Establishing minimally important differences for cardiac MRI end-points in pulmonary arterial hypertension
European Respiratory Journal, vol. 62, pp. 2202225
Abstract
BACKGROUND: Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives". METHODS: Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements. RESULTS: 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening. CONCLUSIONS: This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR.
Authors 27
-
Sheffield Teaching Hospitals NHS Foundation Trust · Insigneo · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK s.alabed@nhs.net
INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico medicine, University of Sheffield, UK
-
Affiliation as printed
Norwich Medical School, University of East Anglia, Norwich, UK
University of East Anglia, Norwich Medical School, Norwich, United Kingdom
-
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Sheffield Teaching Hospitals NHS Foundation Trust · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Sheffield Teaching Hospitals NHS Foundation Trust · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Sheffield Teaching Hospitals NHS Foundation Trust · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Sheffield Teaching Hospitals NHS Foundation Trust · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Sheffield Teaching Hospitals NHS Foundation Trust
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
-
Sheffield Teaching Hospitals NHS Foundation Trust · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Insigneo · University of Sheffield
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico medicine, University of Sheffield, UK
-
Affiliation as printed
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
-
Affiliation as printed
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
-
Affiliation as printed
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
-
Insigneo · University of Sheffield
Affiliation as printed
Department of Computer Science, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico medicine, University of Sheffield, UK
-
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Royal Hallamshire Hospital · University of Sheffield
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Royal Hallamshire Hospital · University of Sheffield
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Royal Hallamshire Hospital · University of Sheffield
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Sheffield Teaching Hospitals NHS Foundation Trust · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Royal Hallamshire Hospital · University of Sheffield
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Royal Hallamshire Hospital · University of Sheffield
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
-
Rob J. van der Geest Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, Leiden, The Netherlands
-
National Institute for Health and Care Research · Sheffield Teaching Hospitals NHS Foundation Trust · Insigneo · NIHR Sheffield Biomedical Research Centre · University of Sheffield
Affiliation as printed
Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
Joint senior authors
National Institute for Health and Care Research, Sheffield Biomedical Research Centre, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico medicine, University of Sheffield, UK
joint senior authors
-
Royal Hallamshire Hospital · National Institute for Health and Care Research · Insigneo · NIHR Sheffield Biomedical Research Centre · University of Sheffield
Affiliation as printed
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
Joint senior authors
National Institute for Health and Care Research, Sheffield Biomedical Research Centre, Sheffield, UK
Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK
INSIGNEO, Institute for in silico medicine, University of Sheffield, UK
joint senior authors
Cited by 27 stored of 27
No patents citing this paper on Lens.org (checked 2026-10-11).