Cardiac Tamponade From Lymphocytic Constrictive Pericarditis in Primary AL Amyloidosis Without Myocardial Involvement

Abstract

Background

Isolated pericardial involvement in systemic light chain (AL) amyloidosis without myocardial infiltration is extraordinarily rare. Constrictive pericarditis with cardiac tamponade as the sole cardiac manifestation has not been previously reported.

Case Summary

A 69-year-old man presented with exertional dyspnea and was diagnosed with a large pericardial effusion with features of constrictive pericarditis. Pericardiocentesis and pericardial biopsy showed lymphocytic effusion without cardiac amyloid involvement. Biopsy of a prevertebral mass later revealed amyloid deposition, confirming systemic AL amyloidosis. He was treated with immunochemotherapy but was unfit for autologous stem cell transplant.

Discussion

This case highlights the diagnostic challenges of AL amyloidosis, especially with concomitant pericardial disease without myocardial involvement. Pericardial disease may reflect an inflammatory process rather than direct amyloid infiltration. Diagnosis is challenging given atypical presentations and limited sensitivities of initial monoclonal protein testing.

Take-Home Messages

Consider AL amyloidosis in unexplained pericardial disease. Negative monoclonal studies do not exclude systemic amyloidosis. Pursue myocardial biopsy if suspicion persists.

Visual Summary

The differential diagnoses for pericardial effusion with constrictive physiology include restrictive cardiomyopathy, cardiac tamponade, right-sided heart failure, and chronic liver disease. Cardiac involvement in systemic light chain (AL) amyloidosis typically manifests as restrictive cardiomyopathy, whereas pericardial presentations such as constrictive pericarditis and tamponade are rare. This case highlights diagnostic uncertainty in distinguishing direct amyloid infiltration from an associated inflammatory process in pericardial disease.

Take-Home Messages

• •Systemic AL amyloidosis may be associated with pericardial disease even in the absence of myocardial involvement; however, causation should not be assumed without histological confirmation of amyloid deposition.
• •Negative initial monoclonal protein studies do not exclude AL amyloidosis, particularly in low-burden disease. Repeat testing and tissue biopsy are essential when clinical suspicion persists.

History of Presentation

A 69-year-old man presented with a 3-month history of exertional dyspnea, worsening over 2 weeks, associated with orthopnea, bilateral leg swelling, and reduced effort tolerance progressing from NYHA functional class I to III. He also reported a 2-week history of productive cough without fever or constitutional symptoms.

He was tachycardic at 110 beats/min but hemodynamically stable. Examination revealed fluid overload with diminished breath sounds on the right and bilateral pitting lower limb edema. Cardiac examination was unremarkable.

Past Medical History

The patient had diabetes mellitus, hypertension, hyperlipidemia, and gout. His mother had a malignancy of unknown primary. There was no tuberculosis exposure or relevant contact history.

Differential Diagnosis

Differential diagnoses included infective pericarditis (tuberculous [TB] or viral), autoimmune disease, lymphoma, amyloidosis, and IgG4-related disease.

Investigations

Laboratory investigations were unremarkable except for elevated C-reactive protein (10.6 mg/L) and erythrocyte sedimentation rate (80 mm/h), with normal procalcitonin. N-terminal pro–B-type natriuretic peptide was 690 pg/mL with normal high-sensitivity troponin T (25 ng/L). Autoimmune work-up was negative. Electrocardiogram (Figure 1) showed sinus rhythm with low-voltage complexes and poor R-wave progression. Transthoracic echocardiogram (Figure 2) revealed a large pericardial effusion with increased respiratory variation, right ventricular diastolic collapse, and a swinging heart suggestive of early cardiac tamponade.

Figure 1.

Initial Electrocardiogram Demonstrating Low-Voltage QRS and Poor R-Wave Progression

Low voltage complexes can be indicative of pericardial effusion or infiltrative cardiac disease.

Figure 2.

Transthoracic Echocardiogram Demonstrating Large Pericardial Effusion With Right Ventricular Diastolic Collapse

(A) Parasternal long-axis and (B) apical 4-chamber views demonstrated a large circumferential pericardial effusion. (C) M-mode imaging through the right ventricular free wall showed early diastolic collapse of the right ventricle.

Pericardiocentesis yielded hemoserous exudative fluid with lymphocytic predominance (90%). Cultures (bacterial, fungal), acid-fast bacilli smears and cultures, TB polymerase chain reaction, adenosine deaminase, and cytology performed on the pericardial fluid were negative.

Computed tomography of the thorax, abdomen, and pelvis noted a large right pleural effusion, mediastinal, and right hilar lymphadenopathy, and a paravertebral mass. Magnetic resonance imaging of the thoracolumbar spine showed a T1-isointense and T2-hyperintense paravertebral thickening (12.2 × 2.3 cm) from T6 to T11 (Figure 3).

Figure 3.

Magnetic Resonance Imaging of the Thoracolumbar Spine Showing Paravertebral Soft Tissue Thickening

Sagittal (A) T1-weighted and (B) T2-weighted MRI revealed a paravertebral soft tissue thickening that is isointense on T1 and hyperintense on T2, measuring 12.2 cm in craniocaudal length, extending from T6 to T11. The yellow line denotes the craniocaudal extent of the lesion. MRI = magnetic resonance imaging.

Neurosurgery deemed the paravertebral mass unsafe for biopsy because of its anterior location.

Cardiac magnetic resonance (CMR) cine sequence (Video 1) showed septal bounce with large pericardial and pleural effusions. Black-blood imaging (Figure 4A) showed pericardial thickening. Native T1 and T2 values were not elevated, and there was no hyperintense areas of myocardial inflammation on T2 STIR sequencing (Figure 4B). Late gadolinium enhancement (Figure 4C) revealed active pericardial inflammation without myocardial involvement.

Figure 4.

Cardiac Magnetic Resonance Imaging Showing Isolated Pericardial Involvement

(A) Black blood imaging showed a thickened pericardium (arrow). (B) T2-weighted STIR sequence showed no hyperintense areas of myocardial inflammation. (C) Late gadolinium enhancement revealed active pericardial inflammation without myocardial involvement. STIR = short time inversion recovery.

Positron emission tomography/computed tomography (PET/CT) showed fluorodeoxyglucose (FDG)-avid mediastinal and right hilar lymph nodes. The paravertebral mass was largely ametabolic, with mild focal uptake. The pericardium showed enhancing thickening, with mild FDG uptake.

Despite a positive TB interferon gamma release assay and empirical tuberculosis treatment, negative microbiology and lack of spondylodiscitis reduced diagnostic certainty. As the suspicion for an alternative diagnosis grew stronger, a multidisciplinary decision between the infectious diseases and cardiology teams was made to pursue tissue diagnosis. The patient was referred to cardiothoracic surgery for biopsy of the paravertebral mass and pericardium.

Uniportal video-assisted thoracoscopic surgery drainage of right pleural effusion, pericardial window creation, and biopsy of the paravertebral mass and pericardial tissue were performed. Histology of the paravertebral mass tested positive for amyloid, and mass spectrophotometry confirmed AL subtype (Figure 5). Pericardial biopsy showed nonspecific chronic lymphoplasmacytic inflammation without amyloid deposition.

Figure 5.

Histological Confirmation of Amyloid in the Paravertebral Mass

(A) Histomorphological examination of the paravertebral mass revealed extensive extracellular eosinophilic material on hematoxylin and eosin staining. (B) Congo red staining confirmed the presence of amyloid deposits by their characteristic salmon-pink appearance. (C) Under polarized light, the deposits exhibited classic apple-green birefringence, confirming amyloid.

Initial serum and urine electrophoresis and immunofixation did not show monoclonality, and the kappa/lambda ratio was not skewed. However, repeat testing revealed an IgG kappa monoclonal gammopathy (M-band 2 g/L). Bone marrow biopsy demonstrated mildly hypocellular trilineage hematopoiesis with erythroid hyperplasia. Congo red staining was negative.

Management

Once the diagnosis of primary AL amyloidosis was reached, the patient was started on immunochemotherapy with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (DVCD). He completed 6 cycles of DVCD and is now on daratumumab maintenance therapy. He was deemed unfit for autologous stem cell transplant because of his comorbidities.

Follow-up

Clinically, the patient improved significantly, with reduction of dyspnea to NYHA functional class II, improved exercise tolerance, and resolution of peripheral edema. There were no recurrent hospitalizations for heart failure. Repeat transthoracic echocardiogram showed a small pericardial effusion with features of constrictive pericarditis, including septal shudder with septal inspirational shift and annulus reversus (Figure 6), without respirophasic variation of mitral, tricuspid, and hepatic vein flows. There was normalization of his kappa and lambda light chain values after 1 month of chemotherapy, and a repeat PET/CT 8 months after starting treatment showed stability in the size of the pericardial thickening and prevertebral soft tissue with reduction of the right pleural effusion and thickening.

Figure 6.

Repeat Transthoracic Echocardiogram Showing Annulus Reversus in Constrictive Pericarditis

(A) Lateral mitral annular early diastolic velocity (E′) (4.46 cm/s) was lower than the (B) medial E′ (5.43 cm/s).

Discussion

Primary AL amyloidosis is a rare plasma cell dyscrasia characterized by extracellular deposition of misfolded monoclonal immunoglobulin light chains, leading to organ dysfunction and high mortality. Cardiac involvement occurs in approximately 60% to 80% of patients with AL amyloidosis, is the main determinant of prognosis, and carries a median survival of about 6 months in symptomatic heart failure without effective therapy.^1,2 It is often under-recognized, contributing to delayed diagnosis and treatment. Although cardiac disease may be the initial manifestation, isolated pericardial involvement is uncommon.

Patients commonly present with nonspecific symptoms such as fatigue and weakness. Cardiac involvement typically manifests as decompensated heart failure with progressive exertional dyspnea and restrictive cardiomyopathy, including impaired diastolic filling and reduced exercise tolerance, as in the present case. With disease progression, right-sided heart failure (peripheral edema, jugular venous distension, and ascites) may develop. Although uncommon, cardiogenic shock can be the initial presentation in advanced disease. Atrial enlargement increases the risk of atrial fibrillation and thromboembolism, while conduction system involvement may lead to heart block. Syncope may arise from arrhythmias or underlying autonomic dysfunction. Angina can occur despite normal epicardial coronaries, likely because of amyloid-related microvascular dysfunction from deposition within the myocardial interstitium and intramural vessels, reducing coronary flow reserve and causing myocardial ischemia.^1,2

In systemic AL amyloidosis, pericardial involvement occurs in approximately 14% of cases, but isolated pericardial disease is rarely reported.³ This case presents a significant diagnostic challenge in distinguishing causation from association. While systemic AL amyloidosis was confirmed on paravertebral biopsy, there was no amyloid detected on pericardial histology, and there were no typical CMR features of AL cardiomyopathy, which is more commonly associated with AL-related pericardial effusion. Two possible mechanisms may explain this presentation. First, the pericardial process may represent an indirect inflammatory or immune-mediated response triggered by systemic AL amyloidosis. Second, the pericardial disease may be unrelated to amyloidosis and represents a separate systemic inflammatory process. This distinction is clinically important, as prior reports of pericardial involvement in AL amyloidosis have typically demonstrated direct amyloid infiltration, often alongside myocardial disease. The absence of both features makes this presentation atypical and precludes definitive classification as pericardial AL amyloidosis. Taken together, the absence of amyloid deposition on pericardial histology and the lack of characteristic CMR findings argue against direct pericardial infiltration. The presence of a lymphocytic infiltrate instead favors an inflammatory or immune-mediated process, indicating that indirect involvement of AL amyloidosis is more plausible than true pericardial amyloid disease, although this cannot be definitively established.

Although echocardiography identified tamponade physiology early, diagnostic evaluation in this case was challenging, as neither blood nor pericardial fluid investigations yielded the diagnosis. AL amyloidosis was not considered initially because of the atypical presentation and the absence of a monoclonal band on initial serum and urine electrophoresis. Bone marrow showed no evidence of plasma cell infiltration, further supporting the absence of overt plasma cell neoplasm at initial evaluation, likely reflecting low circulating monoclonal protein burden or predominantly tissue-localized disease. This highlights the limited sensitivity of monoclonal protein detection in early or low-burden AL amyloidosis, where serum-free light chain assay has a sensitivity of approximately 75%, increasing to 99% when combined with serum and urine electrophoresis and immunofixation.⁴ However, false-negative results may still occur because of low disease burden, rapid tissue deposition, or inherent assay limitations.

Given the location of the paravertebral mass, a surgical biopsy, rather than a percutaneous biopsy, had to be performed. Cardiothoracic surgery, under general anesthesia, was also associated with greater risks. Ultimately, the paravertebral mass biopsy confirmed the diagnosis of primary AL amyloidosis.

Management was 2-pronged, consisting of relief of tamponade and the diagnostic evaluation for the underlying disease. The identification of tamponade physiology during echocardiography prompted urgent pericardiocentesis, which was for both diagnostic and therapeutic purposes. Once the diagnosis of AL amyloidosis was confirmed, systemic therapy with immunochemotherapy was arranged. This regimen has demonstrated efficacy in halting amyloid production and improving outcomes in patients with AL amyloidosis.⁵ Early initiation of therapy is critical, as delayed treatment can result in progressive organ dysfunction and poor prognosis.

Conclusions

This case demonstrates an unusual presentation of AL amyloidosis with isolated lymphocytic constrictive pericarditis and tamponade without myocardial involvement. It illustrates that the coexistence of systemic AL amyloidosis and pericardial disease does not necessarily establish causality. Definitive attribution of pericardial pathology to amyloidosis requires histological confirmation, and in its absence, alternative diagnoses must be carefully considered.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Video 1

Cardiac Magnetic Resonance Cine Sequence Demonstrating Septal Bounce Along With a Large Pericardial Effusion and Pleural Effusion

Classic septal bounce seen on CMR cine sequence, indicating ventricular interdependence consistent with constrictive physiology. CMR = cardiac magnetic resonance.