Recent Updated Pathogenesis and Management of Heart Failure:
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Transcript of Recent Updated Pathogenesis and Management of Heart Failure:
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
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
3.12.9
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
The Donkey Analogy The Donkey Analogy The Donkey Analogy The Donkey Analogy
Ventricular dysfunction limits a patient's ability to perform the routine activities of daily living…
↑↑↑↑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
Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.
↑ CNS sympathetic outflow
Disease progression
↑ Cardiac sympatheticactivity
β1-receptors
β2-receptors
α1-receptors
VasoconstrictionSodium retention
Myocardial toxicityIncreased arrhythmias
↑ Sympatheticactivity to kidneys
+ peripheral vasculature
Activationof RAS
α1- β1-
Sympathetic Activation in Heart FailureSympathetic Activation in Heart FailureSympathetic Activation in Heart FailureSympathetic Activation in Heart Failure
Vasoconstriction
Oxidative Stress
Cell Growth Proteinuria
LV remodeling
Vascular remodeling
Angiotensinogen
Angiotensin I
Angiotensin II
AT I receptor
Renin
AngiotensinConverting
Enzyme
Compensatory Mechanisms: Compensatory Mechanisms: Compensatory Mechanisms: Compensatory Mechanisms:
ReninReninReninRenin----AngiotensinAngiotensinAngiotensinAngiotensin----Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)
↑↑↑↑MAP = (↑↑↑↑SV x ↑↑↑↑HR) x ↑↑↑↑TPR
Renin-Angiotensin-Aldosterone(↓↓↓↓ renal perfusion)
Salt-water retentionThirst
Sympatheticaugmentation
Vasoconstriction
Compensatory Mechanisms: Compensatory Mechanisms: Compensatory Mechanisms: Compensatory Mechanisms:
ReninReninReninRenin----AngiotensinAngiotensinAngiotensinAngiotensin----Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)Aldosterone (RAAS)
Decreased systemic blood pressure
Central baroreceptors
Stimulation of hypothalamus, which producesvasopressin for release by pituitary gland
Release of vasopressin by pituitary glandVasoconstriction
Increased systemic blood pressure
-
Compensatory Mechanisms: Compensatory Mechanisms: Compensatory Mechanisms: Compensatory Mechanisms:
NeurohormonalNeurohormonalNeurohormonalNeurohormonal Activation Activation Activation Activation –––– VasopressinVasopressinVasopressinVasopressin
Compensatory Compensatory Compensatory Compensatory NeurohormonalNeurohormonalNeurohormonalNeurohormonal Stimulation: Stimulation: Stimulation: Stimulation:
Summary Summary Summary Summary
Decreased Cardiac Output
Sympatheticnervous system
Renin-angiotensinsystem
Antidiuretic hormone(vasopressin)
Heartrate
Contractility Vasoconstriction Circulating volume
Anteriolar
Maintainblood
pressure
Cardiacoutput
Strokevolume
+
-+
Venous
Venous return to heart
( preload)
Peripheral edemaand pulmonary
congestion
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 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.
Classification of Heart Failure
ACCF/AHA Stages of HF NYHA Functional ClassificationA 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.
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 Failure
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
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
Pharmacologic Treatment for Stage C HFrEF
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
Drugs Commonly Used for HFrEF
(Stage C HF)
Drug Initial Daily Dose(s) Maximum Doses(s)Mean Doses Achieved in
Clinical TrialsACE InhibitorsCaptopril 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 ---------ARBsCandesartan 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 AntagonistsSpironolactone 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)
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
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
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 appropriate patients
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
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
• EvidenceEvidenceEvidenceEvidence----based guideline based guideline based guideline based 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 health reduces mortality, improves QOL and preserves health reduces mortality, improves QOL and preserves health reduces 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 HF management of hospitalized HF, effective reduction in HF management of hospitalized HF, effective reduction in HF management 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