Left Ventricular Diastolic Collapse in a Multiloculated Malignant Pericardial Effusion

Graphical abstract

Highlights

• •Left ventricular diastolic collapse is a hallmark of regional tamponade.
• •Malignant PEff has high recurrence rate with pericardiocentesis.
• •Pericardial window is a definitive approach in loculated malignant PEff.

Introduction

Cardiac tamponade results from the accumulation of pericardial fluid that increases intrapericardial pressure leading to compression of cardiac chambers, impairment of diastolic filling, and reduction of cardiac output. Classic echocardiographic findings of tamponade due to a circumferential pericardial effusion (PEff) include right atrial and right ventricular collapse as the lower filling pressures in these chambers make them more vulnerable to compression. However, the presence of pericardial adhesions and localized PEffs can cause regional cardiac tamponade, characterized by focal chamber compression. When a PEff is localized adjacent to the left ventricle (LV) and the pericardial pressure exceeds left ventricular diastolic pressure, left ventricular diastolic collapse can occur. This sign is a hallmark of regional tamponade and can be seen in postcardiac surgical patients, loculated malignant PEffs, and traumatic hemopericardium.

In this case report, we highlight a visually compelling example of tamponade due to a multiloculated malignant PEff. We review the echocardiographic features of tamponade, with particular emphasis on the hemodynamic consequences of loculated PEffs and the diagnostic significance of left ventricular diastolic collapse.

Case Presentation

A 63-year-old patient with metastatic epidermal growth factor receptor mutation–positive non-small-cell lung cancer on osimertinib presented for an elective pleural-peritoneal shunt in the setting of recurrent malignant pleural effusions (PLEffs) with multiple prior thoracenteses. Their clinical course (Figure 1) was complicated by cardiac tamponade 3 months prior secondary to a large circumferential malignant PEff requiring pericardiocentesis in the setting of progressive fatigue, shortness of breath, and hypotension. Transthoracic echocardiography (TTE) at that time demonstrated a large circumferential PEff with right atrial invagination and delayed right ventricular relaxation suggestive of tamponade physiology (Figure 2, Videos 1-2). The patient underwent percutaneous pericardiocentesis by a subxiphoid approach with 500 mL of bloody fluid removed from the pericardial cavity. Histopathology of the pericardial fluid was consistent with metastatic adenocarcinoma. The pericardial drain remained in place for 48 hours with minimal output. It was removed without complication, and the patient was discharged home.

Figure 1.

Timeline of the clinical presentation, associated echocardiographic findings, and management.

Figure 2.

Two-dimensional TTE (obtained at initial presentation), parasternal long-axis (A) and apical 4-chamber (B) diastolic views, demonstrates normal left ventricular size with a large circumferential PEff and right ventricular collapse.

Three months later, the patient underwent placement of an elective pleural-peritoneal shunt with an automatic continuous effusion shunt system. Preshunt computed tomography (CT) chest imaging demonstrated a large left PLEff with complete collapse of the left lower lobe as well as a mild to moderate-sized PEff (Figure 3). Preshunt TTE demonstrated a small circumferential PEff measuring 3 to 6 mm in diameter without clear loculations, exaggerated mitral inflow variation (31%), and paradoxical septal motion consistent with constrictive physiology. Right ventricular size was at the upper limits of normal with qualitatively normal right ventricular function.

Figure 3.

Chest CT images, coronal (top panel) and serial axial (middle and bottom panel), before (left) and after (right) pleural-peritoneal shunt placement, demonstrate an initial large PLEff (arrows) that is markedly reduced postprocedure, an initial small PEff that is mildly larger postprocedure, the anatomic relationship and proximity between the left-sided PLEff and the PEff, and the irregular thickening of the pericardium concerning for metastatic disease.

Placement of the pleural-peritoneal shunt was completed without complication, with 2.0 L of serosanguinous fluid aspirated prior to placement. Postshunt chest CT demonstrated proper placement of the shunt with expected postoperative changes as well as a subjectively somewhat larger PEff (Figure 3). On postshunt day 2, the patient was tachycardic (115 bpm) and hypotensive (86/56 mm Hg). An electrocardiogram revealed sinus tachycardia with nonspecific ST changes. Physical exam revealed jugular venous distension, distant heart sounds without a pericardial friction rub, and a pulsus paradoxus of 14 mm Hg. Laboratory testing showed elevated serum lactate at 2.9 mmol/L (normal range, 0.5-2.0 mmol/L) and creatinine 1.83 mg/dL (normal range, 0.6-1.3 mg/dL). A TTE at this time revealed a large PEff with multiple loculated pockets resulting in compression of all 4 cardiac chambers (Figure 4, Videos 3-4). There was prominent diastolic collapse of the apical and lateral walls of the LV (Figure 5, Video 5) in addition to right ventricular diastolic collapse (Video 4). There was pericardial thickening (4.0 mm) with tethering of the right ventricular free wall and lateral LV as seen by the loss of the normal sliding motion between the visceral and parietal pericardium. Loculated effusions were also noted to be impinging on the right and left atria.

Figure 4.

Two-dimensional TTE, subxiphoid diastolic (A) and systolic (B) views, demonstrates a large loculated PEff with septations/adhesions (arrows) and phasic compression on the right atrium, RV, and LV. RV, Right ventricle.

Figure 5.

Two-dimensional TTE, apical 4-chamber diastolic (A) and systolic (B) views, demonstrates the loculated PEff adjacent to the apical and lateral walls of the LV with invagination and collapse of the left ventricular wall during diastole (arrow); the M-mode display (C) from a cursor placed through the abnormal left ventricular wall segment demonstrates the timing of the left ventricular motion to discern the diastolic collapse (arrow).

Paradoxical septal motion consistent with ventricular interdependence was present (Video 4). Additionally, there was significant respirophasic variation in valvular inflow velocities with a 44% tricuspid valve inflow velocity increase with inspiration (Figure 6A) and 25% mitral valve inflow velocity decrease with inspiration (Figure 6B), which represent Doppler surrogates of pulsus paradoxus. With inspiration, left ventricular outflow tract peak velocity decreased 28% from 0.75 m/sec to 0.54 m/sec (Figure 7); the velocity-time integral on 3-chamber view was measured at 8.8 cm and decreased 30% to 6.2 cm with inspiration, consistent with respirophasic reduction in stroke volume. The inferior vena cava was plethoric at 2.3 cm with a 22% decrease in size with sniff (Figure 8A, Video 6). Additionally, there was evidence of expiratory hepatic vein flow reversal (Figure 8B). Collectively, these findings supported the presence of hemodynamically significant tamponade physiology.

Figure 6.

Two-dimensional TTE, apical 4-chamber view guided pulsed-wave spectral Doppler display, demonstrates the exaggerated inspiratory variation in tricuspid (A; 44% increase) and mitral (B; 25% decrease) inflow velocities consistent with tamponade physiology.

Figure 7.

Two-dimensional TTE, apical 3-chamber view guided pulsed-wave Doppler display across the left ventricular outflow tract, demonstrates marked inspiratory variation in peak velocity (28% decrease) and stroke distance (VTI; 30% decrease). VTI, Velocity time integral.

Figure 8.

Two-dimensional TTE, subcostal view (A) and pulsed-wave spectral Doppler display of the hepatic vein (B) with respirometer tracing, demonstrates inferior vena cava dilation with less than 50% inspiratory collapsibility and increased flow reversal during expiration, consistent with elevated right atrial pressure and tamponade physiology.

Emergent surgical subxiphoid pericardial window was performed with approximately 500 mL of dark bloody fluid removed and immediate hemodynamic improvement. Dense pericardial adhesions were palpated and manually dissected. A pericardial drain was placed to continuous suction, and the patient was subsequently admitted to the intensive care unit for monitoring. Histopathology confirmed malignant pericardial involvement with detached clusters of adenocarcinoma cells (Figure 9). Pericardial fluid was noted to have rare mesothelial cells in a background of abundant blood without malignant neoplasm identified. C-reactive protein was found to be elevated to 10.2 mg/dL (normal, <0.05 mg/dL), and colchicine was subsequently initiated for the concomitant treatment of pericardial inflammation. The pericardial drain was removed after 72 hours given decreasing output. The patient was subsequently discharged home with close outpatient follow-up. One-month follow-up TTE was without evidence of reaccumulated PEff or signs of constriction. Interval CT imaging at this time demonstrated worsening sclerotic skeletal metastasis, and the patient was started on chemotherapy (pemetrexed and carboplatin) in addition to osimertinib given the high oncological disease burden.

Figure 9.

(A) Hematoxylin and eosin staining at ×4 (A) and ×10 (B) magnification, demonstrates clusters of malignant cells consistent with adenocarcinoma within the pericardium; immunochemistry for thyroid transcription factor-1 (C) and claudin-4 (D) demonstrates nuclear positivity in malignant cells and membranous positivity, respectively, consistent with primary lung adenocarcinoma.

Discussion

Malignant PEffs are often seen in advanced stages of cancer and are associated with poor prognosis.¹ Prevalence of cardiac and pericardial involvement among all malignancies varies between 5% and 20%, with lung cancer being the most common metastatic malignancy with pericardial involvement.^2,3 Given their underlying etiology, malignant PEffs have high recurrence rates. Following isolated pericardiocentesis for malignant PEffs, the recurrence rate was observed to be 38%.⁴ Reduced recurrence rates were observed with extended catheter drainage (12%), pericardial sclerosis (10%), balloon pericardiotomy (10%), and pericardial window strategies (<7%).⁴ An additional observational study demonstrated that 26% of malignant PEffs were noted to reoccur following pericardiocentesis, and among those, 42% required subsequential pericardial windows.⁵ Colchicine has been shown to improve clinical outcomes including all-cause death and rate of PEff reoccurrence in the setting of malignant PEffs, whereas NSAIDs and steroids have not demonstrated similar benefit.⁵ Additionally, 80% of malignant PEffs were found to develop adhesions following pericardiocentesis, predisposing for the formation of loculated PEffs.⁵

Unlike tamponade caused by a circumferential effusion producing uniform increases in pericardial pressure and hallmark signs such as right atrial and right ventricular collapse, loculated PEffs can cause regional compression with atypical or absent classic TTE findings in cardiac tamponade. In this case, the patient was found to be in shock secondary to tamponade in the setting of a recurrent multiloculated PEff resulting in both right- and left-sided cardiac chamber collapse. Although uncommon, left ventricular diastolic collapse was accompanied by additional classic echocardiographic signs of tamponade including right ventricular diastolic collapse, systolic right atrial compression, exaggerated respiratory changes in tricuspid and mitral valve inflow velocities, inferior vena cava plethora, and expiratory hepatic vein flow reversal.

Although tamponade is ultimately a clinical diagnosis, echocardiography remains essential in the assessment of PEffs and identification of tamponade physiology. In this case, echocardiography was critical to guide management; the observed multiloculated PEffs with significant adhesions were not amenable to percutaneous drainage, and a surgical window was felt to be the only definitive management option.⁶ A percutaneous pericardiocentesis approach would likely have been ineffective in the acute management of tamponade, given the loculated nature of the PEff and the presence of fibrinous adhesions that significantly limit accessibility between fluid pockets. Prior case reports demonstrated feasibility of a percutaneous pericardiocentesis approach if there was a single large PEff pocket.⁷ Furthermore, percutaneous pericardiocentesis would have been insufficient to prevent recurrence and may not have addressed underlying or evolving effusive-constrictive physiology, thereby necessitating more definitive surgical intervention such as pericardiectomy.

The finding of left ventricular diastolic collapse is a hallmark of regional cardiac tamponade. In this case, the loculated PEff at the apical and lateral wall of the LV resulted in greater pericardial pressure compared to left ventricular filling pressure during diastole, resulting in collapse. Left ventricular diastolic collapse was first systematically described by Chuttani et al.,⁸ when it was observed to be a frequent sign of tamponade in postoperative cardiac surgery patients due to postsurgical adherence of the right heart chambers to the anterior chest wall and predilection for regional posteriorly located PEffs. Subsequent studies in canine models of acute regional left heart tamponade demonstrated that left ventricular collapse was associated with significant hemodynamic compromise. Using latex balloons placed within the pericardial space and incrementally filling with saline, the onset of left ventricular diastolic collapse was observed when the mean arterial pressure had decreased by 13% from baseline and cardiac output had decreased by 20%. Notably, diastolic collapse occurred when the pressure within the left pericardial compartment exceeded left ventricular diastolic pressure by just 3 mm Hg, resulting in a reversal of the transmural pressure gradient.⁹ Left ventricular diastolic collapse is an important echocardiographic finding to recognize that carries significant hemodynamic implications.

Histopathology confirmed malignant pericardial involvement. Malignant PEffs are often hemorrhagic due to neoplastic invasion of the pericardium and pericardial capillary-venule network. The bloody nature of the PEff can complicate cytological interpretation.^10,11 However, in confirmed cases of malignant pericardial disease, systemic antineoplastic treatment is recommended.¹² The patient's acute decompensation is likely multifactorial, related to the preexisting PEff, presence of malignant pericardium, thoracic intervention with the placement of a pleural-peritoneal shunt, and fluid and pressure shifts stemming from the shunt.

In particular, the placement of a pleural-peritoneal shunt may have altered thoracic pressure dynamics by reducing intrathoracic pleural pressure, thereby increasing the transmural pressure gradient across the pericardium. This could facilitate further pericardial expansion and fluid accumulation, especially in the context of malignant involvement of the pericardium. Additionally, the close anatomical relationship between the pleural and pericardial spaces allows for pressure transmission between compartments. As pleural pressure falls, pericardial restraint may diminish, potentially unmasking or exacerbating tamponade physiology.

The coexistence of PLEffs and PEffs, particularly in malignancy, is not uncommon and can complicate both diagnosis and management. These effusions may exert additive compressive effects on the heart and lungs, contributing to hemodynamic compromise and respiratory distress.¹³ Interestingly, there are reports describing resolution of tamponade physiology following thoracentesis alone, without direct pericardial drainage. This phenomenon is thought to occur due to a reduction in intrathoracic pressure, which in turn improves cardiac filling by restoring a favorable pressure gradient across the pericardium, particularly when the pericardium is otherwise normal and elastic. In select cases, particularly when the PEff is moderate in size and the PLEff is large, thoracentesis may transiently relieve cardiac tamponade physiology and delay or obviate the need for immediate pericardiocentesis. However, in patients with loculated or high-pressure PEffs, especially those with malignant or hemorrhagic characteristics accompanied by noncompliant pericardial thickening, definitive management often still requires surgical intervention.

Although echocardiography remains the standard and first-line modality for evaluating pericardial disease, advanced imaging modalities such as cardiovascular magnetic resonance and cardiac CT play important roles in the comprehensive assessment of pericardial pathology as second-line modalities.^14,15 Cardiovascular magnetic resonance with late gadolinium enhancement is particularly useful in detecting active inflammation, neoplastic infiltration, or fibrosis within the pericardium, offering superior tissue characterization compared to other modalities. Cardiovascular magnetic resonance can also identify associated myocardial involvement and assess for hallmarks of constrictive physiology including ventricular interdependence, diastolic septal bounce, and pericardial constraint. However, due to its prolonged image acquisition time, cardiovascular magnetic resonance is not suitable for hemodynamically unstable patients.

Cardiac CT provides high-resolution anatomical detail and is especially useful in visualizing pericardial thickening, calcification, or masses that may suggest neoplastic infiltration. Computed tomography can also delineate the extent of loculated PEffs, identify extrinsic compression of cardiac chambers, and assess the relationship of pericardial fluid to surrounding thoracic structures, which can aid in preprocedural planning, particularly when surgical intervention is anticipated.

Conclusion

Multiloculated malignant PEffs can result in focal chamber compression, including left ventricular diastolic collapse with or without other classic echocardiographic findings of tamponade physiology. Surgical pericardial window offers a more definitive approach than percutaneous pericardiocentesis in these cases, particularly since percutaneous drainage limits anatomic access and a high likelihood of recurrence is anticipated.

Ethics Statement

The authors declare that the work described has been carried out in accordance with the following guidelines: The authors declare that the work described was conducted in accordance with the principles of the Declaration of Helsinki.

Consent Statement

Complete written informed consent was obtained from the patient (or appropriate parent, guardian, or power of attorney) for the publication of this study and accompanying images.

Funding

The authors declare that this report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosure Statement

The authors reported no actual or potential conflicts of interest relative to this document.

Supplementary Data

Video 1

Two-dimensional TTE, parasternal long-axis view, demonstrates normal left ventricular size with a large circumferential PEff, right ventricular diastolic collapse, and delayed right ventricular filling suggestive of tamponade physiology.

Video 2

Two-dimensional TTE, apical 4-chamber view, demonstrates normal left ventricular size with a large circumferential PEff with right ventricular diastolic collapse and delayed right ventricular filling suggestive of tamponade physiology.

Video 3

Two-dimensional TTE, subxiphoid 4-chamber view, demonstrates large loculated PEff with septations/adhesions with compression on the right atrium, right ventricle, and LV. Diastolic collapse is noted on the right ventricle.

Video 4

Two-dimensional TTE, subxiphoid 5-chamber view, demonstrates large loculated PEff with septations/adhesions with compression on the right atrium, right ventricle, and LV. Diastolic collapse is noted on the right ventricle.

Video 5

Two-dimensional TTE, apical 4-chamber view, demonstrates loculated PEff abutting the apical and lateral walls of the LV. Collapse of the left ventricular wall is observed during diastole.

Video 6

Two-dimensional TTE, subcostal view, demonstrates inferior vena cava dilation with less than 50% inspiratory collapsibility, consistent with elevated right atrial pressure and tamponade physiology.