The Impact of Stretching Intensities on Neural and Autonomic Responses: Implications for Relaxation.

Stretching is an effective exercise for increasing body flexibility and pain relief. This study investigates the relationship between stretching intensity and relaxation effects, focusing on brainwaves and autonomic nervous system (ANS) activity. We used a crossover design with low- and high-intensity conditions to elucidate the impact of varying stretching intensities on neural activity associated with relaxation in 19 healthy young adults. Participants completed mood questionnaires. Electroencephalography (EEG) and plethysmography measurements were also obtained before, during, and after stretching sessions. The hamstring muscle was targeted for stretching, with intensity conditions based on the Point of Discomfort. Data analysis included wavelet analysis for EEG, plethysmography data, and repeated-measures ANOVA to differentiate mood, ANS activity, and brain activity related to stretching intensity. Results demonstrated no significant differences between ANS and brain activity based on stretching intensity. However, sympathetic nervous activity showed higher activity during the rest phases than in the stretch phases. Regarding brain activity, alpha and beta waves showed higher activity during the rest phases than in the stretch phases. A negative correlation between alpha waves and sympathetic nervous activities was observed in high-intensity conditions. However, a positive correlation between beta waves and parasympathetic nervous activities was found in low-intensity conditions. Our findings suggest that stretching can induce interactions between the ANS and brain activity.

Cluster Analysis of Subjective Shoulder Stiffness and Muscle Hardness: Associations with Central Sensitization-Related Symptoms.

Background and Objectives: Understanding the relationships between subjective shoulder stiffness, muscle hardness, and various factors is crucial. Our cross-sectional study identified subgroups of shoulder stiffness based on symptoms and muscle hardness and investigated associated factors. Materials and Methods: measures included subjective stiffness, pain, muscle hardness, and factors like physical and psychological conditions, pressure pain threshold, postural alignment, heart rate variability, and electroencephalography in 40 healthy young individuals. Results: Three clusters were identified: Cluster 1 with high stiffness, pain, and muscle hardness; Cluster 2 with low stiffness and pain but high muscle hardness; and Cluster 3 with low levels of all factors. Cluster 1 had significantly higher central sensitization-related symptoms (CSS) scores than Cluster 2. Subjective stiffness is positively correlated with psychological factors. Conclusions: our results suggest that CSS impacts subjective symptom severity among individuals with similar shoulder muscle hardness.

ß-Blockers are associated with increased B-type natriuretic peptide levels differently in men and women in heart failure with preserved ejection fraction.

ß-Blocker (BB) use is a mainstay for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF), whereas its efficacy for heart failure with preserved ejection fraction (HFpEF) remains controversial. Women outnumber men in HFpEF, whereas men outnumber women in HFrEF. Plasma B-type natriuretic peptide (BNP) is established as a biomarker for HF. We examined whether BB use is associated with plasma BNP levels differently in men and women with HFpEF. The study subjects comprised 721 patients with HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] (184 men, mean age 78.2 ± 9.2 yr and 537 women, mean age 83.1 ± 8.8 yr), 179 on BB (66 men and 113 women) and 542 no BB (118 men and 424 women), 583 in sinus rhythm (SR) and 138 in atrial fibrillation (AF). A multivariable logistic regression test was used. Plasma BNP levels were higher (P = 0.0005), systolic blood pressure and LVEF lower (P = 0.0003, and P = 0.0059, respectively) on BBs than on no BBs in women, whereas in men, plasma BNP levels, systolic blood pressure, and LVEF were not altered significantly (P = 0.0849, P = 0.9129, and P = 0.4718, respectively) on BBs compared with no BBs in patients with SR. Multivariable logistic regression analysis revealed that BB use and women were a positive and a negative predictor for high BNP levels (P = 0.003 and P = 0.032, respectively) in SR but not in AF. BB use was associated with high-plasma BNP levels and lower LVEF in women but not in men with HFpEF and SR, suggesting that the pathogenesis and treatment of HFpEF may differ in men and women in SR.NEW & NOTEWORTHY Pathogenesis and treatment for heart failure with preserved ejection fraction (HFpEF) may differ in men and women in sinus rhythm (SR).

East Asian variant aldehyde dehydrogenase type 2 genotype exacerbates ischemia/reperfusion injury with ST-elevation myocardial infarction in men: possible sex differences.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes generated during ischemia/reperfusion (I/R) injury in ST-elevation myocardial infarction (STEMI). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. Whether ALDH2*2 exacerbates I/R injury of in patients with STEMI is not known. The study subjects comprised 218 Japanese patients with STEMI (158 men and 60 women, mean age 67.9 ± 11.9) who underwent successful percutaneous coronary intervention. Of these, 120 (55.0%) were the carriers of variant ALDH2*2 and 98 (45.0%) those of wild ALDH2*1/*1 on genotyping. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit (14.2% vs 46.3%, P < 0.001) in the ALDH2*2 group. The peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, however, were significantly higher in the patients with ALDH2*2 than in those with ALDH2*1/*1 [a median 275.0 (175.8-407.5) vs 177.5 (126.9-344.3) U/L, P = 0.001] among men but not among women (P = 0.811). There was a significant interaction between men (male sex) and ALDH2*2 for I/R injury (χ2 = 4.425, P = 0.040). The variant ALDH2*2 was associated with more severe I/R injury than the wild ALDH2*1/*1 in STEMI patients in men with possible sex differences.

East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina.

BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD.Methods and Results:The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH2*2than in theALDH2*1/*1group (P=0.0499) and decreased significantly in both groups (P<0.0001 and P<0.0001, respectively) after GTN, with significantly lower levels in theALDH2*2group (P=0.0002). FMD decreased significantly in bothALDH2*1/*1andALDH2*2groups (P<0.0001and P=0.0002, respectively) after continuous GTN administration, with no significant differences between the 2 groups both before and after GTN. CONCLUSIONS: Continuous administration of GTN produced endothelial dysfunction as well as nitrate tolerance in bothALDH2*1/1andALDH2*2patients with CSA.ALDH2*2attenuated GTN response and exacerbated GTN tolerance, but not endothelial dysfunction, as compared toALDH2*1/*1in patients with CSA.

Association of East Asian Variant Aldehyde Dehydrogenase 2 Genotype (ALDH2*2*) with Coronary Spasm and Acute Myocardial Infarction.

Coronary spasm plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, acute myocardial infarction (AMI), silent myocardial ischemia, and sudden death. The prevalence of coronary spasm is higher among East Asians probably due to genetic as well as environmental factors. ALDH2 eliminates toxic aldehydes including 4-hydroxy-2-nonenal (4-HNE) derived from lipid peroxidation and acrolein in tobacco smoking as well as ethanol-derived acetaldehyde and thereby protects tissues and cells from oxidative damage. Deficient variant ALDH2*2 genotype is prevalent among East Asians and is a significant risk factor for both coronary spasm and AMI through accumulation of toxic aldehydes, thereby contributing to oxidative stress, endothelial damage, vasoconstriction, and thrombosis. Toxic aldehydes are thus identified as risk factors to be targeted for the treatment of coronary spasm and AMI.

Phase-Amplitude Coupling of Neural Oscillations Can Be Effectively Probed with Concurrent TMS-EEG.

Despite the widespread use of transcranial magnetic stimulation (TMS), knowledge of its neurophysiological mode of action is still incomplete. Recently, TMS has been proposed to synchronise neural oscillators and to thereby increase the detectability of corresponding oscillations at the population level. As oscillations in the human brain are known to interact within nested hierarchies via phase-amplitude coupling, TMS might also be able to increase the macroscopic detectability of such coupling. In a concurrent TMS-electroencephalography study, we therefore examined the technique's influence on theta-gamma, alpha-gamma, and beta-gamma phase-amplitude coupling by delivering single-pulse TMS (sTMS) and repetitive TMS (rTMS) over the left motor cortex and right visual cortex of healthy participants. The rTMS pulse trains were of 5 Hz, 11 Hz, and 23 Hz for the three coupling variations, respectively. Relative to sham stimulation, all conditions showed transient but significant increases in phase-amplitude coupling at the stimulation site. In addition, we observed enhanced coupling over various other cortical sites, with a more extensive propagation during rTMS than during sTMS. By indicating that scalp-recorded phase-amplitude coupling can be effectively probed with TMS, these findings open the door to the technique's application in manipulative dissections of such coupling during human cognition and behaviour in healthy and pathological conditions.

Coronary artery spasm - Clinical features, pathogenesis and treatment.

Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, myocardial infarction, and sudden death, occurring most often from midnight to early morning. CAS is prevalent among East Asians and is associated with an aldehyde dehydrogenase 2 (ALDH2)-deficient genotype (ALDH2*2) and alcohol flushing, which is prevalent among East Asians but is virtually non-existent in other populations. ALDH2 eliminates not only acetaldehyde but also other toxic aldehydes from lipid peroxidation and tobacco smoking, thereby protecting tissues and cells from oxidative damage. Risk factors for CAS include smoking and genetic polymorphisms including those of ALDH2*2, endothelial NO synthase, paraoxonase I, and interleukin-6. Accordingly, oxidative stress, endothelial dysfunction, and low-grade chronic inflammation play an important role in the pathogenesis of CAS, leading to increased coronary smooth muscle Ca2+ sensitivity through RhoA/ROCK activation and resultant hypercontraction. Ca-channel blockers blocking the intracellular entry of Ca2+ are specifically effective for treatment for CAS.

B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction　- Relevance to Age-Related Left Ventricular Modeling in Japanese.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) is increasing with aging of the population. Plasma levels of B-type natriuretic peptide (BNP) increase in proportion to the severity of left ventricular (LV) dysfunction. The object of this study was to examine the plasma levels of BNP in HFpEF to better understand the pathogenesis of HFpEF as compared with HF with reduced EF (HFrEF).Methods and Results:The study subjects comprised 468 HFpEF patients (158 men, 310 women, mean age 81.3±9.6 years) and 126 HFrEF patients (77 men, 49 women, mean age 75.4±12.0 years) who underwent echocardiography and routine clinical examinations including plasma BNP. Age, female prevalence, systolic blood pressure and pulse pressure were higher in the HFpEF patients than in the HFrEF patients (P<0.0001, P<0.001, P<0.0001, and P<0.0001, respectively). Plasma BNP levels, LV diastolic dimensions, and LV mass index (LVMI) were lower (P<0.0001, P<0.0001, and P<0.0001, respectively), while relative wall thickness was higher (P<0.0001) in the HFpEF patients than in the HFrEF patients. Multiple regression analysis revealed that LVMI, EF, plasma levels of albumin, C-reactive protein, and uric acid were the predictors of BNP levels (P<0.001, P<0.001, P=0.009, P=0.012, and P=0.018, respectively). CONCLUSIONS: Plasma BNP levels were lower and related to aging-related LV concentric remodeling/hypertrophy in HFpEF patients as compared with HFrEF patients, who were associated predominantly with eccentric LV hypertrophy.

East asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: possible roles of reactive aldehydes and implications of alcohol flushing syndrome.

BACKGROUND: Coronary spastic angina (CSA) is a common disease among East Asians, including Japanese. The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians. We examined whether CSA is associated with the ALDH2*2 genotype in Japanese. METHODS AND RESULTS: The study subjects consisted of 202 patients in whom intracoronary injection of acetylcholine was performed by angiography on suspicion of CSA (119 men and 83 women; mean age, 66.2±11.4 years). They were divided into CSA (112 patients) and control groups (90 patients). ALDH2 genotyping was performed by the direct application of the TaqMan polymerase chain reaction system on dried whole blood. Clinical and laboratory data were examined using conventional methods. The frequencies of male sex, ALDH2*2 genotype carriers, alcohol flushing syndrome, tobacco smoking, and the plasma level of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, and P=0.007, respectively) and the plasma high-density lipoprotein cholesterol levels were lower (P<0.001) in the CSA group than in the control group. The multivariable logistic regression analysis revealed that ALDH2*2 genotype and smoking were significantly associated with CSA (P<0.001 and P=0.024, respectively). CONCLUSIONS: East Asian variant ALDH2*2 genotypes and, hence, deficient ALDH2 activity were associated with CSA in Japanese. These data support further investigation of treatment targeting aldehydes for CSA.

Variant Aldehyde Dehydrogenase 2 (ALDH2*2) in East Asians Interactively Exacerbates Tobacco Smoking Risk for Coronary Spasm　- Possible Role of Reactive Aldehydes.

BACKGROUND: Coronary spastic angina (CSA) is common among East Asians and tobacco smoking (TS) is an established risk factor for CSA. Aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing reactive toxic aldehydes and a deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined the interaction between TS andALDH2*2as a risk factor for CSA to better understand the disease pathogenesis.Methods and Results:The study subjects comprised 410 patients (258 men, 152 women; mean age, 66.3±11.5) in whom intracoronary injection of acetylcholine was performed on suspicion of CSA.ALDH2genotyping was performed by direct application of the Taqman polymerase chain reaction system. Of the study subjects, 244 had CSA proven and 166 were non-CSA. The frequencies of male sex,ALDH2*2, alcohol flushing syndrome, TS, coronary organic stenosis, and plasma levels of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.015, respectively) and that of high-density lipoprotein cholesterol lower (P=0.002) in the CSA than non-CSA group. Multivariable logistic regression analysis revealed thatALDH2*2and TS were significant risk factors for CSA (P<0.001 and P=0.002, respectively).ALDH2*2exacerbated TS risk for CSA more than the multiplicative effects of each. CONCLUSIONS: ALDH2*2synergistically exacerbates TS risk for CSA, probably through aldehydes.

Blue rubber bleb nevus syndrome with knee joint disorder.

Blue rubber bleb nevus syndrome (BRBNS) involves cutaneous vascular malformation characterized by multiple venous malformations. This commonly affects the skin and gastrointestinal tract. BRBNS is associated with anemia and occasionally involves orthopedic manifestations. A 6-year-old boy was referred to hospital for evaluation of anemia. He presented with a rubber-like soft-tissue mass in the left knee and the right side of the neck, recurrent pain, and fixed flexion contracture of the knee. Blood examination indicated consumption coagulopathy and anemia caused by not only iron-deficiency anemia but also microangiopathy. Endoscopy of the gastrointestinal tract indicated multiple bluish-black sessile venous malformations. Ultrasonography and magnetic resonance imaging of the knee showed intra-articular and intramuscular involvement. Based on these findings, BRBNS with knee joint disorder was diagnosed. With regard to vascular malformations, like other diseases such as inflammatory arthropathy, ultrasonography of the joint may become a new diagnostic approach for evaluating orthopedic manifestations.

Neural dynamics in motor preparation: From phase-mediated global computation to amplitude-mediated local computation.

Oscillatory activity plays a critical role in the brain. Here, we illustrate the dynamics of neural oscillations in the motor system of the brain. We used a non-directional cue to instruct participants to prepare a motor response with either the left or the right hand and recorded electroencephalography during the preparation of the response. Consistent with previous findings, the amplitude of alpha-band (8-14Hz) oscillations significantly decreased over the motor region contralateral to the hand prepared for the response. Prior to this decrease, there were a number of inter-regional phase synchronies at lower frequencies (2-4Hz; delta band). Cross-frequency coupling was quantified to further explore the direct link between alpha amplitudes and delta synchrony. The cross-frequency coupling of showed response-specific modulation, whereby the motor region contralateral to the preparation hand exhibited an increase in coupling relative to the baseline. The amplitude of alpha oscillations had an unpreferred and a preferred delta phase, in which the amplitude was modulated negatively and positively, respectively. Given the amplitude of alpha-band oscillations decreased over the analyzed period, the alpha amplitude might be down-regulated by the phase-amplitude coupling, although we do not have direct evidence for that. Taken together, these results show global-to-local computation in the motor system, which started from inter-regional delta phase synchrony and ended at an effector-specific decrease in the amplitude of alpha-band oscillations, with phase-amplitude coupling connecting both computations.

Increased urinary aldosterone excretion is associated with subcutaneous not visceral, adipose tissue area in obese individuals: a possible manifestation of dysfunctional subcutaneous adipose tissue.

BACKGROUND: Aldosterone is reported to be associated with obesity and is a risk factor for metabolic syndrome. Metabolic abnormalities are more strongly associated with visceral adipose tissue (VAT) than with subcutaneous adipose tissue (SAT). OBJECTIVE: We examined whether aldosterone is more closely associated with VAT area than with SAT area in obese individuals. METHODS: We enrolled 81 Japanese patients (46 men, mean age 43 ± 13 years and 35 women, mean age 53 ± 10 years) suspected of metabolic disorders and measured plasma and 24-h urinary aldosterone, as well as SAT and VAT areas. SAT and VAT areas were measured at the umbilical level by computed tomography. RESULTS: Spearman's rank correlation analysis showed that urinary aldosterone was significantly and positively correlated with body mass index, waist circumference, SAT area, alanine aminotransferase, C-reactive protein, plasma immune-reactive insulin, plasma renin activity and estimated glomerular filtration rate, and negatively correlated with age and blood glucose. Urinary aldosterone was not correlated with VAT area (r = 0·013, P = 0·906). Multivariate regression analyses revealed that log SAT area, age and diastolic blood pressure were significant (P = 0·001, 0·001 and 0·032, respectively) predictors of log urinary aldosterone excretion rate. CONCLUSION: Our results indicate that urinary aldosterone excretion is positively associated with SAT but not with VAT area in the middle-aged obese individuals.Urinary aldosterone is also negatively correlated with age.

Cardiac production of B-type natriuretic peptide is inversely related to the plasma level of free fatty acids in obese individuals - possible involvement of the insulin resistance -.

B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is increased with the severity of left ventricular (LV) dysfunction/hypertrophy. The normal heart preferentially utilizes fatty acids as energy substrates. Plasma BNP levels are reported to be lower in obese individuals. We examined the relationship between BNP production and plasma free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/ hypertrophy. We examined the plasma BNP levels and FFA at the aortic root (AO) and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men and 24 women, 62.5±11.7 yrs) who underwent cardiac catheterization. Log BNP (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877, P<0.001). Log BNP(CS-AO) had a significant negative correlation with BMI (r=-0.558, P<0.001), waist circumference (WC) (r=-0.574, P<0.001), log FFA(AO) (r=-0.643, P<0.001), log triglyceride (r=-0.431, P<0.001), and log HOMA-IR (r=-0.463, P<0.001) and a significant positive correlation with left ventricular mass index (LVMI) (r=0.403, P=0.001). The multivariable regression analyses including log HOMA-IR, LVMI, and age as an independent variable revealed that HOMA-IR and LVMI were significant predictors of log BNP (CS-AO) or BNP production (P=0.001 and 0.004, respectively). We conclude that plasma BNP levels are determined primarily by cardiac production and that insulin resistance is a significant predictor of cardiac BNP production independent of LV hypertrophy in obese individuals.

Deterioration of Phosphate Homeostasis Is a Trigger for Cardiac Afterload　- Clinical Importance of Fibroblast Growth Factor 23 for Accelerated Aging.

Background: After the discovery of the Klotho gene, phosphate came into focus as a pathogenetic aging agent. Phosphate homeostasis is controlled by phosphate-regulating hormones: fibroblast growth factor 23 (FGF23), vitamin D3, and parathyroid hormone. This study investigated the relationship between the deterioration in phosphate homeostasis and arterial stiffness by measuring serum FGF23 concentrations. Methods and Results: The study subjects comprised 82 hospitalized patients (31 males, 51 females; mean [±SD] age 78.6±10.5 years). All patients underwent chest computed tomography, measurement of central blood pressure (BP), and blood chemistry tests. Arterial calcification and/or stiffness was evaluated using the Agatston calcification score (ACS) and pulse wave velocity (PWV). PWV was significantly correlated with age (t=23.47, P<0.0001), estimated glomerular filtration rate (eGFR; t=-4.40, P<0.0001), and ACS (t=4.36, P<0.0001). Serum FGF23 concentrations were significantly correlated with age (t=2.52, P=0.014), eGFR (t=-3.37, P<0.001), serum inorganic phosphorus concentrations (t=3.49, P<0.001), serum vitamin D3 concentrations (t=-4.57, P<0.001), ACS (t=2.30, P=0.025), augmentation pressure (t=2.48, P=0.015), central systolic BP (t=2.00, P=0.049), plasma B-type natriuretic peptide (BNP) concentrations (t=3.48, P<0.001), and PWV (t=2.99, P=0.004). PWV was positively related to augmentation pressure (t=4.09, P<0.001), central systolic BP (t=3.13, P=0.002), and plasma BNP concentrations (t=3.54, P<0.001). Conclusions: This study shows that the increase in serum FGF23 concentrations reflects deterioration of phosphate homeostasis and is an important predictor for arterial stiffness, which intensifies cardiac afterload.

CORRIGENDUM: Deterioration of Phosphate Homeostasis Is a Trigger for Cardiac Afterload　- Clinical Importance of Fibroblast Growth Factor 23 for Accelerated Aging.

[This corrects the article DOI: 10.1253/circrep.CR-22-0124.].

A case of erythema multiforme-like rash induced by everolimus in a patient with a pancreatic neuroendocrine tumor.

A 66-year-old Japanese woman had been diagnosed with a neuroendocrine tumor of the pancreatic head (G2) 3 years previously and undergone pancreaticoduodenectomy. Nine months postoperatively, recurrence with multiple liver metastases developed and she was referred to our department. A regimen of 10 mg of everolimus for 2 weeks plus 1-week washout was instituted, and no adverse events were observed. Fourteen months after treatment initiation, she developed severe generalized erythema multiforme (EM). Skin biopsy revealed spongiosis in the epidermis and interface change and edema in the superficial dermis. Mast cells were observed from the dermis to the subcutaneous tissue, as well as perivascular eosinophilic infiltration, leading to EM being diagnosed. Oral everolimus was discontinued, and the EM was relieved by treatment including steroid therapy. Everolimus is an inhibitor of the mammalian target of rapamycin, and its indications include neuroendocrine tumors. Skin disorders are commonly seen in the early stages of everolimus treatment, but their severity is almost always mild and never severe. This is the first report on a patient who presented with severe generalized EM more than 1 year after everolimus treatment initiation. Patients on everolimus therapy should be monitored for skin disorders on a long-term basis.

Incidence, clinical characteristics, and diagnostic approach in transthyretin amyloid cardiomyopathy: The Kumamoto Cardiac Amyloidosis Survey.

BACKGROUND: In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has received increasing attention; however, the epidemiology of ATTR-CM in Japan is not yet understood. In the Kumamoto Cardiac Amyloid Survey, we evaluated the current incidence, clinical characteristics, diagnostic approaches, and treatment strategies for ATTR-CM and compared tafamidis-prescription hospitals with regional hospitals. METHODS: We conducted a retrospective multicenter observational cohort study. The registry included patients with ATTR-CM diagnosed in two tafamidis-prescription hospital institutes [Japanese Circulation Society (JCS)-certified facilities] and 15 regional cardiovascular facilities in Kumamoto between January 2018 and December 2020. RESULTS: In total, 174 patients were diagnosed with ATTR-CM. The incidence of ATTR-CM was estimated to be approximately 1 per 10,000 person-years in the elderly population (>65 years old) in Kumamoto. Compared with that in the JCS-certified facilities cohort (n=115), age at diagnosis was significantly older (84.5 ± 5.6 vs. 77.5 ± 6.3 years old; p<0.01) in the regional hospitals cohort (n=59). Histological (25% vs. 81%; p<0.01) and genetic diagnosis (7% vs. 82%) were also less frequently performed. Probable (as indicated by positive bone scintigraphy findings with confirmation of monoclonal protein absence) and possible (as indicated by positive bone scintigraphy findings without confirmation of monoclonal protein absence) ATTR-CM accounted for the majority of cases (75% vs. 19%; p<0.01) in the regional hospitals cohort compared to the JCS-certified facilities cohort. There were no cases of hereditary ATTR-CM among the patients who underwent TTR genetic testing (n=98). CONCLUSIONS: We confirmed the incidence of ATTR-CM in Kumamoto and the diagnostic approach used in patients with ATTR-CM. Further prospective studies with a larger sample are needed to validate our results and to further shed light on the epidemiology of ATTR-CM in Japan.