Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy

Joost Lumens, Bhupendar Tayal, John Walmsley, Antonia Delgado-Montero, Peter R Huntjens, David Schwartzman, Andrew D Althouse, Tammo Delhaas, Frits W Prinzen, John Gorcsan

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

BACKGROUND: Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates.

METHODS AND RESULTS: First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35%) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7% had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95% confidence interval, 0.19-0.53; P<0.001) and less deaths, transplants, or LV assist devices (hazard ratio, 0.28; 95% confidence interval, 0.15-0.55; P<0.001). Furthermore, in a subgroup of 113 patients with intermediate electrocardiographic criteria (QRS duration of 120-149 ms or non-left bundle branch block), SSI≥9.7% was independently associated with significantly less heart failure hospitalizations or deaths (hazard ratio, 0.41; 95% confidence interval, 0.23-0.79; P=0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95% confidence interval, 0.12-0.60; P=0.001).

CONCLUSIONS: Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone.

Original languageEnglish
Article numbere003744
JournalCirculation-Cardiovascular Imaging
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 2015

Keywords

  • Aged
  • Cardiac Resynchronization Therapy
  • Computer Simulation
  • Echocardiography
  • Electrocardiography
  • Female
  • Heart Failure
  • Heart Ventricles
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Treatment Outcome
  • Ventricular Function, Left
  • Ventricular Remodeling

Cite this

Lumens, Joost ; Tayal, Bhupendar ; Walmsley, John ; Delgado-Montero, Antonia ; Huntjens, Peter R ; Schwartzman, David ; Althouse, Andrew D ; Delhaas, Tammo ; Prinzen, Frits W ; Gorcsan, John. / Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy. In: Circulation-Cardiovascular Imaging. 2015 ; Vol. 8, No. 9.
@article{377f69e45110458bb3b3d06db18cc3f1,
title = "Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy",
abstract = "BACKGROUND: Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates.METHODS AND RESULTS: First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35{\%}) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7{\%} had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95{\%} confidence interval, 0.19-0.53; P<0.001) and less deaths, transplants, or LV assist devices (hazard ratio, 0.28; 95{\%} confidence interval, 0.15-0.55; P<0.001). Furthermore, in a subgroup of 113 patients with intermediate electrocardiographic criteria (QRS duration of 120-149 ms or non-left bundle branch block), SSI≥9.7{\%} was independently associated with significantly less heart failure hospitalizations or deaths (hazard ratio, 0.41; 95{\%} confidence interval, 0.23-0.79; P=0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95{\%} confidence interval, 0.12-0.60; P=0.001).CONCLUSIONS: Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone.",
keywords = "Aged, Cardiac Resynchronization Therapy, Computer Simulation, Echocardiography, Electrocardiography, Female, Heart Failure, Heart Ventricles, Humans, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Treatment Outcome, Ventricular Function, Left, Ventricular Remodeling",
author = "Joost Lumens and Bhupendar Tayal and John Walmsley and Antonia Delgado-Montero and Huntjens, {Peter R} and David Schwartzman and Althouse, {Andrew D} and Tammo Delhaas and Prinzen, {Frits W} and John Gorcsan",
note = "{\circledC} 2015 American Heart Association, Inc.",
year = "2015",
month = "9",
doi = "10.1161/CIRCIMAGING.115.003744",
language = "English",
volume = "8",
journal = "Circulation-Cardiovascular Imaging",
issn = "1941-9651",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",
number = "9",

}

Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy. / Lumens, Joost; Tayal, Bhupendar; Walmsley, John; Delgado-Montero, Antonia; Huntjens, Peter R; Schwartzman, David; Althouse, Andrew D; Delhaas, Tammo; Prinzen, Frits W; Gorcsan, John.

In: Circulation-Cardiovascular Imaging, Vol. 8, No. 9, e003744, 09.2015.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy

AU - Lumens, Joost

AU - Tayal, Bhupendar

AU - Walmsley, John

AU - Delgado-Montero, Antonia

AU - Huntjens, Peter R

AU - Schwartzman, David

AU - Althouse, Andrew D

AU - Delhaas, Tammo

AU - Prinzen, Frits W

AU - Gorcsan, John

N1 - © 2015 American Heart Association, Inc.

PY - 2015/9

Y1 - 2015/9

N2 - BACKGROUND: Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates.METHODS AND RESULTS: First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35%) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7% had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95% confidence interval, 0.19-0.53; P<0.001) and less deaths, transplants, or LV assist devices (hazard ratio, 0.28; 95% confidence interval, 0.15-0.55; P<0.001). Furthermore, in a subgroup of 113 patients with intermediate electrocardiographic criteria (QRS duration of 120-149 ms or non-left bundle branch block), SSI≥9.7% was independently associated with significantly less heart failure hospitalizations or deaths (hazard ratio, 0.41; 95% confidence interval, 0.23-0.79; P=0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95% confidence interval, 0.12-0.60; P=0.001).CONCLUSIONS: Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone.

AB - BACKGROUND: Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates.METHODS AND RESULTS: First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35%) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7% had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95% confidence interval, 0.19-0.53; P<0.001) and less deaths, transplants, or LV assist devices (hazard ratio, 0.28; 95% confidence interval, 0.15-0.55; P<0.001). Furthermore, in a subgroup of 113 patients with intermediate electrocardiographic criteria (QRS duration of 120-149 ms or non-left bundle branch block), SSI≥9.7% was independently associated with significantly less heart failure hospitalizations or deaths (hazard ratio, 0.41; 95% confidence interval, 0.23-0.79; P=0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95% confidence interval, 0.12-0.60; P=0.001).CONCLUSIONS: Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone.

KW - Aged

KW - Cardiac Resynchronization Therapy

KW - Computer Simulation

KW - Echocardiography

KW - Electrocardiography

KW - Female

KW - Heart Failure

KW - Heart Ventricles

KW - Humans

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Prospective Studies

KW - Treatment Outcome

KW - Ventricular Function, Left

KW - Ventricular Remodeling

U2 - 10.1161/CIRCIMAGING.115.003744

DO - 10.1161/CIRCIMAGING.115.003744

M3 - Article

C2 - 26338877

VL - 8

JO - Circulation-Cardiovascular Imaging

JF - Circulation-Cardiovascular Imaging

SN - 1941-9651

IS - 9

M1 - e003744

ER -