Supplemental Figure 1. Patterns of fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scans.A: No abnormal FDG uptake.B: Diffuse FDG uptake in the left ventricular wall, which could either signify diffuse sarcoid activity or an inadequate dietary preparation. C: Patchy FDG uptake in the septum of the left ventricle. D: Patchy uptake in the lateral left ventricular wall on top of mild diffuse uptake in the left ventricle. Of note, “patchy” and “patchy on diffuse” patterns are more specific for cardiac sarcoidosis. E: Abnormal right ventricular FDG uptake. F: Poor preparation with nonspecific uptake throughout.
Ning N, Guo HH, Iagaru A, Mittra E, Fowler M, Witteles R. Serial cardiac FDG-PET for the diagnosis and therapeutic guidance of patients with cardiac sarcoidosis. J Card Fail. 2019;25(4):307-311.
Sarcoidosis is a disease in which the body’s own immune system causes damage to its own organs. This kind of disease is sometimes called “auto-immune”. Damage from sarcoidosis can occur in any part of the body.
In people with sarcoidosis, inflammation occurs in what are called “granulomas” (masses of inflammatory tissue). Over time, if sarcoidosis is not treated, these granulomas may replace healthy organ tissue and cause scarring and fibrosis (hardening) of the affected tissue.
Sarcoidosis can occur in any organ, but the most common locations are the lungs (pulmonary) and the heart (cardiac). Traditionally, approximately 90-95% of sarcoidosis patients have had evidence of involvement of the lungs – though this may be an overestimate because of the traditional challenges in diagnosing patients with primarily heart involvement. Other common organs affected by sarcoidosis include the skin (15% of cases), lymph nodes (15% of cases), eyes (12% of cases) and liver (11% of cases). Less common body sites are the spleen, neurologic system/nerves, kidneys and bones.
At one point it was felt that cardiac involvement of sarcoidosis was relatively rare; some prior estimates have stated that as few as 5% of people with sarcoidosis have cardiac involvement. However, this is clearly a large underestimate, as prior to the availability of PET imaging for the diagnosis (see below), it was very challenging to make the diagnosis of cardiac sarcoidosis. More recent estimates in the United States have suggested that approximately 27% of people with sarcoidosis have cardiac involvement, and the true number is likely more. In reviews of autopsies of people with known sarcoidosis, up to 70% of people with known sarcoidosis had cardiac involvement.
The symptoms of sarcoidosis depend on the organs affected. When the lungs are affected, the most common symptoms are cough or shortness of breath. When the heart is affected, the most common symptoms are palpitations, dizziness or passing out, shortness of breath, or swelling. Sarcoidosis can follow a ‘waxing and waning’ pattern (even without treatment), such that symptom flares can get better and worse with time even without treatment – adding increasing challenges to the diagnosis. Generally, more flares over time lead to more scarring and fibrosis. This leads to more severe disease manifestations.
Cardiac sarcoidosis occurs when the inflammatory granulomas of sarcoidosis deposit in the heart tissue. This inflammation can lead to acute heart dysfunction, as well as chronic heart dysfunction from scarring in the sites of previous inflammation. The inflammation can occur in any part of the heart, but most commonly affects the heart’s electrical system (leading to an abnormal cardiac rhythm/palpitations) and/or the heart’s muscle itself (leading to decreased squeezing/relaxation of the heart muscle, which can cause congestive heart failure).
Abnormal electrical rhythms (called “arrhythmias”) can cause the heart to beat either too fast or too slow. Either of these abnormalities can lead to palpitations, dizziness/passing out, or – in a worst case scenario – sudden death. Abnormal electrical rhythms can originate from the upper chambers (the ‘atria’) or the lower chambers (the ‘ventricles’) of the heart. Your doctor will recommend the appropriate evaluation of arrhythmias, and may recommend treatment with medications or device placement (see below).
The specific cause of sarcoidosis remains unknown. Though it is likely that both environmental and inherited factors play a role, large studies of sarcoid patients haven’t shown a single gene or specific environmental agent that causes sarcoidosis.
Sarcoidosis is considered a rare disease. In the United States it is estimated there are between 150,000-200,000 people living with sarcoidosis – but because of the challenges in diagnosis, it is likely significantly underdiagnosed. About half of the people with sarcoidosis (45%) are diagnosed before 55 years of age, though it can occur at any age. Sarcoidosis is more prevalent in African-Americans, people of Scandinavian background, and women, but it is found worldwide in people of all ages and backgrounds. Interestingly, epidemiological studies show sarcoidosis is likely increasing in prevalence.
Diagnosing sarcoidosis can be challenging. Currently, there is no blood test to diagnose sarcoidosis. For pulmonary sarcoidosis, imaging tests with chest X-rays or chest CT scans may reveal findings typical for sarcoidosis, but such imaging tests usually aren’t sufficient to confirm the diagnosis. Tests to mention lung function called “pulmonary function tests” can be useful to measure the severity of the disease and to track response to treatment, but also will not separate out sarcoidosis from other lung disease. Sometimes, diagnosis is made by performing a biopsy of a site of disease, such as a nodule in the lung, an enlarged lymph node, or a rash on the skin. Other times, a diagnosis is made by a combination of symptoms, physical exam, and imaging findings.
In the case of cardiac sarcoidosis, biopsies are rarely used because cardiac sarcoidosis involvement of the heart is “patchy” –not uniformly affecting all of the heart muscle. Even in a patient with active inflammation, a biopsy showing normal heart muscle can be seen, and does not exclude the diagnosis. For that reason, most of the time a diagnosis of cardiac sarcoidosis is based on a combination of symptoms, imaging, and evaluation of the heart’s electrical rhythm. Imaging will almost always include an ultrasound of the heart (called an “echocardiogram”) and a nuclear medicine scan called Positron Emission Tomography (PET).
A PET scan is a nuclear medicine scan that takes place in a special scanner. The main principle of a PET scan is that areas of inflammation use more energy stores than normal tissues. For 24 hours prior to the test you will be asked to fast from any form of carbohydrates to cause the normal heart muscle to switch its primary energy source use from sugar (called “glucose”) to fats. Because areas with active inflammation need more energy, they will continue to use glucose as well. During the test, a special form of sugar called FDG (a form of sugar which can be tracked by the scanner) is administered. The scanner then detects how the FDG is used in the body, with areas of inflammation in the heart appearing “bright” on the PET scan. The PET scan may also identify other areas of the body where there is active inflammation from sarcoidosis (such as lymph nodes and the lungs), which can be helpful for confirming the diagnosis and/or tracking response to treatment. For cardiac sarcoidosis, serial PET scans are often used to determine the right dose of treatment for you, particularly in the first 6-12 months after diagnosis.
In some cases, an magnetic resonance imaging (MRI) scan of the heart can be useful, both because it gives high-resolution pictures of heart function, and because it can demonstrate areas of scar/inflammation. However, because it cannot differentiate well between areas of active inflammation and past inflammation, it is often less useful than PET scans for diagnosing cardiac sarcoidosis and for guiding ongoing therapy decisions.
The primary treatment goal in sarcoidosis is to stop the inflammation which damages the body’s organ. This is done with medications called “immunosuppressants”. Because these medicines suppress the immune system, it leaves patients more vulnerable to certain kinds of infections. Depending on the medications used, there are other side-effects which may occur as well. Therefore, the overall goal in treating sarcoidosis is to suppress the inflammation – but to do so using medications with the least risk possible. Common medications used include:
Steroids: These medications have the longest track-record for treating sarcoidosis, and have the advantage of acting quickly and (sometimes) most effectively to calm the inflammation. The most commonly used steroid is called prednisone. Steroids are often used at the time of initial diagnosis, or when there is a disease flare, for this reason. However, steroids can have significant side-effects, including weight gain, elevated blood sugar, decreased bone density, and insomnia – so the goal is typically to treat patients long term with either no steroids or a low maintenance dose.
Steroid-sparing agents: These medications often aren’t as strong as steroids, but can have the advantage of having fewer long-term side-effects. The most common steroid-sparing agent used is called methotrexate, though others such as azathioprine or hydroxychloroquine can be used as well. Most of the time, a steroid-sparing agent will be started early after diagnosis, with a goal to use it for long-term disease control as the steroids are weaned. These medications usually require periodic laboratory monitoring for safety.
TNF (Tumor Necrosis Factor) inhibitors: This class of steroid-sparing medication come in intravenous or injectable forms, and are often used if inflammation cannot be well-controlled with steroids, or if a patient would otherwise require high long-term doses of steroids to control the disease. Most commonly, this medication is prescribed by a Rheumatologist.
Prophylactic medications: For patients taking methotrexate, the vitamin folic acid is usually prescribed to help minimize side-effects. Depending on the doses of other immune-suppressing medications, you may be prescribed an antibiotic to help prevent certain kinds of infection.
Like other forms of sarcoidosis, cardiac sarcoidosis usually requires long-term immunosuppressive medications like those outlined above. However, patients with cardiac sarcoidosis may also need medications to treat their heart muscle dysfunction and/or electrical arrhythmias. Patients with a heart rhythm called “atrial fibrillation” or “atrial flutter” usually require blood-thinners. Additionally, depending on the specifics of heart structure and/or the electrical rhythm abnormalities which are present, patients may need placement of a “pacemaker” or “defibrillator (ICD)” device. Pacemakers are used if patients have a heart rate which is too slow, whereas defibrillators are used if patients are at high risk for having potentially life-threatening electrical rhythms which cause the heart to beat too fast.
Most of the time, serial PET scans are used early in the treatment course for cardiac sarcoidosis, in order to find the right balance of immunosuppressants which prevent significant inflammation in the heart while minimizing side-effects.