Cardiac Amyloidosis

Table of Contents

1. Overview
2. AL vs ATTR: The Two Main Types
3. Pathophysiology
4. Clinical Presentation
5. ECG, Echocardiography, and Cardiac MRI
6. Tc-99m Pyrophosphate Scan for ATTR
7. Biopsy and Histologic Confirmation
8. Treatment: TTR Stabilizers, Gene Silencers, and Supportive Care
9. Prognosis and Monitoring
10. Key Research Papers
11. Connections
12. Featured Videos

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1. Overview

Cardiac amyloidosis is the deposition of misfolded proteins, as amyloid fibrils, in the extracellular space of the heart. Under polarized light after Congo red staining, the deposits show a characteristic green birefringence (2021 ESC Working Group position statement). In transthyretin disease, the rigid, space-occupying fibrils stiffen the heart, with associated fibrosis and dysfunction, and the result is a restrictive cardiomyopathy (Ruberg 2019 review; 2020 AHA scientific statement).

The ESC statement describes cardiac amyloidosis as more frequent than traditionally considered, now that a diagnosis can be made without a biopsy. The Ruberg 2019 review reports studies suggesting that up to 10–15% of older adults with heart failure may have unrecognized wild-type transthyretin amyloidosis. Bone-scintigraphy imaging (the Tc-99m pyrophosphate, or PYP, scan and related tracers) and the 2019 FDA approval of tafamidis for transthyretin amyloid cardiomyopathy changed how the disease is found and treated.

More than 30 proteins can form amyloid in the body, but only nine are known to build up in the heart enough to cause significant disease, and more than 98% of diagnosed cardiac amyloidosis is one of two forms (ESC 2021):

• AL amyloidosis — amyloid derived from immunoglobulin light chains made by a clonal plasma cell disorder
• ATTR amyloidosis — amyloid derived from transthyretin (TTR), a liver-made carrier protein for thyroxine and retinol-binding protein

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2. AL vs ATTR: The Two Main Types

AL (Light-Chain) Amyloidosis

AL amyloidosis is a clonal plasma cell disorder in which fragments of immunoglobulin light (or heavy) chains are deposited in tissues. Depending on the organs involved, it can present as heart failure with preserved ejection fraction, nephrotic syndrome, liver dysfunction, peripheral or autonomic neuropathy, or an “atypical” smoldering myeloma or MGUS picture (Gertz 2024 review).

• How often the heart is involved: The ESC statement gives about 70% of AL patients; the Ruberg review gives 50–75%.
• Survival: The ESC statement's table lists a median survival from diagnosis of 24 months, and 6 months when heart failure is present at diagnosis and untreated.
• Testing for the clone: Under the ESC statement, a plasma cell disorder is looked for with a serum free light chain assay plus serum and urine protein electrophoresis with immunofixation; the statement reports that this combination has 99% sensitivity for the abnormal precursor protein in AL amyloidosis. The Ruberg review describes serum and urine protein electrophoresis without immunofixation as insensitive for this purpose.
• Cardiac biomarkers: NT-proBNP and troponin T, together with the free light chain difference, are the variables of the Mayo 2012 staging system (see section 9).
• Treatment: Directed at the plasma cell clone. The ANDROMEDA trial added daratumumab (an anti-CD38 antibody) to bortezomib, cyclophosphamide and dexamethasone and raised the hematologic complete response rate (details in section 8).

ATTR (Transthyretin) Amyloidosis

Transthyretin circulates as a tetramer of four subunits made mainly by the liver. The rate-limiting step in TTR amyloid formation is dissociation of the tetramer into monomers, which partly unfold and then misassemble into aggregates, including amyloid fibrils (Ruberg 2019). ATTR amyloidosis has two subtypes:

Wild-Type ATTR (ATTRwt) — Senile Cardiac Amyloidosis

• Pathogenesis: The TTR gene sequence is normal. The Ruberg review states that it is not clear why the wild-type protein becomes kinetically unstable and aggregates, but that the process appears to involve aging.
• Demographics: Average age at diagnosis 74 years in the cohorts reviewed by Ruberg, with rare patients diagnosed in their 40s. Over 90% of patients in most cohorts were male and Caucasian, though whether this is a true predilection or referral bias is unknown; in a study that actively screened older patients hospitalized with HFpEF using bone scintigraphy, about 13% had ATTR cardiomyopathy and 50% of them were women.
• Autopsy prevalence: Autopsy studies find wild-type TTR deposits in the heart in as many as 20–25% of people in their eighties and 37% of people over 95 (Ruberg 2019).
• Musculoskeletal clues: Carpal tunnel syndrome is present in about 50% of referred patients and often precedes overt cardiomyopathy by an average of 5–10 years; lumbar spinal stenosis and spontaneous rupture of the distal biceps tendon (reported in 33%) are other associations (Ruberg 2019).
• Clinical course: The Ruberg review gives a median survival from diagnosis of about 3.5 years in untreated patients, depending on stage; the ESC table lists 57 months.

Hereditary/Variant ATTR (ATTRv) — Familial Amyloid Cardiomyopathy

• Pathogenesis: Single amino-acid variants in the TTR gene destabilize the tetramer and make aggregation more efficient (Ruberg 2019).
• V122I (p.Val142Ile): The most common variant in the United States, found almost exclusively in people of West African descent and in 3.4% of African Americans, about 1.5 million carriers. It causes a late-onset restrictive cardiomyopathy with minimal neuropathy, average age at onset 69 years; true penetrance is unknown (Ruberg 2019). The ESC table lists a median survival of 31 months for Val142Ile disease.
• V30M (p.Val50Met): The most common variant worldwide and the prototype of hereditary ATTR polyneuropathy, endemic in parts of Portugal, Japan and Sweden; a late-onset form outside those areas can present with heart block and heart failure (Ruberg 2019).
• T60A (p.Thr80Ala): The second most common cardiac variant in the United States, originating in the north of the Republic of Ireland; a mixed cardiac and neuropathic picture with carpal tunnel syndrome in up to 70% (Ruberg 2019).
• Genetic testing: The ESC statement and the Ruberg review both describe TTR genetic testing in every patient with ATTR cardiomyopathy, whatever their age, to separate wild-type from variant disease, and the ESC statement recommends genetic testing with counselling for relatives of patients with an inherited form.

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3. Pathophysiology

Amyloid is deposited in the extracellular space of the myocardium (ESC 2021). The Ruberg review describes cardiac amyloidosis as not a simple infiltrative disorder but a “toxic-infiltrative cardiomyopathy”.

Restrictive Physiology

The ventricles become thick and stiff, with markedly reduced capacitance (Ruberg 2019). Consequences described in the review:

• Falling stroke volume, cardiac output and blood pressure as the disease progresses, with a compensatory rise in heart rate
• A narrow margin for fluid balance: volume overload follows dietary indiscretion quickly, while aggressive diuresis brings low blood pressure and worse kidney perfusion
• Ejection fraction is often preserved, but reduced ejection fraction (<40%) has been reported in 30–50% of wild-type cases

Conduction System Involvement

TTR amyloid infiltrates the conduction system (Ruberg 2019):

• Conduction disease is more common in wild-type than hereditary disease, with up to a third of wild-type patients needing a permanent pacemaker
• Atrial arrhythmias occur in 40–60% of wild-type patients at diagnosis in recent series and in almost all during the course of the disease
• Conduction disease and arrhythmias may appear years before heart failure

Autonomic Neuropathy (especially ATTRv)

Hereditary ATTR can present as a primary peripheral and autonomic neuropathy, often mixed with cardiomyopathy. Severe autonomic neuropathy can mask the degree of cardiac involvement because blood pools in the splanchnic bed. Peripheral and autonomic neuropathy can occur in wild-type disease but is less severe (Ruberg 2019).

Direct Amyloid Toxicity

The Ruberg review notes that in AL amyloidosis imaging findings may be subtle despite rapidly progressive heart failure, and attributes this to a more significant direct cardiotoxicity of circulating free light chains and pre-fibrillar aggregates in AL than in ATTR. Non-amyloid aggregates also appear to be proteotoxic in ATTR cardiomyopathy.

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4. Clinical Presentation

Heart Failure Symptoms

The natural history of ATTR cardiomyopathy is progressive heart failure complicated by arrhythmias and conduction disease (Ruberg 2019). Clues described by the ESC statement and the Ruberg review:

• Heart failure with an NT-proBNP out of proportion to the findings on echocardiography
• “Unexplained” right heart failure with apparently normal ventricular and valve function, or an “idiopathic” pericardial effusion
• Low blood pressure, or normal blood pressure in someone who used to be hypertensive — the “natural cure” of hypertension in which blood pressure medicines have to be reduced or stopped
• Poor tolerance of beta-blockers in newly diagnosed heart failure
• Persistently raised troponin, low QRS voltage for the degree of wall thickness, or early conduction disease

Extra-Cardiac Clues

The ESC statement's “red flags” and the type of amyloidosis each is most often found in:

• Bilateral carpal tunnel syndrome — ATTRv and ATTRwt
• Lumbar spinal stenosis — ATTRwt (amyloid thickens the ligamentum flavum, per Ruberg 2019)
• Ruptured biceps tendon — ATTRwt
• Deafness — ATTRwt
• Macroglossia (enlarged tongue) — AL
• Skin bruising — AL
• Polyneuropathy — ATTRv, AL (and rarer types)
• Dysautonomia — ATTR and AL
• Vitreous deposits in the eye — ATTRv
• Proteinuria and kidney impairment — AL and several rarer types
• Family history — ATTRv

Physical Examination

Low blood pressure, or normal blood pressure in a previously hypertensive person, is on the ESC list of cardiac red flags for both ATTR and AL.

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5. ECG, Echocardiography, and Cardiac MRI

Electrocardiogram (ECG)

• Low voltage for the wall thickness: Increased wall thickness with a low-voltage ECG helps separate ATTR cardiomyopathy from hypertensive or hypertrophic heart disease, but only 25–40% of ATTR patients meet low-voltage criteria, and in one series of Val122Ile disease 25% met criteria for left ventricular hypertrophy (Ruberg 2019).
• Pseudoinfarct pattern and AV conduction disease are ESC red flags in all types.
• Atrial fibrillation: present in 40–60% of wild-type patients at diagnosis (Ruberg 2019).

Echocardiography

ESC 2021 criteria start from unexplained left ventricular wall thickness of 12 mm or more, plus either at least two of: grade 2 or worse diastolic dysfunction; tissue Doppler s′, e′ and a′ velocities below 5 cm/s; and reduced global longitudinal strain (absolute value below 15%) — or a multiparametric echo score of 8 points or more. Other echo red flags in the statement:

• Granular sparkling of the myocardium
• Increased right ventricular wall thickness and increased valve thickness
• Pericardial effusion
• Apical sparing: reduced longitudinal strain with relatively normal strain at the apex and worse values at the mid and basal segments; apex-to-base strain ratios have good accuracy for separating amyloid heart disease from other causes (Ruberg 2019)

Cardiac MRI

ESC 2021 characteristic findings on cardiac magnetic resonance (CMR):

• Diffuse subendocardial or transmural late gadolinium enhancement
• Abnormal gadolinium kinetics: myocardial nulling before or at the same time as the blood pool
• Extracellular volume (ECV) of 0.40 or more: strongly supportive but not essential
• The Ruberg review gives the late-enhancement findings a sensitivity and specificity approaching 85–90%, and describes native T1 and ECV mapping as even more sensitive. Neither echocardiography nor CMR reliably tells ATTR from AL amyloidosis.

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6. Tc-99m Pyrophosphate Scan for ATTR

Bone-seeking technetium tracers — Tc-99m PYP in the United States, and Tc-99m DPD or HMDP in Europe — accumulate in ATTR-infiltrated myocardium. The Ruberg review states that the mechanism is unknown but has been attributed to microcalcifications, which are more common in ATTR than in AL cardiac tissue. It is the only imaging method that can diagnose ATTR cardiomyopathy without a heart biopsy.

Technique and Interpretation

• Visual grading (0–3): grade 0, no myocardial uptake; grade 1, less than bone; grade 2, similar to bone; grade 3, greater than bone with reduced or absent bone uptake (ESC 2021)
• Heart-to-contralateral chest ratio: a ratio above 1.5 on PYP imaging separated AL from ATTR cardiomyopathy (Ruberg 2019)
• SPECT: the ESC statement describes SPECT as necessary to confirm that the uptake is in the myocardium and not blood pool in the cardiac chambers

Diagnostic Performance

In the 2016 multicentre study by Gillmore and colleagues (1,217 patients with suspected cardiac amyloidosis):

• Sensitivity: myocardial uptake was more than 99% sensitive for cardiac ATTR amyloid
• Specificity: 86% overall, with false positives almost entirely from cardiac AL amyloidosis
• Grade 2 or 3 uptake with no monoclonal protein in blood or urine: specificity and positive predictive value of 100% for cardiac ATTR, which the authors proposed as non-biopsy diagnostic criteria; the 2021 ESC statement adopted this as its non-invasive criterion for ATTR
• The ESC statement also lists rare false positives (for example hydroxychloroquine cardiac toxicity, some apolipoprotein amyloid types, recent myocardial infarction) and false negatives (some TTR variants such as Phe84Leu and Ser97Tyr, very mild disease)

Practical Workflow

The diagnostic algorithm in the 2021 ESC statement:

1. Bone scintigraphy together with serum free light chains and serum and urine immunofixation
2. Grade 2 or 3 uptake with all monoclonal tests negative: ATTR cardiac amyloidosis can be diagnosed, followed by genetic testing to separate ATTRv from ATTRwt. Grade 1 uptake requires tissue confirmation.
3. Any abnormal monoclonal test: AL amyloidosis has to be ruled out promptly, with CMR and cardiac or extracardiac biopsy, and haematology involvement
4. No uptake and negative monoclonal tests: cardiac amyloidosis is unlikely, but if suspicion persists, CMR followed by biopsy is described, because some variants and rare types are scan-negative

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7. Biopsy and Histologic Confirmation

Congo red staining showing apple-green birefringence under polarized light is required to diagnose AL amyloidosis on tissue (Gertz 2024). Under the ESC criteria, an endomyocardial biopsy showing amyloid confirms cardiac amyloidosis whatever the wall thickness; amyloid in an extracardiac biopsy also confirms it when echo or CMR shows the characteristic features.

Biopsy Sites

• Abdominal fat pad aspirate: sensitivity varies, and in wild-type ATTR it is only 15% (Ruberg 2019), so a negative fat pad does not exclude ATTR.
• Endomyocardial biopsy: nearly 100% sensitive and specific when samples are taken from several sites (four or more) and stained with Congo red (Ruberg 2019).
• Other organs: the Gertz review reports that a biopsy of the affected organ itself is not needed in 85% of AL patients.

Amyloid Typing

Treatment differs completely between AL and ATTR, so the amyloid protein has to be identified. Mass spectrometry (laser-capture mass spectrometry) is the gold standard; immunohistochemistry or immunoelectron microscopy are used routinely in specialized centres (ESC 2021; Gertz 2024; Ruberg 2019).

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8. Treatment: TTR Stabilizers, Gene Silencers, and Supportive Care

What follows reports trial results and FDA labeling; decisions about any treatment belong with a clinician.

Tafamidis (ATTR-CM): Disease-Modifying Therapy

Tafamidis binds the thyroxine-binding sites of TTR and slows the dissociation of the tetramer into monomers (Ruberg 2019).

• ATTR-ACT trial (Maurer 2018, PubMed PMID: 30145929): phase 3 trial in 441 patients with wild-type or variant ATTR cardiomyopathy, randomized 2:1:2 to tafamidis 80 mg, tafamidis 20 mg or placebo for 30 months, with the two tafamidis doses analysed together (264 vs 177 patients). All-cause mortality was 29.5% vs 42.9% (hazard ratio 0.70) and the cardiovascular hospitalization rate was 0.48 vs 0.70 per year (relative risk ratio 0.68). The decline in 6-minute walk distance and KCCQ quality-of-life score was slower; adverse events were similar.
• Subgroups: the Ruberg review reports that hazard ratios favoured tafamidis in every pre-specified subgroup except NYHA class III patients, in whom cardiovascular hospitalizations were higher on tafamidis.
• FDA approval: May 2019, for the cardiomyopathy of wild-type or hereditary transthyretin amyloidosis in adults (Drugs@FDA). The label lists two dosages, tafamidis meglumine 80 mg (four 20-mg capsules) once daily or tafamidis 61 mg once daily, and states that the two forms are not substitutable on a per-mg basis.
• Limitations: tafamidis slows progression; the 2021 ESC statement notes that therapy is more effective in the early stages of the disease.

Acoramidis (ATTR-CM)

• ATTRibute-CM trial (Gillmore 2024, PubMed PMID: 38197816): a second TTR stabilizer, tested in 632 patients randomized 2:1 against placebo for 30 months. The four-step hierarchical primary outcome (death, cardiovascular hospitalization, NT-proBNP change, 6-minute walk change) favoured acoramidis, win ratio 1.8; adverse events were similar.
• FDA approval: November 2024, for the cardiomyopathy of wild-type or variant transthyretin amyloidosis in adults; labeled dosage 712 mg twice daily (Drugs@FDA).

TTR Gene Silencers (Hereditary ATTR)

Silencers lower the liver's production of transthyretin:

• Patisiran: a small interfering RNA (RNAi) given by intravenous infusion every 3 weeks. In APOLLO (Adams 2018, PubMed PMID: 29972753), 225 patients with hereditary ATTR polyneuropathy: at 18 months the neuropathy score (mNIS+7) changed by −6.0 points on patisiran vs +28.0 on placebo, a difference of 34.0 points; infusion reactions occurred in about 20% vs 10%. In APOLLO-B (Maurer 2023, PubMed PMID: 37888916), 360 patients with hereditary or wild-type ATTR cardiomyopathy: at 12 months the decline in 6-minute walk distance was smaller on patisiran (median difference 14.69 m) and the KCCQ score rose 3.7 points relative to placebo, while the composite of death, cardiovascular events and walk distance did not differ significantly. FDA approval: August 2018; the current label lists only the polyneuropathy of hereditary ATTR (Drugs@FDA).
• Inotersen: an antisense oligonucleotide injected weekly. In NEURO-TTR (Benson 2018, PubMed PMID: 29972757), 172 patients with hereditary ATTR polyneuropathy: at 66 weeks the mNIS+7 difference was −19.7 points and the quality-of-life difference −11.7 points. There were five deaths on inotersen and none on placebo; glomerulonephritis and thrombocytopenia each occurred in 3%, with one death linked to grade 4 thrombocytopenia. The FDA approved it in October 2018 with a monitoring program for platelets and kidney function (Ruberg 2019); Drugs@FDA now lists the product as discontinued.
• Vutrisiran: an RNAi drug injected under the skin every 3 months. In HELIOS-B (Fontana 2025, PubMed PMID: 39213194), 655 patients with ATTR cardiomyopathy: hazard ratio 0.72 for death from any cause and recurrent cardiovascular events, 0.65 for death from any cause through 42 months, with smaller declines in walk distance and KCCQ score. FDA approval: June 2022 for hereditary ATTR polyneuropathy; a March 2025 supplement added the cardiomyopathy of wild-type or hereditary ATTR (Drugs@FDA approval letter).
• Eplontersen: a ligand-conjugated antisense oligonucleotide injected monthly. NEURO-TTRansform (Coelho 2023, PubMed PMID: 37768671) was open-label and compared 144 treated patients with the NEURO-TTR placebo group as a historical control: serum TTR fell 81.7% vs 11.2%, with better neuropathy and quality-of-life scores. FDA approval: December 2023 for hereditary ATTR polyneuropathy (Drugs@FDA).

AL Amyloidosis: Anti-Plasma Cell Therapy

Treatment of AL amyloidosis targets the clonal plasma cells that make the light chains:

• CyBorD: cyclophosphamide, bortezomib and dexamethasone — the control arm of ANDROMEDA
• Dara-CyBorD: in ANDROMEDA (Kastritis 2021, PubMed PMID: 34192431), 388 newly diagnosed patients: hematologic complete response 53.3% with added subcutaneous daratumumab vs 18.1% without; cardiac responses at 6 months 41.5% vs 22.2%. The Gertz 2024 review describes this four-drug combination as the current first-line therapy with the best outcome.
• Autologous stem cell transplant: listed by the Gertz review among consolidation options, with pomalidomide, venetoclax and bendamustine, for patients who do not reach at least a very good partial response; the ESC statement lists cardiac assessment for transplant among the cardiologist's roles.

Supportive Heart Failure Management

What the 2019 Ruberg review (written for ATTR cardiomyopathy) and two digoxin cohort studies report:

• Diuretics: maintaining normal fluid balance with sodium restriction and diuretics is described as central; loop diuretics with higher bioavailability (torsemide, bumetanide) are described as preferred, often with an aldosterone antagonist.
• ACE inhibitors/ARBs/ARNi: there are no guideline-based recommendations for them in cardiac amyloidosis, and they may be poorly tolerated because of low blood pressure.
• Beta-blockers: described as poorly tolerated, especially at higher doses, because they blunt the faster heart rate needed to maintain cardiac output.
• Non-dihydropyridine calcium channel blockers: the review advises against them, citing case reports of high-degree heart block and shock in AL amyloidosis.
• Digoxin: long regarded as contraindicated because of older toxicity reports. In a Mayo Clinic cohort of 107 AL patients given digoxin, significant arrhythmias developed in 11%, almost all newly diagnosed (Muchtar 2018, PubMed PMID: 29529877); in a cohort of 69 ATTR and AL patients, suspected digoxin-related arrhythmias or toxicity occurred in 12% and no deaths were attributed to it (Donnelly 2020, PubMed PMID: 32800294). Both groups concluded it may be used cautiously in selected patients with close monitoring.
• Anticoagulation: the risk of intracardiac thrombus is raised in all cardiac amyloidosis and can occur in sinus rhythm; one study found left atrial appendage thrombus in 33% of ATTR patients presenting for cardioversion, most already on anticoagulants. The review describes long-term anticoagulation as preferred once atrial fibrillation is found, whatever the CHA₂DS₂-VASc score.
• Pacemaker/ICD: pacing follows the ACC/AHA/HRS indications. The review finds no clear indication for primary-prevention ICDs in ATTR cardiomyopathy, since no overall survival benefit has been shown and guidelines do not support them when expected survival is under a year; secondary prevention is described as reasonable.

Heart Transplantation

The Ruberg review describes heart transplantation, combined with liver transplantation for some hereditary variants, as an option for selected patients with advanced ATTR cardiomyopathy, but not a viable option for most because of donor shortage and the age of most patients. Liver transplantation for hereditary ATTR has declined sharply since TTR stabilizers arrived, and is not used for wild-type disease. The ESC statement lists heart transplant evaluation among the cardiologist's roles in AL amyloidosis.

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9. Prognosis and Monitoring

Prognostic Staging

AL amyloidosis — Mayo 2012 staging system (Kumar 2012, 810 newly diagnosed patients):

• One point each for free light chain difference (involved minus uninvolved) ≥18 mg/dL, troponin T ≥0.025 ng/mL and NT-proBNP ≥1,800 pg/mL
• Stage I (0 points): median overall survival 94.1 months
• Stage II (1 point): 40.3 months
• Stage III (2 points): 14 months
• Stage IV (3 points): 5.8 months
• The Gertz 2024 review gives 5-year survivals of 82%, 62%, 34% and 20% across the four stages.

ATTR cardiac amyloidosis — UK National Amyloidosis Centre (NAC) staging (Gillmore 2018, 869 patients):

• Stage I: NT-proBNP ≤3,000 ng/L and eGFR ≥45 mL/min; Stage III: NT-proBNP >3,000 ng/L and eGFR <45 mL/min; Stage II: the rest. Median survival was 69.2, 46.7 and 24.1 months.
• The Mayo wild-type staging (troponin T >0.05 ng/mL and NT-proBNP >3,000 pg/mL) gave median survivals of 66, 42 and 20 months (as reported in Ruberg 2019 and the ESC statement).

Monitoring on Therapy

The ESC statement notes that no study has yet defined the best follow-up scheme, and describes a common one:

• Visits every 6 months with ECG and blood tests, including NT-proBNP and troponin
• Yearly echocardiogram and 24-hour Holter monitoring
• For AL: monthly blood counts, biochemistry, NT-proBNP, troponin and serum free light chains during initial haematological treatment, and blood counts, biochemistry, NT-proBNP and troponin every 3–4 months after it
• For carriers of a hereditary variant: assessment generally starting about 10 years before the age at which disease began in affected relatives

Overall Outlook

The ESC statement and Ruberg review describe early diagnosis as essential because therapy is more effective in the early stages. In the 2018–2025 trials summarised above, tafamidis, acoramidis and vutrisiran each improved outcomes against placebo in ATTR cardiomyopathy, and adding daratumumab raised hematologic and cardiac response rates in AL amyloidosis. The ESC statement notes that data on how the disease progresses over time, and on how to measure progression on treatment, remain limited.

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Key Research Papers

1. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. PubMed PMID: 30145929
2. Adams D, Gonzalez-Duarte A, O'Riordan WD, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018;379(1):11-21. PubMed PMID: 29972753
3. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021;385(1):46-58. PubMed PMID: 34192431
4. Maurer MS, Kale P, Fontana M, et al. Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis. N Engl J Med. 2023;389(17):1553-1565. PubMed PMID: 37888916
5. Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018;379(1):22-31. PubMed PMID: 29972757
6. Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016;133(24):2404-2412. PubMed PMID: 27143678
7. Kittleson MM, Maurer MS, Ambardekar AV, et al. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation. 2020;142(1):e7-e22. PubMed PMID: 32476490
8. Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. N Engl J Med. 2025;392(1):33-44. PubMed PMID: 39213194
9. Gillmore JD, Judge DP, Cappelli F, et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2024;390(2):132-142. PubMed PMID: 38197816
10. Coelho T, Marques W Jr, Dasgupta NR, et al. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 2023;330(15):1448-1458. PubMed PMID: 37768671
11. Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. PubMed PMID: 33825853
12. Ruberg FL, Grogan M, Hanna M, et al. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(22):2872-2891. PubMed PMID: 31171094
13. Gertz MA. Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment. Am J Hematol. 2024;99(2):309-324. PubMed PMID: 38095141
14. Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30(9):989-995. PubMed PMID: 22331953
15. Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799-2806. PubMed PMID: 29048471
16. Muchtar E, Gertz MA, Kumar SK, et al. Digoxin use in systemic light-chain (AL) amyloidosis: contra-indicated or cautious use? Amyloid. 2018;25(2):86-92. PubMed PMID: 29529877
17. Donnelly JP, Sperry BW, Gabrovsek A, et al. Digoxin Use in Cardiac Amyloidosis. Am J Cardiol. 2020;133:134-138. PubMed PMID: 32800294

FDA approval dates and labeled indications and dosages are from the Drugs@FDA records and current labels (accessed 2026-10-14): tafamidis (NDA 211996), acoramidis (NDA 216540), patisiran (NDA 210922), inotersen (NDA 211172), vutrisiran (NDA 215515), eplontersen (NDA 217388).

PubMed Topic Searches

1. Tc-99m PYP scintigraphy for ATTR diagnosis: sensitivity and specificity
2. Non-biopsy diagnosis of ATTR by PYP scan
3. Prevalence and clinical profile of wild-type ATTR amyloidosis
4. V122I ATTR cardiomyopathy in African Americans
5. Myocardial amyloid regression on patisiran: CMR studies
6. Response to treatment of AL cardiac amyloidosis and survival

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Connections

• Cardiology
• Heart Failure
• Cardiomyopathy
• Atrial Fibrillation
• Long QT Syndrome
• Ventricular Tachycardia
• Arrhythmia
• Hypertension
• Multiple Myeloma
• Nephrotic Syndrome
• Peripheral Neuropathy
• Edema
• Fatigue
• Syncope
• Electrocardiogram (ECG)
• Potassium
• Carpal Tunnel Syndrome
• AL Amyloidosis — the light-chain systemic amyloidosis that infiltrates the heart in most patients and carries the worst cardiac prognosis.

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