Pressure Assessment to Improve Outcomes After TAVR: a Registry

At the Malcom Randall Veterans Affairs Medical Center (MRVAMC), invasive cardiac pressures are routinely recorded after transcatheter aortic valve replacement (TAVR) procedures. Our research has disclosed that patients with abnormal hemodynamics (narrow aortic to ventricular end-diastolic pressure difference, indexed to heart rate) suffer from high long-term mortality, compared with patients with normal hemodynamics.This hemodynamic value can be referred to as the aortoventricular index (AVi). Hypertension and diastolic dysfunction are highly co-morbid conditions among these patients. The selective aldosterone receptor antagonist eplerenone (Inspra) is approved for use in the treatment of hypertension. Research also supports that eplerenone may be able to improve diastolic function.

This prospective study is interested in determining 1) the tolerability of eplerenone, and 2) feasibility of administering the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) among subject with abnormal cardiac hemodynamics after TAVR. This study will set the stage for a pilot randomized trial to evaluate eplerenone versus placebo among patients with abnormal hemodynamics after TAVR.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Hypertension; Heart Failure With Preserved Ejection Fraction; Aortic Stenosis, Calcific
• Intervention / Treatment: Drug: Eplerenone

Detailed Description

Our research has disclosed that patients who have abnormal invasive cardiac hemodynamics (narrow aortic to ventricular end-diastolic pressure difference, indexed to heart rate) after TAVR suffer from poor long-term survival. This hemodynamic value can be referred to as the aortoventricular index (AVi). In a single center observational study, the 2-year mortality rate for patient with a value ≥0.6 mm Hg/bpm was 25% compared with 36% for patients with a value <0.6 mm Hg/bpm. An abnormal AVi was an independent predictor for poor survival. Hypertension and diastolic dysfunction are 2 highly co-morbid conditions among these patients. Currently, there is lack of appreciation that pressure measurements obtained at the time of TAVR can provide long-term prognostic value. There is also a lack of understanding on how to improve outcomes and quality of life among such patients.

Eplerenone is a selective aldosterone receptor antagonist approved for use for treatment of hypertension. Animal studies have shown that aldosterone receptor antagonists can decrease interstitial myocardial fibrosis. The non-selective aldosterone receptor antagonist, spironolactone 25 mg daily compared with placebo was shown to improve diastolic function, as assessed by echocardiography, among 28 elderly subjects. A meta-analysis of eleven studies in 942 subjects found that aldosterone receptor antagonists improve diastolic function and markers of cardiac fibrosis without significant changes to left ventricular mass or dimensions. In a randomized controlled trial, eplerenone was found to be safely tolerated among asymptomatic patients with moderate to severe aortic stenosis.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • Malcom Randall VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

1. Enroll 10 subjects with hypertension and abnormal hemodynamics after TAVR.

2. This is a greater than minimal risk study.

   1. Inclusion criteria:

      • TAVR procedure performed at the Malcom Randall VA Medical Center within the last 2 years.
      • Intracardiac pressures recorded 5 to 10 minutes after TAVR and AVi < 0.6 mm Hg/bpm.
      • History of hypertension, taking anti-hypertensive medications, or recent systolic blood pressure ≥130 mm Hg.

   2. Exclusion criteria:

      • Serum potassium >5.5 mEq/L at initiation.
      • Concomitant administration of strong CYP3A inhibitor (i.e. ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir).
      • Type 2 diabetes with microalbuminuria.
      • Serum creatinine >2.0 for men and >1.8 for women.
      • Creatinine clearance <50 cc/min.
      • Concomitant administration of potassium supplements or potassium-sparing diuretics.

3. Subjects who are eligible to participate and signed an informed consent will be given eplerenone 50 mg daily. Study drug (eplerenone) will be paid by the North Florida Foundation for Research and Education for the duration of the study.

   a. Down-titration or termination of non-essential anti-hypertensive agents is permissible so that eplerenone does not result in hypotension. Essential medications are as follows:

   • Angiotensin converting enzyme inhibitors (ACE-inhibitors) or angiotensin receptor blockers, if intolerant to ACE-inhibitors are indicated for treatment left ventricular dysfunction (i.e. left ventricular ejection fraction ≤40%), diabetes, and proteinuric chronic kidney disease.
   • Beta-blockers are indicated 3 years after an acute myocardial infarction, unless there is persistent left ventricular dysfunction (i.e. left ventricular ejection fraction ≤40%).

4. Monitoring.

   a. Serum potassium within the last 30 days is required before initiating eplerenone. Repeat blood draw is required within the first week, and one month after the start of treatment with eplerenone.

5. Quality of life questionnaire. a. The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) will be administered at baseline and 8 weeks. The KCCQ-12 instrument will be mailed to the subject. Study coordinator will call the subject at 8 weeks to confirm vital status, assess if any adverse reactions from eplerenone, and provide assistance to completing the KCCQ-12, if needed.

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: Eplerenone; Eplerenone 50 mg daily, administered orally for 8 weeks.	Drug: Eplerenone; Eplerenone 50 mg daily; Other Names: Inspra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.	Baseline, 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.	Baseline, 8 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.	Baseline, 8 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.	Baseline, 8 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a self-administered health status survey. The KCCQ-12 has 4 domains (physical limitation, symptom frequency, quality of life, social limitation) and one summary score. Score are scaled 0-100, where 1 denotes the lowest reportable health status and 100 the highest.	Baseline, 8 weeks
Systolic Blood Pressure	Cuff systolic blood pressure	Baseline, 8 weeks
Diastolic Blood Pressure	Cuff diastolic blood pressure	Baseline, 8 weeks

Collaborators and Investigators

• Sponsor: North Florida Foundation for Research and Education
• Collaborators: Malcom Randall VA Medical Center
• Investigators: Principal Investigator: Anthony Bavry, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2019
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): February 27, 2020

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: April 19, 2019
• First Posted (Actual): April 22, 2019

Study Record Updates

• Last Update Posted (Actual): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Aortic stenosis; TAVR; Diastolic dysfunction; KCCQ; Invasive hemodynamic assessment
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: 201901097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes