Post on 21-Dec-2015
description
Bambang Irawan SpPD [K], SpJP [K],
FIHA, FASCC, FINASIM
Internist [SpPD] 1981
Cardiovascular Consultant [KKV] 1996
Cardiologist [SpJP] 2004
Fellow of Indonsian Heart Association[FIHA] 2004
Cardiologist Consultant [ K ] 2005
Professor in Cardiology [ Prof ] 2006
Fellow of Asean College Cardiology[FASCC] 2008
Fellow of Ind Society of Internal Medicine 2009
NEUROHUMORAL ACTIVATION
& THERAPEUTIC APPROACH
IN HEART FAILURE
BAMBANG IRAWAN MD FIHA FASCC FINASIM
Professor in Cardiology and Vascular Medicine
Departement of Cardiology, Faculty of Medicine,
Gadjah Mada University Yogyakarta
PREVENTING & THERAPEUTIC IN HEART
FAILURE
HEART FAILURE IS A COMMON DISEASE
HEART FAILURE IS DISEASE WITH A HIGH
MORBIDITY & MORTALITY
ASSOCIATED WITH HIGH COST BOTH THE PATIENTS
& HEALTH-CARE SYSTEMS
65 YEARS AGO, BEFORE ANTIHYPERTENSION DRUG,
HEART FAILURE WAS THE MOST COMMON
COMPLICATIONS OF HYPERTENSION
FRAMINGHAM [1971] DEMONSTRATED THAT
HYPERTENSION WAS THE MAJOR FACTOR IN
CAUSED OF HEART FAILURE
MAJOR RISK FACTOR FOR THE
DEVELOPMENT OF HEART FAILURE
HYPERTENSION
MYOCARDIAL INFARCTION
ANGINA PECTORIS
DIABETES
LEFT VENTRICULAR HYPERTROPHY
VALVULAR DISEASE
HEART FAILURE & DIABETES
HEART FAILURE 2X COMMON IN DIABETIC MAN & 5X IN DIABETIC WOMEN
12% TYPE 2 DIABETICS BECOME HEART FAILURE
EACH YEAR 3.3% TYPE 2 DIABETICS BECOME HEART FAILURE
Bell Diabetes Care 2003Amato et al Diabetes Metab 1997
CAUSE of HEART FAILURE
MYOCARDIAL DISEASE: MYOCARDIAL INFARCTION, MYOCARDITIS, TOXIN [ALCOHOL]
ELEVETED PRELOAD: MITRAL REGURGITATION, AORTIC REGURGITATION, INTRA-CARDIAC SHUNT
ELEVATED AFTERLOAD: AORTIC STENOSIS HYPERTENSION, AORTIC COARTATION
OTHERS
MORTALITY IN PATIENTS WITH HEART
FAILURE IN FRAMINGHAM STUDY
MORTALITY FROM MEN WOMEN
DIAGNOSE OF HF
2 YEARS 37% 33%
6 YEARS 82% 67%
Kannel (1991)
HEART FAILURE
SYMPTOM OF HERAT FAILURE [breathlessness at rest or exercise, fatigue, tiredness]
SIGN OF HEART FAILURE [tachycardia,tachypnea,pulmonary rales,pleuraleffusion,raised jugular venous pressure,peripheraloedema,hepatomegaly]
STRUCTURAL ABNORMALITY [cardiomegaly, 3rd heart sound, cardiac murmurs]
NEW YORK HEART ASSOCIATION [NYHA]
CLASS I : ORDINARY ACTIVITY DOES NOT CAUSE FATIGUE PALPITATION DYSPNEA OR ANGINAL PAIN
CLASS II: COMFORTABLE AT REST BUT ORDINARY ACTIVITY CAUSE COMPLAIN
CLASS III: COMFORTABLE AT REST, LESS THAN ORDINARY ACTIVITY CAUSE COMPLAIN
CLASS IV: INABILITY TO PERFORM ANY ACTIVITY WITHOUT COMPLAIN
NormalLV structure and function
Hypertension HF
Overt heart failure
SmokingDyslipidaemiaDiabetes
ObesityDiabetes
LV remodelling
LVH
MISystolic
dysfunction
Diastolicdysfunction
Subclinical LV dysfunction
Time: decades Time: months
Death
PROGRESSION HYPERTENSION – HEART FAILURE
.
NEUROHUMORAL ACTIVATION IN
PROGRESSION OF HEART
FAILURE
ACUTE RESPONSE SNS ACTIVATION [AFTERLOAD]
NEUROHUMORAL PATHWAY [PRELOAD]
CHRONIC REMODELLING
SYSTEMIC & LOCAL CYTOKINE OR GROWTH FACTOR FAMILIES
HYPERTROPHY WITH CHAMBER DILATATION [ECCENTRIC]
HYPERTROPHY NOT ASSOCIATED MYOCYTE STRETCHING [CONCENTRIC]
THE RENIN – ANGIOTENSIN – ALDOSTERON SYSTEM
Blood vessel
KIDNEY Adrenal cortex
LIVER
Endothelial cells
Angiotensinogen
Angiotensin I
ACE
Angiotensin II
Aldosteron
Renin
Kidney Kidney
Intraglomerular
hypertension
Tissue RAS
Long-term effects
Circulating RAS
Short-term effects
Sodium/water reabsorption
via aldosterone secretion
Vasoconstriction
HeartHeart
t
Positive chronotropic
effects/
arrhythmogenic
effects
Angiotensin II
Myocardial
hypertrophy
Vascular
hypertrophy
Circulating and tissue RAS influence on the cardiovascular system
Dzau VJ. Arch Intern Med. 1993;153
LVH & THE RAAS
CIRCULATING LEVELS OF ANGIOTENSIN II &
ALDOSTERONE ARE DIRECTLY TO LVM
ANGIOTENSIN II
INCREASES BP
PROMOTESS MYOCYTE GROWTH
INDUCES HYPERTROPHY OF SMOOTH MUSCLE
CELLS
ALDOSTERON : INCREASES FIBROBLAST
COLLAGEN CONTENT & STIMULATES MYOCARDIAL
FIBROSIS
Kim, Iwao. Pharmacol Rev 2000;52:11–34
Vascular inflammation
Progression and clinical complications of atherosclerosis
Angiotensin II
Vascular ROS production
Endothelial dysfunction(Reduced NO availability)
LDL oxidation
Pro-inflammatory
gene expression
(eg. VCAM-1 and MCP-1)
(Landmesser & Drexler, 2003)
Angiotensin II
Direct vasoconstriction
Sympathetic activationEndothelial
dysfunctionCell growth Na reabsorption
aldosterone
Vasoconstriction Inflammation
cytokine
Superoxide
Cardiac and
vascular
remodelling
Volume
ATHEROSCLEROSIS
BLOOD PRESSURE
(SKK/2000)
Pleiotropic Cardiovascular Effects of Angiotensin II
Pleiotropic effects of ACEI
Lonn E et al. Eur Heart J Suppl. 2003;5(suppl A):A43-A8.Wassman S and Nickenig G. Eur Heart J Suppl. 2004;6(suppl H):H3-H9.
Mason RP et al. Arterioscler Thromb Vasc Biol. 2003;23:2155-63.
Fibrinolysis
Platelet aggregation
Mononuclear cell migration
Collagen matrix formation
Endothelial function
Oxidative stress Inflammation
Plaque stability
Arterial compliance
NO
MMP activity
VSMC proliferation
Cholesterol depositionin membrane
MMP = matrix metalloproteinase
AHTN
agents
BP-
lowering
agents
Both
ACE inhibition: BP-lowering mechanisms
A II synthesis
Bradykinin, prostacyclin, NO production
Endothelin synthesis
Parasympathetic tone
Central and peripheral sympathetic tone
Natriuresis/diuresis
HEART FAILURE AND NEUROHORMONAL STIMULATION
Cytosolic
Ca ++
Arrhythmias
Inotropy
Myocardial O2
expenditure
Myocardial cell
death
Heart
+
+
Vasoconstriction
Afterload
Myocardial O2
expenditure
Myocardial cell
death
Circulation
_
+
Heart failure
Cardiac output
Neurohormonal stimulation
Renin – Angiotensin
Sympathetic - adrenergic
Modified after Dzau & Braunwald Am Heart J 1991
Risk factors• Hyperlipidemia• Hypertension• Diabetes• Smoking
Atherosclerosis
CAD
Myocardialischemia Neurohormonal
activation
Loss of muscle Sudden
death
Remodeling
Ventriculardilation
Heart Failure
Coronary thrombosis
Myocardial infarction
Arrhythmias
Stroke
Renal failure
LV Hypertrophy
CHAIN LEADING TO HEART FAILURE
SUMMARY
ANGIOTENSIN II ARE RISK FOR NOT JUST HYPERTENSION
BUT ATHEROGENESIS WITH RUPTUR PLAQUE,
REMODELLING WITH THE RISK OF STROKE, HEART FAILURE
EVEN RENAL FAILURE
ANGIOTENSIN II RECEPTOR BLOCKER, ACE – I & ANTI –
RENNIN ACT NOT JUST TO COMBAT HYPERTENSION BUT
MORE IMPORTANT IS TO PROTEC TARGET ORGAN
RECOMENDATION: THESE KIND OF DRUGS MUST INCLUDE IN
THE TREATMENT OF ALL HYPERTENSION, HEART FAILURE,
RENAL FAILURE & STROKE