The No-Reflow Phenomenon in Below-the-Knee Vessels After Percutaneous Revascularization of the Superficial Femoral Artery

Reprinted with permission from VASCULAR DISEASE MANAGEMENT 2019;16(8):E100-E102.

Abstract
Sluggish distal perfusion after successful percutaneous revascularization with no obvious residual anatomical stenosis is known as “no reflow” or “slow flow,” depending on the extent of the sluggish flow. The pathophysiology of the no-reflow phenomenon is not well understood. The proposed mechanisms are likely multifactorial, including distal embolization of plaque or thrombus, systemic inflammatory response, oxygen free radical formation, and microvascular capillary damage. There is no general consensus on prevention and management of no reflow. However, the use of intra-coronary vasodilators such as calcium channel blockers, nitroprusside, and adenosine has been shown to be effective in treating patients with coronary no reflow. We present the case of a patient with lifestyle-limiting claudication that was progressively worsening over a period of 2-3 weeks. Peripheral angiography showed occlusion of the right superficial femoral artery (SFA) with robust collaterals from the profunda femoris artery. A sub-intimal approach to crossing the occlusion was followed by balloon dilation and stent placement, and this treatment was successful in restoring in-line flow to the foot. Completion angiography revealed significantly sluggish flow in all 3 below-the-knee vessels. Intra-arterial nitroglycerine and adenosine were administered via a microcatheter placed at the level of the popliteal artery and flow improved significantly.

Key words: peripheral artery disease, no-reflow phenomenon

Peripheral artery disease (PAD) is one of the leading causes of morbidity, affecting more than 200 million people worldwide.¹ Timely improvement and/or restoration of blood flow in vessels with stenosis or occlusion is helpful for relieving symptoms in claudicants and in salvaging limbs in critical limb ischemia. The evolution of endovascular modalities has reduced the need for open surgical repair, even in TASC (TransAtlantic Inter-Society Consensus II) C and D lesions. Endovascular therapy is associated with a shorter recovery period and reduced complications.² However, endovascular treatment modalities are associated with known complications, such as vessel trauma and distal embolization. Sluggish flow after percutaneous revascularization has been reported and is a well-known entity in the coronary vasculature. Sluggish flow is less widely reported in cases of peripheral arterial revascularization. We present a patient with claudication who underwent right superficial femoral artery (SFA) revascularization that was followed by sluggish flow in all 3 below-the-knee vessels. The sluggish flow resolved with intra-arterial nitroglycerine and a high dose of adenosine.

Case

A 58-year-old man presented to the outpatient clinic complaining of right lower-limb claudication. The man had a medical history of peripheral vascular disease after a prior percutaneous balloon angioplasty and stent placement in the left leg. He also had a history of chronic obstructive lung disease, hyperlipidemia, and coronary artery disease. Ankle-brachial indices and segmental pressures revealed a probably occluded right SFA. This occlusion was confirmed at the time of revascularization of his left lower extremity.

The patient was scheduled for urgent invasive angiography and revascularization, as appropriate. An occluded right SFA (Figure 1) was recanalized using a subintimal approach, which included the use of an Outback Re-Entry catheter (Cordis, a Cardinal Health Company), balloon angioplasty, and placement of drug-eluting stents (Figure 2). Completion angiography showed a satisfactory result throughout the length of right SFA. However, sluggish flow was noted in all three below-the-knee vessels (Video 1: See https://tinyurl.com/VDMAug2019). Given the involvement of all three vessels and the appearance of the angiography, this sluggish flow was felt to be a slow-flow phenomenon rather than thrombo-embolism. A wire was reintroduced. Intra-arterial nitroglycerin and high doses of adenosine were administered via a microcatheter placed at the level of the popliteal artery, and imaging revealed a significantly improved appearance (Video 2: See https://tinyurl.com/VDMAug2019).

Discussion

The response to intra-arterial nitroglycerine and high-dose adenosine confirmed probable peripheral no-reflow or slow-flow phenomenon. Intra-coronary vasodilators are both useful and safe during coronary angiography for coronary spasms and no flow, respectively, but little has been reported regarding their use in the peripheral circulation.

No reflow is defined as suboptimal reperfusion through part of the circulation, without angiographic evidence of mechanical vessel obstruction. The prevalence of this phenomenon in peripheral angiography is largely unknown and probably underestimated. To our knowledge, no cases have been reported documenting peripheral no reflow.

Extrapolating from the coronary literature, the no-reflow phenomenon is poorly understood. However, there are theories that try to explain the possible mechanisms for coronary no reflow, and the same possible mechanisms apply to the peripheral no-reflow phenomenon. Initially, the mechanism was thought to be related to prolonged ischemia that led to tissue damage and microvascular capillary damage that resulted in incomplete reperfusion.^3,4 More recently, other factors have been thought to play a role in the development of the no-reflow phenomenon, such as distal embolization of the thrombus and/or plaque elements following balloon inflation. This explanation has been further supported by a higher incidence of no reflow in patients with greater amounts of embolic material trapped in distal protective devices compared to patients with normal flow.⁵ Other partially contributing mechanisms may include a systemic inflammatory response, platelet and endothelial activation, microvascular vasoconstriction, edema, free radicals, and calcium overload.^6,7

The patient described herein had symptoms of claudication for a few weeks, along with an occluded SFA that potentially could have created tissue damage and microvascular capillary damage. Balloon dilatation of a heavily calcific, occluded vessel could easily have led to distal embolization of small fragments of thrombus and/or plaque, leading to microvascular obstruction.

Although more research is needed to precisely determine the pathophysiologic mechanisms involved in the no-reflow phenomenon, the typical techniques for prevention and treatment of no reflow involve pre-procedural use of pharmacologic agents (aspirin and heparin) and reducing the time to intervention. Other modalities used for coronary no reflow include distal protective devices and glycoprotein IIb/IIIa inhibitors, but there are no randomized controlled data to support their use.

Adenosine, nitroprusside, and calcium channel blockers are potent vasodilators that are frequently used in coronary no reflow. Adenosine inhibits neutrophil adhesion and migration, and has also been shown to decrease formation of oxygen free radicals, which is one of the mechanisms of no reflow. Adenosine has been found to be effective in coronary no-reflow patients.⁸ Similarly, nitroprusside was found to be effective in 82% of coronary no-reflow patients.⁹

While the observed sluggish flow in our patient may have been due to embolic occlusion, the involvement of all 3 below-the-knee vessels and the angiographic appearance are more consistent with a slow-flow/no-reflow mechanism.

With this explanation in mind, nitroglycerine was administered to treat any element of vasospasm and adenosine was administered for its vasodilatory effects on the microcirculation.

Conclusion

We report a patient presenting with diminished distal flow in all 3 below-the-knee vessels, despite successful recanalization and patency of the upstream SFA, and absence of significant residual stenosis. The diminished distal flow resolved soon after administration of intra-arterial nitroglycerine and adenosine.  Potent vasodilators may be administered in cases felt to be related to no reflow in the peripheral arterial circulation. 

¹Division of Cardiovascular Medicine, University of Toledo Medical Center, Toledo, Ohio; ²Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest and report no conflicts of interest regarding the content herein.

Manuscript submitted April 14, 2019; accepted April 18, 2019.

Address for correspondence: Luai Alhazmi, MD, Division of Cardiovascular Medicine, University of Toledo Medical Center, 3000 Arlington Avenue,
Toledo, Ohio 43614. Email: Luai.Alhazmi@Utoledo.edu

Reprinted with permission from VASCULAR DISEASE MANAGEMENT 2019;16(8):E100-E102.

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