Cardiac Magnetic Resonance Stress-perfusion Study in Patinets with Fontan Circulation (CMR_TCPC)

Att Överleva Och Leva Som Vuxen Med Enkammarhjärta I Sverige

Univentricular heart (UVH) is a severe congenital heart disease. Accurate advanced non-invasive diagnostic methods is limited. Cardiovascular magnetic resonance (CMR) imaging has evolved as a particularly useful tool for the study of patients with adult congenital heart disease (ACHD) considering its ability to determine detailed anatomy and detect early cardiac dysfunction without the need for radiation exposure. Most of contemporary treatment recommendations are based on consensus opinions/documents and small studies from local, or national registries. Improved knowledge is needed in all these areas to facilitate clinical decisions regarding treatment, monitoring and follow-up.

This study seeks to answer if early detection of deterioration in cardiac function, venous pressure and microvascular dysfunction can identify patients before the symptoms progress and thus help to initiate early treatment. The hypothesis is that quantitative myocardial stress-perfusion maps improves the pathophysiological insight in patients with UVH.

The overall goal with this research proposal is to implement combined advanced CMR imaging for a comprehensive non-invasive mapping of functional cardiovascular behavior in patients with complex UVH disease. The outcome of this research may benefit this young adult patient population due to early detection of cardiac disease, less hospitalizations because of heart failure, and eventually decrease morbidity and mortality.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Univentricular Heart; Microvascular Dysfunction; Magnetic Resonance
• Intervention / Treatment: Diagnostic test: Cardiac magnetic resonance stress-perfusion

Detailed Description

CMR is performed supine with a Magnetom Aera® 1.5 Tesla (T) scanner (Siemens Healthcare, Erlangen, Germany), with a phased-array 18-channel body matrix coil and a spine matrix coil. A venous blood sample is drawn to determine hematocrit and blood creatinine prior to imaging. Full coverage retrospective electrocardiographic (ECG)-gated balanced steady state free precession (bSSFP) cine imaging is acquired in standard three long-axis and short-axis slices. Typical imaging parameters are flip angle 68°, pixel size 1.4 × 1.9 mm2, slice thickness 8.0 mm, echo time (TE)/repetition time (TR) 1.19/37.05 ms, matrix size 256 × 144 and field of view (FOV) 360 × 270 mm2.

Using first-pass perfusion imaging, quantitative perfusion maps (ml/min/g) are acquired in one short-axis and one long-axis slice (mid-ventricular, 2-chamber) during administration of an intravenous contrast-agent bolus (0.05 mmol/kg, gadobutrol, Gadovist, Bayer AB, Solna, Sweden), during adenosine infusion (110 µg/kg/min or increased according to clinical routine to 140 µg/kg/min in the absence of adequate response to adenosine (Adenosine, Life Medical AB, Stockholm) and in subsequent rest. Adenosine response is assessed clinically based on symptoms and heart rate response. Adenosine and contrast agent are administered in two different cannulas. Subjects abstained from caffeine for 24 hours prior to CMR examination. A distributed tissue exchange model is used to compute the perfusion maps and the Gadgetron (reconstruction computer) inline perfusion mapping software is used to generate the perfusion maps.Typical imaging parameters were bSSFP single shot readout, flip angel 50°, slice thickness 8.0 mm, TE/TR 1.04/2.5 ms, bandwidth 1085 Hz/pixel, FOV 360 × 270 mm2 and saturation delay/trigger delay (TD) 95/40 ms.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Peder Sorensson, MD, Associate professor; Phone Number: +46 731 400059; Email: peder.sorensson@ki.se
• Study Contact Backup: Name: Ayse-Gul Ozturk, MD; Email: ayse-gul.ozturk@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden, 17176
    • Recruiting
    • Karolinska University Hospital
    • Contact: Peder Sorensson, MD, Associate professor; Phone Number: +46 731 400059; Email: peder.sorensson@ki.se
    • Contact: Ayse-Gul Ozturk, MD; Phone Number: +46 72 578 02 72; Email: ayse-gul.ozturk@ki.se
    • Contact: Peder Sorensson, MD, Associate professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The project is planned as a prospective cohort study where approximately 30 patients with Fontan circulation will be included. The cohort is out-clinic patients at the tertiary adult congenital heart disease center at the Karolinska University Hospital in Stockholm, Sweden. The patients will be asked to participate in the study when they have a clinical visit at Karolinska by the treating physician or nurse. Inclusion and exclusion criteria are shown above.

Additional data will be collected from the patient cohort; age, gender, underlying diagnoses, interventions, medication, symptoms, NYHA functional class, ECG, cardiac pulmonary exercise results, self-reported level of physical activity, pacemaker / implantable cardioverter defibrillator (ICD), and quality of life assessed by EuroQoL 5-dimensional questionnaire (EQ-5D).

Description

Inclusion Criteria:

• Patients who had undergone total cavo-pulmonary connection (TCPC) surgery resulting in Fontan circulation.
• NYHA (New York Heart Assosiation) class I-II.
• Understanding the study information (signed informed consent).
• >18 years old.

Exclusion Criteria:

• Device therapy (pacemaker, ICD).
• Failing Fontan (NYHA III-IV).
• Kidney failure (GFR<30ml/h).
• Arrythmia (atrial fibrillation).
• Pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Univentricle heart, operated with TCPC (total cavo pulmonary connection)

Diagnostic test: Cardiac magnetic resonance stress-perfusion; Included patients will be examined at the Karolinska University Hospital in a 1.5T Siemens Sola magnetic resonance camera at rest and during adenosine stress with specific CMR sequences (adenosine stress-perfusion, myocardial velocities, and tissue characterization) for non-invasive determination of macro- and microvascular dysfunction, global myocardial function, pulmonary artery pressure and scarring of the myocardium. Adenosine or Regadenoson will be used as stress medication which is according to clinical routine. Adenosine will be infused over approximately 5 minutes (110-140 μg / kg/min), Regadenoson (5 ml) will be a 10-second injection (400 μg single dosage). Intravenous gadolinium-based contrast agents will be administered, Gadovist (1 mmol/ml, gadobuterol), 0.15 mmol/kg during stress and rest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of microvascular dysfunction in patients with UVH	This project aims to evaluate microvascular dysfunction using quantitative stress-perfusion CMR in patients with different morphological systemic chamber (left vs right).	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To detect and compare tissue characterization.	Investigate whether positive findings in tissue characterization is higher in different systemic ventricles (left vs right) using T1 and T2-mapping, LGE (late gadolinium enhancement, myocardial scar).	Through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous pressure in TCPC	Calculate venous delta pressure (customized in-house software) in the cavo-pulmonary connection using CMR 4D-flow imaging.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Karolinska University Hospital

Publications and helpful links

General Publications

• Rychik J, Atz AM, Celermajer DS, Deal BJ, Gatzoulis MA, Gewillig MH, Hsia TY, Hsu DT, Kovacs AH, McCrindle BW, Newburger JW, Pike NA, Rodefeld M, Rosenthal DN, Schumacher KR, Marino BS, Stout K, Veldtman G, Younoszai AK, d'Udekem Y; American Heart Association Council on Cardiovascular Disease in the Young and Council on Cardiovascular and Stroke Nursing. Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association. Circulation. 2019 Aug 6;140(6):e234-e284. doi: 10.1161/CIR.0000000000000696. Epub 2019 Jul 1.
• Di Salvo G, Miller O, Babu Narayan S, Li W, Budts W, Valsangiacomo Buechel ER, Frigiola A, van den Bosch AE, Bonello B, Mertens L, Hussain T, Parish V, Habib G, Edvardsen T, Geva T, Baumgartner H, Gatzoulis MA; 2016-2018 EACVI Scientific Documents Committee. Imaging the adult with congenital heart disease: a multimodality imaging approach-position paper from the EACVI. Eur Heart J Cardiovasc Imaging. 2018 Oct 1;19(10):1077-1098. doi: 10.1093/ehjci/jey102.
• Dalen M, Odermarsky M, Liuba P, Johansson Ramgren J, Synnergren M, Sunnegardh J. Long-Term Survival After Single-Ventricle Palliation: A Swedish Nationwide Cohort Study. J Am Heart Assoc. 2024 Mar 19;13(6):e031722. doi: 10.1161/JAHA.123.031722. Epub 2024 Mar 18.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: CMR; Fontan circulation; tissue characterization; stress-perfusion; univentricle heart; TCPC
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Univentricular Heart
• Other Study ID Numbers: Dnr 2022-04574-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD used i the results publication.
• IPD Sharing Time Frame: April 2024 - April 2026.
• IPD Sharing Access Criteria: On written request to the PI from researchers in the same field of interests.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No