Heart Failure Flashcards
General heart facts
- Consumes more energy than any other organ
- Cycles 6kgs of ATP / day
- Beats about 100,000 / day (over a billion times in a life time)
- Pumps 10 tons of blood through the body
Heart failure
- The heart is unable to pump blood at a rate commensurate with the requirements of metabolizing tissues
Prevalence of heart failure
- 2 million patients
- 400,000 new cases/yr
- 200,000 deaths/yr
- Most common DSC dx in patients > 65
Classifications of heart failure
- Acute
- Chronic
- Systolic Dysfunction
- Diastolic Dysfunction
- Low / High Output Failure
- Forward / Backward Failure
Systolic dysfunction
- Progressive deterioration of myocardial contractile function
- Left ventricular systolic dysfunction
- Increased end diastolic volume (EDV)
- Left ventricular dilatation
- Ejection fraction < 45%
Diastolic dysfunction
- Inability of the heart chamber to relax/expand
- Increased stiffness of left ventricle
- Inadequate filling of left ventricle
- Diminished stroke volume (SV)
- Ejection fraction > 45%
Hypertropic cardiomyopathy histological findings
- Disarray of myocytes
- Interstitial fibrosis
Compensatory mechanisms in heart failure in maintaining perfusion
- Frank Starling mechanism
- Myocardial hypertrophy
- Neurohormonal systems
Frank Starling mechanism
- Increase venous return
- Increases ventricular preload
- Increases stroke volume
- Stretching myocytes increases force generation (enhances contractility)
- Heart ejects additional return
Neurohormonal regulatory systems
- Release of neurotransmitters (such as NE)
- Activation of the renin-angiotensin-aldosterone system
- Release of atrial natriuretic peptide
Results of neurotransmitter release as a compensatory mechanism
- Increases HR
- Augment myocardial contractility
- Increases vascular resistance
Precipitating causes of actue heart failure
- Myocardial Infarction (LV)
- Pulmonary Embolism (RV)
- Malignant Hypertension
Precipitating causes of chronic heart failure
- Systemic Hypertension (LV)
- Valvular Heart disease (LV)
- EtoH related DCM
- COPD (RV)
Mitochondrial biogenesis and enzyme production
- Peroxisome proliferator-activated receptor gamma coactivator - 1 alpha (PGC-1alpha) (Master Regulator)
- Mitochondrial oxidative energy metabolism is regulated at the level of gene transcription
Physiological hypertrophy is associated with
- Increased PGC-1 expression
- Expansion of mitochondrial volume density and oxidative capacity
Pathological hypertrophy is linked to
- Decreased PGC-1
- Mitochondrial dysfunction
Transcriptional control of PGC-1
- PGC-1 coactivators dock to transcription factor
- Targets protein complexes that activate transcription
- PPAR binds nuclear receptor response elements (NRRE)
- PPAR recruits PGC-1
- PGC-1 facilitates interactions with other coactivators with enzymatic activity
- PGC-1 directly interacts with the transcription initiation machinery (TRAP/DRIP)
- Provides a molecular bridge between the coactivator complex and RNA polymerase II (Gene Expression)
Early heart failure progression to heart failure
- Perturbations in energy utilization (Glucose)
- Metabolic shift due to:
- Myocyte energy insufficiency
- Reduced capacity of mitochondrial ATP production
Hypertrophic pathway activation (metabolic event precipitating heart failure)
- Ca2+ / Calcineurin / Nuclear Factor of Activated T Cells
- Myocardial G-protein–coupled receptors (GPCRs)
- Adrenergic, angiotensin, and endothelin (ET-1) receptors
- Phosphoinositide 3-Kinase / Akt / Glycogen Synthase
- Myocyte Enhancer Factor-2 / Histone Deacetylases
- Small G Proteins
Myocardial G-protein coupled receptors serve a fundamental role in
- Cardiac hypertrophy by activating hypertrophic gene program activation
Pathology of heart failure sequence (1st half)
- Increased mechanical load = increased subcellular components
- Increased myocytes (sarcomeres) without increase in capillary nuumber
- Increased intercapillary distance = increased oxygen consumption (hypertrophy)
Pathology of heart failure sequence (2nd half)
- Enlarged muscle mass with increased metabolic demands
- Increased wall tension
- Heart rate increases
- Increased contractility (inotropic state, or force of contraction)
Patterns of hypertrophy
- Pressure overloaded ventricles
- Volume overloaded ventricles
Pressure overloaded ventricels
- Essential hypertension
- Aortic stenosis
Pressure overloaded ventricles (concentric hypertrophy) results
- Stimulates deposition of new sarcomeres (Parallel)
- Hypertrophy of the left ventricle (concentric)
- Reduction in cavity diameter
Volume overloaded ventricles
- Ventricular dilation
- Dilated cardiomyopathy
Volume overloaded ventricles (eccentric hypertrophy) results
- New sarcomere deposition (in series)
- Increased cell length and width
- Dilation with increased ventricular diameter
- Wall thickness may be increased, normal or less than normal
Measure of hypertrophy
- Heart weight
Pressure vs. volume overload hypertrophy
- Hypertrophy with and without dilation
Characteristics of cardiomyopathic remodeling
- Damaged and dysfunctional mitochondria
- Energy-deficient state
- Intra-myocellular lipid accumulation
- Reactive oxygen species generation
Hallmark of myocardial remodeling
- Increased myocardial volume and mass with net loss of myocytes
- Larger myocytes die
- Increased load placed upon remaining myocytes
- Progenitor cell stimulation
Counter-regulatory effects that decline in myocyte and myocardial remodeling
- Nitrous oxide
- Prostaglandins
- Bradykinin
- Atrial natriuretic peptide and B-type
Decline in counter-regulatory effects during myocardial remodeling results in
- Reduction of cardiac output
Consequences in reduction of cardiac output
- Release of vasoconstrictors
- Vasoconstriction increases calcium concentrations in myocytes
Vasoconstriction increasing calcium concentrations in myocytes causes
- Contractility augmentation
- Impairment in relaxation
Impairment of relaxation secondary to increased calcium concentration in myocytes results in
- Increased β-adrenergic activity
- Activation of RAAS
Peroxisome proliferator-activated receptors cause
- Abnormalities in myocardial energy metabolism
- Maladaption
Abnormalities in myocardial energy metabolism
- Suppression of FA oxidation
- Increased glucose utilization
Maladaptions caused by peroxisone proliferator-activated receptors
- Lipid accumulation
- Lactic acid accumulation
- Diminished maximal ATP generation
Systemic manifestations of left and right ventricular heart failure
- Accumulation of excess fluid behind one or both ventricles
- Activation of neurohormonal mechanisms
- Organ dysfunction secondary to inadequate perfusion
Left ventricular failure morphological findings seen in
- Heart
- Lungs
- Kidneys
- Brain
Morphological findings of left ventricular heart failure in the heart
- Hypertrophy and fibrosis in the myocardium
- Secondary enlargement of the left atrium with resultant atrial fibrillation
Morphological findings of left ventricular heart failure in the lungs
- Pulmonary congestion and edema
- Widening of alveolar septa
- Fluid in the alveolar spaces
- Heart failure cells
Pulmonary congestion and edema radiographic findings
- Kerley B lines on x-ray
- Perivascular and interstitial transudate
Clinical manifestations of left ventricular heart failure in the lungs
- Dyspnea
- Orthopnea
- Paroxysmal Nocturnal Dyspnea
Left ventricular heart failure morphology in the kidneys
- Activation of the RAAS
- Prerenal Azotemia
- Manifestations of edema
Left ventricular heart failure morphology in the brain
- Hypoxic Encephalopathy
Hypoxic Encephalopathy causes
- Impaired judgement / memory
- Inattentiveness
- Confusion
- Motor incoordination
Causes of right ventricular heart failure
- Consequence of left-sided heart Failure
- Pure right-sided heart failure
- Cor Pulmonale
Morphological findings of right ventricular failure in the liver and portal system
- Congestive Hepatomegaly (cardiac cirrhosis)
- Centrilobular Necrosis
- Congestive Splenomegaly
- Ascites
Morphological findings of right ventricular failure in the subcutaneous tissues
- Peripheral dependent edema
- Ankle (pedal) edema
- Pretibial edema
- Presacral
Coronary circulation
- Right coronary artery (RCA)
- Left coronary artery (LCA)
- Left anterior descending
- Left circumflex
Evolution of morphological changes in MI
- ½ - 4hr: waviness of fibers
- 4 - 12hr: coagulation necrosis, edema, hemorrhage
- 1 - 3days: loss of nuclei, coagulative necrosis, neutrophil infiltrate
- 3 - 7days: dead myofibrils, phagocytosis by macrophages
- 7 - 10days: Fibrovascular, granulation tissue
- > 2mo: collagenous scar
Myocardial infarction laboratory findings
- CK - MB (elevated)
- Troponin T (elevated)
- Troponin I (elevated)
- LDH (elevated)
- CK = Creatine Kinase
- LDH = Lactate Dehydrogenase
Complications associated with MI
- Cardiac rupture (7-10 days)
- Arrhythmias
Diabetic cardiomyopathy (DCM) is characterized by
- Progressive cardiac hypertrophy
- Dilation
- Contractile dysfunction
Causes of diabetic cardiomyopathy
- Myocarditis
- EtoH and toxins
- Pregnancy associated
- Genetic
- Idiopathic
Pathology of diabetic cardiomyopathy
- Large flabby heart
- Dilation of all chambers
- Thinning of ventricular walls
- Mural thrombi (source of thromboemboli)
Mechanism of HF in DCM
- Impairment of contractility (systolic dysfunction)
Gross morphology of DCM
- 4 chamber dilation
- Mural thrombi
- Functional regurgitation
Clinical presentation of DCM
- Commonly affects 20 – 60 yo individuals
- Slow progressive congestive heart failure
- End stage / ejection fraction < 25%
- Cardiac failure
- Arrhythmia’s
Characteristics of Hypertrophic Cardiomyopathy (HCM)
- Myocardial hypertrophy
- Abnormal diastolic filling
- Intermittent left ventricular outflow obstruction
Pathogenesis of HCM
- Familial disease
- Autosomal dominant
Mutations of genes for cardiac contractile elements associated with HCM
- β-myosin heavy chain (most frequently; 403 Arg –> Gln)
- Cardiac Troponin T
- α-Tropomyosin
- Myosin binding protein C
Pathology of HCM
- Thickening of the ventricular septum (asymmetrical)
- Thickening of anterior mitral leaflet
- Myocyte hypertrophy
- Haphazard disarray of myocyte bundles
- Interstitial and replacement fibrosis
Venturi Phenomenon
- Outflow tract obstruction
HCM is the most common cause of unexplained death in
- Young athletes
Clinical presentation of HCM
- Reduced chamber size
- Reduced stroke volume
- Impaired diastolic filling
- Ventricular outflow obstruction
- Focal myocardial ischemia
- Exertional dyspnea
- Atrial fibrillation
