Clinical trial NCT04686253: Internal Microstructure of Patent Foramen Ovale Related to Stroke
Official title: Internal Microstructure of Patent Foramen Ovale Related to Cryptogenic Stroke, Transient Ischemic Attack or Migraine
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Patent Foramen Ovale
Keywords: patent foramen ovale
stroke
transient ischemic attack
migraine
microstructure
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Beijing Anzhen Hospital
name: The Affiliated Hospital of Xuzhou Medical University
name: Tibet Autonomous Region People's Hospital
First posted: 2020-12-28
Enrollment: 1200
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll subjects with PFO, and enrollment will be divided into three cohorts.

Cohort 1: PFO patients with CS or/and TIA (transcatheter closure of PFO was performed). A minimum of 100 patients is reached.

Cohort 2: PFO patients with migraine (transcatheter closure of PFO was performed). A minimum of 100 patients is reached.

Cohort 3: PFO patients without symptom (5-year follow-up). A minimum of 100 patients is reached.

Brief summary: This study aims to (1) investigate the internal microstructure of patent foramen ovale related to cryptogenic stroke, transient ischemic attack or migraine and determine the effectiveness of transcatheter closure in these patients; (2) evaluate the microstructural features of asymptomatic patients with PFO and make a follow-up；(3) perform an untargeted metabolomics analysis using plasma samples from right atrium and left atrium and shunt provocative test was conducted;(4) collect the blood sample from PFO tunnel;(5) cardiac CTA was performed to evaluate the position and morphology of device.

Detailed description: Patent foramen ovale (PFO) is associated with a variety of pathological conditions, and it is presumed to be related to the occurrence of cryptogenic stroke (CS), transient ischemic attack (TIA) or migraine. In addition, the main hypothesized pathophysiologic mechanism is paradoxical embolization, namely microemboli or metabolites from the venous circulation to enter the systemic circulation. The morphological characteristics of PFO have the potential to predict risks and screen the appropriate candidates for transcatheter closure. The structure features for predicting risk included atrial septal aneurysm, a large right-left shunt, long-tunnel PFO and so on. However, the in-vivo internal microstructure of PFO is still unclear. The microstructural features might provide important information for better understanding the PFO and risk stratification.

The aim of this study is to (1) investigate the internal microstructure of patent foramen ovale related to cryptogenic stroke, transient ischemic attack or migraine and determine the effectiveness of transcatheter closure in these patients; (2) evaluate the microstructural features of asymptomatic patients with PFO and make a follow-up；(3) perform an untargeted metabolomics analysis using plasma samples from right atrium and left atrium and shunt provocative test was conducted;(4) collect the blood sample from PFO tunnel;(5) cardiac CTA was performed to evaluate the position and morphology of device.

This study will enroll subjects with PFO, and enrollment will be divided into three phases.

Phase 1: PFO patients with CS or/and TIA (transcatheter closure of PFO was performed). A minimum of 500 patients is reached.

Phase 2: PFO patients with migraine (transcatheter closure of PFO was performed). A minimum of 500 patients is reached.

Phase 3: PFO patients without symptom (5-year follow-up). A minimum of 200 patients is reached.

In addition, blood samples were obtained, including inferior vena cava, superior vena cava, right atrium, PFO-tunnel, left pulmonary artery, left atrium and left pulmonary vein. Then, another 20 ml blood sample was obtained from right atrium (near PFO) and injected into left atrium immediately. During a ten-minute waiting period, any symptom was recorded.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 16 to 65 years without any known vascular risk factor, including hypertension, hypercholesterolemia, diabetes mellitus, atrial fibrillation, smoking and obesity;
2. Documented PFO with right-to-left shunt ≥ 20 micro-bubbles by c-TCD;
3. Stroke group: history of ischemic stroke (based on brain magnetic resonance imaging) or TIA within 6 months without other identifiable causes (Phase1);
4. Migraine group: history of migraine headaches more than one year without other identifiable causes (Phase2);
5. Control group: incidental finding of PFO without neurological or systemic symptoms (Phase3).

Exclusion Criteria:

1. Any identifiable cause of ischemic stroke/TIA or migraine other than PFO;
2. History of stroke or TIA within the past one month;
3. Presence of cardiac enlargement or dysfunction;
4. Presence of coexisting cardiovascular structural malformations/diseases;
5. Presence of carotid artery lesions or coronary artery disease;
6. Presence of deep vein thrombosis or pulmonary embolism;
7. Presence of implanted cardiac devices;
8. Evidence of hypercoagulable state;
9. Allergic to contrast medium;
10. Echocardiographic evidence of intra-cardiac thrombus, mass, tumor or vegetation;
11. Active endocarditis or other infections.

Primary outcomes:
measure: Adverse Events after evaluation of PFO internal microstructure
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chaowu Yan
state: Beijing
city: Beijing
country: China
facility: National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences,Fuwai Hospital
state: Beijing
Study officials:
References:
citation: Yan C, Li H, Wang C, Yu H, Guo T, Wan L, Yundan P, Wang L, Fang W. Frequency and Size of In Situ Thrombus Within Patent Foramen Ovale. Stroke. 2023 May;54(5):1205-1213. doi: 10.1161/STROKEAHA.122.041524. Epub 2023 Mar 9.
citation: Yan C, Li H. Preliminary Investigation of In situ Thrombus Within Patent Foramen Ovale in Patients With and Without Stroke. JAMA. 2021 May 25;325(20):2116-2118. doi: 10.1001/jama.2021.4359.