No abstract

Background and Purpose: Pulmonary arteriovenous fistulas (PAVFs) are a treatable cause of acute ischemic stroke (AIS), not mentioned in current American Heart/Stroke Association guidelines. PAVFs are recognized as an important complication of hereditary hemorrhagic telangiectasia. Methods: The prevalence of PAVF and hereditary hemorrhagic telangiectasia among patients admitted with AIS in the United States (2005–2014) was retrospectively studied, utilizing the Nationwide Inpatient Sample database. Clinical factors, morbidity, mortality, and management were compared in AIS patients with and without PAVF/hereditary hemorrhagic telangiectasia. Results: Of 4 271 910 patients admitted with AIS, 822 (0.02%) were diagnosed with PAVF. Among them, 106 of 822 (12.9%) were diagnosed with hereditary hemorrhagic telangiectasia. The prevalence of PAVF per million AIS admissions rose from 197 in 2005 to 368 in 2014 ( P trend , 0.026). Patients with PAVF were younger than AIS patients without PAVF (median age, 57.5 versus 72.5 years), had lower age-adjusted inpatient morbidity (defined as any discharge other than home; 39.6% versus 46.9%), and had lower in-hospital case fatality rates (1.8% versus 5.1%). Multivariate analyses identified the following as independent risk markers (odds ratio [95% CI]) for AIS in patients with PAVF: hypoxemia (8.4 [6.3–11.2]), pulmonary hemorrhage (7.9 [4.1–15.1]), pulmonary hypertension (4.3 [4.1–15.1]), patent foramen ovale (4.2 [3.5–5.1]), epistaxis (3.7 [2.1–6.8]), venous thrombosis (2.6 [1.9–3.6]), and iron deficiency anemia (2 [1.5–2.7]). Patients with and without PAVF received intravenous thrombolytics at a similar rate (5.9% versus 5.8%), but those with PAVF did not receive mechanical thrombectomy (0% versus 0.7%). Conclusions: Pulmonary arteriovenous fistula–related ischemic stroke represents an important younger demographic with a unique set of stroke risk markers, including treatable conditions such as causal PAVFs and iron deficiency anemia.

The potential of covert pulmonary arteriovenous malformations (PAVMs) to cause early onset, preventable ischemic strokes is not well known to neurologists. This is evident by their lack of mention in serial American Heart Association/ American Stroke Association (AHA/ASA) Guidelines, and the single case-report biased literature of recent years. To inform, we performed PubMed and Cochrane database searches for major studies on ischemic stroke and PAVMs published from January 1, 1974 through April 3, 2021. This identified twenty-four major observational studies, three societal guidelines, one nationwide analysis, three systematic reviews, twenty-one other review/opinion articles, and eighteen recent (2017-2021) case-reports/series that were synthesized. Key points are that patients with PAVMs suffer ischemic stroke a decade earlier than routine stroke, losing nine extra healthy-life-years per patient in the recent US nationwide analysis (2005-2014). Large-scale thoracic CT screens of the general population in Japan estimate PAVM prevalence to be 38/100,000 (95% confidence interval 18-76), with ischemic stroke rates exceeding 10% across PAVM series dating back to the 1950s, with most PAVMs remaining undiagnosed until the time of clinical stroke. Notably, the rate of PAVM diagnoses doubled in US ischemic stroke hospitalizations between 2005-2014. The burden of silent cerebral infarction approximates to twice that of clinical stroke. Over 80% patients have underlying hereditary hemorrhagic telangiectasia (HHT). The predominant stroke mechanism is paradoxical embolization of platelet-rich emboli, with iron-deficiency emerging as a modifiable risk-factor. PAVM related ischemic strokes may be cortical or subcortical, but very rarely cause proximal large vessel occlusions. Single antiplatelet therapy maybe effective for secondary stroke prophylaxis, with dual antiplatelet or anticoagulation therapy requiring nuanced risk-benefit analysis given their risk of aggravating iron deficiency. In conclusion, this review summarizes the current ischemic stroke burden from PAVMs, the implicative pathophysiology, and relevant diagnostic and treatment overviews to facilitate future incorporation into AHA/ASA guidelines.