Clinical Feasibility of Cardiac Neuromodulation Therapy for Heart Failure With Preserved Ejection Fraction

Clinical Feasibility of Cardiac Neuromodulation Therapy (CNT) as Treatment for HFpEF

This is an open-label pilot study to evaluate the feasibility of Cardiac Neuromodulation Therapy (CNT) in patients with high blood pressure and heart failure who require dual-chamber pacemaker implantation or replacement. The study will assess blood pressure and heart function at rest and during exercise, with and without CNT, for up to 12 months. Participants will receive the Moderato Plus device and complete scheduled follow-up visits. After study completion, CNT therapy will be discontinued and participants will return to standard medical care.

This study is a pilot, open-label, non-randomized feasibility investigation of Cardiac Neuromodulation Therapy (CNT) in patients with high blood pressure and heart failure who are indicated for dual-chamber pacemaker implantation or replacement. The purpose of the study is to assess the feasibility of applying CNT and to evaluate its effects on blood pressure, heart failure status, and cardiac function at rest and during exercise over a follow-up period of up to 12 months. Eligible participants who provide informed consent and meet all inclusion and exclusion criteria will receive implantation of the Moderato Plus device. Following implantation, participants will complete scheduled study visits including two baseline visits and follow-up visits at approximately 3, 6, and 12 months. Study assessments may include blood pressure measurements, New York Heart Association (NYHA) functional class, echocardiographic evaluations, laboratory biomarkers, functional exercise testing, and patient-reported outcome questionnaires. At selected visits, cardiac performance during rest and standardized exercise conditions will be assessed to compare responses with CNT therapy activated and deactivated according to a predefined protocol. These comparisons are intended to evaluate short-term physiological responses to CNT and support feasibility assessments.

The first group of enrolled participants will undergo initial study assessments prior to long-term CNT activation to confirm the feasibility and appropriateness of the evaluation procedures. Based on this review, the study will continue as planned. Upon completion of the study follow-up, CNT therapy will be discontinued, and participants will resume standard clinical care.

Inclusion Criteria:

• Adults aged 18 years or older
• Clinical indication for dual-chamber pacemaker implantation or replacement
• Diagnosis of heart failure with preserved ejection fraction (HFpEF), defined as left ventricular ejection fraction ≥50%
• History of hypertension
• NYHA functional class II or III
• On stable guideline-directed medical therapy
• Able and willing to provide written informed consent

Exclusion Criteria:

• NYHA class IV heart failure
• Permanent or persistent atrial fibrillation
• Recent acute decompensated heart failure
• Significant valvular heart disease requiring intervention
• Severe comorbid conditions that, in the investigator's judgment, would make study participation unsafe
• Pregnant or breastfeeding individuals