Microvascular Obstruction:

The Unsolved Frontier in Acute STEMI Therapy

Modern interventional therapy for acute myocardial infarction has matured in recent years with impressive clinical results.  STEMI mortality at 30 days has dropped from over 30% to less than 5% today.  These results derive from recognizing the need for reperfusion as soon as possible, and result from streamlined clinical care systems of emergent PCI.  Primary PCI is now the undisputed optimal acute MI therapy.

Challenges in STEMI therapy remain, the most important being heart failure, ventricular rupture, persistent angina, LV aneurysm and thrombus, and ventricular arrhythmias.  Heart failure complicates 25-50% of acute STEMI, and causes contractility loss in damaged myocardium. It is frequently worsened when concomitant left ventricular remodeling occurs. Nearly half of new heart failure in patients under 75 years are due to ischemic cardiomyopathy.

The major cause of all complications listed above is myocardial Microvascular Obstruction (MVO).  MVO is residual and severe obstruction and occlusion of myocardial arterioles and capillaries. It is very common in STEMI patients, even when epicardial coronary arteries are widely patent following acute stent placement.  MVO occurs to varying degrees in over half of STEMI patients with TIMI 3 epicardial flow.

The extent of microvascular obstruction during acute coronary occlusion is key to myocardial damage and patient prognosis.  Cardiac MRI (CMR) is the gold standard for MVO characterization and quantitation.  CMR images show MVO as regions of profound microvascular obstruction at the infarct core, with  (white arrows, left figure) very dark, contrast-poor regions of myocardium.  Myocardial segments with acute MVO correlate well with late myocardial scar, suggesting that acute MVO heals as myocardial scar (white arrows, right figure).

MVO is thus a key impediment to myocardial salvage.  An obvious hypothesis is that restoring microvascular patency and function within hours of the STEMI would reduce infarct size and lessen long term complications.  This concept is supported by multiple clinical studies demonstrating MVO as a very strong correlate of both acute and 2-year cardiovascular morbidity and mortality, even after controlling for infarct size.

No therapy effectively treats MVO today.  Recent trials tested combinations of thrombus aspiration and intracoronary abciximab combined with bivalrudin infusion (INFUSE-AMI) using 30-day infarct size reduction as an endpoint. The interventional strategy was catheter aspiration to remove embolic debris, and intracoronary abciximab (high concentration since intracoronary injection) to lyse thrombus.  Results however showed only a small (3%) reduction in infarct size with intracoronary abciximab, and aspiration showed marginal to no added benefit.

The CorFlow technology is designed to acutely restore myocardial microvascular flow and thus improve salvage. 

Microvascular Obstruction (MVO) Factoids

  • MVO is the principal cause of “no-reflow” or “low-reflow” and is characterized by very slow contrast filling epicardial coronary arteries.
  • MVO causes myocardial cell injury and death from prolonged ischemia. Histologic characterization shows nonviable myocardium, myocyte cell death, and endothelial cell death along intramyocardial capillaries.
  • MVO histopathology shows arterioles and capillaries occluded by platelet thrombi, platelet-neutrophil aggregates, dying blood cells and embolic debris.
  • MVO in acute myocardial infarction causes greater myocardial damage, proven by echocardiography. It correlates strongly with marked global ventricular function loss in the early post infarction phase.
  • MVO is very common in Acute Coronary Syndromes. It occurs in:

    • 53% of all STEMI and NSTEMI regardless of epicardial flow/no-reflow

    • 90% of Large Transmural MI

    • 40% of MI with TIMI III flow

    • MVO is the most potent prognostic marker of events after controlling for infarct size

  • Patients with microvascular obstruction have more cardiovascular events than those without (45% versus 9%) in one study
  • Microvascular status predicts acute and chronic cardiovascular adverse outcomes such as infarct extent
  • MVO acutely is associated with fibrous scar formation and adverse LV
  • MVO is one of the best prognostic markers for postinfarction complications

CorFlow Therapeutics™ technology offers a New Approach to Diagnose and Treat MVO STEMI patients

CorFlow was incorporated to specifically treat MVO/no reflow in the cath lab, during the angioplasty procedure. The company is developing proprietary technology for real time, in-lab MVO diagnosis and treatment. This will be completed in the cath lab at any time before or after stent implant in acute coronary syndromes.

Short Overview of the CorFlow Technology & Therapy™

  • User friendly
  • Compact CorFlow Control Console™
  • Rapid exchange antegrade CorFlow Therapeutic Catheter™
  • Standard cath lab techniques
  • No change in STEMI workflow
  • Easy and fast
  • Passes the ‘Will I use it at 2 am’ test
    • Fast easy to use, antegrade approach, no additional access or lines needed
  • Adds little time to the procedure – can be completed in the cath lab
  • Proprietary delivery technology

The CorFlow Diagnostic Catheter™ for Catheter-based MVO Diagnosis

  • Real time, continuous myocardial microvascular function status
  • Allows the operator to determine and follow CorFlow Therapy™ efficacy in real time

Animation of the CorFlow Controlled Flow Infusion (CoFI™) Approach

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