Heart Failure heart unable to pump sufficient blood to meet metabolic needs of body tissues the heart will

ll try to compensate and will fall back on its reserves Compensatory Mechanisms: 1. Frank-Starling Principle INCREASED PRELOAD a. Tension of muscle enhanced via: i. Increasing muscle length b. Diastolic muscle length determined by: i. End-diastolic volume and its relation to: 1. end diastolic filling pressure 2. pre-load 2. Increase of Muscle Mass via Remodeling of Myocardium (alter structure/function) a. Hypertrophy i. Increase myofiber size and muscle mass ii. Help heart to overcome pressure overload iii. Fibers laid in parallel to increase wall thickness 1. NOT increase size of cavity of chamber a. Increase vent mass relative to volume iv. Concentric hypertrophy 1. leads to stretching of vessels and less blood to cells heart fail a. normally, every myofiber has 2-4 caps that are 2m away v. an adaptive process 1. in accordance to balanced equilibrium btw myocardium and its muscular, vascular, and CT components 2. non-myocyte cell proliferation can produce remodeling of extra myofiber space a. reduces ventricular compliance vi. a self-limiting process 1. often followed by failure dilatation a. factors that contribute to transition to failure: i. increased myocyte capillary distance ii. alterations in contractile proteins iii. cellular energy production/utilization iv. excitation/contraction coupling v. decreased ratio of myofibrils to mitochondria vi. decreased coronary reserve vii. impaired left ventricular relaxation 1. inability to use Frank-Starling principle to increase EDV and SV during exercise b. Increased Weight of Heart i. Indicates hypertrophy ii. Measured via M mode echocardiography 1. evaluates left vent mass as index of body surface area a. normal men: 131 gm/m2 b. normal female: 100 gm/m2 c. Changes in Myosin Heavy Chains i. Greater expression of Myosin Heavy Chain (V3) in hypertrophied myofibers 1. repression of Myosin Heavy Chains (V1) ii. seen best in human atria 1. isoform switch from V1 to V3 to response to increased workload a. gene reversion to fetal characteristics AND repress adult iii. other alterations: 1. reversion of skeletal actin in hypertrophied vent myocytes 2. alteration of myosin light chain 1 3. alteration of tropomyosin and troponin 4. isoform change in Na/K ATPase (cardiac glycoside receptor) d. Production of ANP i. Production concentrated postnatally in atria but also in hypertrophied vent myofibers
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3.

ii. Molecular changes in hypertrophy: 1. altered myosin/myosin ATPase activity a. isoform switch from fast to slow myosin ATPase i. slower rate of hydrolysis 2. relative decrease in density of SR Ca+2 ATPase pumps relative to mass a. diminish capacity to sequester calcium rapidly e. Increased expression of proto-oncogenes i. C-myc, C-fos, C-jun ii. TF Egr-1 iii. C-myc is part of heat shock or stress proteins iv. Postulated that proto-oncogenes lead to reversion of fetal isoforms of myofibrillar proteins f. Induction of Peptide Growth Factors in Myocardium under stress i. Some growth factors include: 1. FGF basis 2. TGF-beta 1 3. insulin-like growth factor 4. epidermal growth factor 5. myotrophin 6. Cardiotrophin-1 a. Cytokine show to produce myofiber hypertrophy in vitro 7. protein kinase C a. induce phosphorylation of transcription factors, gene expression and promotion of cell growth 8. TNF-alpha and IL-6 9. Ang II and endothelin-1 a. Potent growth factors for cardiac myocytes b. Activate mitogen activated protein (MAP) cascade g. Increased synthesis of contractile proteins i. Due to tension on myofibers induce protein and mRNA synthesis ii. Myofiber has load sensing cytoskeletal elements as adenylate cyclase 1. activated by membrane tension AND 2. activation of protein kinase C (accompanying pressure overload) iii. pressure-dependent mechanotransducer/mechanosensitive ion channels iv. Na+ influx increased with stretched cells v. Hypertrophied muscle fibers operate at a lower inotropic state than normal myofiber h. Volume Overload increases Diastolic Wall Stress i. Compensatory dilation of chamber accompanied by concominant hypertrophy ii. Leads to increase in CO by Frank-Starling iii. Myofibrils are laid down in series in order to increase myofiber length i. Systolic Dysfunction i. Increase in chamber volume ii. Ventricular dilation is initial compensatory response to restore SV 1. same SV but with lesser degree of fiber shortening 2. increase in O2 consumption and diastolic/systolic wall stress a. leads to afterload mismatch 3. chamber volume increase compensatory initially, but leads to overt HF when preload reserve exceeded j. Dilatation in absence of volume overload i. Indicator of ventricular failure ii. LaPlace equation: tension = blood pressure * radius iii. Increase vent size increase wall tension increase energy requirement with rise in O2 consumption and decline in efficiency k. Apoptosis i. due to re-expression of fetal genes ii. loss of viable myocytes Increase in HR a. due to initial withdrawal of vagal influence followed by SNS action b. compensate for decrease SV by maintaining multiple of the two factors at constant level
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in order for failing heart to maintain wall stress and SV, it must remodel all its constituents; myocytes, microvasculature, mesenchymal cells and interstitial tissue FOUR CLASSES/GRADES of CHF
Class I (7 METS or greater) Original Criteria Pt w/ cardiac disease but w/o limitation of physical activity. Ordinary activity NOT CAUSE undue fatigue, palpitation, dyspnea or anginal pain Pt/ w cardiac disease resulting in slight limitation of physical activity/ comfortable at rest. Ordinary activity RESULTS in fatigue, palp, dysp, angina Pt w/ cardiac disease resulting in marked limitation of physical activity. Comfortable at rest. Less than ordinary activity CAUSES fat.,pap, dysp., angina Pt w/ cardiac disease result in inability to carry out any physical activity without discomfort. Symptoms/anginal may be present even at rest Revised Criteria Cardiac status uncompromised Activity Scale Carry 24 lbs up eight steps Carry 80 lb object Shovel snow Skiing Play basketball, touch football, squash, handball Jog/walk five miles per hour Carry anything up 8 steps Have sexual intercourse Garden, rake, weed Walk four miles/hr Walk down 8 steps Take shower Change bed sheets Mopping floors, clean windows Walk 2.5 miles/hr Bowling Dress without stopping None of the above

II (5 METS)

Cardiac status slightly compromised Cardiac status moderately compromised

III (2 METS)

IV (< 2 METS)

Cardiac status severely compromised

MET = metabolic equivalent of O2 consumption -quantity of O2 consumed by body from inspired air under basal conditions Respiratory gas analysis most reproducible criteria for exercise tolerance VO2 o Product of CO by arterio-venous difference for O2 o VO2 max Maximal capacity of body to transport O2 to tissue and use it in exercise Closely related to maximal cardiac output Dependent upon age, gender, activity status, disease states Characterizes pts peak physical fitness levels Measure of maximal reserve of the CV system o Translated into METS by dividing by 3.5 DECOMPENSATION occurs when compensation mechanisms NOT maintain normal CO HF due to exhausation of reserve force of heart muscle Heart size Ejection Fraction Compliance Diastolic Pressure Diastolic Volume Thickness S3 S4 Systolic HF II DD N/D I/II II N/D ++ +/Diastolic HF N/I N/I/D DD II N/D/I I I/ I I +/++

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BASIC CAUSES OF HEART FAILURE (chart 117) 1. Increased requirement by the body tissues for O2 a. Thyrotoxicosis b. Anemia c. Beri-beri d. Left-to-right shunts e. Arteriovenosus fistulas f. Pagets disease of bone g. Pregnancy h. All have peripheral vasodilation with drop in peripheral resistance and high CO lead to high output failure 2. Increased resistance with increase in ventricular work (pressure load) a. Left ventricle or aorta i. Coarctation ii. Aortic stenosis iii. Subaortic stenosis iv. Systemic HTN v. Outflow tract obstruction hypertrophic obstructive cardiomyopathy b. Right ventricle i. Pulmonary stenosis ii. Pulmonary HTN iii. Atresia pulmonary artery 3. Disturbance of Volume a. Volume Overload i. Incompetence of valves especially mitral and aortic ii. Hydremia (transfusions, IV therapy) iii. Septal defects b. Diminution of volume with inadequate filling i. Mitral and tricuspid stenosis ii. Compression of heart by cardiac tampondae or constrictive pericarditis iii. Outflow tract obstruction 4. Impaired of Myocardial Contractility a. Myocardial ischemia b. Myocarditis c. Cardiomyopathy d. Pericarditis e. Arrhythmias PATHOPHYSIOLOGY OF CHF: LEFT-SIDED FAILURE diminished output by left vent (forward failure) due to: o coarctation (narrowing of aorta) o aortic/subaortic stenosis, outflow tract obstruction o HTN (increased peripheral resistance) o Mitral stenosis/insufficiency or atrial myxoma (impairment of left atrial function) o Diseases of the coronary arteries o Disturbance of impulse conduction system Can lead to passive hyperemia of lung o With left side failing, damming back of blood into pulmonary veins w/ increased intravascular pressure Transmitted to pulmonary venules alveolar caps ENGORGED o Results in transudation of fluid into interstitial compartment and alveolar sac o Passive movement of RBCs into alveoli via diapedesis o RBC phagocytosed by septal macrophages Breakdown Hb to hemosiderin Macrophages known as siderophages (heart failure cells) Can be easily distinguished using Prussian blue stain, and if turn blue, means that cells is iron-containing o Phlebosclerosis Pressure within veins leading to fibrosis of venous wall
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Stagnant anoxemia causes vasoconstriction of pulmonary arterioles with increased resistance to action of right ventricle Lead to HYPERTROPHY OF RIGHT VENT which try to compensate and pump blood through lung and left side of heart Chronic Passive congestion of the lungs Venous, venular and alveolar cap engorgement Edema of interstitial tissue and alveolar sacs RBCs and siderophages in alveoli Gives the cut surface a brown color Lungs are indurated Brown induration of the lungs Transudate present with the interlobular septa Seen in CXR as Kerley B lines Upon inspiration: Transudate in alveolar sacs churn up frothy fluid o Expectoration of frothy material sign of pulmonary edema On auscultation, best heard as rales/crackles Expectoration of RBCs bloody sputum (hemoptysis) Expectoration of siderophages rusty brown sputum Can lead to secondary bacterial infections, especially pneumonia Dyspnea Manifested first on effort ONE OF THE CARDINAL SIGNS OF HF With time, will occur at rest especially when patient lying down Due to diminution of vital capacity caused by elevation of diaphragm on lying People must sit up in order to breathe orthopnea May be woken up from sleep with respiratory distress Paroxysmal nocturnal dyspnea OR cardiac asthma Diminution of Left Ventricular Output Insufficient CO for normal activity fatigue May lead to obtundation due to less than normal perfusion to the brain Diminution to the kidneys decrease in GFR oliguria/albuminuria Increased aldosterone production by adrenal cortex Increased catecholamine production by adrenal medulla the higher the levels of catecholamines, the worse the prognosis plasma NE levels predictor of adverse outcomes increase in arginine vasopressin ANP inhibits arginine vasopressin release Prostaglandins Inhibit renal vasodilation Decrease sodium reabsorption Inhibit ADH action in distal convoluted tubules Response of Peripheral Circulation Arteriolar vasoconstriction To maintain BP Redistribution of blood with a diminution in blood supply to kidneys, skin, splanchnic organ, skeletal muscles to maintain blood flow to heart and brain Increased venous tone Shift blood from peripheral to central circulation Increase venous return and maintain CO by Frank-Starling mechanism Mg+2 homeostasis Major importance in CHF ANP and BNP
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Elevated in HF higher numbers means poorer Px An imbalance of neuroendocrine responses in HF as forces subserving vasoconstriction and Na retention dominate vasodilator/NP forces In normal: SNS inhibited by baroreceptors In HF: ability lost There is a chronic stimulation of SNS o Vasoconstriction o Arrhythmia o Myocardial hypertrophy o Direct toxicity to myofiber

PATHOPHYSIOLOGY OF CHF: RIGHT-SIDED FAILURE if occur alone, due to: o pulmonary stenosis o disease of the lung o idiopathic/primary pulmonary HTN o NO pulmonary venous congestion Most common cause: left-sided heart failure o Less blood pass R vent more blood in R atrium than can handle Increase in R atrial pressure deflected into systemic veins Systemic venous congestion hallmark of R-sided HF Stasis of venous blood o Leads to cyanosis o Generalized edema due to action of aldosterone retaining Na/water Most marked in the feet Edema present throughout all of body (including serous sacs, systemic viscera) o cyanotic induration increased consistency of systemic viscera and cyanosis seen best with the spleen marked rubbery consistency and plum color of cut surface o liver and RHF venous blood dammed back in hepatic veins and central veins of lobules sinusoids of central zone of lobules engorged appears cyanotic sinusoids of peripheral zone become fatty degenerated appears pale and yellow the two appearances give the liver its nutmeg appearance if left standing, the chronic passive congestion of liver atrophy and loss of centrilobular cells with condensation of supporting cells leads to central cirrhosis (cardiac cirrhosis or sclerosis) can lead to petechial hemorrhages in GI tract and brain o coughing up coffee ground color gastric bleeding o puncta cruenta in the brain o development of pulmonary embolism due to inability of heard to maintain circulation stasis of intracavitary blood and formation of thrombi, especially in right atrial appendage Systolic or Inotropic Failure o HF due to diminished contractility of the myofibers o Inadequate contractile force during systole o Inadequate emptying of chambers Decrease in SV Increase in end-systolic volume Diastolic or Lusitropic Failure

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HF caused by increased myocardial stiffness diminished distensibility or diminished ventricular compliance is associated with abnormalities of relaxation and inadequate filling in diastole Leads to rise in diastolic pressure o HF with preserved systolic function/left vent ejection faction o Increased end-diastolic pressure out of proportion to end-diastolic volume Best seen in hypertrophic cardiomyopathy and restrictive cardiomyopathy o Chief risk factors: Age, HTN, DM, left vent hypertrophy, tachyarrhythmias, mitral/aortic stenosis, women Therapy attained only by taking into account whether ventricular failure is due to systolic or diastolic failure o Beta and alpha-1 partial agonists shown to improve both systolic and diastolic dysfunction in mild-moderate CHF o

Energy depletion in HF imbalance between energy production and energy utilization both contraction and relaxation DEPENDENT on energy in systole: o actin and myosin hydrolyze terminal phosphate of ATP and transduces chemical energy of ATP into mechanical energy in diastole: o Ca+2 pumped out of cytosol in SR and extracellular space against concentration gradient Contractile elements become deactivated with return of myofilaments to pre-contractile length Role of Cytokines in HF TNF is a profound negative inotropic compound that causes: o Aberrant myocyte hypertrophy and chamber dilatation Significance of HF 4 million US pts Txed for HF 400,000 new cases/year leading Dx for in-patient care in pts over age of 65 Px: have a 50% mortality rate over 5 years o Major causes of death: Progressive HF associated with diminished myocardial perfusion and sudden cardiac death because of lethal arrhythmia Tx of HF approach should be to conserve cardiac energy o reduce energy expenditure by: slowing HR lower BP lower wall stress Dynamic Cardiomyopathy for Chronic HF (Class III) surgical procedure where pedicled left latissimus dorsi muscle flap transposed onto chest and wrapped around ventricles o muscle flap electrically stimulated to contract in synchrony with ventricular systole o transform muscle fibers from Type II (fatigue prone) to Type I (fatigue resistant) improvement in ventricular systolic function with reduction of HF Sx Transmyocardial Revascularization lasers used to produce transmyocardial channels o puncture through epicardium o percutaneou procedure through endocardium reduction in anginal Sx o may be due to denervation for the ametioration of angina
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Reduction of ventricular size by means of partial ventriculectomy (Batista Technique) applies LaPlace equation size of dilated failed ventricle reduced by surgical excision of a segment of ventricular myocardium Therapeutic Angiogenesis indicated for patients with ischemic heart disease who are not candidates for revascularization by means of bypass graft nor precutaneous transluminal coronary angioplasty 16 known angiogenic proteins o most promising: vascular endothelial growth factor and fibroblast growth factor o other investigated: angiopoietin 1, PDGF, NO introduced into heart via intracoronary injection, intramyocardial injection, transndocardially or into epicardium Definitions of Types of HF acute HF o medical emergency allied to acute left vent failure with pulmonary edema o occurs within minutes or hours central circulatory failure (pump failure) o low CO, low BP, oliguria High Output HF (hyperkinetic or hyperdynamic state) o Heart fails despite resting CO beyond normal range in human adults (2.3-4.0 L/m2/min) o CO raised by: Increase in SV Increase in HR o Reduction in afterload: Peripheral shunthing of blood-systemic arteriovenous fistula, Pagets disease of bone Central shunting of blood-patent ductus arteriosus Peripheral dilatation thyrotoxicosis Reduced blood viscosity anemia o Other causes: Pregnancy Associated with increased BV, CO, SV, HR And decreased vascular resistance Placental circulation acts as an afterload sink Cor pulmonale Septicemia Beri-beri Basic hemodynamic differences between high output and low output failure o In high output: Due to peripheral vasodilation, diastolic pressure is NORMAL or low Extremities are warm and flushed Pulse pressure is normal or widened In presence of arterio-venous shunt, aterial-mixed venous O2 difference normal or decreased o In low output: Neurohumoral response leads to systemic vasoconstriction Extremities are cold and pale With advancing failure and progressive disease of SV, pulse pressure narrows

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