Impact of Beta-blockers Among Patients Undergoing TAVI: a Randomized Multicenter Trial

1. INTRODUCTION AND RATIONALE Aortic Stenosis is the most common valvulopathy in the developed world. Approximately, 5% of people over 65 years old, in the general population, suffer from aortic stenosis, and the percentage increases with aging. The natural progress of the disease consists of a long-term asymptomatic period with low morbidity and mortality, followed by the symptomatic period. However, the symptoms manifestation (such as syncope, angina, dyspnea and heart failure) is accompanied by a serious increase in morbidity and mortality. The standard diagnostic technique is the transthoracic cardiac ultrasound. Transcatheter aortic valve implantation (TAVI) is an established and valuable treatment option for patients with both severe symptomatic aortic stenosis and increased risk for surgical aortic valve replacement (SAVR). The use of TAVI is rapidly expanding worldwide and the indications are widening into lower-risk populations in view of favorable outcomes among high and intermediate-risk patients.

Treatment with beta-blockers is a cornerstone for patients belonging to the wide range of heart failure, especially in those with heart failure with reduced ejection fraction. They are also widely used for the management of various arrhythmias and sudden cardiac death prevention as well as coronary artery disease. Severe valvulopathy is a major cause of heart failure and arrhythmogenesis but the role of beta-blockers in the valvulopathies per se is not clarified.

Increased left ventricular intracavital gradient leading to mid-ventricular or outflow tract obstruction with potentially severe hemodynamic compromise has been described in patients with left ventricular hypertrophy undergoing SAVR. The term "suicide left ventricle" has been adopted for this clinical setting and is possible to be revealed after TAVI as well. Beta-blocker administration is a recognized way to alleviate left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy and may also prevent or decrease intracavital gradients after TAVI. However, as a way to avoid conduction abnormalities and permanent pacemaker implantation (PPI) after TAVI, it is common for operators to withdraw beta-blockers before TAVI.

A large observational trial from the OCEAN-TAVI registry comparing with propensity-matching patients undergoing TAVI with or without beta-blockers exhibited no significant differences in PPI between the two groups. Another observational trial investigating arrhythmic risk in TAVI patients regarding beta-blocker administration concluded that beta-blocker withdrawal was associated with increased arrhythmic burden and more PPIs. The latter paradoxical outcome was attributed by the authors to sick sinus syndrome revelation secondary to increased atrial fibrillation (AF) development in patients who discontinued beta-blockers.

Clinical data concerning this topic are scarce and the safety and efficiency of beta-blockers during and post-TAVI are not well-documented. The aim of this clinical trial is to investigate the impact of beta-blocker administration among patients undergoing TAVI. 2. DESCRIPTION OF THE PROTOCOL 2.1 Study design This a prospective, multicentre, investigator-initiated, randomized clinical trial investigating the impact of beta-blockers administration among patients undergoing TAVI.