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

Not Applicable

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Nebivolol treatment	Nebivolol	10 week open label nebivolol treatment.

Primary Outcome Measures

Name	Time	Method
Metabolic Equivalent (METS) Level	10 Weeks	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.
Resting Systolic BP	10 Weeks
Exercise Duration	10 Weeks

Secondary Outcome Measures

Name	Time	Method
LV End Systolic Diameter	10 week
Peak Stress Diastolic BP	10 Week
Resting Heart Rate	10 Week
LV Mass	10 week
Mitral Valve Deceleration Time	10 Week
Mitral Valve Tissue Doppler Velocity (a')	10 Week
E/e' Ratio	10 Week
Stress Heart Rate	10 Week
Mitral Valve E/A Ratio	10 Week	mitral valve doppler E velocity to A velocity
Diastolic BP	10 Week
Peak Stress Systolic BP	10 Week
Resting EF	10 Weeks
Stress EF	10 Week
Resting Stroke Volume	10 weeks
Stress Stroke Volume	10 week
Stress Cardiac Output	10 week
Resting Cardiac Output	10 week
LV End Diastolic Diameter	10 week
Mitral Valve Inflow (E) Velocity	10 Week
Mitral Valve Inflow (A) Velocity	10 Week
Mitral Valve Tissue Doppler Velocity (e')	10 Week
Pulmonary Vein Peak Systolic Velocity	10 Week
Quality of Life	10 Weeks	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".
Pulmonary Vein Peak Diastolic Velocity	10 Week