Projected clinical and economic benefits of improved patent foramen ovale testing among cryptogenic stroke patients in the United States

Background: Accurate determination of stroke etiology is essential for effective secondary stroke prevention, yet 25% to 40% of ischemic strokes are classified as cryptogenic. Patent foramen ovale (PFO), a common finding in cryptogenic stroke, elevates the risk of strokes. However, underuse of diagnostic practices may lead to underdiagnosis of PFO, missing opportunities for guideline-recommended PFO closures and preventable recurrent strokes. This study estimates the value of improving testing for PFO among patients with cryptogenic stroke in the US. Methods: A cost-effectiveness analysis was conducted, employing a hybrid model including a decision tree and a Markov model to assess health outcomes and economic impacts from a US payor perspective over a life-time horizon. The model compared two PFO testing scenarios: the Current Diagnostic Scenario (54% testing) and Optimal PFO Diagnostics (100% testing). The decision tree evaluated diagnostic pathways for PFO (TTE, TEE, TCD), while the Markov model simulated patient progression through various health states (recurrent ischemic stroke, TIA, and death). Cost-effectiveness was determined using the incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $75,000 per Quality-Adjusted Life Year (QALY). Results: In a simulated cohort of 1,000 patients, increasing the diagnostic testing rate for PFO from 54% to 100% is expected to prevent 63 recurrent strokes, resulting in 23 life years saved and 286 QALYs gained. This led to cost-savings of $1.9 million for payors, indicating a dominant economic position (ICER = -$6,770/QALY). The model estimated screening four patients would lead to identifying and closing one PFO, while screening seven would prevent one recurrent stroke. Thorough sensitivity analyses confirmed the robustness of these findings. Conclusions: Improving PFO diagnostic testing among patients with cryptogenic stroke is projected to result in improved health outcomes for patients, while yielding cost-savings, underscoring the importance of adhering to PFO diagnostic guidelines.