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

NCT02076711 | Completed Phase 2 DMC

• 1 other identifier: 201300114731
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aortic Stenosis

Keywords

Aortic Stenosis; Myocardial efficiency

Outcome Measures

Primary Outcomes (1)

• LV myocardial efficiency

  Changes will be evaluated after an expected average of 22 weeks of treatment

Secondary Outcomes (10)

• LV oxygen consumption

  Changes will be evaluated after an expected average of 22 weeks of treatment

• LV perfusion

  Changes will be evaluated after an expected average of 22 weeks of treatment

• LV myocardial function

  Changes will be evaluated after an expected average of 22 weeks of treatment

• LVmass

  Changes will be evaluated after an expected average of 22 weeks of treatment

• Aortic valve area

  Changes will be evaluated after an expected average of 22 weeks of treatment

Study Arms (2)

Active

ACTIVE COMPARATOR

Metoprololsuccinate

Drug: Metoprololsuccinate

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Metoprololsuccinate DRUG

Active

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• ᵒ or 3ᵒ 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

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

Aarhus University Hospital, Department of Cardiology, Brendstrupgaardsvej 100

Aarhus N, 8200, Denmark

Location

Related Publications (1)

• Hansson NH, Sorensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frokiaer J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H. Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial. Circ Cardiovasc Imaging. 2017 Oct;10(10):e006557. doi: 10.1161/CIRCIMAGING.117.006557.

  PMID: 28956773 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Henrik Wiggers, DMSc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior consultant, Assoc. professor, DMSc

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 4, 2014
• Study Start: June 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 11, 2015

Record last verified: 2015-11

Locations

DK (1)