Aortic Stenosis, Calcific, Heart Failure With Preserved Ejection Fraction, Hypertension, Quality of Life
Conditions
Keywords
TAVR, KCCQ, Aortic stenosis, Diastolic dysfunction, Invasive hemodynamic assessment
Brief summary
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.
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.
Interventions
DRUGEplerenone
Eplerenone 50 mg daily
Sponsors
Malcom Randall VA Medical Center
North Florida Foundation for Research and Education
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Enroll subjects who underwent TAVR and had documentation of abnormal invasive cardiac hemodynamics.
Eligibility
Sex/Gender
ALL
Age
55 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score | Baseline, 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score | Baseline, 8 weeks | 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. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score | Baseline, 8 weeks | 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. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score | Baseline, 8 weeks | 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. |
| Systolic Blood Pressure | Baseline, 8 weeks | Cuff systolic blood pressure |
| Diastolic Blood Pressure | Baseline, 8 weeks | Cuff diastolic blood pressure |
| Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score | Baseline, 8 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment at Malcom Randall VA Medical Center
Participants by arm
| Arm | Count |
|---|---|
| Eplerenone All subjects will receive study drug daily.
Eplerenone: 50mg daily
Kansas City Cardiomyopathy Questionnaire: administered at baseline and 8 weeks
Serum potassium: within the last 30 days is required before initiating eplerenone, repeat blood draw within the first week and starting eplerenone and 4 weeks after starting eplerenone | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | screen failure | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Eplerenone |
|---|---|
| Age, Continuous | 73.1 years STANDARD_DEVIATION 8.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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.
Time frame: Baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score | Baseline | 59.4 score on a scale | Standard Deviation 19.7 |
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Summary Score | 8 weeks | 74.1 score on a scale | Standard Deviation 20 |
Comparison: Change from baseline to 8 weeksp-value: 0.12t-test, 2 sided
Secondary
Diastolic Blood Pressure
Cuff diastolic blood pressure
Time frame: Baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Diastolic Blood Pressure | Baseline | 56.2 mm Hg | Standard Deviation 7.7 |
| Eplerenone | Diastolic Blood Pressure | 8 weeks | 55.0 mm Hg | Standard Deviation 6.2 |
Comparison: Change from baseline to 8 weeksp-value: 0.76t-test, 2 sided
Secondary
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.
Time frame: Baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score | Baseline | 53.0 score on a scale | Standard Deviation 21.4 |
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Physical Limitation Score | 8 weeks | 61.5 score on a scale | Standard Deviation 14.8 |
Comparison: Change from baseline to 8 weeksp-value: 0.49t-test, 2 sided
Secondary
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.
Time frame: Baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score | Baseline | 54.9 score on a scale | Standard Deviation 40.5 |
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Quality of Life Score | 8 weeks | 73.6 score on a scale | Standard Deviation 30.8 |
Comparison: Change from baseline to 8 weeksp-value: 0.27t-test, 2 sided
Secondary
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.
Time frame: Baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score | Baseline | 65.6 score on a scale | Standard Deviation 32.2 |
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Social Limitation Score | 8 weeks | 80.1 score on a scale | Standard Deviation 26 |
Comparison: Change from baseline to 8 weeksp-value: 0.18t-test, 2 sided
Secondary
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.
Time frame: Baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score | Baseline | 63.5 score on a scale | Standard Deviation 20.7 |
| Eplerenone | Kansas City Cardiomyopathy Questionnaire (KCCQ-12)-Symptom Frequency Score | 8 weeks | 81.5 score on a scale | Standard Deviation 14.4 |
Comparison: Change from baseline to 8 weeksp-value: 0.03t-test, 2 sided
Secondary
Systolic Blood Pressure
Cuff systolic blood pressure
Time frame: Baseline, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eplerenone | Systolic Blood Pressure | Baseline | 122.5 mm Hg | Standard Deviation 16.5 |
| Eplerenone | Systolic Blood Pressure | 8 weeks | 120.0 mm Hg | Standard Deviation 26.3 |
Comparison: Change from baseline to 8 weeksp-value: 0.8t-test, 2 sided