A Nomogram for Predicting Patent Foramen Ovale-Related Stroke Recurrence

Good luck understanding anything here. But the takeaway is to not have a cryptogenic stroke since your doctor has nothing to prevent the next one.

Nomogram: diagram representing the relations between three or more variable quantities by means of a number of scales, so arranged that the value of one variable can be found by a simple geometric construction, for example, by drawing a straight line intersecting the other scales at the appropriate values.

A Nomogram for Predicting Patent Foramen Ovale-Related Stroke Recurrence

Zhuonan Wu^1†, Chuanjing Zhang^2†, Nan Liu³, Wenqing Xie³, Jinjin Yang⁴, Hangyuan Guo⁵ and Jufang Chi^5*

• ¹Shaoxing University School of Medicine, Shaoxing, China
• ²Ningbo University School of Medicine, Ningbo, China
• ³Zhejiang Chinese Medical University of Medicine, Hangzhou, China
• ⁴Zhejiang University School of Medicine, Hangzhou, China
• ⁵Department of Cardiology, The First Affiliated Hospital of Shaoxing University (Shaoxing People's Hospital), Shaoxing, China

Background: The high prevalence of patent foramen ovale (PFO) in cryptogenic stroke suggested a stroke-causing role for PFO. As risk factors for recurrence of such stroke are not recognized, clinicians cannot sufficiently identify, treat, and follow-up high-risk patients. Therefore, this study aimed to establish a prediction model for PFO-related stroke recurrence.

Methods: This study included 392 patients with PFO-related stroke in a training set and 164 patients with PFO-related stroke in an independent validation set. In the training set, independent risk factors for recurrence identified using forward stepwise Cox regression were included in nomogram 1, and those identified using least absolute shrinkage and selection operator(LASSO)regression were included in nomogram 2. Nomogram performance and discrimination were assessed using the concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analyses (DCA). The results were also validated in the validation set.

Results: Nomogram 1 was based on homocysteine (Hcy), high-sensitivity C-reactive protein (hsCRP), and albumin (ALB), and nomogram 2 was based on age, diabetes, hypertension, right-to-left shunt, ALB, prealbumin, hsCRP, and Hcy. The C-index of nomogram 1 was 0.861, which was not significantly different from that of nomogram 2 (0.893). The 2- and 5-year AUCs of nomogram 1 were 0.863 and 0.777, respectively. In the validation set, nomogram 1 still had good discrimination (C-index, 0.862; 2-year AUC, 0.839; 5-year AUC, 0.990). The calibration curve showed good homogeneity between the prediction by nomogram 1 and the actual observation. DCA demonstrated that nomogram 1 was clinically useful. Moreover, patients were successfully divided into two distinct risk groups (low and high risk) for recurrence rate by nomogram 1.

Conclusions: Nomogram 1, based on Hcy, hsCRP, and ALB levels, provided a more clinically realistic prognostic prediction for patients with PFO-related stroke. This model could help patients with PFO-related stroke to facilitate personalized prognostic evaluations.

Introduction

Approximately 30–40% of ischemic strokes are known as “cryptogenic strokes” because they have no identified cause (1). In the last century, epidemiological surveys have found a significantly higher prevalence of patent foramen ovale (PFO) in the cryptogenic stroke population than in the normal population, suggesting a stroke-causing role for PFO (2). The main mechanism of PFO-related stroke is currently believed to be paradoxical embolism, in which a thrombus from the vein (especially the deep vein of the lower extremity) travels through the venous system to the right atrium and through the PFO to the left atrium, which is known as a right-to-left shunt (RLS), then the thrombus followed by blood flow into cerebral arteries, leading to stroke. In 2017, the publication of the results of the RESPECT long-term follow-up, the CLOSE trial, and the Gore-REDUCE trial verified that PFO can cause stroke and strongly demonstrated that PFO closure is superior to drug treatment alone in reducing the recurrence of PFO-related stroke (3–5). Consequently, scholars formally proposed the concept of “PFO-related stroke” in 2020 (6). Although PFO closure resulted in a relative (65%) reduction in the risk of stroke recurrence compared with antiplatelet treatment alone (7), the relatively low absolute recurrence rate of PFO-related stroke itself and the lack of accurate assessment of patient prognosis allow that a large number of patients remain on conservative drug therapy and some even remain untreated. Despite the absence of data on the long-term risk of stroke recurrence (>10 years) in patients with PFO-related stroke receiving drug therapy, more than 50% of patients were followed up for 5 years or longer. In these trials (3), the Kaplan-Meier curves for drug treatment did not show a decrease in the rate of stroke recurrence over time. In some studies, the annual recurrence rate of PFO-related stroke remained as high as approximately 4.8%, and this figure even increased to 8.2% in some patients with PFO-related stroke (8). Therefore, it is essential to identify the population at a high risk of PFO-related stroke recurrence, which is also a current clinical limitation. There is no consensus regarding risk factors for PFO-related stroke recurrence or clinically available biological markers. Although some studies have identified larger PFO size, larger RLS, atrial septal aneurysm (ASA), and high homocysteine (Hcy) levels as risk factors for PFO-related stroke recurrence, there is still a lack of consistent understanding and integration of risk scores for each independent risk factor.

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