Inclusion Criteria:

Enrollment Criteria:

• Men or women.
• 18 years of age.
• Confirmed diagnosis of WHO Group 2 Pulmonary Hypertension (PH) with heart failure and preserved ejection fraction (HFpEF).
• WHO Group 2 Pulmonary Hypertension subjects with heart failure and preserved ejection fraction as defined by:
  • Mean pulmonary arterial pressure (mPAP) >35 mmHg at rest or with legs up (at baseline right heart catheter/Lead-In);
  • Pulmonary capillary wedge pressure (PCWP) ≥20 mmHg at rest or with legs up (at baseline right heart catheter/Lead-In);
    NYHA Class II or III d. LVEF ≥40% by echocardiogram within three months of enrollment with no change in clinical status suggesting the potential for deterioration in systolic function.
• Signed (by the subjects or their legally acceptable representatives) informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Ability to walk at least 50 meters, but not more than 550 meters in a six-minute walk test.
• Long term oxygen treatment (if applicable) must be stable for 30 days prior to enrollment.
• Subjects on a chronic medication or therapy for any underlying cardiac condition must be on a stable dose for ≥30 days prior to randomization, with the exception of diuretics and antihypertensive medication for blood pressure control which may be discontinued if deemed appropriate. 
• Subjects on chronic medications for any underlying respiratory condition must be on a stable dose for ≥30 days prior to randomization.
• Note: With regard to Inclusion Criteria 7-9, “stable” refers to changes in oxygenation therapy or medications no greater than a 100% increase or a 50% decrease, as needed to optimize the patient.

Randomization Criterion:

• Response to Lead-in Levosimendan: Patients who demonstrate a ≥ 4mmHg reduction in PCWP from baseline measured during bicycle exercise (25 watts) with no more than a 10% decrease from baseline in cardiac index following the 24-hr infusion of levosimendan.

Exclusion Criteria:

• Previous PCI or cardiac surgery (CABG) unless documented to have negative stress test within the last 12 months.
• Clinically symptomatic mitral or aortic valvular heart disease.
• Cardiac index greater than 4.0 L/min/m2.
• In the opinion of the Principal Investigator, the subject has a primary diagnosis of PH other than WHO Group 2 PH-HFpEF.
• Congenital heart disease other than surgically corrected pre and post tricuspid shunts for at least 10 years.
• Symptomatic coronary artery disease and/or CAD based on positive stress test.
• Patients planning lung or heart transplant or cardiac surgery in the next 4 months.
• Patients diagnosed with pulmonary hypertension associated with clinically significant lung disease at the time of initial diagnosis, or patients with a congenital defect of the lung.
  • Clinically significant obstructive lung disease is defined as FEV1/FVC <60% of predicted, unless a high resolution chest CT scan shows no more than mild areas of emphysematous changes;
  • Clinically significant restrictive lung disease is defined as a FVC of <60% of predicted, unless a high resolution chest CT scan shows no more than mild areas of interstitial lung disease or pulmonary fibrosis.
• Dialysis at randomization (either hemodialysis, peritoneal dialysis, continuous venovenous hemofiltration, or ultrafiltration).
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2.
• Liver dysfunction with Child Pugh Class B or C.
• Evidence of systemic bacterial, systemic fungal, or viral infection in last 2 weeks.
• Weight > 150kg.
• Symptomatic low systolic blood pressure (SBP) that cannot be managed to ensure SBP > 100 mmHg at initiation of study drug.
• Heart rate ≥ 100 bpm with study drug, symptomatic and persistent for at least 10 minutes at screening.
• Hemoglobin < 80 g/L.
• Serum potassium < 3.0 mmol/L or > 5.5 mmol/L at baseline.
• Pregnant, suspected to be pregnant, or breast-feeding.
• Known allergic reaction or sensitivity to levosimendan or excipients.
• A history of Torsades de Pointes.
• Received levosimendan within 30 days before the planned start of study drug.
• Received an experimental drug or used an experimental medical device within 30 days before the planned start of study drug.
• Concomitant administration of pulmonary vasodilator therapy, or taken within 14 days of randomization.
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
• Inability to comply with planned study procedures.