Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pulmonary Hypertension Secondary to Heart Failure With Preserved Systolic Function: a Target of Phosphodiesterase - 5 Inhibition in a 1- Year Duration Study
Brief Summary: Prevalence of heart failure (HF) with left ventricular (LV) diastolic dysfunction and preserved ejection fraction (EF) (HFpEF) is increasing. Prognosis worsens with development of pulmonary vasoconstriction and hypertension (PH) and right ventricular (RV) failure. The investigators aimed at modulating pulmonary vascular tone and RV burden in HFpEF due to high blood pressure (HBP), by using the phosphodiesterase-5 (PDE5) inhibitor sildenafil.


Options:
A: Inclusion Criteria:

* Clinical diagnosis of IPF
* 40-85 years of age
* 6-minute walk distance 150-500 m
* FVC 40-90% predicted
* DLCO 30-90% predicted

Exclusion Criteria:

* Severe pulmonary hypertension
* Severe heart failure
* FEV1/FVC \< 0.7
B: Inclusion Criteria:

* LVEF \>50%
* sinus rhythm and stable clinical condition defined as no changes in therapeutic regimen, or hospitalization in the 6 months preceding recruitment.
* pulmonary artery systolic pressure \> 40 mm Hg,

Exclusion Criteria:

* Patients receiving nitrates
* A history of pulmonary disease
* Alternative causes of PH other than cardiac-related
* Renal failure (creatinine \> 2mg/dL)
* Anemia
* Pericardial disease
* Cardiac amyloidosis
C: Inclusion Criteria:

* Male or female subjects aged from 1 to 17 years old and weighing \>= 8 kg with a mean pulmonary artery pressure \>= 25 mmHg at rest, PCWP \<= 15 mmHg, and PVRI \>= 3 Wood units x m2 (if PCWP is not available, then mean LA pressure \<= 15 mmHg or LVEDP \<= 15 mmHg in the absence of left atrial obstruction).
* Females of child bearing potential who were sexually active must have been practicing a suitable method of birth control so that in the opinion of the investigator, they would not become pregnant during the study.
* Subjects who have symptomatic pulmonary arterial hypertension due to: primary pulmonary hypertension; pulmonary arterial hypertension in the presence of a small or hemodynamically insignificant congenital systemic to pulmonary shunt lesion that in the opinion of the investigator is not the cause of pulmonary hypertension; collagen vascular disease; congenital systemic-to-pulmonary shunts with a baseline resting room air oxygen saturation \>= 88% unrepaired or repaired at least 6 months prior to screening; d-transposition of the great arteries repaired within the first 30 days of life; or surgical repair of other congenital heart lesions at least 6 months prior to screening and do not have clinically significant residual left-sided heart disease consistent with the exclusion criteria.
* Subjects, developmentally able to exercise, whose CPX exercise test functional capacity is within the following parameters: Peak VO2 \>= 10 mL/kg/min and \<= 28 mL/kg/min during screening CPX test;
* Written informed consent and assent where applicable before the subject is screened for the study.
* Subjects who undergo a large shift in altitude (defined as approximately 5000 feet or 1524 meters) in order to participate in the study must reside at the "in study" altitude for at least 90 days prior to baseline and during the study period.

Exclusion Criteria:

* Subjects with pulmonary hypertension secondary to sickle cell disease, any other disease known to be associated with PAH, or any etiology other than those specified in the inclusion criteria.
* Left-sided heart disease, including aortic or mitral valve disease (greater than mild), restrictive or congestive cardiomyopathy; PCWP or LVEDP \> 15 mmHg; LVEF \< 40% determined by MUGA, angiography or echocardiography; LV shortening fraction \< 22% determined by echocardiography, symptomatic coronary disease (demonstrable ischemia).
* Pericardial constriction; significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation; acutely decompensated heart failure within previous 30 days from screening; atrial septostomy within previous 6 months of screening;
* Hemodynamic instability or hypo- or hypertension at screening, i.e., SBP outside of 70-140 mmHg.
* A history of stroke, myocardial infarction or life threatening arrhythmia within 6 months of screening.
* Moderate to severe restrictive pulmonary disease (Total Lung Capacity or Forced Vital Capacity \<= 60% of normal) or history of severe lung disease.
* Subjects with bronchopulmonary dysplasia (BPD) and other chronic lung diseases.
* History of pulmonary embolism.
* Subjects whose CPX test is limited by conditions other than pulmonary hypertension-associated dyspnea or fatigue.
* Subjects who are known to be HIV positive
* Subjects with impairment of renal function (serum creatinine \> 2.5x ULN ) or hepatic function (ALT and/or AST \> 3x ULN; and/or bilirubin \>= 2 mg/dL). Hematological abnormalities (e.g., severe anemia, Hgb \< 10 g/dL, leukopenia, WBC \< 2500/mL).
* Subjects who previously received bosentan and whose liver function tests taken at screening are \> 2x ULN.
* Subjects with any medical condition which in the opinion of the investigator may interfere with treatment, evaluation of safety, and/or efficacy.
* Change in class of medication for CHF or PAH within the 10 days prior to qualifying right heart catheterization.
* Subjects who are currently prescribed and/or taking nitrates or nitric oxide donors in any form. Acute vasodilator testing with nitric oxide is permitted during hemodynamic evaluation; taking chronic arginine supplementation including Heart Bar; therapy involving parenteral inotropic medication or parenteral vasodilators within 3 months of screening; current therapy with alpha-blockers, potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole and protease inhibitors), Ritonavir or Nicorandil; chronic treatment with off-label sildenafil, an endothelin antagonist or prostacyclin/prostacyclin analogue within 30 days of randomization.
* Pregnant or lactating female.
* Any medical or psychological condition or social circumstances that would impair their ability to participate reliably in the study or who were not likely to complete the study for any reason; current or past illicit drug use or alcoholism excepting if abstinence can be documented for \>= 1 year.
* Participation in another clinical trial of an investigational drug or device (including placebo) within 30 days of screening for entry into the present study.
* Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischemic optic neuropathy (NAION).
D: Inclusion Criteria:

1. Signed informed consent prior to initiation of any study-mandated procedures.
2. Males or females ≥ 12 years of age (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception).
3. Symptomatic patients with the following types of PAH belonging to World Health Organization (WHO) Pulmonary Hypertension Classification Group I:

   * Idiopathic (IPAH)
   * Familial (FPAH)
   * Associated with PAH (APAH):

     * Collagen vascular disease
     * Drugs and toxins
4. Patients naïve to treatment with advanced PAH therapies (i.e., endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors or prostacyclins) with a right heart catheterization (RHC) showing all of the following:

   * Mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg
   * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mm Hg when PCWP is not accurately obtained
   * Pulmonary vascular resistance ≥ 3 Wood units
5. 6-MWT distance ≥ 150 meters and \< 360 meters.

Exclusion Criteria:

1. Patients with Pulmonary Hypertension (PH) belonging to WHO Classification Group II-V.
2. Patients with PAH (WHO PH Classification Group I) other than that listed in the Inclusion Criteria.
3. Pregnant and/or nursing.
4. Women of childbearing potential not using a reliable method of contraception.
5. Patients with known human immunodeficiency virus (HIV) infection.
6. Patients with significant vasoreactivity during right heart catheterization (i.e., a fall in mPAP to \< 40 mm Hg with a decrease of ≥ 10 mm Hg and with a normal cardiac index ≥ 2.5 l/min.m\^2).
7. Patients with restrictive lung disease (i.e., total lung capacity (TLC) \< 60% of normal predicted value).
8. Patients with obstructive lung disease (i.e., forced expiratory volume/ forced vital capacity (FEV1/FVC) \< 0.5).
9. Patients with impaired left ventricular function (LVEF \<50%) or diastolic dysfunction.
10. Patients with portal hypertension, cirrhosis, moderate to severe liver impairment (Child-Pugh Class B or C), or liver enzymes (Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) \> 3.0 times the upper limit of normal range.
11. Treatment with glibenclamide (glyburide) and calcineurin inhibitors (cyclosporine A, tacrolimus) sirolimus, everolimus up to 1 week prior to Baseline (Day 1).
12. Patients currently receiving or predicted to require treatment, during the course of the study, with nitrates, protease inhibitors, or alpha-blockers.
13. Patients with a hemoglobin concentration \< 75 % of the lower limit of the normal range or \< 8.5 g/dL.
14. Patients currently receiving or predicted to require treatment with a prostanoid during the course of the study.
15. Patients with systolic blood pressure \< 85 mm Hg.
16. Patients with body weight \< 40 kg.
17. Patients who have received any investigational product within 90 days prior to Baseline.
18. Patients who previously received any advanced therapy for PAH (e.g., ERAs, PDE-5 inhibitors or prostacyclins).
19. Patients with hypersensitivity to sildenafil or any excipients of its formulation.
20. Patients with any contraindication to sildenafil treatment (i.e., nitrates).
21. Patients with any recent medical condition limiting the ability to comply with the study requirements (i.e., stroke, myocardial infarction).
22. Patients with unstable PAH whose disease state would prohibit the completion of study procedures, in the opinion of the investigator.
23. Patients unable to complete a MRI scan (e.g., claustrophobia).
24. Patients with permanent cardiac pacemakers, automatic internal cardioverter defibrillators (AICD's), neurostimulators, hearing aides, and other implanted metallic devices that are contraindicated during a MRI study.
25. Patients with conditions that would interfere with proper cardiac gating during MRI, such as atrial fibrillation or multiple premature ventricular contractions (PVCs)/premature atrial contractions (PACs).
26. Patients with conditions that prevent compliance with the protocol or the ability to adhere to therapy.

Answer: B