Cardiomyopathy, Myocarditis, Pericarditis & Heart Failure PDF

CARDIOMYOPATHY, MYOCARDITIS, PERICARDITIS & HEART FAILURE Causes of heart failure Left ventricular failure Volume overload = regurgitative valve Pressure overload = hypertension & outflow obstruction Loss of muscles = Post MI, chronic ischemia & connective tissue diseases Restricted filling = perica...

CARDIOMYOPATHY, MYOCARDITIS, PERICARDITIS & HEART FAILURE Causes of heart failure Left ventricular failure Volume overload = regurgitative valve Pressure overload = hypertension & outflow obstruction Loss of muscles = Post MI, chronic ischemia & connective tissue diseases Restricted filling = pericardial diseases restrictive cardiomyopathy & tachyarrhythmia Right heart failure Left heart failure = most common Rare but generally caused by lung disorders Morphology of left ventricular failure Gross = depends on disease processes, LVH & dilation Microscopy = myocyte hypertrophy & interstitial fibrosis Morphology of right ventricular failure Heart = varies with cause, typically RVH and dilation possibly atrial dilation Liver = nutmeg liver (chronic passive congestion) = centrilobular necrosis & cardiac cirrhosis Subcutaneous tissue = pedal & sacral oedema Dilated cardiomyopathy / congestive heart failure Progressive cardiac dilation and contractile dysfunction (usually concomitant hypertrophy) Gross morphology = Enlarged ”flabby” heart due to dilation of all chambers Microscopic morphology = non specific, may see hypertrophic myocytes Pathogenesis = secondary to ischaemic heart disease, familial, post-myocarditis, toxins, haemochromatosis, sarcoidosis & peripartum Hypertrophic cardiomyopathy Secondary is caused by hypertension & aortic stenosis Primary is caused by mutations in genes encoding sacromeric proteins (HOCM or HCM) = most common is beta-myosin heavy chain = autosomal dominant Gross = massive myocardial (septal) hypertrophy no ventricular dilation, banana ventricle Microscopic = myocyte hypertrophy, myofiber disarray, interstitial & replacement fibrosis Restrictive cardiomyopathy Primary decrease in ventricular compliance = impaired ventricular filling in diastole Idiopathic or associated with radiation fibrosis, amyloidosis & sarcoidosis Gross = Ventricles are normal with no dilation, myocardium is firm (possible atrial dilation) Microscopic = patchy/diffuse interstitial fibrosis, possibly to determine specific aetiology Symptoms of heart failure Left heart failure Paroxysmal nocturnal dyspnea Elevated pulmonary capillary wedge pressure Pulmonary congestion Tachypnea & tachycardia Restlessness & confusion Orthopnea Exertional dyspnea Fatigue cyanosis Myocarditis aetiology “Inflammation of heart muscle” Viral infections = Coxsackie A&B, CMV & HIV Non viral = Trypanosoma cruzi & Lyme disease Hypersensitivity to drugs Immune diseases = SLE & polymyositis Right heart failure Fatigue Peripheral venous pressure Ascites Enlarged liver & spleen Distended jugular veins Anorexia Weight gain Dependent edema Myocarditis morphology Gross = often normal Microscopic = lymphocytic infiltrate, focal myocyte necrosis Myocarditis clinical features Asymptomatic HF= arrhytmias & sudden death Late = dilated cardiomyopathy Pericarditis causes Usually secondary and acute Primary = viral Causes of acute pericarditis Infectious = virus, pyogenic bacteria, TB, fungi etc Immunologically mediated = Rheumatic fever, SLE, post-MI & drug hypersensitivity Miscellaneous = MI, uraemia, post-cardiac surgery neoplasia, trauma & radiation Pericarditis morphology Serous Fibrinous/ serofibrinous Purulent Hemorrhagic Caseous Chronic / healed = fibrinous thickenings/ adhesions ANEURYSMS “Localized, abnormal, permanent, dilation of a blood vessel “ True or False True aneurysm = surrounded by complete vessel wall; all layers affected Congenital Atherosclerotic Syphilitic False aneurysm (pseudoaneurysm) = extravascular hematoma which communicates with intravascular space Anastomotic leak between vascular graft & native artery Abdominal Aortic Aneurysm Most infra renal Aetiology = Atherosclerosis, trauma, infection, inflammatory disease & connective tissue disorder Risk factors = smoking x4, male, age, hypertension, COPD, hyperlipidemia & family history Pathophysiology Loss of elastic fibres Attenuation of aortic media, Collagen degradation Imbalance between proteolytic enzymes & antiproteases Decreased density of smooth muscle cells in medial Mural thrombus formation à local hypoxia à medial neovascularization & inflammation EXPANSILE PULSATILE MASS Complications = distal embolization ( blue toe syndrome, ureterohydronephrosis & rupture Types of aneurysm Saccular = Berry Fusiform = AAA Mycotic = weakened arterial wall secondary to infection Septic embolus = IE Extension of adjacent infection Infection by circulating organisms Cerebral aneurysm Associations = autosomal dominant PKD, fibromuscular dysplasia, Marfan’s & Ehlers-Danlos 2-4% re-bleed within first 24 hours & 20% re-bleed within first 2 weeks Rupture associated with straining or orgasm Syphilitic Aneurysm Pathogenesis = endarteritis obliterans of vasa vasorum of aortic adventitia à ischaemia of mediaà inflammation à dilation Usually involve arch of aorta Clinical presentation Mediastinal compression Respiratory obstruction Dysphagia Aortic regurgitation Rupture Aetiology Atherosclerosis = medial destruction = common in abdominal aorta Cystic medial degeneration = congenital Kawasaki syndrome = coronary artery aneurysms Polyarteritis nodosa = intrarenal aneurysm Trauma = arteriovenous aneurysm Aortic Dissection Most (>80%) develop without pre-existing thoracic aortic aneurysm Risk factors = hypertension, old age, atherosclerosis, Marfan’s, Turner’s, bicuspid aortic valve, Takayasu’s arteritis, familial & pregnancy Histology Cystic medial degeneration Decreased vascular smooth muscles Mucoid deposition Elastin deficiency & fragmentation Hemorrhage between middle & outer 1/3 of media Clinical presentation Unequal upper limb pulses Aortic regurgitation murmur Features of connective tissue disease Widened mediastinum AMYLOID Amyloid is a protein in abnormal fibrillar form resistant to degradation Amyloid formation Relies on polymerization of fibrils from an unstable intermediate state “Nucleus” or “seed” of peptides in the form of micelle or conglomeration of peptides starts the process Free fibrils nucleate within these, elongating by irreversibly binding monomers to their free ends Beta sheet structure is the most common motif Diagnosis History = chronic disease, hemodialysis, dementia, neuropathy Examination = macroglossia & hepatosplenomegaly Sparkling on echocardiogram Tissue diagnosis is definitive (can be seen on H&E stains, stains pink) Other protein determined diseases Huntington’s = associated with amyloid like fibrils in brain & heart, heritable & associated with trinucleotide repeats Prions Kuru = neurodegenerative disorder that causes tremors = cannibalism CJD = sporadic or inherited = exposure to brain or spinal tissue Transmissible spongiform encephalopathies Fatal familial insomnia Amyloidosis is a diverse group of disorders characterized by extracellular deposits of amyloid Types of amyloid Systemic AL = Ig LC (lambda) = plasma cell dyscrasias = myeloma AA = SAA = reactive systemic = chronic inflammatory Abeta2M = Beta2-macroglobulin = dialysis associated = chronic renal failure Localised Abeta2 = APP = senile cerebral = Alzheimers ACal = Calcitonin = Endocrine = Medullary thyroid carcinoma AA = SAA = Familial Mediterraenea fever ATTR = Transthyretin = Familial amyloidotic neuopathies or systemic senile amyloidosis Treatment Depends on underlying disease AL Chemotherapy Autologous stem cell transport Hereditary Possible liver transplant Stabilize proteins (clinical trials) Cardiac Heart failure = diuretics Rarely transplant Ventricular assist device How is damage caused If amyloid accumulation occurs in sensitive areas it causes significant problems Heart = cardiac amyloid Brain = amyloid angiopathy & Alzheimer’s GI = If a lot of amyloid accumulation occurs it can degrade the tissues causing problems Large vessels liver Classification of Amyloid By protein fibril Primary or secondary Anatomical category Systemic or localized Hereditary Disease association