Cardiomyopathy and Myocardial Disease - Mackinnon Flashcards
Give the 5 WHO classification categories of cardiomyopathy
- Dilated
- Hypertrophic
- Restrictive
- Arrhythmogenic RV dysplasia
- Unclassified
Describe the general features of dilated cardiomyopathy
- progressive cardiac dilation: enlarged (hypertrophic), flabby, heavy heart
- systolic dysfunction
- potential thrombus formation
- functional regurgitation (due to ventricular dilation)
List some potential etiologies of dilated myopathy
- ischemia
- valvular dysfunction
- hypertension
- familial factors (genetic)
- idiopathic
- inflammation (infectious and non-infectious)
- toxins
- abnormal metabolism
- nutrition
- neuromuscular dysfunction (ex: Duchenne MD)
List (3) genetic inheritance patterns seem in dilated cardiomyopathy and the gene product(s) generally affected
- Autosomal dominant mutations - affecting cytoskeletal proteins (alpha-cardiac actin, desmin, nuclear laminins A/C)
- X-linked inheritance - dystrophin
- Mitochondrial genome mutations - oxPhos and FA beta-oxidation dysfunction
Describe the mechanism and epidemiology of acute viral myocarditis
Coxsackie B or Echovirus
Unclear mechanism leading to myocyte death and fibrosis. May be immune-mediated, but reaction unaltered by immunosuppressive drugs
Usually affects young people, self-limited
Name two sources of iron overload seen in dilated cardiomyopathy
- hemochromatosis
- multiple transfusions
What is beriberi heart disease?
Thiamine deficiency that triggers a dilated cardiomyopathy. Related to alcohol consumption
Describe the effects of alcohol on the heart that contibute to dilated cardiomyopathy
- Direct toxic effects on the myocardium
- Indirect toxic effects due to thiamine definiency (beriberi)
What type of antibiotics feature dilated cardiomyopathy as an adverse effect?
anthracyclines
*dose-dependent*
When does peripartum cardiomyopathy occur?
What probable causes underlie this condition?
Late pregnancy or several week s post-partum
- pregnancy-associated hypertension
- volume overload
- nutritional deficiency
- metabolic derangement
- immunological reaction
- prolactin
What is functional regurgitation?
regurgitation that occurs due to excessive dilation of the atria
Describe some epidemiological factors associated with increased risk of idiopathic dilated cardiomyopathy
- Male gender
- black race
- hypertension
- chronic beta-agonist use
Describe some clinical presentation features of dilated cardiomyopathy
- Heart failure symptoms
- anginal chest pain
- emboli
- syncope
- sudden cardiac death
What etiology of dilated cardiomyopathy has an especially bad prognosis (<25% @ >5 years)?
Cardiomyopathy due to HIV infection
When might Warfarin be used for dilated cadriomyopathy?
Chronic or paroxysmal Afib, LV thrombus, or prior thrombotic event
What drug(s) might be indicated for dilated cardiomyopathy in patients intolerant to ACE inhibitors?
ARBs, hyralazine/nitrates
What might also be given in addition to an ACE inhibitor for dilated cardiomyopathy to reduce heart failure symptoms?
Beta-blocker
Persistent heart failure symptoms in dilated cardiomyopathy despite diuretics and ACE inhibitors might indicate use of what drug?
digoxin
What drug(s) are most commonly indicated for management of dilated cardiomyopathy?
ACE inhibitors (symptomatic heart failure or asymptomatic LV dysfunction) + diuretics (volume overload)
Describe the major features of Arrhythmogenic Right Ventricular Cardiomyopathy
- Inherited, autosomal dominant
- Right-ventricular failure and various arrhythmias
- can cause sudden death
- may be related to defective desmosome linking of cardiac myocytes
- severely thinned RV wall due to cardiac myocyte death and fatty infiltration with fibrosis
Describe some pertinent clinical features of ARVC
- young adult
- arrhythmia (ventricular tachycardia)
- sudden death
- RV failure
Fatty infliltration of the RV wall is classic for what?
Arrhythmogenic Right Ventricular Cardiomyopathy
(ARVC)
Describe the major features of Hypertrophic Cardiomyopathy
- Myocardial hypertrophy with poor LV compliance
- Poor diastolic filling, with relative preservation of systolic function
- Thick-walled, heavy, hypercontracting heart
- Intermittent outflow obstruction (mitral valve obstructs aortic outflow)
What type of cardiomyopathy features a characteristic ‘banana’ shape in the subaortic region?
Hypertrophic cardiomyopathy (HCM)
Describe the major histological finding(s) observed in HCM
Marked hypertrophy of cardiac myocytes (diameter >40um, nl ~ 15um)
General myofiber disarray
Interstitial fibrosis
What are the three (3) most common mutated sarcomeric proteins in HCM?
- myosin heavy chain beta-MHC
- myosin binding protein MYBP-C
- cardiac TnT
What is the most common cause of sudden, otherwise unexplained death in young athletes?
HCM
Describe the pathophysiology of HCM
- left ventricular outflow obstruction
- mitral regurgitation
- diastolic dysfunction
- myocardial ischemia
- cardiac arrhythmias
In HCM, what causes the outflow tract obstruction?
- narrowed outflow due to hypertrophied interventricular septum
- anterior displacement of the mitral valve leaflets during systole
What is the venturi effect?
anterior mitral valve leaflets & chordae sucked into outflow tract during mid- late systole
What mechanisms underlie the ischemia seen in HCM?
**Not atherosclerosis**
- supply/demand mismatch due to increased muscle mass
- increased wall tension due to decreased wall compliance
- abnormal intramyocardial arteries
What is the most common lethal event that occurs in patients with HCM?
sustained ventricular tachycardia or ventricular fibrillation
What feature of HCM is usually well-tolerated in the general population, but is especially poorly tolerated in HCM?
atrial fibrillation - they lose the atrial ‘kick’ that helps to compensate for the filling issues.
Describe some risk factors for suddent cardiac death in HCM
- marked ventricular wall hypertrophy (>30mm)
- young age at presentation (<14y)
- hypotension during exercise (<40y)
- history of syncope
- history of aborted cardiac arrest
- family history of sudden cardiac death
- cetain genetic mutations
What is the first-line therapy for HCM?
beta-blockers
What therapy is indicated in patients with HCM who are intolerant of beta-blockers
What else might be useful for achieving negative inotropy?
Calcium channel blockers
Disopyramide
Name (5) non-pharmacological interventions that are useful in the treatment of HCM
- Surgial septal myectomy
- Alcohol-induced septal ablation
- Dual-chamber pacemaker
- Cardiac transplantation
- Implantable cardioverter-defibrillator
Describe the major features of restrictive cardiomyopathy and the possible etiologies
Primary decrease in ventricular compliance, resulting in impaired diastolic filling
Etiologies:
- idiopathic
- secondary effects:
- post-radiation
- amyloidosis
- sarcoidosis
- metastases
- inborn metabolic disorders (deposition)
Bi-atrial dilation is a common gross morphological feature of what?
Restrictive cardiomyopathy (RCM)
How is RCM diagnosed?
Clinical presentation
Endomyocardial biopsy
Rule out constrictive pericarditis (similar symptoms)
Describe some clinical features of RCM
Left and right sided heart failure
severe pulmonary congestion
hepatic congestion
Name the debris deposited in amyloid RCM
Where does it commonly deposit?
What population is especially susceptible?
Transthyretin (prealbumin)
Deposits in ventricles and atria
African Americans (4:1)
What produces an apple-green birefringence under polarized light when stained with congo red?
Cardiac amyloidosis
Identify:
underlying eosinophilia and release of major basic protein causes endomyocardial necrosis and scarring
Endomyocardial fibrosis, large mural thrombi, peripheral eosinophilia, and eosinophilic infiltrates in organs
Loeffler endomyocarditis
Describe endocardial fibroelastosis
In what patient population(s) is this found?
Uncommon heart disease featuring focal or diffuse fibroelastic thickening, usually involving mural left ventricular endocardium (usually in ventricles)
Affects children and young adults in Africa, most commonly within the first two years of life
Describe the cardiac effects of iron overload
- usually dilated
- heart is rust-brown in color
- hemosiderin deposition in cardiac myocytes - seen via Prussian Blue stain
- Possible fibrosis
Discuss the cardiac effects of hypothyroidism and hyperthyroidism
Hypothyroidism
- decreased cardiac output
- heart is flabby, enlarged, dilated
- myofiber swelling with loss of striations, basophilic degeneration, interstitial mucopolysaccharide edema
- pericardial fluid accumulation
Hyperthyroidism
- tachycardia
- palpations
- cardiomegaly
Sarcoidosis is associated with what cardiac dysfunctions?
- Restrictive cardiomyopathy
- conduction system disease
- ventricular arrhythmias (sudden cardiac death)
Name some common cardiotoxic drugs
- Lithium
- Phenothiazines
- chloroquine
- cocains
What is Takotsubo Cardiomyopathy?
What might be observed (grossly) on the heart
Catecholamine surge due to intense emotional stress (sometimes pheochromocytoma) leading to acute left ventricular dysfunction.
Sometimes also called “broken heart disease”
Grossly: apical ballooning seen during systole
