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BMC Musculoskeletal Disorders Jan 2021Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid...
BACKGROUND
Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid deposits may lead to orthopedic conditions before cardiac manifestations occur. Pharmacologic treatments reduce further amyloid deposits in these patients. Thus, early diagnosis improves long term survival.
QUESTIONS/PURPOSES
The primary purpose of this systematic review was to characterize the association between amyloid deposition and musculoskeletal pathology in patients with common orthopedic conditions. A secondary purpose was to determine the relationship between amyloid positive biopsy in musculoskeletal tissue and the eventual diagnosis of systemic amyloidosis.
METHODS
We performed a systematic review using PRISMA guidelines. Inclusion criteria were level I-IV evidence articles that analyzed light-chain or transthyretin amyloid deposits in common orthopedic surgeries. Study methodological quality, risk of bias, and recommendation strength were assessed using MINORS, ROBINS-I, and SORT.
RESULTS
This systematic review included 24 studies for final analysis (3606 subjects). Amyloid deposition was reported in five musculoskeletal pathologies, including carpal tunnel syndrome (transverse carpal ligament and flexor tenosynovium), hip and knee osteoarthritis (synovium and articular cartilage), lumbar spinal stenosis (ligamentum flavum), and rotator cuff tears (tendon). A majority of studies reported a mean age greater than 70 for patients with TTR or AL positive amyloid.
CONCLUSIONS
This systematic review has shown the presence of amyloid deposition detected at the time of common orthopedic surgeries, especially in patients ≥70 years old. Subtyping of the amyloid has been shown to enable diagnosis of systemic light-chain or transthyretin amyloidosis prior to cardiac manifestations.
LEVEL OF EVIDENCE
Level IV.
Topics: Aged; Amyloid Neuropathies, Familial; Humans; Immunoglobulin Light-chain Amyloidosis; Orthopedic Procedures; Osteoarthritis, Hip; Osteoarthritis, Knee
PubMed: 33419417
DOI: 10.1186/s12891-020-03912-z -
Journal of Neurochemistry Mar 2021The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization...
The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.
Topics: Amyloid; Amyloidosis, Familial; Animals; Gene Knockdown Techniques; Humans; Prealbumin
PubMed: 33155274
DOI: 10.1111/jnc.15233 -
Journal of the American Heart... Oct 2020Background The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature. Methods and...
Background The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature. Methods and Results A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was performed on MEDLINE, PubMed, and Embase databases on November 29, 2019. Studies were selected based on the following predefined eligibility criteria: English-language randomized controlled trials (RCTs), non-RCTs, or observational studies, which included adult patients with variant/wild-type transthyretin-CA, assessed specific therapies for transthyretin-CA, and reported cardiovascular outcomes. Relevant data were extracted to a predefined template. Quality assessment was based on National Institute for Health and Care Excellence recommendations (RCTs) or a checklist by Downs and Black (non-RCTs). From 1203 records, 24 publications were selected, describing 4 RCTs (6 publications) and 16 non-RCTs (18 publications). Tafamidis was shown to significantly improve all-cause mortality and cardiovascular hospitalizations and reduce worsening in 6-minute walk test, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in variant/wild-type transthyretin-CA. Patisiran showed promising results in a subgroup analysis of patients with variant transthyretin-CA, which have to be confirmed in RCTs. Inotersen showed conflicting results on cardiac imaging parameters. The one study on AG10 had only a 1-month duration and cardiovascular end points were exploratory and limited to cardiac biomarkers. Limited evidence from noncomparative single-arm small non-RCTs existed for diflunisal, epigallocatechin-3-gallate (green tea extract), and doxycycline+tauroursodeoxycholic acid/ursodeoxycholic acid. Conclusions This systematic review of the literature supports the use of tafamidis in wild-type and variant transthyretin-CA. Novel therapeutic targets including transthyretin gene silencers are currently under investigation.
Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Cardiomyopathies; Cardiovascular Agents; Genetic Therapy; Humans
PubMed: 32969287
DOI: 10.1161/JAHA.120.016614 -
Heart Failure Reviews Jan 2021Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by deposition of insoluble amyloid fibrils in the myocardium,...
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by deposition of insoluble amyloid fibrils in the myocardium, resulting in cardiac structural and functional abnormalities and ultimately heart failure. Disease frequency is reportedly lower in women than men, but sex-related differences have not been well established. We conducted a systematic literature review (SLR), based on PRISMA-P guidelines and registered with PROSPERO, to assess whether the epidemiology and clinical presentation of ATTR-CM differ between women and men. MEDLINE, Embase, and Cochrane databases and selected conference proceedings were searched (August 16, 2019) to identify observational and clinical studies reporting sex-specific data for patients with wild-type or hereditary ATTR-CM. Of 193 publications satisfying final eligibility criteria, 69 studies were included in our pooled analysis. Among the 4669 patients with ATTR-CM analyzed, 791 (17%) were women, including 174 (9%), 366 (29%), and 251 (18%) in studies of wild-type, hereditary, and undefined ATTR-CM, respectively. Data available on disease characteristics were limited and very heterogeneous, but trends suggested some cardiac structural/functional differences, i.e., lower interventricular septal and posterior wall thickness and left ventricular (LV) end diastolic diameter, and higher LV ejection fractions, in women versus men across ATTR-CM subtypes. Because LV wall thickness > 12 mm is generally the suggested threshold for ATTR-CM diagnosis in both sexes, smaller cardiac anatomy in women with the disease may lead to underdiagnosis. Additional research and studies are needed to elucidate potential disparities between sexes in ATTR-CM frequency, clinical characteristics, and underlying biological mechanisms. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) database of the University of York (CRD42019146995).
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Female; Humans; Male; Prealbumin
PubMed: 32794090
DOI: 10.1007/s10741-020-10010-8 -
Journal of Neuromuscular Diseases 2021Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid...
BACKGROUND
Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.
OBJECTIVE
We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies.
METHODS
We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale.
RESULTS
Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH).
CONCLUSIONS
The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
Topics: Amyloid Neuropathies, Familial; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Humans
PubMed: 32773395
DOI: 10.3233/JND-200546 -
European Journal of Hospital Pharmacy :... Jul 2020To carry out a systematic review of the literature to analyse the efficacy and safety of treatments available or under investigation for amyloidosis due to mutations in...
OBJECTIVE
To carry out a systematic review of the literature to analyse the efficacy and safety of treatments available or under investigation for amyloidosis due to mutations in the transthyretin gene (ATTR).
METHODS
A bibliographic search was carried out in the following electronic databases up to September 2017: PubMed, Cochrane Library and EMBASE. The inclusion criteria were: efficacy and/or safety studies conducted in humans, studies that included treatments, including treatments in the research phase, and studies that included 10 or more patients.
RESULTS
A total of 21 articles were included; 16 were clinical trials, eight of them (50%) phase III trials, and five were observational studies. Of the total number of studies selected, 11 were on tafamidis, four on diflunisal, two on liver transplantation, two on patisiran and two on other therapeutic alternatives. Of the 11 studies related to the drug, the pivotal trial, the results of its two extension studies and an additional post hoc analysis were selected. In addition, two phase III trials were included in specific populations, two phase II studies, one safety study and two observational studies. Regarding the four included studies related to the drug, one was the pivotal trial that gave the indication to diflunisal, another a safety summary of the pivotal trial, and the other two trials were carried out in specific populations, one in a Japanese population and another phase I trial in cardiac amyloidosis in the USA. As far as other alternatives are concerned, of the six studies included in this section, two were related to liver transplantation, two to patisiran and two to different therapeutic alternatives.
CONCLUSIONS
Sufficient evidence has not been found that demonstrates superiority among the available oral alternatives, diflunisal or tafamidis, in the treatment of ATTR. Direct comparisons between both drugs and pharmacoeconomic studies would be necessary to select the most efficient treatment.
Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Diflunisal; Humans; Liver Transplantation; RNA, Small Interfering
PubMed: 32587078
DOI: 10.1136/ejhpharm-2018-001823 -
JACC. Cardiovascular Imaging Jun 2020This study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging for evaluating cardiac amyloidosis (CA).
BACKGROUND
CA is a progressive infiltrative process in the extracellular space that is often underdiagnosed and holds a poor prognosis. Cardiac magnetic resonance (CMR) offers novel techniques for detecting and quantifying the disease burden of CA.
METHODS
We searched PubMed for published studies using native T1, ECV, or LGE to diagnose and prognosticate CA. A total of 18 diagnostic (n = 2,015) and 13 prognostic studies (n = 1,483) were included for analysis. Pooled sensitivities, specificities, diagnostic odds ratios (DORs) of all diagnostic tests were assessed by bivariate analysis. Pooled hazard ratios (HRs) for mortality for the 3 techniques were determined.
RESULTS
Bivariate comparison showed that ECV (DOR: 84.6; 95% confidence interval [CI]: 30.3 to 236.2) had a significantly higher DOR for CA than LGE (DOR: 20.1; 95% CI: 9.1 to 44.1; p = 0.03 vs. ECV). There was no significant difference between LGE and native T1 for sensitivity, specificity, and DOR. HR was significantly higher for ECV (HR: 4.27; 95% CI: 2.87 to 6.37) compared with LGE (HR: 2.60; 95% CI: 1.90 to 3.56; p = 0.03 vs. ECV) and native T1 (HR: 2.04; 95% CI: 1.24 to 3.37; p = 0.01 vs. ECV).
CONCLUSIONS
ECV demonstrates a higher diagnostic OR for assessing cardiac amyloid than LGE and a higher HR for adverse events compared with LGE and native T1. In addition, native T1 showed similar sensitivity and specificity as ECV and LGE without requiring contrast material. Although limited by study heterogeneity, this meta-analysis suggests that ECV provides high diagnostic and prognostic utility for the assessment of cardiac amyloidosis.
Topics: Adult; Aged; Amyloid Neuropathies, Familial; Cardiomyopathies; Female; Gadolinium; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Predictive Value of Tests; Reproducibility of Results; Stroke Volume; Ventricular Function, Left
PubMed: 32498919
DOI: 10.1016/j.jcmg.2020.03.010 -
The Cochrane Database of Systematic... Apr 2020Disease-modifying pharmacological agents for transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) have become available in the last decade, but evidence on...
BACKGROUND
Disease-modifying pharmacological agents for transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) have become available in the last decade, but evidence on their efficacy and safety is limited. This review focuses on disease-modifying pharmacological treatment for TTR-related and other FAPs, encompassing amyloid kinetic stabilisers, amyloid matrix solvents, and amyloid precursor inhibitors.
OBJECTIVES
To assess and compare the efficacy, acceptability, and tolerability of disease-modifying pharmacological agents for familial amyloid polyneuropathies (FAPs).
SEARCH METHODS
On 18 November 2019, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. We reviewed reference lists of articles and textbooks on peripheral neuropathies. We also contacted experts in the field. We searched clinical trials registries and manufacturers' websites.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) or quasi-RCTs investigating any disease-modifying pharmacological agent in adults with FAPs. Disability due to FAP progression was the primary outcome. Secondary outcomes were severity of peripheral neuropathy, change in modified body mass index (mBMI), quality of life, severity of depression, mortality, and adverse events during the trial.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
The review included four RCTs involving 655 people with TTR-FAP. The manufacturers of the drugs under investigation funded three of the studies. The trials investigated different drugs versus placebo and we did not conduct a meta-analysis. One RCT compared tafamidis with placebo in early-stage TTR-FAP (128 randomised participants). The trial did not explore our predetermined disability outcome measures. After 18 months, tafamidis might reduce progression of peripheral neuropathy slightly more than placebo (Neuropathy Impairment Score (NIS) in the lower limbs; mean difference (MD) -3.21 points, 95% confidential interval (CI) -5.63 to -0.79; P = 0.009; low-certainty evidence). However, tafamidis might lead to little or no difference in the change of quality of life between groups (Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score; MD -4.50 points, 95% CI -11.27 to 2.27; P = 0.19; very low-certainty evidence). No clear between-group difference was found in the numbers of participants who died (risk ratio (RR) 0.65, 95% CI 0.11 to 3.74; P = 0.63; very low-certainty evidence), who dropped out due to adverse events (RR 1.29, 95% CI 0.30 to 5.54; P = 0.73; very low-certainty evidence), or who experienced at least one severe adverse event during the trial (RR 1.16, 95% CI 0.37 to 3.62; P = 0.79; very low-certainty evidence). One RCT compared diflunisal with placebo (130 randomised participants). At month 24, diflunisal might reduce progression of disability (Kumamoto Score; MD -4.90 points, 95% CI -7.89 to -1.91; P = 0.002; low-certainty evidence) and peripheral neuropathy (NIS plus 7 nerve tests; MD -18.10 points, 95% CI -26.03 to -10.17; P < 0.001; low-certainty evidence) more than placebo. After 24 months, changes from baseline in the quality of life measured by the 36-Item Short-Form Health Survey score showed no clear difference between groups for the physical component (MD 6.10 points, 95% CI 2.56 to 9.64; P = 0.001; very low-certainty evidence) and the mental component (MD 4.40 points, 95% CI -0.19 to 8.99; P = 0.063; very low-certainty evidence). There was no clear between-group difference in the number of people who died (RR 0.46, 95% CI 0.15 to 1.41; P = 0.17; very low-certainty evidence), in the number of dropouts due to adverse events (RR 2.06, 95% CI 0.39 to 10.87; P = 0.39; very low-certainty evidence), and in the number of people who experienced at least one severe adverse event (RR 0.77, 95% CI 0.18 to 3.32; P = 0.73; very low-certainty evidence) during the trial. One RCT compared patisiran with placebo (225 randomised participants). After 18 months, patisiran reduced both progression of disability (Rasch-built Overall Disability Scale; least-squares MD 8.90 points, 95% CI 7.00 to 10.80; P < 0.001; moderate-certainty evidence) and peripheral neuropathy (modified NIS plus 7 nerve tests - Alnylam version; least-squares MD -33.99 points, 95% CI -39.86 to -28.13; P < 0.001; moderate-certainty evidence) more than placebo. At month 18, the change in quality of life between groups favoured patisiran (Norfolk QOL-DN total score; least-squares MD -21.10 points, 95% CI -27.20 to -15.00; P < 0.001; low-certainty evidence). There was little or no between-group difference in the number of participants who died (RR 0.61, 95% CI 0.21 to 1.74; P = 0.35; low-certainty evidence), dropped out due to adverse events (RR 0.33, 95% CI 0.13 to 0.82; P = 0.017; low-certainty evidence), or experienced at least one severe adverse event (RR 0.91, 95% CI 0.64 to 1.28; P = 0.58; low-certainty evidence) during the trial. One RCT compared inotersen with placebo (172 randomised participants). The trial did not explore our predetermined disability outcome measures. From baseline to week 66, inotersen reduced progression of peripheral neuropathy more than placebo (modified NIS plus 7 nerve tests - Ionis version; MD -19.73 points, 95% CI -26.50 to -12.96; P < 0.001; moderate-certainty evidence). At week 65, the change in quality of life between groups favoured inotersen (Norfolk QOL-DN total score; MD -10.85 points, 95% CI -17.25 to -4.45; P < 0.001; low-certainty evidence). Inotersen may slightly increase mortality (RR 5.94, 95% CI 0.33 to 105.60; P = 0.22; low-certainty evidence) and occurrence of severe adverse events (RR 1.48, 95% CI 0.85 to 2.57; P = 0.16; low-certainty evidence) compared to placebo. More dropouts due to adverse events were observed in the inotersen than in the placebo group (RR 8.57, 95% CI 1.16 to 63.07; P = 0.035; low-certainty evidence). There were no studies addressing apolipoprotein AI-FAP, gelsolin-FAP, and beta-2-microglobulin-FAP.
AUTHORS' CONCLUSIONS
Evidence on the pharmacological treatment of FAPs from RCTs is limited to TTR-FAP. No studies directly compare disease-modifying pharmacological treatments for TTR-FAP. Results from placebo-controlled trials indicate that tafamidis, diflunisal, patisiran, and inotersen may be beneficial in TTR-FAP, but further investigations are needed. Since direct comparative studies for TTR-FAP will be hampered by sample size and costs required to demonstrate superiority of one drug over another, long-term non-randomised open-label studies monitoring their efficacy and safety are needed.
Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Diflunisal; Disease Progression; Humans; Oligonucleotides; Patient Dropouts; Quality of Life; RNA, Small Interfering; Randomized Controlled Trials as Topic
PubMed: 32311072
DOI: 10.1002/14651858.CD012395.pub2 -
International Journal of Molecular... Mar 2020Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDs), presenting a broad range of symptoms from motor dysfunctions...
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDs), presenting a broad range of symptoms from motor dysfunctions to psychobehavioral manifestations. A common clinical course is the proteinopathy-induced neural dysfunction leading to anatomically corresponding neuropathies. However, current diagnostic criteria based on pathology and symptomatology are of little value for the sake of disease prevention and drug development. Overviewing the pathomechanism of NDs, this review incorporates systematic reviews on inflammatory cytokines and tryptophan metabolites kynurenines (KYNs) of human samples, to present an inferential method to explore potential links behind NDs. The results revealed increases of pro-inflammatory cytokines and neurotoxic KYNs in NDs, increases of anti-inflammatory cytokines in AD, PD, Huntington's disease (HD), Creutzfeldt-Jakob disease, and human immunodeficiency virus (HIV)-associated neurocognitive disorders, and decreases of neuromodulatory KYNs in AD, PD, and HD. The results reinforced a strong link between inflammation and neurotoxic KYNs, confirmed activation of adaptive immune response, and suggested a possible role in the decrease of neuromodulatory KYNs, all of which may contribute to the development of chronic low grade inflammation. Commonalities of multifactorial NDs were discussed to present a current limit of diagnostic criteria, a need for preclinical biomarkers, and an approach to search the initiation factors of NDs.
Topics: Alzheimer Disease; Anti-Inflammatory Agents; Biomarkers; Cytokines; Humans; Huntington Disease; Inflammation; Kynurenine; Neurodegenerative Diseases; Parkinson Disease; Reactive Oxygen Species; Tryptophan
PubMed: 32244523
DOI: 10.3390/ijms21072431 -
Current Cardiology Reviews 2020There is a growing interest in the observed significant incidence of transthyretin cardiac amyloidosis in elderly patients with aortic stenosis. Approximately, 16% of...
BACKGROUND
There is a growing interest in the observed significant incidence of transthyretin cardiac amyloidosis in elderly patients with aortic stenosis. Approximately, 16% of patients with severe aortic stenosis undergoing aortic valve replacement have transthyretin cardiac amyloidosis. Outcomes after aortic valve replacement appear to be worst in patients with concomitant transthyretin cardiac amyloidosis.
METHODS
Publications in PubMed, Cochrane Library, and Embase databases were systematically searched from January 2012 to September 2018 using the keywords transthyretin, amyloidosis, and aortic stenosis. All studies published in English that reported the prevalence, association and outcomes of transthyretin cardiac amyloidosis in patients with aortic stenosis undergoing were included.
RESULTS/CONCLUSION
The relationship between aortic stenosis and transthyretin cardiac amyloidosis is not well understood. A few studies have proven successful surgical management when both conditions coexist. This systematic review suggests that transthyretin cardiac amyloidosis is common in elderly patients with aortic stenosis and tend to have high mortality rates after AVR. The significant incidence of the two diseases occurring simultaneously warrants further investigation to improve management strategies in the future.
Topics: Amyloid Neuropathies, Familial; Aortic Valve Stenosis; Female; Humans; Male; Treatment Outcome
PubMed: 31544701
DOI: 10.2174/1573403X15666190722154152