CardiomyopathiesCardiomyopathies

• Heart disease resulting from a primary abnormality in myocardium• most causes are idiopathic

a) most likely genetic defects• Types:

a) Dilatedi) “congestive” ii) most common (~90%)

b) Hypertrophicc) Restrictive (lease common)

1.- Dilated Cardiomyopathy (DCM)Dilated Cardiomyopathy (DCM)

• Progressive cardiac dilationa) systolic dysfunction

• ~35% of patients have genetic forma) “primary”

• large variety of acquired DCM (2o)a) toxicities (e.g., alcohol)b) myocarditis (inflammations)c) pregnancy d) unknown (“idiopathic DCM”)

i) likely to be genetic

• Myocarditis (inflammatory)a) viral in nature (most often)

i) coxsackievirus A and Bii) other enteroviruses

- cleave dystrophin (later)b) progression from myocarditis to DCM in some patients

• Alcohol (alcoholic cardiomyopathy)

a) alcohol toxicity or 2o nutritional disturbances may be causeb) ethanol metabolite –

acetaldehyde- have direct toxic effect on heart

i) however, no distinguishing features from DCM

Toxicitya) chemotherapeutic agents

i) doxorubicin (Adriamycin)ii) Cobalt

Pregnancy-associateda) “peripartum cardiomyopathy”

i) late in pregnancy or weeks to months postpartum

ii) poorly understood- hypertension- volume overload- nutritional deficiency- etc. ?

• Genetic Influencesa) ~ 35% of patients have familial occurrenceb) autosomal dominant

predominatesc) affects on cytoskeleton,

oxidative Phos., fatty acid β – oxidation,

etc

d) Mitochondrial defects most frequently cause DCM in

children e) X-linked induces DCM in

teenagersi) rapidly progressiveii) linked to gene for

“dystrophin”- cytoskeleton protein

iii) diseases with dystrophin mutations (myopathies

such as Duchenne and Becker muscular dystrophy) present with DCM

f) Clinical:i) common at 20-50 yrsii) progress slowly

- shortness of breath- easy fatigue- poor exertional capacity

iii) may rapidly slip in decompensation

- EF < 25%- 50% die within 2 yrs- 25% survive > 5 yrs.

iv) hypo contracting

• Arrhythmogenic Right Ventricular Cardiomyopathy (right ventricular dysplasia)

a) associated with right sided heart failure

b) various rhythm disturbancesi) Ventricular tachycardia

c) right ventricular thinningi) due to loss of myocytes

2.- Hypertrophic Hypertrophic Cardiomyopathy(HCM)Cardiomyopathy(HCM) Is a genetic disease• other names:

a) idiopathichypertrophic subaortic stenosis

b) hypertrophic obstructive cardiomyopathy

• Characteristics:a) hypertrophy (mainly septal vs. free wall) 1:3 ratio)b) abnormal diastolic fillingc) hyper contracting

• Primary diastolic dysfunction• Systolic function is preserved• 2 diseases which must be differentiated from HCM are:

a) amyloidosisb) hypertensive heart disease

• Most cases familial a) autosomal dominantb) several gene mutations found

i) see fig. 12-35- β-myosin heavy chain is

most common

- MYBP-C and troponinT are next in frequency

- these 3 genes account for ~80% of all cases of HCM

c) these gene mutations mainly effect proteins of sarcomere

•Clinical:a) complianceb) chamber sizec) Vs

d) diastolic filling

e) ~ 25% have obstruction to ventricular outflowi) systolic ejection murmur

f) focal cardiac ischemia and angina

g) major problems:i) atrial fibrillation ii) mural thrombus formationiii) embolizationiv) IE

h) one of most common causes of death in young athletes !!

DIASTOLE SYSTOLE

An illustration of the obstructive form of HCM during relaxation (diastole, left) and during active contraction (systole, right). The thickened septum and the mitral valve leaflets come in close proximity, effectively narrowing the pathway that blood must travel to get out of the heart. Additionally, the forces on the mitral valve can lead to variable degrees of backward leakage (regurgitation) that can also lead to symptoms.

3.- Restrictive CardiomyopathyRestrictive Cardiomyopathy Impairs diastolic function

a) primary in compliance- impaired diastolic filling

• least common of the CM• Ventricles approximately normal size•Systolic function unaffected•Biatrial dilation commonly seen•Myocardial fibrosis

a) radiationb) amyloidosisc) sarcoidosis

d) metastatic carcinomae) sarcoid granulomasf) any factor which increases endomyocardial fibrosis

Primary Cardiac TumorsPrimary Cardiac Tumors

BENIGNBENIGN MALIGNANTMALIGNANT Myxoma

RhabdomyosarcomaLipoma MesotheliomaHemangioma FibrosarcomaMesothelioma LymphomaFibroma OsteosarcomaTeratoma Angiosarcoma

Rhabdomyoma LiposarcomaNeurofibroma Leiomyosarcoma

• MyxomaMyxomaa) most common 1o tumor of heart

i) most within atria (~90%)ii) left-to-right prevalence (4:1)

b) benignc) almost always single neoplasmd) 10% familial (i.e., “Carney syndrome”)e) Clinical:

i) “ball-Valve” obstructionii) constitutional effectsiii) embolization

• Rhabdomyomas Rhabdomyomas a) most common cardiac tumor in children

i) often diagnosed within 1st year of life

- obstructive diseaseNon Cardiac NeoplasmsNon Cardiac Neoplasms

a) most common are metastases from

i) lungii) breastiii) melanomasiv) leukemias and lymphomas

b) clinical:i) pericardial spreadii) obstruction (i.e., filling)iii) cardiomyopathy via

radiation