Prevention and Management of Heart Failure – Stage A/B Framework from Japan Heart Failure Society (JHFS)

Latest Insights from the 2025 JHFS Scientific Statement on Heart Failure Prevention – Stage A/B Diagnosis and Treatment Flowchart

The aging population has precipitated an epidemiological crisis known as the “heart failure pandemic,” characterised by recurrent hospitalisations and a steady decline in patients’ activities of daily living (Japanese Heart Failure Society, 2025). Because heart failure (HF) originates from upstream lifestyle-related diseases, early intervention by primary care and non-specialist healthcare professionals (HCPs) is essential to prevent the silent progression from at-risk states to highly morbid symptomatic disease (JHFS, 2025). The 2025 JHFS Scientific Statement on Heart Failure Prevention – Stage A/B Diagnosis and Treatment Flowchart  provides a pragmatic, evidence-based roadmap for recognising and managing these early disease stages.

This executive summary outlines the core clinical directives for Stage A and B HF management, integrating the JHFS framework with recent paradigm-shifting cardiovascular outcome trials.

1. Which Patients Are at High Risk?

The JHFS Scientific Statement categorises high-risk individuals into two distinct, asymptomatic stages based on their comorbidity profiles and the presence of cardiac remodeling (JHFS, 2025):

• Stage A (At-Risk for Heart Failure): These patients possess significant vascular and metabolic risk factors but lack structural heart disease. High-risk profiles include essential hypertension, asymptomatic coronary artery disease, diabetes mellitus accompanied by cardiovascular risk, diabetes complicated by chronic kidney disease (CKD), non-diabetic proteinuric CKD, and clinical obesity (BMI ≥ 27) combined with atherosclerotic cardiovascular disease.
• Stage B (Pre-Heart Failure): These patients may remain asymptomatic but exhibit objective structural or functional cardiac abnormalities. This cohort includes individuals with a left ventricular ejection fraction (LVEF) < 50%, left ventricular hypertrophy, hemodynamically significant valvular heart disease, evidence of a prior myocardial infarction, or atrial fibrillation.

2. What Should Be Evaluated?

Proactive evaluation relies heavily on biomarker surveillance to detect subclinical hemodynamic stress, alongside vigilant clinical monitoring for the subtle onset of symptomatic disease (JHFS, 2025).

• Biomarker Screening: The JHFS recommends the routine measurement of B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP). Patients in Stage A must be screened at least once a year. If a patient transitions to Stage B, this testing cadence should intensify to at least twice a year.
• Diagnostic Thresholds: A BNP level < 35 pg/mL or an NT-proBNP level < 125 pg/mL indicates a low probability of HF. Conversely, a BNP ≥ 35 pg/mL or an NT-proBNP ≥ 125 pg/mL definitively signals that a Stage A patient has crossed the pathophysiological threshold into Stage B pre-heart failure.
• Early Detection Caveats: Data from the Toon Health Study emphasises that even if NT-proBNP levels remain below the universal 125 pg/mL threshold, close monitoring is warranted if levels exceed 52.4 pg/mL, as this indicates a higher risk for future pre-HF development (Miyazaki et al., 2025). The JHFS formally advises follow-up when NT-proBNP exceeds 55 pg/mL (Miyazaki et al., 2025).
• Confounding Variables: Clinicians must evaluate these biomarkers with an understanding that advancing age, systemic inflammation, renal dysfunction, anemia, atrial fibrillation, and the use of Angiotensin Receptor-Neprilysin Inhibitors (ARNI) can elevate peptide levels. Conversely, substantial obesity can falsely suppress natriuretic peptides.
• Clinical and Physical Surveillance: HCPs must actively interrogate patients for “red flag” symptoms indicating a transition to Stage C, such as unexplained fatigue, malaise, exertional shortness of breath, paroxysmal nocturnal dyspnea, or orthopnea. Physical evaluations should screen for pulmonary rales, S3 gallops, jugular venous distention, lower limb edema, and rapid weight gain exceeding 2 kg per week. Routine chest X-rays should assess for cardiomegaly or pleural effusion, and 12-lead ECGs must be checked for new pathological Q-waves or atrial fibrillation.

3. How Should One Intervene?

Intervention requires aggressive lifestyle modifications—including aerobic exercise, weight management, strict dietary sodium restriction, smoking cessation, and alcohol moderation—paired with disease-modifying pharmacotherapies (JHFS, 2025).

• Hypertension: Standard targets demand an office blood pressure < 130/80 mmHg and home blood pressure < 125/75 mmHg. For diabetic cohorts, the BPROAD trial demonstrated that pursuing an intensive systolic target of < 120 mmHg yields a primary composite cardiovascular outcome hazard ratio (HR) of 0.79 (95% CI 0.69–0.90; P<0.001) and reduces the risk of HF treatment or hospitalisation (HR 0.66, 95% CI 0.41-1.04) compared to standard targets (Bi et al., 2025). In Stage B, pharmacological escalation to diuretics, ACE inhibitors, ARBs, or ARNIs is indicated.
• Diabetes and Obesity: Glycemic control must be managed with cardiovascular-protective agents. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), Glucagon-like peptide-1 receptor agonists (GLP-1RA), and dual GIP/GLP-1 receptor agonists are highly recommended.
  • The SELECT trial proved that semaglutide reduces major adverse cardiovascular events (HR 0.80, 95% CI 0.72-0.90) and the composite of cardiovascular death or HF hospitalisation (HR 0.82, 95% CI 0.71-0.96) in obese, non-diabetic patients with established cardiovascular disease (Lincoff et al., 2023).
  • Similarly, the SUMMIT trial demonstrated that the dual agonist tirzepatide reduces cardiovascular death or worsening HF events (HR 0.62, 95% CI 0.41-0.95; P = 0.026) and specifically worsening HF events (HR 0.54, 95% CI 0.34-0.85) in obese patients with pre-existing HFpEF (Packer et al., 2025).
• Chronic Kidney Disease (CKD): Protecting renal function is imperative to prevent myocardial fibrosis. ACEi/ARBs combined with SGLT2 inhibitors are the foundation of therapy (JHFS, 2025).
  • The EMPA-KIDNEY trial validated that empagliflozin limits CKD progression or cardiovascular death (HR 0.72, 95% CI 0.64-0.82) and reduces all-cause hospitalisations (HR 0.86, 95% CI 0.78-0.95) (Herrington et al., 2023).
  • In diabetic CKD, the FLOW trial established that semaglutide reduces HF events and cardiovascular death by approximately 27%, with benefits remaining consistent regardless of baseline mineralocorticoid receptor antagonist (MRA) use (Pratley et al., 2024).
  • Furthermore, the nonsteroidal MRA finerenone is highly recommended; the FIDELITY pooled analysis confirmed it reduces the composite cardiovascular outcome (HR 0.86, 95% CI 0.78-0.95) and composite kidney outcome (HR 0.77, 95% CI 0.67-0.88), with the FIGARO-DKD cohort specifically showing a reduction in HF hospitalisations (HR 0.71, 95% CI 0.56-0.90) (Agarwal et al., 2022).
• Asymptomatic Reduced Ejection Fraction (LVEF < 50%): Immediate initiation of Beta-blockers and ACE inhibitors/ARBs is mandated to halt left ventricular remodeling (JHFS, 2025).
• Atrial Fibrillation and Arrhythmias: Intervention may involve catheter ablation, Direct Oral Anticoagulants (DOACs), or Beta-blockers for rate control (JHFS, 2025). The 2024 JCS/JHRS guidelines highlight that catheter ablation significantly improves cardiovascular outcomes in patients suffering from both AF and HF (Iwasaki et al., 2025). Furthermore, prophylactic implantable cardioverter-defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) should be actively considered for patients with reduced ejection fraction, non-ischemic/ischemic HF, or specific structural asynchrony (Iwasaki et al., 2025).

4. When Should a Patient Be Referred to a Cardiovascular Specialist?

Timely co-management between primary care HCPs and cardiologists is the linchpin of the JHFS strategy (JHFS, 2025).

• Transition to Stage C (Symptomatic Heart Failure): The presence of any “red flag” clinical symptoms (e.g., unexplained fatigue, orthopnea, nocturnal dyspnea) or physical signs (e.g., S3 gallops, pulmonary congestion on radiography, rapid lower limb edema, weight gain > 2 kg/week) signifies a highly probable transition to symptomatic Stage C disease. These findings mandate an immediate, expedited cardiology referral for comprehensive echocardiography and the prompt initiation of guideline-directed medical therapy for symptomatic HF.
• Transition to Stage B (Pre-Heart Failure): Any patient whose biomarker screening reveals an elevated BNP (≥ 35 pg/mL) or NT-proBNP (≥ 125 pg/mL) must be referred to a cardiovascular specialist at least once.
• Structural and Diagnostic Discoveries: The identification of structural abnormalities via echocardiography (such as LVEF < 50% or valvular disease) or new, concerning abnormalities on a 12-lead ECG requires specialist evaluation to ascertain the etiology. Early specialist referral is also critical for evaluating advanced device interventions (ICD/CRT) or catheter ablation if electrical dyssynchrony or symptomatic atrial fibrillation is identified (Iwasaki et al., 2025).