# Impact of Cardiac Resynchronization Therapy in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-analysis

Miloud Cherbi, Paul Gautier, Raphaël Martins, Romain Itier, Laurence

Barde, Philippe Maury, Clément Delmas

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Miloud Cherbi, Paul Gautier, Raphaël Martins, Romain Itier, Laurence Barde, et al. Impact of Cardiac Resynchronization Therapy in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-analysis. Jhlto, 2026, pp.100476. 10.1016/j.jhlto.2025.100476. hal-05442303

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Impact of Cardiac Resynchronization Therapy in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-analysis
Running title: CRT and LVAD

Miloud Cherbi, Paul Gautier, Raphael Martins, Romain Itier, Laurence Barde, Philippe Maury, Clément Delmas

<figure><img src="image_2.png" /></figure>

PII: S2950-1334(25)00275-7

DOI: https://doi.org/10.1016/j.jhlto.2025.100476

Reference: JHLTO100476

To appear in: *JHLT Open*

Please cite this article as: Miloud Cherbi, Paul Gautier, Raphael Martins, Romain Itier, Laurence Barde, Philippe Maury and Clément Delmas, Impact of Cardiac Resynchronization Therapy in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-analysis
Running title: CRT and LVAD, *JHLT Open*, (2025) doi:https://doi.org/10.1016/j.jhlto.2025.100476

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# Impact of Cardiac Resynchronization Therapy in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-analysis

Running title: CRT and LVAD

Miloud Cherbi, MD<fnref n="1" />, Paul Gautier, MD<fnref n="1" />, Raphael Martins, MD, PhD<fnref n="2" />, Romain Itier, MD<fnref n="1" />,
Laurence Barde, MD<fnref n="1" />, Philippe Maury, MD, PhD<fnref n="1" />, Clément Delmas, MD, PhD<fnref n="1" />

## Corresponding author

Miloud CHERBI, MD

Cardiology Department, Toulouse University Hospital, Toulouse cedex, France

Email: cherbi.m@chu-toulouse.fr

Phone: +33561322044

## ABSTRACT

**Background:** Many patients with left ventricular assist devices (LVADs) have cardiac resynchronization therapy (CRT). However, the impact of CRT on their clinical and hemodynamic outcomes remains unclear.

**Methods:** We conducted a systematic review and meta-analysis to evaluate CRT's impact on survival in LVAD patients. We searched PUBMED, EMBASE, and Cochrane databases from inception through April 30, 2025, for studies reporting outcomes in LVAD patients with CRT. The primary outcome was all-cause mortality in patients with versus without CRT. Secondary clinical outcomes included ventricular arrhythmias (VAs) and shocks delivered. Hemodynamic outcomes included heart rate, right atrial pressure, mean pulmonary artery pressure, pulmonary

<footnote n="1">¹ Cardiology Department, Toulouse University Hospital, Toulouse, France</footnote>

<footnote n="2">² Univ Rennes, CHU Rennes, CIC 1414, INSERM, LTSI - UMR 1099, F-35000 Rennes, France.</footnote>
capillary wedge pressure, thermodilution cardiac output, pulmonary artery saturation, right ventricular stroke work index, and left ventricular end-diastolic diameter.

**Results:** 13 studies including 3,665 patients were analyzed. CRT did not demonstrate any significant survival benefit, whether comparing CRT-D versus ICD (OR 1.12 [0.85–1.48]), CRT on versus CRT off (OR 1.48 [0.87–2.53]), CRT versus no device (OR 0.99 [0.61–1.59]), or CRT versus no device or ICD (OR 1.00 [0.16–6.31]). Similarly, none of the tested comparisons showed significant differences in VAs incidence or shock rates. Biventricular pacing demonstrated no advantage for any hemodynamic outcomes, whether compared to right ventricular pacing or intrinsic rhythm.

**Conclusion:** In this meta-analysis, CRT was not associated with overall survival benefit in LVAD recipients, nor with hemodynamic improvement. Future randomized trials may be warranted to definitively establish CRT's value in this population and refine patient selection criteria for optimal outcomes.

**KEYWORDS:** left ventricular assist device; cardiac resynchronization therapy; ventricular arrhythmia; ventricular tachycardia; ventricular fibrillation; heartmate; heartware

**Abbreviations**

BTT, bridge-to-transplant; CI, confidence interval; CRT, cardiac resynchronization therapy; DT, destination therapy; HF, heart Failure; HM2, Heartmate 2; HM3, Heartmate 3; HR, heart rate; HVAD, Heartware; ICD, or implantable cardioverter-defibrillator; LVAD, left ventricular assist devices; LVEDD, left ventricular end-diastolic diameter; MPAP, mean pulmonary artery pressure; OR, odds ratios; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure;
PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RAP, right atrial pressure; RCT, randomized controlled trial; RoB, Risk of Bias; RV, right ventricular; RVSWI, right ventricular stroke work index; SE, standard error; SMD, standardized mean difference; TDCO, thermodilution cardiac output; VA, ventricular arrhythmia

Introduction

The growing incidence of advanced heart failure (HF) has led to the widespread use of left ventricular assist devices (LVADs) as a cornerstone of management in selected patients. These devices offer significant improvements in both survival and quality of life and are now routinely used as either bridge-to-transplant (BTT) or destination therapy (DT). Clinical practice guidelines reflect this role, recommending LVAD implantation with strong evidence for patients with INTERMACS profiles 1 to 3, and with more limited endorsement for profile 4 (1).

Despite these therapeutic advances, many aspects of LVAD patient management remain insufficiently defined. Among them is the role of cardiac resynchronization therapy (CRT), which is frequently present at the time of LVAD implantation due to preexisting indications in patients with systolic dysfunction (2). While CRT has demonstrated clear benefits in patients with native hearts (3), its clinical value in the context of mechanical circulatory support remains uncertain, as observational studies have not consistently shown any survival or symptomatic advantage in LVAD recipients (4, 5). Furthermore, maintaining CRT in LVAD recipients may expose patients to additional risks, including device-related complications and procedural morbidity—particularly during pulse generator replacements—such as pocket hematomas, pocket infections, and even LVAD-related infections (6). In the absence of definitive evidence or standardized guidance, clinical decision-making regarding CRT in LVAD recipients remains highly variable (2, 7). Most studies conducted to date, however, have not been adequately
powered to assess meaningful clinical endpoints such as all-cause mortality or rehospitalization, and their findings may be limited by small sample sizes or the single-center nature of their designs.

Therefore, we conducted this meta-analysis to evaluate the potentials benefits of CRT in LVAD recipients.

## Methods

### Search strategy

Databases (PubMed, Embase, and the Cochrane Central Register of Controlled Trials) were systematically searched, without language restrictions, for all studies—both observational and randomized controlled trials (RCTs)—reporting the outcomes and prognosis of LVAD recipients with CRT, using keywords such as "cardiac resynchronization therapy", and "left ventricular assist device" (full strategy in *Supplementary Table I*), from inception to April 30, 2025. Searches of unpublished grey literature were performed manually on Google Scholar, OpenGrey, and pre-print servers (MedRxiv). ClinicalTrials.gov was also searched for ongoing studies on CRT and LVAD. The search was kept up to date through automated alerts from PubMed for newly published articles. Institutional review board approval was not required, as this study is a meta-analysis of previously published data. The study was registered in PROSPERO, CRD420251042839. The meta-analysis was performed in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement (PRISMA checklist provided in *Supplementary Table 2*) (8, 9).

### Outcomes

The primary outcome was all-cause mortality in LVAD recipients with versus without CRT. Secondary clinical outcomes included the incidence of ventricular arrhythmias (VAs) and the
number of shocks delivered by CRT-D or implantable cardioverter-defibrillators (ICDs).
Hemodynamic parameters assessed comprised heart rate (HR), right atrial pressure (RAP),
mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP),
thermodilution cardiac output (TDCO), pulmonary artery (PA) saturation, right ventricular
stroke work index (RVSWI), and left ventricular end-diastolic diameter (LVEDD).

## Article selection

Titles and abstracts of studies retrieved using the search strategy were independently screened
by two investigators (C.D. and M.C.) to identify studies meeting our inclusion criteria: (1)
studies reporting outcomes of patients after their first LVAD implantation; and (2) reporting
rates of at least one of the clinical or hemodynamic outcomes of interest mentioned above.
Conference abstracts and case reports were not included. The full texts of potentially eligible
studies were retrieved and independently assessed for eligibility by the two investigators.
Discrepancies were resolved through discussion, and final decisions were made by consensus.

## Data extraction

Two authors (C.D. and M.C.) independently extracted data on study characteristics (including
study ID, design, protocol, sample size, and follow-up period), baseline patient characteristics
(such as sex, age, ejection fraction, ischemic cardiomyopathy, history of VA), and all clinical
and hemodynamic outcomes.

## Risk of bias, quality assessment and certainty of evidence

Given the limited number of studies per comparison (<10), formal statistical tests for
publication bias (Egger's test, funnel plots) were not performed as they lack sufficient power to
detect bias reliably (8, 9). Instead, we conducted a comprehensive search strategy including
grey literature and trial registries to minimize publication bias. For observational studies,
quality was assessed using the ROBINS-I tool (10), which considers seven domains:
confounding factors, classification of interventions, selection of participants, deviations from intended interventions, missing data, measurement of outcomes, and selection of the reported results. For RCTs, quality assessment was performed using the Cochrane Risk of Bias (RoB2) tool for crossover trials (11). Two authors (C. D. and M. C.) independently assessed the quality of the studies, using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to assess the quality of evidence for each outcome (12). Disagreements between reviewers were resolved by discussion.

## Statistical analysis

For dichotomous outcomes, the number of events and total sample size in each group were extracted from each study for each outcome of interest. A pooled analysis was then conducted by aggregating the data to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for each dichotomous outcome. For quantitative outcomes, standardized mean differences (SMDs) and their standard errors (SEs) were calculated using Cohen's d. For studies reporting raw data (means, standard deviations, and sample sizes), SMDs and their corresponding SEs were computed using standard formulas (13). For studies providing pre-calculated SMDs with standard deviations of the difference, the standard deviations were converted to standard errors using $SE = SD/\sqrt{n}$, where n represents the total sample size. The DerSimonian and Laird random-effects model was employed because, based on preexisting clinical and pathophysiological considerations (2, 4, 5, 7), we could not rule out the possibility that the observed estimates of CRT effect might vary across studies because of real differences in the CRT effect in each study as well as sampling variability (8, 14). Between-study heterogeneity was estimated using the restricted maximum likelihood method. The Hartung-Knapp-Sidik-Jonkman correction was applied to derive more robust CIs (8). Statistical heterogeneity was initially assessed using the I² statistic, which represents the proportion of total variation observed between trials that is attributable to differences between trials rather
than sampling error (chance), with I² ≥ 50% considered indicative of substantial heterogeneity
(8). Analyses were performed using R software (version 4.3.2) with the *meta* and *metafor*
packages.

## Results

### Baseline characteristics

From 2,797 references retrieved through the search strategy, 37 studies were selected for full-text assessment of inclusion criteria based on title and abstract screening. Flow chart of literature retrieval and reasons for article exclusion are shown in Figure 1. Finally, 13 studies met inclusion criteria, that included a total of 3,665 patients. Among them, 2 were RCTs (45 patients) and 4 were multicentric studies (2,694 patients). For clinical outcomes, four comparisons were possible based on available data: (1) patients with CRT-D versus ICD (4 studies, 2,141 patients); (2) patients with CRT in whom biventricular pacing was turned off after LVAD implantation (CRT on vs. CRT off, 3 studies, 640 patients); (3) patients with CRT versus those with no device (2 studies, 973 patients); and (4) patients with CRT versus those with either ICD or no device (2 studies, 1,911 patients). For hemodynamic outcomes, three comparisons were feasible: (1) biventricular pacing versus right ventricular (RV) pacing (4 studies, 74 patients); (2) biventricular pacing versus intrinsic rhythm (2 studies, 37 patients); and (3) CRT on versus CRT off (2 studies, 327 patients). The main characteristics of the studied populations are presented in *Table 1*.

### Clinical outcomes

In the first analysis comparing patients with CRT-D versus ICD, no significant differences were observed between groups for any clinical outcomes, including all-cause mortality (OR 1.12 [0.85–1.48]; low heterogeneity, I² = 0%), incidence of VAs (OR 1.38 [0.81–2.35]; low heterogeneity, I² = 23%) (*Figure 2A*). Moreover, there was no significant difference in the rate
of delivered shocks between CRT-D and ICD (14.8 vs. 9.4 per 100 person-years, OR 1.66 [0.03–95.48]; high heterogeneity, I²=80%). Similarly, in the comparison between CRT on and CRT off, no significant differences were found in all-cause mortality (OR 1.48 [0.87–2.53]; I² = 0%), or incidence of VAs (OR 0.80 [0.10–6.53]; high heterogeneity, I² = 84%) (Figure 2B). Finally, no significant differences in all-cause mortality were observed between patients with CRT and those with either no device or an ICD (OR 1.00 [0.16–6.31]; I² = 30%, Figure 2C), or between patients with CRT and those without any device (OR 0.99 [0.61–1.59]; I² = 0%, Figure 2D).

## Hemodynamic outcomes

In the first comparison between biventricular pacing and RV pacing, no significant differences were observed across all hemodynamic parameters tested, including HR (SMD –0.04 [–0.19 to 0.10], I² = 0%), RAP (SMD –0.22 [–1.18 to 0.75], I² = 69%), MPAP (SMD –0.08 [–0.28 to 0.13], I² = 0%), PCWP (SMD –0.33 [–1.37 to 0.71], I² = 70%), TDCO (SMD 0.15 [–0.45 to 0.76], I² = 0%), PA saturation (SMD 0.01 [–1.46 to 1.48], I² = 0%), and RVSWI (SMD 0.04 [–0.81 to 0.88], I² = 0%) (Figure 3A). Similarly, no differences in any of these hemodynamic parameters were found when comparing biventricular pacing to intrinsic rhythm (Figure 3B). Finally, no difference was observed for LVEDD between CRT on and CRT off (SMD –0.43 [–7.71 to 6.84], I² = 93%) (Figure 3C).

## Quality assessment and GRADE framework results

Among the studies included, 6 were assessed as having a low risk of bias and 7 as high risk of bias. A detailed quality assessment for each study is presented in *Supplementary Table 3*. The certainty of evidence for all outcomes across all comparisons was rated as low or very low according to the GRADE system, primarily due to the non-randomized design of the included studies, risk of confounding, limited number of studies, and/or imprecise effect estimates. Further details and justifications are provided in *Supplementary Table 4*.
Discussion

To date, we present the largest meta-analysis evaluating the impact of CRT on clinical outcomes and hemodynamic parameters in LVAD recipients, including a total of 3,665 patients. Our main findings are as follows: (1) CRT was not associated with an overall survival benefit in LVAD patients, nor with an increased incidence of VAs, whether compared to patients without CRT or with ICD; (2) Biventricular pacing was not associated with any advantage for any hemodynamic parameters, including RAP, MPAP, PCWP, TDCO, PA saturation, or RVSWI, whether compared to RV pacing or intrinsic rhythm; and (3) despite CRT being frequently pre-existing in LVAD recipients, very few prospective studies have assessed its impact, and further research is needed to clarify its exact role.

With the increasing burden of advanced HF and persistent limitations in organ availability (15), the use of LVADs is anticipated to grow substantially, making the optimization of care for these patients a key therapeutic objective. While many individuals undergoing LVAD implantation have previously been treated with CRT, the most effective approach to managing CRT in the post-implantation setting remains to be defined (2, 7). Our findings reinforce the current lack of robust clinical evidence supporting a survival benefit from maintaining CRT after LVAD implantation. Despite some heterogeneity across studies, there was also no indication of an increased risk of VAs. Notably, all assessed hemodynamic parameters—including pressure and flow measurements impacting both the left and right ventricles—remained unchanged with the use of biventricular pacing compared to either right ventricular pacing or intrinsic rhythm.

The lack of clinical or physiological benefit observed with CRT in patients supported by LVADs highlights the need for further focused research. One possible explanation is that the continuous unloading of the left ventricle by the LVAD may diminish the relevance of achieving electrical synchrony or optimizing ventricular loading conditions—mechanisms through which CRT typically exerts its effects. This "LVAD dominance" hypothesis is particularly relevant for right
ventricular function, where CRT has been shown to improve hemodynamics in native hearts, especially in patients with elevated right-sided pressures (3, 16). However, in our meta-analysis, no significant improvement was observed in any RV hemodynamic parameter (RAP, RVSWI) with biventricular pacing, suggesting that the profound hemodynamic effects of mechanical unloading may supersede any potential benefit from electrical resynchronization. Furthermore, in the presence of continuous mechanical support, electrical dyssynchrony may become physiologically silent—that is, while ventricular dyssynchrony persists electrically, its mechanical and hemodynamic consequences are masked by the LVAD's continuous flow output, rendering CRT's corrective effect clinically irrelevant. In addition, there is a theoretical concern that biventricular pacing could unintentionally disrupt ventricular mechanics, potentially displacing the septum or lateral wall toward the inflow cannula, which might predispose to suction-related complications, RV dysfunction, or arrhythmic events. The altered hemodynamic environment created by continuous-flow devices—marked by diminished pulsatility and disturbed vascular signaling—may further reduce the physiological effectiveness of CRT. It is conceivable, however, that CRT may offer selective advantages in specific clinical scenarios, depending on individual cardiac mechanics or structural characteristics. Further research is warranted to clarify these contexts and refine patient selection criteria, in order to guide the appropriate use of CRT in the setting of mechanical circulatory support.

In real-world settings, the lack of observed clinical or hemodynamic benefit from continued CRT following LVAD implantation may have practical implications for long-term device strategy. Indeed, biventricular pacing is known to accelerate battery depletion, and procedures associated with generator replacement can be particularly risky in this population, with a higher incidence of complications such as pocket hematomas, infections, and even LVAD-related infections (6, 16). For patients with CRT-P who maintain an intrinsic rhythm, deferring generator exchange may be a reasonable approach to minimize procedural hazards—especially
in light of our findings showing no added hemodynamic benefit from biventricular pacing over intrinsic conduction. Similarly, for pacing-dependent individuals, a transition to RV-only pacing could be considered, as it may preserve battery life without negatively impacting hemodynamic performance, particularly given our findings showing no hemodynamic advantage of biventricular over RV pacing. In patients with CRT-D systems, downgrading to ICD-only therapy while abandoning the LV lead may offer a simpler, lower-risk, and more economical alternative. Finally, emerging conduction system pacing modalities, such as left bundle branch area pacing, represent a promising area for future investigation (17). By more closely mimicking physiological activation with a single depolarization wavefront, this strategy could offer distinct effects in the LVAD setting and merits further study.

Overall, these findings emphasize the need for improved methods to identify patients unlikely to respond to CRT prior to device implantation. Those progressing to LVAD support after receiving CRT probably derived limited benefit from resynchronization therapy. Early recognition of such non-responders could prevent unnecessary CRT use, streamline treatment pathways, and enable timely access to advanced therapies like LVAD implantation—or potentially guide CRT removal at the time of LVAD surgery. Considering the lack of proven survival benefit and the associated procedural risks, well-designed randomized controlled trials are crucial to establish the true value and patient selection criteria for CRT in the setting of LVAD support.

## Limitations

This meta-analysis is mainly limited by the nature of the available data, which predominantly originate from retrospective, single-center studies, thus exposing the results to potential information bias. Additionally, HeartMate 3 devices were underrepresented among the included patients, which restricts the generalizability of our findings to the current LVAD population. Indeed, HeartMate 3 is now the sole device used for new implantations in clinical practice,
although HeartMate 2 and HeartWare still account for a significant proportion of previously
implanted devices. Additionally, hemodynamic outcomes were derived from a limited number
of studies, several with small sample sizes, and should therefore be interpreted as exploratory
findings requiring validation in larger, adequately powered studies. However, these small
studies did not contribute to our primary endpoint of all-cause mortality, which demonstrated
consistent results with low heterogeneity across larger cohorts. Another important limitation is
the absence of device-related complication data across the included studies, which should be
included in dedicated studies for a comprehensive benefit-risk assessment. Furthermore, despite
being the largest meta-analysis on this subject to date, the overall quality of evidence remains
modest, and no definitive causal inferences can be drawn without data from large randomized
controlled trials.

Conclusion

In this large meta-analysis, CRT was not associated with an overall survival benefit in LVAD
recipients, nor with any hemodynamic improvement. Future randomized controlled trials may
be warranted to definitively establish the role of CRT in LVAD recipients and to refine patient
selection criteria for optimal outcomes.

Sources of Funding

None.

Acknowledgements

None.

Conflict of Interest Disclosures

None.
**Data availability statement**

The authors declare that all supporting data are available within the article [and its online supplementary files].

**References**

1. Saeed D, Feldman D, Banayosy AE, et al. The 2023 International Society for Heart and Lung Transplantation Guidelines for Mechanical Circulatory Support: A 10-Year Update. *J Heart Lung Transplant*. 2023 Jul;42:e1-e222.

2. Amir O, Adamopoulos S, Burri H, et al. Cardiac implantable electronic and other monitoring devices in continuous-flow left ventricular assist device patients. A clinical consensus statement of the Heart Failure Association and the European Heart Rhythm Association of the ESC. *Eur J Heart Fail*. 2025 Apr 1. Epub ahead of print.

3. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. *Eur Heart J*. 2021 Sep 21;42:3599-3726.

4. Sayer G, Ahmed MM, Mehra MR, et al. Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist DevicesA MOMENTUM 3 Trial Analysis. *J Card Fail*. 2025 Jan 22:S1071-916400012-0.

5. Oates CP, Lawrence LL, Bigham GE, et al. Impact of Cardiac Resynchronization Therapy on Ventricular Arrhythmias and Survival After Durable Left Ventricular Assist Device Implantation. *ASAIO J*. 2025 Feb 1;71:157-163.

6. Tattevin P, Flécher E, Auffret V, et al. Risk factors and prognostic impact of left ventricular assist device-associated infections. *Am Heart J*. 2019 Aug;214:69-76.

7. Peichl P, Bayes-Genis A, Deneke T, et al. Drug therapy and catheter ablation for management of arrhythmias in continuous flow left ventricular assist device's patients: a
Clinical Consensus Statement of the European Heart Rhythm Association and the Heart Failure Association of the ESC. *Europace*. 2024 Nov 1;26:euae272.

8. Higgins J, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions Version 6.4. Cochrane; 2019. www training cochrane org handbook

9. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. *BMJ*. 2021; 372:n71.

10. Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016 Oct 12;355:i4919.

11. Cochrane RoB 2: A Revised Cochrane Risk-of-Bias Tool for Randomized Trials. Available online: https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials.

12. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. *BMJ*. 2008;336:924-6.

13. Lin L, Aloe AM. Evaluation of various estimators for standardized mean difference in meta-analysis. *Stat Med*. 2021 Jan 30;40:403-426.

14. Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta-analyses. *BMJ*. 2011; 342:d549.

15. Khush KK, Zaroff JG, Nguyen J, et al. National decline in donor heart utilization with regional variability: 1995-2010. *Am J Transplant*. 2015 Mar;15:642-9.

16. Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. *Eur Heart J*. 2021 Sep 14;42:3427-3520.

17. Vijayaraman P, Sharma PS, Cano Ó, et al. Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy. *J Am Coll Cardiol*. 2023 Jul 18;82:228-241.
Figures legends

<figure><img src="image_3.png" /><figcaption>Figure 1. Flow chart of the study.</figcaption></figure>

<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /><figcaption>Figure 2. Meta-analysis of clinical outcomes assessing the impact of CRT in LVAD recipients.</figcaption></figure>

Panel A shows the comparison between CRT-D and ICD. Panel B presents the comparison
between CRT on and CRT off. Panel C illustrates the comparison between CRT and no device or ICD. Panel D shows the comparison between CRT and no device. CI, confidence interval; CRT, cardiac resynchronization therapy; ICD, implantable cardioverter-defibrillator; LVAD, left ventricular assist device; OR, odds ratio

<figure><img src="image_6.png" /></figure>

Figure 3. Meta-analysis of hemodynamic outcomes assessing the impact of CRT in LVAD recipients. Panel A shows the comparison between biventricular and RV pacing. Panel B presents the comparison between biventricular pacing and intrinsic rhythm. Panel C illustrates the comparison between CRT on and CRT off for LVEDD. CI, confidence interval; CRT, cardiac resynchronization therapy; HR, heart rate; LVAD, left ventricular assist device; LVEDD, left ventricular end-diastolic diameter; MPAP, mean pulmonary artery pressure; OR, odds ratio; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; RAP, right atrial pressure; RV, right ventricular; RVSWI, right ventricular stroke work index; TDCO, thermodilution cardiac output
## Graphical abstract

<figure><img src="image_7.png" /></figure>

# CRT Benefit in LVAD Patients
Meta-analysis of 13 studies including 3,665 patients

CRT-D vs ICD

CRT on vs CRT off

CRT vs No device

<figure><img src="image_8.png" /></figure>

* No survival advantage for all-cause mortality

* No hemodynamic benefit on right heart catheterization parameters

* Potential for device-related complications (pocket hematoma, local or systemic infections)

Refining patient selection criteria and conducting adequately powered studies may help identify potential CRT responders among LVAD patients

## Declaration of interests

[x] The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

[ ] The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: