1. Dilated decrease in contractility systolic HF 2. Hypertrophic & Restrictive - distensibility & ventricular filling diastolic HF Congenital Heart Disease Valvular Heart Disease due to defective valves the blood has difficulty moving forward pressure within the heart cardiac workload diastolic HF Systemic and Pulmonary Hypertension - afterload workload of the heart to overcome the high pressure hypertrophy of cardiac muscle impaired hearts ability to fill properly during diastole HF B. PRECIPITATING CAUSES Infections - cause sympathetic activity HR < time in diastole coronary flow and impede filling of the ventricle Arrhythmias due to altered electrical stimulation impaired myocardial contraction Physical, Dietary, Fluid, Environmental, and Emotional Excesses Myocardial Infarction (MI) Pulmonary Embolism C. FACTORS THAT MAY PRECIPITATE ACUTE DECOMPENSATION IN PATIENTS WITH CHRONIC HF 1. Dietary indiscretion 2. Myocardial ischemia/infarction 3. Arrhythmias (tachycardia or bradycardia) 4. Discontinuation of HF therapy 5. Infection 6. Anemia 7. Initiation of medications that worsen HF Ca2+ antagonists -blockers Nonsteroidal anti-inflammatory drugs (NSAIDs) Antiarrhythmic agents 8. Anti-TNF antibodies 9. Alcohol consumption 10. Pregnancy 11. Worsening hypertension 12. Acute valvular insufficiency COMPENSATORY MECHANISMS A. Frank Starlings Mechanism/Law ability of the heart to change its force of contraction and therefore stroke volume in response to changes in venous return -It states that the greater the volume of blood entering the heart during diastole (end-diastolic volume), the greater the volume of blood ejected during systolic contraction (stroke volume) and vice-versa B. Renin-Angiotensin-Aldosterone System maintains the CO through increased retention of salt and water. Angiotensin II 1. Aldosterone secretion NaCl excretion 2. Arteriolar Vasoconstriction BP 3. ADH secretion water excretion 4. NaCl reabsorption C. Sympathetic Nervous System maintain blood pressure vital organ perfusion

D. Activation of Cytokine System - offset the excessive peripheral vascular vasoconstriction vasodilatation Atrial and Brain Natriuretic Peptides (ANP and BNP) Prostaglandins (PGE2 and PGI2) Nitric Oxide (NO) ACTIVATION OF NEUROHORMONAL SYSTEMS IN HF
Heart failure

CO

Unloading of high pressure baroreceptors in the LV, carotid sinus and aortic arch

Generation of afferent signals to CNS

Cardioregulatory stimulation

Post. pituitary stimulation AVP/ADH

Efferent sympathetic NS pathways activation Kidney stimulation

Increase in the permeability of collecting ducts

Renin

Water and Na reabsorption/ retention

RAAS activation

Vasoconstriction of peripheral vasculature

BP maintained

Vital organ perfusion

SHORT TERM AND LONG TERM RESPONSES TO IMPAIRED CARDIAC PERFORMANCE Response Salt and water retention Vasoconstriction Sympathetic stimulation Cytokine activation Hypertrophy collagen Short Term Effects
Augments preload

Long Term Effects

Pulmonary congestion; Anasarca Pump dysfunction, energy expenditure energy expenditure Skeletal muscle catabolism; LV remodelling Cardiomyopathy of overload Impairs relaxation

Maintains perfusion of vital organs HR and ejection Vasodilation

Unloads individual muscle fibers May reduce dilatation

I. 1. 2. 3. 4.

FRAMINGHAM CRITERIA FOR DIAGNOSIS OF HF MAJOR CRITERIA Paroxysmal Nocturnal Dyspnea (PND) Neck vein engorgement Cardiomegaly Acute Pulmonary Edema

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5. 6. 7. II. 1. 2. 3. 4. 5. 6. III.

S3 gallop venous pressure (>16 cmH2O) Positive hepatojugular reflux MINOR CRITERIA Edema of extremities Night cough Dyspnea on exertion Hepatomegaly Pleural effusion Tachycardia MAJOR/MINOR Weight loss > 4.5-5kg over 5 days treatment CHRONIC CONGESTIVE HEART FAILURE EVOLUTION OF CLINICAL STAGES NORMAL Asymptomatic Normal exercise Normal LV function ASYMPTOMATIC LV DYSFUNCTION Asymptomatic Normal exercise Abnormal LV function COMPENSATED CHF Asymptomatic exercise Abnormal LV function DECOMPENSATED CHF Symptomatic exercise Abnormal LV function REFRACTORY CHF Symptoms are common even at rest and not controlled with treatment ACC/AHA HF STAGE vs. NYHA FUNCTIONAL CLASS
ACC/AHA HF STAGE NYHA FUNCTIONAL CLASS I

3.

4.

A.

5.

6.

B.

7.

C.

D.

central circulation during recumbency, with a resultant increase in pulmonary capillary pressure Manifestation: Nocturnal cough Relieved by sitting up Paroxysmal Nocturnal Dyspnea The patient is asleep Sudden episode of SOB and awakens with coughing Generally at night awakening patient from sleep pressure in the bronchial arteriesairway compression Interstitial pulmonary edema airway resistance Cheyne-Stokes Respiration Common in advanced CHF Due to diminished sensitivity of the respiratory center to pCO2 GIT Edema of the bowel wall and/or a congested liver anorexia, early satiety, abdominal pain, jaundice CNS Cerebral arteriosclerosis and reduced cerebral perfusion confusion, disorientation, sleep and mood disturbances GUT Pumping function of the heart flow to kidney Oliguria Carlsberg: Maam, how can CHF cause Nocturia? Dra. Locnen: When the patient is in supinefluid redistributeskidney perfusionNocturia

E.

A At risk for HF but

without structural heart disease or symptoms (eg.

DM, HTN, CAD, hyperlipidemia, etc.)

-Asymptomatic -No limitations of ADLs -Good Prognosis -Symptomatic with moderate exertion -Slight limitations of ADLs -Good Prognosis -Symptomatic with minimal exertion -Marked limitations of
ADLs

B Structural heart

II

disease but without symptoms of HF

III

C Structural heart
HF

disease with prior or current symptoms of

IV

D Refractory HF requiring specialized intervention

-Fair Prognosis Symptomatic at rest -Poor Prognosis

CLINICAL MANIFESTATIONS A. SYMPTOMS 1. Cardinal Symptoms Fatigue Shortness of Breath (SOB) 2. Orthopnea Dyspnea in a recumbent position and relieved when the patient sits up Results from the redistribution of fluid from the splanchnic circulation and lower extremities into the

B. PHYSICAL EXAMINATION 1. General Mild CHF - may not be in distress or discomfort during recumbency Severe CHF - patient sitting upright and in labored breathing 2. Jugular veins: engorge/distended (measure the JVP at the Right Internal Jugular Vein) 3. Lungs Transudation of fluid from the intravascular space to the alveoli Pulmonary Crackles 4. Cardiac Examination: frequently does not provide useful information regarding severity of CHF PMI may be displaced Volume overload with tachycardia and tachypneaS3 heart sound 5. Abdomen and Extremities Hepatomegaly - important sign in patients with HF hepatic congestion and hepatocellular hypoxia impairment of hepatic function both direct and indirect bilirubin Jaundice Peripheral edema - a cardinal manifestation but non-specific -usually symmetric and dependent in HF and occurs predominantly in the ankles and pretibial region in ambulatory patients. -In bedridden patients, edema may be found in the sacral area (presacral edema) and the scrotum Late Sign: Increased hepatic vein pressureAscites 6. Cardiac cachexia: severe HFweight loss and cachexia DIAGNOSIS A. Routine Laboratory Tests CBC, electrolytes, BUN, creatinine, hepatic enzymes and urinalysis

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Selected patients may need blood glucose monitoring, lipid panel and thyroid tests B. Electrocardiogram (ECG) Assess rhythm Determine presence of LV Hypertrophy Determine prior AMI (+/- Q wave) Determine QRS width to ascertain whether the patient may benefit from resynchronization therapy A normal ECG virtually excludes LV systolic dysfunction C. Chest X-Ray Assess cardiac size and shape Assess state of pulmonary vasculature Identify non-cardiac causes of symptoms D. 2-D Echocardiogram/Doppler Most useful tool to assess LV size and function It gives an idea about the underlying problem of the heart. It shows pattern of contractility Provide a semi quantitative assessment of LV size and function as well as the presence or absence of valvular and/or regional wall motion abnormalities E. MRI provides a comprehensive analysis of cardiac anatomy and function Gold standard for assessing LV mass and volumes F. Biomarkers Circulating Natriuretic Peptides 1. B-type Natriuretic Peptide (BNP) - secreted by the ventricles of the heart in response to excessive stretching of myocytes 2. Pro-BNP -Released from the failing heart -Useful adjunctive tools in the diagnosis and of CHF -Level of BNP or Pro-BNP in the blood is related to the severity of HF -The higher the levels of BNP or Pro-BNP the poorer the prognosis TREATMENT A. NEW APPROACH TO THE TREATMENT OF HF STAGES TREATMENT
- HTN=give ACEi and/or ARB - Hyperlipidemia= give Statins -Identify and correct underlying cause -Modify Risk Factors -ACEi, -Blockers -Aggressive Medical Treatment= give ACEi and/or ARB -Slow Progression= give -Blockers -Care Management= Aldosterone -Advanced Therapies -Cardiac Transplant -Device implantation= eg. pacemakers -Palliative Care

A= High risk for

developing HF
(eg. DM, HTN, Hyperlipidemia)

B= Asymptomatic HF C= Symptomatic HF D= Refractory endstage HF

Daily weight measurement Patient and relative education Avoid excessive alcohol limit to 2 standard drinks per day in men or 1 per day in women Avoid temperature extremes and tiring trips Avoid heavy physical exertion Avoid certain drugs which may worsen HF Patients should receive immunization with influenza and pneumococcal vaccines to prevent respiratory infections Meals should be small in quantity in acute-severe HF blood supply to the GIT and in the heart Rest tends to lower arterial pressure but absolute bed rest is rarely required C. CONTROL OF EXCESSIVE FLUID DIURETICS Major mechanism of action of diuretics in HF is to reduce venous pressure and ventricular preload. General Effect: fluid excretion edema cardiac size improved pump efficiency I. Thiazide Diuretics + + Reduces the reabsorption of Na and Cl in the first of the distal convoluted tubule and a portion of the cortical ascending limb Water follows the unabsorbed Na+ excretion May cause electrolyte derangements Effective as long as the GFR exceeds approximately of normal II. Loop Diuretics Eg. Furosemide, Bumetanide and Torsemide Reversibly inhibit the reabsorption of Na+, K+ and Cl+ in the thick ascending limb of Henles loop Useful in all forms of HF May be potentiated by other diuretics (+) Metabolic side effects III. Potassium-Sparing Diuretics Eg. Spironolactone Not as potent as Thiazide and Loop Act on the distal convoluted tubule and the cortical collecting duct Relatively weak & rarely indicated solely Competitively inhibits Aldosterone Combined with Loop and/or Thiazide diureticsmore effective remodelling of the heart Improves survival Adverse Effects of Diuretics Electrolyte and volume depletion Worsening azotemia In addition Worsening neurohormonal activation + Alterations in K homeostasis risk of arrhythmias. Hypokalemia- in loop and thiazide Hyperkalemia- in spironolactone, eplerenone and triamterene D. PREVENTION OF DETERIORATION OF MYOCARDIAL FUNCTION Chronic activation of the RAAS and the Adrenergic System in HFVentricular Remodelling Drugs which block the two systems are beneficial in the management of HF I. Angiotensin-Converting Enzyme (ACE) Inhibitors Eg. Captopril, Enalapril (pril) Inhibits conversion of angiotensin I to angiotensin II Prevent and treat HF at almost all stages Reduce peripheral resistance afterloadSlow maladaptive remodelling

B. GENERAL MEASURES Every effort should be made to prevent HF in those with risk factors + Moderate dietary Na restriction (23 g/day) Fluid restriction (<2 L/day) in: Hyponatremic patients Patients whose fluid retention is difficult to control despite high doses of diuretics and Na+ restriction

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II.

III.

Reduce aldosterone secretion Na+ & water retention Reduce the impedance of LV function (+) Anti-myocyte fibrosis prevents myocardial remodelling Prevent and retard HF in those with LV dysfunction but without frank HF Reduce long term mortality Reduce symptoms and hospitalization Increase exercise performance Side Effects: non-productive cough, angioedema, hyperkalemia, hypotension, mild azotemia When ACE is inhibited break down of bradykinin non-productive cough Angiotensin Receptor Blockers (ARB) Eg. Losartan, Valsartan (sartan) Selective high affinity antagonists of AT1 receptors Antagonize the effects of Angiotensin II regardless of its origin Used in patients who cannot tolerate ACEi due to cough, leukopenia and angioedema As effective as ACEi in reducing mortality Little or of no value in diastolic HF (hypertrophic CMP, myocarditis) -Adrenergic Blockers Eg. Metoprolol, Carvedilol (lol) Gradually escalating doses has been reported to improve symptoms and reduce mortality Large doses may intensify heart failure Inhibition of catecholamines HR, remodelling When given in concert with ACEi or -blockers, it reverses the process of LV remodelling, improve patient symptoms, prevent hospitalization, and prolong life. Metoprolol, Carvedilol and Bisoprolol shown to improve survival Indication: Moderate-severe HF Contraindications: Unstable HF Hypotension Severe fluid overload Recent use of Inotropic Agent Bradycardia AV block Bronchospastic disorder (Asthma, COPD) ENHANCEMENT OF MYOCARDIAL CONTRACTILITY Cardiac Glycosides Eg. Digitalis (Digoxin) + + Inhibit the Na+ pump (Na /K ATPase) + intracellular Na activation of Na+-Ca2+ exchanger intracellular Ca2+ Ca2+ to the cardiac myofilaments cardiac contraction ((+) Inotropy) Effective in systolic HF complicated by atrial fibrillation Doesnt improve survival but decreases hospitalization Sympathomimetic Amines Dopamine and Dobutamine - effective in acutesevere HF (+) Inotropic agents contractility Administered by continuous IV infusion in intractable severe HF Dobutamine acts on 1, 2 and 1.

III.

Dopamine is naturally occuring, a precursor of norepinephrine; used in several doses Intermittent Dobutamine infusion may benefit some patients with Chronic HF. Phosphodiesterase Inhibitors (Bipyridines) Eg. Amrinone, Milrinone Non-cathecholamine and non-glycoside agents Inhibit phosphodiesterase III cAMP contractility ((+) Inotropy) & vasodilation

END OF TRANS As of Nov. 26, 2010:

29 days PTC (Prior to Christmas) 126 days PTC (Prior to Clerkship)

Greetings! Hi to Bimbys Circle of Friends. To Gayle & Niz, salamat sa audio. To our Lantern Queen, bring home the crown. Pia, manlibre ka naman minsan ng frutti froyo. Hi to all the Boys and Men of AGAPE 2012. Hi to my preceptorial groupmates. Good job to all the champions. Hi to Janella-MVP (Most Vulnerable Player); Happy Birthday! Hi to Jessa Ang Pag-asa-MVP (Most Voluptuous Player) Hi to Kimi-MVP (Most Vibrant and Violent Player) Hail for Gayle and to Maki The Key MACASAIB. Swabe! To Sai Sadorra7... Hi Im James. Blessed are the PURE in HEART for they will see GOD -Matthew 5:8

E. I.

GODBLESS2012

II.

TRANSCRIBED BY: JAMES A. RONDAL

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