Go for the right left ventricular lead position at initial implantation of a cardiac resynchronization therapy device

Cardiac resynchronization therapy (CRT) with biventricular pacing has substantially altered the clinical course of patients with heart failure (HF), reduced left ventricular (LV) ejection fraction (EF), and prolonged QRS duration. Multiple randomized controlled trials (RCTs) have documented that CRT significantly reduces HF hospitalization, cardiac morbidity, and mortality.1Glikson M. Nielsen J.C. Kronborg M.B. et al.ESC Scientific Document Group2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy.Eur Heart J. 2021; 42: 3427-3520Crossref PubMed Scopus (328) Google Scholar However, approximately one-third of patients derive no measurable clinical or echocardiographic benefit from CRT,2Abraham W.T. Fisher W.G. Smith A.L. et al.Cardiac resynchronization in chronic heart failure.N Engl J Med. 2002; 346: 1845-1853Crossref PubMed Scopus (4179) Google Scholar,3Cleland J.G. Daubert J.C. Erdmann E. et al.The effect of cardiac resynchronization on morbidity and mortality in heart failure.N Engl J Med. 2005; 352: 1539-1549Crossref PubMed Scopus (5181) Google Scholar and such patients often are classified as so-called “nonresponders.” In this issue of Heart Rhythm O2, Borgquist et al4Borgquist R. Mörtsell D. Chaudhry U. Brandt J. Farouq M. Wang L. Repositioning and optimization of left ventricular lead position in nonresponders to cardiac resynchronization therapy is associated with improved ejection fraction, lower NT-proBNP values, and fewer heart failure symptoms.Heart Rhythm O2. 2022; 3: 457-463Abstract Full Text Full Text PDF Scopus (1) Google Scholar report a nice case series of 25 CRT “nonresponders,” presumably due to a suboptimal LV lead position, who clinically improved after the LV lead was repositioned in another branch of the coronary sinus (CS). These data are of clinical interest because they indicate that a thorough review of LV lead position and CS venography obtained during the initial CRT implantation should be performed in patients who do not benefit from CRT. If the LV lead position is judged to be suboptimal and another CS branch is available, reintervention should be considered. Although this strategy is often discussed in the literature and in daily practice, not much data exist supporting its use. The current study was retrospective, and the cohort consisted of patients with a CRT device referred to a tertiary center between 2015 and 2020 for LV lead repositioning because of CRT “nonresponse” and a suboptimal, anterior, inferior, or apical LV lead position.4Borgquist R. Mörtsell D. Chaudhry U. Brandt J. Farouq M. Wang L. Repositioning and optimization of left ventricular lead position in nonresponders to cardiac resynchronization therapy is associated with improved ejection fraction, lower NT-proBNP values, and fewer heart failure symptoms.Heart Rhythm O2. 2022; 3: 457-463Abstract Full Text Full Text PDF Scopus (1) Google Scholar How large a proportion of all “nonresponders” was referred for LV lead repositioning or how they were selected is unclear, particularly whether fluoroscopy and review of CS venography from the initial implantation procedure were performed before referral. Identifying alternative and presumably more optimal potential CS target branches on CS venography before deciding for reintervention may help to explain the large success rate with repositioning reported in the current study. In addition, how many of the patients were treated with quadripolar LV leads at their initial implantation was not reported. Using quadripolar LV leads results in more programming options for LV pacing, which may enable noninvasive solutions for initially nonoptimal pacing sites in a proportion of these patients. Defining so-called “nonresponse” to CRT has varied widely, with poor agreement among definitions.5Fornwalt B.K. Sprague W.W. BeDell P. et al.Agreement is poor among current criteria used to define response to cardiac resynchronization therapy.Circulation. 2010; 121: 1985-1991Crossref PubMed Scopus (242) Google Scholar In the current study, a combined score including subjective improvement or worsening/unchanged LV EF and QRS duration as well as N-terminal pro–brain natriuretic peptide level was used. Even though it may be difficult to investigate subjective parameters unblinded and without a control group, the mean improvement after repositioning is supported by the mean improvement in the remaining objective parameters. However, whether all patients ultimately scored better remains unclear, and whether this arbitrary categorization into “responders” and “nonresponders” is too simple and might underestimate the true benefit of CRT requires further discussion. Severe HF is a progressive disease state in many patients in whom freedom from progression and clinical worsening may be the beneficial effect that can be obtained from CRT. Such patients often are falsely counted as nonresponders in the binary classification between “responders” and “nonresponders.” Hence, the effect of CRT in any individual instead should be seen as continuous disease modification.6Mullens W. Auricchio A. Martens P. et al.Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care: a joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology.Eur H Heart Fail. 2020; 22: 2349-2369Crossref PubMed Scopus (62) Google Scholar A series of smaller RCTs has investigated the potential benefit of individualized strategies targeting the LV lead toward the latest activated segment. Different modalities and methods were used, and the results were divergent. However, RCTs have not documented better results from placing the LV lead in any specific position. Placing the LV lead in an inferior, anterior, or apical position has been found to be associated with less favorable outcomes in observational studies.7Kronborg M.B. Johansen J.B. Riahi S. et al.An anterior left ventricular lead position is associated with increased mortality and non-response in cardiac resynchronization therapy.Int J Cardiol. 2016; 222: 157-162Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 8Thébault C. Donal E. Meunier C. et al.Sites of left and right ventricular lead implantation and response to cardiac resynchronization therapy observations from the REVERSE trial.Eur Heart J. 2012; 33: 2662-2671Crossref PubMed Scopus (140) Google Scholar, 9Singh J.P. Klein H.U. Huang D.T. et al.Left ventricular lead position and clinical outcome in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial.Circulation. 2011; 123: 1159-1166Crossref PubMed Scopus (443) Google Scholar These LV lead positions often are closer to the right ventricular (RV) lead position and unlikely to result in successful resynchronization. However, strong guidelines on LV lead placement are unlikely to be published given the lack of well-performed RCTs comparing different strategies for LV lead placement. Even though few complications occurred in this small cohort, it is well known that reinterventions for CRT systems are associated with a high risk of complications. Overall, the complication risk was 5%–15% for such interventions in a Danish national cohort study,10Kirkfeldt R.E. Johansen J.B. Nohr E.A. Jorgensen O.D. Nielsen J.C. Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark.Eur Heart J. 2014; 35: 1186-1194Crossref PubMed Scopus (503) Google Scholar and the risk of device-related infection resulting in system extraction was 3.4% after CRT reintervention in a large 2-center cohort.11Frausing M. Kronborg M.B. Johansen J.B. Nielsen J.C. Avoiding implant complications in cardiac implantable electronic devices: what works?.Europace. 2021; 23: 163-173Crossref PubMed Scopus (4) Google Scholar Therefore, reinterventions should be minimized by all means. It is reassuring that repositioning the LV lead in some patients who do not experience any clinical improvement after CRT implantation seems to reduce symptoms and measures of HF severity. However, the strongest signal from the current case series may be that implanters should be trained to implant the LV lead in a posterolateral and nonapical position, if possible, and with a relatively large anatomic distance to the RV lead. Implantation of a CRT device preferentially should be performed in large-volume centers with several CRT implanters, and inexperienced implanters should have access to immediate backup from experienced colleagues if posterolateral placement of the lead is not readily possible. As indicated by the current data, prolongation of the QRS complex after CRT may be an indicator that optimal resynchronization has not been obtained and that an alternative LV lead position should be considered. Implementing these strategies potentially may reduce the proportion of patients with suboptimal placed LV leads and reduce the number of reinterventions. Today, conduction system pacing is an option that should be considered for patients in whom CRT does not yield the expected benefit and in whom the LV lead is not positioned optimally,12Sharma P.S. Vijayaraman P. Conduction system pacing for cardiac resynchronisation.Arrhythm Electrophysiol Rev. 2021; 10: 51-58Crossref PubMed Google Scholar especially if a presumably more optimal LV lead position cannot be obtained because of difficult anatomy or technical obstacles. Dr Fyenbo is funded by Aarhus University, the Danish Heart Foundation (Grant Number R140-A9482- B2407), Health Research Foundation of Central Denmark Region (Grant Number R64-A3194-B1667), and Gangstedfonden.