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In this study, nanostructures were introduced into bulk Si, and the P content in Si was increased. Arc melting, ball milling, and spark plasma sintering were used to prepare excess P-doped Si samples (Si1−xPx, x = 0.01, 0.03, 0.06, 0.09, and 0.12). In Si0.94P0.06, thermal conductivity decreased to 18 W m−1 K−1 at room temperature, which is about 10% of that of bulk Si. Transmission electron microscopy observation of Si0.94P0.06 revealed a linearly localized alignment, in addition to the nanostructures observed in the previous studies of P-doped Si samples. Linear alignments were composed of Si-P nanoprecipitates and defects linearly localized around dislocations. These sub-microstructures can reduce thermal conductivity; as a result, ZT at 973 K increased to 0.43, which is approximately three times higher than that of single-crystal Si. [ABSTRACT FROM AUTHOR]

Enthesitis is a characteristic manifestation of spondyloarthropathy (SpA). Historically, Behçet's syndrome (BS) was classified within SpA. Although they are now classified separately, the association between BS and SpA remains controversial. The concept of MHC-I (major histocompatibility complex class I)-opathy has been proposed based on the overlap in immunopathological mechanisms among diseases associated with human leukocyte antigen (HLA) class I. Enthesitis is a frequent complication in patients with BS who also have acne and arthritis. However, information regarding enthesitis in patients with BS without arthritis (BS-WA) is limited. Herein, we report a case of vascular BS complicated by enthesitis. In this case, heel pain was the dominant symptom at presentation. Laboratory tests revealed chlamydia antibody positivity, leading to a tentative diagnosis of reactive arthritis. Despite treatment, C-reactive protein (CRP) levels remained elevated. Imaging revealed numerous aneurysmal lesions in the large vessels. Based on these findings and other symptoms, patient was diagnosed with vascular BS. He tested positive for HLA-B15 and HLA-B46, which are associated with peripheral SpA. Subsequent remission induction therapy for BS was effective and the patient was discharged without complications. Our case and a literature review suggest that there exists a subgroup of BS-WA with a complication of enthesitis, possibly belonging to the spectrum of MHC-I-opathies. It is important to consider BS as a differential diagnosis in patients presenting with enthesitis and to conduct a precise medical history review regarding the symptoms of BS. [ABSTRACT FROM AUTHOR]

Objective To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. Methods Patients were randomized to riociguat (n  = 60) or placebo (n  = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. α-Smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. Results By week 14, cGMP increased by 94 (78)% with riociguat and 10 (39)% with placebo (P  < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (P  = 0.004 and P  = 0.008, respectively). There were no differences in skin collagen markers between the two groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies was associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P -values 0.004 and 0.02, respectively). Conclusion Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide–soluble guanylate cyclase–cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. Trial registration Clinicaltrials.gov, NCT02283762. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) treated with tafamidis (VYNDAQEL®) in Japan using the Japanese Medical Data Vision (MDV) database. Methods and results: This study was a non‐interventional, retrospective cohort study of adult (≥18 years old) patients in the Japanese MDV claims database diagnosed with ATTR‐CM and with at least two tafamidis prescriptions of dose strength 4 × 20 mg/day between 1 March 2019 and 31 August 2021. The date of the first prescription was defined as the index date, with follow‐up time defined as the time between the first and last prescription plus the days' supply from the last refill. Baseline characteristics were assessed during a 12 month pre‐index period. Adherence was measured using two metrics: (i) the modified medication possession ratio (mMPR), calculated by taking the sum of days supplied for all fills within the follow‐up period, divided by the number of days of follow‐up, and reported as a percentage, with patients classified as adherent with an mMPR of ≥80%, and (ii) the proportion of days covered (PDC), calculated by taking the total number of days' supply dispensed during the follow‐up period divided by the number of days of follow‐up, adjusting for any days' supply overlap. A total of 210 patients were identified; the mean (standard deviation) age of the cohort was 77 (5.9) years, and the majority (89%) were male. The most common baseline cardiovascular comorbidities were heart failure (85%), ischaemic heart disease (66%), hypertensive diseases (49%), and diabetes (35%); 75% of patients received heart failure medications in the 12 months prior to index, with the most common being beta‐blockers (49%), diuretics (48%), angiotensin receptor blockers (30%), angiotensin‐converting enzyme inhibitors (22%), and sodium–glucose cotransporter‐2 inhibitors (8.1%). Over an average 14 month follow‐up, mean mMPR was 96% with a median of 100% [inter‐quartile range (IQR): 97–101%]; 93% of patients were adherent (defined as an mMPR ≥ 80%). In the same follow‐up period, mean PDC was 93.6% with a median of 99% (IQR: 93–100%). Persistence was high with 78% of patients having a 0 day gap between prescription refills. Conclusions: This study found high adherence rates to tafamidis in this real‐world Japanese patient population. Adherence rates in this study were similar to those reported by the tafamidis clinical trial and a previously published US commercial claims adherence analysis. Further studies should be conducted to assess the impact of real‐world adherence on real‐world outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to assess real-world, long-term safety/effectiveness of mepolizumab for eosinophilic granulomatosis with polyangiitis (EGPA) in Japan. Methods: The Mepolizumab long-term study to Assess Real-world Safety and effectiveness of EGPA in Japan (MARS) (GSK ID: 213684/NCT04551989) is an ongoing 96-week study of patients with EGPA who received four-weekly mepolizumab 300 mg subcutaneously for ≥96 weeks before study entry (baseline) and continued treatment. This interim analysis included safety from baseline to Week 48 (observation period) and clinical outcomes before mepolizumab and during the observation period. Results: Of 118 patients enrolled, 29% (34/118) experienced adverse events (AEs), of which 13% (15/118) experienced serious AEs; none were considered mepolizumab related. The median oral corticosteroid (OCS) dose decreased from 6.9 (pre-mepolizumab) to 3.0 (baseline) and 2.0 mg/day (Weeks 45–48); the proportion of patients receiving no OCS increased from 8% to 32% and 38%, respectively. Patients experiencing clinical symptoms decreased from 94% (pre-mepolizumab) to 73% (baseline) and 67% (Week 48). During the observation period, 5% of patients experienced EGPA relapse; the rates of EGPA-related hospitalisations, EGPA-related emergency room/unscheduled visits, and asthma exacerbations were 0.05, 0.09, and 0.08 event/person-year, respectively. Conclusions: The results of mepolizumab treatment for ≥144 weeks (before baseline plus observation) were consistent with the known safety profile and allowed OCS dose reduction while improving disease control versus pre-treatment among patients with EGPA. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is associated with interstitial lung disease (ILD) and malignancy. However, the coexistence of ILD and malignancy (DM–ILD–malignancy) is rare, and limited information exists regarding its management. Herein, we report the case of a 70-year-old man who developed DM with rapidly progressive ILD and advanced gastric cancer and provide a literature review of managing DM–ILD–malignancy. The patient presented with typical DM skin rashes and shortness of breath, which worsened within 1 month, without muscular symptoms. Additionally, the patient tested negative for myositis-specific autoantibodies (MSAs). Computed tomography revealed ILD and advanced gastric cancer, which was confirmed on endoscopic examination to be a poorly differentiated adenocarcinoma. Although the patient's ILD progressed rapidly, surgical treatment of the cancer was prioritized. Prednisolone (PSL) 0.5 mg/kg was initiated 3 days before surgery and increased to 1 mg/kg at 7 days postoperative. Remarkable improvement in the skin rash and ILD was observed, and the PSL dose was tapered without immunosuppressants. A literature review revealed that anti-melanoma differentiation-associated gene 5 and anti-aminoacyl transfer RNA synthetase antibodies are the predominant MSAs in DM–ILD–malignancy, and the optimal treatment should be determined based on several factors, including ILD patterns, and malignancy type and stage. In particular, lung cancer may be a risk factor for the acute exacerbation of ILD, and preceding immunosuppression would be useful. Furthermore, prioritizing surgery for gastric cancer is effective because of its paraneoplastic nature. [ABSTRACT FROM AUTHOR]

Objectives To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Methods Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median age of onset 69.3 years (interquartile range 62.1–77.6)]. Peptide nucleic acid–clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR or targeted amplicon deep sequencing was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and -negative patients and assessed the diagnostic value of our system using receiver operating characteristics (ROC) curve analysis. Results Forty patients (44.9%) with reported pathogenic UBA1 variants were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering age >50 years, cutaneous lesions, lung involvement, chondritis and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). Conclusion Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants. [ABSTRACT FROM AUTHOR]

Objective: To develop a proposal for giant cell arteritis remission criteria in order to implement a treat-to-target algorithm. Methods: A task force consisting of 10 rheumatologists, 3 cardiologists, 1 nephrologist, and 1 cardiac surgeon was established in the Large-vessel Vasculitis Group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis to conduct a Delphi survey of remission criteria for giant cell arteritis. The survey was circulated among the members over four reiterations with four face-to-face meetings. Items with a mean score of ≥4 were extracted as items for defining remission criteria. Results: An initial literature review yielded a total of 117 candidate items for disease activity domains and treatment/comorbidity domains of remission criteria, of which 35 were extracted as disease activity domains (systematic symptoms, signs and symptoms of cranial and large-vessel area, inflammatory markers, and imaging findings). For the treatment/comorbidity domain, ≤5 mg/day of prednisolone 1 year after starting glucocorticoids was extracted. The definition of achievement of remission was the disappearance of active disease in the disease activity domain, normalization of inflammatory markers, and ≤5 mg/day of prednisolone. Conclusion: We developed proposals for remission criteria to guide the implementation of a treat-to-target algorithm for giant cell arteritis. [ABSTRACT FROM AUTHOR]

Hereditary transthyretin (ATTRv) amyloidosis is a rare and autosomal dominant disorder associated with mutations in the transthyretin gene. Patients present with diverse symptoms related to sensory, motor, and autonomic neuropathy, as well as gastrointestinal, ocular, cardiac, renal and orthopedic symptoms, resulting from the deposition of transthyretin amyloid fibrils in multiple organs. The progressive nature of ATTRv amyloidosis necessitates pre- and post-onset monitoring of the disease. This review article is primarily based on a collation of discussions from a medical advisory board meeting in August 2021. In this article, we summarize the best practices in amyloidosis centers in three major endemic countries for ATTRv amyloidosis (Japan, Brazil, and Portugal), where most patients carry the Val30Met mutation in the transthyretin gene and the patients' genetic background was proven to be the same. The discussions highlighted the similarities and differences in the management of asymptomatic gene mutation carriers among the three countries in terms of the use of noninvasive tests and tissue biopsies and timing of starting the investigations. In addition, this article discusses a set of practical tests and examinations for monitoring disease progression applicable to neurologists working in diverse medical settings and generalizable in non-endemic countries and areas. This set of assessments consists of periodic (every 6 to 12 months) evaluations of patients' nutritional status and autonomic, renal, cardiac, ophthalmologic, and neurological functions. Physical examinations and patient-reported outcome assessments should be also scheduled every 6 to 12 months. Programs for monitoring gene mutation carriers and robust referral networks can aid in appropriate patient management in pre- to post-onset stages. For pre- and post-symptom onset testing for ATTRv amyloidosis, various noninvasive techniques are available; however, their applicability differs depending on the medical setting in each country and region, and the optimal option should be selected in view of the clinical settings, medical environment, and available healthcare resources in each region. [ABSTRACT FROM AUTHOR]

The article presents a case of relapsing polychondritis (RP) with pulmonary arteritis that was treated successfully with prednisolone (PSL), MTX and infliximab. Topics include medical history of the patient evaluated in the study, treatment given to the patient, and effectiveness of high-dose corticosteroids and biological agents for RP associated with large-vessel vasculitis (LVV).

Although Takayasu arteritis (TAK) is a form of large vessel vasculitis, complications of glomerulonephritis have occasionally been observed, with mesangial proliferative glomerulonephritis as the most common. The aim of this work was to present a case-based review regarding the association of glomerulonephritis and IgA nephropathy (IgAN) with TAK. A literature search was carried out using the PubMed and Scopus databases for articles published in English, and the Ichu-shi Web for Japanese. A 34-year-old Japanese man was evaluated for proteinuria, and IgAN was diagnosed by renal biopsy. Simultaneously, aortic wall thickening and right renal artery stenosis confirmed a coexisting TAK. Prednisolone and methotrexate improved both diseases, and percutaneous transluminal renal angioplasty resulted in right renal artery reopening. Our case and literature review revealed that membranous proliferative glomerulonephritis and IgAN are common in eastern Asia, while focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis are common in other regions. The incidence of IgAN is higher in TAK cases and is mostly reported in Asia. Abdominal aortic involvement and renal artery stenosis are common in cases with preceding TAK. IgAN could be related to the cytokine network involving interleukin-6, suggesting the usefulness of tocilizumab in patients with TAK accompanied by IgAN. The type of glomerulonephritis complicated with TAK differs among regions, and patients with TAK are more likely to experience IgAN than the healthy population. [ABSTRACT FROM AUTHOR]

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disorder classified under anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, predominantly affecting small- to medium-sized vessels, characterized by asthma, eosinophilia, and necrotizing granulomatous inflammation. Most patients with EGPA experience peripheral neuropathy, whereas intracerebral hemorrhage is rare as EGPA-related presentation in central nervous system involvement, causing severe morbidity and mortality. Here, we present a 45-year-old man with refractory EGPA who developed intracerebral hemorrhage as the first manifestation, followed by cardiac involvement. This patient with a history of bronchial asthma developed a right putaminal hemorrhage caused by EGPA. Although intravenous cyclophosphamide (IVCY) and mepolizumab (MPZ) induced remission, relapse was frequently observed. Subsequently, he developed cardiomyopathy despite administration of rituximab (RTX) substituted from IVCY and MPZ. Combined immunosuppressive therapy, including IVCY, MPZ, and RTX was required to inhibit vascular inflammation, leading to sustained remission. We review previously published literature while focusing on the clinical features of patients with intracerebral hemorrhage caused by EGPA and describe clinical characteristics for detecting EGPA in patients with intracerebral hemorrhage, emphasizing rapid evaluation and recognition of EGPA and adequate intervention in the early vasculitic phase of this disease. We also refer to the immunological aspects of this case. It is important to consider "multi-targeted therapy" through interleukin-5 suppression and B cell depletion in the management of refractory EGPA. [ABSTRACT FROM AUTHOR]

Objectives To assess the efficacy and safety of branched chain amino acids (BCAAs) in the treatment of PM/DM prior to official approval of their use in Japan. Methods Treatment naïve adults with PM/DM were enrolled in a randomized, double-blind trial to receive either TK-98 (drug name of BCAAs) or placebo in addition to conventional treatment. After 12 weeks, patients with an average manual muscle test (MMT) score <9.5 were enrolled in an open label extension study for a further 12 weeks. The primary endpoint was the change of the MMT score at 12 weeks. The secondary endpoints were the clinical response and the change of functional index (FI). Results Forty-seven patients were randomized either to the TK-98 (n  = 24) or placebo (n  = 23) group. The changes of MMT scores at 12 weeks were 0.70 (0.19) [mean (s. e. m.)] and 0.69 (0.18), respectively (P  = 0.98). Thirteen patients from the TK-98 group and 12 from the placebo group were enrolled in the extension study. The MMT scores in both groups improved similarly. The increase of the FI scores of the shoulder flexion at 12 weeks was significantly greater in the TK-98 group [27.9 (5.67) vs 12.8 (5.67) for the right shoulder flexion, and 27.0 (5.44) vs 13.4 (5.95) for the left shoulder; P  < 0.05]. Frequencies of adverse events up to 12 weeks were similar. Conclusion BCAAs showed no effect on the improvement of the muscle strength evaluated by MMT and the clinical response. However, they were partly effective for improving dynamic repetitive muscle functions. Trial registration UMIN-CTR Clinical Trial, https://center6.umin.ac.jp/ , UMIN000016233 [ABSTRACT FROM AUTHOR]

Although pregnancy is an important risk factor for autoimmune rheumatic diseases, little is known regarding the association between pregnancy and dermatomyositis (DM) or polymyositis (PM). Herein, we present two patients with DM that developed during the perinatal period. The first patient was positive for anti-aminoacyl synthetase (ARS) antibody and developed DM in the 14th week of pregnancy. Despite treatment, her foetus died of intrauterine growth restriction in the 27th week. The second patient was positive for anti-melanoma differentiation-associated gene 5 (MDA-5) antibody and developed DM 1 week after miscarriage at 9 weeks of gestation. The patient developed severe interstitial pneumonia, and intensive therapy including tofacitinib and rituximab administration was required. Our cases and a literature review revealed that various myositis-specific autoantibodies, including anti-ARS, anti-Mi-2, anti-TIF-1γ, and anti-MDA-5, are associated with DM and PM triggered by pregnancy. We also found that delay in commencing treatment in case of active disease including myositis and interstitial pneumonia, and poor response to corticosteroids were related to poor foetal outcomes in DM and PM. Although rare in pregnant women, it is critical to consider the possibility of DM and PM in patients presenting with rash, fever, weakness, and cough, and testing for myositis-specific autoantibodies is recommended. [ABSTRACT FROM AUTHOR]

Relapse of Takayasu arteritis (TAK) is frequent, and the use of biologics is required in refractory cases. Tocilizumab (TCZ), a biological agent used in TAK, is known to increase the incidence of diverticulitis in patients with rheumatoid arthritis. Adverse events of TCZ in TAK have been poorly recognised. This study aimed to investigate the occurrence of severe colitis among patients with TAK receiving TCZ. We enrolled 116 patients with TAK who met the criteria of the American College of Rheumatology and visited our department between 2018 and 2020. The occurrence of severe colitis and its clinical characteristics were retrospectively evaluated. TCZ was introduced in 34 of 116 patients (29.3%). Severe colitis that required hospitalisation was observed in three of the 34 patients receiving TCZ (8.8%). All patients were female and had Numano type V artery lesions, and the ascending colon was commonly affected. Wide lesions that reached the sigmoid colon, colonic perforation, bacteraemia, or positive stool cultures were observed in some patients. All patients received antibiotics and intestinal rest, and TCZ was resumed in one patient. IL-6 plays a physiological role in the intestine, including recovery from ischaemic damage. In addition to infectious aetiology, blocking the physiological roles of IL-6 by TCZ is considered important for the development of colitis in TAK. Severe colitis is an important adverse event in patients with TAK who receive TCZ. The risk of bloodstream infection associated with colitis should be recognised, especially in patients who have undergone vascular surgery. Key Points • Severe colitis was observed in 8.8% of patients with TAK receiving tocilizumab • Patients had type V artery lesions and ascending colon involvement and were under long-term use of corticosteroids • Inhibition of the physiological roles of IL-6 in the intestinal tract might also be involved [ABSTRACT FROM AUTHOR]

Transthyretin amyloid cardiomyopathy (ATTR‐CM) is caused by the cardiac deposition of insoluble amyloid fibrils formed by misfolded transthyretin proteins and is associated with various cardiac symptoms, such as progressive heart failure, conduction disturbance, and arrhythmia. The implementation of 99mtechnetium (99mTc)‐labelled bone radiotracer scintigraphy for diagnosing ATTR‐CM has enabled accurate diagnosis of the disease with high sensitivity and specificity and positioned this diagnostic modality as an integral part of disease diagnostic algorithms. In 2020, 99mTc‐pyrophosphate scintigraphy received exceptional approval for Japanese national health insurance reimbursement as a diagnostic method of ATTR‐CM. Nevertheless, the utility of 99mTc‐labelled bone radiotracer scintigraphy and the importance of an early diagnosis of suspected ATTR‐CM using this technique have yet to be internalized as common practice by general cardiologists, and guidance on daily clinical scenarios to consider this technique for a diagnosis of suspected ATTR‐CM is warranted. In this review, we discuss the utility of 99mTc‐labelled bone radiotracer scintigraphy for the early diagnosis of ATTR‐CM based on published literature and the outcomes of an advisory board meeting. This review also discusses clinical scenarios that could support early diagnosis of suspected ATTR‐CM as well as common pitfalls, correct implementation, and future perspectives of 99mTc‐labelled bone radiotracer scintigraphy in daily clinical practice. The clinical scenarios to consider 99mTc‐labelled bone radiotracer scintigraphy in daily practice may include, but are not limited to, patients with a family history of the hereditary type of disease; elderly patients (aged ≥60 years) with unexplained cardiac findings (e.g. cardiac hypertrophy associated with abnormalities on an electrocardiogram, heart failure with preserved ejection fraction associated with unexplained left ventricular hypertrophy, and heart failure with reduced ejection fraction associated with atrial fibrillation and left ventricular hypertrophy); and patients with cardiac hypertrophy associated with diastolic dysfunction, right ventricular/interatrial septum/valve thickness, left ventricular sparkling, or apical sparing. Cardiac hypertrophy and persistent elevation in cardiac troponin in elderly patients are also suggestive of ATTR‐CM. 99mTc‐labelled bone radiotracer scintigraphy is also recommended in patients with characteristic cardiac magnetic resonance findings (e.g. diffuse subendocardial late gadolinium enhancement patterns, native T1 increase, and increase in extracellular volume) or patients with cardiac hypertrophy and bilateral carpal tunnel syndrome. [ABSTRACT FROM AUTHOR]

Wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM) is caused by the deposition of wild‐type transthyretin (TTR) amyloid fibrils in the heart. The age at diagnosis of ATTRwt‐CM is reported to be approximately 70–80 years, and patients commonly present with non‐disease‐specific cardiac abnormalities, such as heart failure with preserved ejection fraction and diastolic dysfunction. The disease can be fatal if left untreated, with an approximate survival of 3–5 years from diagnosis. An oral TTR stabilizer, tafamidis, has enabled early intervention for the treatment of ATTRwt‐CM. However, awareness of ATTRwt‐CM remains low, and misdiagnosis and a delay in diagnosis are common. This review discusses the epidemiology, characteristics, treatment strategy, and red‐flag symptoms and signs of ATTRwt‐CM based on the published literature, as well as recent advances in diagnostic modalities that enable early and accurate diagnosis of the disease. We also discuss an algorithm for early and accurate diagnosis of ATTRwt‐CM in daily clinical practice. In our diagnostic algorithm, a suspected diagnosis of ATTRwt‐CM should be triggered by unexplained left ventricular hypertrophy (LVH), which is LVH that cannot be explained by an increased afterload due to hypertension or valvular disease. In addition, heart failure symptoms, laboratory test results (N‐terminal pro‐B‐type natriuretic peptide, high‐sensitivity troponin T, or high‐sensitivity troponin I), electrocardiogram and imaging (echocardiogram or cardiac magnetic resonance) data, age (≥60 years), and medical history suggestive of ATTRwt‐CM (e.g. carpal tunnel syndrome) should be examined. Detailed examinations using bone scintigraphy and monoclonal protein detection tests followed by tissue biopsy, amyloid typing, and TTR genetic testing are warranted for a definite diagnosis of ATTRwt‐CM. [ABSTRACT FROM AUTHOR]