Clinical Editor's Corner: Kern

Coronary Thrombosis in the Time of COVID-19 – A Puzzling Entity

Morton Kern, MD, with contributions from Drs. David Cohen, St. Francis Hospital, Roslyn, New York; Kirk Garratt, Wilmington, Delaware; Steven L. Goldberg, Monterey, California; Timothy D. Henry, MD, The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, Ohio; Lloyd W. Klein, Sonoma, California; Mitchell W. Krucoff, Duke University Medical Center, Durham, North Carolina; Bernard Meier, Bern, Switzerland; Stephen R. Ramee, Ochsner Clinic New Orleans, Louisiana; Arnold H. Seto, Long Beach, California; Paul S. Teirstein, Scripps Clinic, La Jolla, California; Bonnie H. Weiner, Worchester, Massachusetts; George Vetrovec, Virginia Commonwealth University, Richmond, Virginia

Morton Kern, MD, with contributions from Drs. David Cohen, St. Francis Hospital, Roslyn, New York; Kirk Garratt, Wilmington, Delaware; Steven L. Goldberg, Monterey, California; Timothy D. Henry, MD, The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, Ohio; Lloyd W. Klein, Sonoma, California; Mitchell W. Krucoff, Duke University Medical Center, Durham, North Carolina; Bernard Meier, Bern, Switzerland; Stephen R. Ramee, Ochsner Clinic New Orleans, Louisiana; Arnold H. Seto, Long Beach, California; Paul S. Teirstein, Scripps Clinic, La Jolla, California; Bonnie H. Weiner, Worchester, Massachusetts; George Vetrovec, Virginia Commonwealth University, Richmond, Virginia

Listen/watch Morton J. Kern, MD, with Arnold H. Seto, MD, MPA, in this 30-minute webcast, as they discuss his Clinical Editor's Corner column from May 2021, Coronary Thrombosis in the Time of COVID-19 – A Puzzling Entity.

 

We had a puzzling case. A 37-year-old man was admitted to the hospital with 1 day of anterior chest pain at rest, somewhat positional. Three months ago, he had COVID-19 flu syndrome without hospitalization. He had none of the traditional atherosclerotic coronary artery disease risk factors and took no meds. His current COVID-19 antibody test was also negative. On the current admission, his electrocardiogram (ECG) showed inferior STE, no anterior ST reciprocal changes, or anterior ST elevation (Figure 1). Laboratory data included negative inflammatory markers, HS troponin >15000u, normal left ventricular ejection fraction (LVEF), and anterior wall motion by echocardiography.

Because of the high troponins and inferior ST elevation, the patient was taken to the cardiac catheterization lab. Coronary angiography revealed large thrombus in the left anterior descending (LAD) artery, a normal and dominant large circumflex (Cx) branch, and a presumed small, non-dominant right coronary artery (RCA) that was not well visualized and presumed occluded (Figure 2).   

The Dilemma – Managing a Silent Thrombus in the LAD?

Before proceeding, we must ask several key questions. For example, given the extensive LAD thrombus and elevated troponins, how can there be no anterior ECG or LV wall motion abnormalities? While the RCA appeared small or atretic, was it truly absent or occluded, to explain the inferior ST segment elevation? Is this a long-haul COVID effect? Should we leave the clot? What supports a decision to intervene? If intervention is to be done, what’s the best thrombectomy device currently available?

Because of the acute coronary syndrome, the operator attempted to remove the LAD clot by manual thrombus aspiration, which failed with both a thrombectomy catheter and the guide catheter deeply seated. The patient remained stable without additional problems. He was then transferred for potential thrombectomy with an AngioJet (Boston Scientific) or Indigo (Penumbra) while being maintained on anticoagulation as the sole treatment. At the receiving facility, thrombectomy was deferred and anticoagulation continued. We are planning to bring him back after computed tomography angiography (CTA) to see the RCA, left coronary artery (LCA) patency, and fate of the LAD thrombus (see follow-up discussion at end).

Initial Approach: Thrombectomy?

This case generated a great deal of controversy. Let’s see what some of our cath lab experts said about this problem.

George Vetrovec, Virginia Commonwealth University, Richmond, Virginia: First, if flow is good in the LAD, I would not do thrombectomy. My experience is that with blood flow, the body will resolve this. The risk of trying to remove [the thrombus] is distal embolization and then potentially an infarct with wall motion abnormality. Importantly, one needs to “see” the RCA, as that’s where the ECG is abnormal. I wonder why a root shot wasn’t done electively; that’s now an option. Lastly, COVID is the current possibility or another inflammatory disease is possible, but importantly, I would also look for source of embolus — LV, patent foramen ovale (PFO), etc.

David Cohen, St. Francis Hospital, Roslyn, New York: I’m with George on this one. This doesn’t look like something that formed in situ. I would spend most of my time and energy looking for a source of the embolus. I’ve seen a couple of these removed by advancing a guide (or a guide extension) into the LAD and applying vigorous manual suction.

Arnold Seto, Long  Beach, California [Case Operator]: Despite the ECG changes, given the large, dominant-appearing LCx and inability to find an RCA ostium, I believed the LAD thrombus was the culprit. I attempted to aspirate using the GuideLiner guide extension (Teleflex), but was unable to aspirate any thrombus. At the time, we did not have the Penumbra system available.

Paul Teirstein, Scripps Clinic, La Jolla, California: Obviously, there is no real data on this, which is why this discussion is valuable. But I would not want that huge filling defect in my proximal LAD. I would have removed it. Yes, there’s a risk, but I think the risk is higher to leave it where it is. Especially because he has symptoms.

Lloyd Klein, Sonoma, California: I get that his symptoms are atypical and the ST elevations were inferior, and this LAD does not appear to be a huge wraparound; nevertheless, I wouldn’t want to discharge him with that thing in his LAD. I’d give him antiplatelet and perhaps anticoagulant therapy. No procedure unless there is ongoing chest pain, ischemia, ECG changes, or enzyme rise. There are no data, but my guess is that anything mechanical is apt to create distal embolization. One thing we do badly and don’t think enough about is that opening the epicardial vessel but closing those small arterioles we can’t see on an angiogram is no great benefit to the patient.

Steven Goldberg, Monterey, California: I agree with Paul, but I rather like the idea of a few days of eptifibatide, heparin, and dual antiplatelet therapy (DAPT), and repeat angiogram. I favor that over CTA. Also, in addition to PFO, work up for hypercoagulable disorder.   

Bernard Meier, Berne, Switzerland: COVID maybe, PFO almost certainly. A 5 French guiding catheter should get it out in one piece.

Steve Ramee, Ochsner Clinic, New Orleans, Louisiana: I have an interest in this scenario as one who used to treat acute stroke. Pneumbra has an aspiration catheter and Imperative Care makes an aspiration catheter for stroke that has an .088-inch lumen. It sucks middle cerebral artery (MCA) clots in seconds. This is largely replacing all other treatments (e.g., Stentrievers) for embolic stroke. It doesn’t matter if it’s hard or soft thrombus. It would be something to try if you have a coronary embolus that you do want to remove. Speak with your stroke guys.

Kirk Garrett, Delaware: I can’t disagree about looking for a PFO or LV clot in a young guy with this presentation, but it’s surprising that he’d have 2 big emboli to his coronaries (one apparently occluded his RCA and accounts for the troponin of 15,000) at the same time and nothing anyplace else.  I wouldn’t discount the possibility of a late COVID-19 effect — we’re still learning. Did the echo suggest anything in his LV apex? [MK: Nope].

Mitchell Krucoff, Duke University Medical Center, Durham, North Carolina: In the lab a few weeks ago, 4 of 6 cases were long-haul syndromes post COVID-19, 2 with very odd findings. One symptomatic non-STEMI, dyspnea without angina or MI, and a coronary thrombus in very distal right posterior atrioventricular (PAV) branch associated with an apparently tight lesion, and the other with a mid-LAD thrombus not clearly associated with a flow-limiting plaque. Both treated medically after a big discussion on use of DAPT vs direct oral anticoagulant plus single antiplatelet therapy (DOAC + SAPT).

Bonnie Weiner, Worchester, Massachusetts: There is something to be said for less is more. Although thrombectomy can be (and is generally) performed without complication, I suspect there is still some endothelial damage that occurs. Does that become a nidus for new thrombus or even longer-term issues of plaque development? I have no idea if these are real or theoretical concerns, but if there is no compelling clinical reason to do anything mechanical, that might make sense. As Mitch points out, we have a lot to learn.

Mitch Krucoff, Duke University Medical Center, Durham, North Carolina: No question that thrombectomy is not a free lunch. The Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) thrombectomy trial made [the downside of thrombectomy] so visible it changed practice and guidelines on both sides of the Atlantic. Even with the most advanced designs, just delivering a thrombectomy catheter can be a major challenge.   

The other part of “learning” that is the most haunting and difficult part is how many post-COVID syndrome patients harbor coronary thrombus and with what range of cardiac symptoms do they present? The American Heart Association stood up a COVID-cardiac registry in record time last fall. Might be something to look at.

Kirk Garrett, Wilmington, Delaware: We’re far away from understanding long-haul COVID, as your cases illustrate, Mitch. I ran across the attached pre-publication article on this topic with the most shocking title: “More Than 50 Long-Term Effects of COVID-19: A Systematic Review and Meta-Analysis.”1 This team of investigators from North America, South America, Europe, and a pharmaceutical company actually came up with 55 findings linked to late COVID-19 manifestation (Figure 3). Scary!

Timothy D. Henry, MD, The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, Ohio: It is a fascinating case. I think the clinical signs and hemodynamics dictate the treatment strategy. The mismatch between troponin (>15000) and LVEF (normal is surprising). Likewise, we need to understand the RCA. Regarding longer effects of COVID-19, it’s a very challenging issue, and difficult to know cause and effect. The same applies to post vaccination reports. As part of the North American COVID-19 ST-Segment- Elevation Myocardial Infarction (NACMI) registry, we have a wide range of unusual cases reported and discussed. Millions of people had COVID, and millions of people have had the vaccination. We have always seen strange and unusual presentations, even before COVID TIME!

Was This Patient a Long-Haul COVID Presentation?

COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), can produce late sequelae and complications that present after presumed resolution of the acute illness and can last weeks to months after initial recovery.  This phenomenon has come to be called Long-COVID or COVID long-haulers. Lopez et al1, in their review on the effects of COVID-19, estimated the prevalence of 55 long-term effects reported in 21 meta-analyses that included 47,910 patients. The follow-up time ranged from 14 to 110 days post viral infection. Study participants ranged between 17 and 87 years old. The most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13).

Talasaz et al2 reported on the COVID-19 related microvascular and macrovascular thrombotic complications, including arterial and especially venous thromboembolism (VTE), common among hospitalized and critically ill patients. Their metanalysis found the overall incidence of VTE among COVID-19 inpatients was estimated at 17%. There was a fourfold higher incidence rate in patients in intensive care units (ICUs) compared with non-ICU settings (28% vs 7%).

It is noteworthy that postmortem studies show frequent evidence of microvascular thrombosis in patients with COVID-19.3 However, the influence of these events on mortality rates remains unknown. COVID-19 can potentiate all 3 components of Virchow’s triad and increases the risk of thrombosis (Figure 4). Several mechanisms come into play as SARS-CoV-2 infection may trigger endothelial dysfunction. Using the ACE2 receptors on the surface of many cells, SARS-CoV-2 enters endothelial cells and may impair their intrinsic antithrombotic properties, which together with other factors disrupt the hemostasis equilibrium, and promote endothelial activation and thrombosis (thromboinflammation), including pulmonary microthrombosis and pulmonary intravascular coagulopathy.

The Bottom Line

In this era of COVID-19, we should be alert to the unusual presentations and bizarre constellation of thrombotic presentations. The young man with silent LAD thrombosis illustrates our dilemma requiring discussions on best management of thrombotic conditions, always keeping in mind the risk/benefits of our approach. 

Disclosures: Dr. Morton Kern reports he is a consultant for Abiomed, Abbott Vascular, Philips Volcano, ACIST Medical, and Opsens Inc.

Dr. Kern can be contacted at mortonkern2007@gmail.com.

On Twitter @drmortkern

References
  1. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, et al. More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis. medRxiv [Preprint]. 2021 Jan 30:2021.01.27.21250617. doi: 10.1101/2021.01.27.21250617
  2. Talasaz AH, Sadeghipour P, Kakavand H, et al. Recent randomized trials of antithrombotic therapy for patients with COVID-19: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Apr 20; 77(15): 1903-1921. doi: 10.1016/j.jacc.2021.02.035
  3. Voicu S, Bonnin P, Stépanian A, et al. High prevalence of deep vein thrombosis in mechanically ventilated COVID-19 patients. J Am Coll Cardiol. 2020 Jul 28; 76(4): 480-482. doi: 10.1016/j.jacc.2020.05.053