Case reports of a double threat: when cancer and hidden congenital heart defects collide: malignant tamponade unveils a hidden pulmonary venous anomaly

Abstract

Background

Malignant pericardial effusion is a life-threatening manifestation of advanced non-small-cell lung cancer (NSCLC). Cardiac tamponade as an initial presentation is uncommon, and coexistent pathologies can complicate diagnosis and management.

Case summary

A 72-year-old man with mild chronic obstructive pulmonary disease (COPD) and a remote 2-pack-year smoking history was admitted with COVID-19 infection and possible superimposed pneumonia. Initial imaging revealed pericardial inflammation and a small effusion, raising concern for pericarditis. Subsequent echocardiography demonstrated a large pericardial effusion with tamponade physiology requiring pericardiocentesis, while cardiac magnetic resonance and computed tomography suggested possible malignancy. Cytology from pericardial and pleural fluid confirmed adenocarcinoma and bronchoscopy established stage IV epidermal growth factor–mutant NSCLC with cerebellar metastases. The patient experienced recurrent malignant effusions, managed successfully with balloon pericardiotomy and was treated with Osimertinib, resulting in sustained remission of effusions and clinical recovery. Careful review of multimodality imaging also revealed partial anomalous pulmonary venous return with significant left-to-right shunting, which may have exerted a protective hemodynamic effect on tamponade physiology. This may suggest a potential, though speculative, contribution of the anomalous pulmonary venous return to the observed tamponade physiology. At 2-year follow-up, the patient remains clinically and hemodynamically stable.

Discussion

This case illustrates the interesting duality of how multiple concurrent pathologies—including COVID-19 pneumonia, pericarditis, malignant pleuro-pericardial effusions, metastatic lung adenocarcinoma, and PAPVR—can coexist and probably shape the clinical course. The case underscores the indispensable role of multimodality imaging, molecular profiling, and minimally invasive pericardial interventions in guiding diagnosis, therapy, and prognosis in complex cardio-oncology presentations.

Learning points.

• This case highlights the danger when cancer and hidden congenital heart defects coexist. Avoid prematurely settling on a single diagnosis in complex cardio-oncology cases.

• Balloon pericardiotomy is a minimally invasive alternative for EGFR-mutant NSCLC patients with recurrent malignant effusion on Osimertinib that are ineligible for surgery.

Introduction

Malignant pericardial effusion (MPE) is an uncommon but potentially fatal complication of non-small-cell lung cancer (NSCLC).¹ Lung adenocarcinoma, particularly when driven by oncogenic mutations such as epidermal growth factor (EGFR), remains one of the most frequent causes of MPE.²

We present a case of MPE as the first sign of EGFR-mutant lung adenocarcinoma in a patient hospitalized with COVID-19 who developed MPE as the initial presentation. Complicated by tamponade and a congenital heart defect (PAPVR), the patient was managed successfully with balloon pericardiotomy and targeted therapy, emphasizing the importance of multidisciplinary approaches in complex cardio-oncology scenarios.

Summary figure

Case presentation

A 72-year-old man with mild chronic obstructive pulmonary disease (COPD) and a remote 2-pack-year smoking history presented with ongoing high fever (105°F), dry cough, malaise, and mild dyspnea 1 day after an outpatient CT chest showed lingular consolidation, a small pericardial effusion, and a small left pleural effusion. He tested positive for SARS-CoV-2 and received remdesivir. He was admitted due to concerns for superimposed healthcare-associated pneumonia, treated with piperacillin–tazobactam and a single dose of vancomycin. He developed flushing consistently with vancomycin infusion reaction, which resolved with diphenhydramine. All infectious workups, including pneumococcal, Legionella urinary antigens, blood cultures, and sputum cultures, were negative. He remained stable and was discharged to complete a 7-day antibiotic course, with follow-up pulmonary function testing and interval CT planned to reassess lingular consolidation. Echocardiography confirmed a pericardial effusion.

Over the following weeks, he developed a persistent cough and worsening exertional dyspnea, eventually present at rest. Pertinent physical examination findings were clinical findings of a frail and cachectic looking patient, no respiratory distress on seated position, visible jugular vein distention. Auscultatory wise, the lungs had bilateral decreased breath sounds with 1/4 inspiratory rales and the heart had distant sounds but regular rate and rhythm, no audible murmurs but soft audible systolic rub. Outpatient echocardiography revealed a large pericardial effusion with right-sided chamber collapse and ventricular interdependence (Figure 1A-1F). He underwent right-heart catheterization and pericardiocentesis (Figure 2), followed by therapeutic thoracentesis, removing 1.5 L of fluid, with symptomatic improvement. Post-procedural pleuritic chest pain, secondary to catheter–pericardial irritation, improved with scheduled ibuprofen, colchicine. Cardiac magnetic resonance imaging confirmed pericardial thickening, edema, and enhancement consistent with pericarditis (Figure 3). The lingular process abutting the pericardium demonstrated heterogeneous and capsular enhancement, raising concern for malignancy. In addition, partial anomalous pulmonary venous return (PAPVR) was identified, with the right superior pulmonary vein draining into the superior vena cava. Right atrial and ventricular volumes, stroke volume, cardiac output, and cardiac index were markedly increased in the setting of preserved left-sided dimensions, with estimated Qp: Qs of 1.92 by volume and 1.93 by flow (see Supplementary Materials Supplementary material online, Table S1). Coronary CT angiography confirmed nonobstructive coronary artery disease (CAD-RADS 1/P1), pericardial thickening, bilateral pleural effusions (right > left), and corroborated PAPVR; the left superior pulmonary vein was small, encased by pleural thickening and left upper-lobe collapse (Figure 4).

Figure 1.

The two-dimensional echocardiogram reveals a pronounced, circumferential pericardial effusion (IB, denoted by yellow arrows). (A and B) Represents a four-chamber apical and a short-axis view demonstrates the circumferentially severe pericardial effusion. (C) Obtained via a subcostal view, illustrates early diastolic collapse of the right ventricle (yellow arrow). (D) Depicts a plethoric inferior vena cava and engorged hepatic veins (yellow arrow), findings collectively indicative of cardiac tamponade physiology. (E) (mitral valve) and (F) (tricuspid valve) Represent respirophasic changes seen in the mitral valve showing a change of >25%.

Figure 2.

Right heart catheterization showing simultaneous pressure tracings of the right atrium and intrapericardial space, revealing pressure equalization and an absent Y descent on the right atrium pressure waveform (red arrows). Following pericardiocentesis, restoration of the Y descent (blue arrows), loss of pressure equalization, and normalization of intrapericardial pressure with respiration were observed, consistent with resolution of tamponade physiology.

Figure 3.

(A) displays cine cardiac magnetic resonance in sequential short-axis slices, illustrating a large circumferential pericardial effusion (yellow arrow) with interventricular interdependence (red arrow with rounded ends, panel 3). Notable findings include pericardial thickening and compression of the right-sided chambers, consistent with tamponade physiology. (B) Presents cardiac magnetic resonance myocardial tagging cine in sequential short-axis slices, demonstrating appropriate tag line deformation at end-systole, which is consistent with independent pericardial and myocardial motion throughout the cardiac cycle. There is no evidence of myocardial adherence to the pericardium or features indicative of effusive–constrictive pericarditis. Finally, part (C) shows late gadolinium enhancement PSIR Fat Sat cardiac magnetic resonance in sequential short-axis slices, revealing diffuse circumferential pericardial enhancement with associated thickening, consistent with malignant pericarditis. The most basal slices reveal an anterosuperior tumour with capsular and heterogeneous enhancement (red tapered arrows). Additionally, there is a large circumferential pericardial effusion compounded by post-procedural inflammatory changes.

Figure 4.

Cardiac computed tomography angiography in the sagittal plane demonstrating partial anomalous pulmonary venous return, with the right superior pulmonary vein draining into the superior vena cava. Note the associated pericardial thickening and adjacent left upper-lobe collapse with pleural involvement, consistent with malignant pericardial disease.

Cytology of pericardial and pleural fluid confirmed adenocarcinoma. Positive emission tomography (PET) and bronchoscopy-diagnosed EGFR-mutant NSCLC, stage IV due to multiple cerebellar metastases. Osimertinib was started.

Despite Osimertinib, he had recurrent effusions and progressive symptoms. He was not a surgical candidate, thus, balloon pericardiotomy was subsequently achieved with a 20–25 mm noncompliant balloon, inflated to a pressure of 3–4 atmospheres for 30–60 s via a subxiphoid approach under local anesthesia, utilizing both fluoroscopic and echocardiographic guidance (see Supplementary materials Supplementary material online, Video S1).

He had a sustained response to Osimertinib with resolution of symptoms and effusions. At 2-year follow-up, he remains stable under oncology and cardiology care.

Discussion

MPE is a well-recognized but ominous complication of advanced NSCLC, particularly adenocarcinoma. Pericardial involvement is observed in up to 20% of cancer patients at autopsy, yet symptomatic effusion or tamponade is an uncommon first manifestation.^3,4 Lung adenocarcinoma accounts for one-third to one-half of MPEs.⁴ Such patients typically present with dyspnea and hemodynamic compromise, and the prognosis is historically poor, with a median survival of only weeks to months.^2–4

Surgical pericardial window has been considered the definitive intervention for recurrent malignant effusions, offering reliable palliation but no survival advantage. In a large surgical series, median survival after subxiphoid pericardial window was 2.6 months overall, and only 2.1 months in lung cancer patients, with just 15% alive at 1 year highlighting the limited durability of surgical drainage in advanced malignancy.²

Less invasive techniques, such as percutaneous balloon pericardiotomy (PBP), have been developed as alternatives for nonsurgical candidates. Since its first description in 1991, it has demonstrated high procedural success and significantly reduced recurrence rates compared with isolated pericardiocentesis.^5,6 Contemporary series confirm its role as a palliative strategy with acceptable safety, and ESC guidelines endorse PBP with a Class IIb recommendation for MPE.⁶ In our case, balloon pericardiotomy effectively controlled recurrent tamponade in a patient deemed unsuitable for surgery.

Beyond procedural management, molecular profiling has transformed outcomes in this population. In a single centre study, nearly half of patients with lung adenocarcinoma and symptomatic pericardial effusion harboured EGFR or ALK alterations, compared with 15%–25% in the general NSCLC population.¹ Although age-adjusted analysis attenuated the association, this trend suggests that mutation-positive tumours may have a predilection for pleuro-pericardial involvement. Importantly, targeted therapy can dramatically alter prognosis. In contrast to prior tamponade reports as the initial presentation of NSCLC, where patients typically succumbed within months despite systemic therapy,^3,4 our patient achieved durable remission of effusions and 2-year survival following initiation of Osimertinib for EGFR exon 19 deletion.

Osimertinib has revolutionized outcomes in EGFR-mutant NSCLC, particularly in patients with central nervous system involvement, malignant pleuro-pericardial disease, and significant frailty. Although it has provided durable systemic and effusion control in our patient, emerging data highlight uncommon yet clinically significant cardiovascular toxicities, including Corrected QT interval prolongation, atrial arrhythmias, and reversible cardiomyopathy. Mechanistically, partial HER2 inhibition and other off-target effects may contribute.⁷ Our patient’s prior pericardial inflammation and PAPVR-associated right heart dilation may increase vulnerability to hemodynamic perturbations, reinforcing the importance of cardio-oncology surveillance with serial ECGs, echocardiography, and biomarker-guided monitoring during therapy. In addition, resistance to Osimertinib remains a clinical challenge, with mechanisms including secondary EGFR mutations, MET amplification, and histologic transformation to small-cell carcinoma.⁸ In our case, the patient has undergone extensive follow-up with serial PET scans and brain magnetic resonance imaging (MRI), all of which have demonstrated stable disease regression.

Although the exact hemodynamic impact of PAPVR as in this case cannot be confirmed, might have led to chronic right-sided volume overload resulting in right atrial (RA) and ventricular (RV) increase in volumes and pressures, thus delaying onset of right ventricular activation collapse. Also, the higher baseline central venous pressure makes the patient less sensitive to hypotension. These structural changes increase pericardial reserve volume and enhance compliance, thereby delaying the development of tamponade physiology. The RV dilation secondary to PAPVR amplifies the interventricular interdependence and pulsus paradoxus by accommodating greater volumes of pericardial effusion before a critical increase in intrapericardial pressure occurs, which is sufficient to impair cardiac function. Furthermore, persistently elevated RV intracavitary pressures necessitate even higher pericardial pressures to elicit classical tamponade manifestations. This adaptive mechanism can obscure early signs of tamponade, potentially resulting in delayed diagnosis and an increased risk of abrupt hemodynamic decompensation once pericardial reserve capacity is surpassed likely altered typical tamponade physiology by raising right-sided pressures and blunting chamber collapse.^9-11

Our case demonstrates how integrating modern imaging, percutaneous intervention, and targeted therapy can lead to sustained remission in MPE from lung adenocarcinoma, historically a condition with poor prognosis.

Conclusion

In summary, the patient presented with overlapping conditions—COVID-19, pericarditis, malignant pleuro-pericardial effusions from metastatic lung adenocarcinoma, and PAPVR. Accurate diagnosis using imaging, cytology, and genomics enabled effective, minimally invasive, and targeted treatments, underscoring the improved outlook now possible for such complex presentations.

Supplementary material

Supplementary material is available at European Heart Journal – Case Reports online.

Lead author biography

Dr. Alexis P. Rodriguez is a distinguished, multi-board-certified cardiologist with expertise in internal medicine, cardiology, echocardiography, cardiac CT, cardiac MRI, and nuclear cardiology and the Co-Founder of Innovation Healthcare Services. He directs Echocardiography and Advanced Cardiac Imaging at the Bruce Carter Miami VA Hospital and is an accomplished interventional echocardiographer for complex structural heart procedures. Dr. Rodriguez has established advanced cardiac CT and CMR programs at multiple leading institutions. A prolific author, he contributes to peer-reviewed literature and serves on national advisory committees for the U.S. Department of Veterans Affairs and the Society of CardiovascularComputed Tomography.

Consent: Written informed consent was obtained from the patient for publication of this case report, in accordance with the COPE guidelines.

Funding

None declared.

Data availability

All data underlying this article are fully available within the main text and the accompanying Supplementary material. No additional source data was generated or analyzed beyond those presented in this case report. Further inquiries can be directed at the corresponding author.