ATTR Amyloidosis: Current and Emerging Management Strategies

Griffin, Jan M.; Rosenthal, Julie; Grodin, Justin L.; Maurer, Mathew S.; Grogan, Martha; Cheng, Richard K.

doi:10.1016/j.jaccao.2021.06.006

Cited by 105 publications

(107 citation statements)

References 112 publications

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“…However, beta blockers may be cautiously used for rate control of atrial arrhythmias. 28,29 ATTR patients with a previous diagnosis of hypertension frequently need gradual down-titration of antihypertensive medications, while orthostatic hypotension due to autonomic dysfunction is typical in AL. 30 Both tachy-and bradyarrhythmias have been reported in CA, with atrial fibrillation and atrioventricular (AV) blocks requiring pace-maker implantation being the most common manifestations.…”

Section: Clinical Red Flagsmentioning

confidence: 99%

Red flags for the diagnosis of cardiac amyloidosis: simple suggestions to raise suspicion and achieve earlier diagnosis

Argirò

Zampieri

Mazzoni

et al. 2022

Journal of Cardiovascular Medicine

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Cardiac amyloidosis is an infiltrative disease characterized by extracellular deposition of insoluble amyloid fibrils in the heart leading to organ dysfunction. Despite recent diagnostic advances, the diagnosis of cardiac amyloidosis is often delayed or even missed. Furthermore, a long diagnostic delay is associated with adverse outcomes, with the early diagnosed patients showing the longest survival. In this narrative review we aimed to summarize the ‘red flags’ that may facilitate the correct diagnosis. The red flags may be classified as clinical, biohumoral, electrocardiographic, echocardiographic, and cardiac magnetic resonance features and should promptly raise the suspicion of cardiac amyloidosis in order to start a correct diagnostic pathway and targeted treatment strategies that may improve patients’ outcomes.

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Section: Clinical Red Flagsmentioning

confidence: 99%

Red flags for the diagnosis of cardiac amyloidosis: simple suggestions to raise suspicion and achieve earlier diagnosis

Argirò

Zampieri

Mazzoni

et al. 2022

Journal of Cardiovascular Medicine

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“…Maintenance of euvolemia is mandatory and, at the same time, challenging, because of the restrictive nature of CA and the reduced LV capacitance [77]. Renin-angiotensin-aldosterone system antagonists and beta-blockers may be not tolerated owing to a propensity to postural hypotension [52], while calcium-channel blockers should be avoided due to their tendency to form complexes with amyloid proteins [60]. Medical therapy also includes managing arrhythmic complications [60].…”

Section: Medical Therapymentioning

confidence: 99%

“…There are three therapeutic strategies for the treatment of ATTR amyloidosis: 1) TTR stabilization; 2) TTR mRNA silencing; and 3) amyloid fibrils disruption and/or extraction (Table 2) [60]. One TTR stabilizer, tafamidis, has been recently approved for use in clinical practice, thanks to the results of the ATTR-ACT trial [52,100]. Tafamidis reduced all-cause mortality and cardiovascular hospitalization in 441 patients with CA-ATTR due to wtATTR or vATTR over a period of 30 months [100].…”

Section: Medical Therapymentioning

confidence: 99%

“…Cardiac amyloidosis (CA) refers to the deposition of amyloid fibrils in the heart. The two prevailing amyloid proteins with cardiac tropism are immunoglobulin light chain (AL) and transthyretin (ATTR) [51,52] (Table 1). Describing AS and CA association has grown interest lately, as a consequence of increased facility of CA-ATTR diagnosis and novel treatments.…”

Section: Aortic Valve Stenosis and Cardiac Amyloidosis 21 Introductio...mentioning

confidence: 99%

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Perspective Chapter: Lipoprotein (a), Cardiac Amyloidosis, and Aortic Stenosis - Underestimated Associations

Santangelo¹,

Bernardi²,

Faggiano³

et al. 2022

Aortic Stenosis - Recent Advances, New Perspectives and Applications

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This chapter aims to address two peculiar aspects of pathophysiology and clinical management of aortic valve stenosis, such as coexistence with cardiac amyloidosis and association with lipoprotein (a). Calcific aortic valve stenosis is the most common heart valve condition requiring surgical or transcatheter aortic valve replacement among adults in Western societies. Lipoprotein (a) has been shown to play an important role in the pathophysiological pathways leading to degenerative aortic stenosis, similar to that in the pathogenesis of atherosclerosis. Studies are needed to verify whether therapies that drastically reduce Lipoprotein (a) serum levels offer the possibility of a first medical treatment to arrest the progression of aortic stenosis. A large percentage of patients with aortic stenosis may have concomitant cardiac amyloidosis, commonly due to wild-type transthyretin. The challenge in this context is to differentiate aortic stenosis alone from aortic stenosis with cardiac amyloidosis, as cardiac amyloidosis shares several clinical, electrocardiographic, and echocardiographic features with the aortic stenosis phenotype. Recognition of transthyretin-related amyloidosis prior to any type of intervention is crucial for adequate risk stratification and to guide downstream management.

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“…Transthyretin amyloid cardiomyopathy (ATTR-CM), the major cause of CA, is categorized into inherited mutations (variant ATTR-CM (ATTRv-CM)) and the aging process without mutations (wild type ATTR-CM (ATTRwt-CM)). Recently, ATTRwt-CM is increasingly recognized as a cause of progressive heart failure, restrictive cardiomyopathy, or LVH in elderly patients [ 2 , 5 , 6 , 8 ]. Furthermore, 13% of elderly patients (mean age, 82 years) who have heart failure with preserved LV ejection fraction, 16% of elderly patients (mean age, 83.7 years) with severe aortic stenosis undergoing transcatheter aortic valve replacement, and 8.2% of patients (mean age, 60 years) initially diagnosed with hypertrophic cardiomyopathy, were all reported to have a diagnosis of ATTR-CM [ 9 , 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Transthyretin Amyloid Cardiomyopathy: Impact of Transthyretin Amyloid Deposition in Myocardium on Cardiac Morphology and Function

Nakano

Onoue

Terada

et al. 2022

JPM

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Background: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is increasingly being recognized as a cause of left ventricular (LV) hypertrophy (LVH) and progressive heart failure in elderly patients. However, little is known about the cardiac morphology of ATTR-CM and the association between the degree of TTR amyloid deposition and cardiac dysfunction in these patients. Methods: We studied 28 consecutive patients with ATTR-CM and analyzed the relationship between echocardiographic parameters and pathological features using endomyocardial biopsy samples. Results: The cardiac geometries of patients with ATTR-CM were mainly classified as concentric LVH (96.4%). The relative wall thickness, a marker of LVH, tended to be positively correlated with the degree of non-cardiomyocyte area. The extent of TTR deposition was positively correlated with enlargement of the non-cardiomyocyte area, and these were positively correlated with LV diastolic dysfunction. Additionally, the extent of the area containing TTR was positively correlated with the percentage of cardiomyocyte nuclei stained for 8-hydroxy-2′deoxyguanosine, a marker of reactive oxygen species (ROS). ROS accumulation in cardiomyocytes was positively correlated with LV systolic dysfunction. Conclusion: Patients with ATTR-CM mainly displayed concentric LVH geometry. TTR amyloid deposition was associated with cardiac dysfunction via increased non-cardiomyocyte area and ROS accumulation in cardiomyocytes.

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ATTR Amyloidosis: Current and Emerging Management Strategies

Cited by 105 publications

References 112 publications

Red flags for the diagnosis of cardiac amyloidosis: simple suggestions to raise suspicion and achieve earlier diagnosis

Red flags for the diagnosis of cardiac amyloidosis: simple suggestions to raise suspicion and achieve earlier diagnosis

Perspective Chapter: Lipoprotein (a), Cardiac Amyloidosis, and Aortic Stenosis - Underestimated Associations

Transthyretin Amyloid Cardiomyopathy: Impact of Transthyretin Amyloid Deposition in Myocardium on Cardiac Morphology and Function

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