This protocol is a prospective pilot study utilizing the intervention of a medically supervised, registered nurse and registered diabetes educator coached low-carbohydrate, ketogenic diet to examine the impact it has as a treatment for heart failure with preserved ejection fraction.

Inclusion Criteria:

• Adults (age 21-80) who meet clinical signs and symptoms of heart failure based on clinical assessment.
• The subject must meet at least one of the following hemodynamic criteria for HFpEF of PH-HFpEF by right heart catheterization (RHC) within 6 months of screening visit;

A) HFpEF:

1. At rest: mean pulmonary artery occlusions pressure (PAOP) > 15, pulmonary vascular resistance (PVR) < 3 Wood Units, or
2. HFpEF with fluid challenge, defined as increase in PAOP post 500 cc fluid bolus: mean PAOP > 18, PVR < 3 Wood Units, or
3. HFpEF with exercise, defined as peak mean PAOP > 17, PVR < 3 Wood Units if age < 50 or peak mean PAOP > 19 and PVR < 3 Wood Units if age >= 50

B) PH-HFpEF:

1. At rest: mean pulmonary artery occlusion pressure (PAOP) > 15, mean pulmonary artery pressure (PAP) >= 25, pulmonary vascular resistance (PVR) > 3 Wood Units, or

2. PH-HFpEF with fluid challenge, defined as increase in PAOP post 500 cc fluid bolus: mean PAOP > 18, mean PAP >= 25, PVR > 3 Wood Units, or

3. PH-HFpEF with exercise, defined as peak mean PAOP > 17, peak mean PAP > 30, peak PVR > 1.34 Wood Units if age < 50 or peak mean PAOP > 19, peak mean PAP > 33, and PVR < 2.1 Wood Units if age >= 50

   • The subject also must meet criteria for metabolic syndrome, defined as: Abdominal obesity (BMI > 30 kg/m2 or abdominal obesity, waist circumference > 102 cm men, > 88 cm women) AND 2 of the following;

a. Currently being treated for systemic hypertension or blood pressure (BP) >= 135/85 b. Glucose intolerance with diagnosis of type 2 diabetes, or fasting blood glucose 110-125 mg/dL or hemoglobin A1c > 6% c. Triglycerides >= 150, or on treatment for high triglycerides d. HDL < 40 men, < 50 women, or on treatment for high triglycerides

• If the subject is on pulmonary hypertension specific vasodilators, they must be on stable medical therapy without changes to pulmonary vasodilator medication within 3 months prior to screening visit.
• The subject must have also had a cardiopulmonary exercise test within 6 months of screening visit.
• The subject must have also had an echocardiogram within 6 months of screening visit.
• The subject must have demonstrated stable weight (less that 5% weight loss) 3 months prior to screening visit. (They cannot already be losing weight).
• The subject owns and uses a smartphone or tablet.
• Must speak English

Exclusion Criteria:

• The subject is already on a significant weight loss trajectory prior to study entry.

• The subject cannot be on an alternative diet plan or strategy (e.g., Weight Watchers, Nutrisystem, Ornish).

• Left ventricular ejection fraction < 50%.

• Severe valvular disease by echocardiogram or dysfunctional prosthetic valve.

• Active pericardial disease (moderate or large pericardial effusion or constrictive pericarditis).

• Active coronary ischemia defined by abnormal stress test, angiogram, or coronary CT angiography per investigator.

• Prolonged corrected QT interval (QTc) > 450 ms

• Significant lung disease on pulmonary function tests (PFT's) within the 6 months of screening visit, (Both post-bronchodilator values and pre-bronchodilator values must meet exclusion criteria. If either post- or pre-bronchodilator values do not, the subject may be included) defined as either:

  1. Irreversible obstructive airways disease (post-bronchodilator forced expiratory volume/forced vital capacity (FEV1/FVC) < 70% predicted) or
  2. Restrictive lung disease (FVC < 70% predicted. If total lung capacity (TLC) is >= 70%, it is acceptable to have an FVC of < 70%) or
  3. More than mild radiographic pulmonary disease as determine don CT scan within the past 2 years per investigator.

• History of non-adherence to diuretics within 3 months of screening visit.

• History or recurrent severe hypokalemia, potassium < 3.0 mg/dL.

• History of kidney stones, gout, or gallbladder disease unless in the opinion of the investigator it will not impact the safety of the patient

• C-peptide < 0.5 ng/mL (increased risk of diabetic ketoacidosis (DKA))

• Uncorrected anemia (hemoglobin < 10 g/dL).

• Unable to participate in the comprehensive ketogenic diet program, including biometric data acquisition and data entry (glucometer self-stick and smartphone use).

• Unable or unwilling to prepare meals for self.

• Unable to perform quantitative cardia testing regimen (cardiopulmonary exercise testing, 6-minute walk).

• Subject is pregnant or planning to become pregnant in the next 14 months.