Redefining response to cardiac resynchronization therapy: a post hoc analysis of the MORE-CRT MPP trial

Q: What are the key findings of this study?

Delayed echocardiographic responders to cardiac resynchronization therapy had clinical outcomes comparable to early responders, while non-responders had 38% shorter event-free survival.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure (n=2732). Intervention: Delayed echocardiographic response vs. Non-response. Primary outcome: Heart failure hospitalization or death (Time ratio 0.62, 95% CI 0.40-0.94, p=0.025).

Q: What does this research mean for the field?

Delayed responders to cardiac resynchronization therapy achieve similar event-free survival for heart failure hospitalization or death compared to early responders, whereas persistent non-responders experience significantly worse clinical outcomes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Vishal Mehta; Nadeev Wijesuriya; Felicity De Vere; Sandra Howell; Mark K. Elliott; Alphonsus Liew; Steven Niederer; Haran Burri; Johannes Sperzel; Leonardo Calò; Bernard Thibault; Wenjiao Lin; Kwangdeok Lee; Andrea Grammatico; Niraj Varma; Marianne Gwechenberger; Giuseppe Boriani; Christophe Leclercq; Christopher A. Rinaldi

doi:10.1093/europace/euag209

Key result

Delayed CRT response yields outcomes comparable to early response, while non-response links to ~38% shorter event-free survival.

Time ratio 0.62
95% CI 0.40-0.94
P=0.025
n=2,732

Figures

Graphical abstract published by EP Europace — Graphical abstract · Published by EP Europace · CC BY

Why the study?

Response to cardiac resynchronization therapy is commonly assessed at 6 months, but response may continue to evolve beyond this time point, and the relationship of these trajectories with longer-term outcomes is unclear.

Key Points

To characterize changes in echocardiographic response to cardiac resynchronization therapy from 6 to 12 months, identify predictors of response trajectories, and assess associations with clinical outcomes.
Post hoc analysis of N=2732 patients (69.4% male; 62.8% non-ischaemic) receiving conventional biventricular pacing in the MORE-CRT MPP trial with LVESV measured at baseline, 6 months, and 12 months.
Classified patients as early responders (>15% LVESV reduction at 6 months), delayed responders (<15% at 6 months but >15% at 12 months), or non-responders (<15% at 6 and 12 months; subclassified as stabilized or deteriorated).
Assessed time to first heart failure hospitalization or death over 12-month follow-up using restricted mean survival time and multivariable accelerated failure time (AFT) models.
Non-responders had significantly shorter event-free survival than early responders (time ratio = 0.48, 95% CI 0.33–0.69; P < 0.001) and delayed responders (time ratio = 0.62, 95% CI 0.40–0.94; P = 0.025), with no difference between early and delayed responders (P = 0.220; 12-month event rate 8.0% vs. 18.1% in non-responders).
Among initial non-responders, deteriorating patients experienced 59% shorter event-free survival than stabilizing patients (time ratio = 0.41, 95% CI 0.25–0.65; P < 0.001; 12-month event probability 24.8% vs. 7.6%).
Independent predictors of delayed rather than early response were ischaemic aetiology (OR 1.76, 95% CI 1.24–2.49, P = 0.002), non-LBBB conduction pattern (OR 0.67, 95% CI 0.46–0.98, P = 0.040), and lower baseline LVEF (OR 0.97, 95% CI 0.95–1.00, P = 0.048).

Study Design

Type

Cohort (n=2,732)

Multicenter

Yes

Structured PICO

P

Population

2,732 patients with heart failure receiving conventional biventricular pacing, followed for 12 months to assess echocardiographic response trajectories.

E

Exposure

Conventional biventricular (BiV) cardiac resynchronization therapy (CRT) for 12 months

O

Outcome

Composite of freedom from heart failure hospitalization or deathcomposite

Main Result

Effect estimate: Time ratio 0.62 (95% CI 0.40-0.94)

Absolute Event Rate: 8% vs 18.1%

p-value: p=0.025

Limitations

Post hoc analysis not designed or powered as an equivalence study
Selection and survivor bias due to exclusion of patients without complete 12-month echocardiographic data or who died before 6 months
Longitudinal changes in pharmacological therapy or device programming were not systematically collected
Follow-up time period was limited to 1 year
post hoc analysis not designed or powered as an equivalence study

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Implication

Patients with a delayed echocardiographic response to CRT at 12 months have clinical outcomes comparable to early responders, suggesting that response assessment should extend beyond 6 months.

Abstract

AIMS: Cardiac resynchronization therapy (CRT) response is commonly assessed at 6 months using left ventricular end-systolic volume (LVESV) and clinical endpoints. However, response may continue to evolve beyond this time point, with some initial non-responders subsequently improving or stabilizing. This study aimed to characterize changes in echocardiographic response from 6 to 12 months, identify predictors of these trajectories, and assess their relationship with longer-term clinical outcomes. METHODS AND RESULTS: This post hoc analysis of the MORE-CRT MPP trial included patients receiving conventional biventricular pacing only. Patients were classified as non-responders (<15% LVESV reduction at 6 and 12 months), early responders (>15% reduction at 6 months), or delayed responders (<15% reduction at 6 months but >15% at 12 months). Six-month non-responders were further classified as stabilized (LVESV reduction at 12 months) or deteriorated (LVESV increase at 12 months). Heart failure hospitalization or death was analysed using restricted mean survival time and adjusted accelerated failure time models. Among 2732 patients (69.4% male; 62.8% non-ischaemic), event-free survival differed between early, delayed, and non-responders (P < 0.001). Non-responders had 52% shorter event-free survival than early responders (P < 0.001), and 38% shorter than delayed responders (P = 0.025). Early and delayed responders had similar outcomes (P = 0.221). Among non-responders, 39.0% stabilized and 61.0% deteriorated; outcomes diverged after 6 months (P < 0.001). The deterioration group had 59% shorter event-free survival (P < 0.001). Ischaemic aetiology, non-LBBB, and lower baseline LVEF predicted delayed response. CONCLUSION: Delayed responders demonstrated similarly favourable clinical outcomes to early responders over the duration of follow-up. These findings support 12-month assessment and trajectory-based definitions of CRT response.

Discussion

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Cite This Study

Mehta et al. (2026) conducted a cohort in Heart failure (n=2,732). Delayed echocardiographic response vs. Non-response was evaluated on Heart failure hospitalization or death (Time ratio 0.62, 95% CI 0.40-0.94, p=0.025). Delayed echocardiographic responders to cardiac resynchronization therapy had clinical outcomes comparable to early responders, while non-responders had 38% shorter event-free survival.

synapsesocial.com/papers/6aae19593bfe916f7157061d https://doi.org/10.1093/europace/euag209

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Redefining response to cardiac resynchronization therapy: a post hoc analysis of the MORE-CRT MPP trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Redefining response to cardiac resynchronization therapy: a post hoc analysis of the MORE-CRT MPP trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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