Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects With Reduced Ejection Fraction

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 enrollment.
• 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 or has undergone transplant.
  • Presence of, or history of, mechanical circulatory support for HF.
  • Planned other advanced HF Therapies in the next 12 months.
• 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.
• 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

• Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) \<12 mm or right ventricular (RV) fractional area change (FAC) \<25% (at screening visit and determined by echo core lab).
• Postural orthostatic tachycardia syndrome or preload insufficiency syndrome or on medical therapy for neurogenic orthostatic hypotension (e.g., midodrine, droxidopa).
• 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.
• Any planned procedure to address valve disease in the past 6 months.
• 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.

Lab values

• Dialysis dependent; or estimated GFR \<20 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 narrowing from supine to standing (+3 minutes) 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.
• LVEDD \> 7.5 cm (at screening visit and determined by echo core lab)
• Estimated peak pulmonary artery pressure (PAP) \> 70 mmHg (at screening visit and determined by echo core lab).

• Chronic heart failure, defined as:
  • Symptoms of HF requiring current (QD or QOD or appropriate dosing as per screening committee) treatment with loop diuretics for at least 30 days prior to screening visit, AND
  • NYHA class II, NYHA class III, or ambulatory NYHA class IV symptoms at screening or signs of HF, AND
  • NT-proBNP \>800 pg/ml in normal sinus rhythm (\>1400 pg/ml in atrial fibrillation or flutter) within 3 months of consent, with no adjustment for BMI
• Ongoing stable GDMT HF management for a minimum of 30 days prior to screening (unless unable to tolerate GDMT) which refers to those HF drugs carrying a Class I indication, including:
  • An inhibitor of the renin-angiotensin system (RAS inhibitor), including an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI) and beta-blocker (BB).
  • A mineralocorticoid receptor antagonist (MRA), Sodium-Glucose Transport 2 inhibitor (SGLT2i), or nitrates/hydralazine, should be used in appropriate patients, according to the published guidelines unless intolerant or not indicated.
  • Drug intolerance, contraindications, or lack of indications must be attested to by the investigator. Patients should be on appropriate doses of diuretics as required for volume control.
  • Stable GDMT refers to consistent dose (change is considered a more than 100% increase or 50% decrease in dose) for at least 30 days prior to screening visit or as appropriate per the screening committee.
• 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.
• Considered for Class I recommended cardiac rhythm management device therapy. Specifically: if indicated by class I guidelines, cardiac resynchronization therapy (CRT), an implanted cardioverter- defibrillator (ICD) or a pacemaker should be implanted at least 3 months prior to enrollment. These criteria may be waived if a patient is clinically contraindicated for these therapies or refuses them and must be attested to by the investigator.
• LVEF 20% - 40% (at screening visit and determined by echo core lab).
• 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.