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Abstract
We report the case of a 57-year-old male patient with prior syncope associated with sustained ventricular tachycardia in the setting of Brugada syndrome, who was submitted to implantation of a cardioverter defibrillator for secondary prevention. During follow-up, he presented a significant increase in lead impedance, and a transthoracic echocardiogram showed a mass attached to the lead. He was started on oral anticoagulation after infective endocarditis was excluded but nevertheless suffered repeated episodes of pulmonary embolism that led to severe chronic thromboembolic pulmonary hypertension. After heart team discussion, he was referred to pulmonary endarterectomy and replacement of the implantable cardioverter defibrillator with a subcutaneous device. This led to significant improvement of functional class and normalisation of pulmonary haemodynamics. More recently, he suffered syncope in the setting of ventricular fibrillation with appropriate shocks and was started on quinidine without further recurrence of arrhythmic episodes.
- arrhythmias
- pulmonary embolism
- pulmonary hypertension
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Background
This report describes the management of a male patient with Brugada syndrome who suffered a rare complication of an implantable cardioverter defibrillator (ICD), which lead to chronic thromboembolic pulmonary hypertension (CTEPH).
CTEPH is classified as group 4 pulmonary hypertension (PH) and is defined by: (1) the presence of precapillary PH in haemodynamic assessment (mean pulmonary artery pressure (PAP)≥25 mm Hg and pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg) after at least 3 months of effective anticoagulation and (2) the presence of at least one mismatched segmental or large perfusion defect detected by pulmonary ventilation/perfusion (V/Q) scan or specific diagnostic signs for CTEPH detected by multidetector CT angiography or conventional pulmonary angiography.1 It is a rare, and probably underrecognised, progressive pulmonary vascular disease caused by obstruction and vascular remodelling of pulmonary arteries, with some data suggesting an annual incidence of five individuals per million population. Although it is thought to develop following a pulmonary embolism (PE) that fails to resolve in 0.57%–9.1% of patients, there are a significant number of patients with CTEPH who have no obvious history of acute PE (25%–63%).2 3 Other risk factors for this condition include splenectomy, infected ventriculoatrial shunts, antiphospholipid antibodies, malignancy, infected pacemaker leads and chronic inflammatory conditions.4 The gold standard for treatment of CTEPH is pulmonary endarterectomy (PEA), which is potentially curative and generally indicated in patients with surgically accessible thrombi.1
With the increase in implantation of cardiac electronic devices, the number of potential complications is expected to increase. This case shows one possible complication associated with cardiac-implanted electronic devices, although the association with PE is rare. It also shows one possible application for the use of subcutaneous ICD (S-ICD) and reinforces the role of PEA as the gold standard for treatment of CTEPH.
In this case, collaboration between PH experts, electrophysiologists and cardiac surgeons was essential in order to define the best approach that would allow significant improvement in the patient’s prognosis and quality of life.
Case presentation
We report the case of a 57-year-old male patient who was referred to our PH unit. The patient had a previous history of smoking and a family history of sudden death of a brother at the age of 50.
Three years earlier, he had presented to another institution with an episode of syncope associated with sustained ventricular tachycardia and was submitted to electrical cardioversion. The ECG after cardioversion was interpreted as showing ST-segment elevation in the precordial leads, and the patient was submitted to emergent coronary angiography that revealed a critical stenosis of the first diagonal branch, so primary percutaneous coronary intervention of this vessel was performed. After careful review of the electrocardiographic recordings, it was concluded that they showed a spontaneous type 1 Brugada pattern (figure 1), so the diagnosis of Brugada syndrome was made according to the guidelines and an ICD was implanted for secondary prevention.5 The transthoracic echocardiogram (TTE) performed at that time was unremarkable.
12 lead ECG showing type 1 Brugada pattern in the right precordial leads.
During follow-up in the referring hospital, an increase in electrical impedance of the ICD lead was documented, and TTE documented a mass attached to the lead. After infective endocarditis was ruled out, oral anticoagulation with warfarin was started. Despite effective anticoagulation the mass persisted, and the patient suffered multiple episodes of PE. During follow-up, he also presented a cardioembolic vertebrobasilar stroke, and a transoesophageal echocardiogram (TOE) showed patent foramen ovale (PFO) with right-to-left spontaneous flow, due to right chamber pressure overload. Later that year the patient was admitted with fatigue and dyspnoea, in WHO functional class IV. TTE confirmed signs suggestive of PH, and he was referred to our centre.
Investigations
At the time of referral, the patient had already undergone several investigations. He had a TTE that showed signs of a high probability of PH and a pulmonary V/Q scan (figure 2), that documented a ventilation-perfusion mismatch after 3 months of oral anticoagulation, suggesting CTEPH.
Pulmonary ventilation/perfusion scan showing multiple bilateral perfusion defects.
Following referral, we repeated the TTE, which documented systolic PAP estimated at 138 mm Hg; dilated main pulmonary artery and branches; dilated right chambers; right ventricle (RV) with hypertrophied walls and depressed systolic function; ICD lead in the right chambers, with a hyperechogenic and hypermobile mass attached to the atrial portion of the lead (figure 3); left ventricle (LV) with anomalous movement of the interventricular septum due to pressure overload; and preserved global systolic function. We also performed a TOE that confirmed the presence of the mass attached to the ICD lead, with a diameter measuring 12 mm, suggestive of thrombus. Both exams showed signs suggestive of PH without significant LV disease.
Transoesophageal echocardiogram (short-axis view) showing a mass attached to the implantable cardioverter defibrillator lead.
Blood work showed an increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (2019 pg/mL; reference range <125 pg/mL). In order to exclude endocarditis, three blood cultures were performed and were negative. Thrombophilia study was not performed, since the patient already had an indication for lifelong oral anticoagulation.
To investigate further the aetiologies of PH, several tests were performed, including (1) a respiratory function test that revealed mild obstruction with reduction of diffusion capacity of the lung for carbon monoxide (DLCO) (corrected DLCO 41.6%) and partial respiratory failure (pO2 56.7 mm Hg) and (2) a chest CT angiography that confirmed bilateral pulmonary thromboembolism. CT angiography of the PA can be helpful in determining whether there is evidence of surgically accessible CTEPH. It can also delineate typical angiographic findings, such as complete obstruction, bands and webs and intimal irregularities.
CT also showed enlarged mediastinal lymph nodes (short-axis dimension up to 24 mm), as well as a hilar conglomerate. Following multidisciplinary team discussion with pneumology, a bronchoscopy was performed. Both the bronchoalveolar lavage and the biopsy were compatible with stage I pulmonary sarcoidosis, without indication for immunosuppressive therapy at the time.
Afterwards, right heart catheterisation (RHC) confirmed severe precapillary PH (mean PAP 44 mm Hg; PCWP 9 mm Hg; cardiac index (Fick method) 1.5 L/min/m2; pulmonary vascular resistance (PVR) (Fick method) 12.6 Wood units) and a diagnosis of CTEPH, in the setting of recurrent pulmonary embolisation due to thrombus attached to the ICD lead, was established.
Differential diagnosis
In the presence of increased lead impedance, a diagnosis of lead failure, namely conductor fracture, should be sought. The first step towards this diagnosis should be the performance of a thoracic X-ray and the interrogation of the device.6 Our initial evaluation was inconclusive, so a TTE was performed. The presence of a mass attached to the lead points to thrombus or vegetation, so it is critical to exclude endocarditis. In this case, three blood cultures were performed and were negative, so thrombus was considered the most likely diagnosis.
In most cases, lead thrombus resolves or at least stabilises with oral anticoagulation therapy, but in this case the mass persisted and the patient suffered several episodes of PE, as well as a vertebrobasilar stroke, which was probably due to paradoxical embolisation through PFO, in the setting of right-to-left shunt, due to PH and right chamber pressure overload. We can speculate that the concomitant presence of an inflammatory condition, such as pulmonary sarcoidosis, contributed to this evolution.
Subsequently, the patient presented in advanced functional class, and TTE showed signs suggestive of PH. According to guidelines,1 investigation of the aetiology of PH should start by identifying the more common clinical groups (group 2, left heart disease and group 3, lung disease), followed by group 4 (CTEPH), and finally recognising the different types in group 1 (pulmonary arterial hypertension) and the rarer conditions in group 5.
The results of TTE and pulmonary V/Q scan, together with the clinical history of the patient, strongly suggested CTEPH to be the likely aetiology in this case. Taking this into consideration, pulmonary CT angiography was performed and showed signs of bilateral pulmonary thromboembolism, while RHC confirmed severe precapillary PH.
The pulmonary CT also revealed the presence of enlarged mediastinal lymph nodes. The investigation of this finding led to the diagnosis of pulmonary sarcoidosis, which is also a potential aetiology of PH (classified in group 5). However, the severity of PH in this patient seems out of proportion with the clinical impact of sarcoidosis; therefore, although the contribution of sarcoidosis on PH cannot be completely excluded, it is unlikely that sarcoidosis is the main aetiology of PH.
The final diagnosis was of CTEPH in the setting of recurrent PE due to thrombus attached to the ICD lead, which had been implanted for secondary prevention in a patient with Brugada syndrome.
Treatment
Following CTEPH heart team discussion, the patient was started on sildenafil 75 mg tid due to severe PH and elevated PVR and also on oxygenotherapy due to partial respiratory failure. In addition, he was referred to a surgical centre abroad and underwent PEA and complete ICD system extraction (figure 4), with subsequent S-ICD implantation (figure 5). He maintained anticoagulation first with warfarin and afterward with edoxaban 60 mg one time per day.
Pulmonary endarterectomy specimen (upper part) and explanted implantable cardioverter defibrillator generator and lead with attached thrombus (lower part).
Chest radiograph after subcutaneous implantable cardioverter defibrillator implantation.
Due to the risk of recurrence of thrombus, S-ICD was the best option for secondary prevention of ventricular arrhythmia, since the patient did not have an indication for pacing. However, during follow-up he had several inappropriate shocks due to oversensing of the T waves, which persisted after several sensing optimisation attempts with the available vectors.
After multidisciplinary discussion, he was submitted to surgical revision of the S-ICD system and lead repositioning to the right parasternal position, allowing adequate T-wave discrimination. A few months later, he was admitted to our department due to syncope associated with three episodes of appropriate shocks in the setting of ventricular fibrillation and was started on quinidine 200 mg tid without further recurrence. Recommendations were made regarding drugs to avoid and management of fever.
Outcome and follow-up
Eleven months after the initiation of quinidine, the patient remains asymptomatic, free of arrhythmic events, in functional class I, with normalisation of NT-proBNP, right ventricular chamber dimensions and mean PAP and PVR.
Discussion
Brugada syndrome is a channelopathy typically transmitted via an autosomal dominant inheritance pattern, although in a significant proportion of patients the disease can be sporadic. The first mutations associated with this syndrome were found in the SCN5A gene, which encodes for the cardiac sodium channel, and whose effect is a decrease in transmembrane sodium current (INa). Nevertheless, only 18%–30% of patients test positive for mutations in this gene.7
Brugada syndrome is characterised by spontaneous or inducible characteristic ST-segment elevation and T-wave inversion in the right precordial leads. High-risk patients may experience ventricular arrhythmias that result in sudden cardiac death (SCD).8 The prevalence of Brugada syndrome has been estimated at 5 in 10 000. However, its actual prevalence may be underestimated, since many patients present silent forms of the disease.4
ICD therapy is currently the only proven effective treatment for life-threatening ventricular arrhythmias in patients with Brugada syndrome judged to be at high risk for ventricular arrhythmias. In a recent meta-analysis, the incidence of arrhythmic events in patients with Brugada syndrome was 13.5% per year in patients with a history of sudden cardiac arrest, 3.2% per year in patients with syncope and 1% per year in asymptomatic patients.9 The 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines give a class I recommendation for ICD implantation in Brugada syndrome patients with cardiac arrest, sustained ventricular arrhythmia or a recent history of syncope presumably due to ventricular arrhythmia.10
ICD therapy is associated with complications, reinforcing the need for proper selection of patients according to the risk stratification of SCD.11 ICD-related complications increase during long-term follow-up, and the most common include lead malfunction and infection. Lead thrombus is a rare complication with a reported prevalence of 0.3% per year.8 Noheria et al reported a prevalence of clinically relevant or symptomatic PE associated with ICD leads of 1.6%.12 Nevertheless, the true incidence of PE may be higher, since only up to 5% of episodes are clinically evident.12 Because most Brugada syndrome patients are young and otherwise healthy, a long survival after ICD implantation is expected, exposing them to a long-term risk of device-related complications.
In this case report, the patient had a clear indication for ICD implantation, although the risk of recurrence of lead-associated thrombus must be considered. In this setting, S-ICD, with its complete extravascular localisation, represents a significant advantage, particularly with respect to lead-associated issues. According to European guidelines, S-ICDs should be considered as an alternative to transvenous defibrillators in patients with indication for an ICD when pacing therapy for bradycardia support, cardiac resynchronisation and antitachycardia pacing are not needed (recommendation class IIa, evidence level C) or as a useful alternative after the removal of a transvenous ICD for infection or in young patients with a long-term need for ICD therapy (recommendation class IIb, evidence level C).5 Our patient had an indication for ICD implantation, without the need for pacing or other therapies, and we had to remove his transvenous ICD due to thrombus associated with repeated PE and CTEPH. After heart team discussion, S-ICD was considered the best option.
Patients with ICD leads also have an increased risk of cardioembolic stroke in the presence of a diagnosed PFO, as was the case with our patient.13 To our knowledge, there has been no publication of ICD lead thrombus associated with CTEPH. Fortunately, the patient was a good candidate for PEA, which is the most effective therapy for CTEPH. In centres with the most experienced surgeons, the overall mortality rate due to PEA is less than 5%.1 14 15 PEA removes obstructive thromboembolic material and significantly improves the haemodynamic profile. It also causes reverse remodelling of the RV, with long-term survival rates reaching 90% at 5 years following surgery.16
This case highlights the importance of the careful selection of patients for implantation of cardiac electronic devices, given the possible complications. It also emphasises the role of teamwork between several specialities and subspecialities, including electrophysiologists, PH experts and cardiac surgeons, and illustrates the central role of the heart team in the safe and effective management of such complex cases.
Patient’s perspective
I was a construction worker and in my free time I was a shepherd. With this disease I was not able to lift even a bucket, or take care of my sheep’s. After the surgery I regained life, and fortunately now I am able to do all again without getting tired.
Learning points
Careful individual risk assessment, selection and counselling of the patient with Brugada syndrome is essential before implantable cardioverter defibrillator (ICD) implantation.
When an increase of lead impedance is detected, the aetiology should be thoroughly investigated. If a thrombus is diagnosed and does not resolve with effective anticoagulation, removal of the device and implantation of a subcutaneous ICD (S-ICD) should be considered, after reassessment of the indication.
S-ICD is a good option for patients with a risk of sudden death and without the need for pacing, antitachycardia pacing or resynchronisation therapies, particularly those with a contraindication for transvenous ICD.
In patients who present with echocardiographic signs suggestive of pulmonary hypertension, with previous pulmonary embolism or without evidence of significant pulmonary or left heart disease, chronic thromboembolic pulmonary hypertension (CTEPH) should be considered and a pulmonary ventilation/perfusion scan performed.
Pulmonary endarterectomy is the first line treatment for CTEPH. In experienced centres it is a safe procedure and can be potentially curative.
Acknowledgments
I acknowledge Dr Pedro Carrilho Ferreira for all the support and contributions in the improvement of the manuscript. I also acknowledge Professor Hélder Pereira for all the support given in our department that allow us to treat in the best possible way our patients.
References
Footnotes
Contributors SA performed substantial contributions to the conception or design of the work, acquisition, analysis; drafting the work and revising it critically for important intellectual content. DR contributed substantially to the conception or design of the work, acquisition, analysis. FF approved the final version published. MJL contributed substantially to the conception or design of the work: revision and final approval. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.