Background: Accurate prediction of prognosis in transthyretin amyloid cardiomyopathy (ATTR-CM) is crucial for optimal treatment selection, including tafamidis, the only approved therapy for ATTR-CM. Although tafamidis has been proven to improve prognosis, the long-term serial changes in comprehensive parameters related to ATTR-CM, including cardiac biomarkers and imaging parameters, under tafamidis remain unknown.

Methods and Results: In this study, we used Cox regression analysis on data from 258 consecutive patients diagnosed with ATTR-CM at Kumamoto University to determine prognostic factors. During clinical follow-up, the serial changes in parameters were compared between tafamidis-treated and tafamidis-naïve patients. An elevated high-sensitivity cardiac troponin T (hs-cTnT) level at baseline was identified as a stronger independent predictor of all-cause death compared with left ventricular ejection fraction (LVEF) and extracellular volume. During follow-up (median: 24.4 months), estimated glomerular filtration rate and LVEF declined significantly with time in both cohorts. Notably, serum hs-cTnT and B-type natriuretic peptide levels were significantly elevated in the tafamidis-naïve cohort compared to baseline, but this increase was prevented by tafamidis treatment.

Conclusions: Of the ATTR-CM-related parameters investigated, an increased hs-cTnT level at baseline was a promising determinant of poor prognosis. Long-term tafamidis treatment prevented a deterioration in cardiac biomarkers, and the measurement of these markers may enable appropriate monitoring of disease progression.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) in older adults. Delayed ATTR-CM diagnosis may result in more advanced symptoms. This study describes the journey of Japanese patients with ATTR-CM.

Methods and Results: This retrospective non-interventional study used the DeSC Healthcare database. Patients aged ≥18 years at the index date (date when ATTR-CM was first diagnosed or date of first tafamidis 80 mg prescription, whichever was earlier) and who had received ≥1 tafamidis 80 mg prescription or ≥1 specific ATTR-CM diagnosis, excepting “suspected diagnosis”, at any time between April 1, 2014 and August 31, 2021 were included. The median age of patients was 79.0 years, and 79.9% (n=239) were male. The most frequently observed comorbidities defined as indicating the onset of ATTR-CM were HF (87.9%), atrial fibrillation/atrial flutter (50.2%), and conduction disorders (17.2%), with a median time from onset to index date of 15.5, 14.0, and 9.0 months for each comorbidity, respectively. Lumbar spinal stenosis (23.9%), neuropathy (13.0%), and carpal tunnel syndrome (7.5%) were common extracardiac symptoms, with a median time from the appearance of these symptoms to index date of 19.0, 5.0, and 18.0 months, respectively.

Conclusions: There was a delay between the appearance of cardiac and extracardiac comorbidities of ATTR-CM and its diagnosis in real-world Japanese clinical settings, emphasizing the need for early diagnosis of ATTR-CM.

Background: The prognostic utility of high-sensitivity cardiac troponin T (hs-cTnT) on clinical outcomes in cardiac sarcoidosis (CS) remains unknown, so we evaluated hs-cTnT in the chronic phase of CS.

Methods and Results: We enrolled 92 consecutive patients with CS in the chronic phase after medical therapies. Patients were divided into 2 groups according to hs-cTnT level: 0.014 ng/mL: high hs-cTnT (n=37); normal hs-cTnT (n=55). The primary endpoint was cardiac death and the secondary endpoint was cardiac death, ventricular tachyarrhythmias, or hospitalization for heart failure. The mean age of patients was 63±11 years, and 75 received steroid treatment. During a median follow-up of 63 months, there were 9 cardiac deaths: 7 (19%) patients with high hs-cTnT and 2 (4%) patients with normal hs-cTnT. The rate of cardiac death was higher in patients with high hs-cTnT than in those with normal hs-cTnT (log-rank, P<0.01). Cox proportional hazard analysis showed that hs-cTnT was an independent predictor of cardiac death. The events rate was higher in patients with high hs-cTnT than in those with normal hs-cTnT (log-rank, P<0.01): cardiac death, ventricular tachyarrhythmias or hospitalization for heart failure occurred in 24 (65%) patients with high hs-cTnT and 11 (20%) patients with normal hs-cTnT.

Conclusions: Elevated hs-cTnT was linked with adverse outcomes in CS patients, suggesting it is an effective prognostic biomarker.

Background: Heart rate typically increases during postural changes from a supine to a standing position due to autonomic and hemodynamic factors. Changes in heart rate during orthostasis may reflect the extent of autonomic dysfunction in patients with heart failure (HF). Thus, orthostatic heart rate changes may be useful for evaluating autonomic function and may predict prognosis. This study examined the association between orthostatic heart rate changes and prognosis in patients with HF.

Methods and Results: We included 320 patients with HF in sinus rhythm (median age 70 years, 70.9% men) who were admitted to Kitasato University Hospital for HF treatment and whose heart rate was evaluated in the supine and upright positions during the stable period before discharge. We calculated heart rate changes based on supine and upright heart rate. We examined the association of orthostatic heart rate changes with patient prognosis (i.e., a composite of all-cause mortality or rehospitalization for HF). During the follow-up period (median 3.8 years; interquartile range 0.8–7.0 years), 129 events occurred. Orthostatic heart rate changes were associated with low composite event rates (log-rank P=0.015). After adjusting for potential confounders, increasing orthostatic heart rate changes were associated with decreased composite event rates (adjusted hazard ratio 0.954; 95% confidence interval 0.925–0.985; P=0.004).

Conclusions: In patients with HF, poor orthostatic heart rate changes were associated with a worse prognosis.

Background: Frailty is highly prevalent and associated with a poor prognosis in older patients with heart failure (HF). In this study, we investigated the association between frailty, as assessed by the Kihon Checklist (KCL), and readmissions in older patients with HF.

Methods and Results: We performed a retrospective cohort study of all consecutive older patients hospitalized for HF aged ≥65 years between September 2016 and March 2018. The KCL was based on the health condition and living situation of each patient prior to hospitalization and was categorized into 4 groups based on quartiles of the total score (Q1–4). The primary outcome was readmission due to HF within 2 years post-discharge. A total of 244 patients (111 males; mean age, 81.7 years [6.9]) were included. During 2 years of follow-up post-discharge, 71 patients (29.1%) experienced an adjudicated readmission for acute HF. Multivariable Cox regression analysis revealed that Q2–4 of the KCL were associated with an increased hazard ratio (HR) for HF readmission when compared with Q1 (Q2; HR [95% confidence interval (CI)]: 9.54 [2.78–32.66], P<0.001; Q3; 8.28 [2.37–28.84], P<0.001; Q4; 9.12 [2.51–33.11], P<0.001).

Conclusions: Our findings revealed an association between frailty, as assessed by the KCL, and readmissions for HF within 2 years of discharge in older patients with HF.

Background: With the aging of the population, the number of patients with chronic heart failure (CHF) and comorbidities is increasing in Japan. Among the comorbidities, cardiorenal anemia syndrome (CRAS) is particularly important, but the age-specific prevalence and prognosis of CRAS remain unclear.

Methods and Results: The KUNIUMI registry chronic cohort is a prospective observational study of CHF (Stages B–D) in Awaji Island. In this study, we analyzed 1,646 patients registered in the KUNIUMI registry and categorized them into 4 groups: Group 1 included patients without cardiac failure (Stage B); Group 2 consisted of patients with cardiac failure but without renal failure or anemia; Group 3 comprised patients with both cardiac failure and renal failure but without anemia; and Group 4 (CRAS) included patients with cardiac failure, renal failure, and anemia. The primary endpoint was composite of all-cause-death and heart failure hospitalization. The proportion of patients with CRAS increased with age. Furthermore, Group 4 showed a significantly worse prognosis than other groups (log-rank P<0.01). On Cox proportional hazard regression analysis, compared with patients without cardiac failure, renal failure, or anemia, the age- and sex-adjusted hazard ratio for the primary endpoint in those with CRAS was 8.94 (95% confidence interval: 5.36–14.92).

Conclusions: The prevalence of CRAS in CHF increases with age, and the prognosis associated with CRAS is generally worse compared with other comorbidities.

Background: Patients with both heart failure (HF) and chronic kidney disease (CKD) are often treated with renin-angiotensin-aldosterone system inhibitors (RAASi), but these drugs can cause hyperkalemia, which may lead to their reduction or discontinuation, resulting in the loss of their beneficial effects. Approaches to managing RAASi-induced hyperkalemia are discordant, so in this study we aimed to establish a cross-specialty consensus on the optimal approach to managing hyperkalemia in patients with HF and CKD.

Methods and Results: The study used a modified Delphi methodology. A steering committee of Japanese cardiologists and nephrologists drafted 26 consensus statements, which were used to create a survey, distributed across Japan. A total of 250 responses were received. Consensus, defined as 75% agreement, was achieved for 21/26 (81%) statements. Respondents agreed on the importance of effective hyperkalemia management based on serum potassium levels and supported the use of potassium binders (PBs), particularly novel PBs such as sodium zirconium cyclosilicate, to treat hyperkalemia while maintaining RAASi therapy. However, when potassium levels exceed 6.0 mEq/L, reduction or discontinuation of RAASi may be considered based on individual risk factors.

Conclusions: This consensus provides proposals that may help support the optimal management of RAASi-induced hyperkalemia in Japanese patients with HF and CKD. It highlights the importance of treating hyperkalemia alongside optimal RAASi therapy.

Background: In Japan, caregiver presence 24 h/day, 7 days a week is required for patients with left ventricular assist devices (LVADs) during the first 6 months after discharge, with ongoing cohabitation recommended thereafter. This study evaluated the incidence of LVAD pump stoppages during home care, the role of caregivers in preventing adverse events, and the need for continuous caregiver support.

Methods and Results: A retrospective analysis was conducted on 264 patients who underwent LVAD implantation between 2010 and 2023 and were managed at home. In all, 116 power loss incidents were documented, with 65 leading to pump stoppages. Notably, no stoppages occurred in patients using the EVAHEART or HeartMate 3 devices, which are equipped with backup battery systems. Of the 65 stoppages, 83% were resolved by patients and only 6% required caregiver intervention. The Zarit Burden Interview revealed a mean caregiver burden score of 30.1, comparable to that of caregivers for patients with severe brain damage.

Conclusions: The burden experienced by caregivers of LVAD patients is substantial, but with the advent of advanced devices like the HeartMate 3, the need for caregiver support 24 h/day, 7 days a week may be reconsidered. The findings of this study suggest that continuous caregiver presence may not be essential for all LVAD patients, potentially easing the burden on caregivers.

Background: Previous studies have demonstrated that a shorter hospital stay reduces adverse outcomes in heart failure (HF), primarily in observational study settings. This trend was further emphasized during the COVID-19 pandemic, resulting in case-control study-like results.

Methods and Results: A subanalysis was conducted on 239 patients from a Japanese multicenter cohort study (HINODE), encompassing 32 months before and 6 months after pandemic onset. The duration of hospitalization and clinical outcomes were compared between these 2 periods in HF patients who received guideline-directed medical and cardiac implantable electronic device (CIED) therapy. The duration of HF hospitalization was significantly shortened by 41.1% (95% confidence interval [CI] 6.7–62.8%) during the pandemic period (median 13 days; interquartile range [IQR] 6–19 days) compared with the prepandemic period (median 21 days; IQR 12–38 days). Nonetheless, the incidence rate (IR) of outcomes in the pandemic group was similar (ventricular arrhythmia, HF events, HF and cardiac hospitalization) or lower (all-cause hospitalization [IR ratio 0.6; 95% CI 0.4–1.0]) compared with the prepandemic group. The odds ratio of adverse events was also similar between the 2 groups.

Conclusions: A significant reduction in hospitalization duration during the COVID-19 pandemic was associated with similar or improved clinical outcomes for guideline-adherent HF patients. Current hospitalization durations for advanced HF patients are likely unnecessarily long, and efforts to reduce them are warranted.

Background: Heart failure (HF) is growing global issue, especially among older adults, and patients can be hospitalized at any time of day. We compared patients’ characteristics, including precipitating factors leading to HF hospitalization, between daytime and nighttime admissions.

Methods and Results: A total of 1,124 patients, who were primarily admitted with a diagnosis of acute decompensated HF were enrolled. Patients were divided according to time of hospitalization into daytime (n=770; 8 am–6 pm) and nighttime (n=354; 6 pm–8 am) groups. The prevalence of hypertension, new-onset HF, and clinical scenario 1 [systolic blood pressure (BP) at admission ≥140 mmHg], frequency of New York Heart Association class IV symptoms, systolic and diastolic BP, heart rate, estimated glomerular filtration rate (eGFR), serum concentrations of albumin and hemoglobin, and treatment with vasodilators and noninvasive ventilation were greater, while the prevalence of atrial fibrillation, duration of persistent HF symptoms ≥24 h, serum concentration of total bilirubin, loop diuretic use and mineralocorticoid antagonist use before admission were lower in the nighttime group. Among the HF-precipitating factors, nonadherence was the most prevalent in both the daytime (32.2%) and nighttime (29.9%) groups. Poorly controlled hypertension was common in nighttime patients (10.5% vs. 5.1% P<0.001).

Conclusions: Prehospital BP control may contribute to preventing nighttime hospitalizations. Additionally, the most essential step in preventing hospitalizations due to HF, day or night, is patient education and disease management.

Background: Recently, the role of a rapid increase in serum osmolality in the inhibition of postnatal ductal closure has garnered attention. This study evaluated the efficacy of high-humidity care in preventing the onset of patent ductus arteriosus (PDA) in extremely premature infants.

Methods and Results: The high-humidity group (HHG) comprised 28 infants (24⁰to 27⁶weeks gestational age) recruited prospectively within 6 h after birth between July 2019 and September 2021; these infants were cared for in 90% humidity for the first 72 h of life. The incidence of PDA within the first 7 days of life and the rate of increase in serum sodium concentrations were compared between the HHG and a conventionally managed historical control group (CG; 29 infants born in 2016–2017). Twelve (43%) infants in the HHG and 22 (76%) in the CG developed PDA (P=0.016). Multivariate logistic regression analysis revealed that high-humidity care was effective in reducing the incidence of PDA onset (odds ratio 0.265; 95% confidence interval 0.078–0.907). The rate of increase in serum sodium concentrations was significantly lower in the HHG than CG (median 0.29 [interquartile range 0.21–0.39] vs. 0.46 [interquartile range 0.32–0.62] mEq/L/h, respectively; P<0.001).

Conclusions: High-humidity care for the first 72 h of life may help reduce the onset of PDA in extremely preterm infants by avoiding rapid increases in serum sodium concentrations.

Background: Evaluating the applicability of quality indicators (QIs) for heart failure (HF) care is crucial to addressing practice variability and improving outcomes by promptly translating guideline recommendations into QIs.

Methods and Results: A 12-member multidisciplinary panel assessed 35 HF care indicators from international guidelines using a Delphi survey (1–9 scale). Consensus (median ≥7) was achieved for 33 indicators (94.3%), but not for implantable cardioverter-defibrillator-related items. Device-related indicators revealed challenges in aligning international standards with the Japanese clinical context.

Conclusions: The study concluded that international HF QIs are generally applicable in Japan, though device-related QIs need further consideration.