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The Subcutaneous Implantable CardioverterDefibrillator – First Single-Center Experience with other Cardiac Implantable Electronic Devices Jürgen Kuschyk MD, Ksenija Stach MD, Erol Tülümen MD, Boris Rudic MD, Volker Liebe MD, Rainer Schimpf MD PhD, Martin Borggrefe MD PhD, Susanne Röger MD www.elsevier.com/locate/buildenv
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S1547-5271(15)00713-4 http://dx.doi.org/10.1016/j.hrthm.2015.06.022 HRTHM6321
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Heart Rhythm
Cite this article as: Jürgen Kuschyk MD, Ksenija Stach MD, Erol Tülümen MD, Boris Rudic MD, Volker Liebe MD, Rainer Schimpf MD PhD, Martin Borggrefe MD PhD, Susanne Röger MD, The Subcutaneous Implantable Cardioverter-Defibrillator – First Single-Center Experience with other Cardiac Implantable Electronic Devices, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2015.06.022 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Subcutaneous Implantable Cardioverter-Defibrillator – First Single-Center Experience with other Cardiac Implantable Electronic Devices
Jürgen Kuschyk MD1,2, Ksenija Stach MD1,2, Erol Tülümen MD1,2, Boris Rudic MD1,2, Volker Liebe MD1,2, Rainer Schimpf MD PhD1,2, Martin Borggrefe MD PhD1,2 and Susanne Röger MD1,2
(1) Medical Faculty Mannheim of the University of Heidelberg, 1st Department of Medicine, Mannheim, Germany (2) DZHK (German Centre for Cardiovascular Research) partner site Mannheim, Germany
Running Title: Subcutaneous Defibrillator in combination with other Cardiac Devices
Disclosures and conflicts of all authors The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Acknowledgement of grant support: This study was initiated by the investigators. There is no grant support to declare. Disclosures: JK has received modest speaker fees from Impulse Dynamics, BioControl Medical, Boston Scientific and serves in the advisory board of Boston Scientific. MB receives speaker’s fee from Impulse Dynamics and serves on their international advisory board. SR has received modest speaker fees from Impulse Dynamics. KS, ET, BR, VL and RS: none.
Address of correspondence: Dr. med Jürgen Kuschyk I. Medical Department Theodor-Kutzer-Ufer 1-3 D-68167 Mannheim Germany Phone:+49(0)621-383-4231 Fax:+49(0)621-383-3061 E-Mail: [email protected] Abstract
Background Subcutaneous implantable cardioverter-defibrillator (S-ICD) is an implantable device for antiarrhythmic therapy with no intravascular leads.
Objective We describe the technical feasibility of combining the S-ICD with other cardiac implantable electronic devices (CIEDs), including pacemakers with trans-venous or epicardial electrodes. We also provide the first experience of combining S-ICD with catheter-based therapies including cardiac contractility modulation (CCM) and vagus nerve stimulation (VNS).
Methods Between 7/2011 and 11/2014 six patients received a CCM device and S-ICD, three patients with a single-chamber pacemaker using either trans-venous or epicardial pacing electrodes received S-ICD, and one patient with an implanted S-ICD received VNS. In all patients intraoperative S-ICD testing, crosstalk tests and postoperative ergometric testing were performed.
Results In all 10 patients device implantations were successfully performed without complications. S-ICD therapy was shown to be technically feasible with concomitant CIED. Mean follow up was nearly 17 months. S-ICD testing and crosstalk testing before and during exercise enabled device programming across a broad range of test conditions and was
associated with no subsequent evidence of adverse device interaction. None of the devices required permanent inactivation or removal and no patient received an inappropriate shock.
Conclusion In suitable patients, combining an S-ICD with CCM or pacemaker may provide an acceptable means to reduce the number of trans-vascular leads. S-ICD appeared safe with CCM over an intermediate follow-up period. Additional prospective randomized controlled trials examining S-ICD in conjunction with CIEDs are warranted.
Key words: Subcutaneous Implantable Cardioverter-Defibrillator, Cardiac Contractility Modulation, Vagus Nerve Stimulation, Heart Failure
Abbreviations ACE inhibitor
Angiotensin converting-enzyme inhibitor
ARB
Angiotensin receptor blocker,
BMI
Body mass index
b.p.m.
beats per minute
CMP
Cardiomyopathy
CCM
Cardiac contractility modulation
CIED
Cardiac implantable electrical device
CPX
Cardio-pulmonary exercise testing
CRT
Cardiac resynchronization therapy
CRT-D
Cardiac resynchronization therapy with defibrillator
CS
Coronary sinus
HF
Heart failure
ICD
Implantable cardioverter-defibrillator
LV
Left ventricle
LVEF
Left ventricular ejection fraction
MLWHFQ
Minnesota living with heart failure questionnaire
MRA
Mineralocorticoid receptor antagonist
N
Noise
NYHA
New York Heart Failure Association
Peak VO2
Peak oxygen uptake
PM
Pacemaker
RA
Right atrium
RV
Right ventricle
S
Sense
S-ICD
Subcutaneous implantable cardioverter defibrillator
VNS
Vagus nerve stimulation
Introduction
In the last years electrical device therapies were established as effective for symptomatic heart failure patients with reduced ejection fraction1, 2. Mortality rates were lowered by implantable cardioverter defibrillators (ICD) for the primary and secondary prevention of sudden cardiac death3-5 and cardiac resynchronization therapy (CRT) reduced morbidity and mortality in heart failure patients with left bundle brunch block6, 7. CRT has failed to show benefit in patients with a narrow QRS8. Other emerging device stimulatory therapies were developed some are currently available in Europe, though not yet FDA approved. Cardiac contractility modulation (CCM) delivers non-excitatory high voltage biphasic electrical impulses during the absolute refractory period that enhance ventricular contractile strength of the failing myocardium9-11. The Optimizer™ device that delivers the CCM impulse has CE mark and is approved for use in Europe in treating advanced HF, with particularly high benefit in patients with a left ventricular ejection fraction (LVEF) 25%, NYHA class III and normal QRS duration12, 13. Vagus nerve stimulation (VNS) is another electrical device-based technique that involves
stimulating the cervical pre-ganglionic parasympathetic fibers with direct activation of the cardiac vagal tone13. First study showed the feasibility of vagal stimulation to treat HF14. Early clinical trials were conducted with vagal stimulation (NECTAR-HF15 and ANTEHMHF16) which suggested the need for additional data from randomized trials. According to the guideline-recommended selection criteria, many patients eligible for CCM or vagus nerve stimulation also qualify for ICD placement. Since there is no currently available device that combines ICD functionality with either CCM or VNS, two devices are implanted in most patients. Since both approaches (CCM and VNS) require a chronic catheter in the RV, there is an elevated risk of lead complications including systemic infection, acute and chronic electrode displacement, lead insulation defects or fractures17, 18. Complication frequency is associated with the complexity of cardiac devices and the number of intracardiac electrodes19. A totally subcutaneous implantable defibrillator system (S-ICD) has been developed that consists of a subcutaneous electrode and pulse generator for arrhythmia sensing and defibrillation20-22. S-ICDs are specially indicated for patients for whom trans-venous electrode insertion is of high risk (e.g. prior trans-venous device procedures, occluded central veins, severe TR, presence of a mechanical tricuspid valve, or prior complication from lead insertion)23. With no intra-cardiac electrodes the S-ICD device cannot provide pacemaker or resynchronization therapy. The aim of this paper is to describe our local experience with the combined use of S-ICD with other cardiac implantable electronic devices (CIEDs). We report on the technical feasibility and clinical safety of this combination with cardiac contractility modulation and with pacing. Similarly, the feasibility of a case of combination with VNS is described.
Methods
Patients
Between July 2011 and November 2014 ten patients received a subcutaneous implantable cardioverter-defibrillator (S-ICD) that was combined with another CIED either during the same operation or in a subsequent procedure. This case series describes the implantation procedure, testing and follow-up specific to these combined devices. The study complies with the Declaration of Helsinki, with approval by the locally appointed ethics committee and with the informed consent of the subjects.
One patient received S-ICD in combination with a trans-venous single-chamber pacemaker with a left ventricular pacing electrode, two patients received S-ICD in combination with an abdominal pacemaker with epicardial pacing electrodes, six patients received S-ICD in combination with cardiac contractility modulation (CCM) and in one patient S-ICD was combined with vagus nerve stimulation (VNS).
Trans-venous pacemaker, S-ICD and CCM were placed under local anesthesia and sedation using fractionated midazolam/fentanyl. Abdominal pacemakers and VNS were implanted under general anesthesia.
S-ICD device description, implantation procedure and device testing The S-ICD implant technique and configuration used in this study has been described23, 24, 25. Briefly, the S-ICD system (Boston Scientific, Marlborough, MA, USA) consists of an electrically active defibrillator can and a 3-mm tri-polar polycarbonate urethane electrode. The electrode is positioned parallel to the sternum and the can is positioned over the sixth rib at the mid-axillary line. The S-ICD automatically selects an optimal vector for rhythm detection from three
independent sensing configurations. An algorithm using a conditional discrimination zone can be programmed between rates of 170 and 250 beats per minute to distinguish supraventricular tachycardia from ventricular tachycardia and to avoid inappropriate discharge. Within the conditional shock zone multiple algorithms mainly based on morphology are used to differentiate supraventricular from ventricular origin of the QRS complex. During implantation, S-ICD testing includes induction of ventricular fibrillation using a high voltage 50 Hz signal generated by the S-ICD followed by a shock.
Ergometric testing and provocation maneuvers
One to seven days after S-ICD implantation, patients underwent bicycle ergometer testing and provocative maneuvers to exclude exercise-induced oversensing. During the test S-ICD was switched “OFF”. The exercise test was stopped either when the patient had reached maximum heart rate (220 minus age b.p.m.) or when muscular fatigue had occurred. Afterwards, different provocation maneuvers (aggregate manipulation, physical maneuvers, standing and supine posture etc.) were performed prior to restoring the “ON” state of the device. The three sensing vectors of the S-ICD were monitored in real time during these tests and the S-ICD was configured to select the clearest signal defined as a stable baseline, high signal amplitude, and a high QRS/T ratio.
When patients had a concomitant CIED, that device was turned “ON” during ergometric testing and the optimal sensing vector was chosen as the one with the clearest signal that avoided double counting and oversensing, and that produced the least noise. This approach was effective independent of whether the S-ICD or CIED was implanted first.
General description of S-ICD implant with a CIED
In most cases, the implantation sequence is S-ICD followed by CIED. In this case, the S-ICD
is tested during the CIED implantation to select a vector for rhythm detection. Then during ergometer testing and provocative maneuvers, the chosen sensing vector can be manually modified in real time to minimize noise, double counting, and oversensing. In each case, all tests are performed with both devices activated: crosstalk test and S-ICD test are performed during the procedure, and reconfiguration during ergometer testing is done after the procedure.
Pacemaker Implantation techniques of pacemakers with trans-venous or epicardial electrodes are described elsewhere26. When a pacemaker is combined with an S-ICD, both the stimulated and the available intrinsic heart beat morphology are evaluated during preoperative patient screening. If the pacemaker is combined with S-ICD it is essential that bipolar pacing electrodes are used to minimize the pacing artefact on the S-ICD electrograms. This avoids the risk of missing the detection of tachycardia in cases of pacemaker improper pacing during the ventricular tachycardia that could prevent discharge of the S-ICD due to misinterpretation of the unipolar pacemaker stimulation spikes, withholding a lifesaving shock. It is important to recognize that older generation pacemaker devices might automatically switch to unipolar mode after a shock occurs.
CCM device description and implantation procedure Cardiac contractility modulation (CCM) delivers an electrical impulse to the ventricular cardiac muscle during the absolute refractory period. The utilized CCM waveform is a double bi-phasic square wave pulse delivered during the QRS. In general, impulses between 10 and 20mA in amplitude, and stimuli durations of about 20msec in total are delivered during the
QRS complex, about 30-50msec after the local depolarization is detected. CCM signals are delivered via an implantable pacing device similar to a pacemaker. Active CCM treatment is typically delivered in for about one hour intervals equally spaced, five, seven or more times a day. To date, the OPTIMIZER™IVs system (Impulse Dynamics Inc., Orangeburg, NJ, USA) is the only clinically available system for CCM delivery. The implantation procedure has been described13. The device is implanted into the pectoral region in a minimally invasive procedure and three bipolar pacemaker leads are introduced into the right side of the heart via the subclavian vein (in the reported cases, TENDRIL ST, SJM, St. Paul, MN, USA). One lead is placed into the right atrium to detect the atrial electrical activity. Two leads are positioned at the ventricular septum for delivery of impulses. The current CCM device contains a built-in algorithm that analyzes the timing between the sensed events in the three leads and inhibits delivery of a CCM signal during irregular rhythms such as premature atrial or ventricular complexes. This is designed to avoid CCM signal delivery during a T-wave. When CCM is implanted in a patient with a defibrillator, a crosstalk test is used to ensure the CCM signals are not detected by the ICD. In common practice with CCM it is known that if VF induction testing is performed the CCM algorithm properly inhibits the CCM delivery during the VF signal. This minimizes erroneous detection of the CCM signal by the S-ICD. The CCM battery is rechargeable. Patients are advised to recharge battery once per week for about one hour.
Vagus nerve stimulation (VNS) device description and implantation procedure The implantable vagal neurostimulator system (CardioFitTMsystem, BioControl Medical Ltd., Yehud, Israel) delivers low current electrical pulses, designed to sense heart rhythm via a standard intra-cardiac electrode and to deliver impulses at a variable delay (70-325ms) from
the R-wave16. The stimulation lead is an asymmetric bipolar multi-contact cuff electrode specifically designed for cathodal induction of action potentials in the vagus nerve while simultaneously applying asymmetrical anodal block, which is expected to preferential activate efferent vagal fibers. The implantation procedure has been described previously13. Briefly, the device is implanted into the right pectoral region using a minimally invasive procedure. Following positioning of the RV sensing electrode (5076 58 cm, Medtronic, Minneapolis, MN, USA) the right vagus is exposed through a lateral cervical incision and encircled by a custom cuff electrode. The stimulation lead is tunneled to the chest and together with the intra-cardiac sensing electrode is connected to the neurostimulator in the subclavicular region. A continuity circuit resistance test and heart rate reduction test are performed to ensure proper device function.
Crosstalk tests between S-ICD and a CIED When a second device (S-ICD or CIED) is implanted, an intra-operative crosstalk test is performed. All three sensing configurations of the S-ICD are monitored while the CIED is activated, to check double counting or oversensing. The vector with the clearest result is programmed as the selected sensing vector. When the coexisting CIED is a pacemaker, the appropriate S-ICD crosstalk test involves using a wide range of pacer settings. This can be done by programmed pacemaker undersensing or by programming the pacemaker to VOO/DOO with maximum output while VF is induced. When CCM is implanted into a patient with S-ICD, optimal lead placement can be tested to minimize CCM artefact in the S-ICD sensing vectors, to avoid oversensing or double counting by the S-ICD. During testing, the Optimizer can be temporarily programmed to vary therapy parameters (e.g. longer delay of CCM signal delivery within the QRS complex, signal amplitude, or selection of one lead to deliver CCM), to exclude any residual double counting
or oversensing by the S-ICD. The signal delivery logic for CCM is different than for a pacemaker. CCM requires three sensed events to be detected (one in the RA and 2 in the RV septum). Only if all are detected within predefined timing intervals will the CCM signal be delivered. The device is programmed so that any undersensing, improper timing, tachycardia, or other arrhythmic episode that affects the ventricle, prevents CCM delivery. The CCM algorithm is developed in complementary fashion to the ICD algorithm to insure that CCM is inhibited when ICD arrhythmia analysis takes place. This has been observed throughout the experience with CCM devices. Crosstalk does not seem to be an issue for VNS, which does not deliver electrical impulses to the heart.
Results Ten patients were successfully implanted with the combination of a S-ICD and a CIED without complications. The average follow-up was 20.4 months for the first five CCM patients (last patient was just recently implanted), 16 months for the one patient with a transvenous single-chamber pacemaker with a left ventricular pacing electrode, 18 months for the two patients with abdominal pacemakers and epicardial electrode, and 13 months for the one VNS patient. Figure 1 shows a chest-x-ray with each of the four combined devices.
S-ICD and pacemaker Baseline characteristics and device history of the three patients with S-ICD and pacemakers are provided in Table 1. Patient 1 had previously received a single-chamber pacemaker with a unipolar stimulation lead in the coronary sinus (CS). Presenting with a class Ia indication for primary ICD prophylaxis, a new bipolar CS electrode was placed instead. The S-ICD was implanted during
the same procedure. Intraoperative S-ICD testing revealed no crosstalk between devices, and ergometry and maneuvers showed no oversensing. Three months after the implantation the patient developed symptomatic monomorphic VT, which was converted effectively by the SICD. Patients 2 and 3 both had histories of multiple complications with trans-venous devices and each was implanted with an epicardial pacemaker lead and an abdominal pacemaker. Both subsequently underwent uncomplicated S-ICD implantation.
S-ICD and CCM Six patients were treated by S-ICD in combination with CCM. Their detailed device history and demographic data are described in Table 1 (Patients 4-9). Patients 4, 6 and 7 were implanted with an Optimizer (CCM) and an S-ICD that replaced a prior trans-venous device due to lead complications. In patients 5, 8 and 9 the S-ICD was implanted first, followed by an Optimizer implant for CCM treatment. Crosstalk testing between S-ICD and Optimizer in Patient 9 is shown in Figure 2. In patients 4, 5, 6, 8 and 9 at least one of the three S-ICD vectors showed “noise-free” ventricular sensing during CCM activity and this vector was selected for use. All five patients had successful intraoperative S-ICD testing during CCM signal delivery and none showed signs of oversensing during exercise testing or provocation maneuvers. Testing examples for patient 9 are shown in Figure 3. Patient 7 with an Optimizer had the trans-venous ICD replaced with an S-ICD. After the replacement procedure “noise” was registered on all three S-ICD sensing vectors during CCM activation, however the S-ICD did not characterize the noise as a sensed event. Despite the observed noise, ergometer testing and provocative maneuvers validated that there were no signs of double counting or T-wave oversensing, and intra-operative S-ICD testing was successful.
Details about LVEF, NYHA class, MLWHFQ and peak VO2 before CCM implantation and at last follow-up are described in Table 2. As of November 2014, all 6 patients were clinically stable.
S-ICD and vagus nerve stimulation (VNS) Patient 10 was treated with S-ICD and VNS. Intraoperative crosstalk testing showed no signs of double sensing. Intraoperative S-ICD testing with activated VNS was performed successfully. During ergometer testing and provocation maneuvers no oversensing occurred. This patient died in August 2013 from end stage heart failure.
S-ICD shocks during implant and subsequent testing Each patient underwent VF induction during implantation. The S-ICD detected all episodes with no undersensing or undue delay, and delivered an appropriate shock to terminate the VF. Specifically, in all three patients with a separately implanted pacemaker the S-ICD was successfully tested with the pacemaker programmed to VVI mode with maximum output. Additionally, in one patient the pacemaker was programmed to VOO with maximum output. Also in the asynchronous mode VF was adequately detected and subsequently successfully terminated by the S-ICD without delay. In no instance was double counting of impulses due to a concomitant CIED. In 3 patients with CCM and S-ICD noise (CCM artefact) was an issue in at least one vector, manual reprogramming of the S-ICD avoided the noise signal in two patients. Patient 7 was discussed in detail in results section “S-ICD and CCM”. Also in this case, settings were identified that allowed both devices to function properly.
S-ICD shocks during follow-up Our cumulative experience with S-ICD and CIEDs includes 10 patients, with 1 month to 35
months of follow-up, (average of 17 months). No inappropriate shocks were delivered throughout the follow-up period. Conversely, in 2 patients (1 and 7) 6 episodes of VT were detected several months after CIED implantation. In each case the arrhythmia was properly detected and terminated by the S-ICD. During follow-up, there were no syncope with an unclear cause and no aborted shocks.
Discussion We provide the first report that S-ICD therapy can safely be combined with concomitant CIEDs. Key observations are that 1) S-ICD devices can be combined with a variety of electronic cardiac device therapies that require intracardiac or epicardial leads; 2) Interference between S-ICD and CIEDs can be minimized sufficiently to allow both devices to function properly and safely; and 3) successful co-existence of both devices is sustained for intermediate time periods. In all 10 patients device implantations were successfully performed without complications, even in those who suffered complications with prior trans-venous devices. Furthermore, it was shown that S-ICD therapy is technically feasible in patients with a single-chamber pacemaker as well as those who have more complex pulse generators used for CCM or VNS. In no case was it necessary to permanently inactivate the device. Patients who suffer from symptomatic bradycardia are not eligible for S-ICD therapy alone, because no device combines S-ICD with cardiac pacing or cardiac resynchronization therapy. The successful combination of the S-ICD with a pacemaker that has either trans-venous left ventricular pacemaker electrode or epicardial electrode is technically feasible and offers both cardiac stimulation and arrhythmia protection even in a patient with a prosthetic tricuspid valve. Approximately 60% of patients with advanced heart failure have narrow QRS complex27, and may be candidates for new electrical device therapies including CCM and VNS. For many
patients eligible for these therapies, a defibrillator is indicated due to reduced ejection fraction. This could result in the need for 4 or more trans-venous electrodes if a traditional ICD is used. While this approach is used widely with a relatively low rate of lead complications, the use of S-ICD could help reducing the overall number of implanted leads and associated potential complications. Hypothetically, S-ICD might be considered for all patients except individuals with bradypacing indication, CRT indication or documented VT < 170 b.p.m., which are about half of the patients with an ICD indication28. Further randomized controlled studies with S-ICD are warranted to determine its role in clinical practice. Due to its potential, it is important to know how safely this device can be used with other implantable devices. This report demonstrates technical feasibility and suggests safety of such an approach. The investigators suggest the following steps for implanting, testing and configuring an SICD with concomitant CIED: •
Through testing during implantation, select a clear sensing vector for the S-ICD implant
•
Perform signal evaluation and confirm or modify vector settings during ergometric testing and provocation maneuvers
•
In cases of S-ICD with concomitant CIED, independent of the order of implantation, while the CIED is active repeat vector selection (crosstalk test), S-ICD testing, ergometric and provocation testing in real-time. Adjust S-ICD sensing and CIED parameters manually to avoid interference from stimulation artefacts (noise) produced by the CIED, thereby avoiding double counting or oversensing. This provides a near real life evaluation for optimizing parameter selection.
Our initial experience suggests that combined device therapy (S-ICD and CIED) can be used safely. This experience extends for an average of 20.4 months with CCM.
The combination of an S-ICD with CCM may be especially useful in younger patients with advanced heart failure or in patients who suffered from lead complications in the past, thus avoiding long-term trans-venous lead complications or endocarditis due to device infections. Furthermore, this combined approach could be beneficial to patients on hemodialysis, or in patients on the waiting list for heart transplantation.
Combined trans-venous pacemakers-ICDs or CRT-Ds are the standard of care in patients, who require ICD therapy and are dependent on pacemaker stimulation29. The combination of an S-ICD with a pacemaker should be reserved for cases in which the patient has an indication for pacing or is at a high risk of becoming pacemaker-dependent in the future, or when a trans-venous ICD is technically or clinically problematic. Future technology will likely lead to combined devices and thereby reduce the trans-venous electrode burden, streamlining implantation. An S-ICD combined with leadless-pacing capabilities, combined CRT functions with S-ICD and combined ICD with CCM would be of benefit.
Limitations of the study This study presents experience with a new technology in a small cohort from a single site as a case series. Further multicenter studies are needed to evaluate the long-term impact of the methods. This work is predominantly focused on the implant technique and feasibility of combined device use, and presents limited data on clinical outcome in a non-randomized controlled manner. The investigators are from a single hospital that functions as a German teaching center for SICD implantations. Success and complication rates of S-ICD implantation are strongly related to the experience of the implanting surgeon30. Thus the reported results may be influenced by
the experience of the implantation team.
Conclusions We conclude that from technical perspective S-ICD can be safely combined with other cardiac devices (pacemaker, CCM device, and VNS device) in relevant patients with heart failure and indications for combined therapy. The implantation procedure requires careful selection of S-ICD vectors using provocative and exercise testing to minimize artefact interference from the other implanted device. The combination of an S-ICD with CCM and VNS may be a useful tool to reduce the number of required trans-venous electrodes. With the good intermediate-term experience to-date, we conclude that S-ICD was successfully implanted and safely co-worked with CCM. Since many times devices are implanted sequentially based on different indications, future development should consider combining defibrillation features and therapeutic features into one device, further reducing the number of implanted trans-vascular leads. Additional experience with combined devices is needed including randomized trials to assess the longterm safety and efficacy of S-ICD combined with CIED compared with an implantable dual device approach.
Literature
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Tables Table 1 Characteristics and device history of the patients with S-ICD and CIED Patient number Age (years) at SICD implantation Gender
BMI= Body mass 61 71 63 56 47 75 65 25 52 56 index; CMP= F M M M M M M M F M 2 Cardio BMI (kg/m ) 24 24 26 30 40 27 25 41 26 myopa ischemic Etiology of thy; and HOCM Ischemic ischemic dilated ischemic Ischemic dilated dilated dilated CMP LVEF valvular =left LVEF 20% 65% 26% 13% 27% 20% 30% 15% 15% 15% ventri NYHA IIIB I II IIIB III III III III III III cular Diabetes + + + ejectio Renal n + + + + + + insufficiency fractio Baseline n, medication ACE ACE + + + + + + + + inhibitor/ARB inhibit Betablocker + + + + + + + + + + or=An gioten MRA + + + + + + sin Digitalis + conver Diuretic + + + + + + + + + ting S-ICD Abdominal Abdominal enzym 7/2013, 11e S-ICD S-ICD S-ICD S-ICD S-ICD S-ICD 1S-ICD chamberchamberinhibit Device chamber 7/2011, 4/2012, 7/2013, 10/2013, 1/2014, 7/2014, 5/2012, PM PM CCM CCM CCM CCM history PM with CCM CCM VNS or; 12/2012, 8/2012, SLV 12/2011 6/2012 6/2010 4/2009 2/2014 11/2014 07/2012 ARB= ICD S-ICD electrode 3/2013 7/2014 Angio 7/2013 tensin receptor blocker, MRA=Mineralocorticoid receptor antagonist, PM=Pacemaker, VNS= Vagus nerve stimulator; HOCM= hypertrophic obstructive cardiomyopathy; CCM= Cardiac contractility modulation
1
2
3
4
5
6
7
8
9
10
Table 2 Cardiac Evaluation of Patients with S-ICD and CCM LVEF, NYHA Class, MLWHFQ and CPX before CCM implantation and at last follow-up Patient number
4
5
6
7
8
9
LVEF before CCM implantation
13%
27%
20%
30%
15%
15%
LVEF at last follow-up
13%
34%
28%
35%
18%
no follow-up
NYHA class before CCM implantation
IIIB
III
III
III
III
III
NYHA class at last follow-up
IIIA
II
III
III
III
no follow-up
MLWHFQ before CCM implantation
88
82
49
50
62
88
MLWHFQ at last follow-up
46
16
17
48
50
no follow-up
CPX peak VO2 (ml/kg/min) before CCM implantation
9.7
16.3
7.3
15.5
10.0
8.9
11.1 (7.3)**
13.3*
14.0
15.7
12.6
no follow-up
CPX peak VO2 (ml/kg/min) at about one year follow-up
LVEF=Left ventricular ejection fraction; MLWHFQ=Minnesota living with heart failure questionnare; CPX=Cardiopulmonary exercise testing, peak VO2= peak oxygen uptake *limited by recent morbid obesity, **patient had 11.1 within the first year and 7.3 after three years
Legends to the Figures Figure 1: Chest x-rays A: S-ICD and trans-venous single-chamber pacemaker with left ventricular pacing electrode: reconstructed mitral valve, prosthetic tricuspid valve, two left ventricular electrodes B: S-ICD and abdominal pacemaker C: S-ICD and Optimizer IVs D: S-ICD and vagus nerve stimulator
RA=right atrial, RV=right ventricular, LV=left ventricular
Figure 2: Crosstalk test between S-ICD and Optimizer IVs in Patient 9: Primary vector and alternate vector not used due to “noise” during CCM activation Secondary vector filters the CCM signals, eliminating noise and double detection Secondary vector was programmed as permanent sensing configuration N= noise, S= sensing
Figure 3: S-ICD testing with activated CCM in Patient 9: After induction of ventricular fibrillation through a 50Hz impulse CCM stimulation is inhibited. The 65 Joule shock terminates ventricular fibrillation successfully. When patient returned to sinus rhythm CCM stimulation reengaged.
The Subcutaneous Implantable CardioverterDefibrillator – First Single-Center Experience with other Cardiac Implantable Electronic Devices Jürgen Kuschyk MD, Ksenija Stach MD, Erol Tülümen MD, Boris Rudic MD, Volker Liebe MD, Rainer Schimpf MD PhD, Martin Borggrefe MD PhD, Susanne Röger MD www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1547-5271(15)00713-4 http://dx.doi.org/10.1016/j.hrthm.2015.06.022 HRTHM6321
To appear in:
Heart Rhythm
Cite this article as: Jürgen Kuschyk MD, Ksenija Stach MD, Erol Tülümen MD, Boris Rudic MD, Volker Liebe MD, Rainer Schimpf MD PhD, Martin Borggrefe MD PhD, Susanne Röger MD, The Subcutaneous Implantable Cardioverter-Defibrillator – First Single-Center Experience with other Cardiac Implantable Electronic Devices, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2015.06.022 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Subcutaneous Implantable Cardioverter-Defibrillator – First Single-Center Experience with other Cardiac Implantable Electronic Devices
Jürgen Kuschyk MD1,2, Ksenija Stach MD1,2, Erol Tülümen MD1,2, Boris Rudic MD1,2, Volker Liebe MD1,2, Rainer Schimpf MD PhD1,2, Martin Borggrefe MD PhD1,2 and Susanne Röger MD1,2
(1) Medical Faculty Mannheim of the University of Heidelberg, 1st Department of Medicine, Mannheim, Germany (2) DZHK (German Centre for Cardiovascular Research) partner site Mannheim, Germany
Running Title: Subcutaneous Defibrillator in combination with other Cardiac Devices
Disclosures and conflicts of all authors The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Acknowledgement of grant support: This study was initiated by the investigators. There is no grant support to declare. Disclosures: JK has received modest speaker fees from Impulse Dynamics, BioControl Medical, Boston Scientific and serves in the advisory board of Boston Scientific. MB receives speaker’s fee from Impulse Dynamics and serves on their international advisory board. SR has received modest speaker fees from Impulse Dynamics. KS, ET, BR, VL and RS: none.
Address of correspondence: Dr. med Jürgen Kuschyk I. Medical Department Theodor-Kutzer-Ufer 1-3 D-68167 Mannheim Germany Phone:+49(0)621-383-4231 Fax:+49(0)621-383-3061 E-Mail: [email protected] Abstract
Background Subcutaneous implantable cardioverter-defibrillator (S-ICD) is an implantable device for antiarrhythmic therapy with no intravascular leads.
Objective We describe the technical feasibility of combining the S-ICD with other cardiac implantable electronic devices (CIEDs), including pacemakers with trans-venous or epicardial electrodes. We also provide the first experience of combining S-ICD with catheter-based therapies including cardiac contractility modulation (CCM) and vagus nerve stimulation (VNS).
Methods Between 7/2011 and 11/2014 six patients received a CCM device and S-ICD, three patients with a single-chamber pacemaker using either trans-venous or epicardial pacing electrodes received S-ICD, and one patient with an implanted S-ICD received VNS. In all patients intraoperative S-ICD testing, crosstalk tests and postoperative ergometric testing were performed.
Results In all 10 patients device implantations were successfully performed without complications. S-ICD therapy was shown to be technically feasible with concomitant CIED. Mean follow up was nearly 17 months. S-ICD testing and crosstalk testing before and during exercise enabled device programming across a broad range of test conditions and was
associated with no subsequent evidence of adverse device interaction. None of the devices required permanent inactivation or removal and no patient received an inappropriate shock.
Conclusion In suitable patients, combining an S-ICD with CCM or pacemaker may provide an acceptable means to reduce the number of trans-vascular leads. S-ICD appeared safe with CCM over an intermediate follow-up period. Additional prospective randomized controlled trials examining S-ICD in conjunction with CIEDs are warranted.
Key words: Subcutaneous Implantable Cardioverter-Defibrillator, Cardiac Contractility Modulation, Vagus Nerve Stimulation, Heart Failure
Abbreviations ACE inhibitor
Angiotensin converting-enzyme inhibitor
ARB
Angiotensin receptor blocker,
BMI
Body mass index
b.p.m.
beats per minute
CMP
Cardiomyopathy
CCM
Cardiac contractility modulation
CIED
Cardiac implantable electrical device
CPX
Cardio-pulmonary exercise testing
CRT
Cardiac resynchronization therapy
CRT-D
Cardiac resynchronization therapy with defibrillator
CS
Coronary sinus
HF
Heart failure
ICD
Implantable cardioverter-defibrillator
LV
Left ventricle
LVEF
Left ventricular ejection fraction
MLWHFQ
Minnesota living with heart failure questionnaire
MRA
Mineralocorticoid receptor antagonist
N
Noise
NYHA
New York Heart Failure Association
Peak VO2
Peak oxygen uptake
PM
Pacemaker
RA
Right atrium
RV
Right ventricle
S
Sense
S-ICD
Subcutaneous implantable cardioverter defibrillator
VNS
Vagus nerve stimulation
Introduction
In the last years electrical device therapies were established as effective for symptomatic heart failure patients with reduced ejection fraction1, 2. Mortality rates were lowered by implantable cardioverter defibrillators (ICD) for the primary and secondary prevention of sudden cardiac death3-5 and cardiac resynchronization therapy (CRT) reduced morbidity and mortality in heart failure patients with left bundle brunch block6, 7. CRT has failed to show benefit in patients with a narrow QRS8. Other emerging device stimulatory therapies were developed some are currently available in Europe, though not yet FDA approved. Cardiac contractility modulation (CCM) delivers non-excitatory high voltage biphasic electrical impulses during the absolute refractory period that enhance ventricular contractile strength of the failing myocardium9-11. The Optimizer™ device that delivers the CCM impulse has CE mark and is approved for use in Europe in treating advanced HF, with particularly high benefit in patients with a left ventricular ejection fraction (LVEF) 25%, NYHA class III and normal QRS duration12, 13. Vagus nerve stimulation (VNS) is another electrical device-based technique that involves
stimulating the cervical pre-ganglionic parasympathetic fibers with direct activation of the cardiac vagal tone13. First study showed the feasibility of vagal stimulation to treat HF14. Early clinical trials were conducted with vagal stimulation (NECTAR-HF15 and ANTEHMHF16) which suggested the need for additional data from randomized trials. According to the guideline-recommended selection criteria, many patients eligible for CCM or vagus nerve stimulation also qualify for ICD placement. Since there is no currently available device that combines ICD functionality with either CCM or VNS, two devices are implanted in most patients. Since both approaches (CCM and VNS) require a chronic catheter in the RV, there is an elevated risk of lead complications including systemic infection, acute and chronic electrode displacement, lead insulation defects or fractures17, 18. Complication frequency is associated with the complexity of cardiac devices and the number of intracardiac electrodes19. A totally subcutaneous implantable defibrillator system (S-ICD) has been developed that consists of a subcutaneous electrode and pulse generator for arrhythmia sensing and defibrillation20-22. S-ICDs are specially indicated for patients for whom trans-venous electrode insertion is of high risk (e.g. prior trans-venous device procedures, occluded central veins, severe TR, presence of a mechanical tricuspid valve, or prior complication from lead insertion)23. With no intra-cardiac electrodes the S-ICD device cannot provide pacemaker or resynchronization therapy. The aim of this paper is to describe our local experience with the combined use of S-ICD with other cardiac implantable electronic devices (CIEDs). We report on the technical feasibility and clinical safety of this combination with cardiac contractility modulation and with pacing. Similarly, the feasibility of a case of combination with VNS is described.
Methods
Patients
Between July 2011 and November 2014 ten patients received a subcutaneous implantable cardioverter-defibrillator (S-ICD) that was combined with another CIED either during the same operation or in a subsequent procedure. This case series describes the implantation procedure, testing and follow-up specific to these combined devices. The study complies with the Declaration of Helsinki, with approval by the locally appointed ethics committee and with the informed consent of the subjects.
One patient received S-ICD in combination with a trans-venous single-chamber pacemaker with a left ventricular pacing electrode, two patients received S-ICD in combination with an abdominal pacemaker with epicardial pacing electrodes, six patients received S-ICD in combination with cardiac contractility modulation (CCM) and in one patient S-ICD was combined with vagus nerve stimulation (VNS).
Trans-venous pacemaker, S-ICD and CCM were placed under local anesthesia and sedation using fractionated midazolam/fentanyl. Abdominal pacemakers and VNS were implanted under general anesthesia.
S-ICD device description, implantation procedure and device testing The S-ICD implant technique and configuration used in this study has been described23, 24, 25. Briefly, the S-ICD system (Boston Scientific, Marlborough, MA, USA) consists of an electrically active defibrillator can and a 3-mm tri-polar polycarbonate urethane electrode. The electrode is positioned parallel to the sternum and the can is positioned over the sixth rib at the mid-axillary line. The S-ICD automatically selects an optimal vector for rhythm detection from three
independent sensing configurations. An algorithm using a conditional discrimination zone can be programmed between rates of 170 and 250 beats per minute to distinguish supraventricular tachycardia from ventricular tachycardia and to avoid inappropriate discharge. Within the conditional shock zone multiple algorithms mainly based on morphology are used to differentiate supraventricular from ventricular origin of the QRS complex. During implantation, S-ICD testing includes induction of ventricular fibrillation using a high voltage 50 Hz signal generated by the S-ICD followed by a shock.
Ergometric testing and provocation maneuvers
One to seven days after S-ICD implantation, patients underwent bicycle ergometer testing and provocative maneuvers to exclude exercise-induced oversensing. During the test S-ICD was switched “OFF”. The exercise test was stopped either when the patient had reached maximum heart rate (220 minus age b.p.m.) or when muscular fatigue had occurred. Afterwards, different provocation maneuvers (aggregate manipulation, physical maneuvers, standing and supine posture etc.) were performed prior to restoring the “ON” state of the device. The three sensing vectors of the S-ICD were monitored in real time during these tests and the S-ICD was configured to select the clearest signal defined as a stable baseline, high signal amplitude, and a high QRS/T ratio.
When patients had a concomitant CIED, that device was turned “ON” during ergometric testing and the optimal sensing vector was chosen as the one with the clearest signal that avoided double counting and oversensing, and that produced the least noise. This approach was effective independent of whether the S-ICD or CIED was implanted first.
General description of S-ICD implant with a CIED
In most cases, the implantation sequence is S-ICD followed by CIED. In this case, the S-ICD
is tested during the CIED implantation to select a vector for rhythm detection. Then during ergometer testing and provocative maneuvers, the chosen sensing vector can be manually modified in real time to minimize noise, double counting, and oversensing. In each case, all tests are performed with both devices activated: crosstalk test and S-ICD test are performed during the procedure, and reconfiguration during ergometer testing is done after the procedure.
Pacemaker Implantation techniques of pacemakers with trans-venous or epicardial electrodes are described elsewhere26. When a pacemaker is combined with an S-ICD, both the stimulated and the available intrinsic heart beat morphology are evaluated during preoperative patient screening. If the pacemaker is combined with S-ICD it is essential that bipolar pacing electrodes are used to minimize the pacing artefact on the S-ICD electrograms. This avoids the risk of missing the detection of tachycardia in cases of pacemaker improper pacing during the ventricular tachycardia that could prevent discharge of the S-ICD due to misinterpretation of the unipolar pacemaker stimulation spikes, withholding a lifesaving shock. It is important to recognize that older generation pacemaker devices might automatically switch to unipolar mode after a shock occurs.
CCM device description and implantation procedure Cardiac contractility modulation (CCM) delivers an electrical impulse to the ventricular cardiac muscle during the absolute refractory period. The utilized CCM waveform is a double bi-phasic square wave pulse delivered during the QRS. In general, impulses between 10 and 20mA in amplitude, and stimuli durations of about 20msec in total are delivered during the
QRS complex, about 30-50msec after the local depolarization is detected. CCM signals are delivered via an implantable pacing device similar to a pacemaker. Active CCM treatment is typically delivered in for about one hour intervals equally spaced, five, seven or more times a day. To date, the OPTIMIZER™IVs system (Impulse Dynamics Inc., Orangeburg, NJ, USA) is the only clinically available system for CCM delivery. The implantation procedure has been described13. The device is implanted into the pectoral region in a minimally invasive procedure and three bipolar pacemaker leads are introduced into the right side of the heart via the subclavian vein (in the reported cases, TENDRIL ST, SJM, St. Paul, MN, USA). One lead is placed into the right atrium to detect the atrial electrical activity. Two leads are positioned at the ventricular septum for delivery of impulses. The current CCM device contains a built-in algorithm that analyzes the timing between the sensed events in the three leads and inhibits delivery of a CCM signal during irregular rhythms such as premature atrial or ventricular complexes. This is designed to avoid CCM signal delivery during a T-wave. When CCM is implanted in a patient with a defibrillator, a crosstalk test is used to ensure the CCM signals are not detected by the ICD. In common practice with CCM it is known that if VF induction testing is performed the CCM algorithm properly inhibits the CCM delivery during the VF signal. This minimizes erroneous detection of the CCM signal by the S-ICD. The CCM battery is rechargeable. Patients are advised to recharge battery once per week for about one hour.
Vagus nerve stimulation (VNS) device description and implantation procedure The implantable vagal neurostimulator system (CardioFitTMsystem, BioControl Medical Ltd., Yehud, Israel) delivers low current electrical pulses, designed to sense heart rhythm via a standard intra-cardiac electrode and to deliver impulses at a variable delay (70-325ms) from
the R-wave16. The stimulation lead is an asymmetric bipolar multi-contact cuff electrode specifically designed for cathodal induction of action potentials in the vagus nerve while simultaneously applying asymmetrical anodal block, which is expected to preferential activate efferent vagal fibers. The implantation procedure has been described previously13. Briefly, the device is implanted into the right pectoral region using a minimally invasive procedure. Following positioning of the RV sensing electrode (5076 58 cm, Medtronic, Minneapolis, MN, USA) the right vagus is exposed through a lateral cervical incision and encircled by a custom cuff electrode. The stimulation lead is tunneled to the chest and together with the intra-cardiac sensing electrode is connected to the neurostimulator in the subclavicular region. A continuity circuit resistance test and heart rate reduction test are performed to ensure proper device function.
Crosstalk tests between S-ICD and a CIED When a second device (S-ICD or CIED) is implanted, an intra-operative crosstalk test is performed. All three sensing configurations of the S-ICD are monitored while the CIED is activated, to check double counting or oversensing. The vector with the clearest result is programmed as the selected sensing vector. When the coexisting CIED is a pacemaker, the appropriate S-ICD crosstalk test involves using a wide range of pacer settings. This can be done by programmed pacemaker undersensing or by programming the pacemaker to VOO/DOO with maximum output while VF is induced. When CCM is implanted into a patient with S-ICD, optimal lead placement can be tested to minimize CCM artefact in the S-ICD sensing vectors, to avoid oversensing or double counting by the S-ICD. During testing, the Optimizer can be temporarily programmed to vary therapy parameters (e.g. longer delay of CCM signal delivery within the QRS complex, signal amplitude, or selection of one lead to deliver CCM), to exclude any residual double counting
or oversensing by the S-ICD. The signal delivery logic for CCM is different than for a pacemaker. CCM requires three sensed events to be detected (one in the RA and 2 in the RV septum). Only if all are detected within predefined timing intervals will the CCM signal be delivered. The device is programmed so that any undersensing, improper timing, tachycardia, or other arrhythmic episode that affects the ventricle, prevents CCM delivery. The CCM algorithm is developed in complementary fashion to the ICD algorithm to insure that CCM is inhibited when ICD arrhythmia analysis takes place. This has been observed throughout the experience with CCM devices. Crosstalk does not seem to be an issue for VNS, which does not deliver electrical impulses to the heart.
Results Ten patients were successfully implanted with the combination of a S-ICD and a CIED without complications. The average follow-up was 20.4 months for the first five CCM patients (last patient was just recently implanted), 16 months for the one patient with a transvenous single-chamber pacemaker with a left ventricular pacing electrode, 18 months for the two patients with abdominal pacemakers and epicardial electrode, and 13 months for the one VNS patient. Figure 1 shows a chest-x-ray with each of the four combined devices.
S-ICD and pacemaker Baseline characteristics and device history of the three patients with S-ICD and pacemakers are provided in Table 1. Patient 1 had previously received a single-chamber pacemaker with a unipolar stimulation lead in the coronary sinus (CS). Presenting with a class Ia indication for primary ICD prophylaxis, a new bipolar CS electrode was placed instead. The S-ICD was implanted during
the same procedure. Intraoperative S-ICD testing revealed no crosstalk between devices, and ergometry and maneuvers showed no oversensing. Three months after the implantation the patient developed symptomatic monomorphic VT, which was converted effectively by the SICD. Patients 2 and 3 both had histories of multiple complications with trans-venous devices and each was implanted with an epicardial pacemaker lead and an abdominal pacemaker. Both subsequently underwent uncomplicated S-ICD implantation.
S-ICD and CCM Six patients were treated by S-ICD in combination with CCM. Their detailed device history and demographic data are described in Table 1 (Patients 4-9). Patients 4, 6 and 7 were implanted with an Optimizer (CCM) and an S-ICD that replaced a prior trans-venous device due to lead complications. In patients 5, 8 and 9 the S-ICD was implanted first, followed by an Optimizer implant for CCM treatment. Crosstalk testing between S-ICD and Optimizer in Patient 9 is shown in Figure 2. In patients 4, 5, 6, 8 and 9 at least one of the three S-ICD vectors showed “noise-free” ventricular sensing during CCM activity and this vector was selected for use. All five patients had successful intraoperative S-ICD testing during CCM signal delivery and none showed signs of oversensing during exercise testing or provocation maneuvers. Testing examples for patient 9 are shown in Figure 3. Patient 7 with an Optimizer had the trans-venous ICD replaced with an S-ICD. After the replacement procedure “noise” was registered on all three S-ICD sensing vectors during CCM activation, however the S-ICD did not characterize the noise as a sensed event. Despite the observed noise, ergometer testing and provocative maneuvers validated that there were no signs of double counting or T-wave oversensing, and intra-operative S-ICD testing was successful.
Details about LVEF, NYHA class, MLWHFQ and peak VO2 before CCM implantation and at last follow-up are described in Table 2. As of November 2014, all 6 patients were clinically stable.
S-ICD and vagus nerve stimulation (VNS) Patient 10 was treated with S-ICD and VNS. Intraoperative crosstalk testing showed no signs of double sensing. Intraoperative S-ICD testing with activated VNS was performed successfully. During ergometer testing and provocation maneuvers no oversensing occurred. This patient died in August 2013 from end stage heart failure.
S-ICD shocks during implant and subsequent testing Each patient underwent VF induction during implantation. The S-ICD detected all episodes with no undersensing or undue delay, and delivered an appropriate shock to terminate the VF. Specifically, in all three patients with a separately implanted pacemaker the S-ICD was successfully tested with the pacemaker programmed to VVI mode with maximum output. Additionally, in one patient the pacemaker was programmed to VOO with maximum output. Also in the asynchronous mode VF was adequately detected and subsequently successfully terminated by the S-ICD without delay. In no instance was double counting of impulses due to a concomitant CIED. In 3 patients with CCM and S-ICD noise (CCM artefact) was an issue in at least one vector, manual reprogramming of the S-ICD avoided the noise signal in two patients. Patient 7 was discussed in detail in results section “S-ICD and CCM”. Also in this case, settings were identified that allowed both devices to function properly.
S-ICD shocks during follow-up Our cumulative experience with S-ICD and CIEDs includes 10 patients, with 1 month to 35
months of follow-up, (average of 17 months). No inappropriate shocks were delivered throughout the follow-up period. Conversely, in 2 patients (1 and 7) 6 episodes of VT were detected several months after CIED implantation. In each case the arrhythmia was properly detected and terminated by the S-ICD. During follow-up, there were no syncope with an unclear cause and no aborted shocks.
Discussion We provide the first report that S-ICD therapy can safely be combined with concomitant CIEDs. Key observations are that 1) S-ICD devices can be combined with a variety of electronic cardiac device therapies that require intracardiac or epicardial leads; 2) Interference between S-ICD and CIEDs can be minimized sufficiently to allow both devices to function properly and safely; and 3) successful co-existence of both devices is sustained for intermediate time periods. In all 10 patients device implantations were successfully performed without complications, even in those who suffered complications with prior trans-venous devices. Furthermore, it was shown that S-ICD therapy is technically feasible in patients with a single-chamber pacemaker as well as those who have more complex pulse generators used for CCM or VNS. In no case was it necessary to permanently inactivate the device. Patients who suffer from symptomatic bradycardia are not eligible for S-ICD therapy alone, because no device combines S-ICD with cardiac pacing or cardiac resynchronization therapy. The successful combination of the S-ICD with a pacemaker that has either trans-venous left ventricular pacemaker electrode or epicardial electrode is technically feasible and offers both cardiac stimulation and arrhythmia protection even in a patient with a prosthetic tricuspid valve. Approximately 60% of patients with advanced heart failure have narrow QRS complex27, and may be candidates for new electrical device therapies including CCM and VNS. For many
patients eligible for these therapies, a defibrillator is indicated due to reduced ejection fraction. This could result in the need for 4 or more trans-venous electrodes if a traditional ICD is used. While this approach is used widely with a relatively low rate of lead complications, the use of S-ICD could help reducing the overall number of implanted leads and associated potential complications. Hypothetically, S-ICD might be considered for all patients except individuals with bradypacing indication, CRT indication or documented VT < 170 b.p.m., which are about half of the patients with an ICD indication28. Further randomized controlled studies with S-ICD are warranted to determine its role in clinical practice. Due to its potential, it is important to know how safely this device can be used with other implantable devices. This report demonstrates technical feasibility and suggests safety of such an approach. The investigators suggest the following steps for implanting, testing and configuring an SICD with concomitant CIED: •
Through testing during implantation, select a clear sensing vector for the S-ICD implant
•
Perform signal evaluation and confirm or modify vector settings during ergometric testing and provocation maneuvers
•
In cases of S-ICD with concomitant CIED, independent of the order of implantation, while the CIED is active repeat vector selection (crosstalk test), S-ICD testing, ergometric and provocation testing in real-time. Adjust S-ICD sensing and CIED parameters manually to avoid interference from stimulation artefacts (noise) produced by the CIED, thereby avoiding double counting or oversensing. This provides a near real life evaluation for optimizing parameter selection.
Our initial experience suggests that combined device therapy (S-ICD and CIED) can be used safely. This experience extends for an average of 20.4 months with CCM.
The combination of an S-ICD with CCM may be especially useful in younger patients with advanced heart failure or in patients who suffered from lead complications in the past, thus avoiding long-term trans-venous lead complications or endocarditis due to device infections. Furthermore, this combined approach could be beneficial to patients on hemodialysis, or in patients on the waiting list for heart transplantation.
Combined trans-venous pacemakers-ICDs or CRT-Ds are the standard of care in patients, who require ICD therapy and are dependent on pacemaker stimulation29. The combination of an S-ICD with a pacemaker should be reserved for cases in which the patient has an indication for pacing or is at a high risk of becoming pacemaker-dependent in the future, or when a trans-venous ICD is technically or clinically problematic. Future technology will likely lead to combined devices and thereby reduce the trans-venous electrode burden, streamlining implantation. An S-ICD combined with leadless-pacing capabilities, combined CRT functions with S-ICD and combined ICD with CCM would be of benefit.
Limitations of the study This study presents experience with a new technology in a small cohort from a single site as a case series. Further multicenter studies are needed to evaluate the long-term impact of the methods. This work is predominantly focused on the implant technique and feasibility of combined device use, and presents limited data on clinical outcome in a non-randomized controlled manner. The investigators are from a single hospital that functions as a German teaching center for SICD implantations. Success and complication rates of S-ICD implantation are strongly related to the experience of the implanting surgeon30. Thus the reported results may be influenced by
the experience of the implantation team.
Conclusions We conclude that from technical perspective S-ICD can be safely combined with other cardiac devices (pacemaker, CCM device, and VNS device) in relevant patients with heart failure and indications for combined therapy. The implantation procedure requires careful selection of S-ICD vectors using provocative and exercise testing to minimize artefact interference from the other implanted device. The combination of an S-ICD with CCM and VNS may be a useful tool to reduce the number of required trans-venous electrodes. With the good intermediate-term experience to-date, we conclude that S-ICD was successfully implanted and safely co-worked with CCM. Since many times devices are implanted sequentially based on different indications, future development should consider combining defibrillation features and therapeutic features into one device, further reducing the number of implanted trans-vascular leads. Additional experience with combined devices is needed including randomized trials to assess the longterm safety and efficacy of S-ICD combined with CIED compared with an implantable dual device approach.
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Tables Table 1 Characteristics and device history of the patients with S-ICD and CIED Patient number Age (years) at SICD implantation Gender
BMI= Body mass 61 71 63 56 47 75 65 25 52 56 index; CMP= F M M M M M M M F M 2 Cardio BMI (kg/m ) 24 24 26 30 40 27 25 41 26 myopa ischemic Etiology of thy; and HOCM Ischemic ischemic dilated ischemic Ischemic dilated dilated dilated CMP LVEF valvular =left LVEF 20% 65% 26% 13% 27% 20% 30% 15% 15% 15% ventri NYHA IIIB I II IIIB III III III III III III cular Diabetes + + + ejectio Renal n + + + + + + insufficiency fractio Baseline n, medication ACE ACE + + + + + + + + inhibitor/ARB inhibit Betablocker + + + + + + + + + + or=An gioten MRA + + + + + + sin Digitalis + conver Diuretic + + + + + + + + + ting S-ICD Abdominal Abdominal enzym 7/2013, 11e S-ICD S-ICD S-ICD S-ICD S-ICD S-ICD 1S-ICD chamberchamberinhibit Device chamber 7/2011, 4/2012, 7/2013, 10/2013, 1/2014, 7/2014, 5/2012, PM PM CCM CCM CCM CCM history PM with CCM CCM VNS or; 12/2012, 8/2012, SLV 12/2011 6/2012 6/2010 4/2009 2/2014 11/2014 07/2012 ARB= ICD S-ICD electrode 3/2013 7/2014 Angio 7/2013 tensin receptor blocker, MRA=Mineralocorticoid receptor antagonist, PM=Pacemaker, VNS= Vagus nerve stimulator; HOCM= hypertrophic obstructive cardiomyopathy; CCM= Cardiac contractility modulation
1
2
3
4
5
6
7
8
9
10
Table 2 Cardiac Evaluation of Patients with S-ICD and CCM LVEF, NYHA Class, MLWHFQ and CPX before CCM implantation and at last follow-up Patient number
4
5
6
7
8
9
LVEF before CCM implantation
13%
27%
20%
30%
15%
15%
LVEF at last follow-up
13%
34%
28%
35%
18%
no follow-up
NYHA class before CCM implantation
IIIB
III
III
III
III
III
NYHA class at last follow-up
IIIA
II
III
III
III
no follow-up
MLWHFQ before CCM implantation
88
82
49
50
62
88
MLWHFQ at last follow-up
46
16
17
48
50
no follow-up
CPX peak VO2 (ml/kg/min) before CCM implantation
9.7
16.3
7.3
15.5
10.0
8.9
11.1 (7.3)**
13.3*
14.0
15.7
12.6
no follow-up
CPX peak VO2 (ml/kg/min) at about one year follow-up
LVEF=Left ventricular ejection fraction; MLWHFQ=Minnesota living with heart failure questionnare; CPX=Cardiopulmonary exercise testing, peak VO2= peak oxygen uptake *limited by recent morbid obesity, **patient had 11.1 within the first year and 7.3 after three years
Legends to the Figures Figure 1: Chest x-rays A: S-ICD and trans-venous single-chamber pacemaker with left ventricular pacing electrode: reconstructed mitral valve, prosthetic tricuspid valve, two left ventricular electrodes B: S-ICD and abdominal pacemaker C: S-ICD and Optimizer IVs D: S-ICD and vagus nerve stimulator
RA=right atrial, RV=right ventricular, LV=left ventricular
Figure 2: Crosstalk test between S-ICD and Optimizer IVs in Patient 9: Primary vector and alternate vector not used due to “noise” during CCM activation Secondary vector filters the CCM signals, eliminating noise and double detection Secondary vector was programmed as permanent sensing configuration N= noise, S= sensing
Figure 3: S-ICD testing with activated CCM in Patient 9: After induction of ventricular fibrillation through a 50Hz impulse CCM stimulation is inhibited. The 65 Joule shock terminates ventricular fibrillation successfully. When patient returned to sinus rhythm CCM stimulation reengaged.
