Inorganic Nitrate as a Treatment for ANOCA: NO-ANOCA

Prior treatment

• History of acute coronary syndrome (ACS) within previous 30 days
• Individuals currently taking nitroglycerine (or inorganic nitrates), PDE-5 inhibitors (ex: Cialis, Viagra), and xanthine oxidase inhibitors (ex: Allopurinol)

Other illness

• History of congestive heart failure, severe pulmonary disease, liver disease
• Stroke within the last 180 days or intracranial hemorrhage at any time.
• Severe valvular disease
• Type 1 diabetes mellitus
• Active malignancy requiring treatment at the time of visit
• History of recurrent UTI/bladder/kidney infections
• Known or suspected bronchoconstrictive or bronchospastic lung disease (ARDS, emphysema)
• Greater than first degree heart block
• Implanted cardiac device
• Profound sinus bradycardia (heart rates\<40 beats per minute)
• Atrial fibrillation or supraventricular arrhythmias at time of imaging
• History of reaction to iodinated contrast agents
• Any orthopedic, neurological, or other condition that prevents participant from exercising

Lab values

• History of non-ischemic cardiomyopathy LVEF \<40% or hypertrophic cardiomyopathy.
• Severe (eGFR \<30 mL/min/1.73 m2 by CKD-EPI), unstable, or rapidly progressing renal disease at the time of randomization

Age

• Life expectancy \<3 years, due to non-cardiovascular comorbidity.

Other

• Pregnancy or women who are breast-feeding
• Symptomatic hypotension or systolic BP\<95 mmHg on 2 consecutive measurements
• Asthma with ongoing wheezing
• Known intolerance of nitrates (other than hypotension)
• Smokers within the last 5 years
• Prisoners
• Cognitively impaired individuals
• Non-English Speaking

• Age ≥18 years.
• Female sex.
• Willing and able to provide written informed consent.
• Signs and symptoms of suspected ischemia prompted referral for further evaluation by cardiac catheterization or CCTA within two years of consent.
• No evidence of obstructive epicardial CAD (stenosis \>50%) of a major epicardial vessel or an FFR ≤0.80 by invasive catheterization or CCTA. Patients who have not undergone cardiac catheterization of CT angiogram within the last 2 years for chest pain can be scheduled for a screening CT angiogram of the coronary arteries to confirm eligibility.
• Impaired coronary flow reserve (cut-off values depending on methodology use between ≤2.0 and ≤2.5 by stress testing PET/CMR or Invasive assessment) or Abnormal index of coronary microcirculatory resistance (e.g., IMR \> 25)
• SGLT2i Naïve