UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) Registry Study

Official title

The UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) Registry

Overview

The goal of this observational study is to develop a large, deeply characterised cohort that will be a platform for collaborative clinical and translational research into cardiovascular (CV) disease (CVD) and Immune-mediated-inflammatory-diseases (IMID). The main aim is to evaluate whether existing blood cardiac biomarkers predict adverse cardiovascular outcomes. The study will capture standard of care CV and associated health data (clinical, biochemistry/pathology and investigations) in patients across the IMIDs. Optional biological and/or imaging sub-studies will provide additional data and/or samples for associated analyses.

Detailed description

Multimorbidity is a rapidly growing burden on our healthcare systems, especially with an ageing demographic. CVD is a major cause of morbidity and mortality. The co-association of IMIDs with CVD needs more sophisticated understanding of the underlying risk, earlier identification and tailored use of targeted therapeutics. Importantly, the investigation of CVD in IMID offers an effective human experimental model to improve not just the lives of people with IMIDs but also the general CVD population.

The UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) registry will be a key platform for United Kingdom (UK) multi-centre clinical and translational CARDIO-IMID research. The aim is that centres across the UK including all the devolved nations will collaborate and contribute patients such that the registry will provide deep phenotyping, linked to clinical outcomes, in, ultimately, many hundreds of patients. The planned study will establish a deeply phenotyped cohort and/or as part of the optional sub-study, an associated bioresource to support individual discrete studies and/or analyses that address the stated aims and objectives. All potential participants will be invited to participate in the longitudinal collection and evaluation of routine comprehensive clinical information, including pathology, imaging and other cardiovascular data. This programme will identify patients within defined IMID clinical cohorts at different stages of (rheumatology and cardiovascular) disease. These data will be invaluable in enabling a full characterisation of CVD in terms of the extent, presentation, risk factors, and pathophysiology. Patients are seen as per standard clinical practice determined by the index IMID and in this setting, also dependent on co-existing CV comorbidity, usually every 3-6 months at time of IMID/CVD diagnosis and then 6 to 12 monthly thereafter. Specific questionnaires and tests requested outside of standard of care (sub-studies) will depend on disease group and clinical context. Not all patients will be required to complete all the relevant questionnaires, instead, based on individual IMID and/or CVD profile.

In addition, there is the opportunity for subjects to include (i) longitudinal biological (blood) samples and (ii) extended cardiovascular magnetic resonance (CMR) imaging protocol for those receiving CMR as part of National Health Service (NHS) standard of care.

Collectively, the study and associated platform with appropriate biostatistical and machine learning approaches will inform on the pathophysiological sequence of events, identification of prognostic biomarkers and risk models; as well as enable evaluation of the influence of IMID-specific vascular +/- immunosuppressive therapies and traditional cardiac pharmacotherapy where indicated. It will also establish a platform for trials in IMIDs to capture CV outcomes. Moreover, it will provide cohorts of patients readily available for recruitment, with linkage in place for outcomes. It could be used to leverage commercial funding and participation, facilitated by simplified, single-point access for industry. It will enable scaled investigation aimed at understanding causes of CARDIO-IMID, improving risk stratification and providing better care.

Primary outcome measures

• Number of participants with abnormal high-sensitivity cardiac troponin I/T levels [Time frame: 5 years]
• Number of participants with abnormal N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels [Time frame: 5 years]

Secondary outcome measures (12)

• Number of participants with atherosclerotic cardiovascular disease (ASCVD) [Time frame: 5 years]
• Number of participants with myopericardial involvement [Time frame: 5 years]
• Number of participants with other cardiovascular events [Time frame: 5 years]
• Atrial and ventricular volumetrics [Time frame: 5 years]
• Systolic and diastolic function [Time frame: 5 years]
• Abnormalities in regional wall motion [Time frame: 5 years]
• Global longitudinal strain [Time frame: 5 years]
• T2 relaxation time [Time frame: 5 years]
• Late gadolinium enhancement [Time frame: 5 years]
• T1 relaxation time [Time frame: 5 years]
• Extracellular volume fraction [Time frame: 5 years]
• Aortic distensibility [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Written informed consent
• Diagnosis of an IMID by a rheumatologist with categorisation into one of the following:

i. IMID-'higher risk' CVD: individuals who have a risk of developing CVD (based on traditional risk factors and/or IMID-specific factors) but no history of CVD

• Coronary artery disease (CAD): specifically, a high pre-test probability of CAD based on clinical risk factors (e.g. QRISK3 score ≥10%) and/or elevated biochemical markers (high-sensitivity C-reactive protein ≥2mg/L and/or Lipoprotein(a) ≥70mg/dL)
• Myopericardial involvement: Specific IMID and/or cardiovascular indicators that place at increased risk e.g. autoantibody associations, presence of peripheral myositis or other major organ involvement; incidental raised serum cardiac biomarkers (troponin and/or NT-pro BNP), on routine testing

ii. Incident (new) IMID-CVD: Patients with IMID that present with a new history of CVD

<!-- -->

• ASCVD i. Major adverse cardiovascular events (MACE):

\- Non-fatal myocardial infarction.

\- Non-fatal stroke of any classification, including reversible focal neurologic

\- Defects with imaging evidence of a new cerebral lesion consistent with ischemia or haemorrhage.

ii. Other cardiovascular events not accounted for in the MACE-3 composite 2)a)i:

\- Hospitalization for unstable angina

\- Coronary revascularization

\- Hospitalization for heart failure

\- Transient Ischemic Attack (TIA)

\- Peripheral Vascular Disease (PVD)

• Deep vein thrombosis (VTE) and/or pulmonary embolism \[PE\].
• Myopericardial involvement: as diagnosed by a cardiology specialist with 'tier 2' cardiovascular imaging and/or other clinical and biochemical criteria in line with usual care

iii. Established IMID-CVD

a) Patients with IMID and a history of past cardiovascular event as detailed in 2) a) above.

b) Patients with a known history of myopericardial involvement as defined above in 2) b)

Biological sub-study inclusion criteria

• There are no additional inclusion criteria for this sub-study

Extended protocol standard CMR sub-study inclusion criteria.

• Participants that receive a CMR scan as standard of care

Exclusion criteria

• Age less than 18 years
• Unable to give informed consent

Biological sub-study exclusion criteria:

\- There are no additional exclusion criteria for this sub-study

CMR sub-study exclusion criteria:

Standard of care contraindications to:

• CMR: metal implant eg metal fragments in the eye, pacemaker; claustrophobia; inability to lie flat
• Magnetic Resonance Imaging (MRI) contrast: renal failure with estimated glomerular filtration rate (eGFR) <30,

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United Kingdom · 2 centers

• Royal Infirmary of Edinburgh — Edinburgh
• Countess of Chester Hospital NHS Foundation Trust — Chester

Publications

• Luscher TF. Heart failure: the cardiovascular epidemic of the 21st century. Eur Heart J. 2015 Feb 14;36(7):395-7. doi: 10.1093/eurheartj/ehv004. No abstract available. PMID 25681826
• Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the PMID 27206819
• Chang PP, Wruck LM, Shahar E, Rossi JS, Loehr LR, Russell SD, Agarwal SK, Konety SH, Rodriguez CJ, Rosamond WD. Trends in Hospitalizations and Survival of Acute Decompensated Heart Failure in Four US Communities (2005-2014): ARIC Study Community Surveillance. Circulation. 2018 Jul 3;138(1):12-24. doi: 10.1161/CIRCULATIONAHA.117.027551. Epub 2018 Mar 8. PMID 29519849
• Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256. PMID 16855265
• Lewis GA, Schelbert EB, Williams SG, Cunnington C, Ahmed F, McDonagh TA, Miller CA. Biological Phenotypes of Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2017 Oct 24;70(17):2186-2200. doi: 10.1016/j.jacc.2017.09.006. PMID 29050567
• Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J; CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003 Sep 6;362(9386):777-81. doi: 10.1016/S0140-6736(03)14285-7. PMID 13678871
• Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A; I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 Dec 4;359(23):2456-67. doi: 10.1056/NEJMoa0805450. Epub 2008 Nov 11. PMID 19001508
• Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O'Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E; RELAX Trial. Effect of phosphodiesterase-5 inhibition on exercise cap PMID 23478662

Identifiers

NCT: NCT06478277 · 341045

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗