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Best wishes to YOU. Heart Failure Basics to Recent Advances. Dr. R.V.S.N. Sarma., M.D., M.Sc.(Canada), FIMSA Consultant Physician and Cardiometabolic Specialist. Definition, Etiology Epidemiology and Pathophysiology. Floor Plan of This Talk. - PowerPoint PPT Presentation
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Best wishes to YOUBest wishes to YOU
www.drsarma.in
Heart Failure Basics to Recent Advances
Heart Failure Basics to Recent Advances
www.drsarma.in
Definition, Etiology
Epidemiology and
Pathophysiology
Definition, Etiology
Epidemiology and
Pathophysiology
Floor Plan of This TalkFloor Plan of This Talk
www.drsarma.in
“The very essence of
cardiovascular practice is early
detection of Heart Failure”
“The very essence of
cardiovascular practice is early
detection of Heart Failure”
HF is a ‘BIG’ SubjectHF is a ‘BIG’ Subject
• It afflicts millions of people worldwide
• Has many diverse causes and risk factors
• Large number of Mega trials and literature
• High mortality; Several drugs and devices
• A paradigm shift in understanding & Rx.
• Extremely costly – huge no. of bed days
• Complicated by many co morbidities
• Truly multidisciplinary in its management
Detection of Heart FailureDetection of Heart Failure
About half of the patients with left
ventricular dysfunction had no symptoms
and therefore would be difficult to identify at
this early stage by clinical examination
alone – underscoring the need for
echocardiography.
Framingham Heart Study has been the most
important longitudinal source of data on the
epidemiology of heart failure.
Why HF is increasing ?Why HF is increasing ?
• Almost any disease of heart can cause it
• More of HT, DM, MS, Obesity - ASCVD
• CAD - which is its commonest cause
• Better tools for diagnosis and availability
• Better detection and treatment of causes
• Better Rx. of RF, CAD, MI - PTCA, CABG
• Increasing longevity of the population
• HF is an aging process – longer life span
Important PointsImportant Points
• Chronic Heart Failure (CHF) can be caused by any type of cardiac dysfunction
• Most commonly attributable to LV Dysfunction
• Rarely HF is due to isolated RV dysfunction
• Most common and best studied cause of CHF is LV Systolic Dysfunction (LVSD)
• Normal Ejection Fraction Heart Failure (NEFHF) is due to LV Diastolic Dysfunction – (HFPSF)
• It is difficult to diagnose and quantify.
Floor Plan of This TalkFloor Plan of This Talk
Definitions of Heart FailureDefinitions of Heart Failure
Heart failure is a clinical syndrome characterized
by decreased systemic perfusion, inadequate to
meet the body's metabolic demands as a result of
impaired cardiac pump function - Cleveland Clinic
A pathophysiologic state in which an abnormality
of cardiac function is responsible for failure of the
heart to pump blood at a rate commensurate with
metabolic requirements of the tissues -E Braunwald
Definition of HFDefinition of HF
Physiological:
Inability of the heart to pump sufficient oxygenated blood to the metabolizing tissues despite an adequate filling pressure.
Working Clinical Definition:
Clinical syndrome consisting of symptoms such as breathlessness, fatigue, and swelling of ankle caused by cardiac dysfunction.
Types of Heart FailureTypes of Heart Failure
• Chronic Heart Failure (CHF)• Acute Heart Failure (Cardiogenic
Shock)• Systolic Failure (LVSD) – Reduced EFHF• Diastolic Heart Failure (LVDD) – NEFHF• Left Heart Failure (LVF)• Right Heart Failure (Congestive CCF)• Forward Failure and Backward Failure• High output failure -Thyrotoxic,
Paget's, Anemia, Pregnancy, A-V fistula
• Low output failure – 95% of HF is this
Floor Plan of This TalkFloor Plan of This Talk
Heart Failure – Some Statistics
Heart Failure – Some Statistics
• Affects 10% of people over 65 years• Affects over 50% of people with 85+ years• Approx 10% of patients with HF die each yr. • It is the most common condition for which
patients 65 + require admission to hospital• It is NOT a single disease – A syndrome
• Results from any cardiac disorder that impairs the ability of the ventricles to fill with or eject blood
Epidemiology of Heart Failure
Epidemiology of Heart Failure
Epidemiology of Heart Failure
Epidemiology of Heart Failure
Data from Framingham Heart Study per 1000 population
Incidence of Heart FailureIncidence of Heart Failure
McKee PA et al. Framingham study; N Eng J Med 1971; 285: 1441-6
Ethnic Differences in HFEthnic Differences in HF
Sosin MD, et al. Eur J Heart Fail 2004;6:669-72
Age, MI and Heart FailureAge, MI and Heart Failure
Prevalence of Chronic AF in HFPrevalence of Chronic AF in HF
Cleland JG, et al. Heart Fail Rev 2002;7:229-42
181 92 9970 11062 11016 No in study
Systolic Heart FailureSystolic Heart Failure• LVSD – Left Ventricular Systolic Dysfunction
• Most common type of Heart Failure; 60-70%
• LV is usually dilated & enlarged.
• Fails to contract normally due to WMA, Ischemia
• Cannot pump sufficient blood to meet needs
• Normal ejection fraction (EF) is at least 50-55%
• In LVSD heart failure the EF is <40 -45%
• This carries a 10% mortality per annum
Diastolic Heart FailureDiastolic Heart Failure• Accounts for 20-40% of patients
• Ventricles are normal-sized with normal emptying
• But there is an impairment in the ability of the ventricles to fill with blood during diastole.
• Because of stiff myocardium due to hypertrophy
• The heart fails to relax normally (relaxation poor)
• Generally older women
• Hypertension is the commonest cause
• This carries a 5-8% mortality per annum
Population Differences in DHF
Population Differences in DHF
McMurray JJ, et al. Lancet 2005;365:1877
Floor Plan of This TalkFloor Plan of This Talk
Causes of Heart FailureCauses of Heart Failure1. Coronary Artery Disease (MI, IHD) (2/3 of cases)
2. Hypertension (common fore runner of LVSD, LVDD)
3. Diabetes Mellitus (via IHD, direct cardiomyopathy)
• Cardiomyopathy (DCM, HOCM, OCM, RCM)
• Valvular Heart Disease (MS, MR, AS, AR)
• Congenital Heart Disease (ASD, VSD)
• Arrhythmias (AF, Brady, Tachy, Heart Block, SSS)
• ‘High output’ failures (Anemia, hyperthyroidism, AV-F)
• Pericardial Disease (Constrictive, Effusion)
• Right Heart Failure (PHT, PE, Cor Pulmonale)
Drugs and Heart FailureDrugs and Heart FailureMany drugs may precipitate HF or cause its deteriorate
Sodium and water retention agents
• Glucocorticoids, androgens, estrogens, NSAIDs (dose
dependent), Aspirins, Alginates
Negative Inotropic agents
• Anti arrhythmics, NDHP CCBS-Diltiazem & Verapamil
• Non selective beta blockers especially in NYHA class IV
particularly when used in large doses
Cardio toxins: Anthracyclines – Anti tumour- doxorubicin
Decongestants, High sodium containing drugs
Precipitating Causes of HFPrecipitating Causes of HF• Arrhythmias, especially atrial fibrillation
• Infections (especially pneumonia)
• AMI, Angina pectoris or recurrent MI
• Anemia, Alcohol excess, Pregnancy
• Iatrogenic - postoperative fluid replacement or
• Poor drug compliance in pts on treatment for HT
• Thyroid disorders—Thyrotoxicosis
• Use of steroids or NSAIDs
• Pulmonary embolism
BMJ Vol . 320, 22 Jan 2000
Changing Pattern of Etiology
Changing Pattern of Etiology
McMurray J J, Stewart S Heart 2000;83:596-602
Major Risk FactorsMajor Risk Factors
Ethnicity – Etiological factors
Ethnicity – Etiological factors
Sosin MD, et al. Eur J Heart Fail 2004;6:831-43
CardiomyopathiesCardiomyopathies
Floor Plan of This TalkFloor Plan of This Talk
Pathophysiology of Heart Failure
Pathophysiology of Heart Failure
Developments in our understanding of the
Pathophysiology of heart failure have been
essential for recent therapeutic advances
After MI, plasma concentration of
norepinephrine is of prognostic value in the
early phase after MI
Natriuretic peptides are also shown to predict
outcome after MI – “The Leukocyte Count of HF”
Cardiac OutputCardiac Output
CO = SV x HRCO is cardiac output expressed in L/min
Normal Cardiac Output is 5 L/min
SV ( Stroke Volume) is volume of blood put out/beat
Pre load, After load and Contractility determine the SV
HR (Heart rate) - number of beats/minute (Chronotrop)
Normally SV = 70 ml/beat. HR = 70/mt; so
CO = 70 x 70 = 4,900 ml/mt or 5 L approximately
Important ConceptsImportant Concepts• Contractility: Contractility is the intrinsic ability of
cardiac muscle to develop force for a given muscle length. It is also referred to as inotropism.
• Pre load: Preload is the muscle (stretch) length prior to contractility, and it is dependent of ventricular filling (or LV end diastolic volume). This is in turn dependent on LV end diastolic pressure and LA pressure. The most important determining factor for pre load is venous return.
• After load: It is the tension (or the arterial pressure) against which the ventricle must contract. After load for the left ventricle is determined by aortic pressure which in turn is dependent on peripheral arterial resistance.
LV Ejection Fraction (EF%)LV Ejection Fraction (EF%)
LV EF% =
LV Diastolic Volume – LV Systolic Volume
LV Diastolic Volume X 100
LV EF% =
(140 ml – 70 ml) = 70 ml
140 ml
LV-EF% = 50% (Normal 50 to 70%)
May go up to 90% with exercise
LV-EF% = 50% (Normal 50 to 70%)
May go up to 90% with exercise
X 100
Mechanisms of Heart failure
Mechanisms of Heart failure
Frank-Starling CurvesFrank-Starling Curves
Sustained LVDF Leads toSustained LVDF Leads to
Complex Mechanisms in HFComplex Mechanisms in HF• Heart Failure is multi system syndrome
– Abnormalities of cardiac and skeletal muscle– Abnormal renal function– Stimulation of sympathetic nervous system– Complex pattern of neuro humoral changes
• Ventricular Remodeling– Damage to the myocytes & extracellular
matrix– Changes in size, shape and function of LV
• Electrical instability – causing arrhythmias• Systemic processes with sequelae in
organs
Pathophysiology of HFPathophysiology of HF
• Decreased cardiac output results in End Diastolic Pressure (LVEDP), LVH, LVD Pulmonary Capillary Wedge Pressure (PCWP)– The development of pulmonary edema
• Activation of Neurohormonal Mechanism– Renin-Angiotensin-Aldosterone- System
(RAAS)– Sympathetic Nervous System (SNS)– Other circulating and paracrine effects
• Counter-regulatory systems– Natriuretic Peptide System (BNP, pro BNP)
Understanding RAASUnderstanding RAAS
Globular
protein
Deca (10 AA)
peptide
Octa (8 AA)peptide
Angiotensin II ReceptorsAngiotensin II Receptors
ARBs ALDO
AT II – Major Effector HormoneAT II – Major Effector Hormone
AT-I (1- 7,9)
Pathological Effects of RAAS
Pathological Effects of RAAS
AT II and Aldosterone Havoc
AT II and Aldosterone Havoc
AT II is the key hormone
• Increased AT II
• Vasoconstriction
• Myocyte hypertrophy
• Myofibril fibrosis Aldosterone release
• Activation of NA
• Activation of ETH
• ED – NO, Inflam.
Aldosterone Excess imp.
• Na and H2O retention
• Hypokalemia
• Volume over load
• Pulmonary edema
• Peripheral edema
• Myocardial apoptosis
• Myocardial fibrosis
• Increased after load
Harmful Effects of Angiotensin II
Harmful Effects of Angiotensin II
Adverse Effects of AldosteroneAdverse Effects of Aldosterone
Glomerulosclerosis
Interstitial Fibrosis
Proteinuria
Renal Failure
LVH
Cardiac Fibrosis
LV Dysfunction
Heart Failure
Endothelial
Dysfunction
Inflammation
Oxidative Stress
Aldosterone
MRA – EplerenoneBrand name: Eplirestat
RAAS Axis and its BlockadeRAAS Axis and its Blockade
RAAS BlockadeRAAS Blockade
Vasoprotection
Sympathetic Nervous System
Sympathetic Nervous System
CO activates baroreceptors - SNS
Effects of Circulating Epinephrine & NE
– Increased Heart Rate
– Increased Blood Pressure
– Increased myocardial oxygen demand
– Toxic effects on myocardium – cell death
– Down regulation of 1 receptors in heart
– Decrease in parasympathetic activity
Effect of Norepinephrine in HF
Effect of Norepinephrine in HF
Circulating Paracrine Effects
Circulating Paracrine Effects
Production of Endothelin (ETH)
– A potent vasoconstrictor through ET1R
in Vasopressin (ADH) from pituitary– Excess water retention and
vasoconstriction
• Excess of Cytokines – TNF, IL-1 & IL-6– Myocyte apoptosis and cardiac cachexia
in circulating Steroids and GH
Counter Regulatory SystemCounter Regulatory System
Natriuretic Peptides in HFNatriuretic Peptides in HF
B-Natriuretic Peptide (BNP)B-Natriuretic Peptide (BNP)
Endothelium – The Endocrine Organ
Endothelium – The Endocrine Organ
Vasodilators
• NO, Bradykinin, Prostacyclin, EDHF, Serotonin, Histamine CNP, Substance P
Inhibitors of SMCG
• NO, Prostacyclin, Bradykinin, Heparin, CNP, TGF-
Inflammation inhibitors - NO
Thrombolytic factors- t-tPA
Vasoconstrictors
• AT-II, Endothelin, TXA2 AA, PGH2,
Promoters of SMCG
• PDGF, BFGF, ILGF Endothelin, AT-II
Promoters of Inflammation
• Superoxide, TNF- ELCAM, ICAM, VCAM
Thrombotic Factors - PAI-1
Vaso Activity of Endothelins
Vaso Activity of Endothelins
Harmful
Helpful
Mixed
Endothelium, Heart, Renal Tubule, VSMC
AT-II, Catacholamines, Insulin, LDL, GF, Stress
Endothelin Antagonists:
Darusentan, Sita
xsentan,
Tezosentan & Bosentan
Other Changes in HFOther Changes in HF
Ventricular RemodelingVentricular Remodeling
McKay RG, et al. Circulation 1986;74:693-702
Ventricular RemodelingVentricular Remodeling
McKay RG, et al. Circulation 1986;74:693-702
• After extensive MI - remodeling occurs – Impaired cardiac contractility– Neuro humoral activation leads to regional
eccentric and concentric hypertrophy of the non-infarcted segment
– Regional thinning and dilation of infarct area
• Factors which affect remodeling are– Large infarct, Anterior infarct, HT, Persistent
occlusion of the artery of the infarct area
Cardiac RemodelingCardiac Remodeling
Na and H2O retention,
Performance
Myocyte hypertrophy, death,
fibrosisDilated and spherical ventricle, thinned
Na and H2O retention,
Performance
Myocyte hypertrophy, death,
fibrosisDilated and spherical ventricle, thinned
The Cardiovascular Continuum
The Cardiovascular Continuum
Ischemia
HT
Important Events after MIImportant Events after MI
“Stunning” and “Hibernation”
“Stunning” and “Hibernation”
• Myocardial “Stunning”– Post ischemic dysfunction– Delayed recovery of the myocardial function
despite restoration of coronary blood flow– In the absence of irreversible damage
• Myocardial “Hibernation”– Persistent myocardial dysfunction at rest– Secondary to reduced myocardial perfusion– Function improves with revascularization– Cardiac myocytes remain viable in
hibernation
“Stunning” and “Hibernation”
“Stunning” and “Hibernation”
• Myocardial “Stunning” and “Hibernation”
– Viable myocardium retains responsiveness to inotropic stimulation
– Can be identified by resting and stress echo, thallium scintigraphy, PET, MR Imaging with gadolinium
– Revascularization may improve the over all ventricular function with beneficial effects on symptoms and prognosis.
Thank You AllThank You All
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Clinical Features,
Staging
Investigations, Scoring
Clinical Features,
Staging
Investigations, Scoringwill follow