ACC & AHA Definition-

Heart failure as a clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.

Because volume overload is not necessary to be present ,the term Heart Failure(HF) is preferred to be term congestive Heart failure.
Systolic heart failure: E/O left ventricular dysfunction.

Diastolic heart failure:E/Odiastolic dysfunction inspite of good systolic function.

Disatolic heart Failure:

When symptoms of heart failure occurs in presence of preserved Left Ventricular function . diastolic dysfunction is impaired relaxation leads to increase in diastolic pressure and increase passive chamber stiffness.

Etiology:
53% non ischaemic cardiomyopathy
38% ischaemic cardiomyopathy

Causes of Heart Failure:

1. Coronary heart disease
2. Hypertensive heart disease
3. Dm and hypertension
4. Valvular heart disease
5. Dilated cardiomyopathy
6. Infiltrative cardiomyopathy
7. Myocardial hypertrophy

 

Mechanism of diastolic dysfunction:

Fibrosis                                                                         Passive chamber stiffness

Cellular disarray

Hypertrophy

Asynchrony                                                                           DIASTOLIC PRESSURE

Abnormal loading

Ischaemia                                                                                 relaxation

Abnormal flux of calcium

 

Stages of heart failure :

ACC/AHA  guidelines:

Stage A: the patient who is at high risk for developing HF but has no structural disorder of heart

Eg:

1. Hypertension
2. Atherosclerotic disease
3. DM
4. patients using cardiotoxins or family h/o CM

↓

THERAPY

 

Goals

1. Treat hypertension
2. Encourage smoking cessation
3. discourage alchohol usage
4. Illicit drug usage
5. Control metabolic syndrome

Drugs: ACE  inhibitors in appropriate patients for vascular disease or DM

Stage B
Structural heart disease but without signs of heart failure

☛ patients with previous MI
☛ LV remodeling including LVH and lowEF
☛ Asymptomatic valvular heart diseases

Therapy

Goals:

All measures under Stage A

Drugs:

☛ ACEI/ARB in appropriate patients
☛ Beta blockers in appropriate patients
☛ Dences in selected patients
☛ Implantable defibrillators

Stage C:

Structural heart disease with prior / current symptoms of heart failure
Eg: Patients with

1. Known structural heart disease amd
2. Shortness of breath , fatigue , reduced exercise tolerance

Therapy

Goals

☛ All measures under Stage A and B
☛ Dietary salt restriction
☛ Diuretics for fluid retention

ACEI

☛ Beta blockers
☛ Drugs in selected Patients:
☛ Aldosterone antagonist

ARBs

☛ Digitalis
☛ Hydralazine/Nitrates

Devices:
☛ Biventricular pacing
☛ Implantable defibrillator

Stage D:

☛ Refractory heart failure requiring specialized interventions
☛ Eg: patients with who have marked symptoms at rest despite maximal medical therapy
☛ Recurrent hospitalized nand cant be discharged with out special interventions

Therapy:

Goals:

1. Appropriate measures in A , B, C
2. Decision re appropriate level of care

Options:

1. Compassionate end of life care / hospice
2. Extra ordinary measures:
3. Heart transplant
4. Chronic ionotropes
5. Permanent mechanical support
6. Experimental surgery or drugs

 

Framingham criteria for CHF :

MAJOR	MINOR
1.     PND 2.     Raised JVP 3.     Cardiomegaly 4.     Rales 5.     S3 gallop 6.     CVP > 16 cm H2O 7.     Acute Pulmonary Edema 8.     Hepato Jugular Reflex 9.     Weight loss >4.5 kg in 5days in response to treatment	1.     Bilateral ankle edema 2.     Nocturnal cough 3.     Dyspnea on ordinary exertion 4.     Hepatomegaly 5.     Pleural effusion 6.     Tachycardia>120 bpm 7.     Vital capacity decreases by 1/3

Presence of 2 major or 1 major and 2 minor indicates heart failure.

Symptoms and signs-

Breathlessness, ankle swelling ,&fatigue are the characteristic symptoms,
Peripheral edema increase JVP & hepatomegaly are the characteristic signs of heart failure.

Signs according to etiology :

1. Left heart failure and pulmonary congestion
   • Pulmonary rales
   • Decreased breath sounds
   • Dullness to percussion
   • Third heart sound
   • Displaced apical impulse
2. Signs of right heart failure
   • Peripheral edema
   • Increase JVP ,prominent V wave and steep Y descent
   • Hepato jugular reflex
   • Ascites
   • Right side third heart sounds
   • Left para sterna heave

3. Low cardiac output:
   • Tachycardia
   • Pulsus alternans
   • Decrease pulsepressure
   • Hypotension
   • Symptoms & correlation of severity of HF is poor relationship because of treatment. Patient having severe dysfunction may show NYHA I symptoms
4. NYHA CLASS
5. KILLIP
6. Minnesota questionnary

 

 

Pathophysiology of symptoms:

1. Increased capillary wedge pressure is responsible for pulmonary edema.
2. Mitral regurgitation – variation in degree influence breathlessness.
3. Abnormalities of pulmonary diffusion , peripheral or respiratory skeletal muscle , general cardiovascular deconditioning or overweight may contribute to sensation of breathlessness
4. Fatigue : more obscure and compounded by difficulties in quantifying this symptoms
5. Peripheral oedema :
6. Increase right heart pressure
7. Capillary permeability for fluid and small proteins
8. Reduced physical activity
9. Impaired cardiac output leads to altered peripheral blood flow –kidney and skeletal muscle.
10. Activation of neuro endocrine system baroreceptor dysfunction important link between vasomotor and neuro endocrine dysfunction . Activation of various cytokines contribute to cardiac dysfunction.

 

Pathophysiologic role of RAS:[renin angiotensin system]

Neuro hormonal effect of impaired cardiac function:
RAS: is get activated in patients with heart failure and important mediator in progression of heart failure.

1. Juxtaglomerular cells of kidney release rennin – proteolytic enzymes in response to decrease in BP and renal perfusion.
2. Generating Angiotensin I from angiotensinogen in lungs cleavage by ACE.

3. Angiotensin II

4. Potent arteriolar and venous vasoconstrictor to return BP and filling Pressure

5. Angiotensin II stimulates release of aldosterone (adrenal cortex) and anti diuretic harmone (ADH) (post pituitary) causing increased Na retention and free water retention respectively

6. Increases blood pressure

7. In long term – angiotension II lead to Na and fluid retention

8. Increase SVR ➙ signs of heart failure

9. Pulmonary congestion

10. Haemodynamic decompression

Neuro hormonal effects of impaired cardiac and effects on circulation

RESPONSE	SHORT TERM	LONG TERM
Salt and water retention	Augments preload	Pulmonary congestion anasarca
Vasoconstriction	Maintain blood pressure of vital organs (brain,heart)	A.Excessive after load , exacerbate dysfunction B. increase cardiac energy expenditure
Sympathetic stimulation	Increase heart rate and ejection	Increase cardiac energy expenditure

 

In addition to cardio renal and cardio circulatory effects . RAS harmones and receptors expressed in myocardium – where they ( AT 1 receptors in myocytes ) contribute for maladaptive growth or remodeling of LV thro complex cascade of

1. Intracellular signal transduction with activate
2. Protein transcription factors initiating RNA transcripts.

Longterm effects of Ang. II on AT1 receptor result in cardiomyocyte hypertrophy , fibroblast proliferation and extracellular matrix deposition ➙ progessive LV remodeling & LV dysfunction

 

Pathophysiology of LV remodeling :

Alteration in myocyte biology

1. Excitation contraction coupling
2. Myosin heavy chain gene expression

• Beta adrenergic desensitization

1. Hypertrophy
2. Myocytolyisis
3. Cytoskeletal proteins

 

Myocardial changes:

1. Myocyte loss – necrosis , apoptosis
2. Alteration in extra cellular matrix
   • Matrix degeneration
   • Replacement fibrosis

Alteration in LV chamber geometry :

1. LV dilation
2. Increase LV sphericity
3. LV wall thickening
4. Mitral valve regurgitation

Mechanical disadvantage because LV remodeling

1. Increased wall stress (after load)
2. Afterload mismatch
3. Episodic subendocardial hypoperfusion
4. Increase O2 utilisation
5. Sustained hemodynamic overloading
6. Worsening activation of compensatory mechanism

In summary : Pathophysiology:

Heart failure as a progressive disorder initiated by an index event which either damages the myocardium directly or disrupts the ability of myocardium to generate force.

Heart failure characterized by declining ventricular functioning and activaton of compensatory adrenergic and salt and water retention pathway

Ejection fraction is maintained initially by

1. Increase LV end diastolic volume
2. Myocardial fiber length
3. Adrenergic mediated myocardial contractility

LV remodeling takes place during this time and while initially adaptive  may independently contribute to HF progression.

Chronic overexpression of molecular mediators of compensation [nor epinephrine , angiotensin II , endothelin , natriuretic peptide , aldosterone , TNF ] lead to detoriation effects on cardiac myocytes and then extracellular matrix

Chronic  exposure of circulating catecholamines result in down regulation of myo beta adrenergic receptors making heart less responsive to ionotropes .

Persistant low CO and increase venous pressure decreases lower and kidney perfusion.

ECG findins in heart failure:

1. Presence of anterior ‘Q’ wave and a LBBB in patients with IHD – good indicator of heart failure.
2. AF
3. S/O left Atrial/LVH .

CXR:

1. Cardiac enlargement
2. Pulmonary venous congestion
3. In acute HF and diastolic failure – cardiac size is normal
4. Interstitial and alveolar pulmonary edema s/o LV dysfunction

LAB: Routine

Specific:

☛ C reactive protein (CRP)
☛ Sr uric acid And Sr urea.BNP levels.
☛ Myocardial enzymes in acute cases
☛ Urine analysis – proteinuria and glycosuria
☛ Hyponatremia and renal dysfunction lead to bad prognosis.

Echocardiography- structural and functional assesment.

                                                                                                                      dr.ajita.

 

Medical management of heart failure :

DRUG CLASS	EXAMPLES
1.     INHIBITORS OF RAS- aldosterone system	ACE inhibitors Angiotension receptor blockers Aldosterone antagonist
2.     Diuretics	Thiazide Loop diurectics Potassium sparing diuretics
3.     Beta blockers	Cardio selective Non selective with vasodilating properties
4.     Digitalis glycosides	Digoxin
5.     Direct acting vasodilators	Inorganic nitrates Hydralazine Cakcium channel blockers
6.     IV positive ionotropes	Dobutamine Phosphor diesterase inhibitors Dopamine
7.     Auxillary Theparies	Anti thrombotic Anti arrhythmic

 

Angiotensin receptor blockers :

Angiotension receptors 2 AT 1 and AT 2

In heart failure stimulation by angiotensin II at At 1 in myocytes – adverse effect

 

AT 1	AT 2
Vaso constriction Cell growth and proliferation Positive ionotropy Aldosterone secretion Catecholamine release	Vasodilation Cell groth inhibition / apoptosis Negative ionotrpy Natriuresis Bradykinin release

 

Mechanism Of Action:

Blocking of AT 1 : Prevents action of Angiotensijn II as the cell preventing vasoconstriction , sodium retention , release of nor epinephrine and delaying or preventing LV hypertrophy and fibrosis

They produce dose dependent decrease in

1. RAP
2. PCWP
3. SVR

e.g;

AGENT	HALF LIFE (HRS)	INTERVAL	INITIAL DOSAGE	TARGET DOSAGE
LOSARTAN	6-9	QID	25	50
VALSARTAN	9	BD	40	160
IRBESARTAN	11-15	QID	75	150
CANDESARTAN	3.5	QID	4	32

 

Aldosterone receptor Antagonist:

Aldosterone- A mineralocorticoid is important component of neurohormonal of HF . Adverse effects of aldosterone as—-

---

ALDOSTERONE

ANG II ENDOTHELIN

SALT

 

AUTONOMIC DYSFUNCTION HRV,     QRS DISPERSION BARO RECEPTOR SENSITIVE MYO UPTAKE NE

 

ROS NO

NF-KB AP- 1

ENDOTHELIAL DYSFUNCTION

 

PAI-1

PLATELET ACTIVATION AND ADHESION

FIBRINOLYSIS FIBROSIS

 

 

 

ATHEROSCLEROSIS

ISCHAEMIC EVENTS

 

 

 

 

CV MORTALITY

 

PROGRESSIVE HEART FAILURE   RENALFAILURE

 

SCD

 

 

 

CELLULAR PROLIFERATION GROWTH/ HYPERTROPHY FIBROSIS APOPTOSIS

---

Trial : RALES MAL – Randomised Aldactone Evaluation Study

•  Spironolactone
• Eplerenone

Indications:

Stages C & D

Adverse effects:

1. Spironolactone occupies androgen receptors leaving unopposed estrogen receptos and thus predispose to effects such as painful gyanecomastia , menstrual disorders.
2. Digoxin also have estrogen like activities , spironolactone have K+ sparing effect so digoxin induced hypokalemia s/e does not occur with spironolactone.

 

Beta Blockers:

Sympathetic nervous system and role in heart failure:

1. SNS leads to pathologic LV growth and remodeling
2. Myocyte thicken and elongate with eccentric hypertrophy
3. Wall stress of LV increase ➔ promoting subendocardial ischaemia ➔ celldeath ➔ contractile dysfunction
4. Leads to altered gene expression with a shift to a fetal like phenotype (down regulation of cardiac alpha action and alpha myosin heavy chain and up regulation of fetal forms of beta myosin heavy chain )
5. Down regulation of calcium ATP ase and impairment of contractility and relaxation .
6. Cause programmed cell death.

Beta adrenergic blocker and heart failure:-

1. Improve systolic function and myocardial enegetics and reversal of pathologic remodeling .
2. Heart rate – determinant of myocardial O2 consumption is reduced by beta 1 receptor blockade
3. Beta blocker reverses genetic expression to focal myocytes with improvement in LV function
4. Beta blocker limit the disturbances in excitation contraction coupling and predisposition to ventricular arrhythmias with HF
5. Evolving concept – beta 3 adreno receptors in HF unlike beta 2 and beta 1

Beta 3 – activation decreases contractility
At present no beta 3 antagonist

Beta blockers classification

First generation

1. Both block B1 and B2 non selective no ancillary effects
   1. Propanolol
   2. Timolol

2. Second generation:- specific beta 1 adreno receptor , no aucillary effects.
   1. Metoprolol
   2. Bisoprolol
   3. Atenolol
3. Third generation:- b1+b2 blockage , vasodilatation, increase insulin
   1. Bucindol sensitivity aand increase antioxidant effect
   2. Carvedilol beta3 adreno receotor selectivity
   3. Labetolol

Trials

☛ Merit – HF – metxl
☛ BEST – Bucinlol
☛ COPERNICUS – carvedilol
☛ CIBIS II – Bisoprolol
☛ Clinicalpractice – all patients EF < 40% stage B to D
☛ No sudden withdrawl
☛ Onset of action comes with in 3 months
☛ Side effect : fatigue , hypotension , brady cardia

 

 

DRUG	RECEPTOR	STANDARD DOSE	TARGET
METOPROLOL CR/XL	BETA 1	12.5 QID	200 QID
BISOPROLOL	BETA 1	1.25 QID	5-10 QID
CARVEDILOL	B1 B2>>BA2	3.125 QID	25-50 QID

 

VASO DILATORS:

Hydralazine – Isosorbide di nitrate
Reduce preload , afterload, decrease heart rate
Improves exercise capacity , increase left ventricular EF

 

Trial

• V-HFT1 – vasodilator HF trial
• African American HF trial

Recommendations:

Class I : in African – American with combination of CAE , beta blockers and diuretics
Class II : stage C
Dosage : nitrates: initial 10 mg 3 tid max 40 mg – poor compliance patient
Hydralazine – dose 100mg tid
S/E : headache , dizziness

 

ADJUNCTIVE DRUGS:

1. Diuretics :
2. Decrease dyspnea
3. Wall stress
4. Correct hyponatremia

Loop diuretics: inhibit Na+ reabsorption at ascending loop of henle

Decrease preload by increasing vascular capacity

S/E:

1. electrolyte depletion
2. prolong action of muscle relaxant
3. hyperglycemia
4. insulin resistance
5. skin rash , hyper, ototoxicity

 

Digoxin :

Indirect mechanism of positive ionotrphy begins with inhibition of myocardial sacrolemmal Na+/K+ ATP ASE – Increase intracellular Na+ from the Na+/Ca+ exchanger to extrude Na+ from the cell increasing intracellular  Ca+

☛ Increase Ca+ ➙ increase contractile function
☛ Vagotonic
☛ Sympatholytic th carotid sinus baroreceptors.
☛ In Af digoxin shows the rate of conduction at A V node
☛ Increase HR variability beneficial action as autonomic NS in HF
☛ Digoxin – narrow theraupeutic / toxicity ratio
☛ Serum level 0.7 to 1.1 ng/ml
☛ Ventricular arrhythmias may be caused by calcium dependent after potentials
☛ Treatment: purified anti digxin FAB fragments from digoxin specific antisera

Trials:

☛ DIG
☛ PROVED
☛ RADIANCE

1. Vasopressin receptor antagonists:
2. Anticytokinins
3. Endothelin receptor antagonists
4. Vasopeptide inhibitors

Studies are going on and not much proven beneficial

 

Non pharmacologic theraphy:

1. Class I :

Stage C – cardiac resynchronization + implantable defibrillator

2. Stem cell theraphy

Pharmacological treatment : DHF

General approach  3 main components

1. Treatment should reduce symptoms by decrease pulmonary venous pressure during rest and exercise by reducing LV volume maintaining AV synchrony and tachycardia
2. Treatment should target underlined disease that cause DHF – ventricular remodeling
3. Neuroharminal activation – alters by the HF and cause ventricular dysfunction
4. Drugs:
   1. Metoprolol XL/LR more beneficial
   2. Diuretics and NTG – small doses
   3. Calcium channel blockers
   4. ACE inhibitors

Management of acute exacerbation of chronic heart failure :

☛ Hospitalization
☛ Vasodilators – NTG 20 to 40 mcg/min
☛ Nesritide
☛ Ionotropes – dobutamine and milrinone
☛ Alternate : MCS devices
☛ Cardiac transplant
☛ CABG
☛ Bi ventricular pacing.