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. 2020 Dec 14;13(23):2745-2752.
doi: 10.1016/j.jcin.2020.09.059.

Patent Foramen Ovale Attributable Cryptogenic Embolism With Thrombophilia Has Higher Risk for Recurrence and Responds to Closure

Kai Liu  1 , Bo Song  1 , Igor F Palacios  2 , Ignacio Inglessis-Azuaje  2 , WenJun Deng  2 , David McMullin  2 , XiaoYing Wang  3 , Eng H Lo  4 , YuMing Xu  5 , Ferdinando S Buonanno  6 , MingMing Ning  7
Affiliations

Patent Foramen Ovale Attributable Cryptogenic Embolism With Thrombophilia Has Higher Risk for Recurrence and Responds to Closure

Kai Liu et al. JACC Cardiovasc Interv. .

Abstract

Objectives: The aim of this study was to investigate the effect of management on the risk for recurrent events among patients with cryptogenic ischemic stroke or transient ischemic attack.

Background: The combination of patent foramen ovale (PFO) and hypercoagulability may greatly increase the risk for paradoxical embolism. However, previous randomized controlled trials evaluating the efficacy of PFO closure excluded these potential high-risk patients.

Methods: Patients diagnosed with PFO attributable cryptogenic embolism were prospectively, without randomization, recruited from January 2005 to March 2018. The relationship between thrombophilia and recurrent events was evaluated in overall patients. Multivariate Cox regression was conducted to assess the relative risk for recurrence in PFO closure and medical therapy groups.

Results: A total of 591 patients with cryptogenic embolism with PFO were identified. The median duration of follow-up was 53 months, and thrombophilia significantly increased the risk for recurrent events (hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.09 to 3.16; p = 0.024). PFO closure was superior to medical therapy in overall patients (HR: 0.16; 95% CI: 0.09 to 0.30; p < 0.001). Of the 134 patients (22.7%) with thrombophilia, there was a difference in the risk for recurrence events between the PFO closure (6 of 89) and medical therapy (15 of 45) groups (HR: 0.25; 95% CI: 0.08 to 0.74; p = 0.012). There was no potential heterogeneity in the further subgroup analysis.

Conclusions: Patients with cryptogenic stroke with PFO and hypercoagulable state had increased risk for recurrent stroke or transient ischemic attack. PFO closure provided a lower risk for recurrent events compared with medical therapy alone.

Keywords: closure; cryptogenic stroke; patent foramen ovale; secondary prevention; thrombophilia.

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Conflict of interest statement

Author Disclosures This study was funded by the National Institutes of Health (grant NS051588 to Dr. Ning). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

FIGURE 1
FIGURE 1. Thrombophilia and Risk for Recurrence in Overall Patients
Kaplan-Meier cumulative estimates indicated that the combination of thrombophilia and patent foramen ovale (PFO) increased the risk for recurrent events in patients with cryptogenic PFO stroke or transient ischemic attack. CI = confidence interval; HR = hazard ratio.
FIGURE 2
FIGURE 2. Primary Endpoint in the PFO Closure Group Versus the Medical Therapy Group
Kaplan-Meier cumulative estimates indicated that patent foramen ovale (PFO) closure significantly reduced recurrent events of stroke or transient ischemic attack compared with medical therapy. CI = confidence interval; HR = hazard ratio.
FIGURE 3
FIGURE 3. Subgroup Analyses of the Primary Endpoint in the 134 Patients With Thrombophilia
Hazard ratios (HRs) were calculated with the use of a Cox proportional hazards model. ASA = atrial septal aneurysm; PFO = patent foramen ovale.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION
Kaplan-Meier Cumulative Estimates of the Rate of the Primary Endpoint in Different Groups
See this image and copyright information in PMC

Comment in

References

    1. Lijfering WM, Brouwer JL, Veeger NJ, et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood 2009;113: 5314–22. - PubMed
    1. Croles FN, Nasserinejad K, Duvekot JJ, Kruip MJ, Meijer K, Leebeek FW. Pregnancy, thrombophilia, and the risk of a first venous thrombosis: systematic review and bayesian meta-analysis. BMJ (Clin Res Ed) 2017;359:j4452. - PMC - PubMed
    1. Vossen CY, Walker ID, Svensson P, et al. Recurrence rate after a first venous thrombosis in patients with familial thrombophilia. Arterioscler Thromb Vasc Biol 2005;25:1992–7. - PubMed
    1. Kenet G, Lutkhoff LK, Albisetti M, et al. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation 2010;121:1838–47. - PubMed
    1. Carod-Artal FJ, Nunes SV, Portugal D, Silva TV, Vargas AP. Ischemic stroke subtypes and thrombophilia in young and elderly Brazilian stroke patients admitted to a rehabilitation hospital. Stroke 2005;36:2012–4. - PubMed

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