Clinical trial NCT04156295: Percutaneous Mitral Valve Intervention: Predicting Improvements in Left Ventricular Performance
Official title: Percutaneous Mitral Valve Intervention: Predicting Improvements in Left Ventricular Performance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mitral Regurgitation
Mitral Valve Insufficiency
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: King's College Hospital NHS Trust
name: Manchester Metropolitan University
First posted: 2019-11-07
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will be performed across two sites, namely Guy's and St Thomas' and King' College Hospitals. Patients will be recruited based on referral to GSTT or KCH, a diagnosis of mitral valve disease and clinical eligibility for percutaneous mitral valve intervention.

Brief summary: The purpose of this study is to assess the role of cardiac imaging combined with demographic, clinical, and biochemical parameters in predicting outcomes following percutaneous mitral valve intervention in order to facilitate more careful risk stratification, interventional planning and avoidance of high risk futile procedures.The principle objective of this study is to determine if transthoracic echocardiography (TTE) can predict changes in left ventricular (LV) size and function following percutaneous mitral valve intervention (PMVI).

Detailed description: Mitral regurgitation (MR) is one of the most common valvular abnormalities affecting an estimated 5 million worldwide. Within Europe it has been recognised as the second most common valve lesion requiring surgery. By 2030, prevalence is expected to more than double as a consequence of an ageing population. Mitral regurgitation can be caused by a range of aetiologies including degenerative or functional abnormalities. Regardless of the underlying cause, severe MR commonly leads to symptoms of breathlessness and/or arrhythmia, frequently requiring hospital admission secondary to decompensated heart failure. Aside from a reduction in cardiac output secondary to the primary lesion, chronic MR also leads to significant left ventricular remodelling with dilatation and dysfunction of the left ventricle. Left untreated, such a lesion carries an annual mortality of 5%.

Conventional mitral valve surgery is the recognised gold standard therapy for patients with moderate to severe or severe mitral regurgitation, symptoms and LV impairment. However for patients with multiple comorbidities and a high surgical risk, percutaneous mitral valve intervention presents a novel viable therapeutic option.

Percutaneous mitral valve intervention offers an alternative to conventional open heart surgery via a minimally invasive route. One such percutaneous technology is the Mitra-Clip which is deployed and positioned to grasp valve leaflets and create a double orifice. The primary aim is to reduce the degree of mitral regurgitation with additional clinical outcomes focussed on symptom relief, enhanced lifestyle and longevity.

Foundation studies focussed on Mitra-clip have supported the usefulness of percutaneous technology with mainstay papers reporting a reduction in mitral regurgitation with improvement in clinical symptoms and quality of life. When compared to conventional surgery this approach has demonstrated high levels of safety and efficacy. Current research has also acknowledged positive left ventricular (LV) remodelling with improvement in ejection fraction and reduction in LV size as a consequence of percutaneous mitral valve intervention.

Cardiac imaging is crucial in the preoperative, device deployment and post intervention phases of PMVI. TTE, recognised as the mainstay imaging modality in valvular heart disease, allows for both quantitative and qualitative evaluation of mitral regurgitation. Moreover, comprehensive assessment of LV size and function can be performed. More recently, very early myocardial impairment has been demonstrated using a number of sophisticated echocardiographic markers. Additionally, functional testing including exercise stress echocardiography has proven diagnostic relevance when uncovering valvular causes of dyspnoea. Unfortunately the usefulness of both of these echo derived markers in patients with significant mitral regurgitation undergoing PMVI is poorly understood, demonstrating the need for further characterisation of these markers in this cohort.

The aim is to assess the impact of percutaneous mitral valve intervention on markers of LV function and the usefulness of functional testing in predicting changes in LV performance. The investigators propose that cardiac imaging, functional testing and clinical and laboratory data can be used to predict changes in left ventricular size and function following percutaneous mitral valve intervention.

Trial objectives and purpose

The purpose of this study is to assess the role of cardiac imaging combined with demographic, clinical, and biochemical parameters in predicting outcomes following percutaneous mitral valve intervention in order to facilitate more careful risk stratification, interventional planning and avoidance of high risk futile procedures.

The principle objective of this study is to determine if transthoracic echocardiography (TTE) can predict changes in left ventricular (LV) size and function following percutaneous mitral valve intervention (PMVI).

The secondary objectives are:

1. Evaluation of the usefulness of functional testing, namely exercise stress echocardiography (ESE), and its role in discriminating mitral regurgitation (MR) patients who demonstrate improved LV parameters following PMVI from those who do not.
2. Assessment of the relationship between TTE, ESE, Cardiac Magnetic Resonance (CMR) and Cardiac Computed Tomography (CT) for these patients.
3. Assessment of the relationship between improvements in LV performance and the degree of residual MR.
4. Exploration and characterisation of the relationship between changes in LV parameters and clinical outcomes.
5. Assessment of the usefulness of TTE parameters combined with functional, clinical, biochemical parameters in providing a better prediction of postoperative outcomes following PMVI.
6. Exploration of the relationship between improved outcomes and right ventricular (RV) size and function and right ventricular systolic pressures (RVSP).

Eligibility criteria: Inclusion Criteria:

1. 18 years or older
2. At least moderate to severe symptomatic mitral regurgitation
3. Life expectancy greater than 1 year post intervention
4. Able to give informed consent

Exclusion Criteria:

1. Patient not eligible for percutaneous mitral valve intervention.

Primary outcomes:
measure: Change in LV size
timeFrame: Within 3-6 months post intervention
measure: Change in LV volume (2D)
timeFrame: Within 3-6 months post intervention
measure: Change in LV volume (3D)
timeFrame: Within 3-6 months post intervention
measure: Change in LV systolic function (2D EF)
timeFrame: Within 3-6 months post intervention
measure: Change in LV systolic function (3D EF)
timeFrame: Within 3-6 months post intervention
measure: Change in LV systolic function (GLS)
timeFrame: Within 3-6 months post intervention
measure: Change in LV systolic function (EF1)
timeFrame: Within 3-6 months post intervention
Secondary outcomes:
measure: Change in clinical outcomes - symptoms
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - NYHA class
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - Quality of Life
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - 6MWT
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - NT Pro BNP
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - ST2, Gal-3, TropT
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - residual MR
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - RV S'
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - RV Strain
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - RV Strain Rate
timeFrame: Within 3-6 months post intervention
measure: Change in clinical outcomes - RVSP
timeFrame: Within 3-6 months post intervention
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Bernard Prendergast, B Med Sc DM
role: PRINCIPAL_INVESTIGATOR
References:
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