Cardiac Resynchronization Therapy (CRT)

Effective Cardiac Resynchronization Therapy (CRT)

Cardiac Resynchronization Therapy, mostly performed by a Bi-Ventricular (BiV) pacemaker, involves placing several electrodes in the heart in an attempt to synchronize a dyssynchronous heart chamber. According to the Ottawa Heart Institute1, however, only 50% of patients respond positively to CRT treatment, based on evidence of reverse remodeling characterized by a 15% decrease in left ventricular (LV) end systolic volume (ESV). Furthermore, in 16% of cases treated with CRT, patient condition actually deteriorates as demonstrated by the PROSPECT study2. Pacing at the wrong lead location can cause an immediate increase in intra-ventricular dyssynchrony. 

Several approaches have attempted to improve patient response by using echocardiographic guidance or hemodynamic feedback from a pressure sensor (+dP/dtmax) to test different pacemaker settings. The attempts to date have been unsuccessful2, 3, 4.

The positioning of the pacing electrodes can vary considerably from patient to patient. The best lead position locations are those that yield an acute improvement in pumping function5, 9 as can be determined by LV pressure-volume (PV) analysis. 

It has been demonstrated that these acute hemodynamic locations predicted the positive response to CRT due to the strong predictive power of the PV analysis7, 8, 9. With guidance from intracardiac PV measurements, positive CRT response rate increased markedly up to 77% positive response based on reverse remodeling.Pressure-volume loops used for cardiac resynchronization therapy (CRT) study

Pressure–volume loops of two different patients during baseline (dotted) and during biventricular pacing (solid line). Figure A shows substantial acute change in a long-term responder. Figure B shows negligible acute change in a long-term non-responder8.

 

A recent editorial by Mafi Rad et al.9 reviewed the study by de Roest et al.8 and stated:

“The strong predictive power of the PV loop measurements as shown in this study, could allow a strategy in which CRT would be denied to patients who do not show a significant PV loop response.” 

“This approach may have important additional value in subsets of patients in whom there is less consensus for a clinical benefit, i.e. patients with right bundle branch block, intraventricular conduction delay, or narrow QRS.” 

”PV loop measurements could also be performed to optimize the LV lead position which has been shown to improve response to CRT.” 

“This approach may particularly benefit patients with ischaemic cardiomyopathy, in whom implantation of the LV lead at areas with myocardial scar has been shown to reduce CRT effectiveness, de Roest et al. performed PV loop-guided lead position optimization and observed a considerably higher response rate compared with those reported in the literature.” 

By adopting PV loops in standard clinical practice to guide Cardiac Resynchronization Therapy, the potential impact on cost savings is significant. These cost savings are based on:

1)  Sixteen percent of patients indicated for CRT show hemodynamic worsening by BiV pacing revealed by the PV technique. In such cases no pacemaker is implanted, resulting in direct cost savings by removing the material expense of the pacemaker2, 8, 9.

2)  The percentage of patients responding to CRT may improve from 50% up to 80%. The non-responder group, post implant, falls back on conventional treatment with frequent hospitalizations. As such, improvements in response rate constitute indirect savings7, 8, 9. Also, benefits of CRT in the positive responder group may be further improved by the PV guided lead positioning contributing to the indirect savings9.

 

References

  1. Birnie DH, ASL Tang. The problem of non-response to cardiac resynchronization therapy. Curr Opin Cardiol 2006;21:20-26.
  2. Chung ES, Leon AR, Tavazzi L, et al. Results of the predictors of response to CRT (Prospect) trial. Circulation 2008;117:2608-2616.
  3. Hawkins NM, Petrie MC, Burgess MC, McMurray JJ. Selecting patients for Cardiac resynchronization Therapy. The fallacy of echocardiographic dyssynchrony. J Am Coll Cardiol 2009;53:1944-59.
  4. Bogaard et al. Baseline left ventricular dP/dtmax rather than the acute improvement in dP/dtmax predicts clinical outcome in patients with cardiac resynchronization therapy. Eur J Heart Fail 2011;13:1126-32.
  5. Stevenson W.G., Sweeney M.O. Single Site Left Ventricular Pacing for Cardiac Resynchronization: Circulation 2004;109:1741-4.
  6. Delnoy et al. Pressure-volume loop analysis during implantation of biventricular pacemaker/cardiac resynchronization therapy device to optimize right and left ventricular pacing sites. Eur Heart J 2009;30:797-04.
  7. Delnoy et al. Upgrading to Biventricular Pacing Guided by Pressure-Volume Loop Analysis During Implantation. J Cardiovasc Electrophysiol 2011;22:677-683.
  8. de Roest et al. Prediction of long-term outcome of cardiac resynchronization therapy by acute pressure-volume loop measurements. Eur J of Heart Failure 2013:15:299-307.
  9. Mafi Rad et al. The role of acute invasive haemodynamic measurements in cardiac resynchronization therapy looping towards prediction of long-term response and therapy optimization. Eur J of Heart Failure 2013;15:247-249.
  10. Lieberman R. et al. Ventricular Pacing Lead Location Alters Systemic Hemodynamics and Left Ventricular Function in Patients With and Without Reduced Ejection Fraction. J Am Coll Cardiol. 2006;48:1634-41.