Takashi Shiroto

Aims: B-type natriuretic peptide (BNP) levels of 35–100 pg/mL, common in preclinical heart failure (HF), are associated with heterogeneous prognosis and are influenced by age and renal function. We aimed to characterize risk heterogeneity in preclinical HF patients with BNP levels of 35–100 pg/mL and to develop a practical risk stratification model. Methods and results: Data from the Chronic Heart Failure Registry and Analysis in the Tohoku District-2 (CHART-2) Study, a prospective multicentre cohort with long-term follow-up, were analysed. Among patients with Stage B HF (n = 4074; age 67.6 ± 12.0 years), the predictability of BNP for 10-year HF-related events was evaluated across strata of age and estimated glomerular filtration rate (eGFR). In patients with BNP levels of 35–100 pg/mL, a composite risk score—the Pre-Heart Failure Assessment and Screening Evaluation (PHASE) Index—was developed using classification and regression tree analysis and multivariable Cox proportional hazards modelling. BNP discrimination varied significantly by age and eGFR (P < 0.05), indicating that a single BNP threshold is insufficient for risk stratification in preclinical HF. The PHASE Index, incorporating age, BNP, eGFR, left ventricular ejection fraction, body mass index, and hypertension, stratified patients with BNP levels of 35–100 pg/mL into four categories and demonstrated superior discrimination compared with BNP alone (c-index 0.723 vs. 0.587, P < 0.05). Conclusion: Patients with preclinical HF and BNP levels of 35–100 pg/mL exhibit substantial risk heterogeneity. The PHASE Index improves identification of high-risk individuals and provides a pragmatic tool for risk stratification beyond the conventional BNP threshold.

Aims: A decline in left ventricular ejection fraction (LVEF) is often observed in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with adverse outcomes. Although baseline LVEF is crucial for assessing the risk of sudden cardiac death in patients with HF, little is known about the relationship between the decline in LVEF and lethal arrhythmic events among patients with HFpEF. Methods and Results: We retrospectively analysed data from the CHART-2 Study. A total of 1,453 patients with HF and LVEF ≥50% at registration (73 years, 39% female) were included and categorised into three groups based on their LVEF at the prespecified 1-year follow-up; 1,316 with LVEF ≥50%, 120 with LVEF 36-50%, and 17 with LVEF ≤35%. The primary endpoint was a composite of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. All-cause death was also evaluated. During a median follow-up of 7.9 years, 79 (5.4%) patients experienced a composite event. Patients with LVEF <50% at 1 year had a significantly higher incidence of the composite event (11.7 vs. 4.8%, P < 0.001), and all-cause death (62.8% vs 51.8%, P = 0.006), compared to those with LVEF ≥50%. Importantly, a decline in LVEF to <50% was independently associated with an increased risk of the composite event (adjusted hazard ratio 1.99, 95% CI 1.04-3.79, P = 0.04). Conclusion: In patients with HFpEF, even a mild decline in LVEF was associated with a higher risk of ventricular tachyarrhythmia, sudden cardiac death and all-cause death. Continuous clinical assessment and re-evaluation of LVEF is crucial for the management of patients with HFpEF.

Background: Clinical characteristics and outcomes of patients with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) are not fully understood, particularly in Japan. Methods and Results: We enrolled a total of 8881 patients with acute MI from the Miyagi Acute Myocardial Infarction Registry Study (2012–2020), with a median age of 69 years. Among them, 239 patients (2.7%) were diagnosed with MINOCA. Compared with those with MI with obstructive coronary artery disease (MI‐CAD), patients with MINOCA were more often women, had a higher incidence of non–ST‐segment–elevation MI and a lower prevalence of dyslipidemia. Compared with patients with MI‐CAD, patients with MINOCA in all age groups (80 years of age) had a higher incidence of non–ST‐segment–elevation MI. Additionally, those ≤59 years of age were more often women and had a lower prevalence of diabetes and dyslipidemia. In‐hospital mortality increased with age in patients with MI‐CAD (3.9% for 80 years of age; P P =0.36). Compared with patients with MI‐CAD, patients with MINOCA had lower in‐hospital mortality for Killip class IV (40.7% versus 20.0%; adjusted odds ratio [OR], 0.31 [95% CI, 0.10–0.94]; P =0.04) and renal dysfunction (20.0% versus 7.1%; adjusted OR, 0.29 [95% CI, 0.09–0.96]; P =0.04). Conclusions: Patients with MINOCA exhibit distinct clinical characteristics and outcomes compared with those with MI‐CAD, particularly in terms of age, sex, prevalence of comorbidities, and in‐hospital mortality. These findings underscore the importance of tailored clinical approaches for patients with MINOCA.

Atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), and clinical outcomes of patients with AF vary depending on its subtype. While AF progression characterized by the transition from paroxysmal AF to persistent AF is sometimes observed, the incidence and clinical impact of AF progression in patients with HFpEF remain to be explored. We enrolled patients with HFpEF and paroxysmal AF from the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study. AF progression was defined as the transition from paroxysmal AF to persistent AF. A total of 718 patients (median age: 72 years, 36% were female) were enrolled. For a median follow-up of 6.0 years (interquartile range: 3.0–10.2 years), AF progression occurred in 105 patients (14.6%), with a cumulative incidence of 16.7% at 10 years. In the multivariable Cox proportional hazards model, previous hospitalization for heart failure [hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.16–2.60; P = 0.007] and left atrial diameter (per 5-mm increase) (HR 1.37, 95% CI 1.20–1.55; P < 0.001) were significantly associated with AF progression. Furthermore, AF progression was significantly linked to worsening heart failure (adjusted HR 1.68, 95% CI 1.18–2.40; P = 0.004). Notably, 27 cases (26%) of worsening heart failure occurred within 1 year following AF progression. In patients with HFpEF, AF progression is significantly associated with adverse outcomes, particularly worsening heart failure. An increased risk is observed in the early phases following progression to persistent AF. Clinical Trials.gov Identifier: NCT00418041