Successful termination of ventricular tachycardia by an extravascular implantable cardioverter-defibrillator in a young patient with arrhythmogenic right ventricular cardiomyopathy

Key Teaching Points.

• •Extravascular implantable cardioverter-defibrillator implantation is a feasible therapy for treating ventricular arrhythmias in young patients with arrhythmogenic right ventricular cardiomyopathy.
• •P-wave oversensing, caused by low R-wave sensing, sensing polarity, and final lead position relative to the right atrial appendage, is the most common reason for inappropriate shocks.
• •Electroanatomic and structural characteristics of the heart and thorax of the individual patient should be considered carefully before implantation to ensure appropriate and successful delivery of antitachycardia therapies.

Introduction

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of arrhythmogenic cardiomyopathy primarily affecting the right ventricle (RV). It is characterized by progressive fibrofatty replacement of the myocardium,¹ predisposing patients to ventricular tachyarrhythmias and sudden cardiac death.² The extravascular implantable cardioverter-defibrillator (EV-ICD) is a novel device featuring substernal lead placement and subcutaneous battery implantation. It combines the advantages of avoiding transvenous (TV) access with the capacity for antitachycardia pacing (ATP), defibrillation, and limited bradycardia support. We present the case of an adolescent patient with ARVC successfully treated with an EV-ICD.

Case report

An 18-year-old man collapsed during physical activity (trampoline jumping). Witnesses reported nausea and sudden loss of consciousness. Immediate bystander cardiopulmonary resuscitation was initiated. Emergency services documented pulseless electrical activity, followed by 3 episodes of ventricular fibrillation (VF) requiring defibrillation. He achieved return of spontaneous circulation after approximately 10 minutes. During ambulance transport, he developed bradycardia owing to presumed high-grade atrioventricular block, requiring additional resuscitation.

Initial evaluation revealed hemodynamic stability and no overt traumatic injury. Blood gas analysis showed metabolic and respiratory acidosis (pH 7.11; lactate 7.2 mmol/L). Computed tomography imaging revealed bilateral ground-glass opacities, right heart enlargement, and a dilated pulmonary artery. Echocardiography confirmed RV dilation, severely reduced function (tricuspid annular plane systolic excursion 10 mm), and mild tricuspid regurgitation.

Therapeutic hypothermia was initiated for 24 hours. He was extubated on hospital day 3 and recovered neurologically. Electrocardiogram revealed sinus rhythm with T-wave inversions in V1–V3, an epsilon wave in V1, and a broad QRS (114 ms) (Figure 1). Cardiac magnetic resonance imaging (MRI) confirmed ARVC with an RV ejection fraction of 30%, severe RV dilation (RV end-diastolic diameter basally 63 mm [normal 23–42 mm], midventricularly 59 mm [20–35 mm], longitudinally 94 mm [56–86 mm]), regional dyskinesia, and pronounced trabeculation. Genetic testing disclosed the heterozygous single-nucleotide splice-site variant c.2146-1G>C of the plakophilin-2 gene.

Figure 1.

12-lead electrocardiogram of the patient at rest. T-wave inversions in V1–V3 and epsilon wave in V1 are evident.

Owing to the patient’s age, history of VF, and bradycardia-induced syncope and the absence of pleural adhesions or anatomic anomalies on thoracic imaging, EV-ICD implantation was selected. The procedure involved the creation of a subcutaneous generator pocket in the left midaxillary line and substernal tunneling for the lead (Figure 2). R-wave sensing was >3 mV. Defibrillation threshold testing was successful at 31 J with a 6.2-second charge time. Final settings included VF zone at >188 beats/min and fast ventricular tachycardia (VT) zone at >250 beats/min. Supraventricular tachycardia discriminators were enabled.

Figure 2.

Chest radiograph after extravascular implantable cardioverter-defibrillator implantation. A: Anterior-posterior view. B: Lateral view. The subcutaneous battery is positioned at the left midaxillary line, and the substernal lead with defibrillation coils (arrows) and ring electrodes (arrowheads) is clearly visible.

One month after implantation, the device recorded 14 nonsustained VTs owing to T-wave oversensing (Figure 3). Sensitivity threshold was increased from 0.15 mV to 0.2 mV.

Figure 3.

EGM demonstrating T-wave oversensing after the ninth ventricular sensed (VS) signal (∗), annotated as TF (interval in the ventricular fibrillation zone). The PQ interval is marked throughout the channel “coil2 to can” by horizontal blue lines, showing a regular PQ interval preceding each QRS and ruling out P-wave oversensing as the cause for tachycardia detection. Perpendicular lines in green color delineate QRS complexes of the regular heart rhythm, whereas perpendicular dashed lines in red color identify oversensed T waves. Calculating the time between green lines gives cycle lengths of 540–560 ms (111–107 beats/min), being congruent to the cycle length of the preceding correctly identified VS tracings. Interposing oversensing of T waves “increases” the heart rate to 214–230 beats/min (cycle lengths 260–280 ms), thus triggering detection in the ventricular fibrillation zone (“TF”). EGM = electrogram.

3 months later, the patient presented after receiving 2 shocks during a night out. Device interrogation showed 9 episodes of ventricular arrhythmias, including fast VT and VF, appropriately treated by ATP (4 episodes) and shock (2 episodes) (Figure 4). The patient had consumed alcohol and been involved in a stressful confrontation before the arrhythmias. He was counseled on lifestyle modification, and his metoprolol dose was increased.

Figure 4.

A: Repeated nonsustained ventricular tachycardia (VT) episodes (arrows) after alcohol intake, indicating heightened sympathetic tone. B: Successful termination of VT by antitachycardia pacing (box). C: Successful termination of ventricular fibrillation by a 41.9 J shock (arrow).

Discussion

ARVC is a genetically and phenotypically diverse cardiomyopathy with high arrhythmic risk. Risk factors for ventricular arrhythmias include male sex, reduced RV function, and a history of sustained VT/VF.³ In this case, the patient fulfilled multiple high-risk criteria, and sudden cardiac death occurred during physical exertion—a common trigger in ARVC.⁴

EV-ICD therapy represents a significant innovation, especially in younger patients who may benefit from avoiding TV leads and their long-term complications. Unlike subcutaneous ICDs (S-ICDs), the EV-ICD allows ATP and bradycardia pacing owing to its substernal lead location. Clinical trials have demonstrated ATP efficacy in 77% of episodes and 100% success in defibrillation.5, 6, 7 So far, no study has explicitly examined the use of EV-ICDs in ARVC. A recent meta-analysis included all data available from the EV-ICD Pilot, the Pivotal, and the Continued Access premarket studies and those of the just-published Enlighten Registry, the first real-world evaluation of the periprocedural outcomes of the EV-ICD.⁸ Altogether, 568 of 598 patients (95%) received a successful EV-ICD implantation. Cardiomyopathy was nonischemic in 33.0% (pooled premarket studies) or 31.4% of cases (Enlighten Registry), demonstrating feasibility for patients with nonischemic cardiomyopathy in controlled and real-world environments. In the Pivotal Study, 1.9% of patients had ARVC,⁹ whereas this information is not available for the other studies. Compared with the “typical” ICD population, the EV-ICD population consisted of younger patients with a left ventricular ejection fraction of >35%, showing a preference for implanting an extravascular device in young patients with presumably other conditions prone to ventricular arrhythmias than ischemic cardiomyopathy. Until discharge, the rate of system- or procedure-related major complications was up to 3.9% in total. Lead dislodgement until discharge was the most frequent complication across all 4 studies (0.8%–0.9%). In the Pivotal Study, inappropriate shocks occurred in 9.7% of patients within the first 10 months and 17.5% within 3 years,^7,9 P-wave oversensing (PWOS) being the most common reason (42%–51%).^7,9 This led to the development of a PWOS discriminator and the calibration of the sensing signal during implantation.¹⁰ Factors causing PWOS were low R-wave amplitude, high P:R ratio, beat-to-beat reduction of R-wave amplitude or transient increase in P-wave amplitude, sensing at ring 1 to ring 2, and lead placement near the right atrial appendage.¹⁰ All episodes primarily classified as T-wave oversensing during the Pivotal Study were later reclassified as PWOS.¹¹ However, in our patient, the low sensitivity level of 0.15 mV programmed after implantation had clearly facilitated oversensing of T waves.

In a large registry of patients with ARVC treated with TV-ICD, complications requiring a surgical procedure developed in 27% of cases.¹² Of those, 91% were lead related. The complication rate was 5.5% after the first year, 14.0% at 5 years, and 32.7% at 10 years. Apart from lead fractures, most common problem in patients with ARVC was low sense values, probably mirroring the ongoing fatty-fibrous replacement of myocardium.¹² Indeed, low R-wave amplitude at implantation and even decreasing values during follow-up in ARVC have been described before.¹³ Low sense values seem to be related to the electroanatomic peculiarity of ARVC. 3-dimensional electroanatomic mapping of the RV showed decreased endocardial bipolar R-wave voltage and increased R-wave duration.¹⁴ Decrease in R-wave voltage was nonuniformly distributed throughout the RV and outflow tract, mirroring the anatomic distribution of fibrous scar tissue and the thickness of the structure. Bipolar and unipolar voltage cutoff values at the subtricuspid region were of the highest sensitivity and specificity for ARVC diagnosis. These findings are in line with the previous findings of te Riele,¹⁵ who discovered a close correlation of the distribution of electrical scarring detected by electroanatomic mapping with the distribution of structural changes detected by cardiac MRI, scar tissue of either kind being most frequently located at the subtricuspid/basal inferior region.¹⁵ Thus, lead parameters of leads placed in diseased areas might result in low sensing voltages, but elevated pacing thresholds. Indeed, this observation was made in a comparison of newly implanted ICDs/cardiac resynchronization therapies with a defibrillator in patients with ARVC with those with dilated cardiomyopathy: in ARVC, R-wave voltage was lower, whereas pacing threshold and amplitude-pulse width product were higher than in dilated cardiomyopathy.¹⁶ For EV-ICDs, the long-term follow-up of the Pivotal Study showed low R-wave voltage at the ring 1 to ring 2 vector at implantation (2.5 mV).⁷ In real-world conditions, epicardial adipose tissue of >20 mm depth anterior to the RV, and specifically in a patient with ARVC, an extensive scar of the epicardial RV free wall prevented adequate R-wave sensing (>1.0 mV) during EV-ICD lead placement.¹⁷ In our patient, epicardial fat tissue anterior to the RV was at most 15 mm in depth as measured on cardiac MRI images, and although dilated, the RV free wall did not contain large scar tissue areas. Both conditions taken together enabled relatively large R-wave sensing during implantation and thereafter (>3.0 mV). Thus, adequate collection of diagnostic findings will help identify patients in whom the function of this device is adequate.

Severe RV dysfunction and RV dilation were recently found to be strongly predictive of the occurrence of VTs in ARVC.¹⁸ Given that our patient displayed these features, the occurrence of VT had to be anticipated and, accordingly, a device capable of delivering ATP was chosen. Additional arguments in favor of choosing EV-ICD in this special patient were young age and absence of pleural adhesions or anatomic anomalies, which might interfere with lead placement. A device able to deliver antibradycardia pacing was deemed necessary, given that this patient had a short episode of bradycardia before admission. As an alternative, placement of a leadless pacemaker in combination with an S-ICD was discussed, but was dismissed owing to anticipated progress of myocardial transformation affecting sensing and capture of the leadless pacemaker. Ablation of VTs is a therapeutic approach to treating this ARVC-related complication. A recent study by Bisceglia et al¹⁹ showed epicardial presence of suitable targets for radiofrequency ablation in 92.4% patients with ARVC by high-density mapping. For patients with ARVC, the epicardial approach was more often chosen than the endocardial approach at the first attempt and at redo VT ablation. Usually, this includes an anteriorly oriented subxiphoidal puncture that allows positioning the needle in the pericardial space, followed by placement of a guidewire and subsequently the ablation catheter via a sheath introduced over the guidewire in the pericardial space.²⁰ The probability that our patient will experience VT ablation by epicardial access during his lifetime is high. However, apart from accessing the thorax by subxiphoidal puncture, subsequent steps of the procedure target different structures and thus are well separated from the EV-ICD lead. Indeed, successful epicardial VT ablation in EV-ICD patients was published only recently.²¹ Thus, the presence of EV-ICD might hinder, but not prevent, future VT ablation in patients with ARVC.

Across the available case reports, EV-ICD was successfully chosen for patients displaying special cardiac or anatomic considerations, such as status post TV-lead extraction and negative screening for S-ICD,²² at high risk of infection,²³ with elevated body mass index (>45 kg/m²),²⁴ severe cardiac hypertrophy,²⁵ or pectus excavatum.²⁶ Our case adds to the existing literature by demonstrating the feasibility and usability of an EV-ICD in ARVC, particularly in secondary prevention settings where both pacing and defibrillation may be needed. Although inappropriate detections occurred, they were correctable by reprogramming. Importantly, the device successfully terminated both VT and VF episodes.

Conclusion

This case highlights the successful application of EV-ICD therapy in a young patient with ARVC and a history of sudden cardiac arrest. The device appropriately detected and terminated multiple ventricular arrhythmias, supporting its use in selected high-risk individuals. Further studies are warranted to evaluate long-term outcomes of EV-ICD therapy in inherited cardiomyopathies.

Disclosures

The authors have no conflicts of interest to disclose.