Awareness of the Role of Atrial Fibrillation as a Cause of Ischemic Stroke

Atrial fibrillation (AF) in the presence of mitral stenosis, a consequence of rheumatic heart disease, was long recognized as the basis for cerebral infarction. Although it had long been acknowledged that atrial stasis resulting from mitral stenosis, often in the presence of AF, predisposed to thrombus formation, investigators questioned whether the AF played a role in the occurrence of systemic embolism, including stroke. As examples, in 1951, the esteemed Boston cardiologists Harris and Levine concluded, “…one wonders whether AF has much importance in influencing thrombus formation in mitral stenosis.”1In his memoirs, Fisher2 recounts the events in 1949 soon after his arrival as a graduate fellow in neuropathology at the Boston City Hospital. He stated> One day, three months after I’d arrived, I had the opportunity to examine the cerebral arteries before slicing three brains that had large hemorrhagic infarcts. The basal vessels were empty of thrombus … People were signing out these cases as cerebral artery thrombosis—but pathologically there was no thrombus. Afterward, I looked up the records on these three cases and they had all been in AF and the general autopsy had shown infarcts in the spleen and kidneys. I speculated that they might be cases of embolism from the heart. The hemorrhagic change was from reperfusion of blocked vessels. This experience led Fisher to conclude AF was indeed frequently associated with stroke attributed to cerebral thrombosis, and the hemorrhagic infarction in such cases was related to lysis of cerebral emboli and reperfusion of the infarct.At about the same time, beginning in 1946, Wright and Foley3 at the New York Hospital-Cornell Medical Center showed that anticoagulation could prevent strokes originating from fibrillating atria in patients with mitral stenosis. This work was later extended to those with nonvalvular AF and was discussed by Wright …