Despite the exhortations of poets and philosophers, the heart is, after all, simply a pump. The ability to “look into any man’s heart” with the goal of understanding the function of this mysterious organ thwarted early generations of scientists and physicians. It would not take long, however, for science to garner the tools needed to peer into the hearts of mankind. Many of the major functions of the cardiovascular system important to our understanding of health and disease states are based on mechanical processes. Cardiac chambers contract and relax, valves open and close, and blood ebbs and flows based on the elementary principles of hydraulics. Contrast this with most other organ systems that exploit complex cellular and biochemical processes to accomplish their designated functions. For example, the kidneys balance fluid and electrolytes and excrete waste via an elaborate cellular array; the liver, pancreas, and intestinal cells digest food and absorb nutrients through a series of complicated biochemical steps, and muscle cells exert their cumulative toil through the elegant dance of complex protein molecules. The latter secrets eluded physicians and scientists, until only recently, when highly sophisticated tools became available to reveal the intricate and minute processes.
Many of the mechanical processes inherent to cardiac physiology can be understood by measuring changes in blood pressure and blood flow; the term hemodynamics refers to this discipline. Numerous brilliant investigators over many years have applied the study of hemodynamics to collectively expand our knowledge of cardiovascular physiology in both normal and pathologic conditions. The lessons learned from these generations of researchers rapidly became assimilated into the contemporary practice of clinical cardiology. Currently, hemodynamics is considered indispensable to the clinician managing patients with cardiovascular disease and forms the foundation of invasive and interventional cardiology.
A Brief History of Hemodynamic Assessment
All-important human endeavors possess histories replete with colorful anecdotes and legendary characters. The saga of cardiac catheterization is no exception.
The practical measurement of hemodynamics in humans required several crucial developments. These included the invention of safe and reliable catheterization techniques to access and study the right and left sides of the heart, the ability to image catheter position, and the creation of devices to convert pressure changes into an interpretable graphic form.
Insertion of tubes into the bladders and rectums of living people and the blood vessels of cadavers has been achieved since primitive times. The first cardiac catheterization and pressure measurement performed on a living animal is attributed to the English physiologist Stephen Hales early in the 1700s and reported in the book Haemastaticks in 1733. By accessing the internal jugular vein and carotid artery of a horse, Hales performed his experiments using a brass pipe as the catheter, connected by a flexible goose trachea to a long glass column of fluid. The pressure in the white mare’s beating heart raised a column of fluid in the glass tube over 9 feet high.
As early as 1844, the famous French physiologist Claude Bernard performed numerous animal cardiac catheterizations designed to examine the source of metabolic activity. Many prominent scientists theorized that “combustion” occurred in the lungs. Using a thermometer inserted in the carotid artery, Bernard compared the temperature of blood in a living horse’s left ventricle with blood in the right ventricle, accessed from the internal jugular vein, and showed slightly higher right-sided temperatures, indicating that metabolism occurred in the tissues, not in the lungs. Bernard also appeared to be the first to record intracardiac pressure using an early pressure recording system connected to the end of a glass tube inserted into a dog’s right ventricle.
Later in the 1800s, in an attempt to address the controversy regarding the nature and timing of the cardiac apex beat, the French veterinarian Jean Baptiste Auguste Chauveau and physician Étienne Jules Marey performed catheterization using rubber catheters placed in a horse’s jugular vein and carotid artery. These meticulous scientists recognized the importance of obtaining the highest quality data and recorded pressures in various cardiac chambers with clever mechanical devices invented by others but modified to suit their needs. The graphic recordings obtained from these early transducers and physiologic recorders appear remarkably similar to those obtained in today’s cardiac catheterization laboratories ( Fig. 1.1 ).
From these early explorations of cardiac pressure measurement, there evolved an interest in quantifying blood flow. In 1870 the German mathematician and physiologist Adolph Fick published his famous formula for calculating cardiac output (oxygen consumption divided by arteriovenous oxygen difference). However, Fick had more interest in the conceptual aspects of cardiac output determination than in its validation or application. The experiments necessary for validation of Fick’s principle would fall to others more than 60 years later. Fick also contributed to the emerging field of hemodynamics with his valuable work refining early pressure recording devices.
Despite numerous animal studies over many years, the placement of a catheter into the deep recesses of a living human heart would have to wait for an accurate method to image the course and position of the catheter. This would, ultimately, be feasible only after Wilhelm Roentgen’s discovery of x-rays in 1895 ( Fig. 1.2 ). The invention of an apparatus allowing us to peer inside the living human body for the first time represented one of the greatest medical advances in human history. At the start of the 20th century, it became possible to consider applying the lessons learned from animal research to humans. However, great trepidation remained among cardiovascular researchers because most considered the placement of a catheter into a living, beating human hearts foolhardy with potentially deadly consequences.
Although the historical record bestows acclaim for the first human cardiac catheterization to Werner Forssmann (performed on himself in 1929), his accomplishment may have been trumped by the little known, often disputed, and poorly documented efforts of fellow Germans Fritz Bleichroeder, E. Unger, and W. Loeb in 1905. In an effort to deliver therapeutic injections close to the targeted organ, these physicians attempted to place catheters, without radiologic guidance, into the central venous circulation via the basilic and femoral veins. During one attempt made on his colleague Bleichroeder, Unger may have actually gotten into the heart because Bleichroeder reported the development of chest pain. They could not prove this theory because they failed to document the catheter position by x-ray or pressure recording and never published their observations, attempting to gain credit only after Forssmann received his in 1929.
The account of Forssmann’s first cardiac catheterization on himself, for which he was awarded the Nobel Prize in Medicine and Physiology in 1956, along with André Frederic Cournand and Dickinson Woodson Richards, has been recounted numerous times and with several versions, some more engaging and colorful than others. The consistently told elements of his narrative are nearly unimaginable to contemporary physicians familiar with the existing training, medicolegal, and practice environments.
The essential facts of Forssmann’s story are as follows. After graduating medical school, Forssmann began training as a surgical intern at the Auguste-Viktoria Hospital in Eberswalde, Germany, a small community hospital outside Berlin ( Fig. 1.3 ). Forssmann’s motivation in pursuing a means of instrumenting the right heart is unclear ; he reported that it evolved from the desire to find a method of infusing lifesaving drugs into the heart that was safer than direct intramyocardial injection. Forssmann discussed his interest with his chief, Dr. Richard Schneider, but Schneider banned the enthusiastic intern from pursuing this work, largely because he thought it unlikely that mainstream German academic medicine would accept medical research from a community hospital. In addition, many considered the placement of a catheter into the heart very dangerous; Schneider did not wish notoriety for his hospital in the event that these investigations ended poorly.
Undeterred by the prevailing lack of support, Forssmann first placed catheters into the hearts of cadavers from an arm vein. Forssmann, impressed with the ease with which the catheters advanced, decided to perform the experiment on himself. As he was forbidden to proceed with any human experimentation by Schneider, he decided to carry out his project in secret. Forssmann recruited a colleague, Peter Romeis, and a surgical nurse, Gerda Ditzen, to assist him. Forssmann’s first attempt failed. Peter Romeis performed the cutdown on Forssmann’s cubital vein and advanced the catheter 35 cm, but Romeis lost courage, believing it too dangerous to continue, and stopped the experiment even though Forssmann felt fine. A week later, Forssmann chose a quiet afternoon when most of the hospital staff napped, and together with his nurse accomplice, he gathered the surgical instruments in an empty room to perform the procedure. Gerda Ditzen insisted on being the first participant and Forssmann played along, fully intending to perform the procedure on himself. After restraining the nurse to the table and preparing her incision site with iodine, Forssmann turned from her, quickly performed the venous cutdown on his own left arm, and inserted the ureteral catheter 65 cm. Ditzen became angry when she realized the deceit but quickly helped him walk down a corridor and two flights of stairs to the x-ray suite, where Forssmann confirmed the position of the catheter tip in his right atrium. Romeis apparently intercepted him in the x-ray suite to try to abort the experiment, but, according to one account, “… the only way Forssmann could hold him off was by kicking him in the shins.”
In his published account of his self-experimentation, Werner Forssmann also describes a case where he used the catheter to deliver a solution of glucose, epinephrine, and strophanthin into the heart of a patient gravely ill with purulent peritonitis from a ruptured appendix. The patient died shortly after a brief period of improvement, and the autopsy confirmed the catheter position in the right atrium.
Forssmann’s stunt did little to advance the field of cardiac catheterization beyond the bold demonstration that a catheter could actually be positioned safely in the human right atrium. No pressure measurements were made, and the catheter was not positioned in any other cardiac chambers. However, Forssmann had crossed the threshold and introduced the world to the potential of human cardiac catheterization.
Great turmoil and controversy followed Forssmann’s publication. He failed to gain support from the medical community, and, while he continued investigations in cardiac catheterization (including at least six more self-experiments), he became increasingly discouraged by the rigid, hierarchical nature of German academic medicine and became a urologist in private practice.
In the immediate years following Forssmann’s success, a few isolated investigators dabbled in right-heart catheterization experiments. However, nearly a decade would pass before there emerged a systematic discipline of right-heart catheterization exemplified by the classical work of André F. Cournand ( Fig. 1.4 ) and Dickinson W. Richards at Columbia University’s First Medical Division of Bellevue Hospital. The development of right-heart catheterization arose out of Cournand and Richards’s interest in pulmonary function, measurement of blood flow, and the interactions between the heart and lungs in both health and disease. In the early 1930s, the group desired to measure pulmonary blood flow using the direct Fick method; however, this would require measuring mixed venous blood from the right heart, a feat considered too dangerous. Aware of Werner Forssmann’s act, the group first demonstrated safety in animals and then placed modified urethral catheters in the right atrium of humans, sampling blood for oxygen content and making determinations of blood flow using Fick’s principle. By the early 1940s a safe and valuable methodology of right-heart catheterization had been established, and Columbia became recognized as the first “cardiopulmonary laboratory” capable of applying these techniques to the study of cardiac and pulmonary diseases. With the onset of worldwide hostilities and imminent war, the group first directed their efforts to the analysis of blood flow in traumatic shock, making important observations valuable in wartime. After the war, Cournand, Richards, and others from their group published many landmark articles describing the hemodynamic findings in congenital heart disease, cor pulmonale, valvular heart disease, and pericardial disease. Much of our current understanding of these conditions has evolved from this important body of work.
Growing confidence and experience in right-heart catheterization techniques led to an interest in catheterization of the left heart. Catheter access to the left heart offered unique challenges and a much greater concern about safety, and initial adventures in accessing the left heart proved highly dangerous. Proposed and attempted methods to access the left ventricle included direct apical puncture, retrograde access from puncture of the thoracic or abdominal aorta, and a subxiphoid entry first into the right ventricle and then followed by puncture of the interventricular septum. Methods to directly access the left atrium included a transbronchial approach via a bronchoscope and a direct, posterior paravertebral left atrial puncture. It is interesting to note that reports of experiments involving self-catheterization similar to Werner Forssmann’s involving the left heart are conspicuously absent from the literature.
Henry Zimmerman et al. reported the first series of retrograde left-heart catheterizations from a left ulnar artery cutdown. This report noted failure to pass a catheter across the aortic valve from a retrograde approach in five normal patients, theorizing that the normal aortic valve prevented “against the stream” passage of the catheter, so they turned their attention to patients with aortic insufficiency. Zimmerman successfully entered the left ventricle in 11 patients with syphilitic aortic insufficiency. However, in a single patient with rheumatic aortic insufficiency, the attempt proved fatal. Present-day cardiologists engaged in the regular performance of left-heart catheterization would find their account shocking. While attempting to pass the catheter into the left ventricle:
… the subject suddenly complained of substernal chest pain and the electrocardiogram which was being recorded showed the abrupt appearance of ventricular fibrillation. The catheter was immediately withdrawn. Nine cubic centimeters of 1 percent solution of procaine with 0.5 cc of a 1:1000 solution of adrenalin were injected directly into the heart without effect on the cardiac mechanism. The heart was then exposed and massaged. This resulted in the restoration of a sinus rhythm, but the ventricular contractions were feeble and fifteen minutes after the onset of ventricular fibrillation the heart ceased beating..
With a failure rate of 100% in normal patients and an initial procedural mortality of nearly 10%, it is a wonder that further attempts at retrograde left-heart catheterization were made. However, perseverance improved the safety and success of retrograde left-heart catheterization to its currently recognized form. Additional advances included the development of transseptal catheterization techniques, simultaneous right- and left-heart catheterization, and, of course, angiography. By the end of the 1950s, right- and left-heart catheterization had become firmly established clinical techniques for the evaluation of valvular, structural, and congenital heart disease.
With most of the basic elements of catheterization techniques in place, investigators turned to refinement in equipment and techniques. Catheter design represented one of the first important refinements. The stiff, unwieldy catheters available to earlier generations of cardiovascular researchers required substantial manipulative skill to position and often caused significant arrhythmia. The invention of the balloon flotation catheter, exemplified by the Swan-Ganz catheter, represented the innovation leading to the universal acceptance and widespread practical application of hemodynamic assessment. The balloon flotation catheter became a clinical reality from the desire of Dr. Harold J.C. Swan, professor of medicine at the University of California, Los Angeles, and director of cardiology at Cedars-Sinai Medical Center, to apply cardiac catheterization techniques to study the physiology of acute myocardial infarction ( Fig. 1.5 ). In the early 1960s cutting-edge hospitals began to develop specialized coronary care units to care for patients with acute myocardial infarction. Designed primarily to monitor and treat arrhythmias, coronary care units also became an obvious place to study the physiology of acute myocardial infarction. Early efforts to measure hemodynamics in potentially unstable patients with acute myocardial infarction using the stiff catheters and primitive techniques available at that time tended to induce life-threatening arrhythmias. Cardiologists considered catheterization dangerous during the acute phase of infarction and that it carried an unacceptable risk.
