The field of interventional cardiology has been driven by technical innovation. In a remarkable progression of needs identification, invention, testing, and refinement, innovators have developed nonsurgical techniques to see into the heart, diagnose a wide array of conditions, and deliver potent therapies. The pathways to innovation were not always simple or straightforward. Many of these inventors persevered despite being told by peers that what they were trying to do was infeasible and foolhardy. Some of most momentous contributions came from innovators who recognized the significance of a serendipitous event, applied newly available technologies to a longstanding clinical need, maximized the value of a previous discovery by casting it in a different light, or refined nascent tools and techniques to make them safer and more effective. Collectively, the efforts of these creative, determined individuals laid the foundations of a dynamic field that integrates diagnostics with the minimally invasive treatment of ischemic heart disease and other cardiac conditions.

The Pioneers

One of the earliest pioneers of cardiac catheterization, Werner Forssmann, was a German surgical resident who saw the need for a safer, more direct way to deliver drugs to the heart for cardiac resuscitation. He was interested in accessing the right heart via the venous system, but was not permitted to conduct a study because of the prevailing certainty that any foreign penetration of the heart would be instantaneously fatal. However, Forssmann was familiar with previous catheter experiments on animals, as well as accounts of accidental incursions in which the patients had survived.¹ In 1929, he threaded a urethral catheter into his own right atrium via his left antecubital vein and documented the catheter position by x-ray. Although the significance of his achievement was recognized by some, its merit was overshadowed by the consensus that his work was unacceptably dangerous. While Forssmann initially persisted in his research, the condemnation of his peers and loss of several academic positions caused him to abandon cardiology.^2,3

Years later, building on Forssmann’s work, André Cournand and Dickinson Richards went on to routinely catheterize both the right heart and the pulmonary artery, establishing the safety of the procedure in association with their groundbreaking research into cardiopulmonary physiology. By analyzing blood taken from the heart via a catheter, Cournand and Richards were able to detect hemodynamic abnormalities characteristic of congenital heart disease and pulmonary heart disease, measure the actions of cardiac drugs, perform studies of traumatic shock, and explore the physiology of heart failure.⁴ For this research, they were awarded the Nobel Prize in 1956, which they shared with Forssmann.³ Notably, while Forssmann was reportedly trying to develop a therapeutic technique, the essential advancements in the understanding of right heart physiology and pulmonary blood flow that followed came from innovators who focused on catheterization as a diagnostic tool.

Serendipity, and the genius to recognize its potential, has also played an important role in the history of interventional cardiology. F. Mason Sones, Jr., a pediatric cardiologist, was interested in improving the ability to visualize the coronary arteries. He conducted numerous animal experiments in which he placed an aortic catheter close to the coronary ostia for the delivery of contrast dye, but experienced little success.¹ In 1958, while performing an aortogram on a patient for an unrelated purpose, the catheter slipped out of position and contrast dye was injected directly into one of the patient’s coronary arteries. Although this caused asystole, Sones was able to resuscitate the patient and recognized in the process that the near-fatal slip had allowed him to clearly visualize the small coronary vessels for the first time. Sones went on to pioneer a technique that used specially shaped catheters to safely produce selective, high-quality images. Although the new imaging technique was initially met with skepticism, the ability to accurately diagnose blockages in the coronary arteries opened the door for the development of tools and techniques for revascularization.^1,5

Up to that point, advances in catheterization had made dramatic contributions to the understanding of human circulation and the ability to diagnose arterial stenoses. However, it took another unexpected event to make the transition to therapeutic intervention. In 1963, Charles Dotter, a vascular radiologist in Portland, Oregon, unintentionally recanalized a patient’s iliac artery by passing a catheter through an occlusion in the attempt to perform an abdominal aortogram.¹ In retrospect, this was the first time a condition that was normally treated with major surgery was approached with a minimally invasive, catheter-based technique.⁶ Dotter’s intervention marked the beginning of endovascular therapeutic techniques. He and his then-fellow, Melvin P. Judkins, went on to develop a technique for percutaneous transluminal dilation of peripheral arteries using a series of sequentially larger, rigid catheters (the “Dotter procedure”).^7,8

Around the same time, Thomas Fogarty, a surgical resident working with Dotter, identified the need for a safer, less traumatic way to remove vascular thrombus than through open surgery. He designed a novel, balloon-tipped catheter that could be inserted through a small incision in the vessel wall and passed through the thrombus. The balloon was then inflated with saline and pulled back so that the balloon dragged the thrombus out with it. Fogarty’s simple, elegant embolectomy technique went on to replace open surgical thrombectomy as the method of choice.⁹ (See text box on Tom Fogarty.) Subsequently, Fogarty and Dotter worked together on a catheter to treat arterial stenoses that used a balloon to increase the lumen diameter. However, their progress was ultimately limited by the fact that the available latex balloon material was too compliant to exert sufficient force on the lesions.¹

The Modern Era

In Europe, where Dotter’s catheter-based angioplasty technique was received with more interest than in the United States, a young German physician, Andreas Gruentzig, learned the method from a mentor. After relocating from Germany to Zurich, Switzerland, in 1970, Gruentzig used the technique to perform peripheral and renal artery recanalizations. Recognizing that Dotter’s approach could only enlarge the lumen to the size of the catheter, he sought to improve the balloon concept by working with a polymer chemist to develop a balloon made of a tougher material that could exert more force on the plaque. Gruentzig launched the modern field of interventional cardiology when he performed the first coronary balloon angioplasty in 1977.¹

Many of the early practitioners of angioplasty were inspired by Gruentzig to be inventive and entrepreneurial. In the years that followed the initial procedure, the innovations conceptualized by these clinicians propelled the field forward. Milestone technologies include John Simpson’s over-the-wire method for the delivery of angioplasty catheters, and his atherectomy device for plaque removal (see text box on John Simpson). Ulrich Sigwart and Julio Palmaz (see text box on Julio Palmaz) addressed problems of arterial recoil and restenosis through the development of coronary stents. Patient outcomes were further improved through numerous refinements to the stent design, as well as successive generations of drug-eluting stents and adjunct protective devices.

Gruentzig’s contribution to the culture of innovation in interventional cardiology was nearly as defining as his balloon catheter. A dynamic, free-spirited physician, Gruentzig was known for his charismatic and enthusiastic style as a clinician and teacher. He pioneered the live-demonstration course, which has become the signature educational and cultural event in the field, and serves as a showcase for new technologies. Gruentzig also provided a role model for much of what was to occur at the interface of innovation, entrepreneurship, and practice in interventional cardiology. He was a principal figure in the company that produced his balloon catheter, and for a while, even personally decided which physicians could purchase the devices.

Similarly, the innovators of the interventional tools that followed also helped found and grow start-up companies that competed to develop the best new technologies. As the industry expanded rapidly, the unusually close interaction between physicians and companies was reinforced by clinical and financial success. Young interventionalists learned from their mentors how to interface with companies and became the next generation of innovators. Other physicians became involved in device testing via preclinical and clinical trials. These individuals and the culture they created propelled interventional cardiology to a unique position at the epicenter of technical innovation and entrepreneurship in the early part of the 21st century. As 1 measure of the rate of technology innovation, cardiovascular devices account for more than half of all devices receiving premarket approval (original and supplements) from the US Food and Drug Administration (FDA)¹⁰ (Fig. 74-4).

The climate for technology innovation in the United States and abroad, however, is undergoing a historic change. Today’s value-oriented healthcare environment in major developed markets means that new technologies must also represent cost-effective solutions. To maximize their chances for reimbursement and adoption, innovators must demonstrate value by comparing a new therapy to the current standard of care in terms of clinical effectiveness, relevant outcomes such as survival and quality of life, and cost reduction.

In addition, heightened regulatory scrutiny in both the United States and Europe has substantially increased the amount of money and time required to bring a new device to market. The protracted timeline has added significantly to the risk profile for investors, reducing traditional venture investment in device technology. Against this backdrop, US innovators are pursuing new pathways such as nontraditional funding sources or moving clinical trials and/or entire companies overseas. Perhaps most importantly, the types of innovations most likely to get funding in this environment will be therapies with the potential to make a major difference in the quality of care, patient satisfaction, or cost reduction, rather than those technologies that offer only an incremental improvement over the existing standard of care.

Coupled with these new forces of value-based innovation and tightened regulatory oversight, the culture of entrepreneurship for physicians has changed dramatically, particularly in the United States. Compared to the early days of angioplasty, there is much stronger attention to potential financial conflicts of interest for physicians who invent and/or test new technologies. In the current climate, transparency of financial involvement with companies is mandated by federal (“sunshine”) laws, and in general, physicians with financial interests in a company or product are strongly discouraged or prohibited from participating in human trials of the technology.

Even as these and other market realities have added additional layers of complexity to the innovation process, new opportunities are emerging. Advanced developing markets such as China and India offer vast patient populations that are increasingly suffering chronic conditions such as heart disease, diabetes, and hypertension. In these countries, the rapidly growing middle class is demanding improved healthcare services, medical technologies, and related interventions, factors that in turn are stimulating improvements in healthcare infrastructure and expanded insurance coverage. However, innovators must approach these markets strategically, since they tend to be highly price sensitive, with unique challenges based on cultural differences and local conditions that must be carefully considered.

In this chapter, we explore the landscape of innovation in our field by examining the common characteristics of successful innovators, describing some of the essential tools required for developing and assessing new cardiovascular technologies, and looking ahead to some of the most significant challenges facing the next generation of innovators.

Careful examination of the lives and careers of several well-known physician entrepreneurs reveals a number of shared characteristics and traits that contributed to their success. Interestingly, many of these qualities contradict commonly held ideas about the interests and innate skills one would expect to find in an innovator. In this section, we outline some of the key factors that lead to important innovations and, in the process, highlight some potential misconceptions and myths about the development of new technologies.