Delphi Consensus on Reporting Standards for Right Ventricular Pressure–Volume Loop Studies in Large Animal Models

Delphi Consensus on Reporting Standards for Right Ventricular Pressure–Volume Loop Studies in Large Animal Models Michaela Orlitová, MD, PhD1, Simone Juel Dragsbaek, MD2,3, Piet Claus, Assoc. Prof. 1, Mads Dam Lyhne, MD, PhD2,4 Affiliations: 1. Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium 2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark 3. Department of Cardiology, Aarhus University Hospital, Aarhus Denmark 4. Department of Anesthesiology and Intensive Care, Horsens Regional Hospital, Denmark Principal investigators: Michaela Orlitová, MD, PhD, KU Leuven, and Mads Dam Lyhne, Aarhus University. Responsible institution: Aarhus University Oversight: Ethical and legal aspects, including data protection, will be overseen by Aarhus University. Background Right ventricular (RV) pressure–volume (PV) loop analysis is considered the gold standard for assessing RV function and cardiopulmonary interactions [1–3]. However, a recent systematic review on current practices using conductance and admittance catheters in large animal research (under review, protocol: https://doi.org/10.17605/OSF.IO/WVSK4) has demonstrated substantial heterogeneity in both methodology and reporting of experimental RV PV loop studies. Variability was observed in catheterization techniques, calibration procedures, respiratory conditions during data acquisition, and presentation of results. Importantly, many studies failed to report essential methodological details, limiting transparency, reproducibility, and comparability across investigations. This lack of consistency hampers the ability to synthesize findings, undermines translation between experimental and clinical research, and reduces the impact of RV PV studies in advancing cardiovascular science [4–6]. Attempts to improve animal research transparency and rigor have been made with the ARRIVE guidelines [7]. However, those are general recommendations, and specific requirements to conducting and reporting RV PV loop recordings with conductance or admittance catheters in large animal research are equally important. To address the current limitations, a structured expert consensus process is needed to define minimum reporting standards and provide guidance on methodological descriptions. Methods Study Design This study will employ a modified Delphi consensus methodology to establish expert agreement on reporting standards for RV PV loop studies. The Delphi method is a structured, iterative process that combines anonymous expert input, controlled feedback, and quantitative analysis of group responses. The Delhi method is appropriate where expert opinion is the only level of evidence [8,9]. Ethical Considerations Participation in this Delphi study poses no risks, side effects, or disadvantages to panelists. Panelists will only be asked to provide expert opinions via online questionnaires. No medical interventions or collection of biological data are involved. Responses will be anonymized, and only the panel convener will have access to individual responses. Informed consent will be obtained from all participants prior to inclusion. Participation is voluntary, and panelists may withdraw at any time without consequences. This protocol will be published online beforehand and sent to potential panelists at the time of invitation. The study was evaluated by The Central Denmark Region Committees on Health Research Ethics (ref. no. 1-10-72-116-25), and according to the Danish Consolidation Act on Research Ethics Review of Health Research Projects (questionaire research, section 2) the project was not considered as a health research study therefore not needing ethical approval. Data Protection All data will be collected and stored in compliance with the General Data Protection Regulation (GDPR) and local data protection laws. Responses will be recorded in REDCap hosted on secure institutional servers. Only members of the steering group will have access to the raw data. Aarhus University is data controller and information on data processing including right to complain will be sent to all invited panelists. The processing of personal data has been registered to the AU record. Panelists’ names and contact details will be used exclusively for the purpose of study administration and authorship recognition and will not be shared outside the steering group. Survey responses will be anonymized before analysis and reported in aggregated form only. Data will be stored securely until completion of the study and then deleted. Panelists have the right to withdraw their participation at any time, in which case their personal data and responses will be removed if technically feasible. Panelists A purposive international panel of experts in RV physiology, PV loop methodology, and relevant clinical specialties will be invited. For the panel to consist of various stakeholders, inclusion criteria will include: ● Researchers from institutions identified in the systematic review, i.e. with present RV PV experiments. Each institution will be allowed to have one panelist with practical PV experience. ● Experts that have demonstrated expertise through peer-reviewed publications or recognized methodological contributions ● Representation from experimental and clinical backgrounds ● Representation from PV catheter manufacturers ● Representation from major physiological societies and high-ranked physiological journal editorial boards with background in RV physiology ● Geographic and demographic diversity to ensure broad perspectives Invitations will be sent to approximately 40 potential panelists for a target panel size of 15-25 by an expected drop-out of 50% [8]. All panelists who complete all Delphi rounds will be included as co-authors, the remaining acknowledged as collaborators. Participants who miss one round will not be allowed to re-enter the panel. Procedures The Delphi process will follow general Delphi recommendations [8] and include three online rounds: ● Round 1: Initial questionnaire developed by the steering group based primarily on the round 0 systematic review (under review), covering a number of domains: 1. Procedures including quality assurance 2. Key parameters and reporting 3. Data presentation For each statement, panelists will be asked to rank their response on a 1-9 Likert scale and to briefly argue the reason behind. Some questions will require yes/no responses by the panelists. Open comments from panelists capturing additional suggestions may be re-phrased into new statements of similar structure as the other questions. ● Round 2: Items refined based on feedback from round 1. Panelists will receive summary statistics (median, IQR), their own previous responses, and all responses and comments provided by the entire panel in an anonymous form (controlled feedback) before re-rating. ● Round 3: Focused on unresolved items. Structured feedback will again be provided, and final ratings collected. All rounds will be conducted via a secure online platform (REDCap). Each round will remain open for 2–3 weeks with reminders sent as needed. Time between rounds will be 2-4 weeks. Analysis Plan Panel characteristics Participants will be asked to provide age, sex, academic rate/title and years of PV experience. Descriptive statistics (median, interquartile range, percentage agreement) without weighting will be calculated for all items in each round. Consensus Criteria Consensus will be defined a priori using RAND/UCLA methodology [8]: ● Consensus in: ≥70% of experts rating an item 7–9 on a 9-point Likert scale and ≤15% rating it 1–3. In yes/no cases, consensus is reach if ≥70% of experts answered yes. ● Consensus out: reverse thresholds (≥70% 1–3, ≤15% 7–9). In yes/no cases, consensus is reach if ≥70% of experts answered no. ● No consensus: items not meeting either criterion Statements will not be subtracted after Round 1 despite consensus is reached. Statements will be included in at least two rounds, even if consensus is reached in the first. This reflects a core principle of the Delphi methodology, which enables participants to revise their responses after considering the perspectives of others. If consensus is reached twice, the statement will be left out of the final round. All non-consensus items will be reported transparently. Stability of ratings across rounds will also be assessed. In the final report, statements with consensus reached will be stated as “recommended” if Consensus In and “not recommended” if Consensus Out with the statements not receiving consensus at Round 3 as “Optional”. Reporting Results will be reported following recommended standards for Delphi studies, including panel flow, response rates, and consensus outcomes. Results and Dissemination Results The primary outcome will be consensus-based recommendations for reporting RV PV loop studies. Results will be presented as: ● Summary tables of consensus in/out/no consensus items ● Narrative synthesis of key recommendations and unresolved issues ● Flow diagram of participant inclusion and retention ● A final checklist or reporting statement Dissemination Presentation will follow Delphi reporting guidelines, such as the ACCORD and DELPHISTAR standards. The final paper and checklist will be published in an international peer-reviewed relevant journal. Feasibility The study is feasible as it builds on an established network of experts identified through a recent systematic review, professional societies, journal editorial boards, and industry representatives. The methodology is simple, low-cost, and relies on secure online survey platforms (e.g., REDCap). The steering group has prior experience with international collaborations. Given the strong international interest in RV PV loop methodology and the clear need for improved reporting standards, successful completion of the project within the proposed timeline is highly realistic. Funding and conflicts of interest No funding h