Don’t Mistake Microthrombi for Myocarditis in COVID-19 STEMI, Case Report Warns
Autopsy analysis shows that myocarditis isn’t the only cause of MI in the absence of occlusive disease.
That COVID-19 can cause STEMI symptoms even in the absence of obstructive disease will come as no surprise to cardiologists tracking the pandemic’s fallout. But a recent case report suggests that standard approaches to what’s presumed to be myocarditis won’t be helpful in some scenarios in which extensive and elusive myocardial thrombosis is actually the root cause of ischemia.
Autopsy analysis brought this unexpected mechanism to the forefront, Giulio Guagliumi, MD (Ospedale Papa Giovanni XXIII, Bergamo, Italy), and colleagues note in their paper published online in Circulation. “This type of injury would not be detectable clinically, as no laboratory test specifically can detect microthrombi,” they say.
Unlike in the pulmonary realm, “few pathology studies have been conducted specifically examining effects of COVID-19 on the heart,” the investigators note, “and most of these did not involve subjects with STEMI or even cardiac injury.” They combined data from several large cardiac-focused series and found that, of 67 hearts examined, only five had “lymphocytic myocarditis of unclear extent and nature.”
Speaking with TCTMD, Guagliumi said their case report demonstrates a newly recognized manifestation of COVID-19: microthrombi so widely dispersed throughout the heart that they impair the microcirculation. “The crucial point is we dissected this [particular] heart at all levels,” he commented, with a pathological exam as well as molecular analysis to confirm the presence of SARS-CoV-2.
Yet this patient had no evidence that the virus had infiltrated the heart. This is an important clue, explained Guagliumi, that there is a parallel mechanism beyond myocarditis that might inform more-targeted care.
The 43-year-old woman had been taking care of her husband, who had been hospitalized due to COVID-19-related pneumonia. After experiencing transient angina 1 day prior, she then developed sudden-onset, persistent chest pain. At admission, she was hypotensive (systolic BP 70 mm Hg) and tachycardic (heart rate 130 beats/min), with coffee-ground emesis. Her high-sensitivity troponin I level was 11,795 ng/L.
In many ways she appeared normal—she had no fever or dyspnea. “While breathing room air, oxygen saturation was 100%, PaO2/FiO2 ratio was normal, and lactate was moderately increased to 4.39 mmol/L,” the authors note.
Two hours after symptom onset, an ECG showed ST-segment elevation in the inferior and lateral leads, so she was transferred for urgent coronary angiography and primary PCI. Angiography, however, showed normal epicardial coronary vessels. Progressive cardiogenic shock led to the use of vasopressors and intra-aortic balloon pump and the patient was ultimately sent to the ICU, where chest radiography showed pulmonary congestion but not interstitial pneumonia. Once her SARS-CoV-2 infection was confirmed, she began antiretroviral therapy (darunavir/cobicistat).
“Despite hemodynamic support, she remained hypotensive (72/34 mm Hg), with a cardiac index of 1.1 L/min/m2, and oliguria (20 mL/hour). Blood lactate increased, requiring escalating doses of inotropes, intubation, and mechanical ventilation,” Guagliumi and colleagues write. “A repeated ECG showed diffuse ST-segment elevation, whereas the echocardiogram confirmed a severe left ventricular dysfunction with progressive impairment of the right ventricle. Pericardial effusion was stable.”
The team tried immunosuppressive therapy with methylprednisolone and immunoglobulin infusion on top of standard IV heparin. Despite their efforts, she continued to worsen, developed multiorgan failure, and died 46 hours after admission.
Autopsy gives some clues as to the mechanism behind her rapid deterioration.
In the case report, Renu Virmani, MD (CVPath Institute, Gaithersburg, MD), describes what they found: “The pathologic examination suggested microvascular thrombi in the inferior wall of the left and right ventricles as the initial cause of the ST-elevation myocardial infarction. Acute inflammatory infiltrates in these territories together with contraction band necrosis suggested an infarct of approximately 1 to 2 days consistent with the onset of her chest pain (ie, 46 hours before presentation). The pathologic cause of death was cardiogenic shock due to myocardial necrosis, which was extensive through the left ventricle and part of the right ventricle and likely due to poor perfusion of the heart.”
The lungs had focal areas of pulmonary edema but few microthrombi. In the kidney and the spleen, microthrombi were present but also rare.
Senior author Aloke V. Finn, MD (CVPath Institute), points out that there was little evidence of the virus’ direct involvement. “SARS CoV-2 was present in the lungs of this subject although there was no evidence of diffuse alveolar damage, a pattern typical of COVID-19 infection,” he writes in their report. “Even with the presence of microvascular thrombi there was no evidence of viral infection in any part of the heart.”
Coagulation and Inflammation
The researchers call for larger series to investigate this phenomenon in COVID-19 patients with myocardial injury. “Physicians should be aware of this possible complication and of the potential of anticoagulant and anticytokine therapies as conceivable therapeutic options which need to be further explored in clinical trials,” they say.
“Absolutely, yes,” the woman’s condition resulted from the coagulation cascade and her inflammatory response to the virus, Guagliumi told TCTMD.
Notably, the group did find evidence of this. As the patient deteriorated, her partial thromboplastin time ratio rose from normal at the time of admission to 6.69, and her international normalized ratio (INR) was 3.5, “hinting at an underlying acute coagulopathy.” Additionally, she had elevated levels of plasminogen activator inhibitor, prothrombin activation fragments, and von Willebrand factor. On subsequent autopsy, the cytokine interleukin-6 was found in the inferior wall, septum, and right ventricle.
These patterns suggestive of heightened coagulability have also been seen in data they’ve gathered on more than 100 patients, Guagliumi added, and additional case reports are on the way.
Much like in COVID-19 patients with pulmonary embolism, there are ways to address this risk, Guagliumi observed. Patients presenting with high levels of myocardial injury are especially vulnerable, so it’s important to find and initiate therapies that can address the coagulation cascade. But to do so effectively, first it’s necessary “to understand the parameters . . . and factors involved in forming thrombi,” he observed.
Guagliumi G, Sonzogni A, Pescetelli I, et al. Microthrombi and ST-segment elevation myocardial infarction in COVID-19. Circulation. 2020;Epub ahead of print.
- Guagliumi reports receiving institutional research grants from Abbott Vascular, Boston Scientific, and Infraredx and being a consultant to Abbott Vascular and Boston Scientific.
- Finn reports receiving honoraria from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Cook Medical, CSI, Lutonix Bard, Sinomed, and Terumo Corporation and serving as a consultant to Amgen, Abbott Vascular, Boston Scientific, Celonova, Cook Medical, Lutonix Bard, and Sinomed.