Acute Heart Failure and Complete Heart Block in a Patient with Recurrent Diffuse Large B-Cell Lymphoma: A Case Report

Introduction

Cardiac tumors are divided into 2 categories: primary, originating from the heart, and metastatic, which spread to the heart from a different location [1]. All metastatic cardiac tumors, also known as secondary cardiac tumors, are essentially malignant and 22 to 132 times more common than primary neoplasms [2]. Depending on the location and size, cardiac masses, regardless of origin, can predispose patients to ar-rhythmic or hemodynamic implications. Esophageal, breast, lung, pancreas, stomach, skin, renal cell, leukemias, and lymphomas are the primary cancers metastasizing to the heart most frequently [2,3].

Cardiac involvement is estimated to be present in up to 15% of patients with lymphoma [4]. While Hodgkin lymphoma prefers the pericardium, non-Hodgkin lymphoma is also described to invade the heart [4]. Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of all non-Hodgkin lymphoma cases and commonly affects older adults in the sixth and seventh decade of life [5,6]. It is an aggressive and highly heterogeneous disease encompassing multiple subgroups of lymphoid malignancies with complex classification. The condition can arise de novo or occur secondary to the progression of other less aggressive forms of lymphoma [5].

In this report, we present the case of a 67-year-old female patient with acute-onset congestive heart failure and complete heart block who was found to have DLBCL invasion of the myocardium.

Case Report

This was a 67-year-old female patient with a history of non-Hodgkin lymphoma in remission for 3 years who presented to her oncologist for worsening night sweats and 2 weeks of progressive shortness of breath with exertion. A positron emission tomography (PET) scan and a computed tomography scan (CT) scan were ordered 6 months prior, but the patient was lost to follow-up, and she did not complete the study at that time. The non-Hodgkin lymphoma the patient was previously diagnosed with was a stage IV double-hit DLBCL, the tumor was c-Myc and B-cell lymphoma 6-positive and was treated with 6 cycles of rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride (R-EPOCH), completed in October 2019. Since that time, she was in remission, based on the results of a follow-up confirmed on PET/CT scan in March 2021 that showed no evidence of malignancy.

On further questioning, the patient was found to have had a concomitant 4.5-kg weight gain over 2 weeks, along with bilateral leg swelling. The patient used to walk 90 min daily but over the prior 2 weeks was unable to complete even half of her usual exercise route. The patient had no cardiac history, such as heart failure, prior to this presentation. Nuclear medicine PET/CT, shown in Figure 1, was obtained and completed 1 week later, revealing hypermetabolic activity localizing to a large, ill-defined right lower anterior mediastinal mass that appeared to extend into the right ventricular myocardium as well as the entire cardiac base, most consistent with malignancy. Additionally, it revealed cardiophrenic adenopathy and mildly active bilateral distal retroperitoneal lymph nodes that were highly worrisome for additional low volume disease. The patient was urged to present to the Emergency Department. Her blood pressure was 106/65 mmHg and heart rate was regular and bradycardic, at 56 bpm. Her vital signs were otherwise unremarkable. On physical examination, the patient’s cardiac and pulmonary examination was unremarkable, but the patient was found to have 2+ pitting edema in the bilateral lower extremities, without skin changes consistent with chronic edema or venous stasis. A complete blood count and comprehensive metabolic panel values were within normal limits. Troponins were trended, and all were negative. Brain natriuretic peptide was found to be elevated at 710 pq/mL (≤100 pq/mL). Lactate dehydrogenase was elevated at 458 u/L (140–271 u/L). Electrocardiogram (EKG) on admission was notable for a complete heart block, with a normal heart rate maintained by a junctional escape rhythm, as shown in Figure 2. Chest X-ray on admission was notable only for moderate right pleural effusion, as shown in Figure 3. Bedside transthoracic echocardiogram was attempted in the Emergency Department but was not able to visualize the right ventricle well.

Oncology and cardiac electrophysiology teams were consulted for management. The patient was determined to have International Prognostic Index of 4. Transcutaneous pacing was discussed but was not indicated, due to the stability of the patient’s junctional escape rhythm. Intravenous furosemide 40 mg twice daily was started. Coronary CT angiogram was obtained and redemonstrated the large mass in the anterior mediastinum, extending along the entire right ventricular free wall and invading the right ventricular myocardium, with impingement into the cavity as well as extension in to the right atrium, interatrial septum, and interventricular groove, as shown in Figure 4.

Biopsies of the anterior mediastinal mass and the patient’s bone marrow were obtained. Biopsy results showed double-hit high-grade B-cell lymphoma. Epstein-Barr encoding region in situ hybridization was negative. The patient was started on rituximab, ifosfamide, carboplatin, and etoposide (RICE) chemotherapy after the pathology was confirmed. The patient was observed inpatient during the first cycle to monitor hemodynamic stability during lymphoma retreat and was discharged with improvement in her heart failure symptoms and close cardiology and oncology follow-up. Abnormal EKG findings resolved following her chemotherapy treatment, and atrioventricular block did not recur (Figure 5). Follow-up PET/CT obtained 7 months later revealed complete resolution of the mediastinal mass and adenopathy, with no remaining evidence of malignancy, as shown in Figure 1.

Discussion

Cardiac tumors can present clinically, with mass effect obstruction leading to blood flow and valve dysfunction, arrhythmias, and symptoms such as dyspnea, syncope, presyncope, and chest pain, which can mimic acute coronary syndrome [2,4]. Other common manifestations include thromboembolism, paraneoplastic syndromes, and other systemic symptoms [2]. Primary cardiac tumors are uncommon, with a prevalence estimated to range from 0.001% to 0.3% based on autopsy studies, with the majority being metastatic tumors from other sources [1,7]. Of these primary tumors, over 90% are benign tumors, such as cardiac myxoma, which occurs in slightly over half of cases. Of the remaining 10% of tumors that are malignant, these tumors are most commonly sarcomas or angiosarcomas [1,8]. Cardiac tumors and cardiac involvement from lymphoma remain rare presentations. DLBCL, a classically aggressive subtype of non-Hodgkin lymphoma, is the most common lymphoid malignancy in Western countries and was seen in our patient [5]. Ease and timing of diagnosis of cardiac tumors depends on the extent of symptoms. Clinical symptoms of dyspnea, lower extremity edema, or other signs of congestive heart failure will likely prompt echocardiography and CT scan, due to compatibility of those symptoms with other cardiac pathology [9]. These interventions will provide visualization of masses with the heart, particularly those large enough to be hemodynamically significant [9].

Physical obstruction causing hemodynamically significant blood flow disruption within the heart can lead to build up of blood and pressure prior to obstruction, mimicking or leading to acute congestive heart failure, with symptoms such as dyspnea on exertion or severe lower extremity edema. In a retrospective analysis of 94 cases of cardiac non-Hodgkin lymphoma from 1990 to 2015, patients presented with heart failure in 34% of cases, and heart failure was identified as a poor prognostic indicator [10]. DLBCL with cardiac involvement carries a poor prognosis, with a 10% 9 to 12 month survival rate if left untreated [9]. Mediastinal DLBCL infiltrating the right atrium and primary intracardiac lymphoma are associated with rapid progression and consequent poor outcomes [9].

Additionally, a number of cases in the literature describe lymphoma causing electrical aberrations due to myocardial invasion. These manifestations range from mild bundle branch blocks and 1° atrioventricular blocks to severe complete heart block, requiring pacemaker placement [11,12]. Even in these cases, conduction abnormalities are reversible, with treatment and regression of the lymphoma. Even in cases with complete heart block, management with a permanent pacemaker is avoided unless hemodynamically necessary, and pacer burden often decreases over the course of treatment if a pacemaker is placed [12,13]. Fortunately, our patient demonstrated a junctional escape rhythm, which further obviated the need for either transcutaneous pacing or permanent pacemaker placement, and was atypical from cases in the literature. Junctional rhythms arise from the atrioventricular node or the His bundle, rather than the heart’s natural and main pacemaker found in the sinoatrial node [14]. These escape rhythms often beat between 40 and 60 bpm and are narrow complex, unlike ventricular escape rhythms, which are wide complex [14].

Our patient had such extensive myocardial involvement that she experienced significant blood flow obstruction from mass effect, resulting in acute onset heart failure, as well as complete dissociation of her conduction pathways, resulting in complete heart block. This extent of cardiac involvement with acute onset heart failure and complete heart block is exceedingly rare and appears to be a novel case in the literature. Treatment in this case was a significant challenge, due to lack of previous reports or data. In most cases, durable remission can be expected in patients with cardiac involvement from non-Hodgkin lymphoma, when treated with chemotherapy [10]. Due to the widespread nature of the lymphoma’s invasion, there was significant concern that treatment could theoretically result in the mass retreating too rapidly and resulting in catastrophic free wall or ventricular septal rupture [15]. Loosely analogous examples have been reported in the past, with gastrointestinal lymphomas occasionally causing bowel perforations during retreat after chemotherapy initiation [16]. Prophylactic pericardial patches and serial echocardiography have been suggested in the literature for use to prevent catastrophic wall rupture; however, there is currently a paucity of reports describing the real-world impact of this application, and there is a lack of strong guidelines regarding interventions or surveillance in this area [17].

Early treatment of DLBCL is crucial, and due to the patient’s relative hemodynamic stability, treatment was ultimately pursued under very close inpatient monitoring, and the patient did not experience any of the aforementioned complications. Our patient’s good response to chemotherapy and early rapid improvement of symptoms appears to have been a relatively typical treatment response [17]. Initial treatment of DLBCL tends to start with R-CHOP (rituximab, cyclophophamide, doxorubicin, vincristine, predinsolone); however, as our patient had relapsed after R-EPOCH treatment, RICE chemotherapy was initiated [18]. In cases such as ours, oncologists tend to approach with a “low and slow” approach to chemotherapy dosing during initiation, to reduce the risk of catastrophic complications, as discussed above [19].

Conclusions

Mediastinal DLBCL infiltrating the myocardium is an aggressive form of non-Hodgkin lymphoma. Although cardiac tumors are rare, they can lead to serious complications, such as intracardiac obstruction and fatal arrhythmias. Although heart failure and electrical aberrations have both been described in the literature independently before, this case appears to be a novel case that exhibits heart failure as well as complete heart block. Treatment can result in rapid symptomatic improvement after just 1 cycle of chemotherapy, and complete heart block usually resolves with underlying cancer treatment and does not require permanent pacemaker placement.