Pathology of Primary Myocardial Disease Flashcards
What are the three main types of cardiomyopathy, and the most common one?
- Dilated cardiomyopathy - most common
- Hypertrophic cardiomyopathy
- Restrictive cardiomyopathy
All three are primary myocardial disorders
What is the cause of most dilated cardiomyopathy? What is the second most common cause?
- Idiopathic - cause unknown
- Genetic abnormalities (1/3 of cases) - usually autosomal dominant, affecting structural proteins of the myocardial cytoskeleton
What are some other important causes of dilated cardiomyopathy not in the top two?
Toxicities:
1. Alcoholism + thiamine deficiency (wet beriberi), leading to myocardial death
2. Drugs - i.e. doxorubicin
S/p myocarditis: usually enteroviruses like Coxsackievirus
3. Pregnancy related - due to hemodynamic alterations / nutritional factors
4. Hypothyroidism - increases Na+, giving volume overload
How does the heart appear in dilated cardiomyopathy grossly and microscopically?
Grossly - Large, heavy, globoid with four-chamber dilatation and variable hypertrophy / mural thrombi
Microscopically - Myocardial hypertrophy with interstitial fibrosis
What is the pathogenesis of dilated cardiomyopathy? What other dysfunctions will be present?
Something causes myocardial dysfunction, leading to progressive SYSTOLIC dysfunction
- > presentation is worsening congestive heart failure
- > can be complicated with arrhythmias, valvular dysfunctions (large annuli), and embolic events
What is arrhythmogenic right ventricular cardiomopathy?
A distinctive form of dilated cardiomyopatthy characterized by RV replacement with fat & fibrous tissue
-> right-sided heart failure and arrhythmias
What is the usual cause of hypertrophic cardiomyopathy?
USUALLY autosomal dominant mutations in sarcomere proteins leading to decreased cardiac myocyte contractility
-> growth-factor induced hypertrophy and fibrosis
What is the ventricular shape in hypertrophic cardiomyopathy and why? What can this damage?
Banana-shaped LV cavity
-> subaortic region will typically have an increased thickness blocking the outflow track of the LV, causing subaortic stenosis and damage to mitral valve and its underlying region
What happens as a result of hypertrophic cardiomyopathy in each stroke?
Impaired diastolic filling -> decreased cardiac output
Systolic ejection murmur may be heard if septum leads to subaortic stenosis
Is hypertrophy in hypertrophic cardiomyopathy symmetric or asymmetric? How will it appear microscopically?
Asymmetric -> LV hypertrophy is much greater, including IV septum
Microscopically -> hypertrophy with myofiber disarray and fibrosis
How will patients with HCM present clinically?
Broad range of findings.
Arrhythmias -> diastolic dysfunction leads to LA dilatation and Afib
Systemic emboli from Afib
Progressive heart failure, angina, shortness of breath
May cause sudden cardiac death in young athletes from ventricular arrhythmias
What does restrictive cardiomyopathy do to the heart?
Impairs diastolic filling, with minimal hypertrophy of the ventricles
-> leads to LA / RA dilatation from lack of compliance of ventricles
What are the important causes of restrict cardiomyopathy?
- Amyloidosis
- Sarcoidosis (granulomatous)
- Radiation-induced fibrosis
- Hemochromatosis
- Metastatic malignancy
What is Takotsubo Cardiomyopathy also called?
“Octopus pot” or broken heart syndrome.
What happens pathophysiologically to cause Takotsubo Cardiomyopathy?
Significant acute emotional or physical distress leads to excessive catecholamine release -> stuns myocardium of LV apex due to high concentration of sympathetic innervation, and causes multivessel coronary spasm
Stunning -> LV apical hypokinesis, looks alot like STEMI
Who is typically affected with Takotsubo Cardiomyopathy and what will be their clinical manifestations / prognosis? What will angiography show? ECG?
Postmenopausal women -> chest pain / dyspnea, ECG abnormalities leads to ST segment elevation / T wave inversion, and elevated cardiac markers.
-> angiography shows no significant coronary obstruction and LV ballooning (looks like octopus pot)
Complete recovery in 1-2 months
What is the most common cause of myocarditis?
Infections, and more specifically viruses
Enteroviruses (Coxsackie A and B, echoviruses)
CMV and HIV in immunocompromised
What bacteria and parasites are known to cause myocarditis?
Bacteria - Borrelia burgdorferi - Lyme disease
Parasites - Trypanosoma cruzi, Toxoplasma in immunocompromised, Trichinella spiralis (helminth)
What immunologic disorders are known to cause myocarditis?
Acute rheumatic fever - Aschoff bodies in myocardium
SLE - although pericarditis and valvular disease is much more common
What are the usual microscopic features of myocarditis? Grossly?
Usually caused by viruses, so there will be interstitial inflammation, mononuclear cells / lymphs with focal myocyte injury (CD8 cells kill infected myocardium), leading to complete resolution or patchy fibrosis
Grossly - Slight color change with possible dilation of cardiac chambers
How will myocarditis look if it is due to a drug-induced hypersensitivity?
Inflammatory cell infiltrate will also have many eosinophils
What is giant cell myocarditis?
An idiopathic, aggressive form of myocarditis characterized by widespread myocardial cell loss, mononuclear infiltrate, and multinucleated giant cells
Where does Chagas disease replicate?
Replicates as collections of amastigotes intracellular in smooth muscle and cardiac myocytes, causing a mixed inflammatory cell infiltrate in the myocardium + damage
What are the clinical results of myocarditis?
Can be simply low-grade constitutional symptoms which are self resolving, to arrhythmias, to development of dilated cardiomyopathy
What will be seen in cardiotoxicity caused by doxorubicin and cyclophosphamide?
Doxorubicin - Myocardial cell vacuolization & lysis, progressing to dilated cardiomyopathy
Cyclophosphamide - Myocardial hemorrhage (targets vessels more)
What can be seen in cardiotoxicity caused by pheochromocytoma or cocaine?
Foci of myocardial contraction-band necrosis
What types of cardiomyopathy does iron overload cause and why?
Early - restrictive cardiomyopathy from accumulation in cardiomycotes
Late - dilated cardiomyopathy from loss of cardiomyocytes from free radical damage
What are the systemic amyloidoses which will affect both the ventricles and atria?
- Senile cardiac amyloidosis - from transthyretin
- Primary amyloidosis - AL light chain
- Secondary amyloidosis - serum amyloid-associated protein (SAA) is a +APP
What amyloidosis leads to amyloid accumulating only in the atrium?
Isolated atrial amyloidosis - derived from atrial natriuretic peptide, often in heart failure from volume overload
What is the usual clinical outcome of cardiac amyloidosis?
Restrictive cardiomyopathy depending on where they deposit, leading to dilation of atria if primarily involving the ventricles for instance.
But again, restrictiveness will vary with location of protein deposition
What will happen microscopically in cardiac amyloidosis?
Extracellular accumulation of amorphous eosinophilic material -> hyaline accumulation of amyloid proteins which stain with Congo red
Accumulation -> pressure atrophy of neighboring cardiac myocytes. Leads to a thickened, weak wall.
