First interventional exchange of a left transvenous phrenic nerve stimulation lead from the novel remedē system

The remedē system is a novel fully implantable transvenous phrenic nerve stimulation (TPNS) device developed to treat central sleep apnea. No information is published on how to explant or replace its leads. An eighty‐one year‐old had a fractured lead and we removed it over a wire. However, unbreachable resistances occurred with a new lead deployed over the enclosed wire and interventional endovascular techniques were performed to reimplant a new fully functioning system. This first report demonstrates TPNS lead exchange is possible but can be challenging. Interventional maneuvers and techniques, including balloon angioplasty, can facilitate this procedure.


| INTRODUCTION
Central sleep apnea (CSA) is a highly prevalent comorbidity in cardiovascular and heart failure patients and is associated with increased morbidity and mortality. 1 Conventional CSA therapies, such as mask-based ventilation treatment, can alleviate symptoms and lead to positive outcomes, 2,3 but are also associated with limitations of effectiveness due to restricted patient compliance and mask tolerance. In addition, contraindications exist for specific algorithms, such as adaptive-servoventilation in heart failure patients with reduced ejection fraction. 4,5 The novel remedē system® (Respicardia Inc.) was developed as a fully implantable transvenous phrenic nerve stimulation (TPNS) device to specifically treat moderate to severe CSA in adult patients. 6 It consists of an impulse generator (IPG) and a stimulation lead, typically placed into the pericardiophrenic vein (PPV) that adjacently accompanies the left-sided phrenic nerve. 7,8 From this transvenous position, the phrenic nerve can be stimulated. 6,9 Recently, Fox et al [6][7][8]10 demonstrated long-term efficacy and safety of TPNS 3 years postimplant.
Briefly, the target PPV is accessed from the left brachiocephalic vein via over-the-wire technique after insertion of a guiding catheter. 8 Venography allows visualization of the stimulation lead as it is advanced to its desired position in the PPV. 8 An optional sensing lead can be implanted into the azygos vein that is used to detect respiration via transthoracic impedance as previously described. 8 However, to date no information is available addressing explantation, replacement, or exchange of TPNS leads. This is the first report to describe effective transvenous TPNS stimulation lead extraction, followed by reimplantation into the same PPV position, restoring effective continuous CSA treatment.

| CASE REPORT
An 81-year-old female patient presented for IPG exchange due to battery depletion, 4 years after initial TPNS device implantation.
This patient exhibited severe and highly symptomatic CSA and was diagnosed with heart failure, with high-grade reduced left ventricular ejection fraction (20%, heart failure with reduced ejection fraction [HFrEF]) and broadened QRS width (150 ms), secondary to dilated cardiomyopathy. She was treated with optimal guidelinederived heart failure medication and cardiac resynchronization therapy-defibrillator (CRTD) had been implanted before TPNS device. Despite receiving optimal treatment, this patient remained in symptomatic HFrEF, with shortness of breath and she suffered from severe symptomatic CSA. Moreover, she complained of mask intolerance and adaptive servoventilation was not an option as it is contraindicated in HFrEF with predominant CSA. Initial TPNS device implantation was then performed 4 years ago and preprocedural sleep lab parameters of polysomnography are depicted in Table 1.

| Primary implantation procedure and TPNS efficacy
A Biotronik Lumax 340 CRTD device was implanted 32 months before the TPNS device in the left pectoral region with transvenously placed right atrial, right ventricular dual shock coil, and bipolar coronary sinus leads. The initial TPNS device implantation was performed in the right pectoral area as previously described. 7

| DISCUSSION
This is the first report to describe the lead exchange of novel fully implantable TPNS therapy, using the remedē system (Respicardia Inc.).
During the procedure, we demonstrate the need to use interventional In addition, in our case, fibrous adhesions from the previously implanted TPNS lead as well as enclosed CRT lead associated scar tissue hampered prompt lead exchange. The practice of balloon angioplasty has been described to overcome fibrous adhesions during lead implantations in CRT, 14  Although technically more challenging, PPV stimulation lead exchange is feasible through wire stabilization using snare catheters, intravenous angioplasty maneuvers, or even stent implantations in selected cases in the context of transvenous lead implantations. 8 As TPNS therapy for moderate to severe CSA becomes more prevalent, 15 it will be important to document and share different interventional techniques to provide optimal and safe therapy.