Limited thoracotomy as a second choice alternative to transvenous implant for cardiac resynchronisation therapy delivery

Andrea Puglisia,*, Maurizio Lunatib, Antonino G.M Marulloc, Stefano Bianchia, Mariano Fecciad, Fabrizio Sgrecciaa, Ilaria Vicinie, Sergio Valsecchie, Francesco Musumecid and Ettore Vitalib

a Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy
b Niguarda Ca'Granda Hospital, Milan, Italy
c "LaSapienza" University, Rome, Italy
d S. Camillo Hospital, Rome, Italy
e Medtronic Italy, Milan, Italy

* Corresponding author. Tel.: +39066837208; fax: +390668300746
E-mail address: puglisiandrea{at}hotmail.com

Received 24 November 2003; revised 18 March 2004; accepted 2 April 2004

Abstract

Aims Left ventricular (LV) pacing via transvenous implantation has an overall success rate ranging from 88% to 92%. The aim of this study was to assess whether LV pacing via limited thoracotomy would be feasible and safe when used on a routine basis for those cases in which standard transvenous procedures proved to be ineffective or unsatisfactory.

Methods and results We enrolled 33 patients (8 females, 65±10 years) who experienced a transvenous implantation failure. All patients underwent a limited thoracotomy and an epicardial lead was implanted. The procedure time was 51±28 min. No surgical or post-operative complications occurred and optimal lateral position was achieved for all patients. In the 12 months follow-up period, 5 patients died from refractory heart failure, the remaining patients did not experience complications. At implant, the mean pacing threshold was 1.3±0.7 V, bi-ventricular pacing impedance was 476±201 {Omega} and R-wave amplitude was 15.0±6.1 mV. No significant differences were found in any of the electrical parameters between baseline and follow-up. Significant improvement was observed in functional and echocardiographic parameters.

Conclusion Our results suggest that a combined approach to cardiac resynchronisation therapy delivery, including a transvenous attempt followed by a back up thoracotomic procedure, could potentially guarantee the success.

Key Words: Thoracotomy • Resynchronisation therapy • Heart failure

Introduction

Cardiac resynchronisation therapy (CRT) is a well accepted option to treat a significant subset of heart failure (HF) patients. It was shown to provide significant benefits in a selected population in terms of quality of life, functional status1,2 and in terms of hospitalisation and mortality.3,4

CRT is usually delivered by means of a triple chamber pulse generator (a pacemaker (PM) or an implantable cardioverter defibrillator (ICD)). The right atrial (RA) and the right ventricular (RV) leads are usually implanted with standard PM implantation procedures. The left ventricular (LV) lead is implanted with a transvenous approach in the majority of the cases. In the transvenous approach, the lead is advanced through the Coronary Sinus (CS) ostium into the vessel, then a cardiac vein is cannulated and the lead is placed in a position inside the vein, resulting in acceptable electrical performances. Recent studies have highlighted the importance of the proper vein selection in order to achieve optimal haemodynamic results.5,6

Unfortunately, LV pacing via transvenous procedure has an overall success rate ranging from 88% to 92% according to different experiences.1,2 Moreover, limited availability of suitable CS tributary veins often increases difficulties in achieving the optimal haemodynamic response. Endocardial procedures are often considerably long and X-ray exposure is in some case unacceptable, even in well-trained centres. Also, post-implant lead displacement or late LV threshold increases still represent an issue, despite substantial progresses made in lead technology and implantation procedures.2

Early experiences of CRT used a thoracotomic approach to implant the LV lead,7,8 but this technique was abandoned due to the frequent serious complications and the invasiveness of the procedure.9,10 Alternative approaches to CRT were not consistently studied, although some experiences have been recently reported.11–14

The purpose of this study was to assess whether epicardial LV pacing, via limited thoracotomy, would be feasible and safe for CRT delivery, when used on a routine basis for those cases in which standard transvenous procedures proved to be ineffective or unsatisfactory.

Methods

Patient selection
Patients with chronic HF and an indication for CRT (left ventricular end diastolic diameter (LVEDD)>=55 mm, left ventricular ejection fraction (LVEF)<=35%, New York Heart Association (NYHA) class III or IV and an inter or intraventricular electrical conduction delay leading to a mechanical asynchrony)15 were candidates for the study. We consecutively enrolled all the candidates who went through a standard transvenous implantation procedure that failed. A transvenous procedure was considered a failure in case of unsuccessful implantation of the lead in a lateral or a postero-lateral cardiac vein, with pacing thresholds less then 3.0 V at 0.5 ms and absence of phrenic nerve stimulation, after at least 2 h of direct attempts. We also enrolled patients that experienced a LV lead dislodgement or a LV pacing threshold increase that made CRT delivery impossible. We did not exclude a priori patients in advanced NYHA class or patients that underwent previous cardiac surgery procedures. Informed Consent was obtained from all patients.

Operative course and follow-up
All the patients received the CRT stimulator in the course of the transvenous procedure. RV and RA transvenous leads were positioned in standard pacing sites and the devices were implanted in the pre-pectoral left upper chest area. No atrial leads were implanted in chronic atrial fibrillation (AF) patients. In case of implant failure, the LV lead connector was temporarily capped in order to allow future LV epicardial lead connection.

The thoracotomic procedure was performed after a time period ranging, depending on patient conditions and cardiac surgery operating room schedule, from 3 days to 1 week, after the failed transvenous procedure, or the detection of the system malfunction for those patients who experienced lead dislodgement or pacing threshold increase during follow-up. Under general anaesthesia and with single right-lung ventilation using a double-lumen endotracheal tube, all the patients underwent a left antero-lateral thoracotomy through the fourth intercostal space. The pericardium was opened longitudinally 1 cm anteriorly to the phrenic nerve and suspended, in order to expose the LV lateral wall. The target area for LV lead implant was the obtuse margin of the left ventricle according to previous experiences.5

A steroid-eluting suture fixation epicardial lead (Medtronic CapSure© EPI Model 4965-50, Medtronic Inc., MN, USA) was used in order to obtain good electrical performances16 with a minimally traumatic fixation mechanism. Once a site with satisfactory pacing threshold was identified, the electrode was sewn with 5-0 non-absorbable suture (Fig. 1). The lead was only sutured in the selected position when electrical parameters were within the following ranges: impedance 200 {Omega} and 2000 {Omega}, sensing (peak-to-peak amplitude of R-wave) greater than 5 mV and pacing threshold measured at 0.5 ms less than 2.0 V.



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Fig. 1 Upper panel: The lead is positioned to perform the pacing threshold test. Bottom panel: The lead is sewed with 5-0 non-absorbable suture. (1) Obtuse marginal branch of the circumflex coronary artery. (2) Opened and suspended pericardium. (3) Left atrial appendage.

 
Once the electrode was sewn in the selected position, the rib retractor was temporarily removed and 10 V stimulation delivered in order to assess the presence of phrenic nerve stimulation in the final anatomical conditions.

The LV electrode was tunnelled and connected to the PM or ICD, in the pocket previously created in the left pectoral area. As soon as the lead was connected, CRT was delivered by means of a 70 bpm DDD bi-ventricular stimulation with a paced atrio-ventricular delay of 120 ms and a sensed atrio-ventricular delay of 100 ms. At the end of procedure a thoracic drain was inserted and removed after 24 h. Prior to hospital discharge, echocardiography-guided atrio-ventricular delay optimisation was accomplished on a patient by patient basis.17 For patients in chronic AF, a 70 bpm VVI bi-ventricular pacing was provided.

Clinical status was evaluated before implantation and after 3, 6, 9 and 12 months. Each visit included electrocardiogram recording, NYHA classification, echocardiographic evaluation, electrical measurements and pharmacological therapy optimisation.

QRS durations were automatically measured as the maximum of leads II, V1 and V6; LVEDD and LV end systolic diameter (LVESD) were determined using M-mode echocardiography, under two-dimensional guidance in the parasternal long-axis view. The severity of mitral regurgitation (MR) was classified as mild or grade 1, moderate or grade 2, severe or grade 3 MR, respectively.

Statistical analysis
The analyses of the clinical and echocardiographic characteristics were performed with a `Last Observation Carried Forward' approach.18

Summary data are expressed as percentages of patients, means±SD for normally distributed variables, and medians and ranges for non-normally distributed variables. The baseline characteristics of the two groups (transvenous and thoracotomic) were compared using an unpaired test for Gaussian variables and the Mann–Whitney U non-parametric test for non-Gaussian variables. Differences in proportions were compared by a analysis or Exact Fisher's Test, as appropriate. To assess intra-group changes in measurements from baseline to follow-up, paired the -test and Wilcoxon non-parametric tests were used for normally and non-normally distributed variables, respectively.

The mortality was summarised by construction of Kaplan–Meier curves and the distributions of the groups were compared by a log-rank test. For all tests, two-sided comparisons were performed and a value 0.05 was used to assess statistical significance. All statistical analyses were performed using SPSS software.

Results

Between April 1999 and May 2002 a total of 315 patients underwent CRT device implantation. In 293 patients the transvenous procedure was successful. In the remaining 22 patients the LV lead could not be implanted due to a failure to catheterise CS (10 patients), excessively high pacing threshold (7 patients) and unstable lead position (5 patients). The mean transvenous procedure time was 187±59 min with a fluoroscopy time of 31±18 min.

During the first two months of follow-up, a LV lead dislodgement was detected in 8 cases and a rise in pacing threshold occurred in 3 patients, leading to CRT discontinuation and inducing exacerbation of HF symptoms in all cases. The rate of failures significantly decreased during the course of the study, as did the procedure and the fluoroscopy time (Fig. 2).



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Fig. 2 Trend of failure rate, procedure and fluoroscopy time during the study in our population.

 
In Table 1, the baseline characteristics are reported for the overall population and for the patients undergoing transvenous and thoracotomic implant. Therefore, 33 patients (8 females, mean age 65±10 years) were addressed to limited thoracotomic approach. At baseline, 27 patients were in NYHA class III, with a mean LVEF of 26±4% and a QRS duration of 180±27 ms. Three patients were in chronic AF while the others were in normal sinus rhythm. The HF aetiology was idiopathic in 23 patients, ischaemic in 8 patients, without a present indication for revascularisation procedures and valvular in 2 patients. Ten patients had an ACC/AHA/NASPE indication15 for ICD therapy, with 4 having a primary prevention indication.


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Table 1 Baseline clinical characteristics and pharmacological treatment

 
At the enrolment, pharmacological therapy included diuretics, angiotensin-converting-enzyme inhibitor or angiotensin-receptor blockers, digitalis and a ß-blocker. No therapy optimisation was attempted before implantation.

The patients undergoing thoracotomic procedure did not differ from all the other patients, except for a larger proportion of idiopathic HF and a more frequent use of digoxin (Table 1).

Successful deployment of the epicardial electrode was accomplished in all the patients. Epicardial procedure time (skin-to-skin) was 51±28 min. No surgical complications occurred and optimal lateral position, close to the obtuse marginal branch of the circumflex coronary artery, was achieved for all patients. Patients with previous cardiac surgery required a longer procedure for a careful dissection of pericardial adhesions, but no additional complications took place.

The mean pacing threshold of the epicardial lead was 1.3±0.7 V at 0.5 ms, bi-ventricular pacing impedance measured at an output voltage of 5 V was 476±201 {Omega} and the peak to peak LV R-wave amplitude was 15.0±6.1 mV. These values did not significantly differ from those obtained with transvenous leads (Table 2).


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Table 2 Clinical, echocardiographic and electrical parameters evaluated between transvenous and thoracotomic groups

 
In the 12-month follow-up period 5 patients died of refractory HF, 4 of them were in NYHA class IV at the time of implant. One patient, in NYHA class IV at baseline, died 10 days after the implant, so the possibility that the surgical procedure in itself could have contributed to the cardiac decompensation is not excluded. All other deaths occurred after more than 2 months since the procedure. In Fig. 3 the cumulative survival curve of the study population is reported and compared to the one of the patients implanted via transvenous procedure.



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Fig. 3 Cumulative survival curves of the patients implanted via thoracotomic and transvenous approaches.

 
No other complications occurred in the pre-discharge period and the median hospital stay after the thoracotomic procedure was 5 days (range 2–14). The remaining patients did not experience complications related to the CRT system.

The 28 patients, which completed the 12-month follow-up period, experienced a significant reduction of hospitalisations for HF: from 1 (range 0–3) with a total of 43 during the 12 months preceding the implant, to 0 (range 0–3) with a total of 8 during the follow-up period (Table 2).

Electrical parameters remained relatively stable at 12 months, when a mean threshold value of 1.3±0.6 V was obtained, the impedance was 480±203 {Omega} and the amplitude of R-wave was 13.3±5.0 mV. No significant differences were found in any of the electrical parameters, with respect to baseline or to the values obtained in the transvenous group at follow-up (Table 2).

The haemodynamic benefits of CRT were apparent in our patient population. Mean LVEF increased (), in association with a reduction of LVEDD () and LVESD (); MR severity showed a non-significant reduction. QRS width decreased () and substantial functional benefits were achieved: NYHA class value significantly improved (). Similar results were also obtained in the population of patients implanted by the classical transvenous procedure (Table 2).

Discussion

The first permanent CRT implantations used LV epicardial leads placed by thoracotomy under general anaesthesia.7,8 Unfortunately, several peri-operative and post-operative complications were reported with this approach, including major arrhythmic events and mortality. Furthermore, LV pacing thresholds at implant using screw-in catheters were usually high, resulting in secondary high pacing thresholds or loss of capture.9,10 These major limitations led to a shift toward a transvenous approach. In such a case LV is paced from one of the tributaries of the coronary veins over the epicardial surface of the LV. The technique, despite the continuous progress in the development of new implantation tools is long, requires a high fluoroscopic exposure and does not guarantee success in all cases.

In the InSync Italian Registry,19 Ricci and co-workers observed an implant success rate of 89% with a mean implant duration of 2.63±1.13 h (mean fluoroscopy time: 37.32±27.86 min), and an overall dislodgement rate of 7.4%. Moreover some patients experienced phrenic nerve stimulation (2.1%) and far field P-wave over-sensing by LV lead (1.6%), sometimes requiring the re-positioning of the lead. In the EASYTRAK Pre-CE-Mark Clinical Investigation, the success rate was 82%, whereas in the European CONTAK Registry a 83% success rate was reported with a 2% complication rate.20 In the Mustic trial the implant success rate was 92%. At the end of the 6-month study period, the percentage of patients with a functional lead in LV was reduced to 88% due to lead dislodgement.1 In the final results of the InSync Study the overall implant success rate was 88%, and the LV lead dislodgement occurred in 11% of patients requiring repositioning or replacement. The procedure duration was 138±58 min with 57±55 min spent for the LV lead placement.21 Finally in the MIRACLE study, about 8% of the 571 participating patients were unable to receive bi-ventricular pacing due to technical failure. In this study, dissection or perforation of the CS or cardiac vein occurred in about 6% of patients and 1.2% of patients experienced serious complications (death in 2 cases). Moreover, lead dislodgement during long-term pacing occurred in 6% of patients requiring re-positioning. The median duration of the implant procedure was 2.7 h (range 0.9–7.3).2 Recent reports,4 and our own experience confirm that a significant rate of failure still persists, in spite of the learning process and the progress in lead technology.

Transvenous implantation procedure proved to be definitively feasible, but highly dependent on the implanter experience, unpredictably long and not free from occasionally severe complications.

Published studies demonstrated that haemodynamic and functional benefits of CRT are highly dependent on the implantation site. Butter et al.5 who compared systolic performance produced by LV free wall and anterior wall stimulation and confirmed this conclusion. Ansalone et al.6 more recently showed that the existence of a subset of patients who are not responders to the therapy might be explained at least partially with a sub-optimal LV lead positioning.

Nevertheless, looking at the published studies, the transvenous LV leads were implanted in widely differing positions, mainly because of anatomical constraints, and the final lead position was not always optimal. Among the 189 LV leads successfully implanted in the Insync Italian Registry, only 71% were in the lateral or postero-lateral vein,19 the same percentage reported in the final results of InSync Study.21 In the Easytrack pre-CE Mark clinical investigation, 36% of the leads were in an anterior position and only 50% in the lateral vein, sometimes in an apical site.20 Finally, Cazeau et al.1 reported that a lateral position was reached in 80% of the patients implanted in Mustic trial. This may represent a second limitation of transvenous approach, even if the influence of stimulation site on the long-term outcome of bi-ventricular pacing is not proven. The thoracotomic approach could permit an easier selection of appropriate pacing site, overcoming all possible limitations caused by the anatomy of coronary veins.

Different authors have suggested that the pacing site should be individualised to maximise the effects of CRT, and proposed to locate the most delayed wall6 or to pre-activate the myocardium segments exhibiting delayed longitudinal contraction by individual tailoring of the inter-ventricular delay.22 However, due to the small number of enrolled patients6,22 and the retrospective study design,6 these observations cannot be considered conclusive. Furthermore, considering that neither the QRS narrowing,23 nor the acute haemodynamic response to CRT24 showed to predicted the improvement of both symptoms status and ventricular remodelling, we preferred to standardise the pacing site, thus minimising the procedure time.

As we showed with our 12 months observation, with limited thoracotomic approach, the LV free wall can be reached and paced without risk of dislodgement or loss of capture. Although this approach is more invasive, we did not observe any surgery-related or peri-operative complications. This is at least partially due to the less aggressive nature of suture fixation leads as compared to standard epicardial screw-in leads.

The excessive pacing threshold and high incidence of exit block with conventional epicardial leads presumably arise from combination of epicardial fibrosis, scar formation and/or pericardial adhesions after surgery. The addition of dexamethasone eluting to myocardial fixation leads reduced the adverse events reported in previous series.16 Procedure duration is favourably low, with a decisive advantage on X-ray exposure; furthermore, this approach allows the selection of site to avoid inadequate areas (ischaemic or necrotic tissues) or phrenic nerve stimulation.

Finally, our patients presented long-term benefits, comparable to patients implanted with a classical transvenous approach, in terms of outcome and clinical improvement.

Limitations

The aim of this study was to assess whether limited thoracotomic approach for LV stimulation would be safe and feasible in the case of failed transvenous procedure. To evaluate this treatment strategy, a proper control group would consist of patients in whom transvenous approach failed and no further implant procedures were attempted. However, the growing evidence of CRT efficacy,1–4 and current recommendations for its use,25 persuaded us to perform this second, even if more aggressive, attempt to provide CRT in all candidate patients, comparing the results with patients successfully implanted via the transvenous approach.

Ultimately, the drug therapy administered at baseline was not optimal for patients in NYHA class III and IV, especially for the low rates of ß-blockers and angiotensin-converting-enzyme inhibitors prescription. This observation is in line with the results of previous Italian studies,26,27 and shows the slow adoption of guidelines for management of HF into normal clinical practice. Nevertheless, pharmacological treatments of the groups did not present differences, which could have affected our results.

Conclusions

Thoracotomic implant permits the avoidance of additional X-ray exposure, allows choice of LV catheter implantation site and tends to obtain low pacing threshold with no dislodgements. Such benefits could counterbalance the need for general anaesthesia and a more invasive procedure.

Prospective randomised studies are required to define the exact indications for the thoracotomic lead implantation as a primary approach, not only investigating safety and outcome aspects, but also evaluating the cost with respect to the established technique. Meanwhile, our encouraging results suggest that a combined approach to CRT delivery, including a transvenous attempt followed by a back-up thoracotomic procedure, could virtually guarantee overall success without increasing patients' risks.

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