key: cord-0754429-w6ouaxvp
authors: Kim, Seulgi E.; Koh, Stephanie; Hamzeh, Ihab
title: A Left Atrial Mass in the Time of COVID
date: 2021-11-20
journal: Am J Med
DOI: 10.1016/j.amjmed.2021.10.029
sha: 70b672818bbd69fafb47bdfb5b85bf3460dc9646
doc_id: 754429
cord_uid: w6ouaxvp

nan

A 60-year-old woman presented to the emergency department with chest pain and worsening dyspnea. On initial vital signs, she was afebrile with a blood pressure of 160/107 mmHg, a heart rate of 89 beats/min, a respiratory rate of 30 breaths/min, and an oxygen saturation of 95% on 4 liters oxygen via nasal cannula (an increase from her home requirement of 2 liters oxygen via nasal cannula). Her weight on presentation was 24 lbs above her baseline. Her exam was notable for elevated jugular venous pressure to 14 cm of water, rales in bilateral lung bases without wheezes, and significant bilateral lower extremity edema to her thighs. She was admitted for management of her heart failure.

Her past medical history included systolic heart failure secondary to non-ischemic cardiomyopathy diagnosed 3 years ago, tobacco use, hypertension, hypothyroidism, and SARS-CoV-2 infection requiring hospitalizations at an outside hospital 11 months prior to presentation. Three months prior to this admission, she completed the Pfizer-BioNTech BNT162b2 SARS-CoV-2 mRNA vaccinations but reported worsening heart failure symptoms with dyspnea, orthopnea, lower extremity swelling after each dose. She required hospitalization following the second dose for acute on chronic systolic heart failure. A transthoracic echocardiogram (TTE) was performed then, which demonstrated left ventricular ejection fraction (LVEF) of 20-24%. She had no prior history of atrial arrhythmias, stroke, deep vein thrombosis, pulmonary embolism, or pregnancy loss.

Initial labs were notable for white blood cell of 7.5 K/uL, hemoglobin of 12.7 g/dL, platelets of 177 K/uL, creatinine of 1.4 mg/dL, troponin I of 0.10 ng/mL, brain natriuretic peptide of 4,387 pg/mL. Electrocardiogram showed sinus rhythm with first degree atrioventricular block with occasional premature ventricular complexes, left axis deviation, left atrial enlargement, and intraventricular conduction delay. A TTE showed a dilated left ventricle with normal wall thickness, LVEF less than 15%, and a mildly dilated left atrium with a new 2.6 cm x 2.4 cm well-circumscribed retro-aortic left atrium mass close to the interatrial septum that was not clearly attached by a stalk (Figure 1 ). There were no significant valvular abnormalities. No left ventricular thrombus was present. There was also mild interstitial fibrosis in the mid-interventricular septum, likely related to long-standing non-ischemic dilated cardiomyopathy, but similar findings could also be seen in post-SARS-CoV-2 infection. 1

The echocardiographic findings were highly suspicious for a thrombus versus a tumor, although tumor was less likely given the rapid growth since the last TTE 3 months prior that did not demonstrate the mass. The lowintensity signal of the mass and lack of contrast enhancement on CMR were also consistent with a thrombus.

During her hospitalization, she was given intravenous diuretics until she was euvolemic. For the left atrium thrombus, she was started on therapeutic subcutaneous enoxaparin for anticoagulation and on discharge was transitioned to apixaban 10 mg b.i.d. for one week then 5 mg b.i.d. indefinitely. Inpatient telemetry did not show any evidence of atrial fibrillation or flutter; she remained in normal sinus rhythm with occasional runs of non-sustained ventricular tachycardia. Hematology was consulted, and hypercoagulable lab studies for beta-2 glycoprotein and anticardiolipin antibodies were sent and came back negative. The etiology of the left atrium thrombus was thought to be due to the low-flow state in the setting of severe left ventricular systolic dysfunction. Therefore, long-term anticoagulation was recommended.

A follow-up TTE two months later showed LVEF of less than 20% and resolution of the left atrium thrombus.

She had a biventricular pacemaker-implantable cardiac defibrillator placed, and subsequent device monitoring has not shown any episodes of atrial arrhythmias. She currently remains on apixaban.

Virchow's triad comprises of three physiological processes that contribute to the formation of thromboses: venous stasis, endothelial damage, and hypercoagulability. The etiology and pathophysiology for intracardiac thrombi is multifactorial and, as in this case, all three components of Virchow's triad likely contributed to the formation of a left atrium thrombus.

Left atrium and left atrial appendage thrombi are usually associated with atrial arrhythmias due to the low-flow state that subsequently induces stagnation and therefore coagulation to occur. However, in cases of atrial thrombi in normal sinus rhythm, there are certain high-risk features associated with increased risk of intracardiac thrombi formation, such as severe systolic dysfunction (as with this patient), severe diastolic dysfunction, and valvular disease. 2 As seen on this patient's CMR, her severe systolic dysfunction caused a low-flow state in her left atrium, likely resulting in stasis and subsequent thrombus formation. On echocardiography, left atrium spontaneous echo contrast (LASEC) is a finding that shows increased echogenicity from ultrasonic backscatter from red blood cell aggregates, a result of non-covalent binding between red cells and plasma proteins in low-flow and low-shear conditions. 3 In cases of patients with LASEC while in sinus rhythm, significant left atrium dilation and decreased left atrial appendage emptying velocity are additional findings. 2 The combination of increased left atrium size along with decreased left atrium contractility likely are predisposing factors for LASEC and thrombus formation. 3 Furthermore, the presence of cardiomyopathy itself can lead to inflammation and endothelial dysfunction, which, in conjunction with left atrium enlargement, place these patients at higher risk of thrombus formation and may necessitate longer anticoagulation for thrombus resolution. [4] [5] Tobacco use is also known to cause endothelial damage and dysfunction through pro-inflammatory pathway activation and induction of oxidative stress. 6 Another potential cause of left atrium thrombus in the absence of atrial fibrillation is cardiac amyloidosis through atrial electromechanical dissociation resulting from extensive amyloid infiltration of the atria and ventricles. 7 However, the findings of left ventricular dilation and absence of wall thickening on this patient's TTE coupled with her CMR findings were not consistent with an infiltrative cardiomyopathy.

Lastly, there remains a possibility that thrombus formation can be a late sequela of SARS-CoV-2 infection or the mRNA vaccination given the relative timing of the onset of symptoms compared to her previous infection and vaccinations. SARS-CoV-2 infection can lead to thrombotic complications, such as pulmonary emboli, strokes, and intracardiac thrombi, although the exact etiology is not well understood but involves the interplay between inflammation and hypercoagulability. 8 While most of the intracardiac thrombi reported in SARS-CoV-2 infections have occurred during the acute period, the pro-thrombotic state may persist for months after the resolution of the infection. 8 There have been adverse events reported of thromboembolism occurring after SAR-COV-2 mRNA vaccinations, although is far less common in patients who received the Pfizer-BioNTech

BNT162b2 vaccine compared to those who received the AstraZeneca ChAdOx1 vaccine based on the EudraVigilance European database. 9 In patients who are in sinus rhythm with no history of atrial arrhythmias or other hypercoagulable disorders, new findings of an intracardiac thrombus should prompt extended telemetry monitoring and hypercoagulability workup. Currently, no guidelines exist on the anticoagulation treatment and duration for left atrium thrombi in patients with sinus rhythm. This patient warrants long-term anticoagulation, which could be revisited if left ventricular systolic function recovers. 

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19) [published correction appears in JAMA Cardiol

Clinical and echocardiographic characteristics of patients with left atrial thrombus and sinus rhythm: experience in 20 643 consecutive transesophageal echocardiographic examinations

Clinical and echocardiographic characteristics of left atrial spontaneous echo contrast in sinus rhythm

The differences of atrial thrombus locations and variable response to anticoagulation in nonvalvular atrial fibrillation with ventricular cardiomyopathy

Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism: mechanistic links and clinical inferences

Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis

Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for atrial electromechanical dissociation

Thrombosis in COVID-19

Blood clots and bleeding events following BNT162b2 and ChAdOx1 nCoV-19 vaccine: An analysis of European data