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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Endovascular treatment (EVT) is the main treatment for peripheral artery disease (PAD). Despite advances in device development, the restenosis rate remains high in patients with femoropopliteal lesions (FP). This study aimed to evaluate the effectiveness of exercise training in reducing the 1-year in-stent restenosis rate of bare metal nitinol stents for FPs. This prospective, randomized, open-label, multicenter study was conducted from January 2017 to March 2019. We randomized 44 patients who had claudication with de novo stenosis or occlusion of the FP into an intensive exercise group (n = 22) and non-intensive exercise group (n = 22). Non-intensive exercise was defined as walking for less than 30 min per session, fewer than three times a week. We assessed exercise tolerance using an activity meter at 1, 3, 6, and 12 months, and physiotherapists ensured maintenance of exercise quality every month. The primary endpoint was instant restenosis defined as a peak systolic velocity ratio > 2.5 on duplex ultrasound imaging. Kaplan–Meier analysis was used to evaluate the data. There were no significant differences in background characteristics between the groups. Six patients dropped out of the study within 1 year. In terms of the primary endpoint, intensive exercise significantly improved the patency rate of bare nitinol stents at 12 months. The 1-year freedom from in-stent restenosis rates were 81.3% in the intensive exercise group and 47.6% in the non-intensive exercise group (p = 0.043). No cases of stent fracture were observed in the intensive exercise group. Intensive exercise is safe and reduces in-stent restenosis in FP lesions after endovascular therapy for PAD. Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry (No. UMIN 000025259).

Background: During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however. Methods: We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant. Results: We found that cardiac expression of Gα o , an inhibitory G protein encoded in humans by GNAO1 , is transcriptionally regulated by NRSF and is increased in the ventricles of several mouse models of heart failure. Genetic knockdown of Gnao1 ameliorated the cardiac dysfunction and prolonged survival rates in these mouse heart failure models. Conversely, cardiac-specific overexpression of GNAO1 in mice was sufficient to induce cardiac dysfunction. Mechanistically, we observed that increasing Gα o expression increased surface sarcolemmal L-type Ca 2+ channel activity, activated CaMKII (calcium/calmodulin-dependent kinase-II) signaling, and impaired Ca 2+ handling in ventricular myocytes, which led to cardiac dysfunction. Conclusions: These findings shed light on a novel function of Gα o in the regulation of cardiac Ca 2+ homeostasis and systolic function and suggest Gα o may be an effective therapeutic target for the treatment of heart failure.

Although high thromboembolic risk was assumed in elderly patients with heart failure (HF) and atrial fibrillation (AF), inadequate control of prothrombin time/international normalized ratio was often observed in patients using vitamin K antagonists (VKAs). We hypothesized that patients treated with direct oral anticoagulants (DOAC) would have a better outcome than those treated with VKAs. The aim of this study was to compare the efficacies of DOACs and VKAs in elderly patients with HF and AF. We retrospectively analyzed data from a multicenter, prospective observational cohort study. A total of 1036 patients who were hospitalized for acute decompensated HF were enrolled. We assessed 329 patients aged > 65 years who had non-valvular AF and divided them into 2 groups according to the anticoagulant therapy they received. A subgroup analysis was performed using renal dysfunction based on estimated glomerular filtration rate (eGFR; mL/min/1.73 m2). The primary outcome was all-cause mortality, and the secondary outcomes were non-cardiovascular death or stroke. The median follow-up period was 730 days (range 334–1194 days). The primary outcome was observed in 84 patients; non-cardiovascular death, in 25 patients; and stroke, in 14 patients. The Kaplan–Meier analysis revealed that all-cause mortality was significantly lower in the DOAC group than in the VKA group (log-rank p = 0.033), whereas the incidence rates of non-cardiovascular death (log-rank p = 0.171) and stroke (log-rank p = 0.703) were not significantly different in the crude population. DOAC therapy was not associated with lower mortality in the crude population (log-rank p = 0.146) and in the eGFR ≥ 45 mL/min/1.73 m2 subgroup (log-rank p = 0.580). However, DOAC therapy was independently associated with lower mortality after adjustments for age, diabetes mellitus, and albumin level (hazard ratio, 0.55; 95% confidence interval, 0.30–0.99; p = 0.045) in the eGFR 2 subgroup. Compared with VKA therapy, DOAC therapy was associated with lower risk of all-cause mortality in the elderly HF patients with AF and renal dysfunction.

Purpose: Information on the relationship between frailty and the outcome of endovascular therapy (EVT) in elderly patients with lower extremity peripheral artery disease (PAD) is scarce. This study aimed to reveal the impact of frailty on the prognosis of super-elderly patients who underwent EVT. Materials and Methods: From August 2015 to August 2016, 335 consecutive patients who underwent EVT were enrolled in the I-PAD registry from 7 institutes in Nagano prefecture. Among them, we categorized 323 patients into 4 groups according to age and the presence or absence of frailty as follows: elderly with frailty (age ≥ 75, Clinical Frailty Scale [CFS] ≥ 5), elderly without frailty (age ≥ 75, CFS ≤ 4), young with frailty (age < 75, CFS ≥ 5), and young without frailty (age < 75, CFS ≤ 4); we analyzed them accordingly. The primary endpoints were major adverse cardiovascular and limb events (MACLE), defined as a composite of cardiovascular death, myocardial infarction, stroke, admission for heart failure, major amputation, and revascularization. The secondary endpoint was cardiovascular death. Results: The median follow-up period was 2.7 years. In the elderly with frailty, elderly without frailty, young with frailty, and young without frailty groups, the freedom rates from MACLE were 34.9%, 55.7%, 35.4%, and 63.0%, respectively (pConclusion: Frailty as defined by CFS might be a predictor of MACLE incidence in patients with PAD who underwent EVT. By considering treatment indications for patients with PAD by focusing on frailty rather than age, we may examine whether EVT policies are appropriate and manage patient and caregiver expectations for potential improvement in functional outcomes. Further studies are expected to investigate whether changes in frailty after EVT change prognosis.

The Reiwa First Year East Japan Typhoon of 2019 caused a torrential flood in Japan. In Nagano City, a large area was flooded due to the collapse of the Chikuma River embankment. After large-scale disasters, an increase in cardiovascular and cerebrovascular events has been reported on account of the stressful conditions. However, few reports of disaster-related diseases associated with flood damage have been described. Thus, our aim was to elucidate the effect of floods on the incidences of cardiovascular and cerebrovascular diseases in Nagano City.The Shinshu Assessment of Flood Disaster Cardiovascular Events (SAVE) trial enrolled 2,426 patients admitted for cardiovascular or cerebrovascular diseases at all five hospitals with an emergency department in Nagano City from October 1 to December 31 in the years 2017, 2018, and 2019. The occurrence of these diseases was calculated in every 2 weeks and the findings of 2019 (year of the flood) were compared with those of 2017 and 2018.Cardiovascular and cerebrovascular diseases significantly increased during the 2 weeks immediately after the flood disaster (149 in 2019 vs average of 116.5 in the previous 2 years, p 0.05). Unstable angina cases significantly increased 1.5-2 months after the flood disaster, and cerebral hemorrhage cases significantly increased in the 2 weeks after the flood disaster.Cardiovascular and cerebrovascular events increased significantly during the 2 weeks immediately after the large-scale flood disaster caused by the Reiwa First Year East Japan typhoon. Because of the increasing frequency of flood disasters, it is necessary to predict the occurrences of cardiovascular and cerebrovascular diseases and to implement guidelines for their appropriate and timely management.

In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old.This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed.A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase.Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.

Transvenous lead extraction (TLE) is an established procedure for the management of cardiovascular implantable electronic devices. However, some difficulties and risks of complications still exist, especially in old and adhered leads. Evolution RL (Cook Medical, Bloomington, IN, USA) is a newly introduced device for TLE; however, no clinical results have been reported in Japan, and the results with older leads are unknown. We investigated the efficacy and safety of Evolution RL and its usefulness for old leads at two TLE centers in Japan.A total of 27 consecutive patients who underwent lead extraction using Evolution RL at Shinshu University Hospital and Tokyo Women's Medical University Hospital from September 2017 to December 2019 were retrospectively enrolled. We examined the backgrounds of the patients and leads and investigated the efficacy and safety of the procedures. We divided the leads into two groups according to the number of years of implantation (10 years) and compared the results.Among the 27 patients, 20 (74.1%) were men, and the median age was 62 (14-91) years. The total number of leads was 58, and the median implantation duration was 136 months (8-448). We achieved clinical success in all patients and complete procedural success in 24 patients (88.9%). In three patients, the broken tip of the lead remained in the heart. No major complications were noted. Of the 58 leads, there were 34 leads with more than 10 years of implantation, with significantly more Evolution RLs used (94.1% vs. 54.2%, p = 0.001) and significantly higher percentages of Evolution 11Fr, 13Fr, and steady sheaths used (79.4% vs. 33.3%, p = 0.001, 52.9% vs. 16.7%, p = 0.006, and 64.7% vs. 20.8%, p = 0.001, respectively).In two TLE centers in Japan, Evolution RL was shown to be safe and effective, even in leads older than 10 years.

We investigated the prognostic effects of hyperuricemia and high or low body mass index (BMI) in peripheral artery disease (PAD) after endovascular therapy (EVT). Between July 2015–2016, 357 consecutive patients with PAD who underwent EVT were enrolled. Patients were divided into 2 groups: BMI < 25 kg/m2 (low BMI) and ≥ 25 kg/m2 (high BMI); they were also divided into 2 more groups based on the presence/absence of hyperuricemia. The primary and secondary endpoints were major adverse cardiovascular and limb events (MACLE), and all-cause death at 3 years post-EVT. Patients with hyperuricemia had significantly lower freedom from MACLE than patients without hyperuricemia at 3 years (57.0 vs 71.9%, p = .0068). The overall survival of patients with hyperuricemia was significantly lower than that of patients without hyperuricemia (63.9 vs 81.7%, p = .0012). Patients with hyperuricemia who had low BMI experienced significantly lower freedom from MACLE than those without hyperuricemia who had low BMI (48.2 vs 69.9%, p = .002). The overall survival of patients with hyperuricemia who had low BMI was significantly lower than that of patients without hyperuricemia who had low BMI (55.2 vs 77.1%, p = .003). Patients with hyperuricemia had significantly more MACLE and a lower survival at 3 years than patients without hyperuricemia, even if they had a low BMI.

BACKGROUND: Polypharmacy is a common problem among patients with acute decompensated heart failure (ADHF) who often have multiple comorbidities. OBJECTIVE: The aim of this study was to define the number of medications at hospital discharge and whether it is associated with clinical outcomes at 1 year. METHODS: We evaluated the number of medications in 2578 patients with ADHF who were ambulatory at hospital discharge in the Kyoto Congestive Heart Failure Registry and compared 1-year outcomes in 4 groups categorized by quartiles of the number of medications (quartile 1, ≤ 5; quartile 2, 6-8; quartile 3, 9-11; and quartile 4, ≥ 12). RESULTS: At hospital discharge, the median number of medications was 8 (interquartile range, 6-11) with 81.5% and 27.8% taking more than 5 and more than 10 medications, respectively. The cumulative 1-year incidence of a composite of death or rehospitalization (primary outcome measure) increased incrementally with an increasing number of medications (quartile 1, 30.8%; quartile 2, 31.6%; quartile 3, 39.7%; quartile 4, 50.3%; P < .0001). After adjusting for confounders, the excess risks of quartile 4 relative to those of quartile 1 remained significant (P = .01). CONCLUSIONS: In the contemporary cohort of patients with ADHF in Japan, polypharmacy at hospital discharge was common, and excessive polypharmacy was associated with a higher risk of mortality and rehospitalizations within a 1-year period. Collaborative disease management programs that include a careful review of medication lists and an appropriate deprescribing protocol should be implemented for these patients.

During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however.We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant.We found that cardiac expression of GαThese findings shed light on a novel function of Gα

Background Polypharmacy would be associated with poor prognosis in patients with heart failure (HF). Methods In 863 patients who discharged after treatment for HF were prospectively enrolled. Number of tablets prescribed at discharge was counted. Death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF were tracked. Results In our study cohort (median age, 78), 447 patients experienced adverse events during median 503 days follow-up. In Kaplan-Meier analysis, a greater number of prescribed tablets was associated with future adverse cardiac events in the crude population. Although patients with the greater number of non-HF medications showed worse outcome, those of HF medications were not associate with the outcome (Figure). Furthermore, the number of tablets was an independent predictor of future cardiovascular events after adjustment for age, gender, B-type natriuretic peptide, hemoglobin, albumin, estimated glomerular filtration rate, and left ventricular ejection fraction (HR 95% CI: 1.295 (1.066–1.573), p=0.009). Conclusions Polypharmacy was associated with poor prognosis. Although the numbers of tablets and non-HF medications were significantly associated with worse out come in HF patients, the number of HF medications was not. Funding Acknowledgement Type of funding sources: None.