Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF

Prior treatment

• MI (type I) and/or percutaneous cardiac intervention within 3 months prior to screening; CABG in past 3 months prior to screening, or current indication for coronary revascularization.
• Cardiac resynchronization therapy initiated within 3 months prior to screening.
• Advanced heart failure defined as one or more of the following:
  • ACC/AHA/ESC Stage D HF or non-ambulatory NYHA Class IV HF.
  • Inotropic infusion (continuous or intermittent) within 6 months prior to screening.
  • Subject is on the cardiac transplant waiting list.
  • Presence of or prior history of mechanical circulatory support for HF.
• Admission for HF within the 30 days prior to planned index procedure.
• Any known history of orthostatic hypotension or orthostatic hypotension at the time of screening (regardless of the presence of symptoms). Orthostatic hypotension is defined as a systolic blood pressure (BP) decrease of \>20 mmHg upon going from supine to standing position or undergoing treatment with Midodrine.
• Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.
• Left ventricular EF \<40% within the 3 years prior to screening unless reduced EF was transient and associated with an acute event.
• Prior weight loss surgery
• Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation of chronic pulmonary disease (including intubation) in the 12 months before study entry OR known history of GOLD Class III or worse chronic obstructive pulmonary disease (COPD).
• Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
• Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the interventional device from the access site to target vessel. This includes previous spine surgery that may impact the ability to access and treat the target sites of T11 and T10.

Other illness

• Poor left heart compliance as determined by pulse-wave Doppler transmitral early-to-late (E/A) ratio \>2.0 assessed by the screening echocardiogram. The Screening Committee will evaluate left heart function if the transmitral A velocity is not measurable or absent.
• Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) \<12 mm or right ventricular (RV) fractional area change (FAC) \<25% assessed by the screening echocardiogram.
• Postural orthostatic tachycardia syndrome or preload insufficiency syndrome.
• Presence of significant valve disease defined by the site cardiologist as:
  • Greater than mild mitral valve stenosis.
  • Greater than moderate mitral valve regurgitation.
  • Greater than moderate-to-severe tricuspid valve regurgitation.
  • Greater than moderate aortic valve stenosis or regurgitation.
• Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
• History of clinically significant liver cirrhosis.
• Any condition, or history of illness or surgery that, in the opinion of the site investigator or Screening Committee, might confound the results of the study or pose additional risks to the patient.
• Any of the following measured by screening right heart catheterization:
  • Mean right atrial pressure (RAP) \>20 mmHg at rest
  • Cardiac index \<2.0 L/min/m2 at rest
  • Pulmonary vascular resistance (PVR) \>4 Wood units

Lab values

• Dialysis dependent; or estimated GFR \<25 ml/min/1.73 m2 by CKD-EPI creatinine equation.

Other

• Body mass index (BMI) \>45 kg/m2.
• 6-minute walk test distance \<100 meters OR \>450 meters.
• Orthostatic pulse pressure change from supine to standing decrease of \>10mmHg in the absence of a HR increase \>15bpm
• Systolic BP \<100 mmHg or \>170 mmHg despite appropriate medical management.
• Baseline screening ECG resting HR \>100 beats per minute or ventricular tachycardia.
• Arterial oxygen saturation \<90% on room air.
• Life expectancy \<12 months for non-cardiovascular reasons.
• Females who are pregnant or lactating or planning to become pregnant during the next year.

• Chronic heart failure, defined as:
  • Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for \>30 days, AND
  • NYHA class II with a history of \>NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND
  • At least one of the following:
  • ≥1 HF hospital admission (with HF as the primary diagnosis) including treatment with intravenous (IV) diuretics or urgent unplanned treatment with IV diuretics in healthcare facility within past 12 months, OR ii. NT-proBNP \>300 pg/ml in normal sinus rhythm (\>450 pg/ml in atrial fibrillation or flutter) within the past 6 months; BNP \>100 pg/ml in normal sinus rhythm (\>300 pg/ml in atrial fibrillation or flutter) within the past 6 months, OR iii. Right heart catheterization (RHC) with PCWP ≥ with PCWP ≥18 mmHg at rest or 25 mmHg during exercise at the time of the screening RHC.
• Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2022 ACCF/AHA Guideline for the Management of Heart Failure (Class 1 and 2a recommendations), with no significant changes \[≥100% increase or ≥50% decrease\] for a minimum of 1 month (30 days) prior to screening, that is expected to be maintained without change for at least 6 months. Participants cannot have started a glucagon-like peptide (GLP)-1 or gastric inhibitory peptide (GIP) agonist within the last 6 months or plan to start a GLP-1 or GIP agonist within the ensuing 6 months after enrollment.
• LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.
• Age ≥40 years.
• Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.