Background: Basic fibroblast growth factor (bFGF) is an angiogenic factor with a short half-life. Because recombinant bFGF is in clinical use, we hypothesized that the localization of recombinant bFGF with atelocollagen would have angiogenic effects at the injection site in normal and hind limb ischemic animal models.

Methods and Results: We administered the recombinant bFGF with atelocollagen intramuscularly to hind limbs in normal rabbits or in a mouse model of femoral artery ligation to explore the pharmacological action for ischemia. We evaluated blood flow in the ischemic/normal limb using laser speckle perfusion imaging and the density of blood vessels by pathological examination. At the administration site in normal rabbits, a significant increase in the number of blood vessels was noted at 14 days post-administration of recombinant bFGF with atelocollagen compared with saline or atelocollagen alone. In mice with femoral artery ligation, blood flow and vessels in the ischemic hind limb increased at 2 weeks after injection and more at 4 weeks after injection, and the effect was most significant in mice administered 100 μg of recombinant bFGF with 3% of atelocollagen.

Conclusions: Intramuscular administration of recombinant bFGF with atelocollagen induced angiogenesis between 2 and 4 weeks in both normal and ischemic hind limbs.

Background: Although comprehensive cardiac rehabilitation (CR) is an effective treatment for cardiovascular diseases, its implementation in Japan remains insufficient. Following the 2022 Basic Act on Cardiovascular Disease Prevention, each prefecture has established specific targets.

Methods and Results: We report our experience implementing and managing CR programs across hospitals of different sizes in Yamaguchi Prefecture, Japan, including Tokuyama Medical Association Hospital (initiated in 2019), Mitajiri Hospital (initiated in 2022), and Yamaguchi Prefectural Grand Medical Center. Hospital size and functionality correlated with the diversity and number of healthcare professionals available to provide CR services. In mixed-care hospitals, both inpatient and outpatient CR participants were older compared with acute-care hospitals. Insurance reimbursement calculations and bed-type restrictions affected CR service delivery. The CR team exemplifies interprofessional collaboration in cardiovascular care.

Conclusions: Even without all the necessary professional roles, patients can benefit significantly from CR implemented using available resources. Building effective organizations requires embracing diversity and enabling each profession to demonstrate its expertise while ensuring the psychological safety of team members.

Background: The basis for the specific age threshold for increasing of ischemic stroke in non-valvular atrial fibrillation (NVAF) patients has not been fully evaluated.

Methods and Results: We conducted a pooled analysis of 3,588 Japanese NVAF patients without anticoagulation therapy from the Shinken Database (n=1,099), the J-RHYTHM Registry (n=1,002), and the Fushimi AF Registry (n=1,487) to determine the incidence of ischemic stroke by age group; patients aged between 31 and 90 years (n=3,455) were analyzed. During a follow-up period of 1.47 years, 69 ischemic strokes occurred (1.33% per year). The incidence of ischemic stroke exhibited triphasic changes as follows: first, it ranged from 0.00% per year to 0.41% per year across the age groups between 31–35 and 46–50 years. Second, it then rose to 1.58% per year in the 56–60-years age group, remaining around 1% per year across the age groups between 56–60 and 71–75 years, with rates ranging from 0.83% to 1.58% per year. Last, it further increased to 2.35% per year in the 76–80-year age group, remaining around 2.5% per year across the age groups between 76–80 and 86–90 years.

Conclusions: The incidence of ischemic stroke in NVAF patients exhibits triphasic changes with age, with notable increases observed in patients aged in their late 50s and late 70s.

Background: Neuromuscular electrical stimulation (NMES) is an alternative therapy for patients unable to perform sufficient voluntary exercises. This randomised crossover study aimed to evaluate the safety and efficacy of home-based NMES as an adjunct to cardiac rehabilitation (CR) for improving physical function in frail older adult patients with chronic heart failure (CHF).

Methods and Results: 8 frail older adult patients with CHF underwent 8 weeks of CR supplemented with home-based NMES and 8 weeks of CR alone in random order, separated with a 4-week washout period. NMES at 50-Hz frequency was administered for 50 min/day, 5 times per week, with electrodes placed on the legs. Changes in the short physical performance battery (SPPB) score, leg strength, and the Barthel index were assessed between patients with CR with and without home-based NMES. No NMES-related adverse events were observed. CR with home-based NMES had a higher total SPPB score and 5-repetition sit-to-stand test time of 2.67 points and −10.67 s, respectively, than CR alone (95% confidence interval [CI] 0.3–5.0, P<0.05 and 95% CI −19.5 to −1.3, P<0.05, respectively). No significant leg strength or Barthel index changes were observed between CR with and without home-based NMES.

Conclusions: Home-based NMES safely improved physical function in frail older adult patients with CHF.

Background: In acute myocardial infarction complicated by cardiogenic shock (AMI-CS), low mean arterial pressure (MAP) can reduce cerebral perfusion, potentially resulting in coma. While both MAP and coma on admission are critical prognostic factors, the relationship between them and their prognostic significance based on coma status remains unclear.

Methods and Results: A retrospective analysis of 543 AMI-CS patients was conducted. The overall median MAP was 77 mmHg, with no significant difference between the coma and non-coma groups. The coma group had a higher 30-day mortality compared with the non-coma group (50% vs. 29%; P<0.001). The area under the curve for MAP predicting 30-day mortality was 0.723 (P<0.001) in the coma group, with a cut-off MAP of 76.3 mmHg (sensitivity 0.66, specificity 0.69), but was insignificant in the non-coma group (AUC 0.543; P=0.176). Kaplan-Meier analysis showed higher mortality with low MAP (<77 mmHg) in the coma group, whereas MAP had no significant impact in the non-coma group. Multivariate Cox regression identified low MAP as an independent prognostic factor in the coma group only.

Conclusions: The associations between MAP and prognosis differ depending on the coma status in AMI-CS. Low MAP is a prognostic factor for mortality only in patients with coma. This study highlights the need for treatment strategies tailored to neurological status.

Background: Previous reports have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefit patients with heart failure (HF), regardless of left ventricular ejection fraction. However, evidence is limited for patients who are underweight, particularly with a body mass index (BMI) <20 kg/m².

Methods and Results: Between February 2022 and July 2023, 533 patients were hospitalized at the Japanese Red Cross Wakayama Medical Center for acute HF. Excluding those who died during hospitalization, we categorized 488 patients according to their BMI at discharge: <20 kg/m²(n=201), and ≥20 kg/m²(n=287). Among the BMI <20 kg/m²group, SGLT2i was prescribed to 53 patients. The cumulative incidence rates of all-cause mortality at 1 year were significantly different between BMI <20 kg/m²patients with and without SGLT2i (11.8% vs. 36.1%; log-rank P=0.004). In the multivariate Cox proportional hazard models, SGLT2i reduced the risk of all-cause mortality independent of age, frailty, walking speed, decreased albumin level, elevated C-reactive protein level, and prescriptions of renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists. However, among patients who received SGLT2i, the SGLT2i prescription continuation rate at 1 year was not significantly different between the BMI <20 kg/m²and BMI ≥20 kg/m²groups (85.4% vs. 84.6%; log-rank P=0.869).

Conclusions: SGLT2i are feasibly effective and well-tolerated drugs, even for patients with low BMI.

Background: Data on clinical outcomes after intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with multivessel disease and left ventricular (LV) dysfunction are scarce.

Methods and Results: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1,010 patients undergoing multivessel IVUS-guided PCI including left anterior descending coronary artery target with an intention to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared clinical outcomes between patients with and without LV dysfunction. The primary endpoint was a composite of death, myocardial infarction, stroke, any coronary revascularization, or hospitalization for heart failure. There were 763 patients (75.5%) with preserved LV function (LV ejection fraction [LVEF] >50%), 176 patients (17.4%) with moderate LV dysfunction (35<LVEF≤50%), and 71 patients (7.0%) with severe LV dysfunction (LVEF ≤35%). The cumulative 1-year incidence of the primary endpoint was 9.5%, 18.9%, and 17.1%, respectively, in patients with preserved LV function, moderate LV dysfunction, and severe LV dysfunction (log-rank P<0.001). After adjusting confounders, there was a significantly higher risk of moderate LV dysfunction and a numerically higher risk of severe LV dysfunction relative to preserved LV function for the primary endpoint (hazard ratio (HR), 1.71; 95% confidence interval (CI), 1.08–2.71; P=0.02; and HR, 1.52; 95% CI, 0.77–2.97; P=0.23).

Conclusions: Among patients undergoing multivessel IVUS-guided PCI with contemporary practice, 1-year clinical outcomes were worse in patients with LV dysfunction.

Background: Prognostic models for cardiovascular death, but not all-cause death, after transcatheter aortic valve implantation (TAVI) have not been established yet.

Methods and Results: In 252 patients with aortic stenosis (AS) who underwent TAVI (men/women 83/169; mean age 85 years), we explored predictive models by machine learning for cardiovascular death using 62 candidates. During the follow-up period (mean 1,135 days), 13 (5.2%) patients died of cardiovascular disease. The least absolute shrinkage and selection operator (LASSO) feature selection identified 8 features as important candidates, including old myocardial infarction, triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, Society of Thoracic Surgeons predicted risk of mortality score (STS-PROM), pulse rate, left atrium volume index, stroke volume index, estimated glomerular filtration rate, and albumin. Cox regression analyses with adjustment for age and sex showed that old myocardial infarction, high levels of TG/HDL-C, STS-PROM, and pulse rate, as well as low levels of glomerular filtration rate and albumin, were independent risk factors for cardiovascular death. Models of logistic regression (LR) and random survival forest (RSF) using the LASSO-selected features, except for STS-PROM, significantly improved predictive abilities for cardiovascular death compared with LR analysis using STS-PROM alone.

Conclusions: Machine learning models of prediction for cardiovascular death of LR and RSF using the LASSO-selected features are superior to a LR model using STS-PROM alone in patients with severe AS who underwent TAVI.

Oral frailty, which encompasses decline in oral health and function with aging, has broader health implications. However, its specific role in individuals with cardiovascular disease (CVD) remains poorly understood. In this scoping review we investigated the prevalence, assessment tools, and potential intervention strategies for oral frailty in patients with CVD. We used the Population, Concept, and Context framework as follows: Population: Patients with CVD; Concept: Existing literature on oral frailty in the context of CVD; Context: Not restricted. Extracted data were synthesized qualitatively. From an initial pool of 3,199 studies, 70 were included in the final analysis, with a cumulative sample size of 891,450 individuals. Among the assessment tools for oral frailty, the number of teeth was the most commonly used measure in 39 studies, followed by the Decayed, Missing, Filled Index. Of the studies, 5 studies indicated that coronary artery disease and diabetes are risk factors for oral frailty, and 8 identified poor oral health as a predictor of cardiac events. However, no study clearly defined oral frailty in the context of CVD. Additionally, only 2 studies explored the relationship between oral health and physical frailty. This results of this review underscore the lack of a standardized definition for oral frailty in CVD. Although associations between oral health and prognosis were observed, further research is needed to clarify the definitions and explore causal relationships.

Background: The appropriateness of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) in malnourished elderly patients is unclear. This study aims to assess the effects of GDMT on acute heart failure (AHF) with reduced ejection fraction in this specific population using the Geriatric Nutritional Risk Index (GNRI).

Methods and Results: We retrospectively collected data of patients aged >75 years who were admitted to St. Luke’s International Hospital for AHF with reduced ejection fraction from 2011 to 2022. Malnutrition was defined as a GNRI score <92. GDMT was defined as the prescription of 3 or more of the medications for HFrEF at the time of discharge. Among 467 patients, 345 (73.9%) had malnutrition. In the low GNRI group, GDMT was associated with a lower all-cause mortality at 1 year (HR 0.46; 95% CI 0.24–0.89; P=0.021), but not in heart failure (HF) readmission (HR 0.83; 95% CI 0.55–1.25; P=0.364) at 1 year after discharge. In the high GNRI group, GDMT was not significantly associated with these outcomes (all-cause mortality: HR 0.59; 95% CI 0.12–3.06; P=0.534; HF readmission: HR 0.55; 95% CI 0.29–1.05; P=0.069).

Conclusions: Implementation of GDMT in AHF with reduced ejection fraction may enhance prognosis, even among elderly patients with malnutrition.

Background: Low peak oxygen uptake (V̇O₂), especially ≤14 mL/min/kg, is a strong indicator of poor prognosis in patients with heart failure (HF). However, measuring this parameter is sometimes difficult if the maximal workload is not reached. This study developed a predictive classification model for low peak V̇O₂in HF patients using machine learning (ML).

Methods and Results: We retrospectively analyzed the data for 343 patients with chronic HF and left ventricular ejection fraction <50% who underwent a symptom-limited cardiopulmonary exercise test and extracted 33 variables from their laboratory, echocardiographic, and exercise data up to the submaximal workload. The dataset was randomly divided into training and testing datasets in a 4 : 1 ratio. ML methods, including an exhaustive search for predictor selection, were used, and a support vector machine algorithm was applied for model optimization. We identified 5 important predictors: age, B-type natriuretic peptide, left ventricular end-diastolic diameter, V̇O₂at rest, and V̇O₂at respiratory exchange ratio of 1.00. Using these 5 predictors, an optimized predictive model was validated on the testing dataset, yielding an accuracy of 85%, F1 score of 0.81, and area under the receiver operating curve of 0.94 (95% confidence interval: 0.89–1.00).

Conclusions: Using readily available parameters, ML methods can enable accurate prediction of low peak V̇O₂in patients with HF.

Background: Depression and anxiety screening has not been adequately examined in patients with pulmonary hypertension (PH). We assessed depression and anxiety prevalence and their determinants in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).

Methods and Results: This cross-sectional study included 234 patients with PH (age 57 [42–68] years; 75% female; PAH/CTEPH/other: 103/126/5). Overall, 24% and 26% of patients had depression (Hospital Anxiety and Depression Scale [HADS]-depression score ≥8) and anxiety (HADS-anxiety score ≥8) respectively. Depression and anxiety prevalence was 18% and 19% in PAH and 27% and 30% in CTEPH, respectively. Among patients with PAH, depression was significantly associated with higher mean right atrial pressure (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.03–1.32; P=0.013), higher pulmonary vascular resistance (OR 1.08; 95% CI 1.01–1.16; P=0.034), lower arterial oxygen saturation (OR 0.89; 95% CI 0.80–0.98; P=0.021), pulmonary artery oxygen saturation (OR 0.93; 95% CI 0.87–0.99; P=0.020), and reduced use of phosphodiesterase-5 inhibitor (OR 0.30; 95% CI 0.11–0.86; P=0.025). In CTEPH, depression was significantly associated with the presence of a psychiatric disorder (OR 4.71; 95% CI 1.24–17.90; P=0.023). Anxiety was not significantly associated with any of the aforementioned parameters in PAH and CTEPH.

Conclusions: Predicting depression and anxiety based on disease severity and hemodynamics was challenging, making individual assessments and approaches crucial.

Background: We have previously reported the advantages of a prehospital 12-lead electrocardiography system (P-ECG) for ST-segment elevation myocardial infarction (STEMI) patients (Circ Rep 2019; Circ J 2022, 2023). Since 2020 with Coronavirus disease 2019 (COVID-19), the patient transport situation has changed dramatically. We investigated how patient transport was changed by COVID-19. The effect of prehospital electrocardiography (ECG) was also evaluated.

Methods and Results: Recent urban STEMI patients who received primary percutaneous coronary intervention (PCI) using P-ECG were assigned to a P-ECG group (n=87; age 69±14 years), and comparable urban STEMI patients not using P-ECG were assigned to a Conventional group (n=87; age 71±13 years). The pre-COVID-19 period is defined as the period before the pandemic began, and the COVID-19 period is the time thereafter. In the Conventional group, first medical contact (FMC)-to-reperfusion time (110±45 vs. 90±31 min; P=0.025) and door-to-reperfusion time (89±41 vs. 70±29 min; P=0.015) in the COVID-19 period were significantly longer than in the pre-COVID-19 period. However, in the P-ECG group, there was no difference in FMC-to-reperfusion time and door-to-reperfusion time between the 2 periods. In the Conventional group, Killip class (2.0±1.3 vs. 1.1±0.5; P=0.001) and left ventricular ejection fraction (49±12 vs. 57±9.0%; P=0.002) were significantly poorer in the COVID-19 period than in the pre-COVID-19 period. However, in the P-ECG group, there was no significant difference between the 2 periods.

Conclusions: During the COVID-19 pandemic, P-ECG might have provided advantages for patient transport and outcomes in urban STEMI patients.

Background: Acute right heart failure (RHF) is a syndrome characterized by sudden right ventricular dysfunction leading to systemic hypoperfusion, which carries a poor prognosis, particularly in patients with pulmonary hypertension (PH). Early reduction of pulmonary vascular resistance (PVR) is crucial for improving RHF and reducing acute mortality. Compared with pulmonary vasodilators approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH), inhaled nitric oxide (iNO) therapy has the advantages of being fast acting, an excellent selective pulmonary vasodilation, and has less effect on systemic blood pressure.

Methods and Results: We describe a phase II, investigator-initiated, randomized, open-label trial (Japan Registry of Clinical Trials jRCT2051220042) to evaluate the efficacy and safety of iNO therapy (INOflo® for inhalation 800 ppm), as an acute-phase treatment for severe RHF associated with PAH or CTEPH over a 1-week course. Thirty patients will be enrolled and randomized to receive the study drug, or not, in addition to conventional therapy. The primary endpoint is the change in PVR from baseline to 30 min after the start of inhalation, measured using right heart catheterization. Secondary endpoints include changes in hemodynamic parameters, arterial blood tests, and echocardiography findings, and the safety of iNO therapy, assessed through blood methemoglobin concentration, blood pressure, and adverse events.

Conclusions: iNO therapy is expected to play a significant role in rapidly improving acute severe RHF associated with PH.