J A C C : C A S E R E P O R T S V O L . 2 , N O . 2 , 2 0 2 0

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C O L L E G E O F C A R D I O L O G Y F O U N DA T I O N . T H I S I S A N O P E N A C C E S S A R T I C L E U N D E R

T H E C C B Y - N C - N D L I C E N S E ( h t t p : / / c r e a t i v e c o mm o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 / ) .

MINI-FOCUS ISSUE: ELECTROPHYSIOLOGY

CASE REPORT: CLINICAL CASE

A Clinical Challenge Overcomeby His Bundle Pacing

Alison Zimmerman, MD,a Hena Patel, MD,b Annabelle Volgman, MD,b Tochukwu Okwuosa, DO,b

Parikshit S. Sharma, MD, MPHb

ABSTRACT

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We highlight a diagnostic challenge in a patient with dyspnea on exertion due to radiation therapy–induced severe

first-degree atrioventricular block and how permanent His bundle pacing was helpful in overcoming these symptoms.

(Level of Difficulty: Intermediate.) (J Am Coll Cardiol Case Rep 2020;2:240–4) © 2020 The Authors. Published by

Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND

license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

HISTORY OF PRESENTATION

A 55-year-old Caucasian woman presented foroutpatient cardiovascular evaluation of progressivedyspnea on exertion and associated lightheadednessfor 1 month. Previously, she was able to climb severalflights of stairs and participate in vigorous aerobicexercise classes with minimal difficulty. However, forthe past few months, she had experienced dyspneawhen climbing 1 flight of stairs, along with occasionalpalpitations lasting about 1 to 2 s. She otherwise de-nied syncope, peripheral edema, claudication, or

EARNING OBJECTIVES

AV dyssynchrony should be considered in thedifferential diagnosis of symptomatic pa-tients with markedly prolonged PR intervalsand histories of radiation therapy.Permanent HBP may be a superior option toRV pacing in patients with a likely need for ahigh burden of ventricular pacing.HBP is a reasonable and safe option in pa-tients with symptomatic pseudo-pacemakersyndrome due to PR prolongation.

N 2666-0849

m the aDepartment of Medicine, Rush University Medical Center, Chic

iversity Medical Center, Chicago, Illinois. The authors have reported that t

s paper to disclose.

ormed consent was obtained for this case.

nuscript received September 3, 2019; revised manuscript received Novem

chest pain. Upon review of the patient’s wearablewrist monitor, sudden drops in heart rate wereevident during exercise and associated with hersymptoms. Her vital signs on examination were asfollows: blood pressure 132/62 mm Hg, heart rate 67beats/min, and weight 72.7 kg. Pertinent findingsincluded a 2/6 crescendo-decrescendo murmur thatradiated to the carotid arteries, as well as bilateralsurgical scars from previous mastectomy.

MEDICAL HISTORY

Medical history included non-Hodgkin’s lymphomastatus post mantle and abdominal radiation therapyand splenectomy; estrogen receptor–positive leftbreast cancer status post chemotherapy with doce-taxel and cyclophosphamide, modified left radicalmastectomy, and prophylactic right mastectomy;factor V Leiden mutation; left subclavian artery ste-nosis and thrombosis; mild to moderate aortic steno-sis; and incomplete right bundle branch block (RBBB).

DIFFERENTIAL DIAGNOSIS

The differential diagnosis included complicationsrelated to prior chemotherapy and/or radiation

https://doi.org/10.1016/j.jaccas.2019.11.077

ago, Illinois; and the bDivision of Cardiology, Rush

hey have no relationships relevant to the contents of

ber 22, 2019, accepted November 24, 2019.

AB BR E V I A T I O N S

AND ACRONYM S

AV = atrioventricular

ECG = electrocardiography

HB = His bundle

HBP = His bundle pacing

RBBB = right bundle branch

block

RV = right ventricular

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therapy, including cardiac arrhythmias, coronaryischemia, valvular heart disease, pericardial disease,restrictive lung disease, and cardiomyopathy; otherdifferential diagnoses included pulmonary embolism,pulmonary malignancy, pleural effusion, pneumonia,and asthma.

INVESTIGATIONS

Blood testing did not reveal any abnormalities, andthere was no evidence of anemia (hemoglobin 13.5 g/dl),thyroid disorders (thyroid-stimulating hormone2.4 mIU/ml), or electrolyte disturbances. Baselineelectrocardiography (ECG) revealed sinus rhythm witha normal PR interval and an incomplete RBBB pattern(Figure 1A), and transthoracic echocardiographyrevealed an left ventricular ejection fraction of about55% and mild to moderate aortic stenosis. Coronaryangiography, cardiac magnetic resonance imaging,and lung function studies were all unremarkable.Repeat resting ECG was performed given progressionof the patient’s symptoms, which demonstrated asignificant prolongation of the PR interval from 160 to330 ms with RBBB (Figure 1B). Subsequent exercisestress testing with the Bruce protocol revealed amaximum heart rate of 173 beats/min (103% ofmaximum predicted heart rate) after 10 min of exer-cise, but with marked PR prolongation (500 ms)associated with dyspnea, similar to her presentingsymptoms. A cardiac monitor showed a marked PRprolongation of more than 500 ms associated withreproduction of symptoms (Figure 1C).

MANAGEMENT

The findings of marked first-degree atrioventricular(AV) block, which worsened during exercise stresstesting leading to AV dyssynchrony, suggestedpseudo-pacemaker syndrome. Given the potential fora high burden of ventricular pacing (given the long PRinterval), we decided to pursue dual-chamber pace-maker implantation with His bundle pacing (HBP).After mapping of the His bundle (HB), an area ofintra-Hisian delay and disease was identified, and thelead was implanted distal to this region at the HB,resulting in narrowing of the RBBB pattern, suggest-ing that the delay in the right bundle branch wasintra-Hisian (Figure 2). The final paced configurationwas nonselective HBP (HB plus septal right ventric-ular [RV] capture) with recruitment and narrowing ofthe RBBB pattern (Supplemental Figure 1). Thepacemaker site healed well, and the patient’s symp-toms completely resolved. She continues to do well10 months after device implantation.

DISCUSSION

There are multiple possible causes of dyspneaon exertion in patients with histories of ma-lignancy after radiation therapy, includingpremature coronary artery disease, valvularheart disease, pericardial disease, cardiomy-opathy and heart failure, restrictive lungdisease, and cardiac conduction systemdisease.

Given significant advances in cancer treatment,cancer-related mortality has declined over the years.As a result, there has been increasing recognition ofcardiovascular diseases that occur as a consequenceof cancer therapy, including damage to the cardiacconduction system. Conduction system injury can bedirectly related to irradiation or secondary tomyocardial inflammation, ischemia, or fibrosis. Up to75% of patients can have changes on ECG followingmediastinal irradiation, but severe conduction ab-normalities are not usually evident until years later(1,2). Abnormalities along the entire conduction sys-tem in the setting of irradiation have been described,including various degrees of AV block, sick sinussyndrome, prolonged corrected QT interval, supra-ventricular arrhythmias, and ventricular tachycardia(3,4). RBBB is more common than left bundle branchblock because the anteriorly located right bundle isparticularly susceptible, which was the case with ourpatient (3). Nonspecific ST- and T-wave changes arealso very common years after radiation (5). The use ofroutine telemetry or ECG for screening of asymp-tomatic patients remains uncertain.

“Pseudo-pacemaker syndrome” refers to theoccurrence of symptoms in the presence of markedfirst-degree AV block, when the conducted P wave istoo close to the preceding QRS complex, producingthe same hemodynamic disturbance as a ventricularpaced rhythm with retrograde ventriculoatrial con-duction. Pseudo-pacemaker syndrome (as noted inour case) can occur as a result of significantly pro-longed PR interval and can result in symptoms due toAV dyssynchrony. After an extensive work-up thatincluded echocardiography and cardiac magneticresonance imaging (neither of which revealed anyabnormalities), as well as chest computed tomogra-phy and pulmonary function testing that was unre-markable for any lung disease, our patient wasdiagnosed with pseudo-pacemaker syndrome, and adecision was made to implant a dual-chamber pace-maker to better achieve AV synchrony.

The choice of type of pacemaker is critical. Thispatient would require ventricular activation 100% of

FIGURE 1 Electrocardiography

(A) Baseline electrocardiogram (before symptom onset): heart rate (HR) 84 beats/min, PR interval 160 ms, incomplete right bundle branch block (IRBBB) 118 ms. (B)

Baseline electrocardiogram (after developing symptoms): HR 94 beats/min, PR interval 320 ms, right bundle branch block 130 ms. (C) Long-term (14-day) cardiac

monitor with markedly prolonged PR interval (>500 ms) and a blocked premature atrial contraction. This strip was associated with a patient diary event when she was

experiencing symptoms.

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the time given the very long PR interval, as it is notpossible to program such long AV delays. It hasbeen well established that long-term RV apicalpacing is associated with adverse clinical outcomes.RV pacing–induced cardiomyopathy is a well-knowncause of left ventricular dysfunction. RV pacing re-sults in dyssynchronous contraction of the ventri-cles and increases the risk for heart failurehospitalization (6–9). HBP reduces ventricular dys-synchrony by simultaneous activation of the ven-tricles via an intact distal His-Purkinje system and

has been shown to reduce the risk for heart failurehospitalizations compared with RV pacing (10–12).HBP has therefore been shown to be a superiorpacing strategy to RV apical pacing, and can be afeasible alternative option to cardiac resynchroni-zation therapy with biventricular pacing in patientswith both AV dyssynchrony and left bundle branchblock and RBBB (13). We therefore chose to proceedwith HBP. As noted in Figure 2A, we were able toidentify the site of disease within the HB thatresulted in PR prolongation and RBBB and

FIGURE 2 After HBP

(A) Proximal site with long HV interval on the left and distal site with short HV interval on the right. (B) His bundle pacing (HBP) lead position on fluoroscopy. (C) Final

HBP electrocardiogram ECG with narrowing of right bundle branch block.

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successfully implant the pacing lead at the HB distalto disease, resulting in narrowing of the QRS com-plex in addition.

FOLLOW-UP

The patient has remained symptom-free since HBPimplantation and has returned to her baseline level ofactivity after 10 months of follow-up. During routinefollow-up in the cardiac device clinic, R-wave ampli-tude, pacer threshold, lead impendence, and per-centage of ventricular pacing were recorded. Thepost-procedural course has been uneventful, withno lead-related complications, including leaddisplacement, significant increase in pacer threshold,or lead dislodgement.

CONCLUSIONS

Cardiac dysfunction from chest radiation can involvethe conduction system. AV dyssynchrony should beconsidered in symptomatic patients with markedlyprolonged PR intervals with histories of radiationtherapy. HBP provides AV synchrony while main-taining interventricular synchrony and can providean effective approach to management of pseudo-pacemaker syndrome due to PR prolongation.

ADDRESS FOR CORRESPONDENCE: Dr. Parikshit S.Sharma, Rush University Medical Center, 1717 WestCongress Parkway, Kellogg Building, Suite 300, Chi-cago, Illinois 60612. E-mail: parikshit_s_sharma@rush.edu.

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2. Desai MY, Jellis CL, Kotecha R, Johnston DR,Griffin BP. Radiation-associated cardiac disease: a

practical approach to diagnosis and management.J Am Coll Cardiol Img 2018;11:1132–49.

3. Larsen RL, Jakacki RI, Vetter VL, Meadows AT,Silber JH, Barber G. Electrocardiographic changesand arrhythmias after cancer therapy in childrenand young adults. Am J Cardiol 1992;70:73–7.

4. Heidenreich PA, Kapoor JR. Radiation inducedheart disease: systemic disorders in heart disease.Heart 2009;95:252–8.

5. Strender LE, Lindahl J, Larsson LE. Incidence ofheart disease and functional significance ofchanges in the electrocardiogram 10 years after

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radiotherapy for breast cancer. Cancer 1986;57:929–34.

6. Sweeney MO, Hellkamp AS, Ellenbogen KA,et al. Adverse effect of ventricular pacing on heartfailure and atrial fibrillation among patients withnormal baseline QRS duration in a clinical trial ofpacemaker therapy for sinus node dysfunction.Circulation 2003;107:2932–7.

7. Khurshid S, Epstein AE, Verdino RJ, et al. Incidenceand predictors of right ventricular pacing-inducedcardiomyopathy. Heart Rhythm 2014;11:1619–25.

8. Wilkoff BL, Cook JR, Epstein AE, et al. Dual-chamber pacing or ventricular backup pacing inpatients with an implantable defibrillator: the DualChamber and VVI Implantable Defibrillator (DA-VID) trial. JAMA 2002;288:3115–23.

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10. Sharma PS, Dandamudi G, Naperkowski A,et al. Permanent His-bundle pacing is feasible,safe, and superior to right ventricular pacing inroutine clinical practice. Heart Rhythm 2015;12:305–12.

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13. Sharma PS, Dandamudi G, Herweg B, et al.Permanent His-bundle pacing as an alternative tobiventricular pacing for cardiac resynchronizationtherapy: a multicenter experience. Heart Rhythm2018;15:413–20.

KEY WORDS cardiac pacemaker, cardiacresynchronization therapy, electroanatomicmapping, electrocardiography,electrophysiology, shortness ofbreath

APPENDIX For a supplemental figure, pleasesee the online version of this paper.