Skip to content

Cardiomyopathies: Pathology review



Cardiovascular system


Vascular disorders
Congenital heart defects
Cardiac arrhythmias
Valvular disorders
Heart failure
Cardiac infections
Pericardial disorders
Cardiac tumors
Cardiovascular system pathology review

Cardiomyopathies: Pathology review


1 / 3 complete

USMLE® Step 1 style questions USMLE

3 questions

A 68-year-old woman comes to the clinic complaining of dyspnea on exertion, fatigue, and chest pain. She also states that she has to use 3 pillows at night when she sleeps. Past medical history includes carcinoma of the breast, for which she received surgery and adjuvant radiation therapy but no chemotherapy. Temperature is 37.2°C (98.9°F), pulse is 80/min, respirations are 20/min, and blood pressure is 100/68. Physical exam shows jugular venous distension and bilateral leg edema. Cardiac auscultation shows S3 and S4 heart sounds. Electrocardiogram (ECG) shows low amplitude signals. Which of the following is the most likely cause of this patient’s disease?  


Aman is a 60 year old male who came into the clinic with shortness of breath and lower limb edema for the past 3 months. He has a history of hypertension, hyperlipidemia and chronic alcohol use. On auscultation, an additional S3 sound is heard. An echocardiogram is performed, which shows dilated ventricular chambers and a reduced ejection fraction. Alexandra is a 23 year old professional volleyball player who came to the clinic after multiple episodes of “passing out” during her games. At first, she presumed it was due to dehydration, but she is now concerned. She has a family history of sudden cardiac death in multiple relatives. An echocardiogram shows asymmetric hypertrophy of the interventricular septum, and a normal ejection fraction.

Both Aman and Alexandra have cardiomyopathies. From outside to inside, the heart is made of the epicardium, myocardium, and endocardium. Diseases that affect the myocardium are called cardiomyopathies. The three main subtypes are dilated, hypertrophic and restrictive cardiomyopathy.

Let’s start with dilated cardiomyopathy, which is the most common one, accounting for almost 90% of all cases. Now, In dilated cardiomyopathy the ventricular walls become thin and weak. As a consequence, the ventricular chambers dilate. Because the ventricular wall is thinner, muscle contraction is weaker and the heart can’t pump blood efficiently throughout the body. So we have a systolic dysfunction with normal diastole.

Okay, when it comes to the etiology of dilated cardiomyopathy, the large majority of cases are idiopathic, meaning the cause can’t be identified. However, there are many secondary causes that must be excluded first. Examples include toxins like chronic alcohol or cocaine abuse, nutritional deficiencies like thiamine deficiency, also called beri-beri, or selenium deficiency. Another cause is myocarditis, which is inflammation of the heart muscle, usually caused by viruses like Coxsackie B, but can also be related to autoimmune diseases like lupus. Hemochromatosis is a disorder of iron overload in which excessive iron can be deposited in many organ sites, including the cardiac muscle. Too much intracellular iron can act as a toxic free radical, resulting in cellular damage.

Other causes include Chagas disease, a parasitic infection caused by Trypan-o-soma cruzi, which is transmitted by the “kissing bug”. A clue on the exam would be someone who recently travelled to South America, and also has other clinical features like periorbital swelling, megaesophagus and megacolon. Also, during pregnancy, the mother’s body demands more cardiac output. Sometimes, the heart fails to meet this high demand, and we get something called peripartum cardiomyopathy, which commonly occurs in the last trimester of pregnancy and up to 6 months after delivery. Dilated cardiomyopathy can also result as a side effect of some medications like doxorubicin, a chemotherapeutic agent, or trastuzumab, a monoclonal antibody. Even severe emotional stress can cause a form of dilated cardiomyopathy called Takotsubo cardiomyopathy.

This is thought to be related to the release of catecholamines, which in large amounts can be toxic to the myocardium. Examiners try to get creative when it comes to these causes. For example, a case of breast cancer treated with chemotherapy, after which the individual develops heart failure. This should raise your concern for doxorubicin toxicity. Another example would be an individual with anorexia nervosa who develops heart failure, raising your concern for a nutritional cause like beri-beri or selenium deficiency. The next subtype of cardiomyopathy is hypertrophic cardiomyopathy. Unlike dilated cardiomyopathy, the heart muscle thickens in a concentric fashion, which means the cells make more myofibrils which are stacked on top of one another. Histologically, there’s myocyte hypertrophy, but the key is myocardial disarray, which is very high yield. This means that they’re disorganized and have bizarre shaped nuclei. Now, it might seem that the heart getting thicker is a good thing.

But the problem with a very thick ventricular wall is that it impairs the ability of the ventricle to relax during diastole, which reduces ventricular filling. In other words, we have diastolic dysfunction but systole is not impaired. Another feature is that the interventricular septum gets thicker, particularly on the side of the left ventricle. This asymmetric hypertrophy can obstruct or narrow the aortic outflow tract during systole or ventricular contraction and this increases blood velocity through the smaller opening and pulls the anterior leaflet of the mitral valve toward the septum which further obstructs the left ventricular outflow tract. In such a case, we call it hypertrophic obstructive cardiomyopathy, or HOCM. At the same time, that mitral valve doesn’t shut all the way, blood can leak back into the left atrium, called mitral valve regurgitation.

All right, now most cases of hypertrophic cardiomyopathy are familial and are inherited in an autosomal dominant fashion, so family history is an important clue! Mutations commonly affect genes coding for components of the cardiac muscle, such as beta-myosin heavy chain, and myosin-binding protein C. Now, a commonly tested cause of hypertrophic cardiomyopathy is Friedreich ataxia. This is a trinucleotide repeat expansion disorder, where the death of myocytes leads to difficulty pumping blood through the heart, which thickens the heart’s lower chambers or ventricles, leading to hypertrophic cardiomyopathy.

Okay, now in restrictive cardiomyopathy, the heart muscle is stiff, preventing it from relaxing during diastole. So, that’s another cause of diastolic dysfunction.But Systole remains normal. Causes include primary diseases, which are often idiopathic, or secondary systemic diseases. An important primary cause is endomyocardial fibrosis, where excessive collagen tissue is deposited in the heart muscle. Sometimes this disease is associated with an elevated eosinophil count and deposition of eosinophils in the endocardium and myocardium, in which case it would be called Loeffler’s eosinophilic endocarditis.

Now, secondary causes are much more common, with the most common being amyloidosis. Other secondary causes include sarcoidosis, hemochromatosis and radiation therapy, all of which cause fibrosis of the myocardium. All right, now, regarding clinical presentation, in all three types of cardiomyopathy, over time the heart may be unable to do its job effectively, leading to heart failure signs and symptoms like fatigue, dyspnea, and swelling of the feet. And because cardiomyopathies affect the cardiac muscle as well as the pacemaker cells that run through the cardiac muscle, they can lead to arrhythmias like atrial fibrillation, ventricular ectopic beats, ventricular tachycardia or fibrillation, and atrioventricular block. Another high yield fact is that specifically, hypertrophic obstructive cardiomyopathy is the most common cause of sudden cardiac death in people less than 35 years, and is especially more common in athletes, due to the development of ventricular arrhythmias.

Another thing to bear in mind for hypertrophic obstructive cardiomyopathy is that due to the obstruction of the aortic outflow tract, perfusion of the brain can get low, so individuals can present with syncope, which is a transient loss of consciousness.

  1. "Pathophysiology of Heart Disease" Wolters Kluwer Health (2015)
  2. "Rapid Review Pathology" Elsevier (2018)
  3. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  4. "Dilated cardiomyopathy" Lancet (2017)
  5. "2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines" J Thorac Cardiovasc Surg (2011)
  6. "Differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis" Heart (2001)