Advancements in technology for patients with congenital heart disease: Implantable rhythm devices

    Advancements in technology for patients with congenital heart disease: Implantable Rhythm Devices Nicholas Von Bergen PII: DOI: Reference:

S1058-9813(16)00035-7 doi: 10.1016/j.ppedcard.2016.02.006 PPC 905

To appear in:

Progress in Pediatric cardiology

Please cite this article as: Von Bergen Nicholas, Advancements in technology for patients with congenital heart disease: Implantable Rhythm Devices, Progress in Pediatric cardiology (2016), doi: 10.1016/j.ppedcard.2016.02.006

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 proof before it is published in its final 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.

ACCEPTED MANUSCRIPT Advancements in technology for patients with congenital heart disease: Implantable Rhythm Devices.

RI

PT

Nicholas Von Bergen University of Wisconsin – Madison Associate Professor of Pediatrics Pediatric Cardiac Electrophysiology

SC

Background:

NU

The field of implantable rhythm devices has been evolving rapidly. This advancement has in part included leadless pacemakers, subcutaneous ICDs and smaller devices with more capabilities. This review will attempt to discuss a broad range of advancements in implantable rhythm devices as it relates to the care of patients with congenital heart disease.

AC CE P

TE

D

MA

Patients with congenital heart disease are at particular risk for rhythm abnormalities, often arising from structural concerns or prior cardiac surgery. This can include AV block as occasionally seen postoperatively, or spontaneous heart block due to conduction system disease as seen with L-Transposition of the Great Arteries. Prior incision lines within the atrium or the ventricle can predispose to reentry such as intra-atrial reentry tachycardia or ventricular tachycardia, and structural abnormalities can predispose to heart failure and dyssynchrony. With the continually increasing numbers of patients with congenital heart disease these concerns will only become more prevalent as the age of the congenital heart disease population continues to advance. Unfortunately, the devices themselves are associated with risks such as lead dislodgement or fracture, inadequate battery longevity and challenges associated with removal and/or replacement. Additionally, device algorithms, such as rate responsive pacing or arrhythmia detection remains imperfect. Lastly, there remain significant concerns regarding the emotional and social wellbeing of patient with implantable rhythm devices. Fortunately, with advancements in technology as it relates to the delivery and sharing of information we have started to more properly address the psychosocial concerns associated with implantable rhythm devices. We will separate this review to discuss advancements in technology as it relates to improvements in the device itself, as it addresses challenges specific to patients heart disease, and how we can utilize technology to support the emotional and social needs of these patients. We will also discuss some of the directions that these devices may take in the future. Advancements in implantable rhythm devices to overcome device related concerns. Devices themselves have intrinsic limitations and faults which may result in additional procedures, device malfunction and even cosmetic concerns. Recent advances have made rapid progress in an attempt to overcome issues caused by the device itself, addressing concerns such as the risk of lead failure, battery longevity/device size limitations, non-physiologic algorithms and MRI interference.

ACCEPTED MANUSCRIPT Lead advancements:

NU

SC

RI

PT

An editorial a few years ago proclaimed the ICD lead as the weakest link in the ICD system.(Maisel 2007) This is highlighted by a few of the more dramatic examples of lead failure as was seen with the Medtronic Sprint-Fidelis and the St. Jude Riata. However, even in the most robust leads, there remain significant concerns about failure due to fracture, insulation break, the need for lead removal or collateral damage due to complications such as vascular obstruction due to the presence of a lead in the vascular space. The risk of lead related complications remains high as evidence by Borleffs et al which showed that ~25% of RV ICD leads had been removed or capped within 10 years.(Borleffs, van Erven et al. 2009) A recent study evaluating (not yet published) pacemaker leads in the pediatric and congenital heart population showed that lead revision (removal, replacement, or addition) occurred at a median of ~7 years after the initial device implant.(Vaverka, Turek et al. 2015) These lead complications are only complicated by the risk with lead removal, including a 1-2% risk for cardiac perforation.

MA

Given these concerns, advancements in pacemaker and ICD leads have been an important focus for both device companies and implanting physicians. Lead improvements have resulted from changing practices by the implanting physicians, advancements in the lead design, and more recently, utilizing devices that avoid leads altogether.

D

Smaller leads:

AC CE P

TE

Due to the risk of vascular injury or vascular obstruction, as seen with thoracic outlet syndrome, many pediatric electrophysiologists have been choosing smaller leads, especially for the smaller patients. The smallest lead is currently the Medtronic 3830, is a 4.1 Fr lead, and has been shown to have excellent durability with (to date) relatively straightforward lead removal, most commonly with traction only. However, miniaturizing the ICD lead has been met with less success. It was in part the desire for smaller ICD leads that led to the development of the Sprint-Fidelis ICD lead, a lead which was eventually recalled due to its high failure rate.(Khan, Zelin et al. 2010, Garnreiter, Whitaker et al. 2015) Single coil ICD leads:

As lead removal is one of the greatest risks to the patient due to the risk of cardiac perforation, implanting physicians have been moving towards leads that have fewer components, and less scar ingrowth. This has prompted a transition towards single (as opposed to dual) coil ICD leads, due to the increased challenges with the SVC coil removal. Is a(Cooper, Stephenson et al. 2003) . This is reinforced by findings, such as in the SCD-HeFT, showing that there was no evidence of additional benefit of the SVC coil.(Aoukar, Poole et al. 2013) Subcutaneous ICD (with no transvenous leads) On way to avoid transvenous lead complications is to avoid the use of transvenous leads altogether. This is being done by the entirely subcutaneous ICD (Boston Scientific). This device is placed in the

ACCEPTED MANUSCRIPT

TE

2012)

D

MA

NU

SC

RI

PT

axillary area with a subcutaneous coil tunneled to near the sternum. (FIGURE 1)(Jarman, Lascelles et al.

AC CE P

This novel device may be appropriate in some patients, but does have its own advantages and disadvantages. Graph 1 title: Advantages and Disadvantages to the Subcutaneous ICD

Advantages No vascular access required Less risk with explantation May be used with an intracardiac shunt Decreased endocarditis risk

Disadvantages Unable to pace Large device Concerns for both over and under-sensing Requires pre-implant screening

As this device does not require transvenous access it can be especially useful in patients with limited or absent venous access, or a history of vascular obstruction; all relatively common concerns in patients with congenital heart disease. Additionally, the avoidance of the transvenous system allows less risk for device related complications secondary to intracardiac shunts or prior endocarditis. Nevertheless, there remain substantial disadvantages. First, as the device is unable to pace for bradycardia or to overdrive ventricular arrhythmias. This may limit its use in patients who require pacing for intrinsic concerns such as sinus node dysfunction, or for iatrogenic causes, such as antiarrhythmic induced bradycardia. The lack of a lead on or in the heart may also limit the ability to accurately discriminate the heart rhythm. To account for this patients are required to undergo preimplantation screening (Figure 1)

ACCEPTED MANUSCRIPT

PT

to confirm that there is adequate QRS voltage and appropriately discriminated T waves. In the initial studies just under 10% of patients failed pre-implant screening.(Olde Nordkamp, Warnaars et al. 2014). Additionally, this disadvantage has led to concerns about inappropriate ICD discharges due to T wave over-sensing, and delayed defibrillation due to QRS under-sensing.(Jarman, Lascelles et al. 2012) Leadless Pacemakers

AC CE P

TE

D

MA

NU

SC

RI

Another significant of technology for those who require single chamber pacing is the leadless pacemaker. There are currently two devices on limited release in the United States, the Nanostim (St. Jude) and the Micra (Medtronic). These devices are placed via the transvenous route via the femoral vein utilizing catheter guidance to affix to the right ventricular apex/low septum. The Nanostim utilizes an active fixation coil, while the Micra use passive fixation tines.(Sperzel, Burri et al. 2015)

Advantages and disadvantages to leadless pacing Advantages No lead No pocket required Relatively long battery life Easier device removal (than lead removal)

Disadvantages Single chamber only Large introducer required for placement May have less optimal pacing site Long term data is absent

The leadless device, though in its first iterations, currently has substantial advantages in the appropriate patient. In particular, there is no lead and no device pocket. This eliminates the risk for lead fracture or pocket related concerns, and limits the risk of vascular injury or obstruction to the time of implant and removal. The current data has suggested that the battery may last as long as 15 or more years, making the battery life a significant advantage.(Reddy, Knops et al. 2014, Knops, Tjong et al. 2015) Additionally, when it does need to be removed, the early data suggests that device removal may have less risk than that associated with lead removal.(Reddy, Knops et al. 2014) Current disadvantages include the absence of dual chamber pacing capabilities as it is currently right ventricular pacing only. It does require a large sheath for placement, and placement itself is more likely to be near the RV apex. This pacing site may be less advantageous then pacing in the low septum (or from the left).

ACCEPTED MANUSCRIPT Device size to battery longevity:

AC CE P

TE

D

MA

NU

SC

RI

PT

Significant advancement has been made in the last few years with the contradictory needs of a longer battery life and a smaller device. In the late 1950s when the first pacemakers were first being implanted, the external pacemaker battery lasted almost 6 weeks (the first device only lasted a few hours). (Picture 1)

Reprinted with permission Medtronic circa 1957. Advancements in battery technology such as the use of Lithium (as opposed to less active elements such as mercury), improvements in battery technology, customizable battery size, improved capacitors and advances in circuit technology has allowed devices to continue to become smaller without sacrificing device longevity. A nice example of this miniaturization is the Medtronic LinQ implantable loop

ACCEPTED MANUSCRIPT recorder. (FIGURE 2) The device continues to have an estimated longevity of 2-3 years, while being small enough to implant with an incision less than 1cm. MRI interference:

D

MA

NU

SC

RI

PT

MRI use is expanding in patients with congenital heart disease. However, there are concerns for MRI interaction with the device and the leads. In particular, the magnetic field may cause to the device to malfunction, or the magnetic field may induce a current within the lead, which may cause heat, and potentially alter the lead and or device function. Due to this concern, devices currently available for implantation are designed to predominately be MRI safe (MRI conditional) and new lead designs have allowed the leads to be less reactive to the MRI energy. However, as with much advancement, there may be unintended downsides. In particular, the somewhat stiffer MRI conditional pacemaker leads may be at an increased perforation risk.(Acha, Keaney et al. 2015) Fortunately, as we gain experience (and as centers perhaps unknowingly placed device patients through MRI scanners) we have found that MRIs can often be done safely in patients with implantable rhythm devices, MRI conditional or not, though there remains a risk for slight changes in longer term findings. This has prompted many institutions to adopt policy and procedures that will allow MRIs in appropriately screened and consented patients as long as appropriate monitoring is performed before, during and after the MRI.(Nazarian, Hansford et al. 2011, Ipek and Nazarian 2015)

TE

Advancements in implantable rhythm devices to treat congenital heart disease related concerns.

AC CE P

As discussed above, patients with congenital heart disease are at risk for multiple long term sequel as a result of their congenital heart disease itself, the prior surgery, or as they are living longer, old age. This has prompted advancements in implantable rhythm devices to improve algorithms for rate control for patients with sinus node dysfunction, to evaluate heart failure, and to treat arrhythmias. Rate responsive algorithms(Kaszala and Ellenbogen 2010) There has yet to be a sensor developed as sophisticated as a healthy sinus node. However, devices have been improving their ability to determine the patient’s appropriate heart rate with improvements in both the technology and mechanism by which they determine activity. The most common rate sensor senses activity by utilizing piezoelectric materials which produce a voltage when the material deforms. Therefore, the quantity of movement can be sensed based on the quantity of deformation of the piezoelectric material, driving the device to pace at the appropriate rate for the presumed level of activity. This type of sensor is considered a tertiary sensor as it detects changes external to the body as a result of movement/vibration. This does have the advantage of being simple and requiring little energy. However, this sensor can inappropriately sense activity (such as when driving on a bumpy road, or when burping a baby) and often has a non-proportional response to activity levels. More recently sensors have been trying to develop secondary sensors, which detect changes that vary as a consequence of activity such as impedance, contractility or respiratory rate. Though it may be a

ACCEPTED MANUSCRIPT goal for the future, there are currently no commercially developed primary sensors, which measure factors that control the sinus node such as autonomic activity or catecholamine level.

RI

PT

Sensing minute ventilation can done by measuring transthoracic impedance changes between the pacemaker lead and generator due to changes in the quantity of air in the lungs. This is thought to have a more proportional response to exercise, but may be slow to respond to early changes in activity, and may be limited in its ability to be accurate in children or in those with lung disease.

Advancements in heart failure monitoring

MA

NU

SC

There are a few contractility based sensors in devices today. The contractility based sensor may be impedance based, but on a smaller scale than the transthoracic based minute ventilation. Instead they measure local changes in impedance within the heart during systole and diastole as an estimate local contractility. This has the advantage of measuring physiologic changes associated with exercise, and even responds to mental stress. It however does require a ventricular lead, and may not work well if there is local myocardial injury near the ventricular lead. Another type of contractility based sensor (not in current devices) measures local acceleration as an estimate of contractility, which has similar advantages and disadvantages to the local impedance contractility based sensor.

TE

D

Heart failure, though not specifically a rhythm issue, can be evaluated and potentially treated with implantable rhythm devices.

AC CE P

When evaluating the pathophysiology of heart failure there is initially cardiac increased filling pressure before increasing fluid retention and eventual hospitalization. (FIGURE 2)

ACCEPTED MANUSCRIPT By evaluating the physiologic and autonomic adaptation within this pathway physicians may be able to more adequately treat heart failure and avoid symptoms or hospitalization.

RI

PT

Changes in intrathoracic impedance are currently being monitored by some of both Medtronic and Biotronik ICDs to track heart failure. These companies use slightly different algorithms to measure the impedance across the chest, though both use alterations in impedance as a surrogate for alterations of fluid within the lungs. Typically the impedance is measured from the RV coil to the ICD, and derivation from the baseline, implying more fluid in the chest, is used as an indication of worsening heart failure.

TE

D

MA

NU

SC

Other devices, such as CardioMEMs (St. Jude), though not a rhythm device, detect increases in cardiac (or pulmonary artery) filling pressure and utilize it as an early warning signs of heart failure. The CardioMEMs is implanted within the pulmonary artery and measures direct pulmonary artery pressure. Utilizing the CardioMEMs to prompt early medical management for heart failure as judged by increased PA filling pressure can substantially reduce hospital admissions for heart failure, at least in the noncongenital heart population.(Abraham, Adamson et al. 2011) The ability to predict heart failure in the congenital heart disease population has been studied utilizing the Medtronic Optival intrathoracic impedance algorithm, however currently is positive predictive value for heart failure exacerbation or uptitration of medications was low.(LaPage, von Alvensleben et al. 2013, Silva, NH et al. 2014) Given the prevalence of heart failure, multiple devices, both implanted or external (such as a wearable necklace) have been or are being developed in an attempt to detect early heart failure signs Cardiac resynchronization therapy

AC CE P

Cardiac resynchronization therapy (CRT), commonly referred to biventricular pacing, can also be utilized for the treatment of heart failure. In the United States there are near 90,000 CRT devices implanted yearly, and this number is expected to continue to grow over the next few years. The classic indications for cardiac resynchronization include poor heart function (of the LV), a wide QRS complex (typically a left bundle branch block), and heart failure in an otherwise structurally normal heart. CRT in a congenital heart population is much more varied due to wide variety of congenital heart disease. To address this concern, a 2014 expert consensus statement on arrhythmias and congenital heart disease provides an excellent summary about the use of CRT in adults with congenital heart disease.(Khairy, Van Hare et al. 2014) A figure from this article is shown here below (Figure 3) indicating class I, class IIa and class IIb indications for placement of CRT in patients with systemic left ventricles, systemic right ventricles and single ventricles.

AC CE P

TE

D

MA

NU

SC

RI

PT

ACCEPTED MANUSCRIPT

Unfortunately, though there are large studies evaluating CRT in adults, there is limited research evaluating CRT in pediatric and adults with congenital heart disease. Currently, there are only 3 relatively large (by pediatric standards) studies in this population.(Dubin, Janousek et al. 2005, Cecchin, Frangini et al. 2009, Janousek, Gebauer et al. 2009) These studies between 60 to just over 100 patients and encompassed a wide variety of types of the congenital heart disease. Because of this there is limited dated the help guide the use of CRT in this population, however a few points could be extracted from our experience thus far. In particular, CRT was used most commonly in patients with less heart

ACCEPTED MANUSCRIPT

PT

failure then the typical population of adult patients undergoing CRT. In the pediatric studies the most likely patient to respond to CRT were those with systemic left ventricles, and of those the greatest responders were those with RV pacing who were upgraded to BiV pacing. However, there continues to be a substantial nonresponse rate with up to 20% of patients having no significant improvement to CRT. Interestingly, nearly 40% of patients who underwent CRT therapy while on the transplant list were taken off the transplant list because of improvement in function.

RI

Advancements in the psychological care surrounding implantable rhythm devices:

SC

Emotional/Psychological care:

D

MA

NU

There are substantial emotional and psychological challenges associated with implantable rhythm devices. The prevalence of depression, anxiety, intimacy avoidance and posttraumatic stress is significant. This has been seen in multiple studies and is summarized nicely and figure 4 (reprinted with permission from Circulation). (Sears, Hauf et al. 2011) Complicating this issue is that many patients are inadequately educated about their device, with as many as 60% of patients not have a plan in place should they received an ICD shock.(Groarke, Beirne et al. 2012) This has prompted many centers to adopt an approach to the care of patients with ICDs which includes early psychological care, long term screening and more standardized education.

AC CE P

TE

These need have necessitated improvements to the care of patients both before and after implantable cardiac rhythm device placement. The University of Wisconsin – Madison pediatric cardiology group has adopted a web based approach to allow improved and more consistent access to patient education materials. These resources are available to all can be found on the uwhealthkids.org website. Additionally, multiple centers have their ICD recipients meet a psychologist before device implantation, and have follow-up on scheduled visits (or as needed based on patient and family needs) post implantation. Screening for signs of depression, post-traumatic stress and anxiety can be done at appointments, and should be reevaluated at routine intervals and after significant changes in status, such as after a ICD shock, or with other changes in health.

ACCEPTED MANUSCRIPT

AC CE P

TE

D

MA

NU

SC

RI

PT

Figure 4 – reprinted with permission from sears.

The Future: Implantable rhythm devices have been rapidly advancing in numerous areas. Some of the most dramatic examples are the increasing miniaturization and increasing connection to our smart phone technology while continuing to improve battery longevity. Additionally, non-device advancements may replace the need for implantable devices altogether. We will highlight a few the potential directions at this technology may advance. Nanotechnology

ACCEPTED MANUSCRIPT

PT

Nanotechnology is the development of sensors in the nanometer range. However, it is difficult to understand a scale of Nanotechnology. One nanometer is 1 billionth of a meter. This is at over 2500 times smaller than a typical red cell (which is ~ 2500 x 8000nm), and 1nm:1m is comparable in proportion between a marble and the entire earth

NU

SC

RI

Some of the technology that has been developed is in the nanometer range. An example is a nanosensor which can measure troponin, potentially alerting of the early signs of a heart attack.(Chua, Chee et al. 2009) With advancement and this technology we could potentially screen for thousands of biomarkers with minimal blood, and it may be able to be done continuously. This nanotechnology may also selectively affect individual cells (for example a group myocardial cell which expresses proteins associated with pathologic cells – such as may be seen with pathologic automaticity as seen with atrial fibrillation) which may aid in selective treatment, injury or repair.

AC CE P

TE

D

MA

Nano tech – picture – reprinted with permission by Chua et al.

Portability/Cell phone technology Device companies are becoming increasingly advanced at making information available on phone-based technology. More sophisticated phone Apps are currently being developed which may allow pacemakers to send in a remote transmission over the patient’s cell phone.

ACCEPTED MANUSCRIPT

SC

RI

PT

Some companies are developing non-implantable rhythm devices that can measure physiologic values in real-time, which is becoming smaller and more portable (such as Scanadu) or being integrated into wearable technology, which is starting to be seen in many mainstream clothing lines. In some cases, such as with Zephyr wearable technology, data can be gathered from up to 50 people at a time suggesting the possibility of population based monitoring. Interestingly, some companies such as Philips (vital signs camera) are developing web cam technology to allow continuous monitoring of vital signs including respiratory rate and heart rate through the web cam image. The further development of increasingly portable less invasive technology which can be used on many people at once opens up interesting implications for the future. Attempts to become more physiologic

TE

D

MA

NU

Advancements in tissue engineering and gene expression may eventually eliminate the need for implantable rhythm devices altogether. By altering gene expression researchers have shown that they can convert quiescent cardiomyocytes to pacemaker cells. Kapoor et al successfully converted ventricular myocardium to develop an action potential very similar to that of the sinus node myocytes. (Kapoor, Liang et al. 2013) Alternatively, tissue engineering may result in engineered AV nodes, which could be utilized in place of pacemakers in patients with heart block. By implanting an engineered AV node of myocardial cells placed on cell scaffolding across the AV groove Choi et al. demonstrated long term conduction (though no AV delay) through the implanted “AV node” of myocardial cells in rats with heart block. (Choi, Stamm et al. 2006)

AC CE P

Advancement in device longevity

Though advancements in technology have improved the battery longevity while decreasing the device size we may eventually transition to even longer lasting power sources. Some of the most interesting possibilities include the use of energy harvesters which rely on the movement of the heart to generate energy which can be used to run the device itself (somewhat like a self-winding clock). This (unlike the watch) is generally based on the use of piezoelectric material, which when placed on the heart, has been shown to provide more energy than required to pace the subsequent heartbeat. This could allow devices to be placed on the heart and be powered continuously without the need for battery replacement.(Karami, Bradley et al. 2012) Summary: There have been considerable advancements in implantable rhythm device technology for use in patients with congenital heart disease over the last few years. Companies have been developing leadless devices, or altering the leads to decrease the risk of fracture, removal or vascular injury. Devices are smaller without sacrificing battery longevity, and devices often no longer limit a patient’s ability to obtain a MRI. Implantable rhythm devices are used for monitoring and improving treatment for heart failure, have developed improve rate responsiveness, and may be used to improve heart function. Given the substantial emotional burden associated with implantable rhythm devices providers have become more sophisticated in the psychological care for patients utilizing implantable rhythm devices, often with the use of technology to assist with the delivery of this care and education.

ACCEPTED MANUSCRIPT Given the significant advancements in the past few years, and the speed of expected advancements in the future, we look forward with anticipation to further advancements in implantable rhythm devices.

SC

RI

PT

Bibliography:

NU

Abraham, W. T., et al. (2011). "Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial." Lancet 377(9766): 658-666.

AC CE P

TE

D

MA

BACKGROUND: Results of previous studies support the hypothesis that implantable haemodynamic monitoring systems might reduce rates of hospitalisation in patients with heart failure. We undertook a single-blind trial to assess this approach. METHODS: Patients with New York Heart Association (NYHA) class III heart failure, irrespective of the left ventricular ejection fraction, and a previous hospital admission for heart failure were enrolled in 64 centres in the USA. They were randomly assigned by use of a centralised electronic system to management with a wireless implantable haemodynamic monitoring (W-IHM) system (treatment group) or to a control group for at least 6 months. Only patients were masked to their assignment group. In the treatment group, clinicians used daily measurement of pulmonary artery pressures in addition to standard of care versus standard of care alone in the control group. The primary efficacy endpoint was the rate of heart-failure-related hospitalisations at 6 months. The safety endpoints assessed at 6 months were freedom from device-related or system-related complications (DSRC) and freedom from pressure-sensor failures. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. FINDINGS: In 6 months, 83 heart-failure-related hospitalisations were reported in the treatment group (n=270) compared with 120 in the control group (n=280; rate 0.31 vs 0.44, hazard ratio [HR] 0.70, 95% CI 0.60-0.84, p<0.0001). During the entire follow-up (mean 15 months [SD 7]), the treatment group had a 39% reduction in heart-failure-related hospitalisation compared with the control group (153 vs 253, HR 0.64, 95% CI 0.55-0.75; p<0.0001). Eight patients had DSRC and overall freedom from DSRC was 98.6% (97.3-99.4) compared with a prespecified performance criterion of 80% (p<0.0001); and overall freedom from pressure-sensor failures was 100% (99.3-100.0). INTERPRETATION: Our results are consistent with, and extend, previous findings by definitively showing a significant and large reduction in hospitalisation for patients with NYHA class III heart failure who were managed with a wireless implantable haemodynamic monitoring system. The addition of information about pulmonary artery pressure to clinical signs and symptoms allows for improved heart failure management. FUNDING: CardioMEMS. Acha, M. R., et al. (2015). "Increased perforation risk with an MRI-conditional pacing lead: a singlecenter study." Pacing Clin Electrophysiol 38(3): 334-342. BACKGROUND: Magnetic resonance imaging (MRI) has been considered contraindicated in patients with cardiac pacemakers (PPMs). Recently, Medtronic (MDT) MRI SureScan PPM

ACCEPTED MANUSCRIPT

MA

NU

SC

RI

PT

(Medtronic Inc., Minneapolis, MN, USA) and leads were introduced into clinical practice in the United States of America. OBJECTIVE: To compare MDT CapSureFix 5086 MRI SureScan leadassociated perforation and dislodgement rates with MDT non-MRI SureScan active fixation leads. METHODS: We retrospectively analyzed the records of all patients implanted with MDT CapSureFix 5086 MRI SureScan leads as well as all patients implanted with MDT 4076 and 5076 leads at our institution from April 2011 to April 2014. RESULTS: Four of 72 patients implanted with MDT CapSureFix 5086 MRI SureScan leads (5.5%) had evidence of lead perforation, necessitating pericardiocentesis in three cases and lead revision in one case. Three of the four perforations were delayed perforations, presenting more than 3 weeks postimplant. Two patients implanted with MDT CapSureFix 5086 MRI SureScan leads (2.8%) had lead dislodgement. Of 420 patients implanted with MDT non-MRI SureScan leads, there were two perforations (0.47%) and four dislodgements (0.9%). There were significantly increased lead perforations associated with MDT CapSureFix 5086 MRI SureScan leads (P = 0.005) and a nonsignificant trend toward increased dislodgements (P = 0.18) when compared with MDT nonMRI SureScan leads. CONCLUSION: In contradiction to prior studies, this retrospective study suggests an increased perforation rate with MDT CapSureFix 5086 MRI SureScan leads. Most perforations were delayed perforations, presenting more than 3 weeks postimplant. Higher volume prospective studies with longer follow-up are needed to confirm our findings.

TE

D

Adamson, P. B. (2009). "Pathophysiology of the transition from chronic compensated and acute decompensated heart failure: new insights from continuous monitoring devices." Curr Heart Fail Rep 6(4): 287-292.

AC CE P

Studies of cardiovascular signals continuously sensed by implantable devices provide unique insight into detailed pathophysiology as patients progress from stable to congested states. These data suggest that volume expansion, autonomic adaptation, and pulmonary interstitial edema begin several weeks before patients develop symptoms or demonstrate changes in daily weight. Monitoring physiologic signals from implanted devices may provide earlier warning of impending decompensation, thereby allowing changes in medical therapy to prevent worsening heart failure. Aoukar, P. S., et al. (2013). "No benefit of a dual coil over a single coil ICD lead: evidence from the Sudden Cardiac Death in Heart Failure Trial." Heart Rhythm 10(7): 970-976. BACKGROUND: Dual coil implantable cardioverter-defibrillator (ICD) leads with a superior vena cava (SVC) electrode have been considered standard of care despite sparse data suggesting improved ICD defibrillation efficacy. SVC coils increase lead complexity, cost, risk of lead failure, and lead removal. OBJECTIVE: To compare all-cause mortality, sudden cardiac death, implant defibrillation threshold (DFT) test energies, appropriate shock rates, and first shock efficacy for ventricular tachyarrhythmias for dual coil vs single coil leads in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). METHODS: In SCD-HeFT, 811 patients with heart failure received a single lead transvenous ICD (Medtronic model 7223) and underwent protocol-driven DFT testing. The selection of a dual vs single coil right ventricular (RV) lead was at the physician's discretion. DFT data were available in 717 patients. RESULTS: Dual coil leads were used in 563 and single coil in 246 patients. After 45.5-month follow-up, overall mortality was similar (19.4% for dual coil vs 21.5% for single coil; adjusted hazard ratio 0.95; 95% confidence interval 0.681.34; P = .78). Sudden cardiac death was also similar (3.6% for dual coil vs 3.7% for single coil; P

ACCEPTED MANUSCRIPT

PT

= .96). First shock efficacy was 82.2% vs 91.9% (dual coil vs single coil; unadjusted odds ratio 0.41; 95% confidence interval 0.15-1.13; P = .085). Mean DFT was 12.1 +/- 4.7 J vs 12.8 +/- 4.8 J (dual coil vs single coil; P = .087). CONCLUSIONS: In the SCD-HeFT, the addition of an SVC coil for left-sided implants was not associated with improved outcome measures. We advocate returning to single coil RV ICD leads as the standard of care to decrease chronic lead complications.

SC

RI

Borleffs, C. J., et al. (2009). "Risk of failure of transvenous implantable cardioverter-defibrillator leads." Circ Arrhythm Electrophysiol 2(4): 411-416.

AC CE P

TE

D

MA

NU

BACKGROUND: Despite the positive effect on mortality in selected patients, implantable cardioverter-defibrillator therapy is also associated with potential malfunction of the implanted system. The present study provides the long-term lead failure rate in a large single-center cohort. METHODS AND RESULTS: Since 1992, a total of 2068 implantable cardioverterdefibrillator patients with 2161 defibrillation leads were prospectively collected. Data of the implant procedure and all follow-up visits were recorded. All cases of lead removal or capping or placing of an additional pace or sense lead were noted and analyzed. Lead models were grouped by manufacturer and approximate lead diameter in French. During a mean follow-up of 36 months, 82 (3.8%) cases of lead failure were identified. Cumulative incidence of lead failure at 1 year was 0.6%; at 5 years, 6.5%; and at 10 years, 16.4%. The highest risk of lead failure was found in small-diameter leads. Adjusted hazard ratio was 6.4 (95% CI, 3.2 to 12.8) for Medtronic 7F leads, when compared with all other leads. CONCLUSIONS: In this large single-center experience, the overall incidence of lead failure was 1.3 (95% CI, 1.0 to 1.6) per 100 lead-years. Comparison of different groups of leads shows major differences in event rates. Specific manufacturer's small-diameter defibrillation leads may have a higher risk of early lead failure. Cecchin, F., et al. (2009). "Cardiac Resynchronization Therapy (and Multisite Pacing) in Pediatrics and Congenital Heart Disease: Five Years Experience in a Single Institution." Journal of cardiovascular electrophysiology 20(1): 58-65. Introduction: Clinical evidence supports the use of cardiac resynchronization therapy (CRT) in adults with heart failure, but experience in pediatrics and congenital heart disease (CHD) is limited in terms of patient numbers and follow-up. We sought to determine the functional assessment and clinical outcomes in pediatric and CHD CRT patients followed uniformly at one institution. Methods: Retrospective review of 60 consecutive patients who underwent CRT between 2002 and 2007. Results: At implantation, median age was 15.0 years (5 months to 47 years). Overall, 46 patients had CHD (77%) and 14 had dilated cardiomyopathy. Prior to CRT, 92% were on heart failure treatment drugs and 55% had pacemakers. Median follow-up time was 0.7 years (1 day-5.3 years). Median QRS width decreased from 149 to 120 ms (P < 0.001). Median ejection fraction (EF) increased from 36% to 42% (P < 0.001) and improvement was particularly evident in the group with CHD. Of note, 8 of 13 patients with single ventricle morphology had a "strong CRT response," defined as either an improvement of 2-3 ordinal points in NYHA classification and/or increased ventricular function by >= 10 EF units. Overall, an improvement in functional status was observed in 39 of 45 patients (87%) with sufficient follow-up data.

ACCEPTED MANUSCRIPT

PT

Conclusions: Children and CHD patients treated with CRT have acute improvement in ventricular function, but implantation may require individualized planning and unconventional approaches. Future important goals include preimplant determination of CRT responders in pediatric and CHD patients, optimizing lead placement and programing, as well as long-term CRT device management issues.

RI

(J Cardiovasc Electrophysiol, Vol. 20, pp. 58-65, January 2009).

SC

Choi, Y. H., et al. (2006). "Cardiac conduction through engineered tissue." American Journal of Pathology 169(1): 72-85.

AC CE P

TE

D

MA

NU

In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal musclederived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal's natural life. Perfusion of hearts with fluorescently labeled lectin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding recipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy. Chua, J. H., et al. (2009). "Label-Free Electrical Detection of Cardiac Biomarker with Complementary Metal-Oxide Semiconductor-Compatible Silicon Nanowire Sensor Arrays." Analytical Chemistry 81(15): 6266-6271. Arrays of highly ordered silicon nanowire (SiNW) clusters are fabricated using complementary metal-oxide semiconductor (CMOS) field effect transistor-compatible technology, and the ultrasensitive, label-free, electrical detection of cardiac biomarker in real time using the array sensor is presented. The successful detection of human cardiac troponin-T (cTnT) has been demonstrated in an assay buffer solution of concentration down to 1 fg/mL, as well as in an undiluted human serum environment of concentration as low as 30 fg/mL. The high specificity, selectivity, and swift response time of the SiNWs to the presence of ultralow concentrations of a target protein in a biological analyte solution, even in the presence of a high total protein concentration, paves the way for the development of a medical diagnostic system for point-ofcare application that is able to provide an early and accurate indication of cardiac cellular necrosis.

ACCEPTED MANUSCRIPT Cooper, J. M., et al. (2003). "Implantable cardioverter defibrillator lead complications and laser extraction in children and young adults with congenital heart disease: implications for implantation and management." J Cardiovasc Electrophysiol 14(4): 344-349.

TE

D

MA

NU

SC

RI

PT

INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are being implanted for primary and secondary prevention of sudden death in children and young adults with congenital heart disease. Over time, ICD leads adhere to venous endothelium and endocardium. Lead removal, when necessary, often requires disruption of this fibrous tissue. METHODS AND RESULTS: We retrospectively reviewed and analyzed our experience with ICD lead extraction in children and young adults with congenital heart disease. From April 1999 through January 2002, 14 patients underwent 15 lead extraction procedures to remove 21 leads (17 ICD leads and 4 pacing or sensing leads). Seven patients had surgically corrected structural heart disease (5 transposition of the great arteries with atrial switch repair and 2 corrected tetralogy of Fallot). Mean patient age at extraction was 17.9 +/- 5.7 years (range 9-32), and mean duration of lead implantation was 42.0 +/- 18.9 months (range 15-75). Fourteen of 15 procedures were performed for lead fracture or failure. A laser sheath was used for 20 of 21 lead extractions. Twenty of 21 leads (95%) were completely extracted. There were three instances of blood loss requiring transfusion. There were no major complications or deaths. CONCLUSION: Young congenital heart disease patients with an ICD are at risk for growth-related lead distortion. The use of a laser sheath is safe and effective for ICD lead extraction in congenital heart disease patients, despite coil adherence and altered anatomy. It may be advisable to avoid dual-coil leads in patients with the potential for future growth.

AC CE P

Dubin, A. M., et al. (2005). "Resynchronization therapy in pediatric and congenital heart disease patients - An international multicenter study." Journal of the American College of Cardiology 46(12): 2277-2283. OBJECTIVES Our objective was to evaluate the short-term safety and efficacy of cardiac resynchronization therapy (CRT) in children. BACKGROUND Cardiac resynchronization therapy has been beneficial for adult patients with poor left ventricular function and intraventricular conduction delay. The efficacy of this therapy in the young and in those with congenital heart disease (CHD) has not yet been established. METHODS This is a multi-center, retrospective evaluation of CRT in 103 patients from 22 institutions. RESULTS Median age at time of implantation was 12.8 years (3 months to 55.4 years). Median duration of follow-up was four months (22 days to 1 year). The diagnosis was CHD in 73 patients (71%), cardiomyopathy in 16 (16%), and congenital complete atrioventricular block in 14 (13%). The QRS duration before pacing was 166.1 +/- 33.3 ms, which decreased after CRT by 37.7 +/- 30.7 ms (p < 0.01). Pre-CRT systemic ventricular ejection fraction (EF) was 26.2 +/- 11.6%. The EF increased by 12.8 +/- 12.7 EF units with a mean EF after CRT of 39.9 +/- 14.8% (p < 0.05). Of 18 patients who underwent CRT while listed for heart transplantation, 3 improved sufficiently to allow removal from the transplant waiting list, 5 underwent transplant, 2 died, and 8 others are currently awaiting transplant. CONCLUSIONS Cardiac resynchronization therapy appears to offer benefit in pediatric and CHD patients who differ substantially from the adult populations in whom this therapy has been most thoroughly evaluated to date. Further studies looking at the long-term benefit of this therapy in this population are needed.

ACCEPTED MANUSCRIPT

Garnreiter, J., et al. (2015). "Lumenless pacing leads: performance and extraction in pediatrics and congenital heart disease." Pacing Clin Electrophysiol 38(1): 42-47.

TE

D

MA

NU

SC

RI

PT

BACKGROUND: Pediatric and congenital heart disease (CHD) patients requiring permanent pacing present unique challenges, including need for long duration of implant, small size, and structural abnormalities. We report 6 years of experience with a novel 4.1-Fr lumenless pacing lead (model 3830, Medtronic Inc., Minneapolis, MN, USA) in this population. METHODS: Retrospective review of M3830 leads implanted at a pediatric center from 2005 to 2011. Data were compared to a population with a conventional pacing lead (model 1488, St. Jude Medical Inc., St. Paul, MN, USA). RESULTS: A total of 193 patients with 198 model 3830 leads (125 atrial, 73 ventricular) were enrolled. CHD was present in 121 (63%). Age and weight at implant were 16.6 +/- 8.5 years and 51.7 +/- 23.5 kg, respectively. Length of follow-up was 26 +/- 19 months (range 0-73). At implant, mean sensing and capture thresholds were good and remained stable over time. There were no significant differences in electrical performance compared to 101 leads in the comparison group. Implant complications were rare. Follow-up complications occurred in 4% of the M3830 leads and 16% of M1488 leads. Eleven M3830 leads required extraction. All were extracted without complications using only manual traction. There were three deaths in each group. One death in the M1488 group occurred during lead extraction. No other deaths were lead related. CONCLUSION: During up to 6 years of use in pediatric and CHD patients, the M3830 lead has demonstrated excellent efficacy, a low rate of complications, and straightforward extractability relative to traditional pacing leads.

AC CE P

Groarke, J., et al. (2012). "Deficiencies in Patients' Comprehension of Implantable Cardioverter Defibrillator Therapy." Pace-Pacing and Clinical Electrophysiology 35(9): 1097-1102. Background: Patients receive education before implantable cardioverter defibrillator (ICD) implantation. Patients understanding of ICD therapy requires investigation. Methods: A retrospective cohort study was carried out at two implant centers where patients are educated during a consenting process pre-ICD implantation. Questionnaires examining understanding of ICD therapy were completed during telephone interviews of patients with ICDs. Results: Of 75 patients interviewed, 62 (83%) were male. The median age at time of ICD implantation was 64 years (standard deviation [SD] = 9.4; range: 2982 years). The median interval from implantation to interview was 3 years (SD = 1.9; range: 0.19.0 years). Despite 83% (62 of 75) claiming to understand the reason for ICD implantation, no patient suggested arrhythmia termination when describing the indication. Of shock recipients, 60% (12 of 20) felt poorly prepared for shock therapy. Of patients who experienced a device-related complication, 83% (10 of 12) reported feeling inadequately forewarned of complications. Excluding patients with cardiac resynchronization therapy defibrillators (n = 6), 65% (45 of 69), 52% (36 of 69), 50% (35 of 69), and 61% (42 of 69) believe their ICD reduces risk of heart attack and improves breathing, exercise capacity, and heart function, respectively. Ninety-three percent (70 of 75) are satisfied with their decision to accept ICD therapy. Only 12% (9 of 75) believe they will want to inactivate therapies in setting of terminal illness. Conclusions: Despite preimplantation education, patient comprehension of the risks and benefits of ICD therapy is poor. Patients expectations of ICD therapy may be inappropriate. Education strategies before and after implantation require improvement. (PACE 2012; 35:10971102)

ACCEPTED MANUSCRIPT Ipek, E. G. and S. Nazarian (2015). "Safety of implanted cardiac devices in an MRI environment." Curr Cardiol Rep 17(7): 605.

SC

RI

PT

Magnetic resonance imaging (MRI) has evolved into an essential diagnostic modality for the evaluation of various conditions. In line with the increase in MRI applications, the use of cardiac implantable electronic devices (CIED) is growing and many of the CEID recipients of today may require MRI examinations in the future. Traditionally, MRI examination of CIED recipients has been considered a contraindication. However, recent studies have provided strong evidence that MRI can safely be performed in selected patients with specific precautions. This review highlights the interactions of MRI with CIEDs, summarizes the literature, and outlines the Johns Hopkins Safety Protocol.

NU

Janousek, J., et al. (2009). "Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates." Heart 95(14): 1165-1171.

MA

Background: Cardiac resynchronisation therapy (CRT) is increasingly used in children in a variety of anatomical and pathophysiological conditions, but published data are scarce. Objective: To record current practice and results of CRT in paediatric and congenital heart disease.

D

Design: Retrospective multicentre European survey.

TE

Setting: Paediatric cardiology and cardiac surgery centres.

AC CE P

Patients: One hundred and nine patients aged 0.24-73.8 (median 16.9) years with structural congenital heart disease (n=87), congenital atrioventricular block (n=12) and dilated cardiomyopathy (n=10) with systemic left (n=69), right (n=36) or single (n=4) ventricular dysfunction and ventricular dyssynchrony during sinus rhythm (n=25) or associated with pacing (n=84). Interventions: CRT for a median period of 7.5 months (concurrent cardiac surgery in 16/109). Main outcome measures: Functional improvement and echocardiographic change in systemic ventricular function. Results: The z score of the systemic ventricular end-diastolic dimension decreased by median 1.1 (p < 0.001). Ejection fraction (EF) or fractional area of change increased by a mean (SD) of 11.5 (14.3)% (p < 0.001) and New York Heart Association (NYHA) class improved by median 1.0 grade (p < 0.001). Non-response to CRT (18.5%) was multivariably predicted by the presence of primary dilated cardiomyopathy (p=0.002) and poor NYHA class (p=0.003). Presence of a systemic left ventricle was the strongest multivariable predictor of improvement in EF/fractional area of change (p < 0.001). Results were independent of the number of patients treated in each contributing centre. Conclusion: Heart failure associated with ventricular pacing is the largest indication for CRT in paediatric and congenital heart disease. CRT efficacy varies widely with the underlying anatomical and pathophysiological substrate. Jarman, J. W., et al. (2012). "Clinical experience of entirely subcutaneous implantable cardioverterdefibrillators in children and adults: cause for caution." Eur Heart J 33(11): 1351-1359.

ACCEPTED MANUSCRIPT

MA

NU

SC

RI

PT

AIMS: This paper describes our clinical experience of using an entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) in children and adults. Maintaining lead integrity and long-term vascular access are critical challenges of ICD therapy, especially in younger patients. The S-ICD has considerable theoretical advantages in selected patients without pacing indications, particularly children and young adults. Although sensing in an S-ICD may be influenced by age, pathology, and posture, there are currently few published data on clinical sensing performance outside the setting of intra-operative testing or in younger patients. METHODS AND RESULTS: Patients were selected by a multi-disciplinary team on clinical grounds for S-ICD implantation from a broad population at risk of sudden arrhythmic death. Sixteen patients underwent implantation [median age 20 years (range 10-48 years)]. Twelve had primary electrical disease and four had congenital structural heart disease. There were no operative complications, and ventricular fibrillation (VF) induction testing was successful in all cases. During median follow-up of 9 months (range 3-15 months), three children required re-operation. Eighteen clinical shocks were delivered in six patients. Ten shocks in four patients were inappropriate due to T-wave over-sensing. Within the eight shocks for ventricular arrhythmia, three were delivered for VF, among which two had delays in detection with time to therapy of 24 and 27 s. CONCLUSION: The S-ICD is an important new option for some patients. However, these data give cause for caution in light of the limited published data regarding clinical sensing capabilities, particularly among younger patients.

TE

D

Kapoor, N., et al. (2013). "Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18." Nature Biotechnology 31(1): 54-+.

AC CE P

The heartbeat originates within the sinoatrial node (SAN), a small structure containing <10,000 genuine pacemaker cells. If the SAN fails, the similar to 5 billion working cardiomyocytes downstream of it become quiescent, leading to circulatory collapse in the absence of electronic pacemaker therapy. Here we demonstrate conversion of rodent cardiomyocytes to SAN cells in vitro and in vivo by expression of Tbx18, a gene critical for early SAN specification. Within days of in vivo Tbx18 transduction, 9.2% of transduced, ventricular cardiomyocytes develop spontaneous electrical firing physiologically indistinguishable from that of SAN cells, along with morphological and epigenetic features characteristic of SAN cells. In vivo, focal Tbx18 gene transfer in the guinea-pig ventricle yields ectopic pacemaker activity, correcting a bradycardic disease phenotype. Myocytes transduced in vivo acquire the cardinal tapering morphology and physiological automaticity of native SAN pacemaker cells. The creation of induced SAN pacemaker (iSAN) cells opens new prospects for bioengineered pacemakers. Karami, M. A., et al. (2012). "Vibration Powered Cardiac Rhythm Devices." Circulation 126: A15551. Kaszala, K. and K. A. Ellenbogen (2010). "Device Sensing Sensors and Algorithms for Pacemakers and Implantable Cardioverter Defibrillators." Circulation 122(13): 1328-1340. Khairy, P., et al. (2014). "PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart

ACCEPTED MANUSCRIPT Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD)." Heart Rhythm 11(10): e102-165.

RI

PT

Khan, A., et al. (2010). "Performance of the lumenless 4.1-Fr diameter pacing lead implanted at alternative pacing sites in congenital heart: a chronic 5-year comparison." Pacing Clin Electrophysiol 33(12): 1467-1474.

AC CE P

TE

D

MA

NU

SC

PURPOSE: United States approval of the Model 3830, 4.1-French (Fr) diameter, lumenless, pacing lead (Medtronic Inc., Minneapolis, MN, USA) in patients under 17 years of age, and those with congenital heart disease (CHD), was in 2005. To date, long-term performance at alternative pacing sites (APS) is limited and chronic efficacy comparisons with more established leads is lacking. The purpose of this study was to evaluate these factors. METHODS: Implant and followup data on leads were compared: group 1 (non-3830 leads) and group 2 (Model 3830 leads). These included acute and chronic sensing and pacing, impedances, implant sites, and complications. Groups were compared using Fischer's exact test, paired, and nonpaired t-tests, with significance defined at P < 0.05. RESULTS: A total of 119 patients (ages 5-48 years) received 171 leads: group 1 (n = 80) and group 2 (n = 91). At implant, there were no differences in patient age, CHD, sensing, or pacing thresholds between groups. Implant lead impedances differed between groups but all were within normal values for each lead design. Chronic data showed no difference in sensing, pacing thresholds, or impedances. There were five (6%) early lead dislodgements in group 1 and one (1%) in group 2. APS were achieved in group 2 with mean 1.6 +/- 1.3 minutes fluoroscopy time. CONCLUSION: The new 4.1-Fr lumenless lead shows similar performance indices to established leads even at APS, yet is thinner and achieves APS with technical ease, permitting more efficient chronic pacing in children and all patients with CHD. Knops, R. E., et al. (2015). "Chronic performance of a leadless cardiac pacemaker: 1-year follow-up of the LEADLESS trial." J Am Coll Cardiol 65(15): 1497-1504. BACKGROUND: A leadless cardiac pacemaker (LCP) system was recently introduced to overcome lead-related complications of conventional pacing systems. To date, long-term results of an LCP system are unknown. OBJECTIVES: The aim of this study was to assess the complication incidence, electrical performance, and rate response characteristics within the first year of follow-up of patients implanted with an LCP. METHODS: We retrospectively assessed intermediate-term follow-up data for 31 of 33 patients from the LEADLESS trial cohort who had an indication for single-chamber pacing and received an LCP between December 2012 and April 2013. RESULTS: The mean age of the cohort was 76 +/- 8 years, and 65% were male. Between 3 and 12 months of follow-up, there were no pacemaker-related adverse events reported. The pacing performance results at 6- and 12-month follow-up were, respectively, as follows: mean pacing threshold (at a 0.4-ms pulse width), 0.40 +/- 0.26 V and 0.43 +/- 0.30 V; R-wave amplitude 10.6 +/- 2.6 mV and 10.3 +/- 2.2 mV; and impedance 625 +/- 205 Omega and 627 +/209 Omega. At the 12-month follow-up in 61% of the patients (n = 19 of 31), the rate response sensor was activated, and an adequate rate response was observed in all patients. CONCLUSIONS: The LCP demonstrates very stable performance and reassuring safety results during intermediate-term follow-up. These results support the use of the LCP as a promising alternative to conventional pacemaker systems. Continued evaluation is warranted to further characterize this system. (Evaluation of a New Cardiac Pacemaker; NCT01700244).

ACCEPTED MANUSCRIPT

LaPage, M. J., et al. (2013). "Utility of intrathoracic impedance monitoring in pediatric and congenital heart disease." Pacing Clin Electrophysiol 36(8): 994-999.

TE

D

MA

NU

SC

RI

PT

BACKGROUND: The utility of cardiac device-based intrathoracic monitoring (OptiVol, Medtronic Inc., Minneapolis, MN, USA) for congestive heart failure (CHF) exacerbation has not been evaluated in pediatric or congenital heart disease patients. METHODS: This was a retrospective study of all patients at a single center with an endocardial OptiVol capable device. OptiVol index values were collected in 2-week bins from January 2007 to December 2010. The clinical outcomes were CHF exacerbation defined as hospitalization or medication change for CHF and device-treated ventricular arrhythmia based on remote or in-office device interrogation. Clinical and OptiVol data were collected by separate investigators blinded to the other parameter. OptiVol data were correlated to the clinical outcomes to determine sensitivity and predictability for multiple threshold values in the entire cohort and pediatric and congenital subgroups. RESULTS: Forty-seven patients were included. A total of 1,106 months of OptiVol data were collected. Median age of the cohort was 18 years (range 6-58 years). There were 23 pediatric, median age 13 years (range 6-16), at device implant, and 18 patients, median age 31 years (range 13-58), considered at risk for heart failure at implant. There were three heart failure exacerbations and 17 treated ventricular arrhythmias. The study population-specific positive predictive value (PPV) of OptiVol was low (sensitivity 33% and PPV
AC CE P

Maisel, W. H. (2007). "Transvenous implantable cardioverter-defibrillator leads: the weakest link." Circulation 115(19): 2461-2463. Nazarian, S., et al. (2011). "A prospective evaluation of a protocol for magnetic resonance imaging of patients with implanted cardiac devices." Ann Intern Med 155(7): 415-424. BACKGROUND: Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns. OBJECTIVE: To define the safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in patients with implanted cardiac devices. DESIGN: Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896) SETTING: One center in the United States (94% of examinations) and one in Israel. PATIENTS: 438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies. INTERVENTION: Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachyarrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist. MEASUREMENTS: Activation or inhibition of pacing, symptoms, and device variables. RESULTS: In 3 patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV [interquartile range {IQR}, -0.7 to 0 V]) and atrial and right and left ventricular lead impedances (median change, -2 Omega [IQR, -13 to 0 Omega], -4 Omega [IQR, -16 to 0 Omega], and -11 Omega [IQR, -40 to 0 Omega], respectively) were reduced

ACCEPTED MANUSCRIPT

NU

SC

RI

PT

immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, [IQR, -1.1 to 0.3 mV]), decreased RV lead impedance (median, -3 Omega, [IQR, -29 to 15 Omega]), increased RV capture threshold (median, 0 V, IQR, [0 to 0.2 Omega]), and decreased battery voltage (median, -0.01 V, IQR, -0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming. LIMITATIONS: Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed. CONCLUSION: With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential. Olde Nordkamp, L. R., et al. (2014). "Which patients are not suitable for a subcutaneous ICD: incidence and predictors of failed QRS-T-wave morphology screening." J Cardiovasc Electrophysiol 25(5): 494-499.

AC CE P

TE

D

MA

BACKGROUND: The subcutaneous cardioverter-defibrillator (S-ICD) relies on a pre-implantation QRS-T morphology screening (TMS) of the ECG to assure that it reliably detects the QRS complexes and T waves. The prevalence and clinical characteristics of the patients who fail this TMS is unknown. METHODS AND RESULTS: QRS-TMS was done in 230 consecutive ICD outpatients (75% male, age 57 +/- 15 years) without an indication for cardiac pacing, using an ECG simulating the 3 sensing vectors of the S-ICD (TMS-ECG). Patients were defined suitable when at least 1 sensing vector was considered appropriate in both supine and standing position. In total, 7.4% of patients, who were all male, were considered not suitable for a S-ICD according to the TMS-ECG. Independent predictors for TMS failure were hypertrophic cardiomyopathy (HCM; odds ratio [OR] 12.6), a heavy weight (OR 1.5), a prolonged QRS duration (OR 1.5) and a R:T ratio <3 in the lead with the largest T wave on a standard 12-lead surface ECG (OR 14.6). CONCLUSION: In patients without an indication for pacing, 7.4% would have been not suitable for a S-ICD according to the TMS. HCM, a heavy weight, a prolonged QRS duration and a R:T ratio <3 in the ECG lead with the largest T wave were independently associated with TMS failure. These data might alert physicians that selection of patients for a S-ICD should be considered with special caution in certain patient groups, because they may not satisfy ECG criteria for adequate sensing. Reddy, V. Y., et al. (2014). "Permanent leadless cardiac pacing: results of the LEADLESS trial." Circulation 129(14): 1466-1471. BACKGROUND: Conventional cardiac pacemakers are associated with several potential shortand long-term complications related to either the transvenous lead or subcutaneous pulse generator. We tested the safety and clinical performance of a novel, completely self-contained leadless cardiac pacemaker. METHODS AND RESULTS: The primary safety end point was freedom from complications at 90 days. Secondary performance end points included implant success rate, implant time, and measures of device performance (pacing/sensing thresholds and rate-responsive performance). The mean age of the patient cohort (n=33) was 77+/-8 years, and 67% of the patients were male (n=22/33). The most common indication for cardiac pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%). The implant success rate was 97% (n=32). Five patients (15%) required the use of >1 leadless cardiac pacemaker during

ACCEPTED MANUSCRIPT

SC

RI

PT

the procedure. One patient developed right ventricular perforation and cardiac tamponade during the implant procedure, and eventually died as the result of a stroke. The overall complication-free rate was 94% (31/33). After 3 months of follow-up, the measures of pacing performance (sensing, impedance, and pacing threshold) either improved or were stable within the accepted range. CONCLUSIONS: In a prospective nonrandomized study, a completely selfcontained, single-chamber leadless cardiac pacemaker has shown to be safe and feasible. The absence of a transvenous lead and subcutaneous pulse generator could represent a paradigm shift in cardiac pacing. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT01700244.

NU

Sears, S. F., et al. (2011). "Posttraumatic Stress and the Implantable Cardioverter-Defibrillator Patient What the Electrophysiologist Needs to Know." Circulation-Arrhythmia and Electrophysiology 4(2): 242250.

MA

Silva, J. N., et al. (2014). "Assessment of intrathoracic impedance algorithm in the pediatric and adult congenital population." Pacing Clin Electrophysiol 37(9): 1174-1180.

AC CE P

TE

D

BACKGROUND: Decreased intrathoracic impedance has been used in adults to predict heart failure (HF) exacerbations. A commercial algorithm, OptiVol(R) (Medtronic Inc., Minneapolis, MN, USA), identifies patients with decreased impedance. We sought to determine the specificity, sensitivity, and positive predictive value (PPV) of OptiVol for predicting HF exacerbation or increased arrhythmia burden in pediatric and adult congenital heart disease (CHD) patients. METHODS: A multicenter retrospective chart review was undertaken. Inclusion criteria were: (1) <19 years or CHD adults, (2) an implanted device with OptiVol capability, (3) implanted between April 9 and September 6, and (4) follow-up of >30 days postimplant. Clinical events were defined as clinical HF exacerbation/hospital admission, initiation/uptitration of medication, or increased arrhythmia burden. RESULTS: Seventy-two patients (19 +/- 9 years) were identified with the following indications: 20% dilated cardiomyopathy (DCM), 11% hypertrophic cardiomyopathy (HCM), 43% CHD, 15% channelopathy, and 11% other. Thirty-nine had 122 OptiVol crossings (median 2, range 1-11); 30% were linked to a cause. The remaining 33 had no crossing, though 17 had 89 clinical events. The clinical event rate was 19% greater in patients with crossings, though not statistically significant (P = 0.4). The algorithm had a 59% sensitivity, 52% specificity, and 62% PPV. Clinical HF exacerbation and arrhythmia burden did not significantly correlate with decreased impedance though uptitration or initiation of HF medication did correlate significantly (P = 0.03). CONCLUSION: The algorithm sensitivity for pediatric DCM, HCM, CHD, and adult CHD was equivalent to the general adult population. Further studies are warranted to assess whether inaccuracy in prediction is secondary to the algorithm or to differences in the clinical response of pediatric/CHD patients. Sperzel, J., et al. (2015). "State of the art of leadless pacing." Europace. Despite undisputable benefits, conventional pacemaker therapy is associated with specific complications related to the subcutaneous device and the transvenous leads. Recently, two miniaturized leadless pacemakers, Nanostim (St. Jude Medical) and Micra (Medtronic), which can be completely implanted inside the right ventricle using steerable delivery systems, entered clinical application. The WiCS-cardiac resynchronisation therapy (CRT) system (wireless cardiac

ACCEPTED MANUSCRIPT

PT

stimulation for CRT, EBR Systems) delivers leadless left ventricular endocardial stimulation for cardiac resynchronization. In addition to obvious cosmetic benefits, leadless pacing systems may have the potential to overcome some complications of conventional pacing. However, acute and long-term complications still remains to be determined, as well as the feasibility of device explantation years after device placement.

AC CE P

TE

D

MA

NU

SC

RI

Vaverka, J., et al. (2015). Long Term Evaluation of Pacemakers in Patients with Congenital Heart Disease and Congenital Arrhythmias