Steroid-Eluting Electrodes Prevent Chronic Pacing Threshold Rise in the Atrial Chamher After Oral Propafenone Administration DANIELE CORNACCHIA,' MAURO FABBRI/ ALEARDO MARESTA/ ANDREA PUGLISI,^ RENATO RICCI,^ PAOLO AZZOLINI,^ PASQUALE FRANCESCO SORRENTINO,' PIKRO SESTU,'' ANTONIO SANNA,^ CIOVANNI QUINTO VILLANI,' CIOVANNI DIECI,' ALESSANDRO CAPUCCI,' and FRANCESCO DE SETA^ From the ^Department of Cardiology, Ospedak) pergli Infermi. Faenza, ^Ospedale Fatebenefratelli, Rome, ^University of Catania. ''Ospedale S. Mic:hcle, Cagliari, ^Ospedale Civile, Piacenza, and ^Medtronic, Rome, Italy CORNACCHIA, D., ET AI..: Steroid-Eluting Electrodes Prevent Chronic Pacing Threshold Rise in the Atrial Chamber After Oral Propafenone Administration. The aim ofthe study was to evaluate chronic atrial pacing threshold increase after oral propafenone therapy. Fifty patients affected by advanced AV block and sick sinus syndrome were studied at least 6 months after pacemaker implantation, before and after oral propafenone therapy (450-900 mg/day based on body weight). The patients were subdivided into three groups as to the type of electrode implanted, all three unipolar: group 1 (20 patients) Medtronic CapSure 4003, group II (13 patients) Medtronic Target Tip 4011, group HI (17 patients] Medtronic 4057 screw-in leads. In all cases, Medtronic unipolar pacemakers were implanted with the same noninvasive autothreshold measurement method. Propafenone and 5-OH-propafenone blood levels were measured 3-5 hours ufter drug administration. The pacing autothreshold was measured at 0.8, 1.6, and 2.5 V by re- ducing the pulse width. After propafenone. groups II and III showed a statistically significant threshold rise (P ranging from < 0.01 to < 0.05), whereas no significant difference was found in group I. Propafenone and 5-OH-propafenone blood levels did not show any significant difference among the three groups. Strength-durution curves were drawn for the three groups before und after propafenone: at baseline the curves shifted to the left with the steep part above the knee, clearly favoring CapSure over the other two groups. After propafenone, the curves shifted to the right, with the flat part progressively more evident in groups II and III. In the atrial chamber, steroid-eluting leads prevented threshold increase after propafenone therapy, in contrast with a significant threshold rise with conventional porous and screw-in leads. (PACE 1997; 20[Pt. I]240-244) propafenone, pacing threshold Introduction It has clearly been shown in previous stud- ies^~*^ that Class IC antiarrhythmic drugs, such as propafenone [Knoll, Liestel, Switzerland), affect chronic ventricular pacing threshold. This thresh- old rise is largely dependent on the type of lead Address for reprints: Daniele Cornacchia, M.D., Depiirtment of Cardiology, Ospedale per gli Infermi, 48018 Faenza (RA), Italy. Fax: 39-546-26484. Received Decembfir 7, 1994; revision June 29, 1995; accepted November 27, 1995. implanted: conventional porous; screw-in; or steroid-eluting electrode. Recently, these different behavioral patterns have been studied for the ven- tricular chamber after propafenone administra- tion, resulting in a clearcut lower threshold in- crease for steroid-eluting leads in comparison with the porous and screw-in ones. In particular, this low threshold rise allowed a safe chronic low output stimulation after propafenone.^ The aim of the present study was to evaluate whether, and to what extent, steroid-eluting elec- trodes can obtain the same results in the atrial 240 February 1997, Part 1 PACE, Vol. 20
Transcript
Steroid-Eluting Electrodes Prevent ChronicPacing Threshold Rise in the Atrial ChamherAfter Oral Propafenone Administration
DANIELE CORNACCHIA,' MAURO FABBRI/ ALEARDO MARESTA/ANDREA PUGLISI,^ RENATO RICCI, PAOLO AZZOLINI,^ PASQUALEFRANCESCO SORRENTINO,' PIKRO SESTU,'' ANTONIO SANNA,^CIOVANNI QUINTO VILLANI,' CIOVANNI DIECI,' ALESSANDRO CAPUCCI,'and FRANCESCO DE SETA^
From the ^Department of Cardiology, Ospedak) pergli Infermi. Faenza, ^Ospedale Fatebenefratelli,Rome, ^University of Catania. ''Ospedale S. Mic:hcle, Cagliari, ^Ospedale Civile, Piacenza,and ^Medtronic, Rome, Italy
CORNACCHIA, D., ET AI..: Steroid-Eluting Electrodes Prevent Chronic Pacing Threshold Rise in theAtrial Chamber After Oral Propafenone Administration. The aim ofthe study was to evaluate chronicatrial pacing threshold increase after oral propafenone therapy. Fifty patients affected by advanced AVblock and sick sinus syndrome were studied at least 6 months after pacemaker implantation, before andafter oral propafenone therapy (450-900 mg/day based on body weight). The patients were subdividedinto three groups as to the type of electrode implanted, all three unipolar: group 1 (20 patients) MedtronicCapSure 4003, group II (13 patients) Medtronic Target Tip 4011, group HI (17 patients] Medtronic 4057screw-in leads. In all cases, Medtronic unipolar pacemakers were implanted with the same noninvasiveautothreshold measurement method. Propafenone and 5-OH-propafenone blood levels were measured3-5 hours ufter drug administration. The pacing autothreshold was measured at 0.8, 1.6, and 2.5 V by re-ducing the pulse width. After propafenone. groups II and III showed a statistically significant thresholdrise (P ranging from < 0.01 to < 0.05), whereas no significant difference was found in group I. Propafenoneand 5-OH-propafenone blood levels did not show any significant difference among the three groups.Strength-durution curves were drawn for the three groups before und after propafenone: at baseline thecurves shifted to the left with the steep part above the knee, clearly favoring CapSure over the other twogroups. After propafenone, the curves shifted to the right, with the flat part progressively more evident ingroups II and III. In the atrial chamber, steroid-eluting leads prevented threshold increase afterpropafenone therapy, in contrast with a significant threshold rise with conventional porous and screw-inleads. (PACE 1997; 20[Pt. I]240-244)
propafenone, pacing threshold
Introduction
It has clearly been shown in previous stud-ies ~* that Class IC antiarrhythmic drugs, such aspropafenone [Knoll, Liestel, Switzerland), affectchronic ventricular pacing threshold. This thresh-old rise is largely dependent on the type of lead
Address for reprints: Daniele Cornacchia, M.D., Depiirtment ofCardiology, Ospedale per gli Infermi, 48018 Faenza (RA), Italy.Fax: 39-546-26484.
Received Decembfir 7, 1994; revision June 29, 1995; acceptedNovember 27, 1995.
implanted: conventional porous; screw-in; orsteroid-eluting electrode. Recently, these differentbehavioral patterns have been studied for the ven-tricular chamber after propafenone administra-tion, resulting in a clearcut lower threshold in-crease for steroid-eluting leads in comparisonwith the porous and screw-in ones. In particular,this low threshold rise allowed a safe chronic lowoutput stimulation after propafenone.^
The aim of the present study was to evaluatewhether, and to what extent, steroid-eluting elec-trodes can obtain the same results in the atrial
240 February 1997, Part 1 PACE, Vol. 20
ATRIAL PACING THRESHOLD RISE AFTER PROPAFENONE
chamber as in the ventricular after propafenonetherapy. Given the growing number of dual cham-ber small pulse generators now available, we alsoevaluated whether low output stimulation in theatrial chamber was safe during propafenone ad-ministration.
Patients and Methods
Our study included a total of 50 patients (29male, 21 female, mean age 72 ± 10 years). Forty-seven received a dual chamber DDD pacing sys-tem; the remaining 3 patients received an AAIstimulation. Implanting indications were sick si-nus syndrome (32 cases) and advanced atrioven-tricnlar (AV) block (18 cases). All patients had un-dergone implantation at least 6 months earlier(between August 1993 and January 1994).
The patients were subdivided in three groupsas to the type of unipolar electrode implanted:group I (20 patients) CapSure® 4003 ( MedtronicInc., Minneapolis, MN, USA), group II (13 pa-tients) Medtronic Target Tip^ 4011, and group III(17 patients) Medtronic 4057 monopolar screw-inlead. In all cases, a Medtronic unipolar pacemakerwas implanted: the Minix model in 2 patients; tbeElite in 47; and the Legend in 1. The same nonin-vasive autothreshoid measurement method wasused in all cases to obtain homogeneous data.
Propafenone was orally administered q8h for7 days in all patients becanse they manifested ven-tricular and/or supraventricular arrhythmias thatrequired antiarrhythmic therapy. Dosage was de-termined by body weight: ^ 60 kg b.w., a dose of150 mg q8h; 61-80 kg b.w., 225 mg q8h; and > 80
kg b.w., a dose of 300 mg q8h. No patient receivedany other antiarrhythmic drug, and all other phar-macological therapy remained unchanged. Dosagebased on body weight was chosen (rather than thetwo fixed doses used in previous clinical stud-ies'*), as this is the most common in clinical prac-tice.
The pacing autothreshold was measured us-ing a Medtronic Programmer 9710 at baseline andafter 7 days of oral propafenone therapy at 0.8,1.6,and 2.5 V. The procedure was performed in thesupine position, in the morning 3-5 hours afterpropafenone administration, and after a short rest(given the presence of rate responsive models).The blood level of propafenone and of its first ac-tive metabolite, 5-hydroxy-propafenone, was alsomeasured at this time to assess the patients' ther-apy compliance and to evaluate if any significantdifference in the electrophysiological parameterswas present by comparing the plasma levels of 5-OH-propafenone and its parent compound. Dur-ing the week of propafenone administration, pace-maker output was set at 5 V in order to avoidcaptnre failure.
Group I was compared with groups II and IIIas to the following parameters: age; weight;propafenone oral dosage; propafenone and 5-OH-propafenone plasma levels. Statistical analysiswas performed for threshold level values beforeand after propafenone at 0.8, 1.6, and 2.5 V in thethree groups (taking into account that in 1 out of17 patients in group III, threshold was not mea-surable at 0.8 V because of loss of capture). The av-erage increment rates were compared and corre-lated with propafenone blood level.
PI = significance between Group I and Group II; P2 = significance between Group II and Group III; P3 = significance between GroupIII and Group I.
PACE, Vol. 20 February 1997, Part I 241
CORNACCHIA.ETAL.
GroupGroupGroup
Atrial Threshold Variation Before
1 (ms)II (ms)III (ms)
Before
0.17 :0.31 :0.65 :
t 0.05b 0.08t 0.41
0.8 V
After
0.21 ± 0.10.49 ± 0.27
1 ± 0.49
and After
P
NS<0.03< 0.01
Table 1
Propafenone
Before
0.09 ± 0.030.2 ± 0.07
0.21 ± 0.1
1.
at Different Outputs in
1.6 V
After
0.11 ± 0.020.32 ± 0.150.42 ± 0.46
P
NS<0.04< 0.04
the Three Groups
Before
0.06 ± 0.010.11 ± 0.050.13 ± 0.08
2.5
of Leads
V
Atter
0.070.220.23
± 0.03±0.11 <± 0.31 <
P
NS0.010.05
Group I: CapSure® 4003; Group II: Target Tip® 4011; Group III: screw-in 4057.
Data were expressed as a mean ± SD, andwere compared using the Student's f-test forpaired and unpaired data. The linear correlationhetween threshold increments and drug hloodlevel was calculated. Low stimulation is com-monly defined as an output not higher than 2.5 Vand 0.5 ms, and the safety margin as the double ofthe voltage or triple the pulse width compared tothe threshold values. These atrial data were com-pared to the ventricular data measured in our pre-vious study with the same leads and the samepacemakers.^
ResultsTable I shows mean age, body weight,
propafenone oral dosage, propafenone, and 5-OH-propafenone plasma concentration: the data con-firmed that for the most part the three groups werelargely homogeneous. Threshold variations afterpropafenone in the three groups at the three out-puts [0.8, 1.6, and 2.5 V) are shown in Table II.
After propafenone. groups II and III showed astatistically significant threshold rise rangingfrom P < 0.01 to P < 0.05; in group I, no signifi-cant difference was found. Propafenone and 5-OH-propafenone plasma levels were measured forall patients, and no significant differences werefound in the three groups either for the activemetabolite or for the parent compound (Table I).No poor metabolizer was present in our series. Wefound a complete lack of linear correlation be-tween threshold increment and plasma concentra-tion of both compounds, in agreement with thelack of correlation well known in the literature,between antiarrhythmic effect and drug plasmalevels.
No sensing failure was found either before orafter propafenone therapy during the follow-up,but no specific P wave measurement was per-formed. Pacing impedance was measured viatelemetry before and after propafenone, with nosignificant difference found among the threegroups: group I: 456 ± 54 to 457±103 O; group II:424 ± 54 to 429 ± 50 li; and 516 ± 74 to 508 ± 76n in group III. Strength-duration curves w^eredrawn for the three groups before and afterpropafenone, measuring the threshold at the threedifferent outputs. The curves were obtained frompacemakers that perform autothreshold by reduc-ing pulse width (G.05-ms steps) at the pro-grammable outputs starting from 0.8 V.
The curve morphologies of the three types ofleads implanted are quite different: the curves areshifted to the left, in comparison with the classicones, with the steep part above the knee clearlyprevailing for CapSure in comparison with theother two groups (Fig. 1).
After propafenone, we found a significantshift of the cnrves to the right, with accentuationof the flat part progressively more evident ingroup II and III in comparison with group I. No pa-tient showed a loss of capture at 2.5 V afterpropafenone.
Comparing this study with the previous studywe carried out on the ventricle using the same pro-tocol,^ CapSure performance was found to be evenbetter in the atrium than in the ventricle (TableIII). In fact, with CapSure implanted in the atrium,no significant threshold increase was found afterpropafenone, whereas a small, but significant risehad been found in the ventricle. Also, at baseline,thresholds were significantly lower in the atrinm
242 February 1997. Part I PACE, Vol. 20
ATRIAL PACING THRESHOLD RISE AFTER PROPAFENONE
- - « « T SCREW IN BEFOREP. • • O . • CArSlWE BBK«E P.
Figure 1. Strength-duration curves for tbe three leads evaluated before and after propafenoneadministration.
with CapSure (P = 0.003) than with Target Tip (P= NS) in comparison with the same leads in theventricle.
Discussion
Several studies on ventricular threshold riseafter propafenone administration comparing dif-ferent leads and pacemakers implanted and theproblem of atrial threshold rise have heen puh-lished.^'^'^In contrast to the previous studies, weadministered an oral dosage of propafenone cor-related with hody weight and divided the pa-
tients into three groups according to the elec-trode implanted. We measured pro-pafenone and5-hydroxy-propafenone in order to assess com-pliance and the type of metabolism in all pa-tients. All generators implanted were made bythe same manufacturer [Medtronic Inc.) and usethe same method of performing autothreshold;therefore, the data obtained were very homoge-neous and reliable.
Our results show that oral administration ofpropafenone causes a rise in stimulation thresholdin the atrial chamber with all the conventional ac-tive and passive leads implanted (groups II and
Table III.
Threshold Comparison Between CapSure® and Target Tip® in the Atrium and in the VentricleBefore and After Propafenone
AC (ms)P
VC (ms)
ATT (ms)P
VTT (ms)
Before
0.17 ± 0.05- 0.003
0.25 ± 0.10
0.13 ± 0.08NS
0.36 ±0.12
0.8 V
P
NS
<0.02
< 0.03
<0.02
After
0.21 ± 0.01- 0.001
0.38 ± 0.14
0.49 ± 0.27NS
0.56 ± 0.25
Before
0.09 ± 0.03<0.02
0.13 ± 0.06
0.20 ± 0.07NS
0.19 ± 0.09
0.6 V
P
NS
< 0.01
<0.04
< 0,01
After
0.11 ± 0.02- 0.003
0.19 ± 0.09
0.32 ± 0.15NS
0.31 ± 0.15
AC = atrial CapSure: VC = ventricular CapSure; ATT = atrial Target Tip; VTT = ventricular Target Tip.
PACE. Vol. 20 February 1997, Parti 243
CORNACCHIA. ET AL.
Ill), but not with the steroid eluting ones (group I).Considering these findings, we can assume thatwith CapSure, the well-known smaller endocar-dial inflammatory and fibrotic reaction^" in theatrial chamber is even less than in tho ventricle,whereas exactly the contrary occurs with TargetTip.
It appears evident that, starting from Ihe base-line, propafonone increases pacing threshold, butthis increase is related to the amount of inflamma-tory and fibrotic reaction caused by the lead im-planted. One possible explanation of this might bethe following: a lead, being a foreign body, causesnot only a fibrotic capsule (thickness varying withtype of lead), but also damage to surrounding my-ocardial fiber cells. Since, as it is well known, themain effect of propafenone [slowing down of con-duction velocity) is much greater in injured thanin normal myocardium, we should assume thatsteroid elution from the lead tip reduces not onlythe capsule thickness, but also the amount of in-jured myocardium, and consequently the effect ofpropafenone.
Since threshold increase after propafenone ishighly significant with porous electrodes (particu-larly with the screw-in), when in clinical practicewe have to pace the atrial chamber in a patientwho is to be chronically treated with propafenone,it is important to take into account the type of leadto be implanted. This is of major concern consid-ering that implantation of screw-in electrodes inthe atrium is not uncommon.
As for the second aim of our study, to find outwhether it is possible to obtain a safe low outputstimulation threshold during propafenone therapy,our results were completely positive for CapSure,whereas they were more problematic for the othertwo groups. In the screw-in group (Fig. 1), consid-ering the curve shape being quite similar to the clas-sic ones, in order to obtain a sufficient safety mar-gin, we were forced to raise the pulse amplitude inmost patients. In the CapSure group, in contrast,operating along the steep part of the strength-dura-tion curve well above the knee, just by increasingthe pulse width (three times) a reliable safety mar-gin could be achieved without exceeding 2.5 V. TheTarget Tip group is located in an intermediate posi-tion between the other two groups, so that in somecases we can operate by lengthening the pulsewidth and in some cases by raising the pulse am-plitude over 2.5 V. The possibility of achieving asafety margin just by prolonging the pulse width,starting from very low values, is a particular char-acteristic of CapSure leads in our case study, re-sulting in a great saving of battery energy.
ConclusionsWith this case study we have shown that in
the atrium, as in the ventricle, chronic pacingthreshold rise during propafenone therapy de-pends primarily on the type of electrode im-planted. In clinical practice, by implantingsteroid-eluting leads, this problem can he greatlyminimized.
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