Heart as a pump, heart failure & its treatment

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Heart as a pump, heart failure & its treatment

  1. 1. HEART FAILURE<br />NORMAL CARDIAC PHYSIOLOGY<br />KAJAREE GIRI Medical College &Hospital Bengal<br /> 88 college street, Kolkata<br />West Bengal<br />India<br />Presented by:<br />
  2. 2. PARAMETERS ON WHICH CARDIAC <br /> PHYSIOLOGY DEPENDS<br /><ul><li>Preload
  3. 3. Afterload
  4. 4. Heart Rate
  5. 5. Ionotropic State</li></li></ul><li>PRELOAD<br />
  6. 6. PRELOAD<br />IN THE WHOLE HEART PRELOAD SHOULD CONSTITUTE THE TENSION IN THE WALL AT THE END OF DIASTOLE ( WHICH DETERMINES THE RESTING FIBER LENGTH).<br />FOR PRACTICAL PURPOSES THE VENTRICULAR EDV/EDP IS USED TO INDICATE PRELOAD.<br />IT AFFECTS HEART PERFORMANCE BY “STARLING’S LAW OF THE HEART”.<br />
  7. 7. AFTERLOAD<br />
  8. 8.
  9. 9. IONOTROPIC STATE<br /> INFLUENCE OF<br /> IONOTROPIC <br /> STATE ON<br /> LENGTH—<br /> TENSION <br /> RELATIONSHIP <br /> OF CARDIAC <br /> MUSCLE.<br />
  10. 10. IONOTROPIC STATE<br />INFLUENCE OF <br />CHANGE IN<br />IONOTROPIC STATE <br />ON FRANK<br />STARLING<br />CURVES.<br />
  11. 11. FACTORS MODIFYING IONOTROPY<br /><ul><li>IN HEART FAILURE, THERE IS A DECREASE IN IONOTROPY— FALL IN STROKE VOLUME AND INCREASE IN PRELOAD – DECREASE IN EJECTION FRACTION.
  12. 12. CARDIOMYOPATHY,</li></ul> ARRHYTHMIA – LOSS OF INTRINSIC IONOTROPY – SYSTOLIC HEART FAILURE.<br /><ul><li>LEFT VENTRICULAR EDP IF GREATER THAN 20 mm Hg – PULMONARY EDEMA.
  13. 13. CHANGES IN IONOTROPIC STATE IMPORTANT DURING EXERCISE.</li></li></ul><li>MUSCLECELL TENSIONIS DETERMINED BY:<br /><ul><li> THE NUMBER OF CROSSBRIDGES FORMATION WHICH IN TURN IS DETERMINED BY THE SARCOMERE LENGTH– MYOFILAMENT OVERLAP (RELATED TO PRELOAD).
  14. 14. THE LOAD AND SHORTENING VELOCITY (RELATED TO AFTERLOAD).
  15. 15. THE RELATIVE ACTIVATION OF THIN FILAMENTS AS DETERMINED BY THE SATURATION OF TROPONIN WITH CALCIUM. (RELATED TO CONTRACTILITY).</li></li></ul><li>The Length-Tension relationship in muscle forms <br />the basis for Frank-Starling’s Law<br />
  16. 16. SERIES ELASTIC ELEMENTS<br />CONTRACTILE COMPONENT<br />(ACTIVE TENSION)<br />PARALLEL ELASTIC ELEMENTS<br />(PASSIVE TENSION)<br />TOTAL TENSION<br />
  17. 17. THE L-T RELATIONSHIP OF FROG SKELETAL MUSCLE(IN BLACK)<br />THE L-T RELATIONSHIP OF CAT CARDIAC MUSCLE FOR THE RANGE <br /> OF PHYSIOLOGICAL SARCOMERE LENGTH(IN RED).<br />
  18. 18. FORCE –VELOCITY RELATIONSHIP<br /><ul><li>THERE’S AN INVERSE RELATION BETWEEN THE SHORTENING VELOCITY OF FIBRES AND AFTERLOAD.
  19. 19. INCREASING PRELOAD INCREASES MAXIMAL ISOMETRIC FORCE AND INCREASES SHORTENING VELOCITY AT A GIVEN AFTERLOAD,DOESNOT ALTER Vmax.
  20. 20. INCREASE IN IONOTROPIC STATE INCREASES BOTH Vmax AND MAXIMAL ISOMETRIC FORCE.</li></li></ul><li>PRESSURE-VOLUME LOOP<br />
  21. 21. PRESSURE-VOLUME LOOP<br />Pes<br />SBP<br />DBP<br />CO = SV x HR<br />EF = SV / EDV<br />
  22. 22. PRESSURE-VOLUME LOOP<br />SYSTOLIC PRESSURE CURVE<br />Isotonic (Ejection) Phase<br />After-load<br />Isovolumetric<br />Phase<br />PRESSURE<br />Stroke<br />Volume<br />DIASTOLIC<br />PRESSURE CURVE<br />Pre-load<br />End Systolic Volume<br />End Diastolic Volume<br />
  23. 23. INDEPENDENT EFFECTS OF PRELOAD<br />
  24. 24. INDEPENDENT EFFECTS OF AFTERLOAD<br />
  25. 25. INDEPENDENT EFFECTS OF IONOTROPISM<br />
  26. 26. MANIPULATING CARDIAC FUNCTION<br />PRELOAD AFTERLOADCONTRACTILITY<br />
  27. 27. INTERDEPENDANT ACTIONS OF PRELOAD AND AFTERLOAD AT CONSTANT IONOTROPY.<br />
  28. 28. TO SUM IT UP<br />
  29. 29. WHAT IS HEART FAILURE?? <br />HEART FAILURE OCCURS WHEN THE <br />HEART IS UNABLE TO PUMP BLOOD AT A <br />RATE SUFFICIENT TO MEET THE <br /> METABOLIC DEMANDS OF THE BODY OF <br />AN INDIVIDUAL.<br />
  30. 30. HOW HEART FAILURE OCCURS??<br /><ul><li>FAILURE OF THE PUMPS.
  31. 31. OBSTRUCTION TO FLOW.
  32. 32. REGURGITANT FLOW.
  33. 33. SHUNTED FLOW THROUGH DEFECTS CONGENITAL OR ACQUIRED.
  34. 34. DISORDER OF CARDIAC CONDUCTION.
  35. 35. RUPTURE OF HEART OR MAJOR VESSELS.</li></li></ul><li>PRINCIPLES OF TREATING HEART FAILURE:<br /><ul><li>POSITIVE IONOTROPIC AGENTS LIKE DIGITALIS.
  36. 36. DIURETICS.
  37. 37. VASODILATORS-- a) NITROPRUSSIDE (BOTH ARTERIAL AND VENODILATORS).</li></ul> b) HYDRALAZINES (ONLY ARTERIAL DILATORS).<br /> c) ACE INHIBITORS.<br /><ul><li>SPECIFIC THERAPIES AIMED AT</li></ul> 1.HEART BLOCK.<br /> 2.SERIOUS VALVULAR LESIONS.<br /> 3. CORONARY ARTERY NARROWING.<br /> 4. SEVERE HYPERTENSION.<br />
  38. 38. THANK YOU..<br />
  39. 39. Cardiac Compensation and Decompensation in Heart Failure<br />Shuvam Roy<br />4th semester student<br />Medical College &Hospital Bengal<br /> 88 college street, Kolkata<br />West Bengal<br />India<br />
  40. 40. Heart failure<br />Definition: failure of heart to pump enough blood to satisfy the needs of body<br />Types: <br /> I) Acute or chronic<br />II) Unilateral (Left/Right) or Bilateral<br />
  41. 41. Cardiac compensation<br />Compensatory mechanisms maintain adequate CO & tissue perfusion<br />Mechanisms:<br />sympathetic stimulation<br />fluid retention of kidney<br />varying degrees of recovery of the heart itself <br />
  42. 42. Sympathetic stimulation <br />Occurs within 30s of acute heart failure<br />CVS reflexes stimulate sympathetic NS and inhibit parasympathetic NS <br />Effects:<br />Increased strength of heart<br />Increased mean systemic filling pressure<br />Maintains pressure for perfusion of vital organs<br />
  43. 43. CVS reflexes<br />Baroreceptor reflex<br />Chemoreceptor reflex<br />CNS ischaemic response<br />Reflexes originating in the heart<br />
  44. 44. Baroreceptor reflex<br />
  45. 45. Chemoreceptor reflex<br />Aortic & carotid bodies stimulated by hypoxia,  local concentration of H + & CO2 impulses travel via vagus and Hering’s nervesstimulation of VMC<br />
  46. 46. CNS ischaemic response<br />VMC is directly stimulated by <br />increase in local concentration of H+ & CO2 <br />hypoxia<br />
  47. 47. Bainbridge reflex<br />Increase in atrial pressure stimulates atrial stretch receptors which causes reflex increase in heart rate and myocardial contractility<br />Afferent pathway: vagus nerve<br />Efferent pathway: sympathetic and vagus nerves<br />
  48. 48.
  49. 49.    <br />   <br />   <br />
  50. 50. Fluid retention by the kidneys<br />Occurs over hours to days<br />Beneficial when pumping ability of heart is not very severely damaged<br />Occurs due to <br />activation of renin- angiotensin-aldosterone system<br />Decrease in renal blood flow causes decrease in GFR<br />Increased aldosterone secretion<br />Increased ADH secretion<br />Effects:<br />Increase in mean systemic filling pressure <br />Decreased venous resistance<br />
  51. 51. Recovery of the heart<br />Occurs over weeks to months<br />Includes<br />Development of collateral blood supply<br />Fringe areas outside the infarct zone become functional<br />Hypertrophy of functional areas occur<br />Increased collagen that may reduce dilatation<br />
  52. 52. Hypertrophy of myocardium<br />In hemodynamic overload it reduces elevated ventricular wall stress to normal<br />In pressure overload,<br /> increased systolic pressureincreased systolic stressparallel addition of new myofibrilswall thickening and consequent concentric hypertrophydecreased systolic stress<br />In volume overload,<br />increased diastolic pressureincreased diastolic stressserial addition of new sarcomeres chamber enlargement and eccentric hypertrophy decreased diastolic pressure<br />
  53. 53.
  54. 54. If heart recovers sufficiently and if adequate <br /> fluid volume has been retained, sympathetic stimulation gradually abates towards normal<br />However, cardiac reserve is reduced.<br />
  55. 55. Decompensated heart failure<br />Occurs when compensatory mechanisms can no longer maintain an adequate tissue perfusion<br />The same factors that are responsible for cardiac compensation can exacerbate cardiac decompensation<br />
  56. 56. Factors behind cardiac decompensation<br />Salt & water retention: pulmonary congestion, anasarca<br />Vasoconstriction: increases cardiac energy expenditure<br />Sympathetic stimulation: increases cardiac energy expenditure<br />Hypertrophy:deterioration and death of cardiac myocytes<br />Increased collagen: impairs relaxation<br />Cardiac remodelling<br />
  57. 57. Progressive oedema<br />Compensatory mechanisms fail to raise CO high enough to make kidneys excrete enough water<br />Detrimental effects of fluid retention- Diagnosed by progressive pulmonary congestion and anasarca, bubbling rales in lung and dyspnoea.<br />Treatment<br />Cardiotonic drugs like digitalis<br />Diuretics<br />Restrict salt and fluid intake<br />ANP and BNP delay decompensation by increasing salt and water excretion by kidneys<br />
  58. 58.
  59. 59.
  60. 60. Right or left heart failure does not lead to immediate peripheral oedema as ,initially ,<br /> there is a fall in capillary pressure.<br />But peripheral oedema begins after one day or so due to fluid retention by the kidneys<br />
  61. 61. Acute pulmonary oedema in heart failure<br />Left heart failure causes pulmonary congestion and oedema<br />Pulmonary oedemadecreased oxygenation of bloodfurther weakening of heart and peripheral vasodilatationincreased venous return due to peripheral vasodilatationmore pulmonary oedema<br />
  62. 62. Cardiogenic shock<br />Low output heart failure<br />shockfall in arterial pressuredecrease in coronary blood flowdamage to heart<br />Vicious cycle<br />Treatment<br />Surgical clot removal with coronary bypass graft<br />Fibrinolytics<br />Cardiotonic drugs<br />Increase blood pressure<br />
  63. 63.
  64. 64.
  65. 65. HEART FAILURE<br />PATHOPHYSIOLOGY AND CLINICAL MANIFESTATIONS<br />Medical College &Hospital Bengal<br /> 88 college street, Kolkata<br />West Bengal<br />India<br />Presented by:<br />AVIK BASU<br />
  66. 66. ETIOLOGIES OF HEART FAILURE<br />
  67. 67. •Depressed Ejection Fraction (<40%)<br />Coronary Artery Disease<br />Chronic Pressure Overload<br />3. Chronic Volume Overload<br />4. Non-ischemic Dilated Cardiomyopathy<br />5. Disorders of Rate and Rhythm<br />
  68. 68. •Preserved Ejection Fraction (40-50%)<br />Pathological Hypertrophy<br />Aging<br />3. Restrictive Cardiomyopathy<br />4. Fibrosis<br />5. Endomyocardial Disorders<br />
  69. 69. •Pulmonary heart disease<br />1. Cor Pulmonale<br />2. Pulmonary Vascular Disorders<br />
  70. 70. •High-output states<br />1. Metabolic Disorders<br />2. Excessive Blood-flow Requirements<br />
  71. 71. FORMS OF HEART FAILURE<br />
  72. 72. •PATHOLOGICAL CLASSIFICATION<br />1. Systolic Heart Failure<br />2. Diastolic Heart Failure<br />
  73. 73. •CLINICAL CLASSIFICATION<br />1. RIGHT-SIDED Heart Failure<br />2. LEFT-SIDED Heart Failure<br />
  74. 74. •OTHER CLASSIFICATIONS<br />1. LOW OUTPUT Heart Failure<br />2. HIGH OUTPUT Heart Failure<br />
  75. 75. PATHOGENESIS OF SYSTOLIC HEART FAILURE<br />
  76. 76.
  77. 77. Activation of Neuro-hormonal Systems in Heart Failure<br />
  78. 78. MOLECULARBASISOF SYSTOLIC FAILURE<br />
  79. 79. The molecular basis of systolic failure involves three components:<br />• Contractile proteins<br />• Calcium homeostasis<br />• Signal transduction pathways<br />
  80. 80. CHANGES IN CONTRACTILE PROTEINS<br />Slowing of cross-bridge cycling rate<br />Increased expression of fetal isoform of Troponin-T<br />Reduced phosphorylation of Troponin-I<br />
  81. 81. FAILING HEART<br />NORMAL HEART<br />
  82. 82. CHANGES IN CALCIUM HOMEOSTASIS<br />Prolonged Calcium transient<br />• Increased threshold for Calcium release from sarcoplasmic reticulum<br />• Increased diastolic Calcium concentration<br />• Decreased Calcium reuptake by sarcoplasmic reticulum <br />• Prolonged action potential<br />
  83. 83. NORMAL HEART<br />FAILINGHEART<br />
  84. 84. CHANGES IN SIGNAL TRANSDUCTION PATHWAYS<br />Decreased number of β-adrenoreceptors<br />Increased expression of β-adrenoreceptor kinase<br />Increased expression of inhibitory G-protein<br />
  85. 85. NORMAL HEART<br />FAILING HEART<br />
  86. 86. CHARACTERISTIC OF HEART IN SYSTOLIC FAILURE<br />Eccentric left ventricular hypertrophy<br />Progressive left ventricular dilatation<br />Abnormal left ventricular systolic properties<br />
  87. 87. PATHOGENESIS OF DIASTOLIC HEART FAILURE<br />
  88. 88. FACTORS REGULATING VENTRICULAR RELAXATION<br />Systolic Load<br /> Myofibre inactivation<br /> Uniformity of the distribution of load and inactivation over space and time<br />Left ventricular relaxation is under the ‘Triple Control’ of:<br />
  89. 89. POTENTIAL MECHANISM FOR DIASTOLIC DYSFUNCTION<br />Extramyocardial<br />Whole heart<br />Extracellular matrix<br />Cardiomyocyte<br />Myofilaments<br />
  90. 90. CHANGE IN TITIN ISOFORM<br />
  91. 91. • Titin protein has two isoforms:<br /> (1) N2BA<br /> (2) N2B<br />• N2B isoform is stiffer than N2BA isoform.<br />• Predominance of N2B isoform in the heart leads to <br /> increased stiffness of the ventricles leading to <br /> diastolic dysfunctioning.<br />
  92. 92. CHARACTERISTIC OF HEART IN DIASTOLIC FAILURE<br />Concentric left ventricular hypertrophy<br />Normal or reduced left ventricular volume<br />Concentric remodelling<br />Abnormal left ventricular diastolic properties<br />
  93. 93. PATHOGENESIS OF LEFT-SIDED HEART FAILURE<br />
  94. 94. CAUSES OF LEFT-SIDED HEART FAILURE<br />Ischemic heart disease<br />Hypertension<br />Aortic and Mitral valvular disease<br />Non-ischemic myocardial disease<br />
  95. 95. MORPHOLOGICAL CHANGES IN THE HEART<br />Hypertrophied and Dilated heart<br />Myocardial fibrosis<br />Secondary left atrial fibrillation<br />
  96. 96. CLINICAL MANIFESTATIONS<br />Paroxysmal Nocturnal Dyspnoea<br />Orthopnoea<br />Pulmonary edema<br />Cheyne-Stokes respiration<br />Pre-renal azotemia<br />Hypoxic Encephalopathy<br />
  97. 97. PATHOGENESIS OF RIGHT-SIDED HEART FAILURE<br />
  98. 98. CAUSES OF RIGHT-SIDED HEART FAILURE<br />Secondary to Left-sided heart failure<br />Severe Pulmonary Hypertension<br />
  99. 99. MORPHOLOGICAL CHANGES IN THE HEART<br />Hypertrophied and Dilated right ventricle<br />Dilated right atrium<br />Bulging of ventricular septum to the left<br />
  100. 100. CLINICAL MANIFESTATIONS<br />Raised Jugular Venous Pressure<br />Congestive hepatomegaly<br />Hepato-jugular reflex<br />Congestive splenomegaly<br />Pedal & Pre-tibial edema<br />
  101. 101. LOW-OUTPUT HEART FAILURE<br />
  102. 102. STAGES OF CARDIOGENIC SHOCK<br />Non-progressive/Compensatory phase<br />Progressive phase<br />Irreversible phase<br />
  103. 103.
  104. 104. HIGH-OUTPUT HEART FAILURE<br />
  105. 105. CONDITIONS LEADING TO HIGH-OUTPUT HEART FAILURE<br />Arterio-venous fistula<br />• Beriberi<br />
  106. 106. ARTERIO-VENOUS FISTULA<br />
  107. 107. OXYGEN LACK THEORY<br />
  108. 108. BERIBERI<br />
  109. 109. Treatment of Heart Failure<br />CHIRANTAN MANDAL <br />4thsemester student<br />Medical College &Hospital Bengal<br /> 88 college street, Kolkata<br />West Bengal<br />India<br />
  110. 110. Therapeutic Overview <br />Problems <br />↓force of contraction<br />↑total peripheral resistance<br />organ hypoperfusion<br />Ventricular remodelling<br />Worsening renal function<br />↑ venous pressure with ↓cardiac output<br />edema<br />↓exercise tolerance<br />
  111. 111.
  112. 112. Therapeutic Challenges<br /><ul><li>Decongest organs
  113. 113. Diurese
  114. 114. Reverse hemodynamic abnormalities
  115. 115. Decreased renal perfusion</li></ul>Rapid relieve of symptoms<br />Prevent Sudden Cardiac Arrest & ventricular remodeling<br />
  116. 116. Diet and Activity<br />Salt restricted diet<br />Fluid restriction<br />weight loss<br />Control Hypertension<br />Reduce cardiac work<br />Rest<br />
  117. 117. Diuretic Therapy<br />fluid volumes overload ↓<br />ECF volume ↓<br />venous return ↓<br />The most effective symptomatic relief<br />Four Flavours:<br />Loop diuretics<br />Thiazide diuretics<br />K+-sparing<br />Carbonic anhydrase inhibitors<br />
  118. 118.
  119. 119. Thiazide<br />ADH Inhibitors<br />
  120. 120. Carbonic Anhydrase<br /> Inhibitors<br />Loop Diuretic<br />
  121. 121. Aldosterone Inhibitors<br />(K+ Sparing Agents )<br />
  122. 122. For More severe heart failure -> loop diuretics<br />Furosemide, Bumetanide , Torsemide<br />Mechanism ofaction: Inhibit chloride reabsortion in ascending limb of loop of Henle results in natriuresis, kaliuresis and metabolic alkalosis<br />Adverse reaction:<br /> pre-renal azotemia<br />Hypokalemia<br /> Skin rash<br />ototoxicity<br />
  123. 123. K+ Sparing Agents Potassium sparing diuretics help in reducing the hypokalemia due to otherdiuretics.<br />Triamterene & amiloride – acts on distal tubules to ↓ K secretion<br />Spironolactone (Aldosterone antagonist)<br /> it improve survival in CHF patients due to the effect on renin-angiotensin-aldosterone system with subsequent effect on myocardial remodeling and fibrosis<br />Aldosterone inhibition minimize potassium loss, prevent sodium and water retention, endothelial dysfunction and myocardial fibrosis.<br />
  124. 124.
  125. 125. Reninangiotensin system<br />Baroreceptor mediated activation of the SNS leads to an increase in renin release and formation of angiotensin II <br />AngiotensinII acts through AT1 and AT2 receptors (most of its actions occur through AT1 receptors) <br />This causes vasoconstriction and stimulates aldosteroneproduction<br />aldosterone may also cause myocardial and vascular fibrosis and baroreceptor dysfunction <br />
  126. 126.
  127. 127. Inhibitors of renin-angiotensin- aldosterone system<br />Angiotensinconverting enzyme inhibitors<br />Angiotensin receptors blockers<br />Spironolactone(Aldosterone antagonist)<br />
  128. 128. Angiotensin Converting Enzyme (ACE) Inhibitors <br />ACE inhibitors improve mortality, morbidity, exercise tolerance, left ventricular ejection fraction.<br />Captopril, Lisinopril, Enalapril, Ramipril, Quinapril.<br />Advantages<br />Improves symptoms significantly<br />Improves exercise tolerance<br />Slows disease progression<br />↓ cardiac remodeling<br />Prolong survival<br />
  129. 129. Scope for ACE Inhibitors…..<br />
  130. 130.
  131. 131. Angiotensin Converting Enzyme Inhibitors MOA<br />They block the R-A-A system by inhibiting the conversion of angiotensin I to angiotensin II -> vasodilation and ↓ Na retention<br />↓ Bradykinin degradation ↑ its level -> ↑ PG secretion & nitric oxide<br />
  132. 132. Angiotensin Receptor AT-1 blockers (ARB) <br />Losartan, Irbesartan, Candesartan<br />Competitive antagonists of Angiotensin II <br />(AT-1).<br />Has comparable effect to ACE I<br />Can be used in certain conditions when ACE I are contraindicated (angioneurotic edema, cough)<br />
  133. 133. ACE-Inhibitors and ARB effects<br />Vasodilation<br />Decreased fluid retention (afterload & preload)<br />Reduction in aldosterone secretion<br />Inhibition of cardiac and vascular remodeling <br />
  134. 134. Animation<br />
  135. 135. Inotropes<br />Increase force of contraction<br />All increase intracellular cardiac Ca++ concentration<br />Eg: <br />Digitalis (cardiac glycoside)<br />Dobutamine (β-adrenergic recepter agonist)<br />Amrinone (PDE inhibitor)<br />
  136. 136.
  137. 137. Digoxin MOA<br />
  138. 138. Cardiac glycosides : Digoxin (Digitalis)<br /> inhibit Na +,K +ATPase,  the membrane-bound transporter<br />increase of intracellular sodium concentration<br />a relative reduction of<br /> calcium expulsion from<br /> the cell by the <br />sodium-calcium <br />Exchanger due <br /> to ↑ Na <br />distinctive increase in<br /> Cardiac contractility<br />during systole<br />increased cytoplasmic calcium is sequestered by SERCA in the SR for later release<br />
  139. 139. early, brief prolongation of the action potential, followed by shortening (especially the plateau phase)<br />The decrease in action potential duration is probably the result of increased potassium conductance that is caused by increased intracellular calcium<br />Effects of Digoxin on Electrical Properties of Cardiac Tissues<br />
  140. 140. inhibition of the Na+ pump and reduced intracellular K+<br />resting membrane potential is reduced <br />oscillatory delayed depolarizing afterpotentials appear following normally evoked action potentials<br />At higher concentrations……..<br />overloading of the intracellular calcium stores and oscillations in the free intracellular calcium ion concentration<br />
  141. 141.
  142. 142. β 1 Agonist<br />Eg: Dobutamine<br />Effects:-<br />↑ cardiac output <br />↓ intraventricular filling pressure<br />direct stimulation of the SA node to↑heart rate<br />↓peripheral resistance by activating alpha2 receptors vasodilation<br />Conduction velocity in the AVnode is ↑<br />refractory period is ↓<br />Intrinsic contractility is ↑<br />ejection time is ↓<br />
  143. 143. β 1 Agonist MoA<br />
  144. 144. Bipyridinesphosphodiesterase 3 inhibitor<br />Targets PDE -3 (found in cardiac and smooth muscle)<br />Inamrinone, milrinone<br />increasing inward calcium flux in the heart during the action potential<br />alter the intracellular <br />movements of calcium by influencing the sarcoplasmic reticulum<br />increase myocardial contractility<br />
  145. 145. Inhibition of PDE3<br />Increase in cAMP<br />the conversion of inactive protein kinase to active form<br />Protein kinases are responsible for phosphorylation of Ca channels <br />increased Ca entry into the cell<br />increase in contractility<br />vasodilation<br />↑ Vascular Permeability leads to <br />↓ in intravascular fluid Volume<br />
  146. 146. β Blockers <br />bisoprolol, carvedilol , metoprolol<br /> MOA<br />Acts primarily by inhibiting the sympathetic nervous system (attenuation of the adverse effects of high concentrations of catecholamines)<br />reduced remodeling (inhibition of the mitogenic activity of catecholamines.)<br /> Increases beta receptor sensitivity<br />
  147. 147.
  148. 148. β blockers<br />
  149. 149. Anti-arrhythmic & Anti-oxidant properties.<br />shows substantial improvement in LV function & improved survival<br />The only contraindication is severe decompensated CHF<br />
  150. 150. Vasodilators<br />Reduction of afterloadby arteriolar vasodilatation (hydralazin) reduce LVEDP, O2 consumption,improve myocardial perfusion,  stroke volume and COP<br />Reduction of preload Byvenous dilation <br /> ( Nitrate)↓ the venous return ↓ the load on both ventricles.<br />Usually the maximum benefit is achieved by using agents with both action.<br />
  151. 151.
  152. 152. Vasodilators<br />Isosorbidedinitrate and hydralazine also used specially in patients who cannot tolerate ACE inhibitors.<br />Amlodipine and prazosin are other vasodilators can be used in CCF.<br />
  153. 153.
  154. 154. Calcium Channel Blockers for VasodialationNisoldipine, Isradipine<br />bind more effectively to open channels and inactivated channels<br />(inner side of the membrane)<br />reduces the frequency of opening in response to depolarization<br />marked decrease in transmembrane calcium current<br />activation of myosin light chain kinase<br />Vascular smooth muscle (the most sensitive<br />long-lasting relaxation <br />
  155. 155.
  156. 156. Nitrates & Nitrites<br />Nitroglycerin is denitrated by glutathione S -transferase in smooth muscle<br />Free nitrite ion is released, which is then converted to nitric oxide <br />activation of guanylylcyclase<br />increase in cGMP<br />dephosphorylation of myosin light chains, preventing the interaction of myosin with actin<br />
  157. 157.
  158. 158. Venous dilators<br />Reduce preload<br />Direct smooth muscle<br /> relaxants<br />Eg: sodium nitropruside<br />
  159. 159. (BNP)-Niseritide<br />Brain (B-type) natriuretic peptide (BNP) is secreted constitutively by ventricular myocytes in response to stretch <br />Niseritide = recombinant human BNP<br />Naturally occurring atrialnatriuretic peptide may vascular permeability may reduce intravascular volume)<br />Main Side Effect:- hypotension<br />
  160. 160. Human BNP binds to the particulate guanylatecyclase receptor of vascular smooth muscle and endothelial <br />intracellular concentrations (cGMP) ↑<br />smooth muscle cell relaxation <br />dilate veins and arteries<br />systemic and pulmonary vascular resistances ↑<br />Indirect ↑ in cardiac output and diuresis. <br />Effective in HF because preload and afterload↓<br />
  161. 161. Conclusion<br /><ul><li>ACE inhibitors are cornerstone in the treatment
  162. 162. β blockers are used in selected patients (mild/moderate failure)
  163. 163. Diuretics and digoxin are other drugs useful in CCF in select patients. </li></li></ul><li>148<br />
  164. 164. Heart Failure Treatment Algorithm<br />
  165. 165. ThankU !<br />

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