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BMC Cardiovascular Disorders Dec 2018Cardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage....
BACKGROUND
Cardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage. The vast majority of CA cases are caused by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). The increased awareness of these diseases has led to an increment of newly diagnosed cases each year.
METHODS
We performed multiple searches on MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Several search terms were used, such as "cardiac amyloidosis", "diagnostic modalities cardiac amyloidosis" and "staging cardiac amyloidosis". Emphasis was given on original articles describing novel diagnostic and staging approaches to the disease.
RESULTS
Imaging techniques are indispensable to diagnosing CA. Novel ultrasonographic techniques boast high sensitivity and specificity for the disease. Nuclear imaging has repeatedly proved its worth in the diagnostic procedure, with efforts now focusing on standardization and quantification of amyloid load. Because the latter would be invaluable for any staging system, those spearheading research in magnetic resonance imaging of the disease are also trying to come up with accurate tools to quantify amyloid burden. Staging tools are currently being developed and validated for ATTR CA, in the spirit of the acclaimed Mayo Staging System for AL.
CONCLUSION
Cardiac involvement confers significant morbidity and mortality in all types of amyloidosis. Great effort is made to reduce the time to diagnosis, as treatment in the initial stages of the disease is tied to better prognosis. The results of these efforts are highly sensitive and specific diagnostic modalities that are also reasonably cost effective.
Topics: Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Echocardiography; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index; Tomography, Emission-Computed
PubMed: 30509186
DOI: 10.1186/s12872-018-0952-8 -
Annals of the Rheumatic Diseases Apr 2015Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology... (Review)
Review
Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique and were accepted if more than 80% agreement was reached. The literature search yielded 3386 articles, of which 25 were considered relevant and scored for validity and level of evidence. In total, 17 articles were scored valid and used to formulate the recommendations. Eight recommendations were accepted with 100% agreement after the consensus meeting. Topics covered were clinical versus genetic diagnosis of FMF, genotype-phenotype correlation, genotype-age at onset correlation, silent carriers and risk of amyloid A (AA) amyloidosis, and role of the specialist in FMF diagnosis. The SHARE initiative provides recommendations for diagnosing FMF aimed at facilitating improved and uniform care throughout Europe.
Topics: Child; Cytoskeletal Proteins; Evidence-Based Medicine; Familial Mediterranean Fever; Humans; Practice Guidelines as Topic; Pyrin; Young Adult
PubMed: 25628446
DOI: 10.1136/annrheumdis-2014-206844 -
American Journal of Cardiovascular... 2022Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an... (Review)
Review
BACKGROUND
Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an underestimated phenotype. We aim to evaluate the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction.
METHODS
This meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar to locate studies whose primary objective was to analyze the prevalence of transthyretin amyloidosis in heart failure preserved ejection fraction.
RESULTS
Of 271 studies initially identified, 5 studies comprising 670 patients were included in the final analysis. The prevalence of transthyretin amyloidosis was 11%. Patients with transthyretin amyloid cardiomyopathy were more likely to be males (RR 1.38; 95% CI 1.09 to 1.75; P<0.01; I=37%), and more likely to have low voltage criteria on ECG (RR 2.98; 95% CI 1.03 to 8.58; P=0.04; I=75%) compared with transthyretin negative group. They also have higher SMD of age (SMD 0.73; 95% CI 0.48 to 0.97; P<0.01; I=0%), and NT-proBNP (SMD 0.48; 95% CI 0.02 to 0.93; P=0.04; I=36%) compared with transthyretin negative group. On reported echocardiogram, they have higher SMD of mass index (SMD 0.77; 95% CI 0.27 to 1.27; P<0.01; I=65%), posterior wall thickness (SMD 0.92; 95% CI 0.62 to 1.21; P<0.01; I=0%), and septal wall thickness (SMD 1.49; 95% CI 0.65 to 2.32; P<0.01; I=87%) compared with transthyretin negative group.
CONCLUSION
Transthyretin amyloidosis affects 11% of HFpEF patients. Therefore, screening HFpEF patients at risk of cardiac amyloidosis is warranted.
PubMed: 35873185
DOI: No ID Found -
Cardiovascular Ultrasound Dec 2019Left ventricular hypertrophy and diastolic dysfunction are common echocardiographic features of both aortic valve stenosis (AS) and cardiac amyloidosis (CA). These two...
BACKGROUND
Left ventricular hypertrophy and diastolic dysfunction are common echocardiographic features of both aortic valve stenosis (AS) and cardiac amyloidosis (CA). These two different entities therefore may mask each other. From recent years, there is a growing body of evidence about the relatively high incidence of wild-type transthyretin (wtTTR) amyloidosis in AS, but there are scarce data on the prevalence of AS in CA, particularly in AL-type amyloidosis. The echocardiographic approach to these patients is not obvious, and not evidence based. We aimed to study the prevalence, severity, and type of AS in patients with CA and also to evaluate the potential of echocardiography in the diagnostic process.
METHODS
Between January 2009 and January 2019, we retrospectively analyzed the clinical and echocardiographic data, and the echocardiographic work up of 55 consecutive CA patients.
RESULTS
80% of our CA patients had AL amyloidosis. We identified 5 patients (9%) with moderate to severe AS: two with moderate AS and three with low-flow, low-grade AS (LFLG AS). Further analysis of the latter three patients with dobutamine stress echocardiography revealed pseudo-severe LFLG AS in two, and true-severe AS in one patient.
CONCLUSION
The prevalence of moderate to severe AS is 9% in our population of CA patients, the majority of whom have AL amyloidosis. Dobutamine echocardiography seems to be appropriate for the further characterization of patients with LFLG AS, even with normal ejection fraction.
Topics: Aged; Amyloidosis; Aortic Valve Stenosis; Cardiomyopathies; Echocardiography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies
PubMed: 31878928
DOI: 10.1186/s12947-019-0182-y -
Journal of Magnetic Resonance Imaging :... Apr 2018Although cardiac MR and T mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T values in healthy and diseased... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although cardiac MR and T mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T values in healthy and diseased myocardium, particular in nonischemic cardiomyopathies (NICM) and populations with increased cardiovascular risk, seem contradictory.
PURPOSE
To determine the range of native myocardial T value ranges in patients with NICM and populations with increased cardiovascular risk.
STUDY TYPE
Systemic review and meta-analysis.
POPULATION
Patients with NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and patients with myocarditis (MC), iron overload, amyloidosis, Fabry disease, and populations with hypertension (HT), diabetes mellitus (DM), and obesity. FIELD STRENGTH/SEQUENCE: (Shortened) modified Look-Locker inversion-recovery MR sequence at 1.5 or 3T.
ASSESSMENT
PubMed and Embase were searched following the PRISMA guidelines.
STATISTICAL TESTS
The summary of standard mean difference (SMD) between the diseased and a healthy control populations was generated using a random-effects model in combination with meta-regression analysis.
RESULTS
The SMD for HCM, DCM, and MC patients were significantly increased (1.41, 1.48, and 1.96, respectively, P < 0.01) compared with healthy controls. The SMD for HT patients with and without left-ventricle hypertrophy (LVH) together was significantly increased (0.19, P = 0.04), while for HT patients without LVH the SMD was zero (0.03, P = 0.52). The number of studies on amyloidosis, iron overload, Fabry disease, and HT patients with LVH did not meet the requirement to perform a meta-analysis. However, most studies reported a significantly increased T for amyloidosis and HT patients with LVH and a significant decreased T for iron overload and Fabry disease patients.
DATA CONCLUSIONS
Native T mapping by using an (Sh)MOLLI sequence can potentially assess myocardial changes in HCM, DCM, MC, iron overload, amyloidosis, and Fabry disease compared to controls. In addition, it can help to diagnose left-ventricular remodeling in HT patients.
LEVEL OF EVIDENCE
2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:891-912.
Topics: Cardiomyopathies; Cardiovascular Diseases; Heart; Humans; Magnetic Resonance Imaging; Myocardium; Reference Values; Risk Factors
PubMed: 29131444
DOI: 10.1002/jmri.25885 -
Orphanet Journal of Rare Diseases Sep 2022Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This...
BACKGROUND
Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This retrospective analysis study aimed to report the genotypes and phenotypes of herediary transthyretin amyloidosis (hATTR) in Chinese through a systematic review of published literature.
METHODS
The systematic review included structured searches of peer-reviewed literature published from 2007 to 2020 of following online reference databases: PubMed, Web of Science and the literature database in China. Extracted data included sample size, personal information (sex, age, natural course, family history), mutation type, clinical milestones and reason of death.
RESULTS
We described 126 Chinese patients with hereditary transthyretin amyloidosis identified through a systematic review of 30 studies. The most common genotype in the Chinese population was Gly83Arg (25, 19.8%), which most likely presented visual and neurological abnormalities without reported death. The second and third most common genotypes were Val30Met (20, 15.9%) and Val30Ala (10, 7.9%). Peripheral neurological manifestations (91, 72%) were dominant in 126 patients. The followed manifestation was autonomic neurological abnormalities (73, 58%). Half of the cases were reported to have visual disorders, and nearly one-third of the cases presented cardiac abnormalities. Among all 126 reported patients, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. In addition. Chinese patients were mostly early onset, with age of onset at 41.8 (SD: 8.9) years, and the median time from onset to death was 7.5 [IQR: 5.3] years. Patients with cardiac involvement had a shorter survival duration (log Rank (Mantel-Cox), χ = 26.885, P < 0.001).
CONCLUSIONS
This study focused on 126 Chinese hATTR patients obtained from a literature review. A total of 26 kinds of TTR mutations were found and the most common one was Gly83Arg. As for phenotype, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. Chinese hATTR patients were mostly early onset (AO 41.8 years), and the median time from onset to death was 7.5 years.
Topics: Amyloid Neuropathies, Familial; Humans; Phenotype; Prealbumin; Retrospective Studies
PubMed: 36056432
DOI: 10.1186/s13023-022-02481-9 -
Journal of Alzheimer's Disease : JAD 2023The negative effects of periodontitis on systemic diseases, including diabetes, cardiovascular diseases, and Alzheimer's disease (AD), have been widely described.
BACKGROUND
The negative effects of periodontitis on systemic diseases, including diabetes, cardiovascular diseases, and Alzheimer's disease (AD), have been widely described.
OBJECTIVE
This systematic review aimed to gather the current understanding of the pathophysiological mechanisms linking periodontitis to AD.
METHODS
An electronic systematic search of the PubMed/MEDLINE, Scopus, and Embase databases was performed using the following PECO question: How can periodontitis or periodontal bacteria influence Alzheimer's disease features?". Only preclinical studies exploring the biological links between periodontitis and AD pathology were included. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), and the Syrcle and Camarades protocols were used to assess the risk of bias.
RESULTS
After a systematic screening of titles and abstracts (n = 3,307), thirty-six titles were selected for abstract reading, of which 13 were excluded (k = 1), resulting in the inclusion of 23 articles. Oral or systemic exposure to periodontopathogens or their byproducts is responsible for both in situ brain manifestations and systemic effects. Significant elevated rates of cytokines and amyloid peptides (Aβ) and derivate products were found in both serum and brain. Additionally, in infected animals, hyperphosphorylation of tau protein, hippocampal microgliosis, and neuronal death were observed. Exposure to periodontal infection negatively impairs cognitive behavior, leading to memory decline.
CONCLUSIONS
Systemic inflammation and brain metastatic infections induced by periodontal pathogens contribute to neuroinflammation, amyloidosis, and tau phosphorylation, leading to brain damage and subsequent cognitive impairment.
Topics: Animals; Alzheimer Disease; Systematic Reviews as Topic; Periodontitis; Inflammation; Cognitive Dysfunction
PubMed: 37927257
DOI: 10.3233/JAD-230478 -
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 -
ESC Heart Failure Oct 2022Aortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve... (Meta-Analysis)
Meta-Analysis
AIMS
Aortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve replacement (TAVR) have a concomitant diagnosis of CA. CA-AS population suffers from reduced functional capacity and worse prognosis than AS patients. As the prognostic impact of TAVR in patients with CA-AS has been historically questioned and in light of recently published evidence, we aim to provide a comprehensive synthesis of the efficacy and safety of TAVR in CA-AS patients.
METHODS AND RESULTS
We performed a systematic review and meta-analysis of studies: (i) evaluating mortality with TAVR as compared with medical therapy in CA-AS patients and (ii) reporting complications and clinical outcomes of TAVR in CA-AS patients as compared with patients with AS alone. A total of seven observational studies were identified: four reported mortality with TAVR, and four reported complications and clinical outcomes after TAVR of patients with CA-AS compared with AS alone patients. In patients with CA-AS, the risk of mortality was lower with TAVR (n = 44) as compared with medical therapy (n = 36) [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.73, I = 0%, P = 0.001, number needed to treat = 3]. The safety profile of TAVR seems to be similar in patients with CA-AS (n = 75) as compared with those with AS alone (n = 536), with comparable risks of stroke, vascular complications, life-threatening bleeding, acute kidney injury, and 30 day mortality, although CA-AS was associated with a trend towards an increased risk of permanent pacemaker implantation (OR 1.76, 95% CI 0.91-4.09, I = 0%, P = 0.085). CA is associated with a numerically higher rate of long-term mortality and rehospitalizations following TAVR in patients with CA-AS as compared with those with AS alone.
CONCLUSIONS
TAVR is an effective and safe procedure in CA-AS patients, with a substantial survival benefit as compared with medical therapy, and a safety profile comparable with patients with AS alone except for a trend towards higher risk of permanent pacemaker implantation.
Topics: Humans; Aged; Transcatheter Aortic Valve Replacement; Aortic Valve; Heart Valve Prosthesis Implantation; Risk Factors; Aortic Valve Stenosis; Amyloidosis
PubMed: 35770333
DOI: 10.1002/ehf2.13876 -
ESC Heart Failure Aug 2023The clinical value of cardiopulmonary exercise testing (CPET) in cardiac amyloidosis (CA) is uncertain. Due to the growing prevalence of the disease and the current... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical value of cardiopulmonary exercise testing (CPET) in cardiac amyloidosis (CA) is uncertain. Due to the growing prevalence of the disease and the current availability of disease-modifying drugs, prognostic stratification is becoming fundamental to optimizing the cost-effectiveness of treatment, patient phenotyping, follow-up, and management. Peak VO and VE/VCO slope are currently the most studied CPET variables in clinical settings, and both demonstrate substantial, independent prognostic value in several cardiovascular diseases. We aim to study the association of peak VO and VE/VCO slope with prognosis in patients with CA.
METHODS AND RESULTS
We performed a systematic review and searched for clinical studies performing CPET for prognostication in patients with transthyretin-CA and light-chain-CA. Studies reporting hazard ratio (HR) for mortality and peak VO or VE/VCO slope were further selected for quantitative analysis. HRs were pooled using a random-effect model. Five studies were selected for qualitative and three for quantitative analysis. A total of 233 patients were included in the meta-analysis. Mean peak VO resulted consistently depressed, and VE/VCO slope was increased. Our pooled analysis showed peak VO (pooled HR 0.89, 95% CI 0.84-0.94) and VE/VCO slope (pooled HR 1.04, 95% CI 1.01-1.07) were significantly associated with the risk of death in CA patients, with no significant statistical heterogeneity for both analyses.
CONCLUSIONS
CPET is a valuable tool for prognostic stratification in CA, identifying patients at increased risk of death. Large prospective clinical trials are needed to confirm this exploratory finding.
Topics: Humans; Exercise Test; Prospective Studies; Oxygen Consumption; Prognosis; Amyloidosis; Cardiomyopathies
PubMed: 37264762
DOI: 10.1002/ehf2.14406