Short summary

This study investigates the possible implications of left atrial dilation in patients with severe asymptomatic aortic stenosis. Size and function of the left atrium may be a surrogate for more advanced heart disease. We wish to identify possible (early) risk factors associated with severe asymptomatic aortic stenosis. The consequences of increased pressure load on the left ventricle is investigated using advanced imaging modalities, functional capacity, and hemodynamic exercise test with right heart catheterization.

Rationale

Aortic valve stenosis (AS) is the most common valvular heart disease in the western world. AS results in increased filling pressures of the heart and left ventricle and thereby progressive dysfunction of the heart. Over time the elevated pressure cause remodelling of the heart chambers and affects the left atrium, which will dilate. Size and function of the left atrium may be a surrogate for more advanced heart disease, in patients with severe aortic stenosis, not presenting any apparent symptoms. Clinical assessment of heart failure symptoms in AS is often challenging, particularly in the elderly and symptoms progress slowly and may mimic age related fragility.

The goal of this study is to investigate the importance and possible implications of left atrial dilation as a surrogate for heart failure in patients with severe asymptomatic aortic stenosis. 100 participants undergo echocardiographic evaluation for diastolic heart failure, and myocardial fibrosis is assessed using magnetic resonance imaging with gadolinium late enhancement technique and biomarkers. Functional capacity is estimated along with invasive hemodynamic measurements (right heart catheterization). Possible arrhythmias are detected through 48 hours of holter monitoring.

Left atrial dilation may potentially identify patients likely benefiting of early surgery. The importance and possible implications of left atrial dilation in asymptomatic AS has not yet been established.

Description of the cohort

100 Eligible patients with asymptomatic severe aortic stenosis referred to/followed at the Department of Cardiology, Odense University Hospital.

Inclusion criteria

• Age > 18 years and signed informed consent
• Asymptomatic severe aortic stenosis (Vmax>3.5 m/sec and aortic valve area < 1.0 cm²).

Exclusion criteria

• Moderate left ventricular systolic dysfunction (EF<50%)
• Patients with concomitant moderate-severe valve regurgitation (aortic, mitral)
• Moderate to severe nephropathy (s-creatinin > 200 mmol/L)
• Chronic or persistent atrial fibrillation.
• Implanted pacemaker or cardio defibrillator
• Poor echocardiographic window or unable to perform treadmill test.

Data and biological material

Venous blood samples: myocardial fibrosis biomarkers.

Echocardiographic parameters of chamber dimensions, systolic and diastolic function.

Myocardial fibrosis estimated by late enhancement MRI.

Invasive hemodynamic

Functional capacity: VO₂max

Questionnaire: Duke Activity Index Score

Collaborating researchers and departments

Department of Cardiology, Odense University Hospital

• Professor and Main Supervisor Jacob Eifer Møller, MD, DMSc
• Co-supervisor Jordi Sanchez Dahl, MD, PhD
• Co-supervisor Lars Melgaard Videbæk, MD, PhD
• Co-supervisor Eva Søndergaard, MD, PhD

Department of Clinical Biochemistry, Odense University Hospital

• Professor Lars Melholt Rasmussen, MD, DMSc

Department of Sports Science and Clinical Biomechanics Muscle Physiology and Biomechanics, Odense University Hospital

• Teaching Associate Professor Kurt Jensen, MSc