Aims : The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.Methods and results : Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.Conclusions : Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Background— Recent studies and current clinical observations suggest that some patients with severe aortic stenosis on the basis of aortic valve area may paradoxically have a relatively low gradient despite the presence of a preserved left ventricular (LV) ejection fraction. The objective of the present study was to document the prevalence, potential mechanisms, and clinical relevance of this phenomenon. Methods and Results— We retrospectively studied the clinical and Doppler echocardiographic data of 512 consecutive patients with severe aortic stenosis (indexed aortic valve area ≤0.6 cm ² · m ⁻² ) and preserved LV ejection fraction (≥50%). Of these patients, 331 (65%) had normal LV flow output defined as a stroke volume index >35 mL · m ² , and 181 (35%) had paradoxically low-flow output defined as stroke volume index ≤35 mL · m ⁻² . When compared with normal flow patients, low-flow patients had a higher prevalence of female gender ( P <0.05), a lower transvalvular gradient (32±17 versus 40±15 mm Hg; P <0.001), a lower LV diastolic volume index (52±12 versus 59±13 mL · m ⁻² ; P <0.001), lower LV ejection fraction (62±8% versus 68±7%; P <0.001), a higher level of LV global afterload reflected by a higher valvulo-arterial impedance (5.3±1.3 versus 4.1±0.7 mm Hg · mL ⁻¹ · m ⁻² ; P 5.5 mm Hg · mL ⁻¹ · m ⁻² (hazard ratio, 2.6; 95% CI, 1.2 to 5.7; P =0.017), and medical treatment (hazard ratio, 3.3; 95% CI, 1.8 to 6.7; P =0.0003) were independently associated with increased mortality. Conclusion— Patients with severe aortic stenosis may have low transvalvular flow and low gradients despite normal LV ejection fraction. A comprehensive evaluation shows that this pattern is in fact consistent with a more advanced stage of the disease and has a poorer prognosis. Such findings are clinically relevant because this condition may often be misdiagnosed, which leads to a neglect and/or an underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery.

Prosthesis-patient mismatch (PPM) is present when the effective orifice area of the inserted prosthetic valve is too small in relation to body size. Its main haemodynamic consequence is to generate higher than expected gradients through normally functioning prosthetic valves. This review updates the present knowledge about the impact of PPM on clinical outcomes. PPM is common (20–70% of aortic valve replacements) and has been shown to be associated with worse haemodynamic function, less regression of left ventricular hypertrophy, more cardiac events, and lower survival. Moreover, as opposed to most other risk factors, PPM can largely be prevented by using a prospective strategy at the time of operation.

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Imaging is pivotal in the evaluation of native valve regurgitation and echocardiography is the primary imaging modality for this purpose. The imaging assessment of valvular regurgitation should integrate quantification of the regurgitation, assessment of the valve anatomy and function, and the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation largely relies on the results of imaging. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing native valve regurgitation. The present document aims to present clinical guidance for the multi-modality imaging assessment of native valvular regurgitation.