HEART FAILURENORMAL CARDIAC PHYSIOLOGY

Presented by:

KAJAREE GIRI Medical College &Hospital Bengal

88 college street, KolkataWest Bengal

India

PARAMETERS ON WHICH CARDIAC

PHYSIOLOGY DEPENDS

Preload

Afterload

Heart Rate

Ionotropic State

PRELOAD

PRELOAD

• IN THE WHOLE HEART PRELOAD SHOULD CONSTITUTE THE TENSION IN THE WALL AT THE END OF DIASTOLE ( WHICH DETERMINES THE RESTING FIBER LENGTH).

• FOR PRACTICAL PURPOSES THE VENTRICULAR EDV/EDP IS USED TO INDICATE PRELOAD.

• IT AFFECTS HEART PERFORMANCE BY “STARLING’S LAW OF THE HEART”.

AFTERLOAD

IONOTROPIC STATE

INFLUENCE OF IONOTROPIC STATE ON LENGTH— TENSION RELATIONSHIP OF CARDIAC MUSCLE.

IONOTROPIC STATE

INFLUENCE OF CHANGE INIONOTROPIC STATE ON FRANKSTARLINGCURVES.

FACTORS MODIFYING IONOTROPY IN HEART FAILURE, THERE IS A

DECREASE IN IONOTROPY— FALL IN STROKE VOLUME AND INCREASE IN PRELOAD – DECREASE IN EJECTION FRACTION.

CARDIOMYOPATHY, ARRHYTHMIA – LOSS OF INTRINSIC

IONOTROPY – SYSTOLIC HEART FAILURE.

LEFT VENTRICULAR EDP IF GREATER THAN 20 mm Hg – PULMONARY EDEMA.

CHANGES IN IONOTROPIC STATE IMPORTANT DURING EXERCISE.

MUSCLE CELL TENSION IS DETERMINED BY:

THE NUMBER OF CROSSBRIDGES FORMATION WHICH IN TURN IS DETERMINED BY THE SARCOMERE LENGTH– MYOFILAMENT OVERLAP (RELATED TO PRELOAD).

THE LOAD AND SHORTENING VELOCITY (RELATED TO AFTERLOAD).

THE RELATIVE ACTIVATION OF THIN FILAMENTS AS DETERMINED BY THE SATURATION OF TROPONIN WITH CALCIUM. (RELATED TO CONTRACTILITY).

The Length-Tension relationship in muscle forms the basis for Frank-Starling’s Law

SERIES ELASTIC ELEMENTS

CONTRACTILE COMPONENT

(ACTIVE TENSION)

PARALLEL ELASTIC ELEMENTS

(PASSIVE TENSION)

TOTAL TENSION

THE L-T RELATIONSHIP OF FROG SKELETAL MUSCLE(IN BLACK)THE L-T RELATIONSHIP OF CAT CARDIAC MUSCLE FOR THE RANGE OF PHYSIOLOGICAL SARCOMERE LENGTH(IN RED).

FORCE –VELOCITY RELATIONSHIP

•THERE’S AN INVERSE RELATION BETWEEN THE SHORTENING VELOCITY OF FIBRES AND AFTERLOAD.

•INCREASING PRELOAD INCREASES MAXIMAL ISOMETRIC FORCE AND INCREASES SHORTENING VELOCITY AT A GIVEN AFTERLOAD,DOESNOT ALTER Vmax.

•INCREASE IN IONOTROPIC STATE INCREASES BOTH Vmax AND MAXIMAL ISOMETRIC FORCE.

PRESSURE-VOLUME LOOP

CO = SV x HR

EF = SV / EDV

SBP

DBP

Pes PRESSURE-VOLUME LOOP

PR

ESS

UR

E

DIASTOLICPRESSURE CURVE

SYSTOLIC PRESSURE CURVE

PRESSURE-VOLUME LOOP

End Diastolic VolumeEnd Systolic Volume

IsovolumetricPhase

Isotonic (Ejection) Phase

StrokeVolume

Pre-load

After-load

INDEPENDENT EFFECTS OF PRELOAD

INDEPENDENT EFFECTS OF AFTERLOAD

INDEPENDENT EFFECTS OF IONOTROPISM

PRELOAD AFTERLOAD CONTRACTILITY

MANIPULATING CARDIAC FUNCTION

INTERDEPENDANT ACTIONS OF PRELOAD AND AFTERLOAD AT CONSTANT IONOTROPY.

TO SUM IT UP

WHAT IS HEART FAILURE??

HEART FAILURE OCCURS WHEN THE HEART IS UNABLE TO PUMP BLOOD AT A RATE SUFFICIENT TO MEET THE METABOLIC DEMANDS OF THE BODY OF AN INDIVIDUAL.

HOW HEART FAILURE OCCURS??

FAILURE OF THE PUMPS.

OBSTRUCTION TO FLOW.

REGURGITANT FLOW.

SHUNTED FLOW THROUGH DEFECTS CONGENITAL OR ACQUIRED.

DISORDER OF CARDIAC CONDUCTION.

RUPTURE OF HEART OR MAJOR VESSELS.

PRINCIPLES OF TREATING HEART FAILURE:

POSITIVE IONOTROPIC AGENTS LIKE DIGITALIS.

DIURETICS.

VASODILATORS-- a) NITROPRUSSIDE (BOTH ARTERIAL AND VENODILATORS).

b) HYDRALAZINES (ONLY ARTERIAL DILATORS).

c) ACE INHIBITORS.

SPECIFIC THERAPIES AIMED AT

1.HEART BLOCK.

2.SERIOUS VALVULAR LESIONS.

3. CORONARY ARTERY NARROWING.

4. SEVERE HYPERTENSION.

THANK YOU..

Cardiac Compensation and Decompensation in Heart Failure

Shuvam Roy4th semester student

Medical College &Hospital Bengal 88 college street, Kolkata

West BengalIndia

Heart failure

• Definition: failure of heart to pump enough blood to satisfy the needs of body

• Types: I) Acute or chronic II) Unilateral (Left/Right) or Bilateral

Cardiac compensation

• Compensatory mechanisms maintain adequate CO & tissue perfusion

• Mechanisms:– sympathetic stimulation– fluid retention of kidney– varying degrees of recovery of the heart itself

Sympathetic stimulation

• Occurs within 30s of acute heart failure• CVS reflexes stimulate sympathetic NS and

inhibit parasympathetic NS • Effects:– Increased strength of heart– Increased mean systemic filling pressure– Maintains pressure for perfusion of vital organs

CVS reflexes

• Baroreceptor reflex• Chemoreceptor reflex• CNS ischaemic response• Reflexes originating in the heart

Baroreceptor reflex

Chemoreceptor reflex

• Aortic & carotid bodies stimulated by hypoxia, local concentration of H + & CO2 impulses travel via vagus and Hering’s nervesstimulation of VMC

CNS ischaemic response

• VMC is directly stimulated by – increase in local concentration of H+ & CO2

– hypoxia

Bainbridge reflex

• Increase in atrial pressure stimulates atrial stretch receptors which causes reflex increase in heart rate and myocardial contractility

• Afferent pathway: vagus nerve• Efferent pathway: sympathetic and vagus

nerves

Fluid retention by the kidneys• Occurs over hours to days• Beneficial when pumping ability of heart is not

very severely damaged• Occurs due to – activation of renin- angiotensin-aldosterone system– Decrease in renal blood flow causes decrease in GFR– Increased aldosterone secretion– Increased ADH secretion

• Effects:– Increase in mean systemic filling pressure – Decreased venous resistance

Recovery of the heart

• Occurs over weeks to months• Includes– Development of collateral blood supply– Fringe areas outside the infarct zone become

functional– Hypertrophy of functional areas occur– Increased collagen that may reduce dilatation

Hypertrophy of myocardium• In hemodynamic overload it reduces elevated ventricular

wall stress to normal• In pressure overload, increased systolic pressureincreased systolic

stressparallel addition of new myofibrilswall thickening and consequent concentric hypertrophydecreased systolic stress

• In volume overload, increased diastolic pressureincreased diastolic stressserial

addition of new sarcomeres chamber enlargement and eccentric hypertrophy decreased diastolic pressure

• If heart recovers sufficiently and if adequate fluid volume has been retained, sympathetic

stimulation gradually abates towards normal

• However, cardiac reserve is reduced.

Decompensated heart failure

• Occurs when compensatory mechanisms can no longer maintain an adequate tissue perfusion

• The same factors that are responsible for cardiac compensation can exacerbate cardiac decompensation

Factors behind cardiac decompensation

• Salt & water retention: pulmonary congestion, anasarca

• Vasoconstriction: increases cardiac energy expenditure

• Sympathetic stimulation: increases cardiac energy expenditure

• Hypertrophy:deterioration and death of cardiac myocytes

• Increased collagen: impairs relaxation• Cardiac remodelling

Progressive oedema• Compensatory mechanisms fail to raise CO high

enough to make kidneys excrete enough water• Detrimental effects of fluid retention- Diagnosed

by progressive pulmonary congestion and anasarca, bubbling rales in lung and dyspnoea.

• Treatment– Cardiotonic drugs like digitalis– Diuretics– Restrict salt and fluid intake

• ANP and BNP delay decompensation by increasing salt and water excretion by kidneys

• Right or left heart failure does not lead to immediate peripheral oedema as ,initially ,

there is a fall in capillary pressure.

• But peripheral oedema begins after one day or so due to fluid retention by the kidneys

Acute pulmonary oedema in heart failure

• Left heart failure causes pulmonary congestion and oedema

• Pulmonary oedemadecreased oxygenation of bloodfurther weakening of heart and peripheral vasodilatationincreased venous return due to peripheral vasodilatationmore pulmonary oedema

• Cardiogenic shock– Low output heart failure– shockfall in arterial pressuredecrease in coronary

blood flowdamage to heart– Vicious cycle– Treatment1. Surgical clot removal with coronary bypass graft2. Fibrinolytics3. Cardiotonic drugs4. Increase blood pressure

HEART FAILURE

PATHOPHYSIOLOGY AND CLINICAL

MANIFESTATIONS

Presented by: AVIK BASU

Medical College &Hospital Bengal 88 college street, Kolkata

West BengalIndia

ETIOLOGIES

OF HEART FAILURE

•Depressed Ejection Fraction (<40%)

1. Coronary Artery Disease

2. Chronic Pressure Overload

3. Chronic Volume Overload

4. Non-ischemic Dilated Cardiomyopathy

5. Disorders of Rate and Rhythm

•Preserved Ejection Fraction (40-50%)

1. Pathological Hypertrophy

2. Aging

3. Restrictive Cardiomyopathy

4. Fibrosis

5. Endomyocardial Disorders

•Pulmonary heart disease

1. Cor Pulmonale

2. Pulmonary Vascular Disorders

•High-output states

1. Metabolic Disorders

2. Excessive Blood-flow Requirements

FORMS OF

HEART FAILURE

•PATHOLOGICAL CLASSIFICATION

1. Systolic Heart Failure

2. Diastolic Heart Failure

•CLINICAL CLASSIFICATION

1. RIGHT-SIDED Heart Failure

2. LEFT-SIDED Heart Failure

•OTHER CLASSIFICATIONS

1. LOW OUTPUT Heart Failure

2. HIGH OUTPUT Heart Failure

PATHOGENESIS OF

SYSTOLIC HEART FAILURE

Activation of Neuro-hormonal Systems in Heart Failure

MOLECULARBASISOF

SYSTOLIC FAILURE

The molecular basis of systolic failure involves three components:

• Contractile proteins

• Calcium homeostasis

• Signal transduction pathways

CHANGES IN CONTRACTILE PROTEINS

• Slowing of cross-bridge cycling rate

• Increased expression of fetal isoform of Troponin-T

• Reduced phosphorylation of Troponin-I

NORMAL HEART FAILING HEART

CHANGES IN CALCIUM HOMEOSTASIS

• Prolonged Calcium transient

• Increased threshold for Calcium release from sarcoplasmic reticulum

• Increased diastolic Calcium concentration

• Decreased Calcium reuptake by sarcoplasmic reticulum

• Prolonged action potential

NORMAL HEART

FAILINGHEART

CHANGES IN SIGNAL TRANSDUCTION PATHWAYS

• Decreased number of β-adrenoreceptors

• Increased expression of β-adrenoreceptor kinase

• Increased expression of inhibitory G-protein

NORMAL HEART FAILING HEART

CHARACTERISTIC OF HEART IN SYSTOLIC FAILURE

• Eccentric left ventricular hypertrophy

• Progressive left ventricular dilatation

• Abnormal left ventricular systolic properties

PATHOGENESIS

OF DIASTOLIC

HEART FAILURE

FACTORS REGULATING VENTRICULAR RELAXATION

(1)Systolic Load

(2) Myofibre inactivation

(3) Uniformity of the distribution of load and inactivation over space and time

Left ventricular relaxation is under the ‘Triple Control’ of:

POTENTIAL MECHANISM FOR DIASTOLIC DYSFUNCTION

• Extramyocardial

• Whole heart

• Extracellular matrix

• Cardiomyocyte

• Myofilaments

CHANGE IN TITIN ISOFORM

• Titin protein has two isoforms: (1) N2BA (2) N2B

• N2B isoform is stiffer than N2BA isoform.

• Predominance of N2B isoform in the heart leads to increased stiffness of the ventricles leading to diastolic dysfunctioning.

CHARACTERISTIC OF HEART IN DIASTOLIC FAILURE

• Concentric left ventricular hypertrophy

• Normal or reduced left ventricular volume

• Concentric remodelling

• Abnormal left ventricular diastolic properties

PATHOGENESIS

OF LEFT-SIDED

HEART FAILURE

CAUSES OF LEFT-SIDED HEART FAILURE• Ischemic heart disease

• Hypertension

• Aortic and Mitral valvular disease

• Non-ischemic myocardial disease

MORPHOLOGICAL CHANGES IN THE

HEART• Hypertrophied and Dilated heart

• Myocardial fibrosis

• Secondary left atrial fibrillation

CLINICAL MANIFESTATIONS

• Paroxysmal Nocturnal Dyspnoea• Orthopnoea• Pulmonary edema• Cheyne-Stokes respiration• Pre-renal azotemia• Hypoxic Encephalopathy

PATHOGENESIS

OF RIGHT-SIDED

HEART FAILURE

CAUSES OF RIGHT-SIDED HEART FAILURE

• Secondary to Left-sided heart failure

• Severe Pulmonary Hypertension

MORPHOLOGICAL CHANGES IN THE

HEART• Hypertrophied and Dilated right ventricle

• Dilated right atrium

• Bulging of ventricular septum to the left

CLINICAL MANIFESTATIONS

• Raised Jugular Venous Pressure• Congestive hepatomegaly• Hepato-jugular reflex• Congestive splenomegaly• Pedal & Pre-tibial edema

LOW-OUTPUT HEART FAILURE

STAGES OF CARDIOGENIC SHOCK

• Non-progressive/Compensatory phase

• Progressive phase

• Irreversible phase

HIGH-OUTPUT HEART FAILURE

CONDITIONS LEADING TO HIGH-OUTPUT HEART FAILURE

• Arterio-venous fistula

• Beriberi

ARTERIO-VENOUS FISTULA

OXYGEN LACK THEORY

BERIBERI

Treatment of Heart Failure

CHIRANTAN MANDAL 4th semester student

Medical College &Hospital Bengal

88 college street, KolkataWest Bengal

India

Therapeutic Overview Problems • ↓force of contraction• ↑total peripheral resistance• organ hypoperfusion• Ventricular remodelling• Worsening renal function• ↑ venous pressure with ↓cardiac output• edema• ↓exercise tolerance

Therapeutic Challenges

• Rapid relieve of symptoms• Prevent Sudden Cardiac

Arrest & ventricular remodeling

• Decongest organs • Diurese• Reverse hemodynamic

abnormalities• Decreased renal perfusion

Diet and Activity

• Salt restricted diet• Fluid restriction• weight loss• Control Hypertension• Reduce cardiac work• Rest

Diuretic Therapy• fluid volumes overload ↓• ECF volume ↓• venous return ↓• The most effective symptomatic relief• Four Flavours:– Loop diuretics– Thiazide diuretics– K+-sparing– Carbonic anhydrase inhibitors

ADH Inhibitors Thiazide

Loop DiureticCarbonic Anhydrase Inhibitors

Aldosterone Inhibitors (K+ Sparing Agents )

• For More severe heart failure → loop diuretics– Furosemide, Bumetanide , TorsemideMechanism of action: Inhibit chloride reabsortion in ascending limb of

loop of Henle results in natriuresis, kaliuresis and metabolic alkalosisAdverse reaction:

pre-renal azotemiaHypokalemiaSkin rashototoxicity

K+ Sparing Agents Potassium sparing diuretics help in reducing the hypokalemia due to

otherdiuretics.

• Triamterene & amiloride – acts on distal tubules to ↓ K secretion

• Spironolactone (Aldosterone antagonist) it improve survival in CHF patients due to the effect on renin-

angiotensin-aldosterone system with subsequent effect on myocardial remodeling and fibrosis

• Aldosterone inhibition minimize potassium loss, prevent sodium and water retention, endothelial dysfunction and myocardial fibrosis.

Renin angiotensin system• Baroreceptor mediated activation of the SNS leads to an

increase in renin release and formation of angiotensin II

• Angiotensin II acts through AT1 and AT2 receptors (most of its actions occur through AT1 receptors)

• This causes vasoconstriction and stimulates aldosterone production

• aldosterone may also cause myocardial and vascular fibrosis and baroreceptor dysfunction

Inhibitors of renin-angiotensin- aldosterone system

– Angiotensin converting enzyme inhibitors– Angiotensin receptors blockers– Spironolactone (Aldosterone antagonist)

Angiotensin Converting Enzyme (ACE) Inhibitors

• ACE inhibitors improve mortality, morbidity, exercise tolerance, left ventricular ejection fraction.

• Captopril, Lisinopril, Enalapril, Ramipril, Quinapril.

Advantages• Improves symptoms significantly• Improves exercise tolerance• Slows disease progression• ↓ cardiac remodeling• Prolong survival

Scope for ACE Inhibitors…..

Angiotensin Converting Enzyme Inhibitors MOA

• They block the R-A-A system by inhibiting the conversion of angiotensin I to angiotensin II → vasodilation and ↓ Na retention

• ↓ Bradykinin degradation ↑ its level → ↑ PG secretion & nitric oxide

Angiotensin Receptor AT-1 blockers (ARB)

Losartan, Irbesartan, Candesartan

• Competitive antagonists of Angiotensin II (AT-1).

• Has comparable effect to ACE I

• Can be used in certain conditions when ACE I are contraindicated (angioneurotic edema, cough)

ACE-Inhibitors and ARB effects

• Vasodilation

• Decreased fluid retention (afterload & preload)

• Reduction in aldosterone secretion

• Inhibition of cardiac and vascular remodeling

Animation

Inotropes

• Increase force of contraction• All increase intracellular cardiac Ca++

concentration• Eg: – Digitalis (cardiac glycoside)– Dobutamine (β-adrenergic recepter agonist)– Amrinone (PDE inhibitor)

Digoxin MOA

increased cytoplasmic calcium is

sequestered by SERCA in the SR for later release

Cardiac glycosides : Digoxin (DIGITALIS) inhibit Na +,K + ATPase,  the membrane-bound transporter

increase of intracellular sodium concentration

a relative reduction of

calcium expulsion from

the cell by the

sodium-calcium

Exchanger due to ↑ Na

distinctive increase in Cardiac contractility during systole

Effects

of Digo

xin on

Electrica

l Properti

es

of Cardiac T

issues

early, brief prolongation of the action potential, followed by shortening

(especially the plateau phase)

The decrease in action potential duration is probably the result of increased

potassium conductance that is caused by increased intracellular calcium

At higher

conce

ntrations…

…..

inhibition of the Na+ pump and reduced intracellular K+

resting membrane potential is reduced

oscillatory delayed depolarizing afterpotentials appear following normally evoked action potentials

overloading of the intracellular calcium stores and oscillations in the free intracellular calcium ion concentration

β 1 Agonist

Eg: Dobutamine

Effects:-• ↑ cardiac output • ↓ intraventricular filling pressure• direct stimulation of the SA node to↑heart

rate• ↓peripheral resistance by activating alpha2

receptors vasodilation• Conduction velocity in the AVnode is ↑• refractory period is ↓• Intrinsic contractility is ↑• ejection time is ↓

β 1 Agonist MoA

BIPYRIDINES phosphodiesterase 3 inhibitor

• Targets PDE -3 (found in cardiac and smooth muscle)• Inamrinone , milrinone

alter the intracellular movements of calcium

by influencing the sarcoplasmic reticulum

increasing inward

calcium flux in the heart during the

action potential

increase myocardial contractility

Inhibition of PDE3 Increase in cAMP

increase in contractility

vasodilation

↑ Vascular Permeability leads to ↓ in intravascular fluid Volume

the conversion of inactive protein kinase to active form

Protein kinases are responsible for phosphorylation of Ca channels

increased Ca entry into the cell

β Blockers

MOA

• Acts primarily by inhibiting the sympathetic nervous system (attenuation of the adverse effects of high concentrations of catecholamines)

• reduced remodeling (inhibition of the mitogenic activity of catecholamines.)

• Increases beta receptor sensitivity

bisoprolol, carvedilol , metoprolol

β blockers

• Anti-arrhythmic & Anti-oxidant properties.

• shows substantial improvement in LV function & improved survival

• The only contraindication is severe decompensated CHF

Vasodilators

• Reduction of afterload by arteriolar vasodilatation (hydralazin) reduce LVEDP, O2 consumption,improve myocardial perfusion, stroke volume and COP

• Reduction of preload By venous dilation ( Nitrate) ↓ the venous return ↓ the load on both

ventricles.

• Usually the maximum benefit is achieved by using agents with both action.

Vasodilators• Isosorbide dinitrate and hydralazine

also used specially in patients who cannot tolerate ACE inhibitors.

• Amlodipine and prazosin are other vasodilators can be used in CCF.

Calcium Channel Blockers for VasodialationNisoldipine, Isradipine

bind more effectively to open channels and inactivated channels(inner side of the membrane)

reduces the frequency of opening in response to depolarization

marked decrease in transmembrane calcium current

activation of myosin light chain kinase

Vascular smooth muscle (the most sensitive

long-lasting relaxation

NITRATES & NITRITESNitroglycerin is denitrated by glutathione S -transferase in smooth

muscle

Free nitrite ion is released, which is then converted to nitric oxide

activation of guanylyl cyclase

increase in cGMP

dephosphorylation of myosin light chains, preventing the interaction of myosin with actin

Venous dilatorsReduce preloadDirect smooth muscle relaxantsEg: sodium nitropruside

(BNP)-Niseritide• Brain (B-type) natriuretic peptide (BNP) is secreted

constitutively by ventricular myocytes in response to stretch

• Niseritide = recombinant human BNP

• Naturally occurring atrial natriuretic peptide may vascular permeability may reduce intravascular volume)

• Main Side Effect:- hypotension

Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial

intracellular concentrations (cGMP) ↑

smooth muscle cell relaxation

dilate veins and arteries

systemic and pulmonary vascular resistances ↑

Indirect ↑ in cardiac output and diuresis.

Effective in HF because preload and afterload↓

• ACE inhibitors are cornerstone in the treatment

• β blockers are used in selected patients (mild/moderate failure)

• Diuretics and digoxin are other drugs useful in CCF in select patients.

Conclusion

STAGE DISABILITY

Stage A MILD

No symptoms Can perform ordinary activities without any limitations

Stage B MILD

Mild symptoms - occasional swelling Somewhat limited in ability to exercise or do other strenuous activities

Stage C MODERATE

Noticeable limitations in ability to exercise or participate in mildly strenuous activitiesComfortable only at rest

Stage D SEVERE

Unable to do any physical activity without discomfort Some HF symptoms at rest

148

Heart Failure Treatment Algorithm

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