Severe Left Ventricular Thrombus in the Context of Heart Failure and COVID-19: A Case Report

Introduction

Left ventricular thrombus (LVT) is a well-recognized consequence of heart failure and acute myocardial infarction (MI) [1,2]. The increasing prevalence of heart failure has made heart failure the leading cause of LVT formation, with 6.1% of patients with low ejection fraction found to have LVT, as detected by trans-thoracic echocardiography, surpassing its historically predominant association with MI [3]. The emergence of thrombus within the left ventricle is influenced by the 3 factors encapsulated in Virchow’s Triad: diminished wall motion and blood flow stasis, endothelial injury due to MI, and inflammation-induced hypercoagulability [4]. These mechanisms, common in heart failure and MI, create a prothrombotic environment within the left ventricle. In particular, poor hemodynamics and blood stasis significantly contribute to the development of LVT by disrupting the normal circulation and enhancing the risk of thrombogenesis [3].

Thrombus accumulation in the left ventricle is undeniably driven by impaired hemodynamic performance and progresses in accordance with Virchow’s Triad [3,4]. However, less attention has been paid to how LVT itself can further compromise cardiac hemodynamics. Emerging evidence suggests that LVT not only results from poor hemodynamics but also actively contributes to their deterioration [3]. By occupying a substantial portion of the left ventricle, the thrombus reduces the available volume for effective ventricular filling and contraction, thereby diminishing the heart’s hemodynamic reserve and exacerbating cardiac dysfunction. In addition, LVT disrupts hemodynamics by obstructing the ventricular cavity, reducing compliance, and altering pressure gradients, all of which promote blood stasis and further thrombus growth [5]. Ultimately, LVT impairs cardiac function by decreasing stroke volume and cardiac output, increasing the risk of systemic embolism, stroke, and mortality [3,5,6]. Mortality data compiled by the American Heart Association from retrospective studies indicate a peak mortality rate of 27.9%, especially among patients with severe LV systolic dysfunction [4,7]. Despite growing evidence linking LVT to worsening hemodynamics, further research is needed to fully elucidate these mechanisms and their impact on clinical outcomes.

In this case report, we present a patient with a massive thrombus occupying more than half of the LV volume. To the best of our knowledge, no previously published case has documented an LVT as large as the one presented here, making the echocardiographic image in this manuscript uniquely valuable [1,5]. We hypothesize that the thrombus, precipitated by SARS-CoV-2 infection, may have resulted from the patient’s poor hemodynamic profile and, in turn, contributed to further hemodynamic deterioration.

Case Report

A 59-year-old woman presented to the Emergency Department with severe dyspnea, particularly when lying down. She had been routinely visiting the outpatient clinic in our hospital for 2 years with heart failure problems requiring routine medication. She missed 1 appointment prior to this emergency visit, because of an episode of hospitalization for treating COVID-19 in another hospital, which occurred within 1 month of the present visit. Her risk factors for cardiovascular disease included hypertension and history of smoking. She had received a diagnosis of severe coronary artery disease 1 year prior to this admission (Figure 1). She was planned for revascularization surgery of coronary artery bypass grafting, but she refused the surgery and was willing to have only routine medication. Her vital signs showed a blood pressure of 94/58 mmHg, heart rate of 110 beats per min, respiratory rate of 30 breaths per min, and oxygen saturation of 91% on room air. The findings on physical examination supported the congestion symptoms of the patient (tachycardia, rales predominantly on the lower part of both lungs, and bilateral leg swelling). Persistent ST-segment elevation was noted from her electrocardiogram, which was similar to her previous result (Figure 2). Subsequent chest X-Ray showed signs of pulmonary edema, including prominent cardiomegaly (Figure 3). Her laboratory test results upon admission were unremarkable (serum creatinine 1.4 mg/dL, eGFR 37 mL/min/1.73 m2, serum albumin level 3.9 g/dL, and D-dimer level 0.44 μg/mL FEU). The primary diagnosis was acute decompensated heart failure, and she admitted to the inpatient ward for aggressive diuretic therapy to relieve congestion.

The patient responded well to diuretic treatment. She experienced relief from congestion during the 5-day hospitalization. Transthoracic echocardiography (TTE) was performed during the hospitalization. Impaired LV function was noted, with an LV ejection fraction (LVEF) of 28%. A massive thrombus in the left ventricle was identified. The thrombus occupied approximately half of the LV cavity. Using the end-diastolic volume (EDV) formula in echocardiography, based on the apical 4-chamber view, it was revealed that the estimated functional LV cavity was 97 mL, compared with the total LV cavity of 237 mL (Figure 4). The functional LV cavity refers to the portion of the chamber available for blood filling and effective circulation. This massive thrombus, approximately 140 mL in volume, was a new finding, compared with her last TTE performed 1 year earlier (Table 1). Due to resource constraints, magnetic resonance imaging (MRI) and 3D imaging could not be performed. Additionally, compatibility issues with the available ultrasound equipment prevented the use of more advanced imaging techniques. The hemodynamic profile of the left ventricle was measured by using the Doppler method for cardiac output estimation. The measurements revealed 44 mL of stroke volume, 2.9 L/min of cardiac output, and a systemic vascular resistance of 1048 dyne·s·cm−5. These findings indicated a low cardiac output with a relatively preserved systemic vascular resistance. Right heart catheterization using a Swan-Ganz catheter was not performed, as the patient refused any invasive procedures. In this situation, echocardiography emerged as the most practical and feasible alternative for measurement. Efforts to dissolve the thrombus included multiple doses of low-molecular-weight heparin, overlapped with oral anticoagulation. Surgical removal of the thrombus was considered. A thorough discussion involving the patient and her family was conducted, outlining the procedural risks and potential long-term survival benefits. However, consistent with her previous refusal of invasive intervention, the patient declined this option. The thrombus persisted until discharge, without signs of improvement despite her better functional capacity. The patient was planned for a more intense follow-up in the outpatient clinic.

The patient experienced 3 additional episodes of rehospitalization, due to decompensated heart failure over the next 3 months, despite receiving optimal doses of heart failure medications. The patient was on key guideline-directed medical therapy medications, including a mineralocorticoid receptor antagonist, angiotensin receptor-neprilysin inhibitor, and beta-blocker; however, some medications were paused due to acute heart failure and hypotension. The beta-blocker and angiotensin receptor-neprilysin inhibitor were temporarily withheld. Her serum creatinine progressively increased, peaking at 5 mg/dL during her final hospital stay. During her final hospitalization, the patient’s condition markedly deteriorated, characterized by hypotension, congestive symptoms, oliguria, and decreased consciousness. In light of her clinical trajectory, the family consented to a do-not-resuscitate order. The patient subsequently died from low cardiac output syndrome.

Discussion

The occurrence of an LVT is a significant complication of heart failure [8]. This aligns with the fact that factors predicting the occurrence of LVT include involvement of anterior MI, LV akinesis or dyskinesis, reduced LVEF, severe diastolic dysfunction, and extensive infarct size [1]. The patient presented in this case report was particularly susceptible to LVT formation, due to her reduced LVEF, global hypokinesis of the left ventricle, and a history of extensive MI, which aligned with these risk factors [1,9]. However, while LVT often reflects the severity of LV dysfunction, its direct role in worsening heart failure remains uncertain. Its potential contribution to heart failure exacerbation, through mechanisms such as reduced cardiac output, requires further investigation.

LVT develops through a complex process involving the components of Virchow’s Triad: hypercoagulability, blood stasis, and endothelial injury [5]. In heart failure with reduced ejection fraction, a predisposition to a hypercoagulable state can elevate the risk of thrombus development. Blood stasis is mainly caused by LV dysfunction with reduced LVEF and/or large apical or anterior LV akinesis or dyskinesis, which facilitates stasis through abnormal vortex formation [3]. Additionally, the patient’s history of severe coronary artery disease prompted rapid regional thinning and dilation of the damaged endothelium in the infarct zone, increasing wall stress and potentially resulting in ventricular aneurysm, further elevating thrombotic risk [4]. All these predisposing conditions were present in our patient, making the occurrence of LVT a reasonable outcome.

The direct role of LVT in the progression of heart failure and the worsening hemodynamics remains uncertain and continues to be a subject of clinical investigation [3]. LVT often develops during later stages of heart failure, when LV function is already severely compromised [7]. This has fueled ongoing debate, suggesting that in advanced heart failure, cardiac function is so severely affected that the presence of LVT may not significantly contribute to hemodynamics. This raises the question of whether LVT is merely a bystander in the ongoing deterioration. In contrast, recent evidence has outlined several mechanisms by which LVT may actively influence and worsen hemodynamic performance [3–7].

Several mechanisms have been proposed to explain how LVT might worsen heart failure. A major concern is that the thrombus can physically occupy the left ventricle, limiting its capacity to fill or pump blood effectively. The presence of LVT reduces the available volume for incoming blood flow, thereby compromising preload and overall cardiac output [5]. TTE examination of our patient revealed a significant change in LVEDV value, due to the massive thrombus occupying a large portion of the left ventricle. The comparison of her LVEDV with and without accounting for the thrombus volume showed a ratio of approximately 1: 2.5. Furthermore, with the thrombus occupying nearly half of the ventricular space, impaired diastolic filling may have contributed to altered flow dynamics and reduced overall LV efficiency [10]. This results in reduced cardiac output, worsening the symptoms of heart failure [9–11]. Our patient experienced a significant deterioration leading to low cardiac output syndrome and recurrent episodes of acute decompensated heart failure. These hemodynamic changes may have contributed to further deterioration in LV function [3]. This turn of event is accurately illustrated by the clinical progression in our case, in which inadequate blood flow to the kidneys and brain led to acute kidney injury, cardiogenic shock, hemodynamic instability, and ultimately death, due to low cardiac output syndrome.

While these pathophysiological mechanisms are well established, additional clinical considerations must be addressed to fully interpret the patient’s deterioration. First, the possibility of ongoing ischemia contributing to the patient’s clinical deterioration must be acknowledged. Second, it is plausible that the heart failure was already at an advanced stage, rendering the LVT a bystander rather than a primary cause of worsening cardiac function. Third, the patient’s adherence to guideline-directed medical therapy could have influenced disease progression. To accurately determine the role of these factors, sequential measurements using invasive diagnostic methods would be necessary; however, they were not performed in our patient. Nevertheless, the hemodynamic impact of LVT has been well documented in previous literature [9–11]. While some uncertainties persist, it is evident that LVT adversely affected the patient’s hemodynamic status and may have significantly contributed to her clinical deterioration.

Adding further complexity to this case is the patient’s history of COVID-19, which may have been a contributing factor in the development of LVT. During the pandemic, the incidence of LVT among patients presenting with MI was reportedly increased, with an incidence of 35.3% in critically ill hospitalized patients [12]. Previous publications have reported the discovery of LVT during the hospitalization of patients with COVID-19 [13,14]. Multiple studies have demonstrated the link between SARS-CoV-2 infection and coagulopathy [12–14]. The findings of intracardiac thrombus had also been reported in patients with SARS-CoV-2 infection [15,16]. The primary mechanism for thrombus development is believed to be the activation of endothelial cells by viral particles [12]. The patient in the present case had a recent history of SARS-CoV-2 infection, which preceded the development of LVT and subsequent heart failure decompensation by a relatively short interval. The close timing of these events suggests a potential pathophysiological connection, with the SARS-CoV-2 infection likely acting as a precipitating factor in the development of LVT.

It is interesting to highlight that previous case reports of LVT typically describe thrombi no larger than 2 cm [1,5]. No previous reports depict a massive LVT occupying more than half of the LV cavity, as observed in our case. Furthermore, the common practice for reporting thrombus size typically involves measuring its dimensions as (a×b) cm, where a and b represent the longest and shortest axes of the thrombus. This method is practical when the thrombus presents as a relatively uniform solid structure [1,5,13]. However, in cases like ours, in which the thrombus exhibits an irregular shape, this method of reporting may not adequately describe its morphology. Instead, we opted to estimate its size using a 2-dimensional (2D) formula for volume quantification, to better capture the complexity of its structure. Nevertheless, this approach has significant limitations. The estimated measurement, derived from 2D imaging techniques, is inherently less accurate than that of 3D imaging modalities or advanced techniques, such as cardiac MRI. Studies have shown that MRI provides superior accuracy in assessing thrombus volume, due to its high spatial resolution and ability to visualize complex structures in 3 dimensions [17].

In terms of management therapy, there is currently no standardized approach for treating LVT. The focus is on dissolving the existing thrombus, with options including low-molecular-weight heparin or unfractionated heparin, combined with oral anticoagulation [7]. However, urgent surgical thrombectomy can be necessary for a large mobile thrombus [9]. Nevertheless, the concern with surgical removal of a large LVT is poor LV function [18]. The prognosis for recurrent LVT formation or increased size is associated with poor treatment adherence, chronic renal failure, and prothrombotic conditions [9]. In the present case, the management prescribed to the patient involved low-molecular-weight heparin overlapped with oral anticoagulants. Although surgical thrombectomy was considered, the patient declined the option.

There are several limitations we found in this case regarding the data history, diagnostic procedures, and management program. First, the patient’s history of COVID-19 as a precipitating prothrombotic factor could not be explored in detail, because it happened during a separate hospitalization episode in another hospital. Known urinary microalbumin levels might have given valuable insight to analyze vascular endothelial function. Second, we could not accurately assess LV performance because the echocardiography being used at that time lacked the technical support for 3D imaging and strain analysis. Similarly, measurements of LV volume were constrained by using only a 2D formula for LVEDV, which lacks accuracy due to its reliance on geometric assumptions that do not account for the presence of LVT. Finally, choosing the definitive therapy for this patient was challenging because the patient refused initial consent for surgery.

Conclusions

We presented a case of a massive thrombus found in the left ventricle of a patient with heart failure, with low LVEF. SARS-CoV-2 infection was a likely precipitating factor, based on the timing and clinical context. We highlighted how the thrombus occupied a large portion of the left ventricle, impairing its hemodynamic performance even further. This ultimately leads to complications involving low cardiac output, multiorgan dysfunction, and death.