Trans-coronary Cooling and Dilution for Cardioprotection During Revascularisation for ST-elevation Myocardial Infarction
- Conditions
- Myocardial InfarctionReperfusion Injury, Myocardial
- Interventions
- Other: Transcoronary cooling and dilutionOther: Standard of care
- Registration Number
- NCT06128993
- Lead Sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Brief Summary
A heart attack (myocardial infarction) occurs when an artery supplying blood to the heart is suddenly blocked resulting in damage to the heart muscle.
Patients presenting to hospital with a heart attack undergo an immediate angiogram (x-ray of the arteries in the heart) and are usually treated immediately with a balloon and stent to open their blocked artery. This procedure is called "primary percutaneous coronary intervention" (or primary PCI for short).
An angiogram is a routine procedure that involves insertion of fine plastic tube (catheter) into either the groin or wrist under local anaesthetic. The tube is passed into the artery in the heart and X-ray pictures are taken to find out if the arteries are blocked. Blocked arteries can usually be opened by passing a small balloon into the artery, via the fine plastic tube followed by placement of a stent (a fine metal coil) into the artery to prevent it from blocking again.
Although this treatment is very successful, it can result in damage to the heart muscle when the artery is opened. Cooling the entire body has been shown to reduce heart muscle damage during heart attacks in some patients but not in others; however, it is uncomfortable due to the shivering, expensive and can result in delays in opening the blocked artery.
The investigators are conducting a series of research studies to find out if cooling the heart muscle directly through the catheter being used for the normal primary angioplasty treatment using room temperature may be effective in preserving heart muscle, without the shortcomings of entire body cooling.
The investigators have already published an initial series of ten cases in which this treatment appeared to be feasible without causing significant clinical problems.
The present study is a pilot study designed to assess the rate of patient recruitment and feasibility of this new treatment while exploring some detailed outcomes measuring the restoration of blood flow within the coronary artery at the end of the procedure.
Ultimately if the present pilot study is successful, the investigators plan to go on to undertake a much larger randomised outcome study to determine definitively whether this treatment can help reduce heart attack size.
- Detailed Description
The study population will comprise 60 patients with ST-Elevation Myocardial Infarction (STEMI) presenting to Harefield Hospital undergoing primary percutaneous coronary intervention (PCI).
The primary aim of this pilot trial is to investigate the recruitment rate feasibility and safety of undertaking a randomised trial of simple intracoronary coronary cooling and dilution through the guiding catheter during primary PCI for STEMI to reduce myocardial infarction size.
The secondary aims are as follows:
1. The study will explore the invasive haemodynamic assessment of coronary flow and microvascular function
2. The study will explore blood biomarkers before and after treatment for myocardial infarction
3. The study will explore myocardial salvage after treatment for myocardial infarction with magnetic resonance imaging (MRI) and subsequent final infarct size.
Patients will be randomised 1:1 in the catheterisation lab when coronary angiography has demonstrated a target lesion with proposed primary PCI. Patients randomised to the intervention will receive transcatheter cooling and dilution in addition to usual clinical care. Patients randomised to control will receive usual care alone.
A combined thermistor and pressure wire Coroventis™ (Abbott Vascular) with comparable tip stiffness to standard guidewires and in routine clinical use, will be used to perform the primary PCI procedure and to measure intracoronary temperature and pressure continually throughout all procedures in all patients. This will therefore limit the procedure to a simple single wire throughout strategy in most cases. In the event that the wire fails to function properly during or after the PCI procedure it may be changed for a new wire using standard interventional techniques as appropriate
Patients randomised to intracoronary cooling and dilution(n=30), will receive an intracoronary infusion of room temperature 0.9% Normal Saline solution through the guiding catheter which will commence immediately prior to crossing the coronary occlusion with the guidewire. Using a 3-way tap in the procedural manifold an infusion pressure of 150mmHg above systolic blood pressure achieved with a pressure bag will be used to achieve a target intracoronary temperature of 6-8 C° below the baseline temperature. The infusion will continue until 10 minutes after the lesion is crossed and distal flow is restored, with only brief interruptions as required for the clinical procedure. A maximum volume of 750ml will be infused. The primary angioplasty procedure itself will be undertaken according to standard local practice. Patients randomised to the control group (n=30) will undergo primary PCI according to standard local practice.
A complete physiological study including Fractional flow reserve (FFR), resting full-cycle ratio (RFR), coronary flow reserve (CFR), resistive reserve ratio (RRR) and index of microvascular resistance (IMR) to assess microcirculation will be measured 10 minutes after reperfusion in all patients.
Patients will go on to have blood taken on the next day for the analysis of a panel of biomarkers and comparison with pre-procedure levels and in addition to have a cardiac MRI scan prior to discharge and at 6 months.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Clinical ST-elevation myocardial infarction or equivalent (e.g. new onset LBBB)
- <12 Hrs after symptom onset
- Thrombolysis in myocardial infarction (TIMI) 0-1 coronary flow in a target vessel
- History of severe asthma
- Pregnancy
- Severe concomitant disease or conditions with a life expectancy of less than one year.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Transcoronary cooling and dilution Transcoronary cooling and dilution Intervention with transcoronary cooling and dilution Standard of care Standard of care Routine clinical care
- Primary Outcome Measures
Name Time Method Feasibility (Number of studies where all the planned measurements have been collected / total studies) 1 year Number of studies where all the planned measurements have been collected / total studies
Safety (Adverse events should not be significantly higher in the treatment arm compared to control, nor plausibly caused by the treatment) 1 year Adverse events should not be significantly higher in the treatment arm compared to control, nor plausibly caused by the treatment as assessed by CTCAE v5.0
Recruitment rate 1 year Patients recruited per month
- Secondary Outcome Measures
Name Time Method Cardiovascular mortality at 12 months 12 months Cardiovascular mortality at 12 months
First pass microvascular obstruction extent (FP MVO) 1-3 days Measured in 3 SAX levels to provide an index of %LV FP MVO
Index of microvascular resistance (IMR) 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour Distal coronary pressure during hyperaemia x mean transit time (mmHg·s)
Fractional flow reserve (FFR) 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour Distal coronary pressure/aortic pressure during hyperaemia
Coronary flow reserve (CFR) 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour Thermodilution-based ratio of hyperaemic coronary flow/basal flow
Resistive reserve ratio (RRR) 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour Index of microvascular resistance rest/hyperaemia
First pass microvascular obstruction extent (FP MVO) at 6 months 6 months Measured in 3 SAX levels to provide an index of %LV FP MVO
Resting full-cycle ratio (RFR) 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour lowest value of distal coronary pressure/aortic pressure over the entire cardiac cycle at rest
Intracoronary temperature change 1 hour Intracoronary temperature change during cooling and dilution (°C)
Infusion volume 1 hour Total volume of intracoronary saline infused (ml)
Infusion rate 1 hour Total volume of intracoronary saline infused/infusion time (ml/min)
Chest pain during study infusion 1 hour Whether new chest pain arises, or chest pain increases during study infusion
ECG changes during study infusion 1 hour Amelioration or worsening of the ECG anomalies during study infusion (ST elevation/depression, T wave inversion, QT prolongation)
Heart rhythm changes during study infusion 1 hour Appearance or resolution of heart rhythm disturbances during study infusion (sinus tachycardia, supraventricular tachycardia, atrial tachycardia/fibrillation/flutter, ventricular tachycardia/flutter, ventricular fibrillation, sinus bradycardia, grade I, II, or III heart block, asystole.
Myocardial blush grade 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour Angiographic myocardial perfusion measurement based on visual assessment of the myocardium after contrast injection. Grading: 0, no myocardial blush or contrast density; 1, minimal myocardial blush or contrast density; 2, moderate myocardial blush or contrast density but less than that obtained during angiography of a contralateral or ipsilateral non-infarct-related coronary artery; and 3, normal myocardial blush or contrast density, comparable with that obtained during angiography of a contralateral or ipsilateral non-infarct-related coronary artery
Thrombolysis in Myocardial Infarction (TIMI) flow 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour Visual angiographic assessment of coronary flow. Grade 0 = no perfusion; grade 1 = penetration without perfusion; 2 = partial perfusion; 3 = complete perfusion
ST segment resolution 10 mins after completion of percutaneous coronary intervention and study infusion 1 hour Null, partial, or complete resolution of the ST elevation
Heart Rhythm disturbance from baseline to 12 hours 12 hours Appearance or resolution of heart rhythm disturbances in the 12 hours after the procedure (sinus tachycardia, supraventricular tachycardia, atrial tachycardia/fibrillation/flutter, ventricular tachycardia/flutter, ventricular fibrillation, sinus bradycardia, grade I, II, or III heart block, asystole.
Haemodynamic compromise from baseline to 12 hours 12 hours Society for Cardiovascular Angiography and Interventions (SCAI) class B or above
Left ventricular ejection fraction (LVEF) at 48 hours 2 days Simpson biplane (diastolic-systolic)/diastolic left ventricular volume on echocardiography
Left ventricular ejection fraction (LVEF) at 6 months 6 months Simpson biplane (diastolic-systolic)/diastolic left ventricular volume on echocardiography
Wall motion score index (WMSI) at 48 hours 48 hours The wall motion score index (WMSI) is an echocardiographic parameter that numerically sums the average scores for all left ventricular segments into a single parameter and then dividing by the number of segments. 1 Normal motion; 2 = hypokinesia; 3 = akinesia; 4 = dyskinesia.
Wall motion score index (WMSI) at 6 months 6 months The wall motion score index (WMSI) is an echocardiographic parameter that numerically sums the average scores for all left ventricular segments into a single parameter and then dividing by the number of segments. 1 Normal motion; 2 = hypokinesia; 3 = akinesia; 4 = dyskinesia.
Global longitudinal strain (GLS) at 48 hours 48 hours Echocardiographic speckle-tracking imaging that measures the systolic shortening of left ventricular segments as percentage of their diastolic length
Global longitudinal strain (GLS) at 6 months 6 months Echocardiographic speckle-tracking imaging that measures the systolic shortening of left ventricular segments as percentage of their diastolic length
Length of stay 3-5 days Duration of hospital length of stay
Peak high-sensitivity cardiac troponin T (hs-cTnT, ng/l) 1-3 days Myocardial injury marker. Highest hs-cTnT measurement during hospital stay
N-terminal pro-brain natriuretic peptide (NT-proBNP, ng/l) 1-3 days Heart failure marker. Highest NT-proBNP measurement during hospital stay
Interleukin-1b 1 day Biomarker of inflammation during myocardial infarction
Interleukin-1 receptor antagonist 1 day Biomarker of inflammation during myocardial infarction
Interleukin-6 1 day Biomarker of inflammation during myocardial infarction
Interleukin-10 1 day Biomarker of inflammation during myocardial infarction
Early MVO extent (% of LV) on 1 min post-gadolinium contrast enhanced MRI, adjusted for area at-risk 1-3 days Cardiac magnetic resonance-based assessment
Early MVO extent (% of LV) on 1 min post-gadolinium contrast enhanced MRI, adjusted for area at-risk, at 6 months 6 months Cardiac magnetic resonance-based assessment
Late MVO (presence / absence) on LGE 1-3 days Cardiac magnetic resonance-based assessment
Late MVO (presence / absence) on LGE at 6 months 6 months Cardiac magnetic resonance-based assessment
Initial infarct size (LGE) 1-3 days Mass of infarcted myocardium calculated with the full-width at half-maximum method
Infarct size (LGE) at 6 months 6 months Mass of infarcted myocardium calculated with the full-width at half-maximum method
Initial MSI (area-at-risk minus initial infarct size/area-at-risk) 1-3 days Percentage of the area at risk (calculated with the Otsu method) that was not infarcted on late gadolinium enhancement (LGE) images using infarct size from the pre-discharge (Acute MSI)
MSI (area-at-risk minus initial infarct size/area-at-risk) at 6 months 6 months Percentage of the area at risk (calculated with the Otsu method) that was not infarcted on late gadolinium enhancement (LGE) images using infarct size from the follow-up (Final MSI) magnetic resonance imaging
Left ventricular end-diastolic volume index (LVEDVI) 1-3 days Cardiac magnetic resonance-based assessment
Left ventricular end-diastolic volume index (LVEDVI) at 6 months 6 months Cardiac magnetic resonance-based assessment
Left ventricular end-systolic volume index (LVESVI) 1-3 days Cardiac magnetic resonance-based assessment
Left ventricular end-systolic volume index (LVESVI) at 6 months 6 months Cardiac magnetic resonance-based assessment
Cardiac Magnetic Resonance-based Left ventricular ejection fraction (LVEF) 1-3 days Cardiac magnetic resonance-based assessment
Cardiac Magnetic Resonance-based Left ventricular ejection fraction (LVEF) at 6 months 6 months Cardiac magnetic resonance-based assessment
Myocardial haemorrhage (presence/absence) 1-3 days Cardiac magnetic resonance-based assessment
Myocardial haemorrhage (presence/absence) at 6 months 6 months Cardiac magnetic resonance-based assessment
Myocardial haemorrhage extent (% of LV) 1-3 days Cardiac magnetic resonance-based assessment
Myocardial haemorrhage extent (% of LV) at 6 months 6 months Cardiac magnetic resonance-based assessment
Composite of all-cause mortality and hospitalization for heart failure at 6 weeks 6 weeks Composite of all-cause mortality and hospitalization for heart failure at 6 weeks
Hospitalization for heart failure at 6 weeks 6 weeks Hospitalization for heart failure at 6 weeks
Cardiovascular mortality at 6 weeks 6 weeks Cardiovascular mortality at 6 weeks
All-cause mortality at 6 weeks 6 weeks All-cause mortality at 6 weeks
Hospitalization for heart failure at 6 months 6 months Hospitalization for heart failure at 6 months
Cardiovascular mortality at 6 months 6 months Cardiovascular mortality at 6 months
Composite of all-cause mortality and hospitalization for heart failure at 6 months 6 months Composite of all-cause mortality and hospitalization for heart failure at 6 months
All-cause mortality at 6 months 6 months All-cause mortality at 6 months
Composite of all-cause mortality and hospitalization for heart failure at 12 months 12 months Composite of all-cause mortality and hospitalization for heart failure at 12 months
Hospitalization for heart failure at 12 months 12 months Hospitalization for heart failure at 12 months
Trial Locations
- Locations (1)
Harefield Hospital
🇬🇧Uxbridge, United Kingdom