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Heart failure
The document discusses key aspects of heart failure, emphasizing its inability to pump blood effectively, leading to a progressive decline in cardiac performance. It details the pathophysiological mechanisms, diagnostic criteria, etiology, and treatment options, including pharmacologic interventions and various drug classes, aimed at managing both acute and chronic heart failure. The document also highlights the classification systems and the stages of heart failure, as well as references for further reading.
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Heart failure
- 1. KEY ASPECTS OF HEARTFAILURE DR. BUSHRA HASAN KHAN DEPARTMENT OF PHARMACOLOGY JNMC, AMU, ALIGARH
- 2. Heart failure isa state in which the heart is unable to pump blood at a rate commensurate with the requirements of body’s tissues or can do so only at elevated pressure Progressive disease gradual reduction in cardiac performance, punctuated by episodes of acute decompensation
- 3. Heart failure Clinical conditionDysfunction of heart Systolic dysfunction Diastolic dysfunction Cardiac output reduced Blood pressure reduces (BP = CO x TPR) Activation of compensatory mechanisms to improve blood pressure
- 4. Pathophysiology Purpose of compensatorymechanisms to improve BP 1. Activation of SNS 2. Activation of RAAS 3. Non osmotic release of AVP
- 5. 1. Activation ofSNS CHF BP Baroreceptor activation (Carotid sinus and aortic sinus) Baroreceptors send signals to VMC present in medulla oblongata Medulla oblongata increases the sympathetic outflow Vasoconstriction BP
- 6. 2. Activation ofRAAS CHF BP Renal perfusion reduces GFR reduces Activation of RAAS Formation of Angiotensin II vasoconstriction BP Aldosterone released Na+ and water retention
- 7. 3. Non osmoticrelease of AVP
- 8. Pathophysiologic mechanisms ofsystolic heart failure (HFrEF) and therapeutic interventions
- 11. Pathophysiological mechanisms ofdiastolic heart failure HFpEF and possible therapeutic interventions
- 12. HF ( FOCand CO) Sympathetic stimulation Renal perfusion Central baroreceptors Beta 1 rec FOC, HR + Alpha 1 rec preload afterload Initially compensation occurs to CO Later CO RAAS + Ag II AT1rec VC Cardiac remodelling Na+ and water reabsorption Aldosterone Ventricular size Vicious cycle Compensatory responses that occur during congestive heart
- 13. Vicious spiral ofprogression of heart failure
- 14. HF ( FOCand CO) Sympathetic stimulation Renal perfusion Central baroreceptors Beta 1 rec FOC, HR + Alpha 1 rec preload afterload Initially compensation occurs to CO Later CO RAAS activation Ag II AT1rec VC Cardiac remodelling Na+ and water reabsorption Aldosterone Ventricular size Vicious cycle RAAS inhibitorsBeta blockers Alpha blockers ACEI ARB + Diuretics
- 15. Hemodynamic responses topharmacologic interventions in heart failure
- 16. Stroke volume versusafterload (outflow resistance): effects of heart failure
- 17. Relation of leftventricular (LV) performance to filling pressure in patients with heart failure
- 19. RV outflow Blood stagnantin RV RA unable to pump blood into RV RA pressure also SVC pressure IVC pressure Hepatic venous pressure increases Tender hepatomegaly Pedal edema Portal HTN (Portal venous pressure) Ascites Splenomegaly (Splenic venous pressure)
- 20. Intestinal wall edema(SMV pressure) Absorption of food Continuous vomiting Weight gain due to fluid overload Nocturia
- 21. • Earliest signof RHF is JVP • PCWP remains normal • PCWP represents LA pressure • PCWP in LHF • On auscultation : RV S3
- 23. LVEDP LA pressure PV pressure PCpressure Fluid enters lungs Pulmonary edema Cough with expectoration (pink, frothy) On auscultation : LV S3 PCWP Bilateral lung crepitations
- 24. Earliest clinical manifestationof LHF : PND Paroxysmal Nocturnal Dyspnea Orthopnea Dyspnea
- 25. FRAMINGHAM CRITERIA INCHF MAJOR MINOR • Crackles • CVP • Cardiomegaly (CXR) • Dyspnea (PND) • Edematous lungs (Pulmonary edema) • Fall in weight of patient in response to treatment (>4.5 kg) • Gallop rhythm • Hepatojugular reflux (RHF) • Hepatomegaly • Night cough (due to pulmonary edema) • Edema (pedal) • Pleural effusion (due to progression of pulmonary edema) • Quantitative pulmonary function test (vital capacity reduced to 1/3 of max) • Rapid pulse • Shortness of breath on exertion
- 26. Diagnostic criteria 2 majorcriteria OR 1 major + 2 minor
- 27. CCF RHF LHF+ • MCCof RHF = LHF • MCC of Acute RHF = Acute pulmonary embolism Acute cor pulmonale RV dilatation with or without RHF secondary to pulmonary or pulmonary vascular pathology • MCC of Chronic cor pulmonale = COPD
- 28. Etiology of LHF Basedon Ejection Fraction (N=55-70%) HFpEF (>50%) HFrEF (<40%) Diastolic heart failure Systolic heart failure
- 29. Etiologies of HFrEF(Systolic HF) Chronic pressure overload DCMPCADs Chronic volume overload Chaga’s Disease (Parasitic infection) MI • HTN • AS • MR • AR
- 30. Etiologies of HFpEF(Diastolic HF) RCMP Fibrosis of heart HCM • Cor pulmonale • Pulm vascular disease Endomyocardial disorders
- 31. Chest X-ray (signsof pulmonary venous HTN) Vascular redistribution Interstitial edema Alveolar edema Upper lobe vein distension Kerley B lines Air space opacities Pleural effusion (if severity increases)
- 32. Cardiac biomarkers whichare increased in HF ANP Pro-BNP (Released from ventricle) Adremedullin Endothelin Released from Atria Released from Endothelium Released from myocardium BNP NT-Pro BNP Most sensitive Prognostic marker of CHF NT Pro-BNP normal value is <300pg/ml
- 33. Other important investigations BUN S.Creatinine ECG 2D-Echo As a part of Pre Renal failure • Ejection fraction • Valve lesions • Chamber enlargement • Ischemia/ Infarction • Arrhythmia
- 34. Treatment of CHFdepends on presentation
- 35. Acute decompensated (CongestiveHF) If cardiogenic shock present Loop diuretics (Furosemide) For flushing out fluids Diuretics Oxygen (Ventilatory support) Morphine Vasodilators Reduce anxiety Reduce sympathetic outflow
- 36. Acute decompensated (CongestiveHF) If cardiogenic shock present Diuretics Oxygen (Ventilatory support) Morphine Vasodilators Reduce anxiety Reduce sympathetic outflow Activation of SNS increases precipitation of HF because it increases cardiac work Afterload with Morphine
- 37. Acute decompensated (CongestiveHF) If cardiogenic shock present Loop diuretics (Furosemide) For flushing out fluids Diuretics Oxygen (Ventilatory support) Morphine Vasodilators Nitrates Nesiritide Preload Afterload Give inotropic agents Dobutamine/ Dopamine/ Epinephrine/ NE Do not give Digoxin in Acute decompensated heart failure
- 38. Congestive HF thatis not decompensated Drugs for relieving congestion Drugs for reversing cardiac remodelling Drugs which will improve progression OR • ACEI • ARB • Beta blockers • Aldosterone antagonists VasodilatorsDiuretics Inotropes Vasoconstrictors Furosemide Thiazides Edema Nitrates Nesiritide Nitroprusside Preload Afterload Digoxin Dopamine Minrinone Levosimendan Improve forward flow Improve congestion
- 39. Thiazide Diuretics Chlorothiazide HCZ 25mg 100 mg Chlorthalidone 50 mg 100 mg Indapamide Metolazone Symptomatic treatment of milder forms of heart failure Looses efficacy at GFR <30-40 ml/min (except indapamide and metolazone) Potentiate effect of loop diuretics in severe heart failure (sequential tubal blockade)
- 40. Loop Diuretics Bumetanide 0.5mg 5 mg Furosemide 20 mg 240 mg Torasemide 5 mg 20 mg Symptomatic treatment of severe heart failure and acute decompensation A/E: hypokalemia, hyponatremia, hypomagnesemia, hyperuricemia, hypocalcemia, glucose intolerance
- 41. Vasodilators ISDN/ Hydralazine A/E: headache,nausea, flushing, hypotension, palpitations, tachycardia, dizziness, lupus syndrome
- 42. Intravenous Vasodilators Nitroglycerine Sodium nitroprusside Maycardiac output in acute congestion via preload and afterload NO released, stimulates soluble guanylyl cyclase Avoid if systolic BP <110 mmhg
- 43. Nesiritide Recombinant human BNP Stimulatesmembrane bound GC May cardiac output via preload and afterload T1/2 18-23 mins IV infusion Vasodilator and Diuretic effect
- 44. Intravenous positive inotropes Dobutamine Dopamine Epinephrine Norepinephrine Beta1mediated stimulation of cardiac output Last option in patients with SBP <85 mmHg Cardiac energy consumption and risk of arrhythmia Use lowest possible doses for shortest possible time Dobutamine causes less tachycardia than EPI and less afterload increase than NE
- 45. Enoximone Milrinone PDE3/4 inhibitors, cellularcAMP Cardiac output and dilated blood vessels (“inodilator”)
- 46. Levosimendan Combined Calcium sensitizer(troponin C binding) and PDE3 inhibitor CO and vascular resistance (“inodilator”)
- 47. Cardiac glycosides • Digoxinused : (contraindicated in renal failure) • Digitoxin hepatotoxic not used • Not first choice in treating heart failure • May exert benefits in heart failure and atrial fibrillation • Half life 1.5 d (digoxin) or 7 days (digitoxin)
- 48. Cardiac excitation-contraction coupling and itsregulation by positive inotropic
- 49. Most common Sideeffects of digoxin Extracardiac: Anorexia, Nausea, Vomiting (Digoxin chemosensors are present in Area Postrema) Cardiac: Ventricular Bigeminy Most specific Side effects of digoxin Extracardiac: Xanthopsia Cardiac: NPAT
- 50. Therapeutic range ofdigoxin : 0.5 – 0.8 ng/ml Digoxin > 1.2 ng/ml UNSAFE Hypokalemia risk of toxicity Injectable K+ : used for treatment of Digoxin toxicity Digoxin toxicity : Ventricular arrhythmia Lignocaine Extreme sinus bradycardia : Atropine IV 0.5 mg to 1 mg Severe Digoxin toxicity : Digibind
- 51. Contraindications of Digoxin •Hypokalemia ( binding affinity of Digoxin to Na+-K+ ATPase) • Hypomagnesemia • Hypercalcemia • Myocardial infarction • WPW syndrome • Heart block • Thyrotoxicosis Favor Sarcoplasmic Ca overload and spontaneous Ca release events
- 52. Drugs which increasetoxicity of Digoxin • Diuretics (Hypokalemia) • Erythromycin • Verapamil • Amiodarone • Corticosteroids • Tetracycline • Quinidine
- 53. • ACEI :most preferred • ARB • Beta blockers • Aldosterone antagonists Mortality benefit
- 54. ACEIs Benazepril Captopril Enalapril Lisinopril Quinapril Ramipril First choice int/t of heart failure Start low (1/10 target dose); go slow (2 to 4 weekly doubling) A/E: cough, angioedema, hypotension, hyperkalemia, skin, rash, neutropenia, anemia, fetopathic syndrome C/I: B/L renal artery stenosis Fosinopril Trandalopril Perindopril Caution in patients with renal or hepatic impairment
- 55. Captopril TDS 6.25mg 50 mg Enalapril BD 2.5 mg 20 mg Lisinopril 2.5 mg 35 mg Ramipril 2.5 mg 10 mg Trandalopril 0.5 mg 4 mg
- 56. ARBs Candesartan 4 mg 32 mg Losartan 50 mg 150 mg Valsartan BD 40 mg 160 mg Olmesartan Telmisartan Irbesartan Only in cases of intolerance to intolerance to ACEI Unwanted effects as ACEI, but no cough or angioedema No evidence for superiority over ACEI In combination with ACEI more harm than benefit
- 57. Beta blockers Bisoprolol 1.25mg 10 mg Carvedilol 3.125 mg 25 mg Metoprolol 12.5 mg 200 mg Nebivolol 1.25 mg 10 mg First choice in t/t of heart failure Start low (1/10 target dose); go slow (2 to 4 weekly doubling) A/E: Bradycardia, AV block, bronchospasm, peripheral vasoconstriction, worsening of acute heart failure
- 58. • Acute CHF: Contraindicated • Chronic CHF : Mortality • Start low dose : Go slow • Most commonly used : Carvedilol Beta blockers
- 59. Potassium sparing Diuretics Eplerenone50 mg 200 mg Spironolactone 50 mg 200 mg Amiloride 5 mg 20 mg Triamterene 50 mg 200 mg A/E: hyperkalemia, hyponatremia, hypomagnesemia, hyperuricemia, hypocalcemia, glucose intolerance
- 60. Aldosterone antagonists First choicein treating symptomatic heart failure Low doses (25-50 mg) S/E: Hyperkalemia Gynecomastia and impotence in men Dysmenorrhea in women Due to nonselective binding to sex hormone receptors Eplerenone 50 mg 200 mg Spironolactone 50 mg 200 mg Amiloride 5 mg 20 mg Triamterene 50 mg 200 mg
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- 62.
- 63. NEPI + ACEI Vasopeptidaseinhibitors Omapatrilat Sampatrilat Fasidotrilat S/E Dry cough Angioedema
- 64. NEPI + ARB Vasopeptidaseinhibitors (Sacubitril + Valsartan) Superior to the ACEI enalapril Degradation of natriuretic peptides S/E Hypotension
- 65. ANP analogue :Vasodilator • Carperitide • Ularitide
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- 68.
- 69. Istaroxime Inhibits Na+-K+ ATPase + Sequestrationof Calcium from SR Contractility
- 70. Omecamtive Mecarbil Activate Myosin + Prolongsystole without O2 demand
- 71. Vasopressin Receptor antagonists Conivaptan Tolvaptan V2receptor antagonist Increased excretion of water
- 72. NYHA I Nolimitation of ordinary physical activity; only strenuous physical activity produces discomfort NYHA II Ordinary physical activity Shortness of breath NYHA III Less than ordinary physical activity Shortness of breath NYHA IV Shortness of breath at rest NYHA Heart failure classification
- 73. STAGE A Highrisk patient for HF, But no structural damage of the heart STAGE B Structural damage of the heart Without clinical features STAGE C Structural damage of the heart With presence of clinical features STAGE D Decompensated heart failure Dyspnea at rest ACC/AHA Stages of Heart failure
- 74. ACC/AHA NYHA DescriptionTreatment STAGE A Pre-failure No symptoms but risk factors present Treat obesity, HTN, DM, dyslipidemia STAGE B I Symptoms with severe exercise ACEI/ ARB, Beta blocker, Diuretic STAGE C II/III Symptoms with marked (class II) or mild (class III) exercise Add Spironolactone, Digoxin, ARNI, Nitrate/ Hydralazine, CRT STAGE D IV Severe symptoms at rest Transplant, LVAD Classification and treatment of chronic heart failure
- 75. Interventions in CCF CRTICD LVAD In patients with medically refractory arrhythmias Acts as a bridge for cardiac transplantation Those patients where medical therapy fails to bring improvement in symptoms
- 76. REFERENCES • National GuidelineCentre (UK). Chronic Heart Failure in Adults: Diagnosis and Management. London: National Institute for Health and Care Excellence (UK); 2018 Sep. (NICE Guideline, No. 106.) 6, Treating Heart Failure. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536070/ • Basic & Clinical Pharmacology, Fourteenth Edition • The pharmacological basis of therapeutics, Thirteenth edition
Editor's Notes
- #2 The management of heart failure has changed significantly over the last 30 years, leading to improvements in the quality of life and outcomes, at least for patients with a substantially reduced left ventricular ejection fraction (HFrEF). This has been made possible by the identification of various pathways leading to the development and progression of heart failure, which have been successfully targeted with effective therapies.
- #3 Overload= primary contractile defect Response to chronic overload = hypertrophy of CM (major risk factor for dev of HF) CM hypertrophy leads to reduced capillary myocyte ratio, hence causes energy deficit and metabolic reprogramming.
- #63 V rec subtypes
- #64 V rec subtypes
- #65 V rec subtypes
- #66 V rec subtypes
- #67 V rec subtypes
- #68 V rec subtypes
- #69 V rec subtypes
- #70 V rec subtypes
- #71 V rec subtypes
- #72 V rec subtypes