Cardiac infiltration of diffuse large B-cell lymphoma manifesting as sustained ventricular tachycardia: a case report

Wei CHEN ,Kun HUANG ,Wei-Wei GUO ,Fan ZHOU ,De-Ning LIAO,?

1.Department of Cardiology,Shanghai Jingan District Zhabei Central Hospital,Shanghai,China;2.Department of Cardiology,Shanghai Changzheng Hospital,Shanghai,China;3.Department of Hematology,Shanghai Jingan District Zhabei Central Hospital,Shanghai,China

Cardiac tumors are rare.However,cardiac metastases can occur in up to 10% of patients with cancer.Among cardiac neoplasms,metastases are much more common than primary cardiac tumors.[1]Metastatic cardiac neoplasms most frequently metastasize from the respiratory system,followed by the hematopoietic system.This is according to a 30-year analysis of cardiac neoplasms at autopsy.[2]Of patients with evidence of cardiac involvement from the hematopoietic system,diffuse large B-cell lymphoma (DLBCL) was the most frequent non-Hodgkin’s lymphoma subtype.[3]The symptoms of cardiac metastasis vary depending on the extent of myocardial infiltration.Arrhythmias,such as atrioventricular block,atrial flutter/fibrillation,ectopy,and ventricular tachycardia (VT) can be present,especially when the conduction system has been infiltrated.[4]We report a case of DLBCL with localized infiltration of the right ventricular myocardium and left bundle branch block (LBBB) morphology VT.

A 77-year-old man presented to the Emergency Department with a cough and low-grade fever.Electrocardiogram (ECG) showed a right bundle branch block(RBBB) and ST-segment elevation in the leads of V1–V3,with a Brugada-like ECG (Figure 1A).Coronary angiography excluded coronary ischemia.Cardiac ultrasound,as well as cardiac 3.0T magnetic resonance imaging (MRI) revealed no significant cardiac mass (Figure 2A &2B).Chest computed tomography (CT) revealed multiple site lymphadenopathy in the mediastinum,and further positron emission tomography (PET)/CT examination found that multiple lymph nodes of different sizes above the mediastinum had different degrees of elevated glucose metabolism (bilateral neck,bilateral axillary,mediastinum,double hilar,and left diaphragm angle;superficial and relatively large lymph node lesions were located deep under the right side of the mandibular,size approximately 1.2 cm,SUVmax=23.7).Glucose metabolism increased unevenly in cardiac ventricles,especially the anterior wall of the right ventricle (SUVmax=7.1),which led to the clinic diagnosis of lymphoma (Figure 2C &2D).Biopsy of the right submandibular lymph node was performed,and pathology reported nongerminal center/activated B-cell type DLBCL.Ten days after the confirmation of DLBCL diagnosis by pathology,the patient exhibited wide QRS complex tachycardia with a heart rate of 200 beats/min (Figure 1B).From the QRS complex of LBBB morphology and positives in leads I and aVL,we inferred the tachy-arrhythmia was originating from the anterior wall of the right ventricle,which was consistent with elevated tracer uptake in the myocardium detected by PET/CT.Intravenous injection of 150 mg amiodarone,followed by 1 mg/min continuous intravenous infusion was administered and the patient deteriorated,beginning to exhibit an electrical storm with frequent episodes of VT.Synchronous electrical cardioversion of 100 joules did not terminate VT.Hemodynamics of the patient then worsened.After administration of lidocaine (50 mg by intravenous injection,2 mg/min continuous intravenous infusion),the frequency of VT episodes was significantly reduced,but with frequent premature ventricular contraction.At that time,we considered that the VT may be related the cardiac infiltration of lymphoma.

Figure 1 Twelve-lead electrocardiogram (40 mm/s). (A): Right bundle branch block,as well as ST-segment elevation in leads V1–V3 in the Emergency Department;(B): wide QRS complex tachycardia with left bundle branch block morphology,originating from the anterior wall of the right ventricle following the confirmation of diffuse large B-cell lymphoma diagnosis by pathology;and (C): sinus rhythm after chemotherapy.

The patient urgently underwent three rounds of induction chemotherapy guided by a hematologist utilizing strategies based on an R-CHOP (rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone)regimen.The electrical storm and ventricular premature contraction were eliminated within 48 h (Figure 1C)and did not recur during three months of follow-up,despite persistence of RBBB on ECG.

An implantable cardioverter-defibrillator (ICD) was not considered because uninterrupted ECG monitoring was ongoing for two months during chemotherapy in hospital and no malignant arrhythmia events were found.Additionally,we believed ICD implantation would be unsuitable because of the patient’s short life expectancy and possible complications from the procedure.

Three months post chemotherapy,PET/CT imaging revealed near-complete disappearance of the previous high uptake lesion and a significant reduction in myocardial uptake irregularities when compared to prior scans (Figure 2E &2F).

Although rare,there have been several cases of cardiac infiltration by lymphoma reported.Most of these cases involved cardiac occupation that was evident through multimodal imaging,including ultrasound and cardiac MRI.We observed a DLBCL patient with electrical storm,without obvious cardiac masses detected by these methods.Similar to our case,Tanaka,et al.[5]reported a long-term survival case of primary cardiac lymphoma with reversible VT and complete atrioventricular block (C-AVB).In this case,a 65-year-old man with VT was treated by oral amiodarone,then a dualchamber pacemaker was implanted because of the CAVB.Echocardiography and chest CT scanning showed a thickened free wall in the right ventricular outflow tract.Later,echocardiography and chest CT scanning detected enlargement of the mass in the free wall of the right ventricular outflow tract.After biopsy,the patient was histologically diagnosed with primary cardiac Bcell lymphoma.Chemotherapy and radiotherapy resulted in the disappearance of the mass,along with the disappearance of VT or C-AVB over the next eight years.In our case,PET/CT scan provided the evidence of cardiac infiltration,so we were able to administer the chemotherapy before the mass grew into a tumor.Huang,et al.[6]reported a case of cardiac involvement of natural killer/T-cell lymphoma presenting with recurrent episodes of VT.Due to frequent attacks of hemodynamically significant VT,despite the continuous use of corticosteroids and antiarrhythmic agents,an ICD was inserted.Four months later,the patient’s ICD was repeatedly discharged,and symptoms of lymphoma,such as fever and lymphadenopathy appeared,with a chest CT revealing a mass in the heart and lungs.Peripheral lymph node biopsy suggested natural killer/T-cell lymphoma.Unfortunately,the patient died during an electrical storm.Earlier diagnosis of the cardiac lymphoma,as well as timely administration of systemic chemotherapy remains the treatment of choice for increasing long-term survival in patients with cardiac lymphoma.

In the current case,the baseline ECG and VT morphology were similar to Brugada-like ECG;however,we did not diagnose it as Brugada syndrome.There were several reasons for this: (1) the patient reported that he had never experienced VT before and did not have any relevant family history;(2) ECG showed monomorphic VT,while Brugada syndrome typically manifests as polymorphic VT or ventricular fibrillation;(3) Brugada syndrome is characterized by no structural heart disease,whereas the involvement of lymphoma in the heart was demonstrated through PET/CT;and (4) Brugada syndrome does not respond to chemotherapy.

Although a myocardial biopsy was not performed and there was no direct evidence of pathology,we inferred that it could be related to lymphoma cardiac infiltration for the following reasons: (1) the QRS complex of VT had an LBBB morphology and was positive in leads I and aVL,which was consistent with the exact location of high tracer uptake in the right ventricular myocardium by PET/CT;(2) the electrical storm and premature ventricular contractions were eliminated within 48 h after chemotherapy,and did not recur during the three months of follow-up,suggesting that the VT was responsive to chemotherapy;(3) PET/CT at three months post-chemotherapy revealed a significant decrease in tracer uptake in the right ventricular myocardium;and(4) the presence of a new RBBB and elevated troponin levels before the VT episode could reasonably be attributed to lymphoma involvement.

We were unable to locate any documented evidence that verifies the effectiveness of the R-CHOP regimen in killing tumor cells within 48 h.A more reasonable explanation for the phenomenon we observed is that the large dose of prednisone in the regimen may have reduced local inflammation surrounding the infiltrated lesion in the heart.Furthermore,the termination of VT may be attributed to anti-inflammatory treatment,with the absence of VT certainly associated with a reduction in cardiac infiltration.

The incidence of cardiac involvement in lymphoma is somewhat infrequent,affecting only 10%–25% of autopsy cases.[7]The heart can be invaded by tumors through hematogenous and lymphatic spread,transvenous extension,and direct extension.[6]Hematogenous and lymphatic metastasis may cause myocardial infiltration.Our case noticed that the infiltration of progressive lymphoma into the cardiac myocardium may not be detected by cardiac ultrasound or MRI,but it may cause malignant arrhythmias and be detected by PET/CT.

DLBCL is the most prevalent subtype of non-Hodgkin lymphoma.The standard global treatment for DLBCL is the R-CHOP regimen,which consists of cyclophosphamide,doxorubicin,vincristine,prednisone,and rituximab administered every three weeks.[8]In patients diagnosed with advanced malignancies and malignant arrhythmias,particularly lymphoma,if antiarrhythmic medications and electronic cardioversions are not effective for the management of arrhythmias,cardiac infiltration should be taken into account as a possible cause of arrhythmias.PET/CT and anti-tumor interventions warrant consideration as a viable approach to detecting and mitigating arrhythmic episodes.

ACKNOWLEDGMENTS

This is a short text to acknowledge the contributions of specific colleagues,institutions,or agencies that aided the efforts of the authors.All authors had no conflicts of interest to disclose.