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
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™
The CorFlow Diagnostic Catheter™ for Catheter-based MVO Diagnosis
- Luo AK and Wu KC. Imaging microvascular obstruction and its clinical significance following acute myocardial infarction. Heart Fail Rev. 2006;11:305-12.
- van Kranenburg M, Magro M, Thiele H, de Waha S, Eitel I, Cochet A, Cottin Y, Atar D, Buser P, Wu E, Lee D, Bodi V, Klug G, Metzler B, Delewi R, Bernhardt P, Rottbauer W, Boersma E, Zijlstra F and van Geuns RJ. Prognostic value of microvascular obstruction and infarct size, as measured by CMR in STEMI patients. JACC Cardiovasc Imaging. 2014;7:930-9.
- Wu KC. CMR of microvascular obstruction and hemorrhage in myocardial infarction. J Cardiovasc Magn Reson. 2012;14:68.
- Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP,
Blumenthal RS and Lima JA. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation. 1998;97:765-72.
- Bekkers SC, Yazdani SK, Virmani R and Waltenberger J. Microvascular obstruction: underlying pathophysiology and clinical diagnosis. J Am Coll Cardiol. 2010;55:1649-60.
- Cuculi F, De Maria GL, Meier P, Dall’Armellina E, de Caterina AR, Channon KM, Prendergast BD, Choudhury RP, Forfar JC, Kharbanda RK and Banning AP. Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2014;64:1894-904.
- Niccoli G, Cosentino N, Minelli S, Cataneo L and Crea F. Microvascular obstruction after primary percutaneous coronary intervention: pathogenesis, diagnosis and prognostic significance. Curr Vasc Pharmacol. 2013;11:245-62.
- Stone GW, Witzenbichler B, Godlewski J, Dambrink JH, Ochala A, Chowdhary S, El-Omar M, Neunteufl T, Metzger DC, Dizon JM, Wolff SD, Brener SJ, Mehran R, Maehara A and Gibson CM. Intralesional abciximab and thrombus aspiration in patients with large anterior myocardial infarction: one-year results from the INFUSE-AMI trial. Circ Cardiovasc Interv. 2013;6:527-34.
- Lesser JR, Johnson K, Lindberg JL, Reed J, Tadavarthy SM, Virmani R and Schwartz RS. Images in cardiovascular medicine. Myocardial rupture, microvascular obstruction, and infarct expansion: elucidation by cardiac magnetic resonance. Circulation. 2003;108:116-7.
- Saber RS, Edwards WD, Bailey KR, McGovern TW, Schwartz RS and Holmes DR, Jr. Coronary embolization after balloon angioplasty or thrombolytic therapy: an autopsy study of 32 cases. J Am Coll Cardiol. 1993;22:1283-8.
- Sangiorgi G, Taylor AJ, Farb A, Carter AJ, Edwards WD, Holmes DR, Schwartz RS and Virmani R. Histopathology of postpercutaneous transluminal coronary angioplasty remodeling in human coronary arteries. Am Heart J. 1999;138:681-7.
- Schmermund A, Schwartz RS, Adamzik M, Sangiorgi G, Pfeifer EA, Rumberger JA, Burke AP, Farb A and Virmani R. Coronary atherosclerosis in unheralded sudden coronary death under age 50: histo-pathologic comparison with ‘healthy’ subjects dying out of hospital. Atherosclerosis. 2001;155:499-508.
- Schwartz RS. Microvascular obstruction in acute coronary syndromes: onward to a new therapeutic target. Catheter Cardiovasc Interv. 2005;66:170-2.
- Schwartz RS, Burke A, Farb A, Kaye D, Lesser JR, Henry TD and Virmani R. Microemboli and microvascular obstruction in acute coronary thrombosis and sudden coronary
death: relation to epicardial plaque histopathology. J Am Coll Cardiol. 2009;54:2167-73.
- Muller O, Trana C and Eeckhout E. Myocardial no-reflow treatment. Curr Vasc Pharmacol. 2013;11:278-85.
- Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO and Judd RM. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000;343:1445-53.
- Ahmed N, Carrick D, Layland J, Oldroyd KG and Berry C. The role of cardiac magnetic resonance imaging (MRI) in acute myocardial infarction (AMI). Heart Lung Circ. 2013;22:243-55.
- Hoole SP, Jaworski C, Brown AJ, McCormick LM, Agrawal B, Clarke SC and West NE. Serial assessment of the index of microcirculatory resistance during primary percutaneous coronary intervention comparing manual aspiration catheter thrombectomy with balloon angioplasty (IMPACT study): a randomised controlled pilot study. Open Heart. 2015;2:e000238.
- Neizel M, Futterer S, Steen H, Giannitsis E, Reinhardt L, Lossnitzer D, Lehrke S, Jaffe AS and Katus HA. Predicting microvascular obstruction with cardiac troponin T after acute myocardial infarction: a correlative study with contrast-enhanced magnetic resonance imaging. Clin Res Cardiol. 2009;98:555-62.
- Wong DT, Leung MC, Richardson JD, Puri R, Bertaso AG, Williams K, Meredith IT, Teo KS, Worthley MI and Worthley SG. Cardiac magnetic resonance derived late microvascular obstruction assessment post ST-segment elevation myocardial infarction is the best predictor of left ventricular function: a comparison of angiographic and cardiac magnetic resonance derived measurements. Int J Cardiovasc Imaging. 2012;28:1971-81.