comparison of a novel single lead atrial sensing (a+)-icd...

Comparison of a novel single lead atrial sensing (A+)-ICD system with a

dual chamber ICD system in patients without antibradycardia pacing

indications: Results of a randomized study

Christian Sticherling, MD*, Markus Zabel, MD*, Sebastian Spencker, MD, Udo Meyerfeldt,

MD, Lars Eckardt, MD, Steffen Behrens, MD, Michael Niehaus, MD,

for the ADRIA investigators

University Hospital Basel, Switzerland, University Hospital Göttingen, Germany, Charité, Campus Benjamin Franklin, Berlin, Germany, Hospital Villingen-Schwenningen, Germany,

University Hospital Münster, Germany, Vivantes Hospital Berlin, Germany, University Hospital Hannover, Germany

* CS and MZ contributed equally to the study

ADRIA= Belos A+ versus DR Clinical Investigation of Arrhythmia Discrimination

Word count: 5’032

Subject code: [22] Ablation/ICD/surgery

Address for correspondence: Prof. Christian Sticherling, MD, FESC University Hospital Basel Division of Cardiology

Petersgraben 4 4031 Basel, Switzerland. E-mail: [email protected] Phone: 0041-61-265 5526 Fax: 0041-61-265 4598

by guest on May 29, 2018

http://circep.ahajournals.org/D

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Abstract

Background: Supraventricular tachyarrhythmias (SVT) are the main cause for inappropriate

therapy by implantable cardioverter-defibrillators (ICD). For better rhythm discrimination, an

atrial electrogram (AEGM) is helpful and usually obtained from an additional atrial lead, even

in the absence of sinus node or atrioventricular nodal disease. An A+- ICD system with

integrated atrial sensing rings mounted 15-18 cm from the tip of an ICD lead may obviate the

need to implant a separate atrial lead. The aim of the study was to compare the novel A+- ICD

and a conventional dual chamber DR-ICD.

Methods and Results: Two-hundred forty nine patients with standard ICD indications but no

requirement for antibradycardia pacing were randomized to receive an A+-ICD (n=124) or

DR-ICD (n=125). Implantation details, need for ICD system revision, long-term sensing,

documented arrhythmia episodes and the respective rhythm discrimination during follow-up

were analyzed.

The implantation time was significantly shorter in the A+ ICD group (67±30 vs. 79±30 min,

P=0.003). Mean P-wave amplitudes were 3.5±0.8 mV (A+) and 3.2±0.6 mV (DR) and

remained stable over the follow-up period of 12 months. Surgical revision was necessary in

13 patients in the DR and 10 in the A+ group. All 593 ventricular tachyarrhythmia (VT)

episodes were correctly discriminated. Sensitivity and specificity of SVT discrimination were

not different between the study groups.

Conclusion: The novel A+- ICD system can be implanted faster and is equivalent to a

standard DR-ICD with regard to the detection of VT and SVT. It represents a useful

alternative to obtain atrial sensing.

Clinical Trial Registration Information: ClinicalTrials.gov number,NCT00324662

Key words: sudden cardiac death, implantable defibrillator, tachyarrhythmias



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Introduction

Therapy with an implantable cardioverter-defibrillators (ICD) is established for secondary and

primary prevention of sudden cardiac death 1-5. Most patients receive their ICD for primary

prevention and only a minority requires antibradycardia pacing. In patients who do not need

cardiac resynchronization therapy (CRT) in combination with ICD treatment, pacing has

untoward effects 6. This notwithstanding, many patients without pacing requirements receive

an atrial lead in order to obtain an atrial electrogram for improved atrial rhythm monitoring

and for better discrimination of supraventricular tachyarrhythmias (SVT) and ventricular

fibrillation (VF) or ventricular tachycardia (VT). Addition of an atrial lead, however, may

increase the risk of complications and may prolong implantation and fluoroscopy time.

The need to implant a separate atrial lead may be obviated by a novel A+-single coil

defibrillation lead with two integrated rings mounted 15-18 cm from the lead tip. The rings

function as a sensing dipole that floats within the right atrium. In conjunction with a dedicated

atrial input stage that filters and amplifies the atrial signal up to 4-fold, the A+-ICD system

has been proven safe and operational 7-10. This prospective study aimed to compare the A+

ICD with the conventional dual chamber ICD (DR-ICD) concept in a large patient cohort at

implantation and over 12 months of follow-up.

Methods

The Belos A+ versus DR Clinical Investigation of Arrhythmia Discrimination (ADRIA) study

enrolled 265 patients in 10 centers in Germany and Switzerland (see Appendix). The study

protocol was approved by the institutional review boards. The aim of the study was to

evaluate potential advantages and disadvantages of an A+ ICD system in comparison to a

conventional DR-ICD. The primary objective of this study was to determine whether there is



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a difference in the specificity of SVT detection between the two systems. Secondary

objectives were the comparison of the sensititivies of the detection enhancement algorithm, of

the complication rates, the implantation and fluoroscopy times and the lead performance over

time.

The study was sponsored by the manufacturer of the devices (Biotronik SE, Berlin,

Germany). Before publication, the data was reviewed but the manuscript was not influenced

by Biotronik.

Patient Selection

Patients with a standard ICD indication were enrolled in the study 3. Exclusion criteria were

the need for antibradycardia pacing, permanent atrial fibrillation, life expectancy under 6

months, pregnancy, and age below 18 years. All patients provided written informed consent.

Device Specifications

Following enrollment, patients were randomized to receive either a standard DR-ICD (Belos

DR, Lexos DR, or Lumos DR-T) that required implantation of two electrodes, or an A+-ICD

(Belos A+ or Lexos A+) with a single A+ lead (Kainox A+ or Kentrox A+). All ICDs and A+

leads were manufactured by Biotronik SE, Berlin, Germany. Other leads could be selected at

the discretion of the operator.

The A+ lead combines a single ventricular shock coil, bipolar sensing and pacing in the

right ventricle, and true bipolar sensing in the right atrium with the aid of two rings spaced 15

mm apart (figure1). The position exactly in the middle between the rings is located 15 or 17

cm from the lead tip. All A+ leads had a passive ventricular fixation mechanism and silicon

lead insulation. The older Kainox A+ lead had a significantly larger surface area of the

ventricular tip electrode (6.0 mm2) than the successor Kentrox A+ lead (1.8 mm2).



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The A+ ICD systems differ from the DR-ICD systems in three aspects: they have no

atrial pacing capability, use a pre-amplifier for the atrial sensing channel and contain only one

right ventricular shock coil. The devices were equal with respect to programmability,

diagnostic memory characteristics, and the employed tachycardia discrimination algorithm

(SMART®). The latter classifies all ventricular events as SVT or VT depending on the RR

and PP interval, and its respective regularity and multiplicity, as described in literature11.

When programmable SVT or VT detection criteria are met, the episode is stored, including

one minute of dual chamber intracardiac electrogram (IEGM) preceding the detection. In case

of SVT without a coexistent VT or VF, antitachycardia therapy is withheld.

Implantation

Implantations were performed according to institutional standards. The total implantation

time, the time between the beginning of lead insertion and lead(s) connection to the ICD (lead

implantation time), and the total fluoroscopy time were recorded in each patient. The

investigators also measured ventricular pacing threshold at 0.5 ms pulse duration, ventricular

pacing impedance, and P- and R-wave amplitudes.

Device Programming

The study protocol recommended the use of lower cut-off rate of 120 or 130 bpm for a VT-1

monitoring zone without therapy. The detection of as many SVT episodes as possible was

thus facilitated in order to compare the efficacy of the SMART detection enhancement

algorithm between the two groups.

The investigators were free to select the cut-off rates for ICD therapy zones. The tachycardia

discrimination algorithm was activated in all VT zones. The VT zone was programmed 50

bpm above the monitor zone with a detection duration of 14, onset of 20%, stability of 12%

and SMART detection and redetection on. The detection for the VF-zone was programmed to



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8 of 12, while the rate cut-off could be programmed individually. The post-ventricular atrial

blanking (PVAB) was 16ms before to 64ms after a ventricular event.In order to avoid

ventricular pacing, pacing was programmed to VVI 40 beats per minute.

Follow-up

During the follow-up visits at 1, 3, 6 and 12 months after device implantation, ICD

interrogation was performed, all documented episodes of SVT or VT/VF were collected and

the need for ICD system revisions documented if applicable.

Analysis of Arrhythmia Episodes

All spontaneous tachyarrhythmia episodes stored by the device were classified by authorized

participants of each study center as VF, VT or SVT. Pre-defined subtypes of SVT were atrial

flutter, atrial fibrillation, sinus tachycardia, and other SVT (figures 2a and 2b). Episodes of

VT or VF with concurrent SVT were classified as VT/VF. Episodes other than VT/VF or

SVT were excluded from analysis. From all episodes atrial and ventricular IEGM were

documented.

Blinded to the classification of the on-site investigator, members of the steering

committee (C.S:, M.Z., M.N.) of the ADRIA study reviewed a sample of 370 randomly

chosen episodes from 85 patients. The concordance of the classification for VT/VF or SVT

between the investigators and the committee was 96.5%. The committee thereafter

recommended that the on-site rhythm classifications should be generally accepted, but

reserved the right to overrule on-site decisions if errors were noticed during analysis of the

documentation for the episodes.

Specificity and sensitivity of the SMART discrimination algorithm were calculated in all

episodes documented in the VT-zone. The specificity of the discrimination algorithm was

defined as the proportion of correctly classified SVT episodes: True negative / (True negative



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+ false positive). The sensitivity was defined as the proportion of correctly classified VT/VF

episodes: True positive / (True positive + false negative).

To account for the bias in deriving of specificity and sensitivity from multiple episodes of the

same type in the individual patients, the results were corrected by the generalized equation

estimation (GEE) 12, 13. Briefly, GEE-method adjusts the effective number of episodes of

every individual patient depending on the correlation of the patients’ episodes, which are not

necessarily independent. The GEE-method is applied before the individual specificity figures

are pooled, and is generally accepted to provide the best estimate of the true specificity and

sensitivity.

Statistics

Statistical analysis of study results was performed using the software packages SPSS 16.0 and

(for GEE) PASW Statistics 17.0 (SPSS Inc., Chicago, IL, USA). Continuous variables are

reported as mean ± SD. The two-sided t-test was used for normally distributed data, and the

Wilcoxon-Mann-Whitney (U) rank test was used for data that were not distributed normally.

Categorical data were compared using a χ2 test according to Pearson or Fisher’s exact test as

appropriate. In all cases, statistical significance was established with p <0.05.

Per-protocol analysis was performed. Cross-over was not allowed. Patients who received a

device that was not compatible with their randomization scheme during follow-up were

considered drop-outs. Arrhythmia episodes and adverse events that had occurred before drop-

out were taken into account.

The necessary sample size to compare the specificities of the study groups was determined to

reject the null hypothesis of inferiority of the A+ specificity with a ∆≥7%. It was assumed

that the specificity in the both study groups is 93% (unpublished data from non-randomized

studies available during study planning). With an α=0.05 and a power of 0.8, we calculated

that we would need 181 uncorrelated SVT episodes per group including a 10% drop-out rate.



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We assumed an interclass correlation of 0.5 between the episodes of individual patients, and

expected 3 episodes per patient. We calculated that it would be possible to disprove the H0

with 120 patients per group.

Results

Patient Population

Of the 265 enrolled patients, 16 (6%) were excluded for violation of the randomization or

withdrawal of informed consent before implantation. Of the remaining 249 patients, 124 were

randomized to the A+- and 125 to the DR study arm. There were no significant differences in

the baseline characteristics between the two groups, except for the presence of previous

myocardial infarction (47% DR vs. 33% A+) and the use of statins (65% DR vs. 43% A+,

Table 1). Seventy-three percent of the patients had ischemic heart disease and 39% a history

of VF or VT. The medication was typical for a contemporary ICD population, with a high

percentage of beta-blocker, ACE-inhibitor and diuretic use.

Implantation

The ICD leads implanted in the A+ group were Biotronik Kainox A+ (n=58) and Biotronik

Kentrox A+ (n=66). In the DR group, the ventricular ICD leads were Biotronik Kainox (n=6),

Biotronik Kentrox (n=69), Biotronik Linox (n=38) and other ICD leads (n=12), and the atrial

leads Biotronik Setrox (n=45), Biotronik Selox (n=44), Biotronik Elox (n=3), Medtronic

Capsure 5076 (n=28) or other leads (n=5).

The mean total implantation time was significantly shorter in the A+ group (67 vs. 79 min;

P=0.003), owing to shorter lead implantation time (26 vs. 36 min; P <0.001, Table 2).

After pre-amplification of the atrial signal in the A+ ICD devices, the mean P-wave amplitude

(3.5 mV, equivalent to approximately 1.1 mV without pre-amplification) was similar to the

figure in the DR-group (3.2 mV) and remained stable in both groups over time.



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The mean R-waves did also not differ between the two groups (11+2 mV). Compared to the

DR-group, ventricular pacing thresholds were higher in the A+-group (1.2+1.0 V/0.5 ms vs.

0.8+0.6 V/0.5 ms) and pacing impedances were lower (Table 2). However, for the newer

generation Kentrox A+ leads, utilized in more than half of the patients in each study arm,

there were no differences in pacing thresholds and pacing impedances between the A+ ICD

(955 Ohm, 0.7 V/0.5 ms) and the DR-ICD (912 Ohm, 0.8 V/0.5 ms).

Follow-up and Adverse Events

The mean follow-up was 370 ± 104 days, with a cumulative follow-up of 251 years. Thirteen

patients (5%) died. None of these deaths were device-related. Fifteen patients (6%) were lost

to follow-up. Arrhythmia episodes and adverse events that had occurred before drop-out were

included in the analysis. There were 23 system-related adverse events requiring reintervention

(Table 3). These included high defibrillation thresholds (DFT) with the initial lead during

implantation or pre-discharge testing (A+-group n=2, DR-group n=1), atrial lead dislocation

(DR-group n=5), or repositioning of the ventricular lead because of dislocation or high pacing

thresholds (A+ group n=7, DR-group n=5). Of the 3 patients with high DFT, one patient in

the DR-arm received a high-energy device and an additional SVC coil was implanted in a

patient in the A+ group. Another patient in the A+ group received a dual-coil lead along with

a single chamber VVI-ICD and was hence counted as a drop-out.

Documented Episodes

A total of 3498 spontaneous episodes of arrhythmia were recorded. Sixty-four

supraventricular episodes were excluded because the tachycardia discrimination algorithm

had been switched off by the investigators because of small atrial signals or permanent atrial

arrhythmias (A+-group n=7, DR-group n=2; P=ns). Another 224 episodes (154 episodes in 20

patients in the DR-group and 70 episodes in 14 patients in the A+-group; P=ns) were



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excluded since the investigators classified them as "other rhythm” or "unclear" (mostly due to

intermittent T-wave oversensing or premature ventricular contractions).

Of the remaining 3210 episodes, 1894 occurred in the A+ group and 1316 in the DR group.

This difference was not statistically significant after correction by the GEE-method (P=0.09).

In total, 18.5% of episodes were VT or VF, and 81.5% were SVT. The distribution of

ventricular and supraventricular arrhythmias was comparable in both groups except for a

slightly higher number of VT episodes in the A+-group. During data analysis, 21 (0.7%)

episode classifications made by the investigator were overruled by the steering committee.

Table 4 compares rhythm classification for the two randomized groups.

The proportion of the different arrhythmias at different rates is illustrated in Figure 3. The

large number of sinus tachycardia episodes (61%) was due to the intentionally low cut-off rate

for the VT-1 zone. The programmed lower cut-off rate for VT1 was equal or less than 130

bpm (as recommended in study protocol) in 58.4% of all episodes, between 131 and 140 bpm,

in 29.2% of episodes and equal or greater than 140 bpm in 12.3%.

Sensitivity and Specificity

All 593 spontaneous episodes classified by the investigators as VF or VT were correctly

discriminated, resulting in a sensitivity of 100% for both groups before and after GEE-

correction.

Of the 2617 SVT episodes, 2564 were detected within the VT rate range and were therefore

evaluated by the tachycardia discrimination algorithm and included in our specificity

calculations in Table 5. The GEE-corrected specificity did not differ between the A+-group

(61.8%) and the DR-group (66.2%, P=0.22), however, the null hypothesis of inferiority of the

A+ specificity cannot be rejected (P=0.39). The overwhelming majority of SVT episodes

were sinus tachycardia. We therefore analyzed a sample of 492 false positive sinus

tachycardia episodes. False positive detection typically resulted from early premature



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ventricular contractions (PVC) activating the onset criterion or intermittent atrial sensing

disturbances. Both over- and undersensing in the atrium rendered the algorithm to assume

different averaged rates in the atrium versus ventricle, precluding proper detection of a sinus

tachycardia. While the prevalence of PVC was similar in both study arms, over- and

undersensing of atrial signals was more often found in the A+ group. Episodes of over- or

undersensing were found in 23 of 63 (36%) A+ patients with sinus tachycardia, as compared

with 5 of 47 (11%) DR patients with sinus tachycardia (P=0.002) This is due to the higher

prevalence of small atrial signals before amplification in the A+-group, which can cause P-

wave undersensing or far-field R-wave oversensing and may explain the slight difference

between the specificities of the study groups. Typical examples of complete undersensing of

the atrial signal (fig. 4a) and intermittent R-wave oversensing (fig. 4b) in the monitor zone did

not result in untoward clinical consequences for the patient.

Despite misclassification of the SVT episodes, only very few patients received shock therapy

since the vast majority of episodes was in the monitor-zone, or the SVT terminated before

shock delivery. In only 46 of 1126 false-positive episodes in the VT or VF-zone, (4.1% not

GEE-corrected), shocks were delivered. Thirty-four episodes occurred in 7 patients of the

A+- and 12 episodes occured in 7 patients of the DR-group.

Discussion

This is the first study to compare a novel single lead ICD system with atrial sensing

capabilities to a conventional dual-chamber ICD. The main finding is that in patients with

standard ICD indication and no need for antibradycardia pacing, the A+ ICD system is faster

to implant and non-inferior in VT and SVT detection and therapy when compared to a DR-

ICD system. It provides an attractive alternative to an additional atrial lead if one wishes to

obtain an atrial electrogram in ICD patients.



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Need for atrial sensing

In the contemporary ICD-population the majority of patients do not require antibradycardia

pacing. The DAVID trial demonstrated that right ventricular pacing even increases mortality

and hospitalization rate in an ICD population and should therefore be avoided 6. In the CRT-

population, even right atrial pacing may have untoward effects 14. Although pacing should be

avoided whenever possible, sensing information from the atrium is desirable for numerous

reasons. First, the integration of the atrial sensing information can be crucial in differentiating

supraventricular from ventricular arrhythmias. Inappropriate shocks not only impair quality of

life but are associated with increased mortality and should thus be avoided by all means 15.

Currently, all manufacturers feature detection enhancement algorithms that achieve high

sensitivities and specificities and often integrate the comparison of ventricular and atrial

signals 11, 16, 17. The SMART detection algorithm used in this study has been described

elsewhere and has been shown to have a sensitivity of 100% along with a specificity of 89%

11. In our study the sensitivity was 100%, i.e. that all ventricular tachyarrhythmias were

detected as such, while the overall specificity was only 64%. The specificity of a detection

enhancement algorithm depends on numerous parameters such as the population studied, the

prevalence of supraventricular tachycardias and the device programming. Hence it is difficult

to compare these algorithms if they were not studied under the same conditions. The relatively

low specificity in the present study may be explained by the fact that the rate cut-off was

unusually low at 130 bpm in order to obtain as many episodes as possible. With faster heart

rates, the impact of PVC on triggering the onset criterion should decrease. In fact, analysis of

a non-prespecified small sample of 321 episodes recorded in 21 patients in whom the cut-off

had been set to > 140 bpm resulted in a GEE-corrected specificity of 86%, a specificity

reported earlier11. It is therefore likely, that the lower specificity stems from a clinically

unusually low study cut-off and not from a performance problem of the SMART algorithm.



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Another important reason for the acquisition of atrial information is the possibility to diagnose

atrial fibrillation and to initiate anticoagulant and possibly antiarrhythmic therapy. A recent

study using remote monitoring found that 13% of a contemporary pacemaker-, ICD- and

CRT-population had previously unknown atrial fibrillation18. Thus, the availability of an atrial

electrogram in combination with remote monitoring may offer accelerated treatment options

for these patients, for instance the potential to reduce strokes 19.

Implantation and complications

Not surprisingly, the use of a single-lead ICD resulted in shorter total implantation times due

to shorter lead implantation time. The use of the single-coil ICD A+ defibrillation lead did not

result in a significantly higher failure rate to defibrillate when compared with the dual-coil

leads. Although dual-coil defibrillator leads offer more flexibility in the choice of the shock

pathway in the rare case of high defibrillation threshold (DFT), randomized trials did either

show no difference 20 or only a small difference (10.2 J vs. 9.8 J) 21 in the DFT between

single- and dual-coil ICD.

Atrial lead dislodgement occurred in 4% of the patients in the DR-group, which is slightly

lower than in previously reported large series 20. Naturally, this complication cannot occur in

the A+-group.

In the A+-group the ventricular pacing threshold was slightly higher than in the DR-

group, which was entirely due to the initial higher usage of the older-generation Kainox A+

leads. For safety purposes, this first pentapolar lead had a relatively large surface area (6.0

mm2) in order to minimize the risk of perforation. Based on the clinical experience, its

successor lead Kentrox A+ had a much smaller surface area (1.8 mm2). After exclusion of the

Kainox A+ leads, the ventricular pacing thresholds did not differ between the two groups.



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The 12-month mortality rate of 5.2% is consistent with the mortality rates in other ICD

studies 1.

Difference to VDD-pacemaker sensing algorithms

The concept of single-lead VDD pacing systems with a floating bipole in the atrium has long

been available but comprises only 7% of the European pacing market 21 . One reason for the

reluctance to use VDD-pacing is the concern of the development of sinus node disease with

subsequent need for pacing. Schaer and colleagues demonstrated in a large cohort of 320

patients with AV-nodal disease only 1% required an upgrade to a DDD-pacemaker during

follow-up 22. Intermittent atrial undersensing during deep breathing, change of body position

or exercise is a well known phenomenon that occurs in both VDD and DDD-pacemaker

systems21. The incidence of atrial undersensing in VDD-systems is between 5 and 7% but is

clinically silent in the vast majority of patients23-25.

During follow-up, the amplified atrial sensing signal remained stable and showed no tendency

for deterioration in the A+ group. The processing of the atrial signal differs between VDD-

pacemakers and the studied ICD, since the latter comprise a special input stage that amplifies

the atrial signal up to 4-fold.

Limitations

This study focused on atrial sensing and its contribution to rhythm discrimination in ICD. Its

impact on AV-sequential pacing has not been evaluated in this study.

Secondly, our study was not designed to investigate the influence of sensing disturbances on

the discrimination, and to give mechanistic explanation of SVT discrimination failure.



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Thirdly, the performance of the A+-single coil ICD lead may be different in the case of a

right-sided implant. Since all our implantions have been performed from the left side our

study does not provide any data for this setting. However, data from VDD-pacemaker studies

actually even showed better atrial sensing behaviour in right-sided implants26.

Fourthly, with the devices used in this study, atrial tachyarrhythmias were only recorded if

their ventricular rate was above the VT cut-off rate. Since atrial tachyarrhythmias with a slow

ventricular rate have been missed the information obtained from the devices studied has not

been validated for the further therapeutic management of patients with suspected atrial

tachyarrhythmias. Finally, it cannot be completely ruled out that the observed higher

incidence of atrial over- or undersensing in the A+-group can be clinically significant in

patients with slow VT and concomittant sinus tachycardia

Conclusion

The use of an A+-single coil ICD lead in defibrillator patients without pacing requirement is a

clinically elegant means to obtain atrial electrograms from only one lead. Compared to ICD

patients with an additional atrial lead this results in shorter implantation times without

sacrificing the accuracy of arrhythmia detection.



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Acknowledgments

The investigators wish to thank Dr. Juergen Schrader (Biotronik, Berlin, Germany) for his

support in data handling and statistical analysis.

Sources of Funding

The study was sponsored by the manufacturer of the devices (Biotronik SE, Berlin,

Germany).

Disclosures

Dr. Sticherling is consultant for Biotronik, Medtronic, and Boston Scientific. Dr. Zabel is

consultant for Biotronik, Medtronic, and Boston Scientific. Dr. Spencker is consultant for

Biotronik and Medtronic. Dr. Niehaus is consultant for Medtronic and Boston Scientific. The

other authors report no potential conflicts.

Appendix

Participating Centers and investigators

University Hopital Basel, Switzerland: Christian Sticherling, MD; Beat Schaer; MD; Heart

Center, University of Göttingen, Germany: Markus Zabel, MD; Dieter Zenker, MD; Charité,

Campus Benjamin Franklin, Berlin, Germany: Sebastian, Spencker, MD; Schwarzwald-Baar-

Klinikum Villingen-Schwenningen, Germany: Udo Meyerfeldt, MD; Hannover Medical

School, Hannover, Germany: Michael Niehaus, MD; University Hospital of Muenster,

Germany: Lars Eckardt, MD, Julia Koebe, MD; Vivantes- Humboldt Klinikum, Berlin:

Steffen Behrens, MD; St.-Johannes Hospital Dortmund, Germany: Ralf Dedner, MD; Sana

Klinikum Berlin, Germany: Olaf Göing, MD; Cardiology Practice Bonn, Germany: Thomas

Klingenheben, MD



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Table 1. Baseline Patient Characteristics

A+ ICD

(n=124)

DR-ICD

(n=125)

P

Female, n (%) 12 (10) 20 (16) n.s.

Mean age ± SD, years 62 ± 11 63 ± 11 n.s.

History of tachyarrhythmia, n (%)

VF 12 (10) 11 (9) n.s.

VT without VF 37 (30) 36 (29) n.s.

Atrial fibrillation 22 (18) 16 (13) n.s.

Atrial flutter 7 (6) 2 (2) n.s.

Ischemic heart disease, n (%) 86 (69) 95 (76) n.s.

Myocardial infarction 41 (33) 59 (47) 0.023

PTCA 50 (40) 56 (45) n.s.

CABG 13 (10) 21 (17) n.s.

Non-ischemic cardiomyopathy, n (%) 27 (22) 26 (21) n.s.

Valvular disease, n (%) 12 (10) 12 (10) n.s.

NYHA functional class: I/II/III/IV, n 17/47/20/0 16/38/31/4 n.s.

*Patients with information on

medication, n (%)

119 (96) 120 (96) n.s.

Beta-blocker 109 (92) 112 (93) n.s.

ACE-inhibitor 98 (82) 95 (79) n.s.



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Angiotensin II-antagonist 13 (11) 20 (17) n.s.

Diuretic 86 (72) 88 (73) n.s.

Amiodarone 35 (28) 38 (30) n.s.

Other antiarrhythmic drugs 2 (2) 3 (2) n.s.

Lipid-lowering therapy 51 (43) 78 (65) <0.001

Anticoagulant 22 (18) 35 (29) n.s.

Thrombocyte aggregation inhibitor 89 (75) 99 (83) n.s.

Digitalis 24 (20) 31 (26) n.s.

*Percentage of patients taking a drug was calculated among 239 patients (96%) with

information on medication. ACE: angiotensin-converting enzyme, CABG: coronary artery

bypass graft, ICD: implantable cardioverter-defibrillator, n.s.: not significant, NYHA: New

York Heart Association, PTCA: percutaneous transluminal coronary angioplasty, SD:

standard deviation, VT: ventricular tachycardia, VF: ventricular fibrillation.



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Table 2. Implantation Data

A+ ICD

(n=124)

DR-ICD

(n=125)

P

Total implantation time, min 67 ± 30 79 ± 30 0.003

Lead implantation time, min 26 ± 19 36 ± 19 <0.001

Fluoroscopy time, min/sec 6'15" ± 6'31" 6'59" ± 5'41" n.s.

Atrium

P-wave amplitude, mV 3.5 ± 0.8 3.2 ± 0.6 n.s.

PI, Ohm - 650 ± 133 -

Ventricle

R-wave amplitude, mV 11 ± 2 11 ± 2 n.s.

PT in all leads, [email protected] ms 1.2 ± 1.0 0.8 ± 0.6 <0.001

PT in Kentrox* leads, [email protected] ms 0.7 ± 0.5

(n=65)

0.8 ± 0.4

(n=69) n.s.

PI in all leads, Ohm 759 ± 297 880 ± 292 0.002

PI in Kentrox* leads, Ohm 955 ± 276

(n=65)

912 ± 311

(n=69) n.s.

Data are shown as mean ± standard deviation. *Newer technology, with a smaller surface area

of the ventricular tip electrode (1.8 mm2). ICD: implantable cardioverter-defibrillator, n.s.: not

significant, PI: pacing impedance, PT: pacing threshold.



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Table 3. Adverse Events During Implantation and Follow-up

A+ ICD

(n=124)

DR-ICD

(n=125)

P

FU duration ± SD, days 361 ± 104 379 ± 106 n.s.

Deaths, n (%) 6 (4.8) 7 (5.6) n.s.

Device related, n (%) 0 0 n.s.

Cardiac* 2 (1.6) 4 (3.2) n.s.

Non-cardiac* 4 (3.2) 3 (2.4) n.s.

Drop-out, n (%) 9 (7.3) 6 (4.8) n.s.

Late informed consent withdrawal, n (%) 0 1 (0.8) n.s.

Lost to FU or poor compliance, n (%) 5 (4.0) 5 (4.0) n.s.

†Received new device (lead or ICD), n (%) 4 (3.2) 0 n.s.

Adverse events (invasive solution), n (%) 10 13 n.s.

Failure to defibrillate (implantation, pre-discharge) 2 1 n.s.

Ventricular perforation 0 1 n.s.

Pneumothorax 1 1 n.s.

Atrial lead dislocation - 5 -

Ventricular lead dislocation or high threshold 7 5 n.s.

*Confirmed or assumed to have this cause. †In two cases, switch to conventional ICD lead

was required because of dislocation or high pacing threshold with the Kainox A+ lead; in one



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patient, high a energy device was used during implantation; and in one patient, upgrade to

cardiac resynchronization therapy was carried out. FU: follow-up, ICD: implantable

cardioverter-defibrillator, n.s.: not significant, SD: standard deviation.



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Table 4. Classified Arrhythmia Episodes

A+ ICD

(n=124)

DR-ICD

(n=125)

P All patients

(n=249)

Patients with episodes, n (%) 88 (71.0) 85 (68.0) n.s. 173 (69.5)

Total number of episodes, n 1894 1316 n.s. 3210

Episodes per patient ± SD, n

Median

21.5 ± 22.3

15.5

15.5 ± 15.0

9

n.s. 18.5 ± 19.2

12

Ventricular tachyarrhythmia, n (%) 328 (17.3) 265 (20.1) n.s. 593 (18.5)

Ventricular fibrillation 62 (3.3) 47 (3.6) n.s. 109 (3.4)

Ventricular tachycardia 266 (14.0) 218 (16.5) 0.017 484 (15.1)

SVT, n (%) 1566 (82.7) 1051 (79.8) n.s. 2617 (81.5)

Atrial fibrillation 172 (9.1) 101 (7.7) n.s. 273 (8.5)

Atrial flutter 23 (1.2) 121 (9.2) n.s. 144 (4.5)

Sinus tachycardia 1223 (64.6) 735 (55.9) n.s. 1958 (61.0)

Other SVT 148 (7.8) 94 (7.1) n.s. 242 (7.5)

Patients with SVT, n (%) 67 (54.0) 60 (48.0) n.s. 127 (51.0)

ICD: implantable cardioverter-defibrillator, SVT: supraventricular tachyarrhythmia, n.s.: not

significant.



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Table 5. Discrimination Algorithm Results and GEE-Corrected Specificity

A+ ICD DR-ICD P All patients

Ventricular fibrillation or tachycardia, n 328 265 n.s. 593

True positive 328 265 - 593

False negative 0 0 - 0

Sensitivity, % 100% 100% n.s. 100%

Supraventricular tachyarrhythmia, n 1521 1043 n.s. 2564

True negative 830 663 - 1493

False positive 691 380 - 1071

Specificity, % 61.8 66.2 n.s. 64.4

Lower 95% confidence interval bound, % 55.7 59.4 - 60.0

Upper 95% confidence interval bound, % 67.9 72.9 - 69.1

GEE: generalized equation estimation, ICD: implantable cardioverter-defibrillator.



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Figure Legends

Figure 1: Picture of the single-coil, passive-fixation Biotronik Kentrox A+ lead. The atrial

bipol can be mounted at a distance of 15 or 17 cm from the lead tip.

Figure 2: Intracardiac electrograms (EGM) depicting an episode of rapidly conducted

recorded AF by an A+ -ICD (a) and an episode of sinus tachycardia stored by an DR-ICD

(b). 25 mm/sec. Top line: annotated marker channel, middle line: atrial channel, bottom line:

ventricular channel).

Figure 3: Prevalence of adjudicated tachyarrhythmias (stratified to < 130 bpm, 130-149 bpm,

and >149 bpm) during follow-up, according to classification made by the investigators or

steering committee. AF: atrial fibrillation, Afl: atrial flutter, ST: sinus tachycardia, SVT:

supraventricular tachyarrhythmia, VF: ventricular fibrillation, VT: ventricular tachycardia.

Figure 4: EGMs recorded by an A+-ICD with examples of complete atrial undersensing (a)

and intermittent atrial R-wave oversensing (b). 25 mm/sec. Top line: annotated marker

channel, middle line: atrial channel, bottom line: ventricular channel).



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Behrens and Michael NiehausChristian Sticherling, Markus Zabel, Sebastian Spencker, Udo Meyerfeldt, Lars Eckardt, Steffen

StudySystem in Patients without Antibradycardia Pacing Indications: Results of a Randomized Comparison of a Novel Single Lead Atrial Sensing (A+)-ICD System with a Dual Chamber ICD

Print ISSN: 1941-3149. Online ISSN: 1941-3084 Copyright © 2010 American Heart Association, Inc. All rights reserved.

Dallas, TX 75231is published by the American Heart Association, 7272 Greenville Avenue,Circulation: Arrhythmia and Electrophysiology

published online December 14, 2010;Circ Arrhythm Electrophysiol.

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