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Can No-Reflow Be Silent?
No-reflow is usually a devastating complication when treating the ST-elevation myocardial infarction (STEMI) patient or working with saphenous vein graft (SVG) interventions. Fortunately, it is uncommon for elective procedures. We recently had a patient undergoing elective stenting and encountered an unusual event, no-reflow that was entirely asymptomatic. I thought it would be worthwhile to review the no-reflow phenomenon and why the uncommon asymptomatic presentation event might occur.
Definition of no-reflow
The angiographic appearance of no flow down a treated vessel after an intervention is called “no-reflow” or “slow flow” and is defined as angiographic TIMI grade ≤2 despite vessel patency and in the absence of dissection, spasm, or visible distal macroembolus.1 No-reflow usually occurs during STEMI reperfusion, stenting of degenerated SVG or percutaneous coronary intervention (PCI) in vessels with thrombus, or Rotablator atherectomy (Boston Scientific) with distal particulate embolization.
In the published literature, the incidence of no-reflow ranges from 12-25%. Large trials such as the PAMI (Primary Angioplasty in Myocardial Infarction) trial and CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) showed 4-7% of treated lesions had TIMI flow ≤2. However, higher rates have been noted when using measurements of microvascular flow other than angiography. For example, using the TIMI myocardial perfusion grade, up to 29% of PCIs have been noted to have slow or no reflow, and the rate is even higher (34-39%) using myocardial contrast echocardiography.
Clinically, no-reflow is most often associated with new or persistent ST elevation, chest pain, and decreased left ventricular (LV) function with hypotension. Clinically asymptomatic, silent no-reflow is a rare event. This case will illustrate exactly why.
Case presentation
A 63-year-old man with treated hypertension had undergone eye surgery during which he had ST-segment changes on the monitor. A post-operative electrocardiogram (ECG) showed ST-segment depressions with T wave inversions in V4-V6, as well as leads II, III, and aVF. A follow-up nuclear stress test a few weeks later showed a large, moderate intensity, reversible inferior-lateral defect consistent with ischemia.
Transradial coronary angiography showed luminal irregularities in the left anterior descending artery (LAD) and a mild 40% circumflex artery stenosis. The right coronary artery (RCA) showed a well circumscribed, 90% narrowed, lobular, nearly occlusive lucency suggesting either calcific nodule or a chronic, well-organized, layered thrombus (Figure 1).
PCI was performed following the diagnostic angiography using an Opsens Optowire2 (OP2) pressure wire, a new tool for FFR.2 Although FFR was not needed, we used the OP2 to evaluate its performance, and to measure pressure before and then again after stenting for prognosis. The OP2 crossed the tight lesion easily and the resting distal coronary artery pressure/aortic pressure (Pd/Pa) was 0.45 consistent with the clinical presentation of asymptomatic ischemia (Figure 2).
To obtain more information about the nature of the intracoronary lucency, we attempted to perform intravascular optical coherence tomography (OCT) imaging, but were unable to cross the severe and likely calcified plaque. We then exchanged the OCT catheter for a 2.5 x 15 mm Trek RX balloon (Abbott Vascular) and inflated it at low pressure (7 atmospheres [atm] for 15 seconds), hoping to then pass the OCT catheter through the lesion again. The balloon inflation and deflation was routine, with no ECG changes or chest pain, but surprisingly, on angiography immediately after inflation, there was TIMI-0 flow past the lesion in the mid RCA (Figure 3).
Equally surprising was the lack of symptoms, ECG changes, or hypotension. We removed the balloon catheter. Since we were working over a pressure wire, we measured the Pd/Pa at 0.25 with an absolute Pd of 28 mmHg with TIMI-0 flow (i.e., no reflow), suggesting a degree of protective collateralization (Figure 4).
Additional heparin and eptifibatide (Integrilin, Merck), a glycoprotein (GP) IIb/IIIa inhibitor, was given, followed by a second balloon inflation. It was then noted that the flow had increased to TIMI flow grade 1-2. OCT imaging was then performed, but the use of a side hole guide produced suboptimal images. Because of difficulty passing a stent across the lesion, a GuideLiner (Vascular Solutions) was inserted, facilitating the delivery of a 4.0 x 15 mm Xience Alpine drug-eluting stent (Abbott Vascular). Immediately after stent implant, we observed that the post stent Pd/Pa was now 0.96, showing complete abolition of the hemodynamically significant RCA lesion. To optimize the stent deployment, several high-pressure balloon inflations were performed. The final Pd/Pa was 0.98, with a 10% narrowing appearing as a layered thrombus on one side of the stent (Figure 5). With TIMI-3 flow, good stent images and a normal final Pd/Pa, the procedure was felt to be complete.
No-reflow: mechanisms and treatment
An acute cessation of coronary flow during PCI can occur due to abrupt occlusion at or distal to the lesion, or from obstruction of outflow related to microembolization. The differential diagnosis of “no reflow” includes in situ thrombus, dissection, severe spasm, plaque rupture, or distal atherothromboembolization. If no reflow is due to thrombus from plaque rupture, manual catheter aspiration is appropriate. Additional anticoagulation with more heparin and/or GP receptor IIb/IIIa inhibitors should be started. Rechecking activated clotting time (ACT) levels is prudent. Additional angioplasty and stenting might be necessary.
If no-reflow is due to dissection, then additional stenting is necessary. If no reflow is due to severe spasm, then intracoronary nitroglycerin (100 mcg/cc) can be given until the vasospasm is relieved. While intracoronary nitroglycerin can help relieve vasospasm, it has not been shown to be effective for the no-reflow phenomenon of distal microembolization. Table 1 lists several of the most common medications found effective for the no-reflow phenomenon. Often, several boluses of these agents, usually in 100 microgram increments, may be necessary to restore flow.
For interventions on SVGs or acute STEMIs, no-reflow from embolization to the microvasculature is believed to be the most common mechanism. In SVGs, prophylactic distal filters or proximal protection are recommended, and can help reduce the embolic burden and prevent no-reflow. Filters continue to be tested in STEMI, but are not standard.
Intracoronary pressure observations during complex PCI
Intracoronary pressure measurements before, during, and after PCI offer unique insights into the physiology to be treated. The first and most common use of translesional pressure is the determination of lesion significance for fractional flow reserve (FFR). In this case, FFR was unnecessary, because of the results of the ischemic resting ECG changes coupled with a positive stress and severe angiographic lesion. However, it was interesting to note the confirmatory severity of the ischemia resting gradient and ratio (Pd/Pa=0.45) wire at the beginning of the intervention. Intracoronary (IC) pressure during the procedure permitted some understanding of why the no-reflow was asymptomatic, as the pressure in the distal bed during no-reflow suggested adequate collaterization. Finally, pressure measured after stent placement provided some information on the additional untreated resistance of diffuse or unappreciated coronary atherosclerotic disease, and the long-term prognosis associated with the final result. (Note: as an aside, the optical coupling of the Optowire2 facilitated the numerous and repeated pressure measurements without drift or signal loss that may occur sometimes with piezo-resistive pressure wires.)
A collateral flow index computed as the Pd/Pa during balloon coronary occlusion of >0.25-.30 is associated with increased tolerance for ischemia and in some patients, negative ischemic testing.3 The higher the coronary occlusion pressure, the more the distal bed is supplied by collateral flow and thus protected against ischemia. We believe the asymptomatic nature of no-reflow in this patient was related to adequate collateralization of the distal inferior myocardial bed, as demonstrated by the distal coronary pressure of 28 mmHg with a Pd/Pa of 0.25.
Lastly, the FFR after stenting is a reflection of residual stent and coronary resistance that impacts long-term prognosis.4 While true FFR was not measured, the resting Pd/Pa after completion of the intervention showed complete return to normal with a post high-pressure balloon dilation of 0.98. On final pressure wire pullback, the Pd/Pa in the guide catheter was 1.00. Performing interventions over a wire that can easily and quickly provide accurate pressure measurements can offer more insights into our stent techniques, complications, and ultimately, prognosis.
This case illustrated an unusual response to no-reflow and use of pressure measurements during PCI. I hope some of our observations were helpful in leading to a better understanding of the role of distal pressure measurements on the changing physiology during and after PCI.
References
- Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review of mechanisms and therapies (Clinical Perspective). European Heart J. 2001; 22: 729-739.
- Kern M. Comparing FFR tools: new wires and a pressure microcatheter. Cath Lab Digest. 2016 May; 24(5): 4-8. Available online at https://www.cathlabdigest.com/article/Comparing-FFR-Tools-New-Wires-Pressure-Microcatheter. Accessed June 7, 2016.
- Traupe T, Gloekler S, de Marchi S, Werner GS, Seiler C. Assessment of the human coronary collateral circulation. Circulation. 2010; 122: 1210-1220.
- Samady H, McDaniel M, Veledar E, et al. Baseline fractional flow reserve and stent diameter predict optimal post-stent fractional flow reserve and major adverse cardiac events after bare-metal stent deployment. J Am Coll Cardiol Intv. 2009; 2(4): 357-363.
Disclosure: Dr. Kern reports he is a consultant and speaker for St. Jude Medical and Volcano Therapeutics, and a consultant for Opsens, ACIST Medical, Heartflow, and Merit Medical.
