Secondary Cardiac Lymphoma Causing High-Grade Heart Block

Abstract

Background

Cardiac lymphoma can cause rapidly progressive high-grade atrioventricular block by infiltrating the conduction system. Because conduction disease may improve with lymphoma-directed therapy, pacemaker decisions are complex.

Case Summary

A 44-year-old man with lymphoma developed extensive secondary cardiac involvement and progressive conduction system disease. Given the possibility of reversibility with immunotherapy, multidisciplinary discussions and shared decision-making were used to determine whether pacemaker implantation was warranted and to select the most appropriate device. An active-fixation leadless pacemaker was ultimately implanted.

Discussion

This case highlights the uncertainty regarding pacemaker management in cardiac lymphoma. Decisions should be individualized based on expected treatment response, infection risk, and patient preferences.

Take-Home Messages

Cardiac lymphoma may present with rapidly progressive conduction disease, and the degree of reversibility following lymphoma-directed therapy can be difficult to predict. Decisions regarding pacemaker implantation should be individualized and informed by the expected treatment response, infectious and procedural risks, and patient preferences.

Visual Summary

History of Presentation

A 44-year-old man presented to the emergency department (ED) with progressive lower back and left leg pain. He denied weakness, saddle anesthesia, or fecal or urinary retention or incontinence. Physical exam was unremarkable, with intact cranial nerves and full strength and sensation bilaterally. Vital signs and routine labs were within normal range.

Past Medical History

The patient had a history of hypertension, hyperlipidemia, type 2 diabetes mellitus, and obstructive sleep apnea. There was no reported history of cardiac disease.

Differential Diagnosis

The initial presentation was most consistent with benign musculoskeletal pain. Spinal cord compression from severe stenosis, abscess, or mass was also on the differential.

Investigations

X-ray revealed an L3 compression fracture, with subsequent spine magnetic resonance imaging (MRI) showing probable metastatic disease. The patient was admitted for an expedited workup, which confirmed the diagnosis of aggressive B-cell lymphoma. He completed a course of chemo-immunotherapy without complication. An electrocardiogram demonstrated a normal sinus rhythm (Figure 1A).

Figure 1.

Electrocardiograms Demonstrating Progression of Heart Block

(A) Baseline electrocardiogram at time of initial lymphoma diagnosis demonstrating normal sinus rhythm. (B) Sinus rhythm with marked first-degree atrioventricular (AV) block. (C) Accelerated junctional rhythm with retrograde P waves. (D) Complete AV block with accelerated junctional escape rhythm (ventricular rate 60).

The patient presented to the ED soon after discharge for a primary gastrointestinal complaint and was incidentally found to have pericarditis with a large pericardial effusion and borderline tamponade physiology. Left ventricular ejection fraction (LVEF) was normal at 66% and left ventricular diastolic function was pseudo-normal (grade II dysfunction). A pericardial drain was placed, with cytopathology confirming a malignant effusion. Chimeric antigen-receptor T-cell therapy (lisocabtagene maraleucel) was initiated as next-line treatment with curative intent. Approximately 3 months following completion, the patient presented for pleuritic chest pain, dyspnea on exertion, cough, chills, and emesis. Imaging demonstrated re-accumulation of pericardial effusion, requiring repeat pericardiocentesis. Serial electrocardiograms and telemetry revealed intermittent isolated first-degree atrioventricular (AV) block (Figure 1B), an accelerated junctional rhythm (ventricular rate 60) with retrograde P waves (Figure 1C), and intermittent complete AV block with junctional escape (ventricular rate 43) (Figure 1D). Cardiac MRI was notable for extensive cardiac involvement of the tumor in the left atrium, interatrial septum, left ventricular outflow tract, and aortic root (Figure 2). A subsequent dedicated computed tomography angiography coronary study confirmed encasement of the left main, right, and left circumflex coronary arteries without evidence of extrinsic compression.

Figure 2.

Cardiac Magnetic Resonance Imaging

There is diffuse circumferential mass-like thickening of the left atrium and interatrial septum measuring up to 15 mm (B). Soft-tissue thickening was also seen encasing the left ventricular outflow tract and aortic root, extending to the ostia of the pulmonary veins (A and B). There was evidence of circumferential encasement of the proximal coronary arteries. In addition, there was diffuse circumferential pericardial enhancement without pericardial thickening, likely related to recent pericardial drainage (A, arrows). The left ventricular ejection fraction was calculated at 55%.

Management

A multidisciplinary team was convened to discuss treatment options. From an oncologic perspective, the ideal treatment would be the urgent initiation of a CD3-CD20 bispecific antibody therapy, Glofitamab, as a bridge to allogeneic stem cell transplantation with curative intent. From a cardiac electrophysiologic perspective, there was uncertainty regarding the anticipated clinical course of conduction system disease. At this time, the patient was far into the treatment course. Given the patient's rapid progression from first-degree AV block to intermittent complete AV block, likely due to lymphoma invasion into the conduction system, further progression to persistent complete heart block and hemodynamic instability was anticipated. Despite the possibility of halting disease progression with urgent initiation of immunotherapy, the risk of further conduction system injury due to the associated inflammatory-fibrotic response was deemed high. Given the patient's young age, potential for cure, and the possibility of future improvement in conduction system disease, the decision was made to implant an active-fixation leadless pacemaker in the right ventricle (RV).

Shortly before the scheduled pacemaker procedure, the patient acutely developed symptomatic bradycardia, with telemetry confirming third-degree AV block with a junctional escape rhythm at a ventricular rate of 43 (Figure 3). The patient was urgently taken to the electrophysiology lab, and a single-chamber ventricular active-fixation leadless pacemaker (Aveir VR, Abbott) was successfully placed and programmed to VVI 40, with 100% pacing through postoperative day 1. The patient was subsequently started on glofitamab without immediate complications. After treatment, the patient was discharged with his device programmed to VVI 50. Interrogation of the device at the 1-month follow-up demonstrated an 8% pacing burden (Figure 4). He reported shortness of breath with stair climbing, so the device was reprogrammed to VVIR 50 to provide rate-responsiveness.

Figure 3.

Telemetry Strip With Complete Atrioventricular Block With Junctional Escape Rhythm (Ventricular Rate 43)

ECG = electrocardiogram.

Figure 4.

Electrocardiogram at the Time of the 1-Month Device Check, Demonstrating Sinus Rhythm With Complete Heart Block and a Junctional Escape Rhythm at a Rate of 61

As the device was programmed to VVI 50, no pacing was required.

Outcome and Follow-Up

Approximately 1 week after the 1-month device check, the patient presented to the ED for shortness of breath and lower extremity edema. Right heart catheterization demonstrated mild pulmonary hypertension, mildly elevated pulmonary capillary wedge pressure, and mildly elevated right heart pressures. The cardiac output/index was normal by thermodilution (4.45/2.08) and slightly decreased by Fick (3.7/1.73). Cardiac MRI was notable for mild circumferential pericardial enhancement and a slightly increased circumferential pericardial effusion from prior without evidence of constrictive physiology. The leadless pacemaker was correctly positioned at the mid-to-distal septal location of the RV. The patient was treated with intravenous diuretics, colchicine, and chemo-immunotherapy (gemcitabine/oxaliplatin/glofitamab). He was discharged after a 3-week hospital stay on increased maintenance loop diuretics, colchicine, and guideline-directed medical heart failure therapy.

The patient re-presented to the ED 1 week later (approximately 2 months from device implantation) with chest pain. Initial echocardiography showed a large pericardial effusion adjacent to the RV, slightly enlarged from 5 days prior, but without tamponade physiology. RV systolic function was mildly decreased like prior, and LVEF was stable at 66%. Within hours, the patient developed severe shock and acute hypoxemic respiratory failure requiring vasopressors and invasive ventilatory support. Repeat echocardiography at 48 hours demonstrated a stable effusion without tamponade, stable LVEF at 66%, but severely decreased RV systolic function. There was no evidence of RV or interventricular septal perforation, pacemaker lead–associated vegetation/thrombus, or significant tricuspid regurgitation to suggest a late complication from pacemaker implantation. The central mixed venous oxygen saturation was elevated, consistent with a primary distributive pathophysiology. In accordance with family wishes, he was transitioned to comfort care only and died shortly thereafter. An autopsy was declined. Ultimately, the cause of death was attributed to undifferentiated shock, with the highest suspicion for sepsis with possible contributions from cardiogenic and/or obstructive processes.

Discussion

Cardiac lymphomas are rare malignancies, most often presenting as extranodal metastasis of diffuse large B-cell lymphoma, the predominant histological subtype of non-Hodgkin lymphoma.¹ Presentation is heterogeneous, often manifesting as pericardial effusion, heart failure, and arrhythmias. Cardiac lymphoma can result in conduction system abnormalities through several mechanisms, including direct neoplastic infiltration of the AV node or His-Purkinje system, ischemia from compression of coronary arteries, localized inflammation or edema, and impingement due to tumor mass effect.^1,2 Several case reports have demonstrated high-grade AV block in this patient population.2, 3, 4, 5, 6 Reports have also demonstrated that high-grade AV block can be entirely or partially reversed with effective cancer treatment.

This case demonstrates how cardiac lymphoma can lead to rapidly progressive conduction system disease and highlights the challenge of determining the timing and necessity of pacemaker intervention in an uncertain, dynamic clinical scenario. Given the highly unpredictable clinical course and the anticipated initiation of lymphoma-directed immunotherapy in our patient, we deemed it appropriate to implant a pacemaker to allow for chronotropic support while receiving cancer-directed therapies. Alternatives to this included implantation of a permanent transvenous pacemaker or a temporary active-fixation single-chamber pacemaker with an externalized generator.⁷ As immunocompromised patients have an approximately 2- to 3-fold higher risk of device-related infection compared with immunocompetent patients,⁸ either of these options would have been associated with an increased risk of infection. Although leadless pacemakers are not without infection risk themselves, current evidence suggests an infection rate of <0.2% at 3 years, compared with 0.4% to 1% for transvenous pacemakers.⁹ Furthermore, the Aveir active-fixation leadless pacemaker can be easily retrieved via its retractable active-fixation helix if pacing is no longer required.⁹ Alternatively, if the patient were to require a higher RV pacing burden, the system could be upgraded by adding a leadless atrial device to minimize AV dyssynchrony. In addition, the procedural risk of perforation was not considered elevated, as imaging did not demonstrate lymphoma infiltration of the interventricular septum.

As the patient died from undifferentiated shock soon after device implantation, it is unclear whether lymphoma immunotherapy definitively improved conduction system disease. Still, a pacing burden of only 8% at the 1-month device interrogation, compared with 100% immediately following implant, suggests some degree of improvement. Importantly, there was no evidence that delayed pacemaker-related complications contributed to the patient's rapid clinical decline. Serial imaging over a roughly 2-month period, including imaging obtained just hours before death, consistently demonstrated stable RV lead position, an unchanged pericardial effusion without signs of perforation, and no evidence of lead-associated thrombus/vegetation or valvular dysfunction. In addition, the patient's prolonged hemodynamic stability and preserved biventricular function made AV dyssynchrony an unlikely driver of the sudden deterioration. Although he did experience dyspnea, chest pain, and volume overload requiring hospitalizations, these symptoms were likely multifactorial and related primarily to progressive cardiac lymphoma, recurrent pericardial disease, pulmonary hypertension, and systemic illness rather than pacing-mediated heart failure.

Conclusions

Cardiac lymphoma is a rare disease process that can lead to conduction system abnormalities through various mechanisms. The clinical course is often ambiguous, and there are no clear guidelines for pacemaker intervention; instead, clinicians and patients should weigh risks and benefits and engage in shared decision-making. This case supports early leadless pacemaker implantation in patients with cardiac involvement from lymphoma, regardless of anticipated treatment improvements. Unique to the active-fixation leadless pacemaker, this device can be removed if no longer needed, and the infectious risk is lower than that of a traditional transvenous pacemaker.

Visual Summary.

Secondary Cardiac Lymphoma Causing High-Grade Heart Block

The case demonstrates a patient with secondary cardiac lymphoma resulting in rapidly progressive atrioventricular block from (A) first-degree to (B) symptomatic complete block with junctional escape rhythm, leading to implantation of a leadless pacemaker (The arrow points to the leadless pacemaker) (C).

Funding Support and Author Disclosures

Dr Karmali has received consulting fees from BMS, Gilead/Kite, Genentech, GenMab, Abbvie, and AvenCell; serves on the speakers bureau for AstraZeneca and BMS; and has received grants/research support from Celgene Corporation/Juno Therapeutics/BMS, Takeda, BeiGene, Gilead Sciences/Kite. Dr Peigh has received consulting fees from Medtronic, Inc and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Take-Home Messages

• •Cardiac lymphoma may present with rapidly progressive conduction disease and the degree of reversibility following lymphoma-directed therapy can be difficult to predict.
• •Decisions regarding pacemaker implantation should be individualized and informed by the expected treatment response, infectious and procedural risks, and patient preferences.