Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention?

Aortic Stenosis Clinical Trial

— MELVAS  

Official title:

Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02076711
• Other study ID #: 201300114731
• Status: Completed
• Phase: Phase 2
• First received: February 27, 2014
• Last updated: November 10, 2015
• Start date: June 2013
• Est. completion date: September 2015

Study information

• Verified date: November 2015
• Source: Aarhus University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines AuthorityDenmark: The Regional Scientific Ethical Committee of Central Denmark RegionDenmark: Unit for "Good Clinical Practice" at Aarhus University Hospital
• Study type: Interventional

Clinical Trial Summary

Background - Aortic valve stenosis (AS) is the most common heart valve disease among adults in the Western world with a prevalence of 3 % in people older than 75 years of age. AS usually deteriorates over time leading to heart failure, with high mortality if aortic valve replacement (AVR) is not performed. Thus optimal timing of AVR is crucial, but can be challenging. Increasing life expectancy in our society will augment the therapeutic and socio economic impact of AS disease on our health care system. Therefore, new techniques for monitoring asymptomatic AS patients are needed. A potential approach is monitoring of LV myocardial efficiency (mechanical work/oxygen consumption). These measures have been suggested to be involved in the progression of non-valvular heart failure and closely related to prognosis, but never applied in a larger population of patients with AS. At present there are no recognized pharmacological treatments of AS. It is known that beta-blocker treatment in non-valvular systolic heart failure reduce heart rate, improves LV myocardial efficiency and reduces mortality. However, in patients with AS, the effects of beta-blockers are unknown.

Hypotheses - Treatment with the beta-blocker metoprolol succinate in patients with asymptomatic moderate to severe AS has beneficial effects on LV myocardial oxidative metabolism, myocardial efficiency and contractile function.

Objectives - To investigate if beta-blocker treatment in patients with moderate to severe, asymptomatic AS has beneficial effects on LV myocardial efficiency, contractile function and physical performance.

Design - A randomized double blind placebo controlled intervention trial. 40 patients with asymptomatic AS will be randomized to either per oral metoprolol succinate (N = 20) or placebo (N= 20) for 22 weeks.

Primary objective - Changes in myocardial efficiency

Secondary objectives - Myocardial oxygen consumption, Myocardial perfusion at rest, LV myocardial function, LVmass, Aortic valve area and transaortic valve velocities, 6 minute walking distance, N-terminal prohormone of brain natriuretic peptide, Quality of life (estimated by Minnesota living with heart failure questionnaire), LV wall stress

Methods - Patients will undergo echocardiography (resting and exercise), [11C]acetate PET and cardiac magnetic resonance imaging.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Aortic valve area =1,2 cm2 and/or transaortic maximal velocity (VmaxAO) of 3,0-5,0 m/s

• Sinus rhythm >60/min after 5 minutes of rest

• LVEF >=50%

• Male or female

• Age 20-100 years old

• Safe birth control management for women of childbearing potential.

• Negative urine-HCG for women of childbearing potential

• Ability to understand the written patient information and to give informed consent

Exclusion Criteria:

• Systolic BP <100 mmHg after 5 minutes of rest

• Left ventricular posterior wall thickness >17 mm

• Signs or history of major myocardial infarction and/or severe ischemic heart disease

• Severe asthma or chronic obstructive pulmonary disease

• New York Heart Association (NYHA) classification > I due to AS

• NYHA > II due to non-cardiac causes

• 2? or 3? atrioventricular block

• Ongoing beta-blocker therapy

• Ongoing verapamil or diltiazem therapy

• Ongoing monoamine oxidase inhibitors therapy (except MAO-B-inhibitors)

• Sick sinus syndrome

• Atrial fibrillation or fluttering

• Lack of stable sinus rhythm

• Pheochromocytoma

• Severe peripheral vascular disease

• Intolerance of Metoprolol succinate or its excipients

• Other disease or treatment making subject unsuitable for study participation

• Intolerance of tracer used for [11C]acetate PET recordings

• Participation in other intervention study

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Drug:
• Metoprololsuccinate

• Placebo
Placebo

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, Department of Cardiology, Brendstrupgaardsvej 100	Aarhus N

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LV myocardial efficiency		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	LV oxygen consumption		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	LV perfusion		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	LV myocardial function		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	LVmass		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	Aortic valve area		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	Transaortic valve velocities		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	6 minute walking distance		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	N-terminal prohormone of brain natriuretic peptide		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	Quality of life - estimated by Minnesota living with heart failure questionnaire		Changes will be evaluated after an expected average of 22 weeks of treatment	No
Secondary	LV wall stress		Changes will be evaluated after an expected average of 22 weeks of treatment	No