Association between acute myocardial infarction and death in 386 patients with a thrombus straddling a patent foramen ovale
Introduction
Right atrial thrombi are rarely found while straddling a patent foramen ovale (PFO). Thrombi identified at the time of straddling a PFO, also known as impending paradoxical embolism, are usually diagnosed in the context of deep venous thrombosis or pulmonary embolism, although the source of the thrombus is not always identified [1]. The term impending paradoxical embolism may not be accurate since, in a considerable proportion of patients, a paradoxical embolism has already occurred at the time of the diagnosis of the straddling thrombus [2,3]. Therefore, thrombus straddling a PFO (TSPFO) would better represent this clinical entity.
With point of care echocardiography becoming more widely used in the setting of acute respiratory insufficiency and pulmonary embolism, TSPFO has been increasingly identified in the last decade [4]. These thrombi are associated with a 9.7% to 11.5% risk of death within 24 h of being diagnosed, and therefore constitute a medical emergency requiring urgent treatment [1]. The finding of a TSPFO should prompt urgent therapeutic decisions aimed to prevent death and long-term functional complications. TSPFO is rarely reported in the medical literature. Thus, the association of clinical presentations such as acute ischemic stroke (IS) and acute myocardial infarction (MI) or available therapeutic options (e.g., anticoagulation, thrombolysis, or surgery) with early death remain unknown.
Paradoxical embolism is a well-recognized source of acute IS and a less frequently reported cause of myocardial infarction (MI) [2,3]. Both acute IS and MI require challenging therapeutic decisions in the context of a TSPFO. Deciding whether to use intravenous thrombolytics for either acute IS or MI, percutaneous coronary intervention for MI or mechanical thrombectomy for IS can be puzzling in the setting of a massive pulmonary embolism or deep venous thrombosis with a documented TSPFO. Furthermore, acute IS, or MI could potentially be associated with worse outcomes in patients with TSPFO if they are not timely identified or left untreated. We therefore conducted a systematic review of individual cases of adult patients with TSPFO to investigate the incidence of IS and MI and their associated risk of in-hospital death. We additionally investigated the association between different therapeutic approaches and outcomes.
Section snippets
Methods
We performed a systematic search including abstracts and full-text papers describing case reports and case series of adult patients (≥18 years of age) with TSPFO published from inception to October 30, 2020 in any language according to a pre-specified study protocol [5]. We excluded articles with incomplete data and duplicated reports. We searched PubMed and Embase by applying predefined search terms (Tables I and II, supplementary files). Three authors (P.S., A.J-R, A.G.) independently
Results
Our systematic search identified 5732 references from January 1, 1950 to October 30, 2020. Of these, we included 359 publications comprising 386 patients (Fig. I, supplemental file), of whom 192 (51.2%) were females (Table 1). The median age was 61 years. Pulmonary embolism (73.1%) and deep venous thrombosis (47.4%) were the most frequent diagnoses upon admission, without differences between patients who survived or died during hospital stay. Fifty (13.0%, 95% CI 9.8–16.7) patients died during
Discussion
In this study, including 386 pooled cases of adults admitted with a TSPFO with clinical data extracted at the patient level, we found that presenting with an acute MI was associated with 8-fold higher risk of in-hospital death. In contrast to our hypothesis, acute IS was not associated with increased mortality. Acute surgical removal of the TSPFO was associated with 65% lower risk of in-hospital death than no surgery.
In our study, 4.7% of patients of TSPFO received a diagnosis of acute MI upon
Limitations
Our results should be interpreted in the context of the study limitations. Data were retrospectively pooled from case series and reports. Despite this, we provided a comprehensive analysis of possible mechanisms causing MIs in patients with TSPFO, causes of death, and available therapeutic interventions. Information on the anatomical structure and size of PFO was seldom reported, so we were unable to analyze the association between PFO characteristics and clinical outcomes. Publication bias may
Conclusions
Patients with massive pulmonary embolism are at risk of experiencing a simultaneous MI, which should be kept in mind as an important diagnosis to investigate in patients with TSPFO since it has relevant prognostic implications [23]. Severe pulmonary embolism can result in increased cardiac troponin levels and right ventricular dysfunction, adding confusion to the clinical picture. Our results suggest that right surgical thrombectomy may be considered the treatment of choice for patients
Funding
LAS is supported by the Kathleen & Dr. Henry Barnett Research Chair in Stroke Research (Western University, London, Canada); the Edward and Alma Saraydar Neurosciences Fund (London Health Sciences Foundation, London, Canada); and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario (AMOSO) (Ontario, Canada). None of these funding sources had a role in the design or results of this study. None of the
Competing Interest
LAS: speaker and consulting honoraria from Boehringer Ingelheim, Pfizer, Bayer and Gore; research grants from Boehringer Ingelheim and Bayer. LAS is member of the Editorial Board of Neurology and Stroke journals, and the World Stroke Academy (Webinar platform of the World Stroke Organization). The remaining authors have nothing to disclose.
Acknowledgements
None.
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Palak Shah and Amado Jimenez-Ruiz contributed equally as first authors.