Herzschr Elektrophys 17:13–18 (2006) DOI 10.1007/s00399-006-0502-4

M. Azizi M. A. Castel S. Behrens W. Rödiger H. Nägele

Received: 26 August 2005 Accepted: 29 December 2005

ORIGINAL CONTRIBUTION

Experience with coronary sinus lead implantations for cardiac resynchronization therapy in 244 patients

Erfahrungen mit der Implantation von Koronarsinuselektroden zur kardialen Resynchronisationstherapie bei 244 Patienten " Zusammenfassung Einleitung Die kardiale Resynchronisationstherapie (CRT) stellt ein neues Verfahren zur Behandlung der Herzinsuffizienz dar. Da die Implantation eines CRT-Systems komplexer als eine normale Schrittmacherimplantation ist, sind Daten zu perioperativer Sicherheit und Komplikationen von besonderer Bedeutung. Methodik Von Januar 1999 bis Juni 2005 wurde in unserem Zentrum bei 244 Patienten (Pat.; mittleres Alter 64 ± 12 Jahre, 82% männlich) die Implantation eines CRT-Systems versucht. Bei 44% lag eine koronare Herzkrankheit und bei 29% Vorhofflimmern vor. Bei 71 Pat. wurde ein vorbestehender Schrittmacher aufgerüstet. Ergebnisse Bei 239 Pat. (97%) gelang eine CRT-Implantation (285 Interventionen). 27% der Systeme verfügten über eine Defibrillationsmöglichkeit. 2 Patienten benötigten epikardiale Elektroden. Insgesamt 130 CS-Elektroden wurden posterolateral implantiert, 97 anterolateral und 28 anterior. 88% der Eingriffe erfolgten mit der „over-the-wire“-Technik. Es kam zu keinen perioperativen Todesfällen, jedoch zu 37 Komplikationen (12,5%): CS-Dissektion (n = 9), CSPerforation (n = 1), Kammerflimmern (n = 4), Asystolie (n = 5), Lungenödem (n = 1), Pneumothorax (n = 2), CS-Elektrodenrevision wegen Dislokation (n = 7) oder Zwerchfellzucken (n = 12) und Explantation wegen Infektion (n = 2). Bei 88% der Patienten besserte sich die NYHA-Klasse, jedoch nur bei 55% mit anteriorer Elektrodenlage. Zusammenfassung Perioperative Komplikationen traten bei ca. 10–15% aller CRT-Implantationen auf, jedoch ohne Todesfall oder bleibende Morbidität. Die meisten Patienten profitierten von dem Eingriff. Während der Implantation müssen externe Defibrillation und Stimulation verfügbar sein. Eine anteriore CS-Elektrodenposition sollte vermieden werden.

Dr. M. Azizi ()) · S. Behrens · H. Nägele Krankenhaus Reinbek St. Adolfstift Medical Clinic Hamburger Str. 41 21465 Reinbek, Germany M. A. Castel Hospital Son Llatzer Palma de Mallorca W. Rödiger Cardiology Center Hamburg

" Schlüsselwörter Kardiale Resynchronisationstherapie – biventrikuläre Stimulation – Herzinsuffizienz – Implantation – Komplikationen " Summary Introduction Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new method for the therapy of congestive heart failure (CHF). Because the intervention is more complex than regular pacemaker implantations, information on the feasibility and side effects of this method are of interest. Methods From 1999 to June 2005, CRT implantations were attempted in 244 patients (pts;

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mean age 64 ± 12 years, range 14–90 years), 82% were male, 44% had coronary artery disease, 29% were in atrial fibrillation, 71 had preexisting pacemakers. Results In 97% of the pts the intervention was successful (27% of the systems with defibrillation capabilities). In 285 interventions, 255 CS leads were positioned according to CS vein anatomy in 130 posterolateral, 97 anterolateral and 28 anterior side branches (16 patients received 2 CS leads). Over-the-wire leads were used in 88%, 71% were additionally preshaped. We observed no mortality but 37 complications (12.5%): CS dissection in 9, CS perforation in 1, ventricular fibrillation in 4, asystole in 5, pulmonary edema in 1, pneumothorax in 2, need for early CS lead revision in 19 (dislodgement n = 7, phrenic nerve stimulation n = 12) and infection with explantation in 2 cases. An improvement in NYHA functional class was found in 88% of pts (only 55% if anterior lead position). Conclusion Perioperative complications during CS lead implantation occur in 10–15% of cases. Most patients responded well to CRT. Patients should be informed about the possible need for a reoperation. During implantation, immediate defibrillation and stimulation capabilities must be available. Anterior lead positions should be avoided. " Key words Cardiac resynchronization therapy – biventricular pacing – heart failure – implantation – complications

Introduction Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new stimulation method for the therapy of patients with congestive heart failure (CHF) and inter- and intraventricular conduction delay. Its ability to augment cardiac hemodynamics is now well characterized [14]. Recently it was even been shown that CRT improves prognosis in selected patients [2, 4]. With regard to non-pharmacologic therapy in heart failure, these were the first positive randomized survival data besides beneficial effects of prophylactic defibrillator therapy [10]. Logically more patients with this indication will be identified and more centers are adopting the implantation method. However the intervention is more complex than regular pacemaker implantation and therefore information on the feasibility and possible complications in daily practice outside clinical trials are of interest. CRT implantation has been performed in our group since 1999 [13]; thus

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a large number of interventions could be analyzed for these questions.

Methods We retrospectively analyzed data of patient files and operative protocols of all CRT system implantations from January 1999 to June 2005. Continuous long-term follow-up of patients was available with the exception of 12 patients who were lost to follow-up out of a total 244 patients. We documented clinical characteristics, cardiac events including death and focused on peri-operative complications. From January 1999–June 2005, 255 transvenous coronary sinus leads were implanted in 244 CHF patients (mean age 64 ± 12 years, range 14–90). The indication for CRT system implantation were made according to guidelines of NASPE [9] and the German Society of Cardiology [12]. Procedures were performed under local anesthesia and mild general sedation with repetitive

doses of midazolame. As access, the left side was chosen in 87% of cases. In the case of submuscular pockets and/or ICD DFT testing intravenous narcosis was induced by the injection of disoprivane. We used standard CE marked products from five different companies. The higher number of systems and leads than patients can be accounted for by exchange and revision procedures. N = 190 non-ICD (pacing only) systems were implanted: TRIPLOS DR (n = 1), STRATOS (n = 11), Biotronik, Berlin, Germany; CHORUS MSP (n = 2), TALENT MSP (n = 1), Ela medical, La Boursidiere, France; CONTAK TR/TR2 (n = 50), Guidant Corp., Indianapolis, IN, USA; INSYNC 8040 (n = 1), INSYNC III (n = 118), Medtronic Inc., Minneapolis, MN, USA; FRONTIER (n = 5), St. Jude Medical Inc., St. Paul, MN, USA; VITATRON 8000 (n = 1), Vitatron, Arnhem, The Netherlands; N = 72 CRT-ICD systems were implanted: TUPOS (n = 1), KRONOS (n = 8): Biotronik, Berlin, Germany; RENEWAL (n = 2), Guidant Corp., Indianapolis, IN, USA; INSYNC ICD (n = 1), INSYNC MARQUIS (n = 26), SENTRY (n = 30), Medtronic Inc., Minneapolis, MN, USA; ATLAS (n = 2), EPIC (n = 2): St. Jude Medical Inc., St. Paul, MN, USA; Following coronary sinus leads were implanted: COROX OTW (n = 10), Biotronik, Berlin, Germany; SITUS (n = 2), Ela medical, La Boursidiere, France;

Experience with coronary sinus lead implantations for cardiac resynchronization therapy in 244 patients

EASYTRAK 4513 (n = 23), EASYTRAK 4512 (n = 28), EASYTRAK II (n = 1), Guidant Corp., Indianapolis, IN, USA; ATTAIN 4193 (n = 122), ATTAIN 4194 (n = 40), Medtronic Inc., Minneapolis, MN, USA; AESCULA (n = 7), St. Jude Medical Inc., St. Paul, MN, USA;

Table 1 Baseline characteristics of CRT patients (n = 244) from 1999–2005 Mean age Male Coronary artery disease NYHA II NYHA III NYHA IV Mean LVEF Atrial fibrillation Observation time

64 ± 12 (14–90) years 82% 44% 10% 68% 22% 24 ± 9% 29% at time of implant 1.7 ± 1.3 years

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Table 2 CRT procedures (n = 285) in 244 pts from 1999–2005 CRT-PM New Implantation CRT-SM Upgrade from RV-PM CRT-ICD New Implantation CRT-ICD Upgrade from RV-PM CRT-ICD Upgrade from CRT-PM CS lead revision Battery replacement Epicardial CS lead Explantation Miscellaneous

38% 19% 13% 7% 4% 10% 4% 2% 1% 2%

Lead technology was over-the-wire in 88%, 71% of the leads were preshaped AND over-the-wire. All interventions were performed by a single operator (HN). In every patient a retrograde coronary sinus angiography with a ballon catheter was performed aiming for coronary sinus sides branches.

n Statistical analysis Differences of data were checked for significance by means of Student’s t-test for non-matched pairs. Nonparametric data were checked for significance by Wilcoxon test. All data were expressed as mean ± standard deviation. Survival rate was calculated by Kaplan-Meier analysis and the log-rank test (Winstat 3.1, Kalmia Inc and SPSS for Windows 6.1).

Results Patients characteristics at entry (all patients with an implant attempt) are provided in Table 1. The cohort represents a typical heart failure population comparable to published studies. Types of procedures are described in Table 2. Overall a predominance of brady-CRT systems could be noted, but with an increase of CRT-D systems over time, reaching 50–60% of all implants in the last period (Fig. 1).

Fig. 1 Successful CRT implantations from 1999 to June 2005 (n = 255): CRT defibrillator vs CRT pacemaker systems

In total there were 285 interventions because some patients needed multiple operations. In detail there were 5 interventions in n = 1 pt, 4 interventions in n = 2 pts, 3 interventions in n = 6 pts, 2 interventions in n = 33. In 188 pts (77%) CRT could be established by a single intervention. 43 (16%) were implanted from the right subclavian vein, the others from the left side. Coronary sinus leads were positioned according to variable vein anatomy: 130 posterolateral (51%, including n = 5 in more posterior veins), 97 anterolateral (38%) and 28 anterior (11%). Mean signal in LV was 17 ± 10 mV, mean threshold in LV at 0.5 ms was 0.9 ± 0.8 V. The mean operation time was 110 min ± 35, mean fluoroscopy time was 15.8 ± 11 min and the mean volume of x-ray contrast

agent was 45 ± 30 ml. We had no success in implanting the system in 10 patients. Failure was due to coronary dissection with contrast media paravasat in n = 1 pt, due to ventricular fibrillation in n = 2 pts and due to inability to locate the ostium of the coronary sinus in n = 7 patients. Six patients of these 10 were succesfully implanted in a second operation (4 × transvenous, 2 × epicardial) giving an overall success rate of 98%. All early complications (37/in 285 procedures = 13%) are listed in Table 3. It has to be emphasized that there was no mortality during the perioperative phase in our series. Complications with a consequence of reoperation were early dislodgement of the CS lead in 13/285 cases (4%). Further problems were CV dissections, i.e., visible contrast

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Table 3 Perioperative complications related to implantation of a resynchronization device according to the literature and own data (mean incidence approximately 15%) Complication (mean rate)

N

%

Reference

CV dissection mean 2.88%

3/154 10/409 23/567 9/285

2 2.5 4 3

Hansky et al. 2001 [11] Cleland et al. 2005 [4] Abraham et al. 2002 [1] This Study

CV perforation mean 1.2%

12/228 1/285

2 0.3

Abraham et al. 2002 [1] This Study

Hemopericardium requiring pericardiocentesis mean 0.25%

3/228 0/285

0.5 0

Abraham et al. 2002 [1] This Study

Pneumothorax mean 1.1%

6/409 2/285

1.5 0.6

Cleland et al. 2005 [4] This Study

Ventricular fibrillation requiring cardioversion mean 1.8%

3/154 4/285

2 1.3

Hansky et al. 2001 [11] This Study

Asystole requiring pacing mean 1.75%

5/285

1.7

This Study

Pulmonary edema mean 0.3%

1/95

0.3

This Study

Thrombus formation mean 1.5%

5/154 0/285

3 0

Hansky et al. 2001 [11] This Study

Intraoperative death mean 0.3%

1/409 8/1212 0/285

0.2 0.6 0

Cleland et al. 2005 [4] Bristow 2004 [2] This Study

Early CS-lead revision mean 5.8%

24/409 30/528 13/285

6 6 4

Cleland et al. 2005 [4] Abraham et al. 2002 [1] This Study

Infection requiring explantation mean 1.7

11/409 7/528 2/285

3 1.3 0.6

Cleland et al. 2005 [4] Abraham et al. 2002 [1] This Study

rapidly by defibrillation or pacing. Rare events were perforation of the CS in one case: free flotation of the lead in the pericardial space could be observed. The lead was pulled back and placed in a CS side branch without development of a hemopericardium. Early infections were observed in two cases, both needed system explantation and new implantation a few weeks later. Chronically we observed a loss of function in some of the CS leads over time up to 18 month after implantation (Fig. 2). After two years, long-term functioning could be demonstrated at a rate of 80% of initial implantations. Late CS lead re-operations were necessary in n = 13 cases. Reasons of late reoperations were phrenic nerve stimulation in n = 2 and chronic exit block in n = 10 cases. Of the successfully implanted patients, 205/239 (86%) showed an improvement of at least 1 NYHA functional class during follow-up (1.7 ± 1.3 years) and could be classified as responders. When CS lead position was taken into account only 16 (58%) pts with anterior leads were responders in contrast to 87/97 (90%) responders with anterolateral and 118/130 (91%) responders with posterolateral CS leads. The number of responders differed significantly between the anterior and the other groups (p < 0.01).

Discussion

Fig. 2 CS lead function over time (all attempts)

media paravasate beside the coronary vein system. However consequences of this finding only were limited to a reduced visualization of side branches, but no hematoma

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or pericardial effusions. Rhythm disturbances were also noted including ventricular tachyarrhythmias (4/285) or asystole (5/285). Both problems could be managed

Coronary sinus lead implantation is a complex procedure with several limitations and hazards. During implantation, a resynchronization device – unlike conventional pacemakers – requires the insertion of an additional pacing lead into the coronary sinus, which is advanced into a cardiac vein to allow pacing of the left ventricle.

Experience with coronary sinus lead implantations for cardiac resynchronization therapy in 244 patients

First the implantation success rate is reduced compared to conventional procedures. In our series the overall success rate was 97%. This is similar or even better than experience in the CARE-HF trial (95% success – rate, [4]) and the MUSTIC, MIRACLE and COMPANION trials (92, 92 and 90% success – rate, respectively [1–3]). Reasons for no success were mostly due to an inability to locate the coronary sinus ostium. Coronary sinus implantation was time consuming, in our series the mean operation time was 110 ± 35 min, shorter than in the MIRACLE trial (mean operation time 162 min). And as expected the fluoroscopy times were longer than in conventional implantations (in our series 15.8 ± 11 min). Secondly we and others observed several acute intra- and perioperative complications. Fortunately, the worst case (intraoperative death) did not occur in our series. Others also reported a very low operative mortality rate of 0% [1] or 0.25%–1/409 pts [4], respectively. It is of interest that the incidence of other than lethal perioperative complications of CRT implantations were only rarely described. A review of the literature in context to our data showed that these events can amount to about 10–15% (Table 3). Major complications with consequences were CS lead dislodgements (due to a non-availability of active CS lead fixation) or intolerable phrenic nerve stimulation. According to this it is of interest that non-tolerable phrenic nerve stimulation sometimes occurred despite an intense intraoperative mapping and high voltage stimulation. It has to be em-

phasized that testing in a flat position did not rule out later phrenic nerve stimulation in other body positions (right or left side). There may also be a difference between pacemaker and ICD implantations; however, in our series there was no significant difference between these groups. On the other hand, 85% of all patients receiving a resynchronization implant have a totally uneventful clinical course despite their severe underlying disease. Comparing the rate of complications and side effects of CS procedures to conventional implantations of DDD pacemakers and defibrillators, it is of note that the exact incidence of the latter is rarely reported in the recent literature [6, 7]. The Danish pacemaker register is a source for comparison of conventional procedures and CS implantations [5]. In the year 2003, a total number of 2582 new conventional pacemaker implantations were performed in Denmark. Following complication rates were noted: atrial lead revision: 1.6% (in our series 0%), RV-lead revision 2% (in our series 0.5%), pneumothorax 0.9%, hematoma 0.1%, infection 0.7%. Reoperations of CRT patients in the long-term were also necessary, mostly due to chronic loss of LV capture (Fig. 2). This may be due to radiologically undetectable microdislocations, scar formation or another yet undefined mechanism. Long-term stability seems to be inferior to conventional leads where a ten year functioning rate of about 98% could be achieved [8]. One study for example showed that leads implanted after January 1993 showed a reliability after 10 years

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of 97.0% for unipolar and 97.8% for bipolar leads [5]. In contrast, CS lead function is superior to ICD leads (cumulative failure probability for ICD leads 37%, confidence interval, 24 to 54% at 68.6 months [6]). The main purpose of this study is to be aware of the more complex nature of CRT procedures and that patients have to be informed about possible complications and the need of reoperations on the basis of available data. However, when taking into account that a significant symptomatic improvement can be achieved by the procedure and even the prognosis can be improved [2, 4], it is justified to recommend the implantation according to guidelines [9, 12]. In addition, several complications can be minimized by precautions such as placing of defibrillation pads on the patients, first implantation of the RV lead to ensure secure stimulation back-up, cannulation of the CS with soft wires and to perform breathing maneuvers under maximum output to uncover otherwise undetectable phrenic nerve stimulation. Anterior CS lead positions should be avoided because responder rates were significantly lower in this group. Apart from these aspects, also the considerable x-ray exposition of the implanter and the personnel should be taken into account and the longer occupancy of the implantation theater in contrast to conventional procedures. Ideally these interventions should be performed in centers with separate rooms without the pressure of coronary interventions or other implantations, comparably to electrophysiological studies.

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