Patent foramen ovale (PFO) was first described by Galen in the early sixteenth century, and presently is a commonly recognized structure in the heart, felt to be found in about 25–30 % of the normal population [1].

1490 – Leonardo da Vinci began drawing sketches of the heart and circulation. These drawings were primarily made from his studies of the circulatory system and organs in pigs and oxen, it was only much later that he had access to study the cardiac anatomy in humans. Di Vinci made significant advances in the understanding of blood flow and of the heart itself. He demonstrated that the heart was indeed a muscle, that it was not responsible for warming the blood, found that it had four chambers, and was able to connect the pulse in the wrist to the contraction of the left ventricle. Given his artistic abilities, Di Vinci took what he had seen and drew sketchings of the heart and circulation. In some of his descriptions and drawings he described a “communication between the auricles”.

1561 – Falloppio and Vesalius, who both described the foramen ovale.

1564 – Dr. Leonardo Botallo, an Italian surgeon, again described the patent foramen ovale, naming it “Botallo’s foramen” in 1564.

1570 – Bartholomaeus Eustachius, a professor of medicine in Rome, was the first to describe the presence and purpose of the patent foramen ovale in the fetus. He also described that it closed at birth by “thin valvular layer”, which often had an “imperfect upper margin”. His works and drawings remained unprinted and forgotten until 1714, when they were published along with the work of the famous physician Lancisi. Eustachius is also credited as being one of the founders of modern anatomy, discovering the Eustacian tube, thoracic duct, the adrenals, and the abducens nerve. He also gave the first accurate description of the uterus.

1805 – A report published by Spry, describing two cases. The first a girl, aged 7 years, with no history of cyanosis during her lifetime, and a finding of a foramen ovale patent to 15 mm. The second case was that of a 21 year old woman who had symptoms of cyanosis, palpitations, and dyspnea, since she was 3 months of age with a finding of a patent foramen ovale to 25 mm.

1846 – Rudolf Virchow, a German pathologist who is recognized as the father of modern pathology, described a phenomenon of simple embolism of particulate matter through the vascular system.

1877 – Julius Friedrich Cohnheim, a German pathologist and a protégé of Virchow, described how the patent foramen ovale could act as a suitable means of by-passing the pulmonary vascular system. It was 4 years later that this theory was substantiated with a finding of an embolus into the frontal lobe, in a 35 year old woman, as well as a thrombus in the lower extremity veins. Upon inspection of the heart, a very large foramen ovale, “through which I could pass three fingers with ease”. He stated that after this discovery, he could “no longer ignore the fact that a torn-off piece of thrombus arising from the inferior vena cava, while traveling through the heart (passed) out of the right atrium into the left atrium and to the frontal lobe.”