Short summary

For decades patients with severe asymptomatic aortic stenosis have been followed up with echocardiographic evaluations 1-2 times per year, and only referred for surgery when symptoms emerge. Recent studies have demonstrated that patients with aortic stenosis have increased mortality and morbidity despite succesfull surgery when compared to an age matchet population, and that the risk of death associates with the degree of left ventricular remodeling.

Rationale

Since the seminal paper by Ross and Braunwald, the development of symptoms has been regarded as one of the most important precursors of a poor outcome in aortic stenosis (AS), and is today half a century later, still the leading reason for referral for aortic valve replacement (AVR). The development of symptoms is however often preceded by structural changes in the left ventricle (LV). These changes including concentric remodeling and LV hypertrophy have been regarded as compensative measures to adapt the LV to increased ventricular afterload. Although LV hypertrophy may preserve wall-stress in the normal range and increase contractility allowing the preservation of stroke volume, this occurs at the expense of increased filling pressures. Diastolic dysfunction with increased filling pressure lead to left atrial (LA) dilatation and significantly contributes to the development of symptoms.

Despite successful surgery, AS patients have increased long-term mortality and morbidity compared to the general population, and the outcome is largely determined by the degree of preoperative structural LV and LA alterations. This has led to the theory that AVR prior to the development of symptoms could improve outcome, a view supported by prospective and retrospective studies. These studies were however small, with some important limitations. In addition, there has been a concern that operative risk and prosthetic valve related long-term morbidity and mortality does not justify surgery on every asymptomatic patient with severe AS. Numerous studies have suggested that markers of LV structure and function, particularly LA volume index and brain natriuretic peptides (BNP) all reflecting LV filling pressures may identify patients with benefit of early AVR. Accordingly, the most recent European guideline for management of valvular disease has implemented BNP as a class IIa recommendation for AVR in asymptomatic AS patients, although no randomized studies have demonstrated that early surgery based on these markers improve prognosis.

The purpose of this study is thus to evaluate if early AVR in patients with signs of elevated LV filling pressures may improve long-term outcome in patients with asymptomatic severe AS, compared to conventional symptom-guided surgery.

Description of the cohort

patients with severe aortic stenosis

Data and biological material

blood, valvular material, myocardial biopsy

Collaborating researchers and departments

Department of Cardiology, Rigshospitalet

• Rasmus Møgelvang MD, PhD
• Nikolaj Ihlemann, MD, PhD
• Professor Lars Køber, MD, DMSCi

Department of Cardiology, Skejby Hospital

• Vibeke Guldbrand MD, PhD
• Henrik Vase, MD, PhD
• Steen Hvitfeldt Poulsen, MD, PhD, DMSCi

Department of Cardiology, Aalborg University Hospital

• Niels Holmark, MD, PhD

Department of Cardiology, Roskilde Hospital

• Hanne Elming MD, PhD
• Anh Thuc Ngo, MD, PhD

Department of Cardiology, Bispebjerg Hospital

• Nana Valeur, MD, PhD

Department of Cardiology, Odense University Hospital

• Ann Banke, MD
• Professor Jacob E. Møller, MD, PhD, DMSCi

Department of Thoracic Surgery, Rigshospitalet

• Morten Smerup, MD, DMSCi

Department of Thoracic Surgery, Odense University Hospital

• Lars Riber, MD, PhD

Department of Thoracic Surgery, Skejby Hospital

• Mariann Tang, MD, PhD