Refining the framework of cardiac prehabilitation: insights from the PREQUEL trial and beyond

We read with interest the editorial commentary (1) on our study, “Effect of exercise prehabilitation on quality of recovery after cardiac surgery: a single-centre randomised controlled trial” (2). We thank the authors for their insightful appraisal of our work and welcome the opportunity to expand upon their observations by integrating recent findings from our published secondary analyses to further refine the “who, what, when, where, and how” of cardiac prehabilitation.

Concept of “dose”: adherence and efficacy

The editorial (1) highlights several limitations encountered in our PREhabilitation for improving QUality of recovery after ELective cardiac surgery (PREQUEL) trial (2). These include a low recruitment rate, higher-than-anticipated attrition because of unpredictable surgical cancellations, and suboptimal adherence to home-based exercise monitoring. Collectively, these challenges underscore the substantial logistical burden associated with supervised, in-person prehabilitation programs for frail older adults.

These systemic barriers become more apparent when considered alongside our recent post hoc causal inference analysis (3). Merely offering prehabilitation is insufficient; frail patients must be able to reliably accrue a therapeutic “dose” before cardiac surgery. In our dose–response analysis, a greater number of consecutive prehabilitation sessions led to reduced disability levels at postoperative day (POD) 90, as measured by the World Health Organization Disability Assessment Schedule (3). Specifically, a minimum of 3 weeks of training (five or more consecutive supervised sessions) was required before improvements in disability were observed, while up to 7 weeks (14 or more sessions) were needed to achieve a clinically meaningful improvement in functional capacity (≥25-metre gain on the 6-minute walk test) (3). Patients who failed to reach this therapeutic threshold—necessary to meaningfully alter postoperative trajectories—may have faced unpredictable surgical scheduling and transportation barriers.

The timing of outcome measurement: early vs. medium-term recovery

Another limitation of our primary trial design, highlighted by the editorial (1), is that measurement of the 15-item Quality of Recovery (QoR-15) score on POD3 may have been too early to capture meaningful differences in recovery trajectories, as patients were still experiencing acute physiological and psychological stress related to major cardiac surgery. However, our clinical workflow in Hong Kong is designed for rapid recovery. Elective cardiac surgery patients are typically extubated within 6 to 8 hours, with mobilization beginning on POD1 and progressing to assisted ambulation by day two; drains are usually removed by day four. Our goal is to facilitate mobilization as soon as possible once patients are stable, consistent with Enhanced Recovery After Cardiac Surgery (ERACS) protocols (4). Because early mobilization depends on effective pain control, patient comfort, and functional independence, we believe that QoR‑15 assessment within 72 hours meaningfully reflects recovery and aligns with enhanced recovery objectives and clinical workflow.

Nonetheless, the goals of prehabilitation should extend beyond postoperative metrics and early survival to optimizing medium- and long-term recovery. This concept is supported by an exploratory secondary analysis of our PREQUEL trial (5). Specifically, we evaluated patients who experienced suboptimal early recovery (defined as a QoR-15 score ≤80 on POD3). Notably, exercise-based prehabilitation was associated with significant improvements in self-rated health status (as measured by the EQ VAS) and with a reduced risk of functional limitations across multiple EQ-5D-5L dimensions at 90 days after surgery—particularly among those with poor early recovery (5).

Long-term outcomes: survival, readmissions, and the need for continuity of care

Few prehabilitation programs have evaluated long-term outcomes. Cardiac prehabilitation alone demonstrated little effect on total time spent at home—defined as the percentage of Days Alive and Out of Hospital—or on hospital readmission rates over a 4-year follow-up period (6). Notably, late readmissions were frequently attributable to non-cardiac infections and frailty-related conditions, highlighting enduring vulnerabilities that a brief preoperative exercise intervention is unlikely to mitigate over the long term. Nevertheless, prehabilitation was associated with a statistically significant, albeit modest, survival benefit of approximately 11 weeks over 4 years (6). This dissociation—whereby physiological gains translate into extended survival without a corresponding reduction in subsequent hospitalizations—highlights that prehabilitation represents only the initial step. To sustain these benefits and reduce frailty-related readmissions, a seamless continuum of care integrating prehabilitation, postoperative cardiac rehabilitation, and coordinated transitional community care is essential.

Future directions: addressing unmet evidence needs

To address the barriers outlined above and build on the foundations established by our PREQUEL trial (2), it is essential to focus on the multidimensional nature of frailty. While our intervention primarily focused on physical exercise, supplemented by basic nutritional and psychological advice, future cardiac prehabilitation programs should adopt a more comprehensive multimodal approach. This will require a more detailed baseline assessment of nutritional deficiencies, cognitive impairment, and psychological distress. Interventions that deliberately target interactions across these frailty domains are likely to generate synergistic benefits that extend beyond those achievable through exercise alone.

To enable patients to achieve the required exercise “dose” without the logistical burden of frequent hospital visits, future trials may use mobile health (mHealth) applications and wearable activity trackers. These technologies facilitate real-time, objective monitoring of adherence to home-based programs, thereby enhancing the safety and effectiveness of hybrid or fully remote prehabilitation models. Notably, a recent cardiac multimodal tele-prehabilitation study (n=394) showed a reduction in major adverse cardiovascular events at 1 year after surgery (8.8%, 95% confidence interval: 0.7–16.8%) (7). Such remote prehabilitation approaches may also improve patient recruitment and retention, particularly among frail individuals who face geographic or transportation barriers to accessing tertiary surgical centres.

Conclusions

As we have previously proposed (3), the perioperative medicine community must undergo a fundamental paradigm shift. The focus must move beyond simply making patients “Fit for Surgery”—that is, ensuring they survive the operation—to a more holistic goal of enabling them to be “Fit for Quality of Life After Surgery”. While evidence from the PREQUEL trial and subsequent secondary analyses has advanced our understanding of the who, what, when, where, and how of cardiac prehabilitation, substantial knowledge gaps remain. Addressing these gaps will require cohesive evaluations of multimodal prehabilitation and postoperative rehabilitation models that span the full perioperative continuum.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1383/coif). A.L. is an active member of the Cardiac Prehabilitation Network (University Medical Center Göttingen, Germany), which received a grant “Prehabilitation prior to cardiac procedure” from the German Research Foundation. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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