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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.

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Heart failure basics to recent advances

Heart Failure Basics to Recent Advances

Dr. R.V.S.N. Sarma., M.D., M.Sc.(Canada), FIMSA

Consultant Physician and Cardiometabolic Specialist




The very essence of cardiovascular practice is early detection of heart failure

“The very essence of cardiovascular practice is early detection of Heart Failure”

Sir Thomas Lewis, 1933


Hf is a big subject
HF is a ‘BIG’ Subject detection of Heart Failure”

  • 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 failure
Detection of Heart Failure detection 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 ? detection of Heart Failure”

  • 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 points
Important Points detection of Heart Failure”

  • 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 talk1
Floor Plan of This Talk detection of Heart Failure”


Definitions of heart failure
Definitions of Heart Failure detection 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 hf
Definition of HF detection of Heart Failure”

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 failure
Types of Heart Failure detection 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 talk2
Floor Plan of This Talk detection of Heart Failure”


Heart failure some statistics
Heart Failure – Some Statistics detection of Heart Failure”

  • 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 detection of Heart Failure”


Epidemiology of heart failure1
Epidemiology of Heart Failure detection of Heart Failure”

Data from Framingham Heart Study per 1000 population


Incidence of heart failure
Incidence of Heart Failure detection of Heart Failure”

McKee PA et al. Framingham study; N Eng J Med 1971; 285: 1441-6


Ethnic differences in hf
Ethnic Differences in HF detection of Heart Failure”

Sosin MD, et al. Eur J Heart Fail 2004;6:669-72


Age mi and heart failure
Age, MI and Heart Failure detection of Heart Failure”


Prevalence of chronic af in hf
Prevalence of Chronic AF in HF detection of Heart Failure”

181 92 9970 11062 11016 No in study

Cleland JG, et al. Heart Fail Rev 2002;7:229-42


Systolic heart failure
Systolic Heart Failure detection of 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 failure
Diastolic Heart Failure detection of 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 detection of Heart Failure”

McMurray JJ, et al. Lancet 2005;365:1877


Floor plan of this talk3
Floor Plan of This Talk detection of Heart Failure”


Causes of heart failure
Causes of Heart Failure detection of Heart Failure”

  • Coronary Artery Disease (MI, IHD) (2/3 of cases)

  • Hypertension(common fore runner of LVSD, LVDD)

  • 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 failure
Drugs and Heart Failure detection of Heart Failure”

Many 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 hf
Precipitating Causes of HF detection of Heart Failure”

  • 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 detection of Heart Failure”

McMurray J J, Stewart S Heart 2000;83:596-602


Major risk factors
Major Risk Factors detection of Heart Failure”


Ethnicity etiological factors
Ethnicity – Etiological factors detection of Heart Failure”

Sosin MD, et al. Eur J Heart Fail 2004;6:831-43


Cardiomyopathies
Cardiomyopathies detection of Heart Failure”


Floor plan of this talk4
Floor Plan of This Talk detection of Heart Failure”


Pathophysiology of heart failure
Pathophysiology of Heart Failure detection 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 output
Cardiac Output detection of Heart Failure”

CO = SV x HR

CO 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 concepts
Important Concepts detection of Heart Failure”

  • 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 LVend diastolic volume). This is in turn dependent on LV end diastolic pressureand 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%) detection of Heart Failure”

LV EF% =

LV Diastolic Volume – LV Systolic Volume

LV Diastolic Volume

X 100

LV EF% =

(140 ml – 70 ml) = 70 ml

140 ml

X 100

LV-EF% = 50% (Normal 50 to 70%)

May go up to 90% with exercise


Mechanisms of heart failure
Mechanisms of Heart failure detection of Heart Failure”


Frank starling curves
Frank-Starling Curves detection of Heart Failure”


Sustained lvdf leads to
Sustained LVDF Leads to detection of Heart Failure”


Complex mechanisms in hf
Complex Mechanisms in HF detection of Heart Failure”

  • 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 hf
Pathophysiology of HF detection of Heart Failure”

  • 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 raas
Understanding RAAS detection of Heart Failure”

Globular protein

Deca (10 AA)

peptide

Octa (8 AA)

peptide


Angiotensin ii receptors
Angiotensin II Receptors detection of Heart Failure”

ARBs

ALDO


At ii major effector hormone

ACE detection of Heart Failure”

ACE2

RENIN

ACE2

AT II – Major Effector Hormone

AT-I (1- 7,9)

Vasoconstriction

 Sympathetic

 Aldosterone

Non ACE pathways


Pathological effects of raas
Pathological Effects of RAAS detection of Heart Failure”


At ii and aldosterone havoc
AT II and Aldosterone Havoc detection of Heart Failure”

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 detection of Heart Failure”


Adverse effects of aldosterone
Adverse Effects of Aldosterone detection of Heart Failure”

Aldosterone

Glomerulosclerosis

Interstitial Fibrosis

Proteinuria

Renal Failure

LVH

Cardiac Fibrosis

LV Dysfunction

Heart Failure

Endothelial

Dysfunction

Inflammation

Oxidative Stress

MRA – Eplerenone

Brand name: Eplirestat


Raas axis and its blockade
RAAS Axis and its Blockade detection of Heart Failure”


Raas blockade
RAAS Blockade detection of Heart Failure”

Vasoprotection


Sympathetic nervous system
Sympathetic Nervous System detection of Heart Failure”

  • 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 detection of Heart Failure”


Circulating paracrine effects
Circulating Paracrine Effects detection of Heart Failure”

  •  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 system
Counter Regulatory System detection of Heart Failure”


Natriuretic peptides in hf
Natriuretic Peptides in HF detection of Heart Failure”


B natriuretic peptide bnp
B-Natriuretic Peptide (BNP) detection of Heart Failure”


Endothelium the endocrine organ
Endothelium – The Endocrine Organ detection of Heart Failure”

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 detection of Heart Failure”

Harmful

Endothelin Antagonists: Darusentan, Sitaxsentan, Tezosentan & Bosentan

Helpful

Mixed

Endothelium, Heart, Renal Tubule, VSMC

AT-II, Catacholamines, Insulin, LDL, GF, Stress


Other changes in hf
Other Changes in HF detection of Heart Failure”


Ventricular remodeling
Ventricular Remodeling detection of Heart Failure”

McKay RG, et al. Circulation 1986;74:693-702


Ventricular remodeling1
Ventricular Remodeling detection of Heart Failure”

  • 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

McKay RG, et al. Circulation 1986;74:693-702


Cardiac remodeling
Cardiac Remodeling detection of Heart Failure”

Na and H2O retention,  Performance

Myocyte hypertrophy, death, fibrosis

Dilated and spherical ventricle, thinned


The cardiovascular continuum
The Cardiovascular Continuum detection of Heart Failure”

Ischemia

HT


Important events after mi
Important Events after MI detection of Heart Failure”


Stunning and hibernation
“Stunning” and “Hibernation” detection of Heart Failure”

  • 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 hibernation1
“Stunning” and “Hibernation” detection of Heart Failure”

  • 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 all
Thank You All detection of Heart Failure”


Clinical features staging investigations scoring

Clinical Features, Staging detection of Heart Failure” Investigations, Scoring

will follow


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