Hypertrophic Cardiomyopathy
Conditions
Keywords
Coronary sinus reducer, angina, myocardial ischaemia, non-obstructive hypertrophic cardiomyopathy, microvascular dysfunction
Brief summary
Hypertrophic cardiomyopathy (HCM) is a common heart condition in which the heart muscle becomes abnormally thick. In non-obstructive HCM, blood flow out of the heart is not blocked, but many patients still experience chest pain, breathlessness and limitation of daily activities. This may be because the small blood vessels within the thickened heart muscle do not supply enough blood and oxygen, particularly during exercise or stress. Current treatment options for symptomatic non-obstructive HCM are limited. This study will test a small device called the coronary sinus reducer (CSR), which is placed into a vein of the heart using a catheter. The CSR is designed to improve blood flow to areas of heart muscle that are short of blood supply. Fifty adults with non-obstructive HCM, ongoing symptoms and reduced blood supply on a heart MRI scan will take part. Participants will be randomly assigned to receive either CSR implantation or a placebo procedure. Neither participants nor the follow-up research team will know which procedure was performed until the 6-month follow-up assessments are complete. The investigators will use detailed heart MRI scans to measure blood flow, a smartphone app to record daily symptoms, coronary sinus blood tests to look for biochemical evidence of reduced oxygen supply, and invasive coronary physiology measurements to assess the small blood vessels of the heart. The main aim is to find out whether the CSR improves blood flow and reduces symptoms. The results may identify a new treatment option for patients with non-obstructive HCM and improve understanding of the disease.
Detailed description
Type of study: Double-blind, randomised, placebo-controlled trial of 50 adult patients with symptomatic non-obstructive HCM and perfusion defects on stress perfusion CMR. Patients will be assessed at 3 time points: enrolment, randomisation and follow-up. Enrolment assessment will consist of symptom questionnaires, onboarding onto the ORBITA-app (a smartphone application for daily symptom reporting), and reviewing the stress perfusion CMR (needed on clinical grounds for enrolment to the study). Patients will then enter a 2-week period prior to randomisation during which participants input their symptoms into the ORBITA-app. Patients without any symptoms during this period will be withdrawn from the study. Eligible participants will proceed to a blinded catheter laboratory procedure involving internal jugular venous access for right atrial pressure measurement and coronary sinus sampling, and randomisation 1:1 to CSR implantation or placebo. Blinding will be maintained for participants with headphones for auditory isolation and a deep level of conscious sedation. A subsection of suitable and consenting participants will also undergo invasive coronary physiology assessment, including coronary angiography, pressure-wire assessment and thermodilution measurements. Participants who are not suitable or who do not consent to invasive coronary physiology will continue in the main study. The invasive physiology assessment will be completed before randomisation so that baseline measurements are not influenced by treatment allocation. Participants will enter a 6-month blinded follow-up period with daily symptom reporting via the ORBITA-app. After 6 months, participants will return for repeat symptom questionnaires and stress perfusion CMR. Participants included in the invasive physiology substudy will be invited to undergo a planned repeat research coronary angiography and invasive physiology assessment at 6 months.
Interventions
DEVICECoronary sinus reducer
The Shockwave Reducer (coronary sinus reducer) is intended to create a controlled narrowing that increases coronary sinus pressure and redistributes venous blood flow from epicardial to subendocardial regions, thereby improving myocardial perfusion in areas of microvascular ischaemia.
PROCEDUREPlacebo procedure
Participants in the placebo group will not have the device implanted, but will remain sedated in the catheter laboratory for 15-30 minutes so that the experience is similar and blinding is maintained.
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinding will be supported by conscious sedation, headphones for auditory isolation, separation of blinded and unblinded staff, standardised documentation and discharge procedures, and formal blinding assessment at discharge and before unblinding. Participants will be informed during consent that they may receive CSR or placebo and will remain blinded until the 6-month follow-up.
Intervention model description
Participants will be randomised 1:1 to CSR or placebo; no device will be deployed in the placebo arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Non-obstructive hypertrophic cardiomyopathy (LVOT gradient ≤30 mmHg at rest on echocardiography) * Ongoing symptoms despite current medical therapy * Significant perfusion defects (≥ 2 myocardial segments) on stress perfusion CMR
Exclusion criteria
* Age \< 18 years * Left ventricular impairment LVEF \<55% * Severe renal impairment (Estimated glomerular filtration rate \<30mL/min/1.73m2) * Right atrial pressure ≥ 15 mmHg * Contraindication to CMR, gadolinium contrast, or adenosine. * Implantable cardioverter defibrillator or other device likely to compromise CMR interpretation. * Disease modifying drug treatment (mavacamten/aficamten) in past 6 months * Contraindication or intolerance to the required antiplatelet therapy * Obstructive epicardial coronary artery disease, defined as significant angiographic stenosis or physiologically significant disease at investigator discretion * Pregnancy * Inability to consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily symptom frequency during blinded 6-month follow-up | During blinded 6-month follow-up | Patient-reported. ORBITA-app daily symptom reporting. |
| The change in ratio of stress MBF in ischaemic versus non-ischaemic myocardial subsegments at 6 months comparing CSR and placebo groups | Baseline and 6 months | Quantitative stress perfusion CMR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coronary sinus lactate concentration during adenosine stress | Randomisation procedure | Coronary sinus blood samples obtained during adenosine stress and analysed immediately using a standard blood gas analyser to determine lactate concentration. |
| Coronary sinus pH during adenosine stress | Randomisation procedure | Coronary sinus blood samples obtained during adenosine stress and analysed immediately using a standard blood gas analyser to determine pH. |
| MacNew Heart Disease Health-related Quality of Life Questionnaire | Baseline and 6-month follow-up | Global score range 1 to 7; higher scores indicate better health-related quality of life. |
| Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) | Baseline and 6-month follow-up | The Kansas City Cardiomyopathy Questionnaire (KCCQ-23) Clinical Summary Score will be derived. Score range 0 to 100; higher scores indicate better health status. |
| EQ-5D-5L | Baseline and 6-month follow-up | EuroQol 5-Dimension 5-Level questionnaire. Each dimension is scored from 1 (no problems) to 5 (extreme problems); lower levels indicate better health status. |
| Index of microcirculatory resistance (IMR) | Baseline and 6-month follow-up in suitable and consenting participants included in the invasive physiology substudy | Coronary angiography with pressure-wire and thermodilution. |
| Coronary flow reserve (CFR) | Baseline and 6-month follow-up in suitable and consenting participants included in the invasive physiology substudy | Coronary angiography with pressure-wire and thermodilution. |
| Fractional flow reserve (FFR) | Baseline and 6-month follow-up in suitable and consenting participants included in the invasive physiology substudy | Coronary angiography with pressure-wire and thermodilution. |
| Absolute flow | Baseline and 6-month follow-up in suitable and consenting participants included in the invasive physiology substudy | Coronary angiography with pressure-wire and thermodilution. |
| Absolute resistance | Baseline and 6-month follow-up in suitable and consenting participants included in the invasive physiology substudy | Coronary angiography with pressure-wire and thermodilution. |
| Microvascular resistance reserve (MRR) | Baseline and 6-month follow-up in suitable and consenting participants included in the invasive physiology substudy | Coronary angiography with pressure-wire and thermodilution. |
Countries
United Kingdom
Outcome results
None listed