Header

Skip to main content

Slider

Cardiomyopathy & Amyloidosis

Cardiomyopathy is a broad term that is used to describe disease of the heart muscle, making it difficult for the heart to provide the body with an adequate blood supply. It can lead to heart failure and even death. In this article, we’ll discuss the types of cardiomyopathy and its connection to amyloidosis. 

 

Risk Factors 

It has no ideal target, as it can affect a person of any age, race, or gender. However, there are a number of risk factors that can put one at an increased chance of developing cardiomyopathy. 

  • Genetic History → Family history of cardiomyopathy, heart failure, or sudden cardiac arrest
  • High Blood Pressure → Over a long period of time
  • Heart Conditions → Past history of heart attack, coronary artery disease, or infection of the heart
  • Obesity → Tends to make the heart work harder to perform its normal function
  • Alcohol Use → Long period of alcohol use
  • Drug Use → Use of illicit drugs, such as cocaine, amphetamines, and anabolic steroids
  • Medications → Drugs used in the treatment of cancer, such as chemotherapy and radiation

Additionally, there are a number of diseases that increase the risk of developing cardiomyopathy, including:

  • Amyloidosis
  • Connective Tissue Disorders
  • Diabetes
  • Hemochromatosis (excess iron storage)
  • Sarcoidosis
  • Thyroid Disease

 

Types of Cardiomyopathy

  • Dilated Cardiomyopathy → Dilation of the left ventricle prevents the heart from pumping effectively. It most commonly occurs in middle-aged men and is typically the result of coronary artery disease, heart attack, or genetic defects.

  • Hypertrophic Cardiomyopathy → Abnormal thickening of heart muscle, most commonly affecting the muscles surrounding the left ventricle. This type of cardiomyopathy is strongly associated with a family history of the disease. There have been genetic mutations linked specifically with this type of cardiomyopathy.

  • Restrictive Cardiomyopathy → Stiffening of the heart muscle results in an inelasticity, making it difficult for the heart to expand and fill. It is most commonly seen in the elder population. The disease can be of idiopathic origin or of disease such as amyloidosis. This is the least common type of cardiomyopathy. 
  • Arrhythmogenic Right Ventricular Dysplasia → Scar tissue replaces healthy tissue of the right ventricle. This form of cardiomyopathy is rare and often the result of genetic mutations.
  • Unclassified Cardiomyopathy → All other forms of cardiomyopathy fall within this category.

 

Amyloidosis

Cardiomyopathy is one of the hallmarks of amyloidosis, often seen in the transthyretin form of amyloidosis (ATTR). ATTR-CM, or transthyretin amyloid cardiomyopathy, is a disease where the transthyretin protein becomes unstable and misfolds. This unstable protein (“amyloid”) then deposits in the heart muscle, resulting in thickening and stiffening of the heart. 

The two types of ATTR-CM are wild-type ATTR-CM (wtATTR) or hereditary ATTR-CM (hATTR). wtATTR-CM is the most common form of ATTR-CM, affecting predominantly white males 60+ years old. hATTR-CM is genetic affecting both men and women, and presents as early as 50+ years old. Interestingly, one of the mutations causing hATTR, V122I, is seen almost exclusively in individuals of African ancestry. It is believed that approximately 3-4% of African Americans carry this mutation, regardless of whether or not they develop symptoms. 

Most importantly, these are the most common and important signs and symptoms to be aware of, in order to diagnose ATTR amyloidosis.

 

Expert Insights – Cardiac Clues and Clinical Signs

In part 1 of a 2-part series, Dr. Keyur Shah, cardiologist from VCU Health’s cardiac amyloidosis care team, discusses the two most common types of transthyretin (TTR) amyloidosis: hereditary and wild-type. He details how ATTR cardiomyopathy amyloidosis presents and manifests itself to impair the heart. Dr. Shah lists clinical clues, “red flags,” and biomarkers which can raise suspicion of the presence of amyloidosis. Next he discusses insights that can be gained from echocardiograms, electrocardiograms, and cardiac MRIs and how they offer possible indicators of the disease presence. Once amyloidosis is suspected, definitive diagnosis testing is next.

In part 2 of a 2-part series, Sarah Paciulli, Heart Failure Nurse Practitioner, from VCU Health’s cardiac amyloidosis care team, continues from where Dr. Keyur Shah ended in Part I and discusses here in Part II the non-cardiac clues of transthyretin (TTR) amyloidosis. She expands the list of clinical clues and “red flags” that clinicians should be alert to, including orthopedic manifestations, erectile dysfunction, and polyneuropathy.

 

 

 

 

===========================================================

References:

https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709

https://www.yourheartsmessage.com

https://healthjade.net/familial-amyloidosis/

 

Cardiac Amyloidosis – AL and ATTR: Two Different Conditions

Dr. Mazen Hanna, cardiologist at the Cleveland Clinic and co-director of the Amyloid Program, explains how cardiac amyloidosis can originate from two very different types of amyloidosis: AL or ATTR. Dr. Hanna illustrates how physicians can identify cardiac amyloidosis and look to different diagnostic work-ups to understand whether the issues are due to AL or ATTR amyloidosis. These two conditions are treated differently and have different prognoses, emphasizing the importance of understanding the type of amyloidosis involved.

Cardiac Clues that Suggest Transthyretin Amyloidosis – Part I

In part 1 of a 2-part series, Dr. Keyur Shah, cardiologist from VCU Health’s cardiac amyloidosis care team, discusses the two most common types of transthyretin (TTR) amyloidosis: hereditary and wild-type. He details how ATTR cardiomyopathy amyloidosis presents and manifests itself to impair the heart. Dr. Shah lists clinical clues, “red flags,” and biomarkers which can raise suspicion of the presence of amyloidosis. Next he discusses insights that can be gained from echocardiograms, electrocardiograms, and cardiac MRIs and how they offer possible indicators of the disease presence. Once amyloidosis is suspected, definitive diagnosis testing is next.  See Part II: “Clinical Signs that Suggest Transthyretin Amyloidosis: Non-cardiac Clues” for more information.

Clinical Signs that Suggest Transthyretin Amyloidosis: Non-cardiac Clues – Part II

In part 2 of a 2-part series, Sarah Paciulli, Heart Failure Nurse Practitioner from VCU Health’s cardiac amyloidosis care team, continues from where Dr. Keyur Shah ended in Part I and discusses here in Part II the non-cardiac clues of transthyretin (TTR) amyloidosis. She expands the list of clinical clues and “red flags” that clinicians should be alert to, including orthopedic manifestations, erectile dysfunction, and polyneuropathy.  See Part I: “Cardiac Clues that Suggest Transthyretin Amyloidosis” for more.

 

Closing the Underdiagnosed Gap of Transthyretin Cardiac Amyloidosis in African Americans

Dr. Kevin Alexander, advanced heart failure and transplant cardiologist at the Stanford Amyloid Center, discusses transthyretin cardiac amyloidosis (ATTR-CM) and how today this is a “common rare disease,” more prevalent than previously appreciated. He summarizes findings from a study to understand diagnosis across the U.S. and how ATTR-CM disproportionately affects black individuals. This statistic is driven by the belief that 3-4% of African descendants carry the V122I TTR variant – translating to over 1 million carriers. Kevin offers a screening algorithm for who to screen for ATTR-CM, and examines sub-groups of African Americans that are important not to overlook.

Bicep Bunching & Amyloidosis

 

 

 

 

 

 

 

 

Often called “Popeye Deformity,” bicep bunching is visible when the patient flexes their arm, giving the appearance of Popeye-like arms. While it is the result of a torn tendon, it can be a leading indicator of more serious issues.

 

WHAT IS IT?

When the bicep tendon is ruptured, patients develop a bunching of the biceps upon flexion of the arm against gentle resistance. Tendon ruptures occur largely in the dominant arm of each patient, with one-quarter of patients developing ruptures in both arms. Interestingly, of those who had a rupture, 37.8% didn’t know it.

 

 

 

 

 

 

 

 

 

Below watch a video from The Lancet showing what bicep bunching looks like.

 

WHAT DOES IT POTENTIALLY INDICATE?

Two things.

1.  Bicep bunching may be a marker for ATTRwt. According to MedPage Today, spontaneous ruptures of the distal biceps tendon may be a marker of wild-type transthyretin (TTR) cardiac amyloidosis, a single-center study found. The presentation of a tendon rupture, an easily elicited diagnostic sign, in a patient with HFpEF should raise suspicion for wild-type TTR cardiac amyloidosis.

The picture below (Source: JAMA September 12, 2017 Volume 318, Number 10) offers examples of ruptured biceps tendon in two patients with biopsy-proven ATTRwt Cardiac Amyloidosis. ATTRwt indicates wild-type transthyretin amyloidosis. Patient 1 with prior rupture of the biceps tendon and bunching of the biceps with flexion. Patient 2 with acute rupture of the biceps tendon in the left arm; the tendon rupture occurred with trivial trauma, five years after Cardiac Amyloidosis diagnosis.

2.  ATTRwt may contribute to heart failure. Wild-type transthyretin amyloidosis (ATTRwt) is increasingly recognized as an important cause of heart failure with preserved ejection fraction (HFpEF).

 

WHY IS IT IMPORTANT?

Bicep bunching may be a marker of wild-type transthyretin (TTR) cardiac amyloidosis, potentially giving physicians an easy way to determine the underlying cause of heart failure with preserved ejection fraction (HFpEF) in some patients. Those who were aware, reported that the distal biceps tendon ruptured approximately five years prior to heart failure diagnosis, thus perhaps offering a leading insight.

In addition, early diagnosis of wild-type TTR cardiac amyloidosis (ATTRwt) is important because treatments are now available to slow, if not halt, disease progression. Unfortunately, the diagnosis of ATTRwt is often not considered in bicep bunching cases due to the perceived rarity of the disease.

“The clinical importance [of this study] is that the detection of a ruptured distal biceps tendon may be a clue for the diagnosis of wild-type TTR amyloidosis as the cause for heart failure. This diagnosis is often overlooked in clinical practice, so this relatively simple evaluation could increase detection of the disease,” said Stuart Katz, MD, of NYU Langone Health. “Enhanced detection could lead to better treatment.”

 

EXPERT INSIGHTS VIDEO ON MUSCULOSKELETAL MANIFESTATIONS

Dr. Shari Liberman, a hand and upper extremities surgeon from Houston Methodist Orthopedics & Sports Medicine, discussed six orthopedic manifestations and their pathology as it relates to systemic amyloidosis. Published studies, coupled with her experience, has led to a belief that these manifestations can offer important evidence of amyloidosis. She concludes with thoughts regarding an orthopedic differential and biopsy considerations for each of these manifestations.

 

Sources ———————————————————————————————————————
https://www.healthline.com/health/popeye-deformity
https://www.medpagetoday.com/cardiology/chf/67850
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818850/
https://www.researchgate.net/publication/319657750_Association_Between_Ruptured_Distal_Biceps_Tendon_and_Wild-Type_Transthyretin_Cardiac_Amyloidosis
https://www.shoulderdoc.co.uk/article/721
https://www.thelancet.com/doi/story/10.1016/vid.2019.02.26.107679
https://www.youtube.com/watch?v=fHXu_0IZ3vU

Diagnosing Amyloidosis: A Two-Step Process

Amyloidosis can present in many types with the three most prevalent being light chain (AL) amyloidosis, hereditary variant transthyretin (ATTRv) amyloidosis, and wild type transthyretin (ATTRwt) amyloidosis. Being a rare disease, diagnosis can be particularly challenging, given that the general medical community is not well educated on the malady and symptoms are often associated with other more common ailments.

Successfully diagnosing the disease requires a two-step process before an appropriate treatment program can be determined and implemented for each patient.

  1. First, if amyloidosis is suspected, testing must be done to confirm the presence of amyloid.
  2. Second, once the presence of amyloid is confirmed, testing must then be done to identify and confirm the type of amyloidosis.

It is crucial that the second step, where the correct type of amyloidosis is identified, as the treatment regime can be different for each type. Here we share two different patient experiences which illustrate successful execution of the two-step diagnostic process.

Patient Case #1

The first case involved a 23-year old female. In 2017 she experienced an episode of coughing up blood, after which she looked in her throat with a flashlight and discovered a sizable lump. The patient met with a local ENT, who incorrectly diagnosed allergies, and prescribed over-the-counter medicine. With no improvement, she met with a second ENT. Testing was performed on the patient’s left oral pharynx utilizing a Congo red staining biopsy process which confirmed the presence of amyloid in the tissue. Additionally, mass spectrometry was performed which successfully differentiated the type of amyloidosis as being ALH (lambda light chain and delta heavy chain). Subsequently, she was referred to a hematologist who ordered a bone marrow biopsy and blood testing. The bone marrow biopsy summary notes read “….in conjunction with the concurrent finding of monoclonal lambda light chain restricted plasma cells in the marrow by flow cytometry, the findings are consistent with involvement of the marrow by a plasma cell neoplasm.”

Additionally, the blood testing confirmed elevated light chains as shown below.

Patient Case #2

The second case involved a man in his mid-fifties. He began experiencing disease symptoms approximately 6-7 years prior to being diagnosed in early 2019. He initially experienced gradually progressing numbness in his feet, legs, hands and forearms, as well as bilateral carpal tunnel syndrome. Soon after, he began experiencing symptoms of lightheadedness and fainting. Additionally, he started experiencing progressive gastro-intestinal issues such as acid reflux, chronic coughing, and frequent bouts of constipation and diarrhea. By 2018, his physical condition was rapidly deteriorating, including a total weight loss of approximately 80 pounds. During this extended period of time he was seen by a variety of physicians including internal medicine, neurology, endocrinology, gastroenterology, oncology, and cardiology, none of who were successful in arriving at a conclusive diagnosis. His list of maladies included cardiomyopathy, peripheral neuropathy, autonomic neuropathy, bilateral carpal tunnel syndrome, and gastroparesis, all which are classic symptoms of amyloidosis.

Finally, in early 2019 his condition was successfully diagnosed by an amyloidosis specialist. An echocardiogram was performed as well as a cardiac MRI (utilizing a gadolinium tracer) to identify amyloid fibrils and related damage in the heart tissue. These tests confirmed the presence of amyloid. A free light chain serum test was performed which ruled out AL amyloidosis, and Transthyretin DNA sequencing was performed to differentiate between the hereditary variant and wild-type of ATTR, which identified the T80A (legacy T60A) variant of transthyretin (ATTRv) amyloidosis. The two tests were successful in identifying the type of amyloidosis. The associated testing results are show below.

Echocardiogram Summary Notes

Associated Cardiac MRI Interpretation

DNA Sequencing Result

 

Once Diagnosed, Next is a Treatment Plan

Once the presence of amyloid is confirmed, and the type is identified, then it is time to treat the disease. In each of these patient cases the disease was diagnosed utilizing the two-step process to identify and confirm the type of amyloidosis. In both cases, successful treatment regimens were implemented which were effective in putting the disease into remission and/or halting disease progression.

Treatment options for amyloidosis have been vastly improved over the past several years. What was previously considered to be a foregone fatal disease can now be a manageable chronic disease. To ensure the best patient outcome, a timely diagnosis utilizing the two-step process, is essential.

 

Expert Insights: Diagnosing AL and ATTR Cardiac Amyloidosis

Dr. Grodin, a cardiologist and co-director of the UT Southwestern Multidisciplinary Amyloidosis Program, goes through the diagnostic process for AL and ATTR cardiac amyloidosis. Understanding that there are key differences and typing of amyloidosis which are paramount to consider in order to subsequently develop a treatment plan. He concludes with diagnostic algorithms to help clinicians arrive at an accurate diagnosis.

Expert Insights: Building an Index of Suspicion for Cardiac Amyloidosis

Understanding that amyloidosis exists BEFORE organs become involved is critical to developing an early diagnosis. Dr. Grodin, a cardiologist and co-director of the UT Southwestern Multidisciplinary Amyloidosis Program, discusses these early symptoms, family history, and red flags to be aware of in order to build an index of suspicion.

Expert Insights: Raising Awareness of Cardiac Amyloidosis

Dr. Barry Trachtenberg, cardiologist at Houston Cardiovascular Associates, shares ways that physicians can raise their awareness of cardiac amyloidosis, whether AL or ATTR. He discusses multiple organ systems and how test results may present clues to consider amyloidosis. He offers a diagnostic algorithm with early red flags that can aid in the identification and typing of amyloidosis. Dr. Trachtenberg concludes with keys to remember, including questions to ask patients, which can elevate the suspicion of amyloidosis.

This website uses cookies

This site uses cookies to provide more personalized content, social media features, and ads, and to analyze our traffic. We might share information about your use of our site with our social media, advertising, and analytics partners who may combine it with other information that you’ve provided to them or that they’ve collected from your use of their services. We will never sell your information or share it with unaffiliated entities.

Newsletter Icon