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 ...

Aims Tafamidis improves prognosis in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM). However, real‐world data on the therapeutic effect of tafamidis are lacking. This study aimed to evaluate the clinical course, outcomes, and effectivity monitoring of the therapeutic effect of tafamidis in patients with ATTR‐CM. Methods and results This is a single‐centre, retrospective observational study. We evaluated the clinical characteristics and outcomes in 125 consecutive patients with wild‐type ATTR‐CM (ATTRwt‐CM) treated with tafamidis (treatment group) and 55 untreated patients (treatment‐naïve group). We monitored the therapeutic effect of tafamidis for 12 months by evaluating serial cardiac biomarker and imaging findings. The treatment group had significantly more favourable outcome in all‐cause mortality and hospitalization due to heart failure than the treatment‐naïve group in both the entire cohort (P < 0.01) and the propensity score‐matched cohort (P < 0.05). Kaplan–Meier survival curves showed that tafamidis treatment significantly reduced all‐cause mortality (P = 0.03, log‐rank test), with the curves diverging after approximately 18 months of treatment in the propensity score‐matched cohort. On inverse probability of treatment weighting analysis, tafamidis treatment showed a reduced all‐cause mortality [hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.11–0.93; P = 0.04]. High‐sensitivity cardiac troponin T (hs‐cTnT) > 0.05 ng/mL, B‐type natriuretic peptide (BNP) > 250 pg/mL, and estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 scored 1 point each. Multivariate logistic regression analysis revealed that a high score (2–3 points) was a significantly poor prognostic factor of composite clinical outcomes, including all‐cause death and hospitalization for heart failure (HR, 1.55; 95% CI, 1.22–1.98; P < 0.01) for patients in the treatment group. After 12 months of tafamidis treatment, hs‐cTnT levels decreased significantly [0.054 (0.036–0.082) vs. 0.044 (0.033–0.076); P = 0.002], with no significant changes in BNP levels, echocardiographic parameters, native T1 value, and extracellular volume fraction on cardiac magnetic resonance imaging. Conclusions The prognosis of patients with ATTRwt‐CM treated with tafamidis was more favourable than that of untreated patients. Patient stratification combined with biomarkers (hs‐cTnT, BNP, and eGFR) predicted clinical outcomes. hs‐cTnT may be a useful biomarker for evaluating the therapeutic effect of tafamidis.

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