Recent Updated Pathogenesis and
Management of Heart Failure:
The role of Angiotensin Receptor Blockers?
Dr. dr. ANWAR SANT...
VBWG
Diabetes is the No. 1 risk factor
for HF in women with coronary disease
Bibbins-Domingo K Jr et al. Circulation.2004;...
The Donkey AnalogyThe Donkey AnalogyThe Donkey AnalogyThe Donkey Analogy
Ventricular dysfunction limits a patient's abilit...
↑↑↑↑MAP = (↑↑↑↑SV x ↑↑↑↑HR) x ↑↑↑↑TPR
Sympathetic Nervous System
↑ Contractility Tachycardia Vasoconstriction
Compensatory...
Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.
↑ CNS sympathetic outflow
Disease progression
↑ Cardiac sympathetic
...
Vasoconstriction
Oxidative Stress
Cell Growth Proteinuria
LV remodeling
Vascular remodeling
Angiotensinogen
Angiotensin I
...
↑↑↑↑MAP = (↑↑↑↑SV x ↑↑↑↑HR) x ↑↑↑↑TPR
Renin-Angiotensin-Aldosterone
(↓↓↓↓ renal perfusion)
Salt-water retention
Thirst
Sym...
Decreased systemic blood pressure
Central baroreceptors
Stimulation of hypothalamus, which produces
vasopressin for releas...
CompensatoryCompensatoryCompensatoryCompensatory NeurohormonalNeurohormonalNeurohormonalNeurohormonal Stimulation:Stimulat...
Proposed Pathogenesis of Heart Failure
Gonzales A, et. al. J Am Coll Cardiol 2011; 58: 1833 - 43
Curry CW, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction
delay as depicted by 3...
Classification of Heart Failure
ACCF/AHA Stages of HF NYHA Functional Classification
A At high risk for HF but without str...
Diagnosis of Heart Failure
M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104
M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104
Diagnosis of Heart Failure
M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104
Diagnostic flowchart for patients suspected Heart
Fa...
M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104
Treatment options for patients with chronic symptoma...
Diuretics, ACE Inhibitors and ARB’sDiuretics, ACE Inhibitors and ARB’sDiuretics, ACE Inhibitors and ARB’sDiuretics, ACE In...
Pharmacologic Treatment for Stage C HFrEF
Pharmacological Treatment for
Stage C HFrEF (cont.)
Diuretics are recommended in patients with HFrEF who
have evidence of ...
Drugs Commonly Used for HFrEF
(Stage C HF)
Drug Initial Daily Dose(s) Maximum Doses(s)
Mean Doses Achieved in
Clinical Tri...
Pharmacological Treatment for
Stage C HFrEF (cont.)
ARBs are reasonable to reduce morbidity and mortality as
alternatives ...
Pharmacological Treatment for
Stage C HFrEF (cont.)
Routine combined use of an ACE inhibitor, ARB, and
aldosterone antagon...
ßßßß----BlockersBlockersBlockersBlockers
Limit the donkey’s speed, thus saving energy
Digitalis CompoundsDigitalis CompoundsDigitalis CompoundsDigitalis Compounds
Like the carrot placed in front of the donkey
VBWG
ACC/AHA stages of systolic HF
and treatment options
Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.*In appropria...
M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104
Pharmacological treatments in (NYHA class II – IV)
s...
M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104
Treatments that may cause harm in
symptomatic Heart ...
• EvidenceEvidenceEvidenceEvidence----based guidelinebased guidelinebased guidelinebased guideline directed diagnosis, eva...
Recent Updated Pathogenesis and Management of Heart Failure:
Recent Updated Pathogenesis and Management of Heart Failure:
Recent Updated Pathogenesis and Management of Heart Failure:
Recent Updated Pathogenesis and Management of Heart Failure:
Recent Updated Pathogenesis and Management of Heart Failure:
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Recent Updated Pathogenesis and Management of Heart Failure:

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DR. Dr. Anwar Santoso, SpJP (K), FIHA, 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com

Published in: Health & Medicine

Recent Updated Pathogenesis and Management of Heart Failure:

  1. 1. Recent Updated Pathogenesis and Management of Heart Failure: The role of Angiotensin Receptor Blockers? Dr. dr. ANWAR SANTOSO, SpJP(K), FIHA, FAsCC, FICA. Dept. of Cardiology – Faculty of Medicine ~ University of Indonesia National Cardiovascular Centre – Harapan Kita Hospital - INDONESIA
  2. 2. VBWG Diabetes is the No. 1 risk factor for HF in women with coronary disease Bibbins-Domingo K Jr et al. Circulation.2004;110:1424-30. Adjusted hazard ratio Diabetes Atrial fibrillation Myocardial infarction >1 event Creatinine clearance <40 Current smoking BMI >35 Left bundle branch block LV hypertrophy Systolic BP ≥140 3.1 2.9 2.5 2.3 2.1 1.9 1.9 1.6 1.5 0 0.5 1 1.5 2 2.5 3 3.5 HERS study
  3. 3. The Donkey AnalogyThe Donkey AnalogyThe Donkey AnalogyThe Donkey Analogy Ventricular dysfunction limits a patient's ability to perform the routine activities of daily living…
  4. 4. ↑↑↑↑MAP = (↑↑↑↑SV x ↑↑↑↑HR) x ↑↑↑↑TPR Sympathetic Nervous System ↑ Contractility Tachycardia Vasoconstriction Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms: Sympathetic Nervous SystemSympathetic Nervous SystemSympathetic Nervous SystemSympathetic Nervous System Decreased MAP
  5. 5. Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52. ↑ CNS sympathetic outflow Disease progression ↑ Cardiac sympathetic activity β1- receptors β2- receptors α1- receptors Vasoconstriction Sodium retention Myocardial toxicity Increased arrhythmias ↑ Sympathetic activity to kidneys + peripheral vasculature Activation of RAS α1- β1- Sympathetic Activation in Heart FailureSympathetic Activation in Heart FailureSympathetic Activation in Heart FailureSympathetic Activation in Heart Failure
  6. 6. Vasoconstriction Oxidative Stress Cell Growth Proteinuria LV remodeling Vascular remodeling Angiotensinogen Angiotensin I Angiotensin II AT I receptor Renin Angiotensin Converting Enzyme Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms: ReninReninReninRenin----AngiotensinAngiotensinAngiotensinAngiotensin----Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)
  7. 7. ↑↑↑↑MAP = (↑↑↑↑SV x ↑↑↑↑HR) x ↑↑↑↑TPR Renin-Angiotensin-Aldosterone (↓↓↓↓ renal perfusion) Salt-water retention Thirst Sympathetic augmentation Vasoconstriction Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms: ReninReninReninRenin----AngiotensinAngiotensinAngiotensinAngiotensin----Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)
  8. 8. Decreased systemic blood pressure Central baroreceptors Stimulation of hypothalamus, which produces vasopressin for release by pituitary gland Release of vasopressin by pituitary glandVasoconstriction Increased systemic blood pressure - Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms:Compensatory Mechanisms: NeurohormonalNeurohormonalNeurohormonalNeurohormonal ActivationActivationActivationActivation –––– VasopressinVasopressinVasopressinVasopressin
  9. 9. CompensatoryCompensatoryCompensatoryCompensatory NeurohormonalNeurohormonalNeurohormonalNeurohormonal Stimulation:Stimulation:Stimulation:Stimulation: SummarySummarySummarySummary Decreased Cardiac Output Sympathetic nervous system Renin-angiotensin system Antidiuretic hormone (vasopressin) Heart rate Contractility Vasoconstriction Circulating volume Anteriolar Maintain blood pressure Cardiac output Stroke volume + -+ Venous Venous return to heart ( preload) Peripheral edema and pulmonary congestion
  10. 10. Proposed Pathogenesis of Heart Failure Gonzales A, et. al. J Am Coll Cardiol 2011; 58: 1833 - 43
  11. 11. Curry CW, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction delay as depicted by 3D tagged magnetic resonance imaging. Circulation 2000 Jan 4;101(1):E2. Compensatory MechanismsCompensatory MechanismsCompensatory MechanismsCompensatory Mechanisms Ventricular Remodeling Alterations in the heart’s size, shape, structure, and function brought about by the chronic hemodynamic stresses experienced by the failing heart.
  12. 12. Classification of Heart Failure ACCF/AHA Stages of HF NYHA Functional Classification A At high risk for HF but without structural heart disease or symptoms of HF. None B Structural heart disease but without signs or symptoms of HF. I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. C Structural heart disease with prior or current symptoms of HF. I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF. III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest. D Refractory HF requiring specialized interventions.
  13. 13. Diagnosis of Heart Failure M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104
  14. 14. M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104 Diagnosis of Heart Failure
  15. 15. M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104 Diagnostic flowchart for patients suspected Heart Failure
  16. 16. M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104 Treatment options for patients with chronic symptomatic systolic Heart Failure
  17. 17. Diuretics, ACE Inhibitors and ARB’sDiuretics, ACE Inhibitors and ARB’sDiuretics, ACE Inhibitors and ARB’sDiuretics, ACE Inhibitors and ARB’s Reduce the number of sacks on the wagon
  18. 18. Pharmacologic Treatment for Stage C HFrEF
  19. 19. Pharmacological Treatment for Stage C HFrEF (cont.) Diuretics are recommended in patients with HFrEF who have evidence of fluid retention, unless contraindicated, to improve symptoms. ACE inhibitors are recommended in patients with HFrEF and current or prior symptoms, unless contraindicated, to reduce morbidity and mortality. ARBs are recommended in patients with HFrEF with current or prior symptoms who are ACE inhibitor- intolerant, unless contraindicated, to reduce morbidity and mortality. I IIa IIb III I IIa IIb III I IIa IIb III
  20. 20. Drugs Commonly Used for HFrEF (Stage C HF) Drug Initial Daily Dose(s) Maximum Doses(s) Mean Doses Achieved in Clinical Trials ACE Inhibitors Captopril 6.25 mg 3 times 50 mg 3 times 122.7 mg/d (421) Enalapril 2.5 mg twice 10 to 20 mg twice 16.6 mg/d (412) Fosinopril 5 to 10 mg once 40 mg once --------- Lisinopril 2.5 to 5 mg once 20 to 40 mg once 32.5 to 35.0 mg/d (444) Perindopril 2 mg once 8 to 16 mg once --------- Quinapril 5 mg twice 20 mg twice --------- Ramipril 1.25 to 2.5 mg once 10 mg once --------- Trandolapril 1 mg once 4 mg once --------- ARBs Candesartan 4 to 8 mg once 32 mg once 24 mg/d (419) Losartan 25 to 50 mg once 50 to 150 mg once 129 mg/d (420) Valsartan 20 to 40 mg twice 160 mg twice 254 mg/d (109) Aldosterone Antagonists Spironolactone 12.5 to 25 mg once 25 mg once or twice 26 mg/d (424) Eplerenone 25 mg once 50 mg once 42.6 mg/d (445)
  21. 21. Pharmacological Treatment for Stage C HFrEF (cont.) ARBs are reasonable to reduce morbidity and mortality as alternatives to ACE inhibitors as first-line therapy for patients with HFrEF, especially for patients already taking ARBs for other indications, unless contraindicated. Addition of an ARB may be considered in persistently symptomatic patients with HFrEF who are already being treated with an ACE inhibitor and a beta blocker in whom an aldosterone antagonist is not indicated or tolerated. I IIa IIb III I IIa IIb III
  22. 22. Pharmacological Treatment for Stage C HFrEF (cont.) Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful for patients with HFrEF. Use of 1 of the 3 beta blockers proven to reduce mortality (i.e., bisoprolol, carvedilol, and sustained-release metoprolol succinate) is recommended for all patients with current or prior symptoms of HFrEF, unless contraindicated, to reduce morbidity and mortality. I IIa IIb III I IIa IIb III Harm
  23. 23. ßßßß----BlockersBlockersBlockersBlockers Limit the donkey’s speed, thus saving energy
  24. 24. Digitalis CompoundsDigitalis CompoundsDigitalis CompoundsDigitalis Compounds Like the carrot placed in front of the donkey
  25. 25. VBWG ACC/AHA stages of systolic HF and treatment options Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.*In appropriate patients
  26. 26. M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104 Pharmacological treatments in (NYHA class II – IV) symptomatic systolic Heart Failure
  27. 27. M’c Murray JJV, et. al. Eur Heart J 2012; doi: 10. 1093/eurhj/ehs.104 Treatments that may cause harm in symptomatic Heart Failure
  28. 28. • EvidenceEvidenceEvidenceEvidence----based guidelinebased guidelinebased guidelinebased guideline directed diagnosis, evaluation and therapy should be the mainstay for all patients with HF. • Effective implementation of guideline-directed best quality care reduces mortality, improves QOL and preserves healthreduces mortality, improves QOL and preserves healthreduces mortality, improves QOL and preserves healthreduces mortality, improves QOL and preserves health care resourcescare resourcescare resourcescare resources. • Ongoing research is needed to answer the remaining questions including: prevention, nonpharmacological therapy of HF including dietary adjustments, treatment of HFdietary adjustments, treatment of HFdietary adjustments, treatment of HFdietary adjustments, treatment of HFppppEF,EF,EF,EF, management of hospitalized HF, effective reduction in HFmanagement of hospitalized HF, effective reduction in HFmanagement of hospitalized HF, effective reduction in HFmanagement of hospitalized HF, effective reduction in HF readmissions, more precise use of devicereadmissions, more precise use of devicereadmissions, more precise use of devicereadmissions, more precise use of device----based therapy,based therapy,based therapy,based therapy, smaller MCS platforms and cellsmaller MCS platforms and cellsmaller MCS platforms and cellsmaller MCS platforms and cell----based regenerative therapybased regenerative therapybased regenerative therapybased regenerative therapy. Conclusions
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