Amyloidosis (am’i – loy- doh’sis) is a disease characterized by extracellular accumulation of amyloid in various organs of the body.1 The cause of this disease is the deposit of amyloid, a type of protein, that when abnormally present in the body, can attach itself within the tissues and organs of the body. If these deposits replace or surround muscle sections, it can make it hard for that muscle or structure to work properly.
This is a rather rare disease that is sometimes also called an infiltrative disease. There are many types of amyloidosis and cardiac amyloidosis is one of them. Cardiac amyloidosis is more common in men than in women and the disease is rare in people under age 40.
This disease can also be known as the ‘stiff heart’ syndrome or secondary cardiac amyloidosis. The primary concern is that when these deposits take the place of normal heart tissue, the heart becomes ‘stiff.’ It is the most typical type of restrictive cardiomyopathy. Other types of restrictive/infiltrative diseases are sarcoidosis (a granuloma disease), hemochromatosis (high deposits of iron in the muscles), fibrosis from radiation, and various tumors and infiltrations of the heart.
The cardiac variation of this disease can present with 4 specific syndromes: restrictive cardiomyopathy, systolic heart failure (cardiomyopathy), orthostatic hypotension (very poor prognosis) and a conduction pathway disease.
The patient who comes to the lab can have many complaints, but some common ones usually occur, which can include palpitations, swelling of the legs and ankles, a history of excessive urination at night, fatigue, shortness of breath at night or trouble breathing while lying down (orthopnea). Because of the effects of the amyloids on the heart muscle, these patients can have congestive heart failure due to the cardiomyopathy.
Unfortunately, the only definitive diagnosis of cardiac amyloidosis is a cardiac biopsy. If you don’t perform those procedures in your lab right now, chances are you never will, since it is usually reserved for transplant and research facilities. With a cardiac biopsy, a special catheter is placed within the heart chambers, and a “bite” is taken out of the tissue (Figure 1). This tissue is then sent to the pathology lab for analysis. Without the use of a biopsy, diagnosis is made by history, signs and symptoms, and by ruling out other diseases. Sometimes a measurement of circulating serum proteins can be helpful in the confirmation of the disease3 or proteins in the urine can provide clues to the cardiologist.
Now you know that these patients suffer from cardiomyopathy because their heart muscle is not allowed to function properly. When these patients receive a cardiac catheterization, we might see some specific things. If the heart muscle is “stiff,” we will see an elevated left ventricular end-diastolic (ED) pressure. If the myocardium is diffusely fibrotic or infiltrated with the amyloid, a very high end-diastolic stretching force may be required to produce even a normal end-diastolic sarcomere length.2 Remember that sarcomeres are the components in the heart muscle that contract and relax. There may need to be more pressure placed on them to relax in order to allow the heart to fill with blood and also get a proper contraction to expel the blood from the ventricle. This “forced filling” pressure of the ventricle results in higher end-diastolic pressures.
On the left ventriculogram, you will likely see the classic cardiomyopathy silhouette (large left ventricle, poor ejection fraction), as well as a large atrium. The large atrium is also part of the cardiomyopathy process due to the inability to get all the necessary flow into the left ventricle. This leaves the atrium “holding the ball.” Over a period of time, the atrium will expand/enlarge to accommodate this flow imbalance.
With today’s echocardiogram technology, there is seldom a need to perform a right heart catheterization (RHC) on these patients. If a RHC were performed on the symptomatic patients, there would likely be the classic ‘dip and plateau’ square root sign. This is indicative of the impairment of chamber filling due to the restrictive pathology (Figure 2).
There may also be times where these patients come in with what appears to be an acute coronary syndrome (chest pain, dyspnea, electrocardiogram changes, etc.), but after angiography, the coronary arteries appear normal. If the amyloids are deposited in the intramural (in the muscle wall) arteries, particularly in the media and adventitia layers, there can be impairments in coronary perfusion.3 This lack of perfusion can create chest pain due to the lack of proper oxygenation to the muscle. However, the main arteries will appear ‘normal’ during angiograms.
These patients have a poor prognosis after symptoms appear and once they are diagnosed. Cardiac involvement generally denotes a high mortality rate, regardless of the method of treatment. The median survival rate from the onset of congestive heart failure is only 6 months.4 Syncope indicates a poor prognosis as well, and is often a precursor of sudden cardiac death.5 In the presentation of cardiomyopathy, these patients may only have a life expectancy of a few years. Heart transplant is generally not an option because amyloidosis will also affect other organs at the same time, excluding the individual from being a transplant patient.
Treatments are generally based upon managing the symptoms without interfering with cardiac output. During left ventricular analysis, a left ventricular ED pressure of 25 or more is not uncommon. However, if the increase in ED pressure is treated, a reduction in the sarcomere stretch can occur, and this will result in an equal decrease in cardiac output. Pacemakers and ICDs may be used in cases where cardiac amyloidosis is thought to be in early stages.
A recent case study we are familiar with involved a 49-year-old male who presented with chest tightness upon exertion, progressive dyspnea and orthopnea. Echo indicated an ejection fraction of approximately 30%, compared to normal left ventricular function a year earlier. Bi-atrial enlargement was also present and there was a positive history of early aged sudden cardiac death in the family. Left heart cardiac catheterization was performed, which yielded normal coronary arteries. The left ventriculogram revealed obvious global myopathy with regurgitation into a very large atrium. (Angiograms can be seen at http:// www.rcisreview.com/AskTheInstructorMarch2008.htm). With this history and normal coronaries, an infiltrative disease must be ruled out. At the time of this article, a definitive diagnosis is not available.
When you have a ‘negative’ case after the patient had presented with acute coronary signs and symptoms, but cardiomyopathy is present, infiltrative disorders, such as amyloidosis, should be considered as a possible pathology. Next month, we will answer a question about procedures to evaluate aortic and mitral valves.
1. Stedman’s Medical Dictionary for the Health Professions and Nursing, 5th edition. Philadelphia: Lippincott Williams & Wilkins, 2004.
2. Baim DS, Grossman W. Grossman’s Cardiac Catheterization, Angiography, and Intervention, 6th edition. Philadelphia: Lippincott Williams & Wilkins, 2000.
3. Libby P, Bonow RO, Mann DL, Zipes DP. Braunwald’s Heart Disease, 8th edition. St. Louis: Saunders, An Imprint of Elsevier, 2007.
4. Grogan M, Gertz MA, Kyle RA, et al. Five or more years of survival in patients with primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol 2000; 85:664–665, A11.
5. Chamarthi B, Dubrey SW, Cha K, et al. Features and prognosis of exertional syncope in light-chain associated AL cardiac amyloidosis. Am J Cardiol 1997;80:1242–1245.