SONOTHROMBOLYSIS IN STEMI

TREATED WITH PPCI: MRUSMI

MICROVASCULAR REPERFUSION UTILIZING SONOTHROMBOLYSIS IN ACUTE MYOCARDIAL
INFARCTION

1ST RANDOMISED STUDY IN HUMANS

Mathias et al JACC VOL. 73, NO. 22, 2019

Dr Soleiman Aria
MBBS MA(Cantab)
MRCP(UK)
MSc (Cardiology) Student
Basic Physician Trainee
 THERAPEUTIC MILESTONES IN MYOCARDIAL
INFARCTION

Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63

 THERAPEUTIC MILESTONES IN MYOCARDIAL
INFARCTION

Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63

 THERAPEUTIC MILESTONES IN MYOCARDIAL
INFARCTION

Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63

 THERAPEUTIC MILESTONES IN MYOCARDIAL
INFARCTION

Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63

 THERAPEUTIC MILESTONES IN MYOCARDIAL
INFARCTION

Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63

 THERAPEUTIC MILESTONES IN MYOCARDIAL
INFARCTION

Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63

 THERAPEUTIC MILESTONES IN MYOCARDIAL
INFARCTION

?
MRUS
MI

Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63

 MRUSMI: INTRODUCTION
• With primary PCI and thrombolysis there are 2 challenges:

• 1ST: Timely delivery of these interventions

• Geographical isolation – Australia, Canada
• Limitation of resources – Developing Countries

• 2ND: No reflow phenomena in ~35%

• Significant microvascular obstruction despite successful epicardial recanalization
• Suggested by increased IMR
 MRUSMI: INTRODUCTION

Continuous infusion of

Thrombolysis
High Mechanical Index Transthoracic impulses from a diagnostic US
Probe
Microbubbles
MICROBUBBLE AND THE EFFECT OF USS
MICROBUBBLE AND THE EFFECT OF USS
MICROBUBBLE AND THE EFFECT OF USS
MICROBUBBLE AND THE EFFECT OF USS
MICROBUBBLE AND THE EFFECT OF USS
 INTRODUCTION

Cardiovasc Intervent Radiol (2001) 24:407–412 Journal of Ultrasound in Medicine, September

2006, Vol.25(9), pp.1161-1168
 INTRODUCTION
• Microbubble movement and rupture creates:
• Shear forces which dissolve thrombi in arteries and microvasculature
• Induces endothelial and red blood cells to release nitric oxide

• Hypothesize that addition of Sonothrombolysis to PPCI for STEMI:

• Improve angiographic and microvascular reflow
• Reduction in infract size
• Improved systolic function at follow up
 METHODS
• Prospective
• Single centre
• Two arm randomised study
• Patients with 1st STEMI
• May 2014 – July 2018
• Objectives:
• Determine safety and feasibility of Sonothrombolysis in humans during acute STEMI
• Potential efficacy in restoring flow, reducing infarct size and improving LV function
 METHODS: OUTCOMES

• Primary outcomes
• Rate of ST-segment resolution
• Angiographic recanalization rate (ARR)

• Secondary outcomes
• Infarct size by delayed enhancement CMR
• Microvascular flow as assessed by contrast perfusion after PCI AND CMR
• LVEF at 6 months
METHODS: STUDY PROTOCOL
METHODS: STUDY PROTOCOL
METHODS: STUDY PROTOCOL
METHODS: PATIENT SELECTION
METHODS: PATIENT SELECTION
METHODS: PATIENT SELECTION
METHODS: PATIENT SELECTION
METHODS: PATIENT SELECTION
METHODS: PATIENT SELECTION
METHODS: PATIENT SELECTION
METHODS: PATIENT CHARACTERISTICS
METHODS: PATIENT CHARACTERISTICS
METHODS: PATIENT CHARACTERISTICS
METHODS: PATIENT CHARACTERISTICS
DOOR TO BALLOON TIME
 RESULTS – PRIMARY OUTCOMES
RATE OF ST-SEGMENT RESOLUTION
 RESULTS – PRIMARY OUTCOMES
RATE OF ST-SEGMENT RESOLUTION
 RESULTS – PRIMARY OUTCOMES
RATE OF ST-SEGMENT RESOLUTION
 RESULTS – PRIMARY OUTCOMES
ANGIOGRAPHIC RECANALIZATION RATE – PRE
PCI
 RESULTS – SECONDARY OUTCOMES
INFARCT SIZE & MICROVASCULAR FLOW BY
CMRI
 RESULTS – SECONDARY OUTCOMES
LVEF PRIOR TO THERAPY, POST PCI & AT 6
MONTHS
 DISCUSSION

• First prospective randomized human study

• Demonstrate a supplemental beneficial effect of Sonothrombolysis
• Simple and safe diagnostic and therapeutic procedure
• No alteration in safety or door-to-dilation times
• Provided both macro and microvascular improvement
 STUDY LIMITATIONS
• Small, single centre study
• Prove of concept paper
• Patients randomised to HI MI/PCI were more frequently taking beta-blockers on admission
• May affect risk area and recovery of function
• However, all patients received betablockers and statins after the study entry
• Furthermore, 6 months ejection fraction was still higher in the high MI/PCI group even after removing
patients who were taking betablockers on admission
 THE FUTURE

• Large multicentre randomized clinical trial

• Development of US probes that can easily be applied to chest wall by ambulance
crew (under development)
• Intracatheter application post angioplasty to treat distal microembolization
• Sonothrombolysis for patients with contraindication to thrombolysis as a sole
therapy
QUESTIONS