Aortic Stenosis
Conditions
Brief summary
Remote-AS aims to develop a remote digital monitoring cohort of people with AS and use these data to establish a digital twin intervention to personalise risks and benefits, and optimise the time of surgical or transcatheter aortic valve replacement (AVR) referral. Our digital solution will also seek modelling for optimal care for patients to whom AVR is indicated who choose not to undergo the procedure, supporting a patient-selected observational strategy for managing heart failure symptoms, facilitating patient education and self-care. Objectives of the study are: * To establish a large-scale interdisciplinary research program to drive implementation of substantial improvements to health care and/or health system effectiveness in patients with aortic stenosis (AS) * To establish a new model of patient-centred management strategy for asymptomatic severe AS to inform the optimal time at which valve intervention should take place * For patients to whom AVR is indicated who choose not to undergo the procedure, to support a patient-selected observational strategy for managing heart failure symptoms * To develop a digital twin with predictive capabilities of artificial intelligence (AI) for guiding the optimal timing of AVR in patients with asymptomatic severe AS Participants will be patients with asymptomatic moderate to severe native AS (n=160) (based on guideline-recommended diagnosis and care with peak aortic velocity \>3.5m/sec). Participants will undergo: Wearables: collection of physiological (e.g., blood pressure, heart rate, rhythm) and behavioural (physical activity) data through a wearable device ('smart watch'), collected through the comprehensive remote heart health monitoring and automated feedback delivery system app SMART. Patient reported outcome measures: KCCQ-CSS; EQ-5D-5L index score; "Toronto Aortic Stenosis" quality of life questionnaires. Advanced cardiovascular imaging: Cardiovascular magnetic resonance (CMR) imaging; 31phosphorus magnetic resonance spectroscopy (31P-MRS); proton magnetic resonance spectroscopy (1H-MRS); echocardiography. Comprehensive plasma proteome profiling: Plasma proteomic preparation coupled with the Orbitrap Astral mass spectrometer. Recording of clinical outcomes.
Interventions
None listed
Sponsors
Baker Heart and Diabetes Institute
The Alfred
Monash Medical Centre
St Vincent's Hospital Melbourne
University of Melbourne
Deakin University
La Trobe University
The University of Western Australia
Melbourne Health
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥18 years of age * Suitable to undergo MRI scans * With asymptomatic moderate to severe native AS (based on guideline-recommended diagnosis and care) * Eligible for Medicare * Ability and willingness to provide written and informed consent and to comply with the requirements of the study.
Exclusion criteria
* Serious comorbidity other than AS that limits the life expectancy (\<2 years), or affects study participation or outcome (severe frailty and mobility issues \[Rockwood frailty score \>6\], severe kidney disease eGFR\<30, infiltrative cardiomyopathy) * Known heart failure or reduced left ventricular ejection fraction (\<50%) * Moderate or above valvular pathology other than AS * Contra-indications to CMR (including presence of foreign metallic bodies) * Known hypersensitivity to adenosine (ever requiring hospital admission with asthma or chronic obstructive pulmonary disease) or gadolinium * Significant renal impairment (eGFR\<30ml/min/m2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LV hypertrophy | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Left ventricular mass index\[g/m2\], imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
| Diastolic function - Mitral inflow E/A ratio | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Mitral inflow E/A ratio, imaging endpoint on echocardiography |
| Diastolic function - average E/e' ratio | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Average E/e' ratio, imaging endpoint on echocardiography |
| Diastolic function - septal e' velocity | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Septal e' velocity, imaging endpoint on echocardiography. |
| Diastolic function - lateral e' velocity | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Lateral e' velocity, imaging endpoint on echocardiography. |
| Diastolic function - left atrial volume index | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Left atrial volume index, imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
| Diastolic function - peak diastolic strain rate | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Peak diastolic strain rate, imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
| Global longitudinal strain (GLS) | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
| Myocardial perfusion | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Rest and adenosine stress CMR-measured myocardial blood flow and myocardial perfusion reserve imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
| Myocardial energetics index | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | 31P-MRS-measured phosphocreatine to ATP ratio, imaging endpoint on cardiovascular magnetic resonance spectroscopy (MRS) |
| Myocardial triglyceride content | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Imaging endpoint as measured by 1H-MRS |
| Myocardial fibrosis index - extra cellular volume [ECV] fraction | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Extra cellular volume \[ECV\] fraction, tissue characteristic imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
| Myocardial fibrosis index - index-ECV | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Index-ECV, imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
| Myocardial fibrosis index - scar percentage | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Late gadolinium enhancement imaging-assessed scar percentage, imaging endpoint on cardiovascular magnetic resonance imaging (CMR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physical activity | Daily for the duration of the participant's participation in the study (six months post guideline-indicated AVR, or if AVR is not performed until completion of the overall study, i.e. maximum 4 years, whichever comes first). | Digital endpoint measured from wearable devices and processed via the SMART architecture |
| Blood pressure | Daily for the duration of the participant's participation in the study (six months post guideline-indicated AVR, or if AVR is not performed until completion of the overall study, i.e. maximum 4 years, whichever comes first). | Digital endpoint measured from wearable devices and processed via the SMART architecture |
| Heart rhythm | Daily for the duration of the participant's participation in the study (six months post guideline-indicated AVR, or if AVR is not performed until completion of the overall study, i.e. maximum 4 years, whichever comes first). | Digital endpoint measured from wearable devices and processed via the SMART architecture |
| Heart rate variability | Daily for the duration of the participant's participation in the study (six months post guideline-indicated AVR, or if AVR is not performed until completion of the overall study, i.e. maximum 4 years, whichever comes first). | Digital endpoint measured from wearable devices and processed via the SMART architecture |
| Oxygen saturation | Daily for the duration of the participant's participation in the study (six months post guideline-indicated AVR, or if AVR is not performed until completion of the overall study, i.e. maximum 4 years, whichever comes first). | Digital endpoint measured from wearable devices and processed via the SMART architecture |
| NTproBNP | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Blood biomarker |
| High sensitivity cardiac troponin (hscTNT) | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Blood biomarker |
| Proteomics | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Advanced, label-free quantitative mass spectrometry-based proteomics blood biomarkers |
| Quality-of-Life questionnaire: KCCQ-CSS | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Patient-reported outcome measure via Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score \[KCCQ-CSS\] |
| Quality-of-Life questionnaire: EQ-5D-5L | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Patient-reported outcome measure via EuroQoL 5-dimension 5-level \[EQ-5D-5L\] index score |
| Quality-of-Life questionnaire: Toronto AS QoL | 6-monthly repeat assessments prior to AVR, with a concluding assessment 6 months after AVR | Patient-reported outcome measure via "Toronto Aortic Stenosis" quality of life questionnaire |
Contacts
CONTACTSjoerd Levelt, PhD
Outcome results
None listed