The exact prevalence of RCM in the general population remains unknown. About 5% of all cardiomyopathy cases are RCM which is believed to be the least common type of cardiomyopathy. Primary RCM is less common than secondary RMC. Different causes of RCM have varying frequencies in different age groups. 

Most adult cases are secondary to another condition called amyloidosis. In amyloidosis, an abnormal protein called amyloid accumulates in different organs and interferes with their function. Amyloidosis affects men and women equally

In children, the most common cause is exposure to radiation or certain chemotherapy agents such as anthracyclines. In infants, RCM may occur secondary to certain metabolic syndromes such as Gaucher’s disease in which the build-up of certain fats reaches a harmful level.

The causes of RCM can be classified into primary or secondary.

Primary RCM

More than half of primary RCM cases run in families, suggesting that it is inherited. Several genes have been associated with primary RCM. These include mutations in troponin T (TNNT2 gene), troponin I (TNNI3), α-actin (ACTC), and β-myosin heavy chain (MYH7). All these genes encode proteins that make up the functional units of muscle cells, known as sarcomeres. Mutations in genes are mostly inherited in an autosomal dominant fashion, meaning that one defective copy of the gene is enough for disease presentation. The cause of primary RCM in the other half is unknown (idiopathic). 

Secondary RCM

Secondary RCM occurs subsequently to another condition that affects the heart. Secondary RCM may occur as a result of infiltrative cardiac conditions which are characterized by the abnormal deposition of substances such as protein or fat within the heart muscle that stiffen the heart. For example, AL amyloidosis (immunoglobulin light chain amyloidosis) occurs when certain immune cells produce an abnormal protein that cannot be degraded by the body, leading to its harmful accumulation in different tissues including the heart muscle. The exact cause of AL amyloidosis is unknown.

In addition to heart infiltrative diseases, certain storage diseases can also cause RCM. Storage diseases are conditions that lead to the abnormal buildup of certain molecules within the cells. Most storage diseases are inherited as either autosomal recessive conditions or less commonly, in an X-linked manner. Autosomal recessive conditions only present if the individual has inherited 2 defective copies of the associated gene, one from each parent. The gene associated with an X-linked condition is located on the X chromosome, one of the two sex chromosomes in human cells. X-linked conditions primarily affect men. Hemochromatosis or iron storage disease is one of the common causes of secondary RCM. It is caused by a mutation in the HFE gene which encodes the HFE protein. HFE protein regulates the uptake of iron from the bloodstream into the cell. 

The last category of secondary causes of RCM is endomyocardial, which are conditions that affect the innermost layer of the heart that lines the insides of the heart chambers. For example, endomyocardial fibrosis can lead to scarring and the subsequent thickening of the inner layer of the heart. Although the exact cause of endomyocardial RCM is unknown, immune system dysfunction, genetic factors, infections, and environmental exposures may be implicated. 

Regardless of the underlying cause, RCM occurs when the heart muscle becomes too stiff and cannot properly expand and fill with blood when the heart is relaxing. Subsequently, when the heart contracts, there is less blood inside the heart to be ejected to the rest of the body. This means body organs receive less oxygen and nutrients and over time this may cause heart failure, a condition in which the heart cannot pump enough blood to meet the demands of the body. Over time, due to the impaired ability of the heart to expand, the blood returning to the heart cannot fully enter it. Therefore, pressure builds up until eventually there is high blood pressure in the pulmonary circuit in the lungs which causes the accumulation of fluids in the lungs. Additionally, the changes to the heart muscle may damage the electrical conduction system in the heart, leading to irregularities in the heartbeat (arrhythmias).

RCM tends to be a progressive condition that worsens over time. Initially, affected individuals may not experience any symptoms. Some symptoms that may develop with RCM include shortness of breath that gets worse with exercise. This is because during exercise, the body needs more oxygen and the heart’s impaired ability to pump blood becomes more pronounced due to the larger oxygen supply-demand imbalance. Affected individuals may also shortness of breath when lying down, fatigue, weakness, lightheadedness, fainting episodes, swelling in the legs and feet, coughing, chest pain or pressure, and abnormal heart rhythms that may be sensed as heart palpitations are heart racing. Due to the progressive nature of this condition, individuals may have very mild symptoms at first that worsen over time.

Additionally, depending on the underlying cause, other associated symptoms may be present. For example, if RCM is secondary to amyloidosis, affected individuals may experience numbness, tingling, or pain in their hands due to carpal tunnel, a condition associated with amyloidosis that causes the compression of the nerve that innervates the hands. Hemochromatosis can present with bronzing of the skin and joint pain. 

RCM may be suspected based on the presence of symptoms, the diagnosis of other conditions that are associated with RCM, family history, and physical examination. During the physical examination, the physician may listen to the heart. Certain abnormal heart sounds can point to certain conditions or abnormalities. The physician may also listen to the individual’s lungs to assess whether there is any fluid accumulation. Symptoms of conditions underlying secondary RCM may also become apparent during physical examination. If symptoms and physical exam findings point to a heart abnormality, a number of tests are needed to narrow down and confirm the diagnosis.  

An electrocardiography (ECG) may be performed to diagnose RCM. During an ECG, a number of small sensors are attached to the individual for a few minutes to record the electrical activity of the heart. Abnormalities in an ECG can point to or support certain diagnoses. A chest X-ray may also be performed to assess the size of the heart. However, both these tests are non-specific and cannot diagnose RCM. Echocardiography is an imaging test that utilizes sound waves to visualize the heart in real-time and can provide more detailed information about the function and anatomy of the heart muscle. In certain cases, an endomyocardial biopsy is required to confirm the diagnosis. This is an invasive procedure that allows for direct sampling of the heart tissue that can be analyzed. This procedure is performed by passing a small cutting device attached to a long, thin sheath through a blood vessel in the body, most commonly the internal jugular vein (a blood vessel in the neck) into the heart.

Currently, there are no cures for RCM. Management targets the underlying condition if identified, heart failure symptoms, and potential complications. For example, if RC is secondary to hemochromatosis, iron chelating medications may be used. These are agents that circulate in the blood and ”collect” the extra iron and facilitate its elimination from the body.

To improve symptoms diuretics may be prescribed. These are medications that increase the urine output, and thus, decrease blood volume and blood pressure. As a result, the heart will need to work less to overcome the pressure in the circulation to eject blood. Other medications include beta blockers that can slow the heart rate and increase the time when the heart is relaxed. This gives more time for the heart to be filled with blood. Angiotensin converting enzyme (ACE) inhibitors lower the blood pressure and reduce the workload of the heart. If the individual is at risk of forming blood clots, anticoagulants may be prescribed to prevent clot formation that could cause a stroke or other complications. In addition, lifestyle changes such as dietary modifications can help lower blood pressure. 

The choice of medication and specific therapy for RCM depends on the underlying condition, risk of complications, the ability of the patient to tolerate the therapy, and other case-specific factors.

The prognosis of RCM varies among affected individuals and depends on the underlying cause, the severity and the rate of progression, the presence of other medical conditions affecting the heart, etc. RCM is a progressive condition and tends to worsen over time and may ultimately lead to heart failure. Generally speaking, half of the individuals who develop heart failure survive beyond 5 years after diagnosis. Prognosis is better for adults with RCM compared to affected children.

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