Left ventricular assist devices (LVADs) serve as critical life-sustaining therapy for patients with end-stage heart failure awaiting heart transplantation, significantly improving survival rates and enabling social reintegration. However, many patients with LVAD face multiple challenges in their daily lives and social reintegration, such as anxiety about the device, low societal awareness, and economic and psychological burdens. In Japan, where prolonged waiting periods for heart transplants are inevitable, these challenges further exacerbate the economic and psychological burdens on both patients and caregivers. We present the case of a patient with an LVAD who expressed the desire to return to employment after receiving psychological counseling, and discuss the specific outcomes and challenges of employment support. A multidisciplinary team, including physicians, psychologists, and employment specialists, developed an individualized support plan. This led to successful steps toward social reintegration, which was accomplished in collaboration with the workplace. This case highlights the importance of early intervention during the heart transplant waiting period, specifically the LVAD implantation period, along with continuous psychological, economic, and employment support to improve quality of life post-transplant. Establishing a coordinated support system that involves healthcare providers, employers, and local communities is crucial for the successful social reintegration of patients with an LVAD. Specific measures, such as regular mental health counseling and flexible employment arrangements, are essential to achieving this goal.

Background: Cardiac rehabilitation (CR) is a comprehensive program designed to help cardiac patients reintegrate into social life. The maintenance phase (phase III) is typically conducted in hospitals or at local exercise facilities, depending on individual lifestyles. Effective collaboration between hospitals and local exercise facilities is essential for maintaining CR in older adults with cardiovascular disease (CVD), but several barriers hinder this linkage.

Methods and Results: Since 2022, the Aichi Health Plaza has maintained CR by developing a unique collaboration handbook (the Cardiac Rehabilitation Exercise Facility Cooperation Medical Institutions [CREpas] handbook). A collaboration system was established with the Department of Cardiology at the National Center for Geriatrics and Gerontology, facilitating seamless transitions through referrals after outpatient center-based CR. Partnerships included methods for information sharing, such as a collaboration diary, training records, occasional telephone calls and emails, and biannual information exchange meetings. A total of 18 collaboration patients was enrolled, and no severe adverse events occurred during exercise. However, 11 (61%) of the 18 patients discontinued the program for various reasons.

Conclusions: Transferring CR from hospitals to fitness centers is crucial for older adults with CVD. While safety was ensured at fitness centers, program interruptions highlight the need for addressing barriers to continuity. Seamless healthcare transitions for older CVD patients remain a key challenge in the context of the heart failure pandemic and require further discussion.

Background: In the context of cardiovascular disease (CVD), iron metabolism assessment plays a pivotal role in the diagnosis of anemia and chronic inflammation. However, data regarding the prevalence of anemia, iron deficiency, and iron overload among outpatients in real-world clinical settings remain limited. Moreover, the influence of specific diseases on iron kinetics within the CVD spectrum has not been fully elucidated.

Methods and Results: We conducted a retrospective analysis of 260 patients attending a cardiology outpatient clinic who had undergone blood sampling for comprehensive evaluation of anemia and iron kinetics. The prevalence of anemia among these outpatients was 36.1%, but iron deficiency was observed in only 13.8% of patients (absolute iron deficiency: 1.5%). Notably, stored iron positively correlated with free iron in patients with sinus rhythm, but not in patients with atrial fibrillation (AF). Intriguingly, this relationship followed a similar pattern in the paroxysmal and longstanding AF subgroups. Moreover, multivariate regression analysis showed that iron dynamics significantly explained hemoglobin levels in patients with sinus rhythm but not in those with AF.

Conclusions: Although chronic inflammation may be a contributing factor, iron dynamics exhibited a distinct profile in patients with AF. The correlation between transferrin saturation and stored iron, evident in sinus rhythm patients, was abolished in AF, which supports the notion of chronic inflammation in patients with AF.

Background: Acute lower extremity limb ischemia (ALI) is a common vascular surgery emergency, primarily caused by embolism or atherosclerotic in situ thrombosis–acute on chronic limb ischemia (AoCLI). This study aimed to examine the clinical features and treatment challenges of AoCLI.

Methods and Results: Between January 2014 and December 2022, 73 patients with AoCLI (n=35) or embolic ALI (n=38) were analyzed. The time from ALI onset was significantly longer (P<0.01), and the rate of contralateral diseases was higher in AoCLI than embolic ALI (P<0.01). Treatment and intraoperative findings showed higher rates of failed thrombectomy (P=0.027), difficulty in crossing lesions (P<0.01), defined as failure of Fogarty catheter crossing despite guidewire navigation and requirement of the balloon angioplasty for the lesions, additional revascularization (P<0.01), and multi-segment treatment (P<0.01) in AoCLI. In multivariate analysis, unfavorable factors for endovascular therapy (EVT) were >2.5 days from ALI onset (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.0–2.0), non-atrial fibrillation (OR 4.2; 95% CI 1.0–16.7), and collateral development (OR 9.0; 95% CI 1.0–81.5). Rates of failed EVT were 0% for no factors, 18% for 1 factor, 43% for 2 factors, and 90% for 3 factors.

Conclusions: AoCLI had more complex and multi-segment arterial lesions, making limb perfusion restoration difficult. The unfavorable factors for EVT could help stratify the optimal treatment of ALI in emergency settings.

Background: In 2023, collaboration between cardiologists and oncologists was recommended as part of Japan’s Basic Plan to Promote Disease Control Programs for both cancer and cardiovascular diseases. This study explores the extent of this collaboration in Niigata Prefecture.

Methods and Results: Self-administered questionnaires about immune checkpoint inhibitor-associated myocarditis (ICIAM) and anthracycline-related cardiomyopathy (ARCM) were distributed to all cardiologists and leading oncologists in hospitals across the Prefecture, of whom 124 cardiologists and 41 oncologists across 29 hospitals responded. Clinical experience with ICIAM was reported by 31.8% of cardiologists and 24.4% of leading oncologists, significantly lower than experience with ARCM (80.0% of cardiologists, P<0.001, and 58.5% of leading oncologists, P=0.009, respectively). Senior cardiologists reported less experience with ICIAM compared with their young counterparts (18.6% vs. 38.5%, P=0.018). Of the 20 hospitals providing immunotherapy, 12 (60%) reported “no consultation” between the cardiology and oncology departments, and only 5 hospitals (25%) had matching answers for consultation after ICIAM onset between these departments. Conversely, only 4 hospitals (20%) answered “no consultation”, and 12 hospitals (60%) had matching answers, for interdepartmental consultation before or after ARCM onset.

Conclusions: Compared with ARCM, cardiologists and oncologists had less experience, fewer organized measures in place, and increased interdepartmental collaboration vulnerability with ICIAM. Collaboration between cardiologists and oncologists should be promoted in hospitals.

Background: Studies have shown an increased risk of cardiovascular events during treatment with febuxostat vs. allopurinol, but comparative data with another xanthine oxidoreductase inhibitor (XORi), topiroxostat, are lacking. In this retrospective study we compared the incidence of cardiovascular/renal events in Japanese patients with newly diagnosed hyperuricemia and/or gout treated with allopurinol, febuxostat or topiroxostat.

Methods and Results: Data came from the JMDC Claims Database from September 2013–September 2019. Participants (n=24,112, age ≥20 years, ≥93% male) were diagnosed with hyperuricemia and/or gout and prescribed XORi treatment in the same month or the following month. Using a Poisson regression model, the adjusted risk (rate ratio [RR]; 95% confidence interval [CI]) of major adverse cardiovascular events was slightly lower with topiroxostat vs. allopurinol (0.63; 0.28–1.41) and febuxostat (0.64; 0.31–1.30). Adjusted risks (RR [95% CI]) for events during treatment with topiroxostat vs. febuxostat and allopurinol were 0.22 [0.10–0.48] and 0.26 [0.11–0.63], respectively, for heart failure, 0.43 [0.27–0.67] and 0.51 [0.31–0.86], respectively, for total cardiovascular events, and 0.46 [0.30–0.69] and 0.62 [0.39–0.98], respectively, for total cardiovascular + renal events. Adjusted risks of atrial fibrillation, heart failure, dialysis, total cardiovascular events, and total cardiovascular + renal events were significantly higher with febuxostat vs. allopurinol.

Conclusions: Topiroxostat may provide a better tolerated option for the treatment of hyperuricemia and/or gout in Japanese patients with respect to cardiovascular events.

Background: In heart failure (HF) patients with a higher left ventricular ejection fraction (LVEF), the B-type natriuretic peptide (BNP) level is yet to be fully assessed. Accordingly, we hypothesized that the BNP level should be higher in patients with a higher LVEF range based on the previous finding that such patients were associated with a worse prognosis.

Methods and Results: In our multicenter, prospective, observational cohort for the composite endpoint of all-cause death and readmission due to HF, including patients with LVEF >40% at hospital discharge, we obtained LVEF, E/e′, and BNP levels in 231 patients. The concurrent atrial fibrillation (AF) was confirmed by electrocardiogram. Patients were divided into HF with mildly reduced EF (HFmrEF), HF with preserved EF (HFpEF) with LVEF ≥50 and <60%, and HFpEF with LVEF ≥60%. The BNP levels were not significantly different among these groups (median [interquartile range]: 195 [110–348] vs. 242 [150–447] vs. 220 [125–320] pg/mL, respectively; P=0.422). In contrast, a BNP level of ≥377 pg/mL could significantly differentiate event-free survival (P<0.001). In the multi-covariate Cox proportional hazards model, the BNP level was significantly related to event-free survival independent of LVEF, E/e′, and concurrent AF.

Conclusions: Without confounding the effects of LVEF, E/e′, and concurrent AF, higher BNP levels are significantly and independently associated with event-free survival in HF patients with LVEF>40%.

Background: To further elucidate the clinical implications of myocardial T1 mapping with cardiac magnetic resonance (CMR) in transthyretin amyloid cardiomyopathy (ATTR-CM), we investigated the relationships of native myocardial T1 value (T1_native) and extracellular volume fraction (ECV) with left ventricular (LV) parameters and cardiac biomarkers in ATTR-CM patients before and after tafamidis treatment.

Methods and Results: We studied wild-type ATTR-CM patients who underwent baseline CMR with LV cine and T1 mapping techniques. T1_nativeand ECV were derived from averaged values of base-to-apex LV myocardium. Cardiac biomarkers, including high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured at baseline. In a subset of the patients, follow-up CMR was performed and cardiac biomarkers were remeasured 1 year after initiation of tafamidis treatment. Both T1_native(n=66) and ECV (n=50) positively correlated with LV end-diastolic volume index, LV mass index, Ln (hs-cTnT), and Ln (NT-proBNP). T1_nativecorrelated negatively with LV ejection fraction. Multivariate analysis showed that Ln (hs-cTnT) independently correlated with increased T1_native(β=0.32; P=0.033). In the tafamidis follow-up group, changes in T1_native(∆T1_native) (n=30) and ECV (n=21) after treatment (follow-up−baseline values) negatively correlated with their baseline values. ∆T1_nativepositively correlated with ∆NT-proBNP concentration (r=0.45; P=0.013).

Conclusions: T1_nativeand ECV are comprehensive indicators of LV characteristics in wild-type ATTR-CM patients and may provide imaging-based evidence of meaningful changes after tafamidis treatment.

Background: Because Regnase-1, encoded by ZC3H12A, suppresses the development of pulmonary arterial hypertension (PAH) by controlling pro-inflammatory cytokines, we aimed to identify ZC3H12A variants in patients with PAH.

Methods and Results: We analyzed whole-genome sequence data of patients with PAH to search for disease-associated ZC3H12A variants. The Regnase-1 p.D426G variant was identified in 2 patients, 1 of whom presented with prominent infiltration of inflammatory cells in the lung. The protein level of the variant was decreased in vitro.

Conclusions: We identified a novel missense variant of ZC3H12A that is directly involved in regulating inflammation in patients with PAH.

Background: Despite the development of effective pulmonary vasodilators, the prognosis for patients with pulmonary hypertension (PH) remains poor, particularly in medication-refractory patients. Catheter-based pulmonary artery denervation (PADN) is an emerging therapeutic strategy targeting the sympathetic nervous system in various types of PH. However, data on its safety and efficacy in refractory patients with PH who truly require non-pharmacotherapy are lacking. Here, we describe a phase II, investigator-initiated, open-label, single-arm trial (Japan Registry of Clinical Trials jRCTs052200017) to evaluate the efficacy and safety of PADN over a 2-year observation period.

Methods and Results: Twenty participants will be enrolled and will undergo PADN. The primary endpoint is the time from PADN to the first occurrence of the composite events of death, lung transplantation, and worsening of PH. The safety endpoints are the occurrence of adverse events related to PADN and bradycardia requiring treatment. The exploratory endpoints include right ventricular function evaluated using cardiac magnetic resonance imaging and Short Form-36 score.

Conclusions: The findings of this study will lead to the adoption of PADN for patients with limited treatment options.