No-reflow occurs when there is a lack of reperfusion to the myocardium after successful coronary recanalization and is defined as inadequate perfusion without angiographic evidence of vessel obstruction. It occurs in 0.6-3.2% of PCI cases and is associated with increased risk of LV dysfunction, remodeling, arrhythmias, heart failure and cardiac rupture. Diagnosis is typically done using myocardial contrast echocardiography or cardiac MRI. Treatment focuses on improving perfusion and includes vasodilators like adenosine, antithrombotics, mechanical strategies like thrombectomy, and preventing no-reflow through measures like pre-conditioning.

1. Management of
No-Reflow

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

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

4. Pathophysiology

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

6. Ischemia
Athero-
embolism
Reperfusion
No
Reflow

7. 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

8. 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)

9. 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

10. 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

11. Pathophysiology 3
• Leukocytes
– ? Neutropenia, CD18 Ab, Free radiacl scavenging
• Microemboli
– Atherosclerotic debris in thrombolysis,
angioplasty, rotablation and stenting – more
common in vein graft interventions

12. 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

13. Diagnosis

14. 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

15. 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.

16. Visual appearance on MCE
Normal Microvascular
obstruction
Galiuto L et al. The No-Reflow Phenomenon. JACC Cardiovasc Imaging. 2009 Jan;2(1):85-6

17. 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

18. Vasodilators
Drug 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

19. 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

20. Prevention Better than Cure

22. 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

23. 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

24. Mechanical Strategies to Prevent
Reperfusion No-Reflow
Jaffe et al. JACC Cardiovasc Interv. 2010 Jul;3(7):695-704

25. 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

26. Distal embolic protection devices
GuardWire, Medtronic Proxis, St Jude Medical

27. Key Points
Treatment 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

28. 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

29. Thank you