Heart Failure Stanko P © Kristína Repová, MD, PhD. Institute of Pathophysiology, Faculty of Medicine, Bratislava
Heart Failure
Stanko P
© Kristína Repová, MD, PhD.
Institute of Pathophysiology, Faculty of Medicine, Bratislava
• Preload
• Afterload
BLOOD PRESSURE(heart work)
Cardiac Output (CO)
Stroke Volume (SV)
Preload
Blood volume
Venous compliance
Contractility
Afterload
Heart Rate (HR)
Peripheral Resistance (PR)
Vessel length
Vessel diameter
Vasoconstriction
Vasodilation
Vessel wall remodelling
Viscosity of blood
Compliance of large arteries
Epidemiology of HF
◼ Prevalency: 2 - 3 %
◼ after 75 years: 10 -20 %
◼ In younger individuals is more frequent in men
◼ 50 % of patients dies within 4 years
◼ 40 % of patients hospitalized with HF dies or is re-
admitted within 1 year
Pathomechanism of HF
◼ Clinical understanding of HF =
congestive HF
• dyspnoea, edema
• compensatory mechanisms
(hypertrophy)
◼ Pathophysiological understanding
of HF = reduced pefusion of
peripheral tissues
• oliguria, muscle weakness, fatigue,
dyspeptic complaints
Causes of HF
1. Chronic hemodynamic overload
2. Restricted filling of ventricles
3. Myocardial impairment
4. Arrythmias
Causes of HF
1. Chronic hemodynamic overload
◼ Pressure:
◼ Left: hypertension, stenosis and coarctation of aorta
◼ Right: pulmonary hypertension, a. pulmonalis stenosis
◼ Volume:
◼ Mitral, aortic insufficiency, arterio-venous shunts, hyperkinetic
circulation
2. Restricted filling of ventricles
◼ Impaired ventricular dilation
◼ Disorder of the ventricular filling
Causes of HF
3. Myocardial impairment
◼ Ischemic heart disease
◼ Cardiomyopathies
◼ Toxic substances: ethanol, diphtheria, drugs
◼ Endocrinopathies: DM, hyper-/hypo-thyreoidism
4. Arrythmias
◼ Extreme tachyarrhythmia: supraventricular tachycardia,
fibrillation, flutter
◼ Extreme bradycardia: sinus, AV block
Forms of Heart Failure (HF)
◼ Acute
◼ Chronic
◼ Right
◼ Left
◼ Systolic
◼ Diastolic
◼ High-output HF
◼ Low-output HF
◼ Compensated
◼ Decompensated
◼ Forward
◼ Backward
Forward / backward HF
◼ insufficient activity of different
organs (GIT, kidney, liver, brain,
etc.).
◼ Dyspnea
◼ Edema
Dyspnoea
➢ Subjectively perceived sensation of breathlessness
◼ Exertional dyspnea◼ Symptomless during rest
◼ physical activity → Sp. → vasoconstriction → venous return → pulmonary pressure → pulmonary compliance
◼ Orthopnea◼ Dyspnea in horizontal position
◼ blood redistribution from distal parts into the heart
◼ Paroxysmal nocturnal dyspnea◼ horisontal position + PSp. during sleeping → contractility and activity of centre of breathing
Edema
◼ RV HF!
◼ Swelling of ankles, feet
◼ Right hypochondrial pain: liver distension
◼ Abdominal swelling (ascites)
◼ Loss of appetite
◼ Malabsorption: bowel edema
◼ ↑ in weight: fluid retention
Pulmonary edema
➢ Accumulation of excessive amount of fluid in pulmonary
interstice or in alveoli
◼ ↑ hydrostatic pressure in pulmonary capillaries
◼ ↑ permeability of capillary wall
◼ ↓ colloid osmotic pressure in blood (hypoproteinemia)
◼ hypoxemia of the liver … ↓ albumin synthesis
◼ renal hypoperfusion … proteinuria
➢ Breathlessness, cyanosis, breath sounds: crackles,
wheezes, decreased breath sounds at bases (effusions);
expectoration of pink foamy sputum, horror mortis
Fatigue and lethargy
◼ Impaired muscle blood flow
◼ Accumulation of lactate
◼ ↓ cerebral blood flow
◼ Somnolence, sleep disorders, confusion
Dyspeptic syndrome
➢ Insufficient perfusion of digenstive organs
◼ Impairment of digestion, absorption of nutrients
◼ ↓ detoxication function of liver
◼ ↓ proteosynthesis in liver
◼ ↓ pancreas functions
◼ Generalized ↓ of muscular mass
◼ Cardiac cachexia
Cyanosis➢ Blue color of the skin and mucose membranes
◼ ↑ reduced hemoglobin (>50 mg/L)
◼ Peripheral cyanosis
◼ Normal saturation
◼ Vasoconstriction: blood stagnating in tissues: cold, shock, HF
◼ Cold, pale auricles, nose, cheeks, external lips, tips of fingers and toes
◼ Central cyanosis
◼ ↓ saturation
◼ ↑ physical exercise, (inborn) heart defects with right-left shunts, pulmonary diseases, HF
◼ Peripheral vasodilation: warm skin, dilated veins
◼ Cyanotic tongue, palate, internal mucose of lips
◼ Polyglobulia, clubbed fingers
Compensatory mechanisms
Pathologic process
Compensated HF Decompensated HF
Without clinical signs of HF With clinical signs of HF
Compensatory mechanisms
◼Acute
◼Frank-Starling mechanism
◼Catecholamines
◼Chronic
◼Myocardial hypertrophy
Acute compensatory mechanismsFrank-Starling mechanism
◼ ↓ ejection fraction ... ↑ end-diastolic volume in ventricles ...
myocyte stretching ... ↑ sarcomere length ... ↑ troponin C
sensitivity to Ca2+ ... ↑ cross-link actin and myosin filaments
... ↑ contraction ... ↑ stroke volume
◼ Maximal force of contraction: sarcomere length near 2.2 um
◼ > 2.2 um ... ↓ myofilament overlapping (HF)
◼ < 2.2 um ... ↓ troponin C sensitivity to Ca2+
↓ ejection fraction ↑ contraction
Low-output vs. high-output HF
◼ Low-output HF
◼ cardiac output lower than before HF, under effort doesn`t increase sufficiently
◼ CAD, hypertension, dilatative cardiomyopathy, valvular, pericardial diseases
◼ High-output HF
◼ cardiac output during HF is HIGHER than before HF, cannot supply inadequately high requests
◼ Thyreotoxicosis, Paget’s disease, beri-beri, anemia, septicaemia, arteriovenous fistulae
◼ Warm extremities, normal or widened pulse pressure
Acute heart failure (AHF)
◼ Sudden deterioration of cardiac function
◼ Acute compensatory mechanisms set on
◼ Hypotension without edemas, acute onset of
dyspnea, pulmonary edema
◼ LV HF: myocardial infarction, arrythmia, acute
valve dysfunction
◼ RV HF: mitral insufficiency, massive pulmonary
embolism
Chronic heart failure (CHF)
◼ Gradual progressive loss of cardiac function
◼ Partly compensated by regulatory mechanisms that
become maladaptive
◼ Peripheral edemas, BP does not change
◼ LV HF: volume (valvular insufficiency) or pressure
(hypertension, valvular stenosis) overload or heart muscle
disease (MI, cardiomyopathy, myocarditis)
◼ RV HF: precapillary, capillary or postcapillary
pulmonary hypertension -> cor pulmonale or
tricuspidal valvular disease.
Systolic dysfunction
◼ myocardial contractility◼ myocardial damage: ischemia, inflammation, intoxication (ethanol, cocain,
amphetamins), ionic changes
◼ volume overload
◼ afterload◼ preddure overload
◼ stenosis of aortic valve, arterial hypertension
◼ Failure of left ventricle to eject blood in systole→ ventricular volume → ventricular pressure → systolic volume → ventricular hypertrophy
Diastolic dysfunction
◼ Impaired ventricular dilation
◼ hypertrophy, fibrosis
◼ increased resistance during ventricular filling: filling pressure →
pulmonary/venous congestion
◼ exertional dyspnoea
◼ aortic stenosis, hypertension, hypertrophic cardiomyopathy
◼ Disorder of ventricular filling
◼ mitral stenosis, tamponade, constrictive pericarditis, tachyarrhythmias
Systolic dysfunction Diastolic dysfunction
↑ end-diastolic volume
atrium
Left side
Pulmonary edema
Right side
Peripheral edema
Inadequate filling of ventricle
↑ end-diastolic pressure
Inadequate empting of ventricle
◼ Physiologic hypertrophy
◼ Pathologic hypertrophy
Chronic compensatory mechanismsMyocardial hypertrophy
Physiologic hypertrophy◼ ontogenetic development
◼ adaptation to increased physical activity
◼ the intensity and duration of overload do not exceed particular measure
◼ overload develops gradually
◼ function of each mass unit is normal or even increased: ◼ enlargement of the muscle mass
◼ improvement of contractility of each mass unit … ↑ systolic function
◼ the content of connective tissue does not increase … elasticity … diastolic function
Chronic compensatory mechanismsMyocardial hypertrophy
Pathologic hypertrophy
◼ hypertrophy of myocytes (↑ length / width)
◼ volume / pressure overload
◼ hormonal stimulation: NE, Ang II
◼ ↑ non-myocytic cells in myocardium
◼ Endothelial cells … endothelins:
◼ Mitogenic ability … stimulation of growth of smooth muscle
cells of vessels and of fibroblasts
◼ Fibroblasts … ↑ production of collagens … fibrosis
Chronic compensatory mechanismsMyocardial hypertrophy
◼ Concentric hypertrophy
◼ Pressure overload (↑ LV end-diastolic wall stress)
◼ ↑ wall thickness / ventricular volume
◼ ↑ afterload
◼ stenosis, coarctation of aorta, arterial hypertension,
obstructive hypertrophic cardiomyopathy, stenosis of a.
pulmonalis, pulmonary hypertension
◼ hypoperfusion of the subendocardium … worsening of
LV function
◼ expression of stretch-activated genes: Ang II,
endothelin, TNF
Chronic compensatory mechanismsMyocardial hypertrophy
◼ Eccentric hypertrophy
◼ Volume overload (↑ LV end-diastolic volume)
◼ ↓ wall thickness / ventricular volume
◼ LV wall thinning, dilating
◼ ↑ preload
◼ aortic, mitral valve insufficiency, pulmonal, tricuspidal
valve insufficiency, atrial septum defect
Chronic compensatory mechanismsMyocardial hypertrophy
◼ Heart enlargement, ventricular wall is absolutely or relatively thinner
◼ Primary dilation
◼ Acute hemodynamic overload
◼ ventricular wall is absolutely thinner vs. normal
◼ Secundary dilation
◼ Chronic hemodynamic overload ... hypertrofic, but failing heart, exhausted compensatory mechanisms
◼ hypertrophied ventricular wall is getting thinner
Myocardial dilation
Peripheral compensatory mechanisms
◼ Neurohumoral: Sp., PSp. activity, RAAS, ADH, ANP
◼ Blood redistribution → centralization of blood flow
◼ Hormonal: tyroxin, growth hormone, dopamine
◼ oxygen extraction from capillary blood → peripheral cyanosis
◼ red blood cells count
Angiotensinogen
Angiotensin I
Angiotensin II
Aldosteron
fluid, Na+
retention
↑ blood volume
↑ preload
adrenalshypophysis
ADHthirst
systemic
vasoconstriction
↑ afterload
Myocardial,
vascular
hypertrophy
Renin
Angiotensin converting
enzyme (ACE)
Renin-angiotensin-aldosteron system (RAAS)
↑ BP
Fibroblasts Cardiomyocytes Endothelium
Tissue Ang II
cardiomyocyte
hypertrophyproliferation vascular wall
hypertrophy
Myocardial remodeling
Myocardial hypertrophy (volume/pressure overload)
↑ preload ↑ afterload ↑ Sp
Systemic (plasma) Ang II
↑ blood osmolarity ↓ blood volume ↓ BP
ADH from hypothalamus
↑ amount of aquaporines in
collecting tubules
↑ water rearpsorption
↓ blood osmolarity ↑ blood volume
Systemic
vasoconstriction
↑ BP
Antidiuretic hormone (ADH) = Vasopressin
Acute atrial
stretching
ANP secretion from atrial cardiomyocytes
↑ glomerular filtration
↑ Na+ excretion
↓ aldosterone, ADH,
renin
↓ preload
↓ peripheral
resistance
↓ BP
↑ extracellular fluid volume
↑ Na+ income
Chron. Heart failure
Volumexpansion
Natriuresis and diuresis
Atrial natriuretic peptide (ANP)
Adrenalin, noradrenalin, ang. II, aldosterone,
ADH
…
preservation of the perfusion of vital organs on
the expense of increased afterload
…
deterioration of heart failure
Centralization of the circulation
Decompensated HF
◼ Exhausted compensatory mechanisms
◼ Stress reaction:
◼ Catecholamines
◼ RAAS
◼ Adequate perfusion through vital organs (heart, brain, kidneys)
◼ Relative ischemia of peripheral organs (skin, digestive tract, muscles, …)