MItral or Severe TRicuspid vALvular regurgitation: the MISTRAL study

MItral or Severe TRicuspid vALvular regurgitation: the MISTRAL study

Mitral and tricuspid regurgitation are among the most prevalent valvular heart diseases and are associated with significant morbidity, mortality and impaired quality of life. Despite major advances in both surgical and transcatheter therapies, substantial gaps remain between guideline recommendations and real-world clinical practice, with many eligible patients not receiving valve intervention.

Over the last decade, the treatment landscape has evolved rapidly. For mitral regurgitation, transcatheter edge-to-edge repair (TEER) and other emerging transcatheter technologies have expanded therapeutic options for both primary and secondary disease. Similarly, for tricuspid regurgitation, transcatheter repair and replacement therapies have emerged as promising alternatives for patients at high surgical risk. In parallel, the 2025 ESC/ EACTS Guidelines have further emphasised the role of multidisciplinary Heart Team assessment, multimodality imaging, and timely intervention to optimise patient outcomes.

However, important knowledge gaps remain regarding the real-world implementation of those recommendations worldwide, including patient selection for intervention, the adoption of transcatheter therapies, the use of multimodality imaging, and potential sex-related differences in management and outcomes.

This study will provide a contemporary overview of the management of severe mitral and tricuspid regurgitation worldwide. By capturing current clinical practice, the MISTRAL study aims to assess adherence to guideline recommendations, identify areas for improvement, and generate insights that may help shape future clinical practice and patient care.

Objectives

The primary objective of the GRASP-MISTRAL study is to assess real-world adherence to the 2025 ESC guideline recommendations for the management of consecutive patients with severe mitral or tricuspid regurgitation encountered in routine practice.

Secondary objectives

To identify the main patient - and disease related reasons for non-adherence to guideline-recommended care, including clinical complexity, frailty, comorbidity burden, procedural ineligibility and patient preference.
To evaluate variations in management and guideline adherence according to center type, institutional setting, geographic region, and local resource availability, with particular attention to potential underdiagnosis and undertreatment.
To assess sex-related differences in clinical presentation, referral pathways, treatment allocation, procedural eligibility, and guideline adherence in patients with severe MR or TR.
To describe the use and clinical impact of multidisciplinary Heart Team evaluation and multimodality imaging in clinical decision-making.
To characterise contemporary treatment pathways in severe MR and TR, including medical, surgical, and transcatheter management.
To evaluate variable ( patients' and imaging characteristics) associated with good response to TEER.
To assess real-world practice regarding amyloidosis diagnosis screening in case of red flags.

Ancillaries analyses will be performed on collected medical imaging (ECG, echocardiography, CMR) after central reading.

Characteristics

The study is prospective, longitudinal, multicenter, international and observational.

The total length of the data collection is 10 months (5-month overall recruitment and 5-month follow-up).

Any scheduled study visit will coincide with any visit performed by the subject according to standard clinical practice, without interfering with the investigators healthcare tasks.

Population

Consecutive enrollment of all consenting patients matching eligibility criteria during a 3-month recruitment period per participating center.

Inclusion criteria:

Age > or = 18 years
Severe TR of any presentation ( either primary or secondary, with or without RV dysfunction, on native valve or already operated on, isolated or associated with any left sided heart diseases including left valvular heart diseases) AND/ OR
Severe MR of any presentation (either primary or secondary, with or without LV dysfunction, on native or already operated on, isolated or associated with any other VHD).

Exclusion criteria:

Refusal to participate/ sign informed consent
Patient under legal protection or deprived of liberty
Life expectancy < 6 months according to investigator's judgement
Severe pre-capillary pulmonary hypertension
Active infective endocarditis at enrolment
Patient with durable mechanical circulatory support
Patient with congenital heart disease ( except for bicuspid aortic valve)
Women with ongoing pregnancy

Steering Committee

A Registry Steering Committee is composed of one national coordinator per participating country. The National Cardiac Societies are responsible for the selection of the national coordinators who are in charge of the registry implementation and running of the registry in their respective countries.

Study Status

The study is currently in the start-up phase with identification of participating sites, ethics submission and administrative requirements ongoing.

Start of patient recruitment is currently expected in Q4.

Should you have any questions about the study, please contact: registries@escardio.org.

Study Task Force

Professor Claire Bouleti

Professor Agnes A Pasquet

Professor Erwan Donal

Professor Stephan Windecker

Doctor Julia Grapsa

Professor Davide Capodanno

Doctor Victoria Delgado

Professor Bogdan Alexandru Popescu

Assistant Professor Tomaz Podlesnikar

Doctor Elena Romero Dorta

Professor Jadranka Separovic Hanzevacki

Associate Professor Marianna Adamo

Doctor Gaby Aphram

Doctor Alexandre Altes