INTRODUCTION

Historical indications for epicardial access include pericardiocentesis/pericardial drain placement, pericardial biopsy, and balloon pericardiotomy,¹ which traditionally have fallen within the domain of the interventional cardiologist. As electrophysiology technology and interventions have advanced, electrophysiologists (EPs) have become increasingly experienced in accessing the epicardium for electroanatomic mapping and catheter ablation and are now often the most experienced operators at a given institution. Future indications for percutaneous epicardial access may include pericardioscopic facilitation of arrhythmia therapeutics, intrapericardial drug delivery, structural interventions including new techniques for left atrial appendage exclusion, autonomic interventions, and epicardial lead placement for cardiac implantable electronic devices.

PERICARDIOSCOPY TO ENHANCE ARRHYTHMIA MANAGEMENT

The ability to directly visualize epicardial structures via pericardioscopy has tremendous potential with broad application. Pericardioscopy has been used to guide pericardial biopsy in order to improve diagnostic yield.² The use of pericardioscopy for electrophysiology procedures, however, is still in its early stages of development.

In a study by Gehi and colleagues, pericardioscopy was performed in a series of 101 patients undergoing a hybrid endocardial-epicardial atrial fibrillation (AF) ablation procedure with direct visualization of the left atrial epicardial surface for creation of a modified Cox lesion set (Figure 12.1).³ These patients had either failed a prior ablation attempt or had persistent AF with enlarged left atrial size or long-standing persistent AF. The success rate at 12 months was 66%, although major complication rates were 6%, including one death due to atrioesophageal fistula.

Figure 12.1 Illustration demonstrating transabdominal, transdiaphragmatic access to the pericardium for pericardioscopy. Reprinted from Gehi AK et al. Hybrid epicardial-endocardial ablation using a pericardioscopic technique for the treatment of atrial fibrillation. Heart Rhythm. 2013;10(1) page 23 with permission from Elsevier.

In another nonrandomized study, 65 patients underwent hybrid approach with pericardioscopically guided epicardial AF ablation combined with endocardial pulmonary vein isolation and were compared to 117 patients undergoing open-chest maze procedure.⁴ The success of the hybrid approach was comparable at 82% in the hybrid group compared to 77% in the open-chest group at 12 months. Of note, two patients in the hybrid group developed atrioesophageal fistulas.

Finally, in an observational study reported by Zembala and colleagues, of 27 patients undergoing a hybrid endocardial and pericardioscopically guided epicardial AF ablation, follow-up data were available for 18 patients with a 6-month success rate of 72%.⁵ Complications included tamponade in one patient, inferior vena cava laceration in another, and death due to unclear etiology within 1 month in a third patient.

Pericardioscopy has been reported as an adjunct for epicardial electroanatomic mapping in ventricular tachycardia (VT) ablation as well.6 Pericardioscopic access via a minimal submammary thoracotomy helped guide ventricular tachycardia ablation in a case report of two patients with successful outcomes in both cases.⁷ In these patients, access was obtained through a 3-4 cm incision in the fifth intercostal space along the midclavicular line with placement of a Hopkins 45-degree endoscope (Karl Storz, Endoscopy America, El Segundo, CA). The ability to enhance VT ablation with the use of pericardioscopy to avoid coronary arteries or circumnavigate epicardial fat pads has immense potential.

Aziz and colleagues described a case report of the use of robotic-assisted epicardial ablation of a patient with premature ventricular contractions (PVCs) originating from the left ventricular summit with associated cardiomyopathy.⁸ The PVCs remained refractory to antiarrhythmic medications and attempts at endocardial and epicardial ablation were unsuccessful. Utilization of a totally endoscopic robotic approach (DaVinci, Intuitive Surgical, Sunnyvale, CA) allowed for direct visualization and dissection of epicardial fat for optimal exposure while avoiding coronary arteries. Ablation in this otherwise inaccessible area led to termination of the patient’s PVCs and recovery of ventricular function.

Ultimately, in order to make this developing technology more clinically useful, the pericardioscopes will need to have sufficiently small size that can accommodate a percutaneous approach without the need for surgical access.

INTRAPERICARDIAL DRUG DELIVERY

Intrapericardial corticosteroids and cytostatic agents have shown effectiveness when delivered in the pericardial space. Intrapericardial corticosteroids can currently be offered for recurrent pericardial effusion when other conventional therapies have failed and systemic corticosteroid effect may be undesirable.^9–11 Additionally, current ESC guidelines give a class IIa recommendation for the use of intrapericardial cytostatic and sclerosing agents in the management of large malignant pericardial effusions.¹¹ Specifically, the guidelines recommend the use of intrapericardial cisplatin for lung cancer and thiotepa for breast cancer.^11–13 Thiotepa is an alkylating agent used commonly in the treatment of solid tumors. In particular, in breast cancer patients with malignant pericardial effusions, intrapericardial thiotepa can extend survival and reduce the likelihood of effusion recurrence.^14,15

Antiarrhythmic Medications

Due to the myriad of adverse effects of systemic administration of antiarrhythmic medications, there is interest in local delivery of these medications via the pericardial space. In a trial performed by Feng et al.,¹⁶ 100 patients undergoing cardiac surgery were randomized in a 1:1 fashion to receive an adhesive amiodarone-releasing hydrogel or a nondrug-eluting hydrogel placed over the atrial epicardium prior to closing the chest. The group receiving the amiodarone hydrogel had significantly less postoperative atrial fibrillation (8% versus 26% in the group without the amiodarone hydrogel). In a proof-of-concept study by Garcia et al.,¹⁷ a minimally invasive, catheter-based delivery system was used to successfully implant an amiodarone-containing hydrogel to the epicardium in pigs. Pigs receiving epicardial amiodarone hydrogel had less sustained atrial fibrillation with rapid atrial pacing compared to control animals up to 21 days after implantation. They also tested drug distribution in a rat model, which showed significantly higher off-target organ amiodarone accumulation in systemically treated rats compared to intrapericardial drug delivery. Due to the overall limited efficacy of antiarrhythmic drugs currently available, epicardial access used in isolation to deliver these drugs is unlikely to be utilized. However, the use of other interventions is promising.

Experimental Agents

Intrapericardial administration of growth factors, genes, and stem cells has been the subject of study as a potential treatment for myocardial ischemia and heart failure and has theoretical utility for the treatment of scar-based arrhythmias as well. Delivery of growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF) have been studied, in particular, as a treatment modality for promoting angiogenesis in models of cardiovascular ischemia. Increased angiogenesis with intrapericardial FGF application has been demonstrated in rabbit,¹⁸ porcine,¹⁹ and canine models.^20,21 The administration of intrapericardial VEGF has been shown to reduce collagen deposition and decrease cardiac wall stress as assessed by echocardiography in a porcine hypertrophy model.²² In a porcine myocardial infarction model, mesenchymal stem cells and an adenoviral vector encoding green fluorescent protein was successfully delivered using a gel foam system with a minimally invasive substernal approach under fluoroscopic guidance.²³ Intrapericardial delivery of reporter genes has been the subject of many animal studies, which in theory can provide a method for inducing genetic modifications for targeted therapies; however, biologic responses of functional genetic modifications have not been investigated in either human or animal models.24 There are no clinical trials that have evaluated the efficacy or safety of intrapericardial stem cell therapy.

Catheter-based methods of ablation of arrhythmias have made significant improvements since their initial use; however, they continue to have limitations, and alternative methods are the subject of continued research. For example, intracoronary ethanol delivery,²⁵ needle-tipped catheter ablation technology,²⁶ and intramyocardial wire ablation²⁷ are a few novel methods for treatment of ventricular arrhythmias. Collagenase is a bioenzymatic agent that can disrupt both normal and fibrotic myocardial tissue, which has the capacity to render slowly conducting scar and border-zone tissue electrically silent. In a study by Yagishita et al., a swine model with myocardial infarcts created via intracoronary microsphere injection subsequently underwent epicardial collagenase application over the area of scar with electroanatomic mapping.²⁸ The collagenase significantly decreased border-zone scar area as well as decreased the number of late potentials encountered (Figure 12.2). With the results of the VISTA trial suggesting superiority of a scar homogenization approach for ablation of ventricular tachycardia,²⁹ the use of chemical agents to achieve this level of substrate modification warrants further study. Whether this technique can be safely and effectively applied in humans is not yet known.

STRUCTURAL INTERVENTIONS

Recent AF guidelines give a class IIb recommendation for consideration of left atrial appendage exclusion in patients who cannot tolerate anticoagulation in order to reduce thromboembolic risk.³⁰ A number of different techniques have emerged for this purpose. These include endovascular devices such as the Watchman (Boston Scientific Corp., Plymouth, MN) and the Amplatzer Amulet (Abbott, Minneapolis, MN). Notably, the Watchman device demonstrated noninferiority to warfarin in the PROTECT-AF and PREVAIL randomized clinical trials.^31,32

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