Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial

Josep Brugada, Peter Paul Delnoy, Johannes Brachmann, Dwight Reynolds, Luigi Padeletti, Georg Noelker, Charan Kantipudi, José Manuel Rubin Lopez, Wolfgang Dichtl, Alberto Borri-Brunetto, Luc Verhees, Philippe Ritter, Jagmeet P Singh, RESPOND CRT Investigators, Josep Brugada, Peter Paul Delnoy, Johannes Brachmann, Dwight Reynolds, Luigi Padeletti, Georg Noelker, Charan Kantipudi, José Manuel Rubin Lopez, Wolfgang Dichtl, Alberto Borri-Brunetto, Luc Verhees, Philippe Ritter, Jagmeet P Singh, RESPOND CRT Investigators

Abstract

Aims: Although cardiac resynchronization therapy (CRT) is effective in patients with systolic heart failure (HF) and a wide QRS interval, a substantial proportion of patients remain non-responsive. The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular (AV) and interventricular (VV) timings. The RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in HF patients undergoing CRT.

Methods and results: RESPOND-CRT was a prospective, randomized, double-blinded, multicentre, non-inferiority trial. Patients were randomized (2:1, respectively) to receive weekly, automatic CRT optimization with SonR vs. an Echo-guided optimization of AV and VV timings. The primary efficacy endpoint was the rate of clinical responders (patients alive, without adjudicated HF-related events, with improvement in New York Heart Association class or quality of life), at 12 months. The study randomized 998 patients. Responder rates were 75.0% in the SonR arm and 70.4% in the Echo arm (mean difference, 4.6%; 95% CI, -1.4% to 10.6%; P < 0.001 for non-inferiority margin -10.0%) (Table 2). At an overall mean follow-up of 548 ± 190 days SonR was associated with a 35% risk reduction in HF hospitalization (hazard ratio, 0.65; 95% CI, 0.46-0.92; log-rank P = 0.01).

Conclusion: Automatic AV and VV optimization using the contractility sensor was safe and as effective as Echo-guided AV and VV optimization in increasing response to CRT.

Clinicaltrials.gov number: NCT01534234.

Keywords: AV and VV optimization; Adaptive CRT; CRT optimization; Cardiac contractility; HF hospitalization; RESPOND; SonR.

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
SonRtip lead.
Figure 2
Figure 2
Patient flow. GCP, Good Clinical Practice; mITT, modified intention to treat; RA, right atrial.
Figure 3
Figure 3
Freedom from all-cause mortality or heart failure hospitalization. CI, confidence interval; HR, hazard ratio.
Figure 4
Figure 4
Freedom from heart failure hospitalization. CI, confidence interval; HR, hazard ratio.
Figure 5
Figure 5
Subgroup analysis.

References

    1. Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bansch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM.. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the european society of cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013;34:2281–2329.
    1. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J.. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845–1853.
    1. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM.. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140–2150.
    1. Auricchio A, Prinzen FW.. Non-responders to cardiac resynchronization therapy. Circulation 2011;75:521–527.
    1. Mullens W, Grimm RA, Verga T, Dresing T, Starling RC, Wilkoff BL, Tang WH.. Insights from a cardiac resynchronization optimization clinic as part of a heart failure disease management program. J Am Coll Cardiol 2009;53:765–773.
    1. Houthuizen P, Bracke FA, van Gelder BM.. Atrioventricular and interventricular delay optimization in cardiac resynchronization therapy: Physiological principles and overview of available methods. Heart Fail Rev 2011;16:263–276.
    1. Gorcsan J III, Abraham T, Agler DA, Bax JJ, Derumeaux G, Grimm RA, Martin R, Steinberg JS, Sutton MS, Yu CM.. Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting–a report from the American society of echocardiography dyssynchrony writing group endorsed by the heart rhythm society. J Am Soc Echocardiogr 2008;21:191–213.
    1. Ritter P, Delnoy PP, Padeletti L, Lunati M, Naegele H, Borri-Brunetto A, Silvestre J.. A randomized pilot study of optimization of cardiac resynchronization therapy in sinus rhythm patients using a peak endocardial acceleration sensor vs. standard methods. Europace 2012;14:1324–1333.
    1. Rickards AF, Bombardini T, Corbucci G, Plicchi G.. An implantable intracardiac accelerometer for monitoring myocardial contractility. The multicenter PEA study group. Pacing Clin Electrophysiol 1996;19:2066–2071.
    1. Tassin A, Kobeissi A, Vitali L, Rouleau F, Ritter P, Gaggini G, Dupuis JM.. Relationship between amplitude and timing of heart sounds and endocardial acceleration. Pacing Clin Electrophysiol 2009;32 (Suppl 1):S101–S104.
    1. Brugada J, Brachmann J, Delnoy PP, Padeletti L, Reynolds D, Ritter P, Borri-Brunetto A, Singh JP.. Automatic optimization of cardiac resynchronization therapy using SonR-rationale and design of the clinical trial of the sonrtip lead and automatic AV-VV optimization algorithm in the paradym RF SonR CRT-D (respond CRT) trial. Am Heart J 2014;167:429–436.
    1. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A.. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the european society of cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33:1787–1847.
    1. Stevenson WG, Hernandez AF, Carson PE, Fang JC, Katz SD, Spertus JA, Sweitzer NK, Tang WH, Albert NM, Butler J, Westlake Canary CA, Collins SP, Colvin-Adams M, Ezekowitz JA, Givertz MM, Hershberger RE, Rogers JG, Teerlink JR, Walsh MN, Stough WG, Starling RC, Heart Failure Society of America Guideline C. Indications for cardiac resynchronization therapy: 2011 update from the heart failure society of America guideline committee. J Cardiac Fail 2012;18:94–106.
    1. Green CP, Porter CB, Bresnahan DR, Spertus JA.. Development and evaluation of the Kansas city cardiomyopathy questionnaire: a new health status measure for heart failure. J Am Coll Cardiol 2000;35:1245–1255.
    1. Sacchi S, Contardi D, Pieragnoli P, Ricciardi G, Giomi A, Padeletti L.. Hemodynamic sensor in cardiac implantable electric devices: the endocardial acceleration technology. J Healthc Eng 2013;4:453–464.
    1. Bordachar P, Garrigue S, Ritter P, Ploux S, Labrousse L, Casset C, Haissaguerre M, Dos Santos P.. Contributions of a hemodynamic sensor embedded in an atrial lead in a porcine model. J Cardiovasc Electrophysiol 2011;22:579–583.
    1. Duncker D, Delnoy PP, Nagele H, Mansourati J, Mont L, Anselme F, Stengel P, Anselmi F, Oswald H, Leclercq C.. First clinical evaluation of an atrial haemodynamic sensor lead for automatic optimization of cardiac resynchronization therapy. Europace 2016;18:755–761.
    1. Oliveira M, Branco L, Galrinho A, da Silva N, Cunha P, Valente B, Feliciano J, Pimenta R, Delgado A, Ferreira R.. Hemodynamic device-based optimization in cardiac resynchronization therapy: concordance with systematic echocardiographic assessment of AV and VV intervals. Res Rep Clin Cardiol 2015;6:1–7.
    1. Johansen JB, Nielsen JC, Sandgaard NCF.. Longevity of implantable cardioverter-defibrillators: still a long way to go. Europace 2016;18:1285–1286.
    1. Glikson M, Von Feldt LK, Suman VJ, Hayes DL.. Short- and long-term results with an active-fixation, bipolar, polyurethane-insulated atrial pacing lead. Pacing Clin Electrophysiol 1996;19:1469–1473.
    1. Shetty AK, Duckett SG, Ginks MR, Ma Y, Sohal M, Bostock J, Kapetanakis S, Singh JP, Rhode K, Wright M, O'Neill MD, Gill JS, Carr-White G, Razavi R, Rinaldi CA.. Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a comparison with acute haemodynamic measures and echocardiographic reverse remodelling. Eur Heart J Cardiovasc Imaging 2013;14:692–699.
    1. Bose A, Kandala J, Upadhyay GA, Riedl L, Ahmado I, Padmanabhan R, Gewirtz H, Mulligan LJ, Singh JP.. Impact of myocardial viability and left ventricular lead location on clinical outcome in cardiac resynchronization therapy recipients with ischemic cardiomyopathy. J Cardiovasc Electrophysiol 2014;25:507–513.
    1. Meisner JS, Nikolic S, Tamura T, Tamura K, Frater RW, Yellin EL.. Development and use of a remote-controlled mitral valve. Ann Biomed Eng 1986;14:339–349.
    1. Inoue N, Ishikawa T, Sumita S, Nakagawa T, Kobayashi T, Matsushita K, Matsumoto K, Ohkusu Y, Taima M, Kosuge M, Uchino K, Kimura K, Umemura S.. Long-term follow-up of atrioventricular delay optimization in patients with biventricular pacing. Circulation 2005;69:201–204.
    1. Gras D, Gupta MS, Boulogne E, Guzzo L, Abraham WT.. Optimization of AV and VV delays in the real-world CRT patient population: an international survey on current clinical practice. Pacing Clin Electrophysiol 2009;32 (Suppl 1):S236–S239.
    1. Altman RK, Parks KA, Schlett CL, Orencole M, Park MY, Truong QA, Deeprasertkul P, Moore SA, Barrett CD, Lewis GD, Das S, Upadhyay GA, Heist EK, Picard MH, Singh JP.. Multidisciplinary care of patients receiving cardiac resynchronization therapy is associated with improved clinical outcomes. Eur Heart J 2012;33:2181–2188.
    1. Ellenbogen KA, Gold MR, Meyer TE, Fernndez Lozano I, Mittal S, Waggoner AD, Lemke B, Singh JP, Spinale FG, Van Eyk JE, Whitehill J, Weiner S, Bedi M, Rapkin J, Stein KM.. Primary results from the smartdelay determined av optimization: a comparison to other AV delay methods used in cardiac resynchronization therapy (smart-AV) trial: a randomized trial comparing empirical, echocardiography-guided, and algorithmic atrioventricular delay programming in cardiac resynchronization therapy. Circulation 2010;122:2660–2668.
    1. Martin DO, Lemke B, Birnie D, Krum H, Lee KL, Aonuma K, Gasparini M, Starling RC, Milasinovic G, Rogers T, Sambelashvili A, Gorcsan J III, Houmsse M, Adaptive CRT. Investigation of a novel algorithm for synchronized left-ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: results of the adaptive CRT trial. Heart Rhythm 2012;9:1807–1814.
    1. Birnie D, Lemke B, Aonuma K, Krum H, Lee KL, Gasparini M, Starling RC, Milasinovic G, Gorcsan J III, Houmsse M, Abeyratne A, Sambelashvili A, Martin DO.. Clinical outcomes with synchronized left ventricular pacing: analysis of the adaptive CRT trial. Heart Rhythm 2013;10:1368–1374.
    1. Gras D, Kubler L, Ritter P, Anselme F, Delnoy PP, Bordachar P, Renesto F, Mabo P.. Recording of peak endocardial acceleration in the atrium. Pacing Clin Electrophysiol 2009;32 (Suppl 1):S240–S246.
    1. Birnie DH, Tang AS.. The problem of non-response to cardiac resynchronization therapy. Curr Opinion Cardiol 2006;21:20–26.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren