Recent Advances in the Diagnosis and Management of Cardiac Amyloidosis

Sher, Taimur; Gertz, Morie A.

doi:10.2217/fca.13.85

Cited by 12 publications

(9 citation statements)

References 99 publications

(86 reference statements)

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“…5,25,26 However, only recently have cardiomyocyte-based proteotoxic entities become a focus of mechanistic studies, which has led to the realization that proteotoxicity may represent a convergent pathway in heart disease and the development of heart failure. 27-29 In this review, we will consider the particular sensitivity of the cardiomyocyte cell population to proteotoxic insult and introduce the relevant pathways that constitute aspects of the cardiomyocyte's PQC response.…”

Section: A Network Of Cellular Defensementioning

confidence: 99%

Proteotoxicity and Cardiac Dysfunction

McLendon

Robbins

2015

Circulation Research

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Baseline physiological function of the mammalian heart is under the constant threat of environmental or intrinsic pathological insults. Cardiomyocyte proteins are thus subject to unremitting pressure to function optimally and this depends upon them assuming and maintaining proper conformation. This review explores the multiple defenses a cell may employ for its proteins to assume and maintain correct protein folding and conformation. There are multiple quality control mechanisms to ensure that nascent polypeptides are properly folded and mature proteins maintain their functional conformation. When proteins do misfold, either in the face of normal or pathologic stimuli or because of intrinsic mutations or post-translational modifications, they must either be refolded correctly or recycled. In the absence of these corrective processes, they may become toxic to the cell. Herein, we explore some of the underlying mechanisms that lead to proteotoxicity. The continued presence and chronic accumulation of misfolded or unfolded proteins can be disastrous in cardiomyocytes as these misfolded proteins can lead to aggregation or the formation of soluble peptides that are proteotoxic. This in turn leads to compromised protein quality control and precipitating a downward spiral of the cell's ability to maintain protein homeostasis. Some underlying mechanisms are discussed and the therapeutic potential of interfering with proteotoxicity in the heart is explored.

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Section: A Network Of Cellular Defensementioning

confidence: 99%

Proteotoxicity and Cardiac Dysfunction

McLendon

Robbins

2015

Circulation Research

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“…Suspicion may be raised by multisystem involvement (carpal tunnel, renal impairment etc.). Laboratory investigations may confirm the diagnosis, classify the CA, trace the specific protein precursor and appraise the stage of cardiac involvement including pump function [ 8 ]. Currently, the most common examination procedures used to evaluate patients or conditions associated with CA include endomyocardial biopsy (EMB), electrocardiography (ECG), echocardiography and cardiac magnetic resonance (CMR) with some nuclear tests contributing (bone scintigraphy for ATTR, SAP scan for AL - but these are not widely available).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of cardiovascular magnetic resonance for patients with suspected cardiac amyloidosis: a systematic review and meta-analysis

Zhao

Tian

Fang

2016

BMC Cardiovasc Disord

110

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BackgroundThis study is a systematic review and meta-analysis of the diagnostic value of cardiovascular magnetic resonance (CMR) in cardiac amyloidosis (CA).MethodsA wide variety of electronic databases were searched for studies of CMR that reported the diagnostic accuracy in patients with suspected CA. Research manuscripts were subjected to further systematic review and meta-analysis. Methodological evaluation was performed under the guidance of the Quality Assessment of Diagnostic Accuracy Studies −2 (QUADAS–2). Heterogeneity was assessed, and a random-effects model was used to assess the diagnostic effects of CMR on pooled sensitivity, pooled specificity, and summary receiver operating characteristics (SROC).ResultsSeven studies that reported the performance of CMR for CA were included in the present systematic review, among which five studies (257 patients) that evaluated the diagnostic accuracy of late gadolinium enhancement (LGE) CMR were analyzed in the present meta-analysis. Heterogeneity was observed only in specificity. A summary sensitivity and specificity of 85 % (95 % CI: 77–91 %) and 92 % (95 % CI: 83–97 %) indicated a high diagnostic accuracy of LGE for CA. The AUC of SROC curve was 0.9530, suggesting that LGE is an effective way of diagnosing patients with possible cardiac involvement in amyloidosis.ConclusionsLGE–CMR seems to have a relatively high diagnostic accuracy for amyloidosis patients with possible cardiac involvement. Combined CMR techniques may provide important information for the selection of suitable therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0311-6) contains supplementary material, which is available to authorized users.

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“…Lanmark and colleagues described alterations in the signaling pathways of B lymphocytes in patients with breast cancer with and without fatigue [29]. More recently, cancer‐related fatigue (CRF) was associated to the over‐expression of alpha‐synuclein (SNCA), which is present in diseases such as Parkinson's [30] and is involved in some cases of hereditary amyloidosis [31]. This may indicate the potential role of inflammatory pathways in the development of CRF [32].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of fatigue related to adjuvant chemotherapy for breast cancer: evaluation of plasma and lymphocyte expression

Cruz

Munhoz

Alves

et al. 2015

Clinical & Translational Med

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Background Fatigue is common in cancer patients receiving adjuvant chemotherapy. To further understand the mechanism of fatigue and search for potential biomarkers, we conducted this prospective study. Methods We enrolled breast cancer (BC) patients before their first adjuvant Adriamycin-based chemotherapy cycle. Patients responded to the brief fatigue inventory (BFI) and Chalder fatigue questionnaires and had their blood drawn for both plasma evaluation and evaluation of the peripheral mononuclear cell fraction (PMNCF) mRNA expression of various biomarkers. We evaluated FSH, LH, estradiol, DHEA, DHEAS, IL6, IL2, ILIRA, IL1β, CRP, Cortisol in the plasma and IL2, IL10, IL6, TGF-β, KLRC1, TNF, BTP, SNCA, SOD1, BLNK, PTGS2 and INF γ expression in the PMNCF. Results 11 patients did not exhibit an increase in their BFI scores and served as controls, whereas 32 patients exhibited an increase in their BFI scores compared with the baseline scores. From the biomarkers we evaluated in the PMNCF, the only one significantly associated with fatigue was TGF-β (p = 0.0343), while there was a trend towards significance with KLRC1 (p = 0.0627). We observed no evidence of significant associations of any plasma biomarkers with the development of fatigue. However when we analyzed patients with more severe fatigue, plasma IL1-RA levels correlated directly with higher fatigue scores (p = 0.0136). Conclusions We conclude that fatigue induced by chemotherapy in BC patients is associated with changes in IL1-ra plasma levels and in TGF-β lymphocyte expression. Its mechanism may be different than that observed in long-term BC survivors or that induced by radiation therapy. Trial registration NCT02041364 [ClinicalTrials.gov]

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Recent Advances in the Diagnosis and Management of Cardiac Amyloidosis

Cited by 12 publications

References 99 publications

Proteotoxicity and Cardiac Dysfunction

Proteotoxicity and Cardiac Dysfunction

Diagnostic accuracy of cardiovascular magnetic resonance for patients with suspected cardiac amyloidosis: a systematic review and meta-analysis

Biomarkers of fatigue related to adjuvant chemotherapy for breast cancer: evaluation of plasma and lymphocyte expression

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