Effects of Nebivolol on Exercise Tolerance and Left Ventricular Systolic and Diastolic Function

Study Overview
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Brief Summary
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The goal of this pilot study is to effectively treat hypertension in subjects with either known or newly diagnosed hypertension and concurrent evidence of diastolic dysfunction. Due to the unique properties of nebivolol, it is hypothesized that there will be improvements in left ventricular (LV) systolic and diastolic function manifesting as increase exercise capacity in this patient population with primarily LV diastolic dysfunction. The present study was performed to determine the effects of nebivolol on blood pressure, exercise tolerance and parameters of left ventricular systolic and diastolic function in a group of hypertensive patients with echocardiographic evidence diastolic dysfunction.

Detailed Description
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Prior to the initiation of Nebivolol and after 10 weeks of Nebivolol therapy, subjects underwent a resting 2D echocardiogram including routine sampling of mitral valve (MV) inflow and LV tissue Doppler imaging as well as a symptom limited exercise treadmill stress test with echocardiographic imaging. Primary endpoints were 1) changes in systolic blood pressure before and after 10 weeks of treatment and 2) changes in exercise capacity as determined by exercise duration and metabolic equivalent (MET) level before and after treatment. Secondary endpoints were changes in exercise hemodynamics and Doppler echocardiographic parameters of LV systolic and diastolic function and quality of life before and after 10 weeks of nebivolol treatment. Subjects completed an EuroQol (EQ-SD) Quality of Life questionnaire which is a standardized measure of health status developed by the EuroQol group as a simple general measure of health at baseline and at conclusion of the 10 week trial period.

Official Title
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Effects of Nebivolol on Exercise Tolerance and Left Ventricular Systolic and Diastolic Function

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Nebivolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis (new or established) hypertension, defined by serial measurements >/= 140/90 Evidence of diastolic dysfunction on echocardiography measured by tissue Doppler Exclusion Criteria: Severe bronchospastic disease/ reactive airway disease Inability to tolerate beta blocker therapy including: >1st degree atrioventricular (AV) block, symptomatic hypotension, symptomatic bradycardia, Subjects with physical limitations that would prevent them from participating in an exercise treadmill test Age <18 or >90 years Those with life expectancy <1 year Subjects with class III/IV New York Heart Association (NYHA) heart failure symptoms Chronic Kidney Disease 3 or greater (CrCl <30 cc/min) Subjects with active ischemia or evidence of ischemia on initial stress echocardiography

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Nebivolol treatment<br>10 week open label nebivolol treatment. | Drug: Nebivolol<br>* Initial dose of 5 mg titrated (doubling of previous dose) to optimal blood pressure. The dose was titrated by doubling the previous dosage to achieve BP less than or equal to 130/80 mm Hg at 2 weeks and 4 weeks. The mean dose of nebivolol used week 4 through week 10 was 7.8 mg. It should be noted that nebivolol was added to the subject's existing stable antihypertensive regimen which included a mean of 2 other medications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting Systolic BP |  | 10 Weeks | 
| Exercise Duration |  | 10 Weeks | 
| Metabolic Equivalent (METS) Level | METs is a measure of exercise capacity. One MET is defined as 3.5 mL 02 uptake/kg per minute which is the resting oxygen uptake in a sitting position. The Bruce protocol consisted of successive 3 minute stages each of which requires the subject to walk at a faster speed and higher grade of incline. Each stage is assigned a MET level. The achieved exercise capacity in METs has been shown to be predictive in older adult population of survival with higher MET levels associated with improved survival. | 10 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diastolic BP |  | 10 Week | 
| Peak Stress Systolic BP |  | 10 Week | 
| Peak Stress Diastolic BP |  | 10 Week | 
| Resting Heart Rate |  | 10 Week | 
| Stress Heart Rate |  | 10 Week | 
| Resting EF |  | 10 Weeks | 
| Stress EF |  | 10 Week | 
| Resting Stroke Volume |  | 10 weeks | 
| Stress Stroke Volume |  | 10 week | 
| Resting Cardiac Output |  | 10 week | 
| Stress Cardiac Output |  | 10 week | 
| LV End Diastolic Diameter |  | 10 week | 
| LV End Systolic Diameter |  | 10 week | 
| LV Mass |  | 10 week | 
| Mitral Valve Inflow (E) Velocity |  | 10 Week | 
| Mitral Valve Inflow (A) Velocity |  | 10 Week | 
| Mitral Valve E/A Ratio | mitral valve doppler E velocity to A velocity | 10 Week | 
| Mitral Valve Deceleration Time |  | 10 Week | 
| Mitral Valve Tissue Doppler Velocity (e') |  | 10 Week | 
| Mitral Valve Tissue Doppler Velocity (a') |  | 10 Week | 
| E/e' Ratio |  | 10 Week | 
| Pulmonary Vein Peak Systolic Velocity |  | 10 Week | 
| Pulmonary Vein Peak Diastolic Velocity |  | 10 Week | 
| Quality of Life | Quality of life was assessed by a visual analogue scale before and after 10 weeks of nebivolol. The subjects self reported assessment of his/her overall health was recorded on a vertical visual analogue scale where 100 is the best imaginable health state and 0 is the worst imaginable health state. | 10 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nebivolol, Diastolic Function