今井 靖

AIMS: Hypoxia-inducible factor (HIF) signalling influences cardiomyocyte differentiation, maturation, and metabolic adaptation under pathological conditions. HIF-Prolyl hydroxylase domain (HIF-PH) inhibitors, which target this pathway, have been introduced for the treatment of renal anaemia. Their precise effect or safety on cardiac function remains unclear because their pharmacokinetics and distribution are not well-understood. This study aimed to examine HIF signalling activation in adult cardiomyocytes (CMs). METHODS AND RESULTS: We used tamoxifen (TAM)-inducible, CM-specific von Hippel-Lindau (VHL) knockout (VHL-MCM) mice to activate CM HIF signalling. Then we subjected the mice to normal ageing or high-fat diet (HFD) and L-NAME feeding, a murine model of heart failure with preserved ejection fraction (HFpEF). In normal ageing group, there was no difference in the echocardiographic parameters or tissue fibrosis between VHL-MCM and control mice. VHL-MCM mice exhibited significantly increased capillary density and higher expression levels of HIF-target genes (P = 0.0248, two-way ANOVA). Under HFD + L-NAME treatment, VHL-MCM mice showed transient but significantly preserved global longitudinal strain (GLS) at 12 weeks post-TAM injection compared to controls (P = 0.0284, two-way ANOVA). Sirius red staining indicated a trend towards reduced whole-heart and interstitial fibrosis with significant increase in capillary density in VHL-MCM mice. CONCLUSION: Sustained HIF signalling activation in adult CM does not impair the cardiac structure and function in normal ageing process and shows transient yet beneficial effect in murine HFpEF model.

BACKGROUND: There are few data verifying the utility of the CHADS-P2A2RC score in comparison with the CHADS2 score for estimating net adverse clinical events (NACE) in chronic coronary syndrome (CCS) patients without atrial fibrillation (AF) in real-world settings. METHODS: We performed analysis for a total of 3985 CCS patients without AF who underwent percutaneous coronary intervention (PCI) between April 2013 and March 2019 for whom information was obtained from the CLIDAS (Clinical Deep Data Accumulation System)-PCI database. The primary endpoint was NACE defined as the composite of 3-point major adverse cardiovascular events (3P-MACE) (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) and GUSTO moderate/severe bleeding events. RESULTS: Kaplan-Meier analysis showed that both the CHADS-P2A2RC and CHADS2 scores stratified the risks. The incidences of NACE were stratified well by the very-high-risk category, which was uniquely defined as a CHADS-P2A2RC score of ≥6 (hazard ratio: 2.38, 95 % CI = 1.91-2.97, p-value <0.001). The area under the curve (AUC) in estimating NACE within 3 years was higher when the CHADS-P2A2RC score was used than when the CHADS2 score was used (0.67 vs. 0.62, p = 0.003). This was mainly due to the accuracy in estimating bleeding events (0.66 vs. 0.60, p = 0.006). CONCLUSIONS: The accuracy in estimating NACE after PCI for CCS patients without AF was higher when the CHADS-P2A2RC score was used than when the CHADS2 score was used, mainly due to the accuracy in predicting bleeding risk. Higher incidences of endpoints were well-stratified by a very-high-risk category defined as a CHADS-P2A2RC score of ≥6.

BACKGROUND: An artificial intelligence algorithm-guided electrocardiogram (AI-ECG) has been developed to detect atrial fibrillation (AF) in patients with sinus rhythm (SR). However, its utility for population-based screening remains unclear in Japan. METHOD AND RESULTS: In this prospective cohort study, "SPAFS" (Stroke Prevention by Early Detection of AF in Shimizu), participants who underwent health examinations at the Shimizu Medical Association Examination Center from January 2022 to July 2023 were enrolled, with known AF excluded. ECGs were categorized by AI as low-, moderate-, or high risk: non-SR were labeled as non-applicable (NA). All participants underwent 7-day single-lead ECG monitoring. Among 362 participants (61.1 ± 10.5 years, 38% male, CHADS2 score 0.49 ± 0.70), AF was newly detected in 3.0% (n = 11), with increasing prevalence across AI risk categories. The non-low-risk group (moderate, high, and NA) had a significantly higher AF detection rate than the low-risk group (OR 9.36, 95% CI 1.99-44.01). Subgroup analysis in those aged ≥65 years showed a similar trend (OR 8.09 [95%CI 1.63-39.7]). When the NA group (not eligible for AI) was excluded, similar trends were observed, although statistical significance was attenuated (OR 4.89 [95% CI 0.88-27.1] in the total, 5.09 [95% CI 0.89-29.0] in those aged ≥65 years). In the total cohort, AI-ECG showed higher discriminative ability than the CHADS2 score ≥1 in both the total cohort (AUC 0.75 vs. 0.68) and participants aged ≥65 years (AUC 0.73 vs. 0.61). CONCLUSIONS: AI-ECG risk determination correlated with AF detection in a Japanese healthy cohort, especially in the aged population, supporting its utility as a population-based screening tool.

BACKGROUND: Patients with surgically repaired tetralogy of Fallot (rTOF) often develop chronic pulmonary regurgitation (PR), necessitating pulmonary valve replacement (PVR). While cardiac MRI is crucial for PVR timing, its availability is limited. This study evaluates electrocardiographic (ECG) findings - specifically the R-wave amplitude in lead V1 (V1R) and the sum of the R-wave amplitude in lead V1 and the deepest S-wave amplitude in lead V5 or V6 (V1R + V5S or V6S) - as predictors of cardiac MRI findings. PATIENTS AND METHODS: We retrospectively analyzed 35 rTOF patients (mean age 34 ± 9 years; 60% male) who underwent cardiac MRI from 2019 to 2022, assessing correlations between ECG parameters (V1R, V1R + V5S or V6S, and QRS duration) and MRI findings (RVESVI and RVEDVI). RESULTS: V1R showed significant correlation with RVESVI (r = 0.486, p = 0.003) and was notably higher in patients with RVESVI ≥ 80 mL/m2. A V1R cutoff of 20 mm identified RVESVI ≥ 80 mL/m2 with 67% sensitivity and 77% specificity. CONCLUSIONS: V1R on ECG may help predict the need for cardiac MRI, aiding in the timely PVR planning for rTOF patients.

BACKGROUND: Lipid-lowering therapy with high-intensity statins has not been widely implemented in Japan for patients with coronary artery disease who undergo percutaneous coronary intervention (PCI). We examined the efficacy and safety of high-intensity statin therapy in a real-world setting. METHODS AND RESULTS: We used the Clinical Deep Data Accumulation System (CLIDAS) to accumulate multimodal data from the electronic medical records of 7 cardiovascular centers. We analyzed 9,690 patients who underwent PCI between 2013 and 2019 and completed a median 2.5-year follow-up (CLIDAS-PCI database). The risk of developing major adverse cardiac and cerebrovascular events (MACCE) was significantly greater in patients with acute (ACS) than chronic (CCS) coronary syndrome. High-intensity statins were prescribed to 49% of ACS patients and 33% of CCS patients within the first 30 days after the index PCI. After propensity score matching, MACCE event rates were similar between the high- and moderate-intensity statin groups. Importantly, among ACS patients, Cox proportional hazard analysis revealed that the rate of myocardial infarction was lower (adjusted hazard ratio [aHR] 0.65; 95% confidence interval [CI] 0.44-0.97) and the rate of stroke was greater (aHR 1.71; 95% CI 1.12-2.62) in the high-intensity statin group, driven mostly by intracranial hemorrhage. CONCLUSIONS: The CLIDAS-PCI database provides real-world evidence for the efficacy and safety of high-intensity statins in Japanese ACS patients who have undergone PCI.