management of no reflow

Management of No-Reflow

Overview• Definition• Historical Perspective• Pathophysiology• Diagnosis• Clinical Presentation• Management– Advantages– Measures– Treatments

• Conclusion

Definition

• LACK OF INTRAMYOCARDIAL REPERFUSION after successful coronary recanalization has been defined as the “no-reflow” phenomenon

• No-reflow is defined as inadequate myocardial perfusion through a given segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction

• No-reflow occurs in 0.6% to 3.2% of PCI casesRamjane K et al. Cardiol 2008;13(3):121-128

Pathophysiology

Niccoli G et al. No-reflow: again prevention is better than treatment. Eur Heart J. 2010 Oct;31(20):2449-55

Ischemia

Athero-embolism

ReperfusionNo

Reflow

Copyright © MedReviews, LLC. Alfayoumi F, Srinivasan V, Geller M, Gradman A. The No-Reflow Phenomenon: Epidemiology, Pathophysiology, and Therapeutic Approach. Rev Cardiovasc Med. 2005; 6:74. Reviews in Cardiovascular Medicine is a copyrighted publication of MedReviews, LLC. All rights reserved.

Pathophysiology of microvascular dysfunction after epicardial perfusion in patients with acute MI

Copyright © MedReviews, LLC. Alfayoumi F, Srinivasan V, Geller M, Gradman A. The No-Reflow Phenomenon: Epidemiology, Pathophysiology, and Therapeutic Approach. Rev Cardiovasc Med. 2005; 6:76. Reviews in Cardiovascular Medicine is a copyrighted publication of MedReviews, LLC. All rights reserved.

Heterogeneity of flow to the area at risk after reperfusion (post-myocardial infarction)

Pathophysiology 1

• Prolonged cessation of epicardial blood flow results in damage to microcirculation, which prevents restoration of normal flow

• Inadequate cardiac scar• Process NOT an immediate event on

reperfusion• NO-Reflow area increases with time

Pathophysiology 2

• Endothelial swelling and intra luminal protrusions (blebs)occlude microvasulature– ? Why dexamethasone and Mannitol help

• Intravasular plugging fibrin and platelets– Ibuprofen, PG E1, heparinised saline, platelet

depletion

Pathophysiology 3

• Leukocytes– ? Neutropenia, CD18 Ab, Free radiacl scavenging

• Microemboli– Atherosclerotic debris in thrombolysis,

angioplasty, rotablation and stenting – more common in vein graft interventions

Clinical Features• Clinical features associated with no-reflow include

age, male sex, hyperglycemia and the absence of preinfarction angina

• Symptoms:– precordialgia of insidious onset (which is continuous and of

increasing intensity), – electrocardiographic abnormalities of the ST segment or T

wave, and arrhythmia• Associated with increased risk of:– LV systolic dysfunction, reduced LV ejection fraction– left ventricular remodelling, – malignant ventricular arrhythmias, – heart failure and cardiac rupture

Diagnosis

Diagnosis

• MCE and contrast enhanced cardiac magnetic resonance (CMR) are the most common techniques for its diagnosis

• MCE can clearly delineate no reflow after primary PCI and helps in prognostication.

• MCE can be used to test if treating no reflow will be useful

Galiuto L et al. The No-Reflow Phenomenon. JACC Cardiovasc Imaging. 2009 Jan;2(1):85-6

Copyright © MedReviews, LLC. Alfayoumi F, Srinivasan V, Geller M, Gradman A. The No-Reflow Phenomenon: Epidemiology, Pathophysiology, and Therapeutic Approach. Rev Cardiovasc Med. 2005; 6:77. Reviews in Cardiovascular Medicine is a copyrighted publication of MedReviews, LLC. All rights reserved.

 Midventricular short-axis MRI image demonstrating acute transmural infarction of the lateral wall (arrowheads). A dense rim of subendocardial signal void (black arrow) corresponds to the region of no reflow or microvascular obstruction. Because gadolinium does not reach this portion of the myocardium, there is no T1 shortening. Therefore, no hyperenhancement can be visualized.

Visual appearance on MCE

Normal Microvascular obstruction

Galiuto L et al. The No-Reflow Phenomenon. JACC Cardiovasc Imaging. 2009 Jan;2(1):85-6

Treatment• No standard, single treatment of the no-reflow

phenomenon

• The focus of reperfusion therapy is shifting toward improved myocardial perfusion, which could increase the delivery of blood-borne components, thereby accelerating the healing process.

Ramjane K et al. Cardiol 2008;13(3):121-128

VasodilatorsDrug Mechanism of action Dose

Verapamil Relieve small vessel spasm, improve Ca+2 homepstasis in ischemic myocardium

50 to 1000 µg intracoronary

Adenosine Relieve small vessel spasm, Reduce neutrophil activation, limit endothelial injury

24 µg to 4 mg intracoronary

Nicorandil Relieve small vessel spasm, reduces Ca+2overload and neutrophil activation

1.67 microg/kg per min

Ramjane K et al. Cardiol 2008;13(3):121-128

Antithrombotic Drugs

• In a recent experimental study (64), administration of tirofiban before coronary reperfusion was associated with improved myocardial perfusion and reduced infarct size

• ADMIRAL Trial: i.v. abciximab is associated with a high incidence of TIMI 3 flow; an 80% reduction in adverse cardiac events was seen compared with controls

Ramjane K et al. Cardiol 2008;13(3):121-128

Prevention Better than Cure

Ischemic Preconditioning (IPC)• Ischaemic preconditioning is able to reduce the infarct size by

half after coronary ligation and reperfusion

• Has been proven to be effective in animal models

• Limiting intake of beverages which increase risk of IPC- alcohol, coffee

• Brief ischaemia in an organ that is distant or remote from the heart, such as limb, also reduces myocardial infarction in experimental models

Ramjane K et al. Cardiol 2008;13(3):121-128

Post-conditioning• In Experimental studies- multiple, short, induced coronary

occlusions immediately after sustained myocardial ischemia are associated with reduced myocardial infarct size compared with sudden reperfusion

• Mechanism:– activation of extracellular signal-regulated kinase– production of nitric oxide– opening of mitochondrial potassium channels and – inhibition of opening of the mitochondrial permeability transition pore

Mechanical Strategies to Prevent Reperfusion No-Reflow

Jaffe et al. JACC Cardiovasc Interv. 2010 Jul;3(7):695-704

Thrombectomy• REMEDIA & DEAR-MI studies, thrombectomy improved

microvascular perfusion

• TAPAS Trial- thrombectomy improved tissue perfusion and reduced cardiac death

• In a pooled analysis of 11 randomized trials that examined the role of different thrombectomy devices in primary PCI, thrombectomy improved survival in patients treated with glycoprotein IIb/IIIa inhibitors

Jaffe et al. JACC Cardiovasc Interv. 2010 Jul;3(7):695-704

Distal embolic protection devices

GuardWire, Medtronic Proxis, St Jude Medical

Key PointsTreatment with aspirin, clopidogrel and statins before PCI reduce periprocedural myocyte damage and should be prescribed when possible

The use of GP IIb/IIIa antagonists in acute coronary syndrome provides additional microvascular protection and improves clinical outcomes

Distal embolic protection has not resulted in improved microvascular flow or function, or reduction of infarct size or event-free survival

Randomized studies do not support routine use of thrombectomy devices with primary PCI in all STEMI patients

Postconditioning reduces myocardial infarct size; however, the effect on clinical outcomes remains to be determined

If no-reflow occurs following PCI, treatment with intracoronary adenosine or verapamil should be administered because this therapy is inexpensive, safe, improves flow, and may reduce infarct size

Thank you