potential benefit from emerging therapies. 2 It has been reported that 13% of elderly patients (mean age, 82 years) who have heart failure with preserved ejection fraction (HFpEF) are diagnosed with ATTRwt. 3 Several postmortem studies found cardiac amyloid deposition in up to 25% of individuals over 80 years of age. 4 The precise diagnosis of CA requires endomyocardial biopsy (EMB) to demonstrate disease-specific deposition. However, EMB is a relatively invasive procedure 5 and so cannot be performed routinely, especially in elderly patients. A recent systematic evaluation of bone scintigraphy C ardiac amyloidosis (CA) is a secondary cardiomyopathy with a hypertrophic appearance caused by deposition of anomalous fibrillar proteins in the myocardial extracellular matrix that originated from a precursor-altered protein called amyloid. 1 There are 3 main types of CA: acquired monoclonal immunoglobulin light chain amyloidosis (AL amyloidosis); mutant transthyretin (TTR) amyloidosis (ATTRm); and wild-type transthyretin amyloidosis (ATTRwt). ATTRwt is becoming increasingly recognized because of aging of populations, advancements in the understanding of the disease's pathobiology, and the

Aims The focus on wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is increasing because of novel treatment options. There is currently no report on a large number of Japanese patients with ATTRwt-CM. The study aimed to examine the characteristics and prognosis of ATTRwt-CM in Japan. Methods and results Consecutive patients (78.5 ± 6.4 years old at diagnosis) with ATTRwt-CM diagnosed at Kumamoto University Hospital between December 2002 and December 2019 were retrospectively reviewed. Data, including demographic characteristics, co-morbidities, clinical manifestations at diagnosis, laboratory results, electrocardiographic and echocardiographic data, imaging and pathological findings, and treatment were obtained. Of 129 patients included in this study, 110 patients (85%) were male. The median period from initial symptom onset to diagnosis was 15.5 (2-75) months. Heart failure was the most common clinical manifestation leading to diagnosis (61%) and initial manifestations (49%). Of 106 patients, carpal tunnel syndrome was observed in 57 patients (54%), and the median period from initial symptom onset to diagnosis was 96 (48-120) months. Histopathological confirmation of transthyretin amyloid was achieved in 94 patients (73%), including 66 (51%) and 28 cases (22%) with endomyocardial and extracardiac biopsies. During the observation period (median 15.0 [inter-quartile range, 5.4-33.2] months after diagnosis), 34 patients (26%) died. Of these, 27 patients (79%) had cardiovascular deaths (heart failure, 25; sudden death, two). The median survival duration was 58.9 months and the 5 years' survival rate was 48%. According to a multivariate Cox hazard analysis, age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.23, P = 0.002] and low serum sodium levels (HR, 0.89; 95% CI, 0.79-0.996; P = 0.04) contributed to all-cause mortality, and low serum sodium levels contributed to hospitalization for heart failure (HR, 0.86; 95% CI, 0.77-0.96; P = 0.005). Conclusions Clinical characteristics and prognosis of ATTRwt-CM patients in Japan were examined. Carpal tunnel syndrome can be considered an indication for diagnosis of ATTRwt-CM. Age and low serum sodium level were significant predictive factors of all survival outcomes. The clinical features of ATTRwt-CM should be recognized to provide appropriate treatment.

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Aims This study was performed to investigate whether left atrial (LA) strain by echocardiography provides prognostic information in patients with wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM). Methods and results Among 129 patients who were diagnosed with ATTRwt‐CM at Kumamoto University Hospital from December 2002 to December 2019, 113 patients who had enough information for two‐dimensional speckle tracking echocardiography were enrolled in this study. During a median follow‐up of 668 days, 28 cardiovascular deaths occurred. Compared with patients in the non‐event group, those in the cardiovascular death group were significantly older (81.5 ± 7.4 vs. 78.1 ± 6.1 years, P < 0.01), had a lower incidence of carpal tunnel syndrome (21% vs. 47%, P < 0.05), and had a higher high‐sensitivity cardiac troponin T [0.085 (0.063–0.105) vs. 0.049 (0.036–0.079) ng/mL, P < 0.01] and B‐type natriuretic peptide concentrations [419 (239–541) vs. 271 (155–462) pg/mL, P < 0.01] and lower estimated glomerular filtration rate (41.8 ± 15.4 vs. 53.4 ± 14.6 mL/min/1.73 m2, P < 0.01). Electrocardiography showed higher rate of a V1–V3 QS pattern (52% vs. 24%, P < 0.01) and complete left bundle branch block (27% vs. 6%, P < 0.01), and echocardiography showed a significantly lower peak LA strain rate during the contraction phase (0.16 ± 0.13 vs. 0.28 ± 0.27 S−1, P < 0.05), LA strain during the reservoir phase (LASr) (5.84 ± 2.41 vs. 8.22 ± 4.05%, P < 0.01), and peak LA strain rate during the reservoir phase (0.26 ± 0.09 vs. 0.33 ± 0.15 S−1, P < 0.05) in the cardiovascular death group than in non‐event group. By contrast, conventional echocardiographic findings were not significantly different between these two groups. After adjusting for conventional predictive factors of ATTRwt‐CM (age, high‐sensitivity cardiac troponin T and B‐type natriuretic peptide concentrations, and estimated glomerular filtration rate), multivariable Cox proportional hazard analyses showed that LASr was significantly and independently associated with cardiovascular death in patients with ATTRwt‐CM (odds ratio, 0.84; 95% confidence interval, 0.72–0.98; P < 0.05). After adjusting for age and echocardiographic findings associated with cardiovascular death (LA volume index and peak LA strain rate during the contraction phase), LASr was significantly and independently associated with cardiovascular death in patients with ATTRwt‐CM (odds ratio, 0.83; 95% confidence interval, 0.70–0.98; P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve of LASr for cardiovascular death was 0.686 and that the best cut‐off value of LASr was 6.69% (sensitivity, 62.4%; specificity, 64.3%). In the Kaplan–Meier analysis, patients with low LASr (<6.69%) had a significantly higher probability of total cardiovascular death (P < 0.05) and heart failure‐related hospitalization (P < 0.05). Conclusions Left atrial strain during the reservoir phase provides significant prognostic value in patients with ATTRwt‐CM even after adjusting for ...

Background We previously reported that a high score (2 or 3 points) according to the Kumamoto criteria, a combination of high‐sensitivity cardiac troponin T (hs‐cTnT) ≥0.308 ng/mL, the length of QRS ≥ 120 ms in electrocardiogram, and left ventricular (LV) posterior wall thickness ≥ 13.6 mm, increases the pretest probability of 99mTc‐labeled pyrophosphate (99mTc‐PYP) scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy (ATTR‐CM). However, some patients with a low score (0 or 1 point) show positive findings on 99mTc‐PYP scintigraphy. Therefore, we evaluated the usefulness of additional examinations, including echocardiographic assessment of myocardial strain, to raise the pretest probability of 99mTc‐PYP scintigraphy for these patients. Methods and Results We examined 109 consecutive patients aged ≥70 years with low scores according to the Kumamoto criteria who underwent 99mTc‐PYP scintigraphy. Nineteen patients (17%) had positive 99mTc‐PYP scintigraphy findings. The relative apical longitudinal strain (LS) index (apical LS/ basal LS + mid LS) (RapLSI) was significantly higher in patients with positive than negative 99mTc‐PYP scintigraphy findings (1.04 ± 0.37 vs 0.70 ± 0.28, P < .01). Multivariable logistic regression analysis revealed that a high RapLSI (≥1.04) was significantly associated with 99mTc‐PYP positivity (odds ratio, 14.14; 95% confidence interval, 3.36‐59.47; P < .01). The sensitivity, specificity, and accuracy of the diagnostic model using the RapLSI for identification of 99mTc‐PYP positivity were 53%, 94%, and 87%, respectively. Conclusions A high RapLSI can raise the pretest probability of 99mTc‐PYP scintigraphy in patients with a low score according to the Kumamoto criteria. The RapLSI can assist clinicians in determining strategies for these patients.