Ischemic Stroke and Pulmonary Arteriovenous Malformations: A Review.
Karan K TopiwalaSmit D PatelJeffrey L SaverChristopher D StreibClaire L ShovlinPublished in: Neurology (2021)
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.
Keyphrases
- atrial fibrillation
- case report
- early onset
- iron deficiency
- percutaneous coronary intervention
- antiplatelet therapy
- heart failure
- risk factors
- systematic review
- clinical practice
- acute coronary syndrome
- late onset
- cerebral ischemia
- pulmonary hypertension
- gene expression
- ejection fraction
- emergency department
- magnetic resonance imaging
- mesenchymal stem cells
- stem cells
- end stage renal disease
- spinal cord injury
- high throughput
- oxidative stress
- blood brain barrier
- dual energy
- ischemia reperfusion injury
- newly diagnosed
- current status
- data analysis
- genome wide
- cross sectional
- combination therapy
- drug induced
- climate change