Spinal stenosis is narrowing of the spinal column that causes pressure on the spinal cord, or narrowing of the openings (called neural foramina) where spinal nerves leave the spinal column.
This can develop as you age from drying out and shrinking of the disk spaces. (The disks are 80% water.) The narrowing can cause compression on nerve roots resulting in pain or weakness of the legs. If this happens, even a minor injury can cause inflammation of the disk and put pressure on the nerve. You can feel pain anywhere along your back or leg(s) that this nerve supplies.1
SYMPTOMS1
Symptoms often get worse slowly over time. Most often, symptoms will be on one side of the body, but may involve both legs. Symptoms include:
Numbness, cramping, or pain in the back, buttocks, thighs, or calves, or in the neck, shoulders, or arms
Symptoms are more likely to be present or get worse when you stand or walk. They often lessen or disappear when you sit down or lean forward. Most people with spinal stenosis cannot walk for a long period. More serious symptoms include:
Difficulty or poor balance when walking
Problems controlling urine or bowel movements
A POTENTIAL CLUE TO AMYLOIDOSIS?
Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and transthyretin has been demonstrated in some deposits. Lumbar spinal stenosis is also a condition of usually elderly individuals in whom narrowing of the lumbar spinal canal leads to compression of nerves to the lower limbs.
“Another very important historical clue is spinal stenosis, and actually that’s much more commonly seen in patients with ATTR than AL, and in fact, again, almost exclusively in wild type,” according to Dr. Mazen Hanna2
WHAT IS SENILE, AKA WILD-TYPE, AMYLOIDOSIS (ATTRwt)?
Amyloidosis is a generic name for a very diverse group of protein folding disorders, all characterized by creation of cross-beta-sheet fibrils. At least 30 different human proteins have been shown to form amyloid fibrils in vivo (7). Two main groups of amyloid conditions exist: systemic and localized. In the systemic conditions, deposits occur in many organs and tissues, and the diseases are usually life-threatening; in each of these diseases one out of at least 15 plasma proteins forms amyloid fibrils far from the place of parent protein synthesis. In the localized conditions, the proteins are expressed at the site of deposition (8). In both groups, fibrils usually deposit extracellularly and can form conspicuous masses that deform a tissue and interfere with its normal functions.5
Senile systemic amyloidosis (SSA), derived from wild-type transthyretin (TTR), is common in association with aging, although symptom-giving disease usually is comparably rare and affects males at least 10 times more often than women. Restrictive cardiomyopathy is the main clinical expression. However, carpal tunnel syndrome is common in SSA, and widely spread wild-type ATTR amyloid deposits at other connective tissue sites have been demonstrated (25).5
Joint cartilage and ligaments are targets of both localized and systemic amyloid. Of the systemic forms, Aβ2-microglobulin [for nomenclature, see (7)] amyloidosis is well-known to engage skeletal and joint structures in patients under hemodialysis due to renal insufficiency (9-13). Also, immunoglobulin light chain (AL) amyloidosis is known to generate a variety of symptoms from joints and skeleton, sometimes with neural lesions. Carpal tunnel syndrome is often noted in transthyretin (ATTR) and Aβ2-microglobulin amyloidosis (15–17).5
HEAR FROM AN EXPERT ON MUSCULOSKELETAL SYMPTOMS RELATED TO AMYLOIDOSIS
Dr. Shari Liberman, a hand and upper extremities surgeon from Houston Methodist Orthopedics & Sports Medicine, discusses 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.
CONCLUSION
From the studies referenced therein, results suggest that transthyretin-derived amyloid deposits may occur more frequently in various ligaments and tendons than originally expected3 and that lumbar spinal stenosis quite frequently may be a consequence of senile systemic amyloidosis [also known as wild-type amyloidosis; ATTRwt]5.
Stay suspicious. It’s more common than you may think.
Sueyoshi T, Ueda M, Jono H, Irie H, Sei A, Ide J, Ando Y, Mizuta H. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011 Sep;42(9):1259-64. doi: 10.1016/j.humpath.2010.11.017. Epub 2011 Feb 21. PMID: 21334722.
Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. doi:10.3109/03009734.2014.895786
Light Chain (AL) Amyloidosis Clinical Practice Guidelines – American Society of Hematology 2026
The American Society of Hematology (ASH) has released new Clinical Practice Guidelines on the diagnosis of light chain (AL) amyloidosis, a rare and life-threatening bone marrow disorder. The guidelines present 12 evidence-based recommendations designed to help clinicians and facilitate early and accurate diagnosis of AL amyloidosis. Participating in the two-year research was a large group of multi-disciplinary amyloidosis experts, as well as Deb Boedicker from Mackenzie’s Mission/Amyloidosis Speakers Bureau. Below we summarize the 12 recommendations, followed by a link to the full publication. In addition, at the end you’ll find a link to a comprehensive Resource Center which support these Clinical Practice Guidelines.
The primary goals of these guidelines are to review, critically appraise and implement evidence-based recommendations that will enhance early detection, timeliness and accuracy of diagnosis of AL amyloidosis. Through improved provider and patient education of the available evidence and creation of evidence-based recommendations, these guidelines aim to provide clinical decision support that will result in clear diagnostic decision making with known potential outcomes and enable timely diagnosis of AL amyloidosis by multidisciplinary teams.
ENHANCING CLINICAL SUSPICION
Should serum and urine immunofixation (SIFE and UIFE) and serum free light chains (sFLC) be used to increase suspicion of AL amyloidosis in individuals with cardiac symptoms? Recommendation 1
For individuals with suspected cardiac amyloidosis, the ASH Guideline Panel recommends the use of serum and urine immunofixation (SIFE and UIFE) and serum free light chain (sFLC) assay to increase clinical suspicion of cardiac AL amyloidosis.
Should serum and urine immunofixation (SIFE and UIFE) and serum free light chains (sFLC) be used to increase suspicion of AL amyloidosis in individuals with unexplained proteinuria? Recommendation 2
For individuals with unexplained proteinuria, the ASH Guideline Panel suggests performing paraprotein testing (SIFE/UIFE/sFLC) to increase clinical suspicion of AL amyloidosis.
Should cardiac MRI (CMR) be used to diagnose cardiac AL amyloidosis in individuals suspected of having cardiac amyloidosis (positivity in any of the following studies: SIFE, UIFE, or sFLC, abnormal cardiac biomarkers, and non-diagnostic echocardiographic findings)? Recommendation 3
For individuals with positivity in any of the following studies SIFE, UIFE, or sFLC, and abnormal cardiac biomarkers, and non-diagnostic echocardiography, the ASH Guideline Panel suggests performing cardiac magnetic resonance (CMR) rather than not performing CMR to increase clinical suspicion of cardiac amyloidosis.
Should cardiac MRI (CMR) be used to diagnose cardiac AL amyloidosis in individuals with abnormal cardiac biomarkers, echocardiography, and positivity in any of the following studies: SIFE, UIFE, or sFLC? Recommendation 4
For individuals with positivity in any of the following studies SIFE, UIFE, or sFLC, and abnormal cardiac biomarkers, and echocardiography consistent with amyloidosis, the ASH Guideline Panel suggests against performing cardiac magnetic resonance (CMR) and instead performing tissue biopsy to diagnose cardiac AL amyloidosis.
DIAGNOSIS
Should Bone Scintigraphy with technetium 99m – pyrophosphate (PYP), technetium 99 m – 3, 3 diphosphono –1,2 propranodicarboxylic (DPD) and technetium 99 m-hydroxymethylene Diphosphonate (HMDP) be used to diagnose amyloidosis in suspected individuals? Recommendation 5
For individuals with a suspicion of AL amyloidosis, the ASH Guideline Panel recommendsagainst the use of bone scintigraphy (PYP, DPD, HMDP) for the diagnosis of AL cardiac amyloidosis.
Should Bone Scintigraphy (PYP, DPD, HMDP) be used to diagnose ATTR amyloidosis in suspected individuals? Recommendation 6
For patients without evidence of a plasma cell disorder (normal serum free light chain levels and no monoclonal proteins on serum and urine immunofixation) and suspicion of cardiac amyloidosis, the ASH Guideline Panel recommends the use of bone scintigraphy (PYP, DPD, HMDP) for the diagnosis of Cardiac ATTR amyloidosis.
Should surrogate biopsy vs. cardiac biopsy be used to diagnose AL amyloidosis in individuals suspected to have cardiac amyloidosis? Recommendation 7
For individuals with suspected AL cardiac amyloidosis with abnormal cardiac biomarkers, diagnostic echocardiogram, and positivity in any of the following studies: SIFE, UIFE, or sFLC, the ASH Guideline Panel suggests either starting with performing both fat pad sampling and bone marrow biopsy or with endomyocardial biopsy.
Should surrogate biopsy vs renal biopsy be used to diagnose AL amyloidosis in individuals suspected to have renal amyloidosis? Recommendation 8
For individuals with suspected light chain renal amyloidosis and positivity in any of the following studies SIFE, UIFE, or sFLC, the ASH Guideline Panel suggests starting with performing both abdominal fat pad sampling and bone marrow biopsy over renal biopsy.
Should surrogate biopsy vs. peripheral nerve biopsy be used to diagnose AL amyloidosis in individuals suspected to have neurological amyloidosis? Recommendation 9
For individuals with a monoclonal gammopathy and generalized small or large fiber peripheral neuropathy or autonomic neuropathy suspected of having AL amyloidosis, the ASH Guideline Panel suggests performing both fat pad sampling and bone marrow biopsy over nerve biopsy.
Should surrogate biopsy vs target organ biopsy be used to diagnose AL amyloidosis in individuals suspected to have AL amyloidosis with multiorgan presentation? Recommendation 10
For individuals with suspected multiorgan AL amyloidosis, the ASH Guideline Panel suggests starting with surrogate biopsies (combination of fat pad sampling and bone marrow biopsy) over target organ biopsy if surrogate biopsies can be performed expeditiously. If endomyocardial biopsy or renal biopsy are more feasible than fat pad sampling and bone marrow biopsy, these symptomatic target tissues should be preferentially biopsied.
Should Congo Red Staining on bone marrow biopsy that has already been performed be used to diagnose AL amyloidosis in individuals with Multiple Myeloma and Smoldering Myeloma? Recommendation 11
For individuals with plasma cell dyscrasias (multiple myeloma and smoldering multiple myeloma), the ASH Guideline Panel suggests performing Congo red staining on bone marrow biopsies that may have already been performed.
ORGAN INVOLVEMENT
In individuals with AL amyloidosis with no cardiac symptoms, should clinicians use cardiac biomarkers/investigations [BNP, NT-proBNP, troponin (I,C,T, Highly Sensitive), 2D Echo with strain, Cardiac MRI] or not to evaluate for cardiac involvement? Recommendation 12
For individuals with proven AL amyloidosis and with no cardiac symptoms, the ASH Guideline Panel recommends performing cardiac biomarkers (high sensitivity troponin, and BNP or NT-proBNP) and cardiac imaging rather than not performing these tests to define the presence and extent of cardiac involvement at diagnosis.
KEY CONCLUSIONS
The use of serum immunofixation, urine immunofixation and serum free light chains enhances the clinical suspicion of AL amyloidosis. The diagnosis of AL amyloidosis can be made effectively through surrogate biopsies which require both a bone marrow biopsy and fat pad sampling. However, target organ biopsies may be favoured in certain clinical situations.
Overarching good practice statements:
1. The ASH panel agreed that it is essential to assess for major organ involvement in patients with confirmed AL amyloidosis, as this guides further management and risk stratification.
2. A multidisciplinary team is typically required for the timely and accurate diagnosis and management of AL amyloidosis.
The red flag signs and symptoms provide a summarized way to elevate suspicion and hopefully accelerate the diagnostic timeline.
RED FLAG SIGNS AND SYMPTOMS FOR CARDIAC INVOLVEMENT
HFpEF (heart failure with preserved ejection fraction)
Moderate or Severe LVH in absence of a significant history of untreated hypertension on imaging.
Echocardiogram: Severe left ventricular hypertrophy, advanced diastolic dysfunction, reduced left ventricular global longitudinal strain with an apical sparing pattern
EKG/Arrhythmia: Low voltage and/or discordance between voltage on EKG and left ventricular wall thickness on imaging, pseudo-infarct pattern, and arrhythmias including atrial fibrillation, heart block, and ventricular tachycardia/ventricular fibrillation
Elevated biomarkers (Troponin and NT-Pro BNP) in absence of CAD
Constellation of symptoms suggesting cardiac, renal, and peripheral nervous system disease
Low Flow, Low Gradient Aortic Stenosis
RED FLAG SIGNS AND SYMPTOMS FOR RENAL INVOLVEMENT
Inability to tolerate ACE/ARB
Change in hypertension status unexplained by medication i.e. intolerance/hypotension on previously tolerated therapy.
Unexplained proteinuria (albumin predominant) without diabetes (or not thought to be related to be diabetes or any other reason) and positive laboratory tests (monoclonal proteins and/or abnormal light chains (must be clonal or above renal limits)
Proteinuria in diabetic with positive monoclonal protein
RED FLAG SIGNS AND SYMPTOMS FOR NEUROLOGICAL INVOLVEMENT
Small fiber neuropathy: pain and temperature impairments, allodynia and hyperalgesia
A snapshot of the ASH Clinical Practice Guidelines — “Diagnosis of Light Chain (AL) Amyloidosis: What You Should Know”
What it covers
Why it matters
Who it affects
What are the highlights
A Disease State Infographic
A Visual Summary: a concise visual aid intended to support understanding of the recommendations and to aid in clinical decision-making.
A Pocket Guide: a brief, evidence-based pocket guide intended to help physicians provide quality care to patients.
Teaching Slides: educational slides intended to teach about the diagnosis of amyloidosis.
Audit Report: A set of metrics intended to assess compliance with the ASH Clinical Practice Guidelines on Diagnosis of Light Chain Amyloidosis. This audit report can be used to identify quality gaps at your institution and improve care for patients with light chain amyloidosis.
ASB Recognized as Leader in Early Medical Education
The Amyloidosis Speakers Bureau (ASB) is recognized as a leader in enhancing medical education and awareness, starting in medical school and continuing through fellowship, which is essential for improving early disease recognition.
The editorial commented on the recent transformation in the field of amyloid cardiomyopathy. It references a comprehensive retrospective analysis leveraging data from the Veterans Health Administration, the nation’s largest integrated health care system, to examine diagnostic patterns in patients with heart failure (HF) and ATTR-CM between 2016 and 2022. This study underscores a critical gap: Even within a highly integrated health system with access to diagnostic tools and longitudinal data, under-recognition and delayed diagnosis of ATTR-CM remain pervasive.
“Why does diagnostic delay matter so much? Although it may seem less urgent given that patients are eventually diagnosed and ATTR-CM is generally considered a more indolent condition than amyloid light-chain amyloidosis, the clinical impact of delayed diagnosis is significant. Studies have shown that even a delay of 3 months can result in patients presenting with a higher NYHA classification, indicating more advanced disease at the time of diagnosis.8 Most importantly, we now have 3 U.S. Food and Drug administration–approved therapies for ATTR-CM that not only extend survival but also reduce HF hospitalizations and improve quality of life. Crucially, these treatments are most effective when initiated in the earlier stages of disease. With this growing arsenal of disease-modifying therapies, timely diagnosis is no longer just ideal, it is imperative.
To reduce diagnostic delays and shift clinical focus from treating isolated comorbidities to the broader picture, we must begin to “see the forest” instead of just the trees. Three strategies may help. First, enhancing education and awareness, starting in medical school and continuing through fellowship, is essential for improving early recognition. Advocacy organizations like the Amyloidosis Speakers Bureau, a nonprofit entity dedicated to educating medical trainees and early-career clinicians, lead the way with raising awareness among providers.9 Second, clinicians should more consistently apply existing diagnostic tools, such as the ATTR-CM score,10 to avoid overlooking amyloidosis in patients with HFpEF. Third, integrating artificial intelligence into diagnostic workflows could identify potential cases by identifying red flags, within electronic medical records, prompting consideration of cardiac amyloidosis alongside common comorbidities such as atrial fibrillation, coronary artery disease, and chronic kidney disease. If we do not think of amyloidosis, we will not diagnose it. In 2025, we have the tools to identify and treat ATTR-CM. We just need to look up from the trees in time to recognize the forest, often hiding in plain sight.”
Accelerating the Diagnosis of Cardiac Amyloidosis with AI
What is Cardiac Amyloidosis?
According to the University of Chicago, “Cardiac amyloidosis is a heart condition in which abnormal proteins build up in the heart muscle, making it stiff and impairing its ability to pump blood. Multiple life-prolonging drug treatments for this condition have recently become available, but without early diagnosis, physicians miss out on opportunities to extend patients’ survival and quality of life.”
“Unfortunately, cardiac amyloidosis can be challenging to diagnose, because it’s often difficult to distinguish from other heart issues without a burdensome amount of testing,” explained co-lead author Jeremy Slivnick, MD, a cardiologist at the University of Chicago Medicine.
The Promise of AI
AI is improving cardiac amyloidosis diagnosis by using algorithms to analyze medical imaging and data, which can lead to earlier and more accurate detection than traditional methods. These tools can automatically analyze echocardiograms, electrocardiograms (ECGs), and scintigraphy scans to identify the disease, which is crucial for timely treatment because new therapies are most effective in the early stages. Some AI models are FDA-cleared and are being implemented in clinical settings.
How AI is used in diagnosing cardiac amyloidosis
Echocardiography: AI tools can analyze echocardiogram videos to detect signs of cardiac amyloidosis with high accuracy, outperforming traditional scoring methods.
Electrocardiogram (ECG): AI-enhanced ECG models can identify patients at high risk for cardiac amyloidosis, helping to flag them for further evaluation and monitor disease progression during treatment.
Scintigraphy: AI systems can analyze nuclear medicine scintigraphy scans to automatically detect cardiac amyloidosis, performing as reliably as medical experts.
Infrared Spectroscopy: A new method uses infrared imaging to identify the molecular “fingerprints” of amyloidosis-causing proteins. AI is used to analyze these fingerprints, providing a faster, non-invasive alternative to biopsies.
Benefits of using AI
Earlier detection: AI can identify the disease at an earlier stage, which is critical for starting treatment when it is most effective.
Improved accuracy: AI tools have shown high sensitivity and specificity in detecting amyloidosis, sometimes outperforming current clinical practices.
Increased efficiency: Some AI systems can provide results within minutes, speeding up the diagnostic process and integrating seamlessly into clinical workflows.
Reduced costs and invasiveness: AI has the potential to reduce reliance on expensive or invasive procedures, like biopsies, especially when used to screen patients.
Broader access: The broad applicability of AI to common tests like echocardiograms and ECGs means it can be implemented in many clinical settings.
Limitations and future directions
Need for prospective validation: While promising, AI models still require more testing in clinical practice to understand their full capabilities and limitations.
Data and transparency: Challenges remain, including the need for more diverse data and improving the transparency of AI decision-making.
Widespread implementation: While some AI tools have received FDA clearance and are being implemented, widespread use in routine care is still a future goal.
Ultromics’ EchoGo Amyloidosis Tool
Researchers from Mayo Clinic and Ultromics, with investigators at the University of Chicago Medicine and collaborators around the world, validated and tested EchoGo Amyloidosis on a large and multiethnic patient population and compared its abilities to other diagnostic methods for cardiac amyloidosis.
“Their findings, published in the European Heart Journal, show that the AI model was highly accurate, with 85% sensitivity (correctly identifying those with the disease) and 93% specificity (correctly identifying those without the disease). Using a single echocardiography videoclip, the model was effective across all major types of cardiac amyloidosis and distinguished it from other conditions with similar characteristics.”
An Example of AI Integrated Into Workflow at the City of Hope
Hear from Dr. Faizi A. Jamal, Chief, Division of Cardiology and Director, Non-Invasive Cardiology Laboratory at the City of Hope National Medical Center who has been at the forefront of evaluating the clinical utility of AI based review of echocardiography in the diagnosis of cardiac amyloidosis. In this video he shares his experience with Ultromics’s EchoGo Amyloidosis, and how the City of Hope has incorporated this into their clinical workflow. He discusses the typical initial reasoning for ordering echocardiograms, which is to understand the severity of issues such as HFpEF or Aortic Stenosis, and how AI can take the analysis further to explore whether cardiac amyloidosis may be an underlying cause of the condition. Dr. Jamal discusses the multiple clinical challenges to diagnosing cardiac amyloidosis and details the numerous benefits experienced from the AI based review of echocardiograms. “EchoGo Amyloidosis is going to be revolutionary, based upon the volume of undiagnosed patients that are out there. It’s going to undoubtedly detect patients and impact morbidity and mortality for this disease.”
Kamel MA, Abbas MT, Kanaan CN, Awad KA, Baba Ali N, Scalia IG, Farina JM, Pereyra M, Mahmoud AK, Steidley DE, Rosenthal JL, Ayoub C, Arsanjani R. How Artificial Intelligence Can Enhance the Diagnosis of Cardiac Amyloidosis: A Review of Recent Advances and Challenges. J Cardiovasc Dev Dis. 2024 Apr 13;11(4):118. doi: 10.3390/jcdd11040118. PMID: 38667736; PMCID: PMC11050851.
Ultromics EchoGo Amyloidosis The first FDA-cleared, AI-based screening tool designed to help identify patients at risk of cardiac amyloidosis from an echocardiogram.
Clinical Utility of AI Based Review of Echocardiography for Diagnosis of Cardiac Amyloidosis
Dr. Faizi A. Jamal, Chief, Division of Cardiology and Director, Non-Invasive Cardiology Laboratory at the City of Hope National Medical Center has been at the forefront of evaluating the clinical utility of AI based review of echocardiography in the diagnosis of cardiac amyloidosis. In this video he shares his experience with Ultromics’s EchoGo Amyloidosis, and how the City of Hope has incorporated this into their clinical workflow. He discusses the typical initial reasoning for ordering echocardiograms, which is to understand the severity of issues such as HFpEF or Aortic Stenosis, and how AI can take the analysis further to explore whether cardiac amyloidosis may be an underlying cause of the condition. Dr. Jamal discusses the multiple clinical challenges to diagnosing cardiac amyloidosis and details the numerous benefits experienced from the AI based review of echocardiograms. “EchoGo Amyloidosis is going to be revolutionary, based upon the volume of undiagnosed patients that are out there. It’s going to undoubtedly detect patients and impact morbidity and mortality for this disease.”
Click HERE, or on graphic below to view Dr. Jamal’s video.
Patient Insights: Think Beyond the Silos
Our patient speakers at the Amyloidosis Speakers Bureau are powerful educators and offer compelling insights. Have a listen to this brief clip from Robert where he talks about the need for broader coordination across specialists and how this is critical for patients with multi-systemic disease.
Amyloidosis’ Hidden Role in Heart Failure
Heart failure is a complex and debilitating condition affecting millions of individuals worldwide. While it has several underlying causes, one often-overlooked contributor to heart failure is amyloidosis.
In this month’s piece we look to the Heart Failure Society of America and their piece titled “The Silent Intruder: Amyloidosis’ Hidden Role in Heart Failure.”
Understanding Amyloidosis
Amyloidosis is a rare but serious disease characterized by the buildup of abnormal proteins in various organs, including the heart. Amyloidosis occurs when a protein called amyloid builds up in different parts of the body, including the nervous system, tissues or even organs. These abnormal proteins (amyloids) are misfolded and can impair the normal functioning of organs, including the heart. There are different types of amyloidosis, but two forms stand out for their connection to heart failure: AL amyloidosis (immunoglobulin light chain) and ATTR amyloidosis (transthyretin). Symptoms of amyloidosis may vary, depending on which organs are affected. Signs and symptoms of amyloidosis may include:
Severe fatigue and weakness
Shortness of breath
Numbness, tingling, or pain in the hands or feet (polyneuropathy)
Swelling of the ankles and legs
Diarrhea, possibly with blood, or constipation
An enlarged tongue, which sometimes looks rippled around its edge
Skin changes, such as thickening or easy bruising, and purplish patches around the eyes
Due to the similarity of these symptoms with other heart conditions, amyloidosis is often misdiagnosed or diagnosed late, emphasizing the importance of raising awareness about its hidden role in heart failure.
The Hidden Role in Heart Failure (HF)
Amyloidosis can affect the heart in several ways, leading to heart failure:
Cardiac Amyloidosis: In cardiac amyloidosis, sometimes called stiff heart syndrome, amyloid deposits take the place of normal heart muscle, disrupting the heart’s normal structure and function. This can lead to restrictive cardiomyopathy, a condition where the heart becomes stiff and less able to pump blood effectively.
Diastolic Dysfunction: Amyloid deposits in the heart can make it difficult for the heart to relax properly during the diastolic phase, impairing its ability to fill with blood. This diastolic dysfunction can result in heart failure with preserved ejection fraction (HFpEF).
Arrhythmias: Amyloidosis can disrupt the heart’s electrical system, leading to arrhythmias (irregular heart rhythms) that can further exacerbate heart failure symptoms.
Diagnosing Amyloidosis
Amyloidosis can be confirmed through specialized tests, including tissue biopsies or imaging scans such as MRIs. Some cases of amyloidosis are hereditary, so if you or anyone else in your family has or had amyloidosis, it can be beneficial for you to take a genetic test to determine if you carry the gene.
Learn More About Amyloidosis
Amyloidosis, which can be a hidden contributor to heart failure, deserves greater recognition and awareness within the medical community and among patients. Timely diagnosis and appropriate management can make a significant difference in the prognosis of individuals affected by amyloidosis.
WATCH: Cardiac Amyloidosis from a Cardiologist
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.
Dr. Julie Rosenthal, Director of the Cardiac Amyloidosis Program at Mayo Clinic in Arizona, introduces us to the cardiovascular system and summarizes cardiac amyloidosis. She then discusses the echocardiogram and how it is used to look for abnormalities, such as thickening of the heart wall and pericardial effusion. Animated patient videos clearly convey how an impaired amyloid heart looks from multiple perspectives. She offers a tutorial on ejection fraction, what it is, how it is calculated, and why not all ejection fractions are the same despite the numbers. Importantly, she highlights that stroke volume is actually the more meaningful measurement of a patient’s cardiac output and why.
AL Amyloidosis: Diagnosis Begins With Suspicion
The diagnosis of amyloidosis can be challenging for several reasons.
First and foremost, presenting symptoms are often nonspecific and common to other conditions that can send clinicians in multiple directions.
Second, due to the variability of presenting symptoms, rarely are two patient presentations identical.
Third, the diagnostic process requires (a) the confirmation of amyloidosis, and (b) the typing of amyloidosis, only after which can an appropriate treatment regimen be developed.
The perceived rarity of the disease itself gives providers pause to consider. Collectively, as a result of these reasons, diagnosis is often delayed and/or misdiagnosed, leading to devastating consequences for patients. Often, the key to diagnosis begins with developing a clinical suspicion.
DEVELOPING A CLINICAL SUSPICION FROM SYMPTOMS
The first step in diagnosing AL amyloidosis is to develop a clinical suspicion, done through connecting the seemingly random presenting symptoms.
As seen in the figure above, multiple pathologies are often present with AL amyloidosis1. The most common is cardiac involvement, which also brings the highest mortality. Other common presentations range from nephropathy, including proteinuria (> 60% of patients), hepatomegaly (>50% of patients), neuropathy, whether autonomic (20% of patients) or peripheral (10-20% of patients), macroglossia (17% of patients), periorbital purpura (15% of patients) and GI manifestations (approximately 7% of patients).
Symptoms do not develop at the same time, nor in the same sequence from patient to patient. As a result, patients and providers often play “whack-a-mole,” going from specialist to specialist for specific symptoms. Misdiagnoses along the way are common, leading patients down paths that prove unproductive and, in some cases, counterproductive. This takes time, which is exactly what patients do not realize they do not have.
Suspicion of amyloidosis should be very high when a patient presents with heart failure combined with a constellation of unexplained extracardiac symptoms such as neuropathy, bleeding, carpal tunnel syndrome, nephrotic syndrome, proteinuria, diarrhea, hepatomegaly, peripheral and autonomic neuropathy, macroglossia, and periorbital purpura.1
ALGORITHM FOR DIAGNOSING AL AMYLOIDOSIS1
The figure below illustrates the current systematic, stepwise process for diagnosing amyloid light chain (AL) amyloidosis and differentiating it from other cardiomyopathies. It identifies each type of test that is essential for suspicion of AL amyloidosis, diagnosing the disease and typing of the amyloidogenic free light chains (FLCs).
Once the presence of amyloid has been confirmed, it is imperative to next identify the type of amyloid fibril in order to avoid misdiagnosis and initiation of incorrect or inappropriate treatment, which could have disastrous consequences for a patient.
The most common methods of amyloid fibril typing include immunohistochemistry or laser capture, followed by mass spectrometry. As the accuracy of immunohistochemistry is dependent on the expertise of the laboratory and needs an extensive panel of antibodies for accurate reporting, laser capture with mass spectrometry has become the method of choice for amyloid fibril typing.
Despite advances in noninvasive imaging, tissue biopsy remains a common and important confirmational step in most cases.
Once a diagnosis of amyloidosis has been confirmed, along with the specific type, an appropriate treatment regime can then be determined.
CONCLUSION – WHY EARLY DIAGNOSIS MATTERS
With AL amyloidosis, time is of the essence for patients. This is an aggressive disease where early treatment intervention can truly extend lives and improve QoL. As recently as the 1990s, this was considered a terminal disease with a high mortality rate, often offering patients months to a few years to live. With earlier diagnosis and advancements in treatments, survival is extending and QoL is improving.
IN CLOSING
The key take-aways are two-fold: (1) when confronted with multiple unexplained symptoms, suspect multi-system diseases like amyloidosis, and (2) remember that early diagnosis is key for patient survival.
For more detail on diagnosing and treating AL amyloidosis, please see the paper referenced below.
Source:
(1) Wechalekar, A, Fontana, M, Quarta, C. et al. AL Amyloidosis for Cardiologists: Awareness, Diagnosis, and Future Prospects: JACC: CardioOncology State-of-the-Art Review. J Am Coll Cardiol CardioOnc. 2022 Nov, 4 (4) 427–441.
Do You Need a Heart Biopsy to Diagnose Cardiac Amyloidosis?
Dr. Ahmad Masri, Director of the Cardiac Amyloidosis Program at Oregon Health & Science University (OHSU), reminds us about the traditional approach to diagnosis of cardiac amyloidosis. Unfortunately, this has not been enough. Thankfully, over the past decade that has all changed. He talks about OSHU’s approach to diagnosis today and what other data is used to arrive at a diagnosis of cardiac amyloidosis, offering four sample patient cases for insights.
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