As we move forward in time to the ancient Egyptians, we find a culture that fully embraced the heart not only medically and physiologically but psychologically as well. Although there is no defined structure of a circulatory system proper, the Edwin Smith Surgical Papyrus (c.1600 B.C.) does record its author’s awareness that the status of the heart can be assessed by the pulse. It also records the first written observation of the heartbeat (◘ Fig. 1.2) . From the beginning, the papyrus’ text suggests that: The counting of anything with the fingers [is done] to recognize the way the heart goes. There are vessels in it leading to every part of the body. When a Sekhmet priest, any sinw doctor…puts his fingers to the head…to the two hands, to the place of the heart…it speaks…in every vessel, every part of the body [3]. Furthermore, it was believed that all the “inner juices of the body” (e.g, blood, air, mucous, urine, semen, and feces) flowed through channels that extended from the heart and were distributed peripherally throughout the body in harmony and collected at the anus and recirculated [3]. Any disruption of the flow resulted in illness.

References to the anatomy and physiology of the heart are also evident in the Ebers Papyrus (circa 1550 B.C.). Aside from its biology, the papyrus described the heart as bearing the ponderous role as the center of emotion, memory, thought, will, and personality. As such, it was the final arbitrator in the afterlife by which one’s integrity and eventual fate were determined. In this final judgment, unlike the other organs that were removed during mummification and placed in canopic jars to be buried with the body, the heart remained in the body. And according to the prescriptions of the Egyptian Book of the Dead, it was weighed in a balance against an ostrich feather, called the feather of Ma’at (◘ Fig. 1.3) . If found worthy, one would join the gods in the Fields of Peace. If the heart of the deceased weighed more than the feather—that is, more evil than good—the heart was immediately devoured by the chimeric demon Ammit. In effect, this condemned the bearer to dying a second death that signaled complete annihilation.

Egyptian medical knowledge of the heart would diffuse through time and eventually influence the early Greeks, including Praxagoras, the Cnidians, and the Sicilians in seeing the primacy of the heart, even as the seat of intelligence [4]. Nevertheless, much of Egypt’s religion-based medicine was largely abandoned by the Greeks for a more rational approach to disease and medicine.

In Greece’s Homeric period (1100–750 B.C.), aspects of cardiovascular anatomy were largely known in the traumatic context of battle wounds and lesions, including the well-known account in Homer’s Iliad (760–710 B.C.) about the dying Alcathous and his still-pulsating heart: “… while fighting Idomeneus stabbed at the middle of his chest with the spear, and broke the bronze armor about him which in time before had guarded his body from destruction. He cried out then, a great cry, broken, the spear in him, and fell, thunderously, and the spear in his heart was stuck fast but the heart was panting still and beating to shake the butt end of the spear” [5].

Although later in the Archaic period , Hippocrates (460–355 B.C.) would hold a prestigious position within Greek medicine because of his compendium of medical practice which sought a rational basis for disease. Actual knowledge of the cardiovascular system within the Hippocratic Corpus was limited and, in many cases, erroneous, including its description of the heart as “a firm thick mass so richly supplied with fluid that it does not suffer harm or manifest pain [6].” Nevertheless, anatomical detail was not only useful but would historically help to define the organ with greater precision, including the heart’s description as four-chambered. Other details included its unidirectional flow of blood through the aortic valve, the shape of the pulmonary valve, and the pericardial sac and fluid.

In the Classical Period (480–323 B.C.), Greek contribution to cardiology was modest, as reflected in the work of Diocles of Carystus (400 B.C.), who is attributed with distinguishing the aorta from vena cava, and Aristotle (384–322 B.C.), who took a cardiocentric position regarding the heart. He noted it as three-chambered and the seat of the soul. He also described the heart and great vessels as the source of all vessels.

Paraxagoras (ca. 340 B.C.) proposed a distinction between arteries and veins , with the former arising from the heart, transporting air, and the latter arising from the liver and transporting the blood. While Herophilus (335–280 B.C.) would further characterize and distinguish arteries and veins, noting that the arterial wall was thicker and pulsated, it was his colleague Erasistratus (304–250 B.C.) who championed the Greek contribution to cardiology with his observations on the nature of vessels, the valves of the heart, and his conceptualization of the vascular angioarchitecture.

Most of what has been preserved about circulation theories comes by way of Galen. Judging from Galen’s references to Erasistratus’ works, Erasistratus was not far from an understanding of circulation—and, certainly, a more contiguous relationship between arteries and veins , both of which he believed arose from the heart: The vein (pulmonary artery) arises from the part where the arteries, that are distributed to the whole body, have their origin, and penetrates to the sanguineous [or right] ventricle; and the artery [or pulmonary vein] arises from the part where the veins have their origin, and penetrates to the pneumatic [or left] ventricle of the heart [7]. Furthermore, he held that arteries contained exclusively air and, when punctured, the air escaped. Blood seeped in from arteries to fill the space which was observed to spill from the cut vessel. Like Herophilus, Erasistratus believed that veins contained and transported blood only.

As Aird (2011) points out in his elegant analysis, the focus of the Greek school of cardiovascular thought was understanding how nourishment is disseminated to all parts of the body [8]. Erasistratus described an open-ended vascular system (◘ Fig. 1.4a) where absorbed nutrients were converted in the liver into blood that flowed via the hepatic vein to the vena cava, and from there, to the rest of the body. A portion of the blood was directed to the right ventricle and, ultimately, to nourish the lungs. Conversely, he said the pulmonary veins take up air and transport it to the left ventricle and ultimately carry it to the tissues by arteries. Although flawed, such a system explained what he thought he observed in his dissections and would continue to influence cardiology until the time of Galen.

Galen (129–216 A.D.), whose name and theories alike would come to cement medical knowledge for thirteen centuries, was a Greek physician born in Pergamon. His seemingly unlimited knowledge of medical science likely was derived from his firsthand knowledge as court physician to several Roman emperors, surgeon to the gladiators, and avid dissector of numerous animal species including the Barbary ape and pigs. His cardiological work builds on a refinement of Greek physiology that relied heavily on the four bodily humors (blood, black and yellow bile, and phlegm). The underlying principle is that, although the heart is the source of innate heat that gives life and soul to the body, it must be cooled. In Aristotle’s interpretation, cooling was the brain’s task, while Galen held the novel idea that the lungs provided this activity. Galen provided an open-ended theory of the vascular system that expanded upon Erasistratus’ scheme—providing an innovative way the blood flowing in both arteries and veins (◘ Fig. 1.4b).

In Galen’s scheme, the heart and arteries stood in parallel with the liver and veins, and the brain and nerves to form a tripartite system of governance. Each provided a functional component of the living system: brain and nerves brought sensation and thought, the heart and arteries replenished life-giving energy, and the liver and veins provided nutrition and growth. Each also generated a pneuma (πνεΰμα, an ancient Greek word for “breath”) or spiritual substance that animated and nourished the body. He believed the heart produced vital pneuma, the liver a natural pneuma , and the brain an animal pneuma.

The actual flow of blood via the Galenic system has not been without debate due to translation and the interpretation that comes with translation. Foibles also arise from Galen’s own ambiguities which can be found in his descriptions. As Henri de Mondeville (1260–1320) would later note, “God did not exhaust all his creative power in making Galen [9].” That said, the following is a simple and generalized scheme of the Galenic system.

His scheme begins with the intake of food. Once digested, it is transported from the intestines to the liver via the portal vein (◘ Fig. 1.5) . In the liver, the nutrients were changed to blood which was suffused with natural pneuma that endowed it with the power of growth and nutrition—signaled by the dark red color of the newly formed blood. From the liver, the vitalized blood passed to several destinations. One portion flowed through the vena cava and downstream veins and throughout the body to bring the nutrient potential to muscles and organs. Some blood, however, diverted from the inferior vena cava to the right ventricle of the heart. Here, some flow continued to the lungs via pulmonary arteries (arteria venialis), while a portion of the flow filling the right ventricle passed through invisible pores located within the interventricular septum and into the left ventricle. Here, the blood mixed with air transported from the lung via arteria venialis and pulmonary vein by ebb and flow motion and infused with the vital spirit. The imbued blood, now bright red, was transported via pulsatile arteries to the rest of the body where it was consumed by the tissues and a portion of flow to the brain. The latter blood diverted to the brain was further vitalized by the animal pneuma, a rarefied pneuma that vitalized the brain and flowed peripherally via nerves to bring power to the muscles and perception via the senses.

Finally, as to pulsation, while Erasistratus saw the heart as a suction-and-force “bellows” that produced a passive distention of the artery due to the expulsive force of pneuma from the left ventricle during its contraction [10], Galen believed the pulse was generated by the active contraction and dilation of the muscular coats within the arterial wall. The stimulus arose in the heart and propagated down the wall [11]. Both were incorrect. For Erasistratus, the pulse arose from the action of the heart, but it was pneuma, not blood, that pulsed through the arteries. For Galen, it was blood that flowed through the arteries—but due to the pulse produced by the arterial wall.

Many clinicians today have asked why Galen, a scientist of discerning and incisive insight, failed to deduce the obvious role of the heart within a circulatory scheme. Many have also proposed answers to this puzzling question. An increasing number support the thesis that Galen became consumed and distracted by his ongoing dispute with the Stoics [12]. His agenda became a polemical dialectic to discredit the Stoics’ concept of an indivisible soul while maintaining his own allegiance to the Platonic concept of the tripartite soul. The intensity of the debate allowed little option of moving beyond this defensive position. The Galenic system would become the predominant paradigm that would influence and guide medical practice and education down through the subsequent ages as it was further emulated and canonized during the Middle Ages.

The Galenic system would eventually be challenged in the thirteenth century by physicians of the Islamic world who had greater familiarity with the ancient Greeks. This included the Arab physician Ibn al-Nafis (1210–1288), who took clear exception to the existence of invisible pores within the interventricular septum that enabled blood passage from right to left ventricle and, furthermore, provided an accurate basis of pulmonary circulation. While the West continued to embrace and teach Galenic principles, new developments in the twelfth century would eventually lead to a reevaluation of Galen’s all-pervasive influence.

Although it has been referred to as a “Civitas Hippocratica,” the School of Salerno represented a fresh and integrated approach to medicine and medical education in an otherwise unresponsive era. Beginning the in the tenth century and arising in the context of Benedictine monasticism, including Monte Cassino, it became the first medical school in the world and, subsequently, an outstanding secular institution. It returned to the earlier historical practice of animal dissection as one of its chief merits. As Castiglioni points out, “up to that time anatomy had been taught simply sicut asserit Galenis (‘thus does Galen declare’)” [13]. At Salerno’s peak in the twelfth century, anatomic dissection, particularly of the pig, was systematically undertaken, and although still steeped in Galenic perspective, faculty members were beginning to embrace the importance of independent observation.

The first public dissection of the human body for medical instruction was performed by Mondino de Luzzi (1275–1326) at the University of Bologna in 1315. Dissection of the body was evident as well in the work of the great Italian Renaissance artists who were less confined by the ideas of Galen or even Aristotle or Hippocrates. They sought to examine firsthand what the visually impoverished medical texts of the period failed to relay. Human dissections, including those of da Vinci, provided the anatomic and mechanical basis that conferred dynamics of motion and function to the body in life. Leonardo da Vinci (1452–1519) has only recently been properly acknowledged for his impressive knowledge of the heart, both in terms of function and anatomical features.

Our temptation is to regard Leonardo exclusively as an artist or illustrator, but he was much more. He was a scientist at heart, driven by an inquisitive nature, open to novel ideas and explanations, and heavily dependent on firsthand observation and experimentation. From age 14, he apprenticed in art and art history in the workshop of Andrea del Verrocchio and at the age of 33 was appointed director of the Academy of Science and Art in Milan. For 17 years, da Vinci undertook numerous engineering and architectural projects for the Duke of Milan. He explored and studied the elements of city planning, military engineering, mathematics, hydrodynamics, and the physics of optics and motion.

The principles applied in these studies and projects were ultimately focused on his abiding interest in anatomy—dynamic anatomy—and recorded in his notebooks anatomical dissections which he had planned to publish. His anatomical works spanned two intervals: 1480–1497 and 1506–1509. Of his 5000 known pages of notes and illustrations largely on mechanics, 190 recorded the anatomy of autopsied human subjects and animals, of which 50 were devoted exclusively to the heart [14]. Aside from the amazingly detailed surface features of the heart (◘ Figs. 1.6 and 1.7) , Leonardo explored the inner aspects of the chambers and conduits, noting the architecture of the valves, papillary muscles—even the moderator band obvious in the ox heart and more difficult to distinguish in the human that he correctly identified as a muscular bridge stabilizing the right ventricle from over-distention. His drawings astutely record and analyze the physics of motion through the trileaflets of the aortic and pulmonary valves.

Aside from the intricacies of the heart itself, Leonardo regarded the heart as a muscle, not flesh, as stated by Galen. He clearly characterized for the first time the heart as four-chambered with atria distinct in configuration and function as they contracted to fill the ventricles. He also elegantly traced and defined the course of the coronary arteries as those that supplied the muscle of the heart itself and provided cogent demonstrations of the bronchial arteries (◘ Fig. 1.8). Nevertheless, all this wealth of knowledge issued from the pen and drawings of da Vinci would never see the light of his age. With his death, his rich insights into the anatomy and function of the heart would be lost for almost 400 years.

During the century of Leonardo’s death, several distinguished anatomists would prove essential to the continuing evolution of cardiology. Perhaps the most well known of these would be the Flemish anatomist Andreas Vesalius (1514–1564) who would publish his De Humani Corporis Fabrica and Epitome in 1543. This was a startling collection of dissected images of the human body illustrated by Jan van Calcar, his friend and pupil of the artist Titian, and unlike anything published to date. Despite the exquisite drawings, including those of the vascular system, his heart images remained modest and illustrated the interventricular pores of Galen (◘ Fig. 1.9). On the other hand, the sentiment expressed in his text would indicate otherwise: