Treatment of cardiac transthyretin amyloidosis: an update

Emdin, Michele; Aimo, Alberto; Rapezzi, Claudio; Fontana, Marianna; Perfetto, Federico; Seferović, Petar; Barison, Andrea; Castiglione, Vincenzo; Vergaro, Giuseppe; Giannoni, Alberto; Passino, Claudio; Merlini, Giampaolo

doi:10.1093/eurheartj/ehz298

Cited by 133 publications

(126 citation statements)

References 53 publications

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“…These significantly reduce cardiovascular hospitalizations and mortality when used in early-stage cardiac ATTR amyloidosis, and tafamidis improved progression in polyneuropathy due to ATTRm. [20][21][22] Serum Amyloid A Serum amyloid A (AA) amyloidosis accounts for 6% of amyloid cases due to deposition of AA protein, an acute phase reactant made by the liver, and has been called secondary amyloidosis. It has been estimated to be the cause of up to 45% of all generalized amyloid cases.…”

Section: Transthyretin Amyloidmentioning

confidence: 99%

An Organ System–Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology

Giannini

Nast

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Amyloidosis is an uncommon but important entity. A protein-based classification of amyloidosis defines the underlying disease process, directing clinical management and providing prognostic information. However, in routine surgical pathology there often is no attempt to classify amyloid other than staining to determine light chain–associated amyloidosis. Systemic and localized amyloidosis vary with respect to frequency of organ involvement by different amyloid types, and most amyloid proteins have commercial antibodies available for identification. Objective.— To provide a guide for the likelihood of amyloid type by organ system. Data Sources.— Literature review based on PubMed searches containing the word amyloid, specifically addressing the prevalence and significance of amyloid proteins in each organ system other than the brain, and the authors' practice experience. Conclusions.— In patients with amyloidosis, determination of the responsible protein is critical for appropriate patient care. In large subspecialty practices and reference laboratories with experience in using and analyzing relevant immunohistochemistry, most amyloid proteins can be identified with an organ-specific algorithm. Referring to an organ-based algorithm may be helpful in providing clinicians with a more specific differential diagnosis regarding amyloid type to help guide clinical evaluation and treatment. When the protein cannot be characterized, mass spectrometry can be performed to definitively classify the amyloid type.

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Section: Transthyretin Amyloidmentioning

confidence: 99%

An Organ System–Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology

Giannini

Nast

2019

Archives of Pathology &Amp; Laboratory Medicine

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“…A further Phase 3 trial of a small‐interfering RNA therapeutic, revusiran, was terminated early due to a mortality imbalance . Other small‐interfering RNAs, or the use of antisense oligonucleotides, could offer alternative therapeutic approaches that remain to be investigated in ATTR‐CM …”

Section: Introductionmentioning

confidence: 99%

Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta‐analysis

et al. 2019

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AimsThe study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis.Methods and resultsMEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light‐chain (AL) amyloidosis. In this meta‐analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra‐cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta‐analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1–99.0% and specificity 11.0–60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS‐2 was generally poor with evidence of bias.ConclusionsCardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non‐invasive diagnostic algorithm that also tests for the presence of monoclonal protein.

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“…Physicians encountering amyloidosis patients are encouraged to be involved in the Transthyretin Amyloidosis Outcomes Survey (THAOS), an international, longitudinal, observational study designed to investigate the disease course and its management among symptomatic patients as well as their asymptomatic mutation-carrying family members [25]. e treatment options for amyloidosis are evolving [26][27][28]. A traditional treatment option was orthotopic liver Case Reports in Medicine transplantation (OLT) that eliminates significant amount of ATTR from the blood and helps alter the course of the disease.…”

Section: Discussionmentioning

confidence: 99%

Senile Systemic Amyloidosis Presenting as Hematuria: A Rare Presentation and Review of Literature

Jayakrishnan

Kamran

Shah

et al. 2020

Case Reports in Medicine

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Introduction. Senile systemic amyloidosis is a multisystem disease where wild-type insoluble transthyretin (ATTRwt) protein gets deposited in the tissues leading to organ dysfunction. Methodology. We present the case of a patient who presented with hematuria and bladder involvement by ATTRwt amyloidosis who ultimately died of multiorgan failure. Results. The patient was an 82-year-old white male with a history of ischemic cardiomyopathy (ejection fraction (EF): 20–25%), chronic atrial fibrillation, chronic kidney disease (CKD), and carpal tunnel syndrome who presented with acute hematuria, urinary retention, and progressive fatigue. He underwent cystoscopy and bladder biopsy which was positive on congo-red stain diagnostic for amyloidosis. Echocardiogram demonstrated worsening of EF to 10–15% and concentric left ventricle hypertrophy. MRI was not performed due to underlying CKD. His condition deteriorated during the hospital stay, and he developed cardiogenic shock and progressive liver dysfunction. Infectious workup was negative. Meanwhile, the biochemical investigations (serum protein electrophoresis, immunofixation, and urine kappa/lambda chains) ruled out plasma cell dyscrasias. Mass spectrometry analysis of the bladder biopsy specimen confirmed wild-type transthyretin (ATTRwt) amyloidosis consistent with senile systemic amyloidosis. Due to patients’ extremely poor prognosis, his family wished to focus on patient’s comfort-oriented measures only, and patient passed away shortly thereafter. Conclusion. Senile systemic amyloidosis can rarely present in an atypical fashion such as hematuria. The treatment options are limited in this disease process. Novel therapies are in the early phases of development. Concern also exists that in patients with multiple comorbidities, this entity is under recognized until the more advanced stages.

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Treatment of cardiac transthyretin amyloidosis: an update

Cited by 133 publications

References 53 publications

An Organ System–Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology

An Organ System–Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology

Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta‐analysis

Senile Systemic Amyloidosis Presenting as Hematuria: A Rare Presentation and Review of Literature

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