Predicting improvements in left ventricular performance
Research type
Research Study
Full title
Percutaneous Mitral Valve Intervention: Predicting improvements in left ventricular performance
IRAS ID
248271
Contact name
Kelly Victor
Contact email
Sponsor organisation
Guy's and St Thomas NHS Foundation Trust
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Summary of Research
Outline of the project
Mitral regurgitation (MR) occurs when the mitral valve leaflets are not able to close appropriately resulting in the backflow of blood. This can occur due to problems with the valve leaflets themselves or changes in the size and shape of the main pumping chamber, the left ventricle. Open heart mitral valve surgery is currently the mainstay treatment for MR patients. However depending on a number of considerations, some patients who have additional health concerns and an increased operation risk may be suitable for a device inserted through the skin. This is performed to try to help with the MR and offer symptom relief for patients. Unfortunately not all patients are suitable.Currently we use echocardiography to help us to select patient who would be suitable for such a procedure. This allows us to interrogate the structure of the mitral valve and how well the left ventricle contracts. In some cases we also use exercise and walking tests to assist with decision-making. Unfortunately the usefulness of these markers in patients with mitral regurgitation undergoing minimally invasive mitral valve intervention is poorly understood, and we are still unable to predict which patients will see the most improvement in symptoms.
What is the purpose of the study?
The purpose of this study is to see if cardiac imaging combined with other information such as patient symptoms, blood results, and exercise capacity can assist in predicting patients who will see an improvement in outcomes following percutaneous mitral valve procedures. This will allow us to perform more careful risk analysis for patients, assist in the most appropriate selection of devices and help to avoid procedures likely to be ineffective in terms of outcomes for patients.Summary of Results
AIMS AND OBJECTIVE:
This was a pilot study aimed at investigating the role of cardiac ultrasound, exercise testing, and medical and blood data in predicting changes in cardiac performance, symptoms and quality of life following keyhole heart valve repair. The study was performed in order to look into ways for more careful risk assessment, better interventional planning and so as to avoid operations which carried an unbalanced high risk for patients. I hypothesised that the combination of echocardiography ( or echo which is cardiac ultrasound) with clinical, exercise and blood information would help to identify those patients who experience the greatest relief from symptoms. The principal objective of this study was to determine whether echo could predict changes in the main heart chamber (left ventricular (LV)) size and function following key hole mitral valve repair (TMVR).The secondary objectives were to: (1) evaluate the practicality and usefulness of walk and bike testing pre surgery, and their role in differentiating patients who see an improvement in quality of life and in their echo findings, from those who do not; (2) assess the relationship between improvements in heart performance and the degree of heart valve leak that remains after the repair; (3) explore the relationship between changes in LV parameters and clinical outcomes (walk distance, degree of breathless); (4) assess the usefulness of echo parameters combined with exercise, clinical and blood data (obtained pre surgery) in providing a better prediction of post-procedural outcomes following mitral valve repair.
METHODOLOGY:
The methodology for this study was as outlined in the protocol which is publicly available on clinicaltrials.gov. Registration number: NCT04156295. Ethical approval for this study was obtained through the London Bridge REC (IRAS: 248271).RESULTS:
A total of eight patients were recruited to this research study. We were hoping for a minimum of 32 patients in order for the findings of the study to be useful, and more generalisable to the population. Unfortunately, all research ceased in March 2020 due to the COVID-19 pandemic. As a result, no further recruitment was permitted and patients were not allowed to attend the hospital for research purposes alone. Where patients were scheduled for clinical follow up, this was undertaken virtually by telephone, thereby precluding the possibility of scheduled research activity aligned with clinical face to face appointments. However, where data was missing, I was able to obtain follow up quality of life data via post. The findings of this study have been described below:1. Demographic and clinical data
Within the cohort, there was an even split between men and women with an average age of 77 years. All were of white ethnicity. Three quarters of the cohort (75%) had either coronary artery disease (CAD) or atrial fibrillation (AF), and half (50%) had hypertension. Two patients had previously undergone cardiac surgery, two patients had intra-cardiac devices (pacemaker or ICD) and one patient had undergone both cardiac surgery and device implantation.
All patients presented to hospital with shortness of breath. Two had a previous diagnosis of heart failure and four had pulmonary and/or peripheral oedema. All patients were in New York heart association (NYHA) classification IV at presentation and five of seven patients reported symptomatic improvement at follow up after valve repair.
2. Intervention
All eight patients underwent keyhole repair using at least one device. Four patients received two devices and one received three. Following the procedure one patient developed urinary retention and another had confusion and acidosis. A separate patient was re-intubation and required transfer to the intensive care unit on day 2 of recovery due to a hospital acquired pneumonia. This patient was known to have underlying chronic obstructive pulmonary disease.
Unfortunately, one patient died approximately four weeks following the procedure. A further patient elected to undergo subsequent high risk mitral valve replacement at a different institution. Two patients were re-admitted to hospital with symptoms of breathlessness within one week - on both occasions the TMVR was deemed satisfactory based on echo examination, and discharge was possible within three days after a review of medicines.
3. Quality of life
Quality of life (QoL) was assessed using eight different categories integrating physical and emotional function. Eight patients completed the pre-procedural questionnaire but matching data were only available for six (1 death and 1 lost to follow up). Analysis showed that three patients reported an improvement in quality of life, two patients experienced deterioration and one saw no real change. The degree of improvement or deterioration varied across the cohort and given the small sample size and risk of bias, further analysis was not performed.
4. Echocardiography
All patients underwent baseline echocardiography (echo) in addition to pre- and peri-procedural transoesophageal echocardiography (TOE).
All patients had severe MR (mitral regurgitation) based upon integrative echo and TOE assessment and half of the cohort had secondary MR. There were three patients with primary MR. The last patient had undergone previous MitraClip implantation and the residual MR jet was complex. Accurate quantitative measurements were not possible in all patients due to MR jet eccentricity. Three patients had a dilated LV and three had impaired heart function. Three patients had a dilated right ventricle.
Post-procedural TTE (0-4 days) demonstrated moderate to severe residual MR in two patients. This had been noted on the peri-procedural TOE, but no further transcatheter intervention was possible. Before and after surgery comparisons could not be drawn due to limited data.
5. Functional testing
At baseline, seven patients were able to perform a six minute walk test (6MWT). One participant was unable to perform the test due to severe fatigue and breathlessness at rest, and one walked 5:32 mins before terminating the test. The mean walking distance was 187m (range 120-245m). At follow up, only two patients performed a 6MWT. One was the patient who was unable to perform the test at baseline so no comparison could be drawn. The other reported a significant deterioration in walking distance (from 180m to 118m) accompanied by a decline in quality of life scores and reduced LV function. Unfortunately, the remaining five patients were unable to attend for follow up assessment as a result of the COVID-19 pandemic.
6. Laboratory results
Baseline blood results were obtained for all patients but additional research samples could not be processed due to batching and the reallocation of resources during the COVID-19 pandemic. Therefore, these results are not available. Post-intervention results were also limited due to reduced face to face follow up, batching and reallocation of resources. Post surgery NT-pro BNP (a marker of heart injury) was available for three patients.
LIMITATIONS:
Unfortunately, the study outlined was significantly curtailed by the effects of the COVID-19 pandemic. Firstly, restrictions on research project activity meant that no further patients could be recruited. Although in-patient recruitment was technically feasible, this would have had no bearing on the study since all TMVR procedures were cancelled during the pandemic. Secondly, all patients scheduled for routine clinical follow up were advised to avoid hospital attendance, meaning that follow up tests including echo, 6MWTs and blood tests could not be performed. This restricted my capacity to draw pre- and post- surgery comparisons. Thirdly, no research blood samples were processed due to limited recruitment and follow up, and as a consequence of the reallocation of blood centre resources (personnel and equipment). Furthermore, follow up QoL questionnaires were sent to recruited patients for completion during the national COVID-19 lock down when the prevailing circumstances would have had significant impact on responses relating to physical and emotion health and assessment of social interactions.CONCLUSION:
This pilot study was unable to successfully meet the proposed objectives as a result of the COVID-19 pandemic and limited recruitment. As a consequence, no solid conclusions could be determined from this work.Reflecting on the small patient cohort recruited, I assessed a combination of patients with primary and secondary MR who underwent TMVR. There was variation across the cohort in terms of comorbidities and underlying left ventricular function. As reported in the literature, there was variation in the extent of symptom relief and QoL following intervention. I hope that further research in this area will result in the identification of echocardiographic and exercise parameters that enable better selection of patients for TMVR.
REC name
London - London Bridge Research Ethics Committee
REC reference
19/LO/0619
Date of REC Opinion
17 Jun 2019
REC opinion
Further Information Favourable Opinion