Gender-affirming hormone treatment generally by cross-sex hormones is an important strategy for transgender people to achieve the physical features affirming their experienced gender. Estrogens and androgens are administrated, usually for a long time, to transgender women and transgender men who would like to physically achieve feminization and masculinization, respectively. Several harmful adverse events have been reported in the literature following the administration of gender-affirming hormones, including worsening of lipid profiles and cardiovascular events (CVE) such as venous thromboembolism, stroke, and myocardial infarction, but it remains unknown whether the administration of cross-sex hormones to transgender people increases the subsequent risk of CVE and death. Based on the findings of the present narrative review of the recent literature, including meta-analyses and relatively large-scale cohort studies, it is likely that estrogen administration increases the risk of CVE in transgender women, but it remains inconclusive as to whether androgen administration increases the risk of CVE in transgender men. Thus, definitive evidence guaranteeing the long-term safety of cross-sex hormone treatment on the cardiovascular system is insufficient because of lack of evidence from well-organized, high-quality, and large-scale studies. In this situation, as well as considering the proper use of cross-sex hormones, pretreatment screening, regular medical monitoring, and appropriate intervention for risk factors of CVE are necessary to maintain and improve the health of transgender people.

Background: Autophagy may contribute to the maintenance of atrial fibrillation (AF), but no previous study has concurrently surveyed all 3 phases of autophagy, namely autophagosome formation, lysosome formation, and autophagosome-lysosome fusion. Here we aimed to identify disorders involving various phases of autophagy during AF.

Methods and Results: We used bioinformatic techniques to analyze publicly available DNA microarray datasets from the left atrium (LA) and right atrium (RA) of 7 patients with AF and 6 patients with normal sinus rhythm who underwent valvular surgeries. We compared gene expression levels in the LA (AF-LA) and RA of patients with AF with those in the LA and RA of patients with normal sinus rhythm. Several differentially expressed genes in the AF-LA sample were significantly associated with the Gene Ontogeny term ‘Autophagy’, indicating that the expression of autophagic genes was specifically altered in this dataset. In particular, the expression of genes known or suspected to be involved in autophagosome formation (autophagy related 5 [ATG5], autophagy related 10 [ATG10], autophagy related 12 [ATG12], and light chain 3B [LC3B]), lysosome formation (lysosomal associated membrane protein 1 [LAMP1] and lysosomal associated membrane protein 2 [LAMP2]), and autophagosome-lysosome fusion (synaptosome associated protein 29 [SNAP29], SNAP associated protein [SNAPIN], and syntaxin 17 [STX17]) was significantly upregulated in the LA-AF dataset.

Conclusions: Autophagy is activated excessively in, and may perpetuate, AF.

Background: The prognostic impact of CHADS₂, CHA₂DS₂-VASc, and CHA₂DS₂-VASc-HS scores on clinical outcomes after drug-eluting stent (DES) placement has not been fully elucidated.

Methods and Results: The present study was a retrospective, non-randomized, single-center, and lesion-based study. Target lesion failure (TLF), comprising cardiac death, non-fatal myocardial infarction, and target vessel revascularization, occurred in 7.1% of 872 consecutive de novo coronary lesions in 586 patients. These patients were electively and exclusively treated by DESs from January 2016 to January 2022 until July 2022 with a mean (±SD) observational interval of 411±438 days. Multivariate Cox proportional hazard analysis revealed that CHA₂DS₂-VASc-HS scores ≥7 (hazard ratio [HR] 1.800; 95% CI 1.06–3.05; P=0.029) was a significant predictor of cumulative TLF among 24 variables evaluated. CHADS₂ scores ≥2 (HR 3.213; 95% CI 1.32–7.80; P=0.010) and CHA₂DS₂-VASc scores ≥5 (HR 1.980; 95% CI 1.10–3.55; P=0.022) were also significant in the multivariate analysis. Pairwise comparisons of receiver operating characteristic curves for CHADS₂ score ≥2, CHA₂DS₂-VASc score ≥5, and CHA₂DS₂-VASc-HS score ≥7 showed they were equivalent in terms of predicting the incidence of TLF, with areas under the curve of 0.568, 0.575, and 0.573, respectively.

Conclusions: All 3 cardiocerebrovascular thromboembolism risk scores were strong predictors of the incidence of cumulative mid-term TLF after elective DES placement, with cut-off values of 2, 5, and 7, respectively, and equivalent prognostic impacts.

Background: The purpose of this study was to investigate the actual conditions of cardiac rehabilitation (CR) for elderly patients with heart failure (HF) in outpatient rehabilitation (OR) facilities using long-term care insurance systems.

Methods and Results: This was a cross-sectional web-based questionnaire survey conducted at 1,258 facilities in the Kansai region (6 prefectures) of Japan from October to December 2021. In all, 184 facilities responded to the web-based questionnaire (response rate 14.8%). Of these facilities, 159 (86.4%) accepted patients with HF. Among the patients with HF, 94.3% were aged ≥75 years and 66.7% were classified as New York Heart Association functional class I/II. Facilities treating patients with HF generally provided exercise therapy, patient education, and disease management, which were components of CR. Many facilities not currently treating patients with HF responded positively stating they will accept HF patients in the future. However, a few facilities responded by stating that they are waiting for clearer evidence demonstrating the beneficial effect of OR on patients with HF.

Conclusions: The present results show the possibility that outpatient CR can be performed for elderly patients with HF in other than medical insurance.

Background: Rivaroxaban, a direct oral anticoagulant, is used as a first-line treatment to prevent venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). However, whether 21 days is optimal for the initial treatment duration has not been investigated.

Methods and Results: In this subanalysis of the prospective multicenter observational J’xactly study, which included 1,039 Japanese patients with acute symptomatic/asymptomatic DVT/PE who were prescribed rivaroxaban, the VTE recurrence rate and incidence of bleeding complications were assessed in 667 patients who underwent intensive rivaroxaban treatment (15 mg, twice daily) for a short (1–8 days), intermediate (9–16), or standard (17–24) duration. The short treatment duration group showed a tendency for increased VTE recurrence/aggravation compared with the standard treatment duration group (6.10% vs. 2.60% per patient-year). The intermediate treatment duration group showed a higher incidence of bleeding events than the standard treatment duration group (9.34% vs. 2.16% per patient-year), without major differences in patient characteristics between the groups.

Conclusions: In this subanalysis of the real-world observational J’xactly study of VTE treatment and prevention in Japanese patients with acute symptomatic/asymptomatic DVT/PE, the standard initial intensive rivaroxaban treatment duration (17–24 days) appeared to be safe and effective, providing important insights into the clinical outcomes of the initial rivaroxaban treatment duration in this population.

Background: Contrast-induced nephropathy (CIN) is clinically important because of its poor prognosis. The incidence of CIN is higher in emergency than elective percutaneous coronary intervention (PCI) because there is no established method to prevent CIN. The aim of this study is to evaluate whether bolus administration of a concentrated solution of sodium bicarbonate can prevent CIN in patients undergoing emergency PCI.

Methods and Results: This multicenter prospective single-arm trial with historical controls will include patients who are aged ≥20 years and will undergo cardiac catheterization for suspected acute myocardial infarction (AMI). Patients will receive an intravenous bolus administration of concentrated sodium bicarbonate solution (7% or 8.4%, 20 mEq) and will be observed for 72±12 h. Data for the control group, comprising all patients who underwent PCI for AMI between January 1, 2020 and December 31, 2020 across participating hospitals, will be extracted. The primary endpoint is the incidence of CIN, defined as an increase in serum creatinine of >0.5 mg/dL or >25% from baseline within 48±12 h. We will evaluate the endpoints in the prospective group and compare them with those in the historical control group.

Conclusions: This study will evaluate whether a single bolus administration of concentrated sodium bicarbonate can prevent CIN after emergency PCI.

Background: A high resting heart rate is an independent risk factor for mortality and morbidity in patients with cardiovascular diseases. Ivabradine selectively inhibits the funny current (I_f) and decreases heart rate without affecting cardiac conduction, contractility, or blood pressure. The effect of ivabradine on exercise tolerance in patients with heart failure with reduced ejection fraction (HFrEF) on standard drug therapies remains unclear.

Methods and Results: This multicenter interventional trial of patients with HFrEF and a resting heart rate ≥75 beats/min in sinus rhythm treated with standard drug therapies will consist of 2 periods: a 12-week open-label, randomized, parallel-group intervention period (standard drug treatment+ivabradine group and standard drug treatment group) to compare changes in exercise tolerance between the 2 groups; and a 12-week open-label ivabradine treatment period for all patients to evaluate the effect of adding ivabradine on exercise tolerance. The primary endpoint will be the change in peak oxygen uptake (V̇O₂) during the cardiopulmonary exercise test from Week 0 (baseline) to Week 12. Secondary endpoints will be time-dependent changes in peak V̇O₂from Week 0 to Weeks 12 and 24. Adverse events will also be evaluated.

Conclusions: The EXCILE-HF trial will provide meaningful information regarding the effects of ivabradine on exercise tolerance in patients with HFrEF receiving standard drug therapies and suggestions for the initiation of ivabradine treatment.