Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

Pulmonary hypertension is common in patients with aortic stenosis and is associated with worse operative and long-term outcomes. Sildenafil has been shown to reduce pulmonary artery pressure and improve exercise performance in patients with left-sided heart failure, but this has not been tested in patients with aortic stenosis. We hypothesize that Sildenafil will produce a clinically significant decrease in pulmonary artery pressure in patients with severe aortic stenosis. The dose of Sildenafil that produces a significant decrease in pulmonary artery pressure will be safe and well tolerated in patients with and without a depressed ejection fraction.

Study Overview

• Status: Completed
• Conditions: Aortic Stenosis
• Intervention / Treatment: Drug: Sildenafil

Detailed Description

Patients with severe aortic stenosis referred for a clinically ordered right and left heart catheterization will be eligible. Twenty subjects will be enrolled: 10 patients will receive 40mg and 10 patients will receive 80mg; each dose will be equally distributed among those with preserved (≥50%) and reduced (<50%) EF. Subjects will get a baseline echo prior to the heart catheterization. Baseline invasive hemodynamic measurements will be performed using a Swan Ganz catheter. A single oral dose of sildenafil will then be administered (40mg or 80mg), followed by invasive hemodynamic measurements at 30 and 60 minutes. Also at 60 minutes, limited echocardiographic images will be obtained.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Severe aortic stenosis (AVA < 1.0 cm2)
• Referred for a clinically ordered right and left heart catheterization
• 18 years of age and older
• Able and willing to comply with all requirements of the study

Exclusion Criteria:

• Nitrate use within 24 hours
• SBP < 110 mmHg or MAP < 75 mmHg
• Severe mitral regurgitation
• Severe aortic regurgitation
• Increased risk of priapism
• Retinal or optic nerve problems or unexplained visual disturbance
• Alpha antagonists or cytochrome P450 3A4 inhibitors use within 24 hours
• Current or recent (≤ 30 days) acute coronary syndrome
• O2 sat < 90% on room air
• Females that are pregnant or believe they may be pregnant
• Any condition which the PI determines will place the subject at increased risk or is likely to yield unreliable hemodynamic data
• Unwilling to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sildenafil 40mg or 80mg; A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (<50%) EF.	Drug: Sildenafil; Single oral dose of 40mg or 80mg of Sildenafil; Other Names: Viagra; Revatio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort.	Baseline and 60 minutes after drug administered

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Pulmonary Vascular Resistance in the Whole Cohort.		Baseline and 60 minutes after drug administered
Percent Change in Cardiac Index.	Cardiac index is cardiac output divided by body surface area.	Baseline and 60 minutes after drug administered
Load Independent Index of Diastolic Filling.	Measurements of the load independent index of diastolic filling were made with the parameterized diastolic filling formalism as previously described and validated with the use of transmitral Doppler E waves recorded during different respiratory states (regular breathing and held expiration and inspiration).	Baseline and 60 minutes after drug administered
Global Longitudinal Strain	Global longitudinal strain was measured at baseline and 60 minutes after drug administration.	Baseline and 60 minutes after drug administered

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Barnes-Jewish Hospital
• Investigators: Principal Investigator: Brian R. Lindman, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Lindman BR, Zajarias A, Madrazo JA, Shah J, Gage BF, Novak E, Johnson SN, Chakinala MM, Hohn TA, Saghir M, Mann DL. Effects of phosphodiesterase type 5 inhibition on systemic and pulmonary hemodynamics and ventricular function in patients with severe symptomatic aortic stenosis. Circulation. 2012 May 15;125(19):2353-62. doi: 10.1161/CIRCULATIONAHA.111.081125. Epub 2012 Mar 25.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: January 28, 2010
• First Submitted That Met QC Criteria: January 28, 2010
• First Posted (Estimate): February 1, 2010

Study Record Updates

• Last Update Posted (Actual): April 25, 2018
• Last Update Submitted That Met QC Criteria: April 16, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Aortic valve stenosis; Phosphodiesterase inhibitors; Sildenafil; Hypertension, Pulmonary
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 09-1780