Do we know, or do we believe?

Clinicians frequently encounter clinical scenarios for which evidence-based therapy is sparse. Formulating appropriate therapeutic strategies can feel frustratingly haphazard but desperation to help our patients can neither create data nor bring certainty where there is none. A Position Statement is published in this issue of Catheterization and Cardiovascular Interventions (The full version of this article, including references, can be found online at www.onlinelibrary.wiley.com/doi/ 10.1002/ccd.24693/pdf) by a group of professional societies regarding the management of patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) [1]. Management of such patients is bedeviled with problems of patient selection and unclear natural history with few data from randomized trials (but not as few as reported in the paper). They point out that in spite of the absence of clear solutions, real patients present with real strokes, and doctors must make real decisions. Fair enough. However, guidelines which, are by nature generated by opinion and interpretation, must be data-guided when possible. Furthermore, recommendations must be cautious and, as is the custom of the American Heart Association, for example, the level of evidence that supports them must be articulated. Pristipino and colleagues recognize the provisional nature of their conclusions and that they are based on opinion. Our criticism of this guideline lies less with specific opinions than in the discrepancy between phrases like “must be” in their recommendations and the quality of the evidence to support them. In many cases, they provide neither supporting data nor a class of recommendation. As for some of the specifics, we are aware of “must be” recommendations that are counter to published data. For example, given that CS patients have a high prevalence of aortic arch disease (detectable only by transesophageal echocardiography [TEE]) and of PFO (TEE sensitivity is twice that of transthoracic echocardiography [TTE]) then anyone without a TEE should be considered “incompletely evaluated” rather than “cryptogenic.” The recommendation that a “standard TTE must be performed in all patients” runs counter to the data. On the other hand, some of their referenced papers do not support the argument being made. For example, reference #38 is not a study of CS patients and, therefore, is not germane. Other recommendations are unsupported and may contribute to patient harm, such as suggesting that stroke patients can be identified for whom secondary prevention with antithrombotic medications can be stopped after PFO closure. Given the putative nature of the PFO–stroke association for any individual, this recommendation may lead to the withholding of proven stroke prevention therapies for some patients after PFO closure. We see this as a particularly troubling recommendation without more supportive data. The scheme in Figure 2 conflates the “risk factors” for a likely pathogenic PFO with those for recurrent stroke. These should not be seen as identical. For example, a Valsalva-associated index event may add evidence that it was PFO-related but perhaps a “provoked” PFO, i.e. requiring Valsalva before a stroke, is LOWER risk than one that generates a paradoxical embolism while at rest. This is biologically plausible and without contradictory data. Nevertheless the opposite is identified as a “risk factor” that should be used for treatment decisions. Other “risk factors” such as multiple acute ischemic lesions on imaging have been shown NOT to be related to PFO in CS [2]. The risk of proposing such a treatment algorithm with such limited data and without