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SMART-AV: The role of electrical delay (QLV) to predict left ventricular reverse remodeling with cardiac resynchronization therapy

Heart Failure (HF)

Presenter | see Discussant report

Michael R Gold (United States of America)

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Presentation slides

List of Authors:


Discussant | see Presenter abstract

Cecilia Linde, FESC Cecilia Linde (Sweden)

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Presentation slides


CRT has become an established therapy for patients in NYHA II-IV heart failure with wide QRS and impaired left ventricular function despite optimal heart failure (HF) medication with a Class I recommendation Level of evidence A (1-5).

Clinical problem: Yet only 60% respond to CRT by the present selection criteria. The addition of mechanical to electrical dyssynchrony criteria recently failed to increase the response to CRT in one RCT- the PROSPECT study. Subgroup analysis of RCTs in both moderate and mild HF has indicated that patients with left bundle branch block (LBBB) and more prolonged QRS duration (> 150 ms) tend to have better response to CRT both regarding reverse remodeling or clinical outcomes (6-7). This has led to the hypothesis in the SMART AV sub-study that left ventricular (LV) electrical delay or electrical dyssynchrony is an important factor for predicting benefit from CRT. The SMART AV study was a multicenter, randomized study that failed to show the value of AV-delay optimization to fixed AV delay among patients with advanced HF undergoing CRT defibrillator implantation (8).

Method: Gold et al assessed the relationship between electrical delay defined by time interval from the first deflection on a surface ECG to local intrinsic activation at the LV stimulation site (QLV) and reverse remodeling in a prospectively designed sub-study of 426 / 1014 patients in the SMART-AV study. At the final lead positions, surface Lead II, RV and LV EGM were recorded simultaneously on paper strips at a sweep speed of 100 mm/sec. QLV was later measured by a blinded core lab with no knowledge of lead position or clinical outcomes. The primary end point was left ventricular end-systolic volume (LVESV) at 6 months assessed by a core lab.
Among secondary endpoints was quality-of-life score (QOL), by the Minnesota Questionnaire.
The CRT responses were compared among subgroups based on QLV median values or quartiles. Multivariate logistic regression models were utilized to analyze the association between QLV and CRT response adjusting for baseline covariates including age, gender, ischemia, left bundle branch block (LBBB), QRS width, NYHA, LVEF and LVESV.

Results: The Median value for QLV was 95 ms. When separated by quartiles of QLV duration, reverse remodeling response rates (>15% reduction of LV end systolic volume) increased progressively from 38.7% to 68.4% and QoL response rate (>10 points reduction) increased from 50% to 72% with the overall response rate for reverse remodeling of 50% and QoL of 60%. Patients in the highest quartile of QLV had a 3.21 fold increase (1.58 – 6.50, p = .001) in their odds of a reverse remodeling response after correcting for QRS duration, bundle branch block type and clinical characteristics by multivariate logistic regression analysis.

Conclusions: Electrical dyssynchrony, as measured by QLV, was a strong and independent predictor of reverse remodeling and quality of life with CRT. Acute measurements of QLV may be useful to guide left ventricular lead placement during CRT implantation. Given the problem with non-responder rates associated with CRT and the disappointing results of trials to identify lead position or programming parameters to enhance response rates, QLV on top of present selection may enhance CRT response beyond present response rate at 60%.

Potential weeknesses: No documentation of LV lead position was given in the study and only 1 QLV measurement / patient was supplied. The study has a relatively short follow up (6 months) no clear impact on morbidity in the higher quartiles of QLV compared to the lowest was shown.

Limitations: Whether these early observations imply effects on morbidity and mortality long term remains to be shown. A randomized controlled trial to compare LV lead placement by QLV guidance to conventional technique is needed to establish whether QLV may enhance response to CRT.

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2. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352(15):1539-1549.
3. Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C; REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heartfailure symptoms. J Am Coll Cardiol. 2008 52(23):1834-1843.
4. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W; MADIT-CRT Trial Investigators. Cardiac-Resynchronization Therapy for the prevention of heart-failure events. N Engl J Med. 2009:361(14):1329-1338.
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6. Gervais R, Leclercq C, Shankar A, Jacobs S, Eiskjaer H, Hagemann A, Freemantle N, Cleland J, Tavazzi L, Daubert C. Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub-analysis of the CARE-HF trial. Eur J Heart Fail 2009;11:699-705.
7. Zareba W, Klein H, Cyqankiewicz, Hall WJ, McNitt S, Brown M, Cannom D, Daubert JP, Eldar M, Gold MR, Goldberger JJ, Goldenberg I, Lichstein E, Pitschner H, Rashtian M, Solomon S, Viskin S, Wang P, Moss AJ. Effectiveness of cardiac resynchronization therapy by QRS morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT). Circulation 2011;123(10):1061-1072.
8. Ellenbogen KA, Gold MR, Meyer TE, Lozano IF, Mittal S, Waggoner AD, Lemke B, Singh JP, Spinale FG, Van Eyk J, Whitehill J, Weiner S, Bedi M, Rapkin J, Stein KM. Primaryresults from the SmartDelay determined AV pptimization: a comparison to other AV delay methods used in Cardiac Resynchronization Therapy (SMART-AV) trial. Circulation. 2010;122:2660-2668.


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Clinical Trial Update II - Rate and rhythm

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.