Comparison of characteristics in responders versus nonresponders with biventricular pacing for drug-resistant congestive heart failure

Studies comparing biventricular (BiV) cardiac resynchronization therapy (CRT) and left ventricular (LV) pacing alone have yielded conflicting results. We recently reported the results of the Greater Evaluation of Resynchronization Therapy for Heart Failure (GREATER-EARTH) trial demonstrating similar clinical benefits of BiV and LV-CRT on exercise tolerance. We report the prespecified secondary outcomes of the GREATER-EARTH trial, comparing the impact of BiV vs LV-CRT on structural and biochemical cardiac remodelling.

Patients with a LV ejection fraction (LVEF) ≤ 35% and a QRS duration ≥ 120 ms were randomized to BiV-CRT or LV-CRT for a 6-month period, followed by crossover. The primary end point was a change in LV end-systolic volume (LVESV). Secondary end points included changes in LVEF, right ventricular (RV) dimensions and function, mitral regurgitation (MR), indices of diastolic function, systolic pulmonary artery pressure (sPAP), and disease-specific biomarkers.

One hundred twenty patients (60.9 ± 8.8 years; 75.0% men; LVEF, 24.4% ± 6.3%) were enrolled. A similar reduction in LVESV was observed, from a baseline of 162.4 ± 57.2 mL to 130.4 ± 63.4 mL with BiV pacing and 130.3 ± 59.9 mL with LV pacing (P = 0.679, BiV pacing vs LV pacing). Improvements in LVEF, RV remodelling, and N-terminal pro b-type natriuretic peptide were similar between groups. BiV pacing yielded superior outcomes with respect to LV diastolic function, indexed left atrial volume, degree of MR, and sPAP (all P < 0.05), together with decreased N-terminal propeptide of type III collagen with LV-CRT.

In this randomized double-blind crossover trial, BiV and LV pacing resulted in similar improvements in the primary LV remodelling end point (LVESV). Analyses of secondary end points revealed advantages of BiV pacing over LV pacing on several other features of cardiac remodelling, providing mechanistic insights to support the main finding of the GREATER-EARTH trial.

Les études qui portent sur la comparaison de la thérapie de resynchronisation cardiaque (TRC) par stimulation biventriculaire (BiV) et par stimulation ventriculaire gauche (VG) seule ont mené à des résultats contradictoires. Nous rapportons les résultats de l’essai de la GREATER-EARTH (Greater Evaluation of Resynchronization Therapy for Heart Failure), démontrant que la TRC-BiV et la TRC-VG ont des avantages cliniques similaires sur la tolérance à l'effort. Nous présentons les résultats secondaires préétablis de l'essai de la GREATER-EARTH qui comparent les répercussions de la TRC-BiV par rapport à la TRC-VG sur le remodelage structurel et biochimique du cœur.

Les patients dont la fraction d’éjection ventriculaire gauche (FEVG) était ≤ 35 % et dont la durée du QRS était ≥ 120 ms ont été répartis de manière aléatoire à la TRC-BiV ou à la TRC-VG sur une période de 6 mois, qui a été suivie d’une période de permutation. Le critère de jugement principal était les changements dans le volume télésystolique du VG (VTSVG). Les critères de jugement secondaires étaient les changements dans la FEVG, les dimensions et la fonction du ventricule droit (VD), la régurgitation mitrale (RM), les indices de fonction diastolique, la pression artérielle pulmonaire systolique (PAPs) et les biomarqueurs de la maladie.

Cent vingt patients (60,9 ± 8,8 ans ; 75,0 % d’hommes ; FEVG, 24,4 % ± 6,3 %) ont été inscrits à l’essai. Une réduction similaire du VTSVG passant de 162,4 ± 57,2 ml à 130,4 ± 63,4 ml lors de la stimulation BiV et à 130,3 ± 59,9 ml lors la stimulation VG (P = 0,679, stimulation BiV vs stimulation VG) a été observée. Les améliorations de la FEVG, du remodelage VD et du propeptide natriurétique de type B N-terminal étaient similaires entre les groupes. La stimulation BiV a donné des résultats supérieurs en matière de fonction diastolique du VG, de volume indexé de l’oreillette gauche, de degré de RM et de PAPs (tous P < 0,05), de même que la TRC-VG en matière de diminution du propeptide N-terminal du collagène de type III.

Dans cet essai croisé, à double insu et à répartition aléatoire, la stimulation BiV et la stimulation du VG entraînaient des améliorations similaires du critère de jugement principal, à savoir le remodelage du VG (VTSVG). Les analyses des critères de jugement secondaires ont démontré les avantages de la stimulation BiV sur plusieurs autres caractéristiques du remodelage cardiaque par rapport aux avantages de la stimulation VG, ce qui offre des informations mécanistiques pour corroborer les principaux résultats de l’essai de la GREATER-EARTH.

To define the differential effect of site-specific ventricular counterpacing efficacy during cardiac resynchronization therapy (CRT) to identify the most informative imaging views to quantify it. Cross-sectional and long-axis views commonly are used to assess left ventricular (LV) contractility.

The effects of LV apical (LVa) and free-wall (LVfw) pacing during CRT on long- and short-axis contraction, cardiac output, and stroke work were assessed in an open-chested acute canine model to determine whether LVa and LVfw would induce earlier apical than basilar LV radial contraction and earlier free-wall than septal contraction, respectively. Apical (CRTa) and free-wall (CRTfw) using right ventricular (RV) pacing-induced dyssynchrony also were examined.

University large animal research laboratory.

Ten acutely anesthetized and instrumented open-chested purpose-bred dogs.

RV pacing served as the model of cardiac dyssynchrony. Selective LVfw and LVa pacing alone or with RV (CRTfw and CRTa, respectively) were studied relative to right atrial pacing (RA) as the control.

Two pairs of 3 ultrasonic crystals were place along the LV longitudinal axis—apex and mid-to-base pairs along septal and free wall lines. Conductance catheter-defined longitudinal LV segmental volumes and pressure-volume data were collected. RV decreased cardiac output and stroke work compared with RA (2.0±0.3 v 1.4±0.1 L/min; 137±22 v 60±14 mJ; p<0.05, respectively). LVfw but not LVa decreased stroke work (130±35 mJ), and CRTa but not CRTfw improved both (2.1±0.2 L/min; 113±13 mJ; p<0.01 v RV pacing). No difference in time to minimal length free wall-to-septal crystal was seen with pacing. Both LVa and CRTa displayed increased apical-to-basilar shortening delay compared with RA, RV, and LVfw (42±47, 9±105, and 1±46 msec, respectively; p<0.05). No matching regional LV volume changes were seen during LVa.

LV functional analysis from only a cross-sectional plane may be insufficient to characterize improved LV contraction synchrony during multisite CRT.

In patients with advanced systolic heart failure and mechanical dyssynchrony, cardiac resynchronization therapy (CRT) is an effective means of improving symptoms and reducing mortality. There are now several recognized approaches to optimize CRT. Imaging modalities can assist with identifying the myocardium with the latest mechanical activation for targeted left ventricular lead implantation. Device programming can be tailored to maximize biventricular pacing, and thereby is its benefit. Cardiac imaging has shown that atrioventricular and interventricular intervals can be adjusted to further reduce dyssynchrony. We review these various approaches that maximize the benefit derived from CRT.

The association between the vectorcardiographic QRS area, bundle branch pattern and clinical long-term prognosis in patients who have undergone cardiac resynchronization therapy (CRT) has been unclear.

We enrolled 50 consecutive patients who underwent CRT. Vectorcardiograms were constructed from preprocedural digital 12-lead electrocardiograms using the inverse Dower method. The vectorcardiographic QRS area was defined as the root of the sum of the square in the integral between the ventricular deflection curve and the baseline from QRS beginning to end in leads X, Y, and Z. The primary endpoints were total mortality and admission due to heart failure.

The vectorcardiographic QRS area in left bundle branch block (N = 13), right bundle branch block (N = 13), interventricular conduction delay (N = 11) and pacemaker rhythm (N = 13) were 218 ± 99, 97 ± 44, 90 ± 40, and 131 ± 58 μVs, respectively (ANOVA p < 0.001). During the mean follow-up period of 28 (2–86) months, 13 primary endpoints occurred. We divided patients into two groups: a large QRS area group (QRS area ≥114 μVs, N = 25) and a small QRS area group (QRS area <114 μVs, N = 25) by the median. The large QRS area group had a significantly lower rate of the primary endpoint compared with that of the small QRS area group (log rank 4.35, p = 0.037). The Cox regression analysis revealed that a QRS area <114 μVs was a significant predictor of the primary endpoint (HR 3.98, 95% CI 1.01–15.63, p = 0.048).

A larger preprocedural vectorcardiographic QRS area was associated with left bundle branch block and good prognosis in patients who underwent CRT.