Screening for HFpEF in pacemaker patients: Study design and protocol of the PM-HFpEF study

Figures

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  Fig 1. Overview of the screening program and diagnostic workflow of the PM-HFpEF study. Abbreviations: HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFrEF, heart failure with reduced ejection fraction; PM, pacemaker; RV, right ventricle; KCCQ-12, Kansas City Cardiomyopathy Questionnaire–12 items. Legend: Patients with permanent pacemakers using right ventricular apical leads, implanted between January 2018 and December 2022, will be screened for eligibility during routine device follow-up at the study center. After exclusions and written informed consent, eligible patients will undergo a 1-day structured screening program within 15 days of enrolment. The screening protocol includes clinical assessment, frailty assessment, quality-of-life evaluation using the KCCQ-12, laboratory assessment, pacemaker interrogation, 12-lead electrocardiogram, and transthoracic echocardiography. Patients with inconclusive resting findings will undergo diastolic stress echocardiography. Patients will be classified as having no HF, pre-HF, HFpEF, HFmrEF, or HFrEF according to ESC guidelines and the Universal Definition…

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  Fig 2. Upper-limb ergometer diastolic stress echocardiography. Legend: The patient is seated upright at the edge of the echocardiography bed with the upper-limb ergometer (THERA-Trainer Mobi) positioned on a removable, height-adjustable table. Once the predefined submaximal target heart rate is achieved, the table is removed to allow immediate transition to the left lateral decubitus position for apical image acquisition. The left panel illustrates the exercise phase, and the right panel the immediate post-exercise transition.

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  Fig 3. Diagnostic adjudication process: resting adjudication, diastolic stress echocardiography referral, and post-exercise adjudication. Legend: The stepwise screening pathway integrates rhythm-adjusted NT-proBNP thresholds, resting echocardiography, and diastolic stress echocardiography (DSE) when resting findings are inconclusive. HFpEF will be adjudicated when symptoms or signs of heart failure are present, natriuretic peptides are elevated, and at least one major functional marker of increased left-ventricular filling pressures is identified. Indeterminate cases (see S3 and S4 Tables) are referred for DSE. Abnormal DSE findings (peak E/e’ ≥ 15 and/or TRV > 3.4 m/s, or a corresponding increase in estimated PASP when measurable) are integrated with resting findings for final diagnostic adjudication. Abbreviations: AF, atrial fibrillation; DSE, diastolic stress echocardiography; HFpEF, heart failure with preserved ejection fraction; LAVI, left atrial volume index; LVEF, left ventricular ejection fraction; LVFP, left-ventricular filling pressures; NT-proBNP, N-terminal pro-B-type natriuretic peptide; PASP, pulmonary artery systolic pressure; TRV, tricuspid regurgitation velocity.