Percutaneous Mitral Valve Intervention: Predicting Improvements in Left Ventricular Performance

Mitral Regurgitation Clinical Trial

— PMVI-PiP  

Official title:

Percutaneous Mitral Valve Intervention: Predicting Improvements in Left Ventricular Performance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04156295
• Other study ID #: 248271
• Status: Completed
• Start date: March 20, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: July 2021
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mitral Regurgitation
• Mitral Valve Insufficiency

Locations

Country	Name	City	State
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London

Sponsors (3)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust	King's College Hospital NHS Trust, Manchester Metropolitan University

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

Attizzani GF, Fares A, Tam CC, Padaliya B, Mazzurco S, Popovich KL, Davis AC, Staunton E, Bezerra HG, Markowitz A, Simon DI, Costa MA, Sareyyupoglu B. Transapical Mitral Valve Implantation for the Treatment of Severe Native Mitral Valve Stenosis in a Prohibitive Surgical Risk Patient: Importance of Comprehensive Cardiac Computed Tomography Procedural Planning. JACC Cardiovasc Interv. 2015 Sep;8(11):1522-1525. doi: 10.1016/j.jcin.2015.04.025. Epub 2015 Aug 19. — View Citation

Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Sep 23;52(13):e1-142. doi: 10.1016/j.jacc.2008.05.007. — View Citation

De Backer O, Piazza N, Banai S, Lutter G, Maisano F, Herrmann HC, Franzen OW, Søndergaard L. Percutaneous transcatheter mitral valve replacement: an overview of devices in preclinical and early clinical evaluation. Circ Cardiovasc Interv. 2014 Jun;7(3):400-9. doi: 10.1161/CIRCINTERVENTIONS.114.001607. Review. — View Citation

Feldman T, Kar S, Elmariah S, Smart SC, Trento A, Siegel RJ, Apruzzese P, Fail P, Rinaldi MJ, Smalling RW, Hermiller JB, Heimansohn D, Gray WA, Grayburn PA, Mack MJ, Lim DS, Ailawadi G, Herrmann HC, Acker MA, Silvestry FE, Foster E, Wang A, Glower DD, Mauri L; EVEREST II Investigators. Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation: 5-Year Results of EVEREST II. J Am Coll Cardiol. 2015 Dec 29;66(25):2844-2854. doi: 10.1016/j.jacc.2015.10.018. — View Citation

Kelley C, Lazkani M, Farah J, Pershad A. Percutaneous mitral valve repair: A new treatment for mitral regurgitation. Indian Heart J. 2016 May-Jun;68(3):399-404. doi: 10.1016/j.ihj.2015.08.025. Epub 2016 Jan 12. Review. — View Citation

Pedrazzini GB, Faletra F, Vassalli G, Demertzis S, Moccetti T. Mitral regurgitation. Swiss Med Wkly. 2010 Jan 23;140(3-4):36-43. doi: smw-12893. Review. — View Citation

Poulin F, Carasso S, Horlick EM, Rakowski H, Lim KD, Finn H, Feindel CM, Greutmann M, Osten MD, Cusimano RJ, Woo A. Recovery of left ventricular mechanics after transcatheter aortic valve implantation: effects of baseline ventricular function and postprocedural aortic regurgitation. J Am Soc Echocardiogr. 2014 Nov;27(11):1133-42. doi: 10.1016/j.echo.2014.07.001. Epub 2014 Aug 7. — View Citation

Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Lung B, Lancellotti P, Pierard L, Price S, Schäfers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M; ESC Committee for Practice Guidelines (CPG); Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg. 2012 Oct;42(4):S1-44. doi: 10.1093/ejcts/ezs455. Epub 2012 Aug 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in LV size	Change in LV size by two dimensional linear dimension (cm)	Within 3-6 months post intervention
Primary	Change in LV volume (2D)	Change in LV volume by Simpson's Biplane method (mL)	Within 3-6 months post intervention
Primary	Change in LV volume (3D)	Change in LV volume by 3D volume method (mL)	Within 3-6 months post intervention
Primary	Change in LV systolic function (2D EF)	Change in LV systolic function by Ejection Fraction by 2D method (%)	Within 3-6 months post intervention
Primary	Change in LV systolic function (3D EF)	Change in LV systolic function by Ejection Fraction by 3D method (%)	Within 3-6 months post intervention
Primary	Change in LV systolic function (GLS)	Change in LV systolic function by Global Longitudinal strain (GLS) by 3D method	Within 3-6 months post intervention
Primary	Change in LV systolic function (EF1)	Change in LV systolic function by First Phase Ejection Fraction (%)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - symptoms	Change in symptoms ( Borg scoring; 0 - lowest = 10 - highest.)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - NYHA class	Change in NHYA class (NHYA class grading)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - Quality of Life	Change in quality of life (Short Form (36) Health Survey) (Score 0-most disability; 100-least disability).	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - 6MWT	Change in exercise capacity (6 min walk test distance in metres)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - NT Pro BNP	Change in biomarkers - NT pro BNP (ng/L)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - ST2, Gal-3, TropT	Change in biomarkers - ST2, Galectin 3 and Trop T (ng/mL)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - residual MR	Change in degree of mitral regurgitation (severity grading; 0-none or trivial; 4-severe)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - RV S'	Change in right ventricular performance (RV S' (ms))	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - RV Strain	Change in right ventricular performance (strain %)	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - RV Strain Rate	Change in right ventricular performance (s-1; (strain per time unit equals velocity difference per unit length).	Within 3-6 months post intervention
Secondary	Change in clinical outcomes - RVSP	Change in right ventricular performance (Right ventricular systolic pressure - mmHg)	Within 3-6 months post intervention