Development of angioplasty spawned 40 years of innovation, exploration

When Andreas Grüntzig, MD, performed the first coronary angioplasty in a human patient in September 1977 in Zurich, he forever altered the landscape of cardiology.

“Forty years later, we can say that coronary angioplasty had the greatest impact of any other advance in the field. It transformed cardiology from a primarily diagnostic discipline into a therapeutic, semi-surgical discipline and essentially gave birth to what we now call interventional cardiology,” Bernhard Meier, MD, senior consultant and former chairman of the department of cardiology at the University Hospital of Bern, Switzerland, told Cardiology Today.

Before the inception of coronary angioplasty, patients with CAD had two treatment options: medical management or revascularization with CABG. The advent of interventional cardiology, however, afforded physicians the opportunity to treat an underlying disease such as CAD more effectively than with medical therapy and less invasively than with surgery, Gregg W. Stone, MD, professor of medicine at Columbia University Medical Center; director of cardiovascular research and education for Columbia University Medical Center/NewYork-Presbyterian Hospital; co-director of medical research and education at the Cardiovascular Research Foundation; and Cardiology Today’s Intervention Editorial Board Member, said.

An unintended consequence, he noted, was a heightened atmosphere of inventiveness.

“Interventional cardiology created a huge field of innovation and investigation,” Stone said. “It spurred the development of lifesaving therapies, allowed us to reduce symptoms and improve quality of life, and also led to the parallel fields of endovascular intervention and structural heart disease interventions. The development of coronary angioplasty was the foundation of a huge revolution in cardiology.”

Additionally, interventional cardiologists have become well-versed in primary and secondary prevention, especially as medical therapies for CAD such as statins became available. These treatments have significantly enhanced patient care, Roxana Mehran, MD, associate medical editor of Cardiology Today’s Intervention and cardiologist and professor of medicine at Icahn School of Medicine at Mount Sinai, noted.

“There are great therapeutic regimens now for patients with diabetes, patients with elevated cholesterol and patients with multiple comorbid conditions,” she said. “We can now manage these patients using risk models, understand who should get what therapy and head into the future of customized patient management modeled on all of the data we currently have available.”

Pushing boundaries

Although percutaneous transluminal coronary angioplasty (PTCA), now commonly known as percutaneous coronary intervention, or PCI, had an enormous impact on cardiology, the initial concept was greeted with skepticism, David P. Faxon, MD, associate chief of cardiology at Brigham and Women’s Hospital and senior lecturer at Harvard Medical School, said in an interview.

“The idea of putting a balloon inside the coronary artery and blowing it up was almost considered blasphemy; it was forbidden,” Faxon, a member of the Cardiology Today Editorial Board, said.

Grüntzig based his work with balloon dilatation on an angioplasty technique introduced by Charles Dotter, MD, based on using catheters of incremental outer diameters. Dotter and Melvin P. Judkins, MD, were the fathers of interventional radiology, which was at the time being used to treat peripheral artery disease, primarily in the lower limbs, Meier told Cardiology Today. Making the leap from the legs to the heart, however, seemed not only audacious but dangerous to many physicians, Meier noted.

“The leg arteries are much larger than the coronary arteries and are, therefore, easier to work with. Furthermore, if you have a serious problem with the leg artery, patients will, at worst, lose a limb, which is a terrible consequence, but they will not die. If you have a serious problem with the coronary artery, the patient dies within minutes,” Meier said.

Despite concerns, Grüntzig forged ahead. He developed a small balloon catheter designed to fit in the coronary arteries and conducted several experiments in dogs. For his first attempt in humans, Grüntzig searched for a patient with a single stenosis to maximize success and minimize complications.

After nearly 2 years, Meier, who was Grüntzig’s fellow at the time, identified the first patient who would successfully undergo PTCA: a 38-year-old man with sudden severe angina pectoris.

“The same year, Grüntzig presented the results of his first four cases at the American Heart Association meeting in 1977,” Spencer B. King III, MD, professor of medicine emeritus at the Emory University School of Medicine and Cardiology Today Editorial Board Member, who recruited Grüntzig to move to Emory and work closely with him in the early days of PCI, told Cardiology Today. “When he showed the films from those first four patients, he received a standing ovation. It was the most astonishing thing.”

A slow start

Although PTCA appeared promising, uptake was slow. Not only did many physicians remain skeptical, but the procedure was tightly regulated by Grüntzig and the manufacturers, King said.

Grüntzig’s original balloon catheter was revolutionary at the time, in that it employed inelastic balloon technology that let the balloon only grow to a predetermined size and place a great deal of force on the lesion, which allowed it to be dilated. Nevertheless, the technology was imperfect, Faxon said, and success rates started out low.

“Nine months after the first procedure, only 50 or 60 cases had been performed around the world. In 30% to 40% of those, balloon angioplasty failed and some patients were sent for emergent CABG,” Peter C. Block, MD, professor, and director of the Structural Heart Disease Intervention Program at Emory University School of Medicine, told Cardiology Today. “With more than one-third of failures and up to 10% of patients being sent for emergency surgery, we had to ask ourselves: Are we really doing something useful?”

Fortunately, the introduction of new technologies rapidly changed the procedure, Block said. The development of steerable guidewires and over-the-wire balloons in the early 1980s by John B. Simpson, MD, PhD, dramatically increased the success of coronary angioplasty, he noted.

“The original catheter had a small wire on the end of the balloon and the catheter itself was stiff and difficult to manipulate. Once we had steerable wires, we were able to treat many more patients with lesions in remote positions or address multiple vessels,” King said.

As success rates improved, coronary angioplasty began to gain some traction about 5 years after the first PTCA procedure, according to David O. Williams, MD, senior physician at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School.

Unfortunately, at the time, the procedure still only involved balloons, which were associated with two major problems: abrupt closure immediately after the procedure and restenosis.

“About 35% to 40% of the blockages fixed would return, which was very discouraging for us and the patient,” Williams told Cardiology Today. “But the advent of stents changed all of that.”

Evolution of technology

In 1986, the first coronary stents were implanted by Jacques Puel, MD, in France, and Ulrich Sigwart, MD, in Switzerland, marking a paradigm shift in the approach to coronary angioplasty.

After the concept of PCI became more accepted, an era of exploration occurred during which researchers investigated novel methods, such as lasers and atherectomy devices, to improve balloon angioplasty, but most were abandoned, King said.

“The stent was the one that survived and became the next most important technology in PCI,” King said. “Almost all angioplasty resulted in some dissection to the artery, but we were able to seal the dissection with a stent and prevent acute closures, so the need for emergent CABG immediately after the procedure dropped precipitously once stents became available.”

Over time, the technology continued to evolve, with researchers and physicians soon realizing that the first coronary stents — bare-metal stents — were suboptimal, according to Martin B. Leon, MD, professor of medicine and director of the Center for Interventional Vascular Therapy at Columbia University Medical Center/NewYork-Presbyterian Hospital and founder of the Cardiovascular Research Foundation. This led to the more incremental advance of drug-eluting stents.

“DES were the first biotechnology introduced to medicine in which a drug, a drug carrier vehicle and a permanent implantable device were used to treat a specific disease,” Leon said.

The initial DES prompted concerns about stent thrombosis, Faxon and Williams noted in a paper published in Circulation in 2016. However, the second-generation DES improved the issue, and are associated with very low rates of stent thrombosis and improved long-term outcomes.

“The thinner struts and more flexible structure coupled with the use of more effective antiproliferative agents such as everolimus, biolimus, and tacrolimus in comparison with sirolimus and paclitaxel have been responsible. The everolimus chromium cobalt stent, in particular, has been shown to result in a lower late stent thrombosis rate in comparison with [BMS] and is one of the most commonly used stents today,” they wrote.

Although DES has become the standard for patients undergoing PCI, experts who spoke with Cardiology Today said they expect even more progress in the future. Bioresorbable vascular scaffolds, for example, hold promise, especially as interventional cardiologists begin to see more patients with stents already in place.

Early results for first-generation BVS (Absorb GT1 Bioresorbable Vascular Scaffold System, Abbott Vascular) have been less than encouraging, Stone noted, partially because of the mechanical nature of these early devices and the suboptimal technique that was used for implantation.

However, the future of stenting may lie beyond refining DES for its current purpose, according to Deepak L. Bhatt, MD, MPH, chief medical editor of Cardiology Today’s Intervention, Cardiology Today Editorial Board Member, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital Heart & Vascular Center and professor of medicine at Harvard Medical School.

“Ultimately, the DES may evolve beyond just delivering the drug to prevent restenosis and may perhaps eventually deliver therapeutic agents downstream in the artery,” Bhatt told Cardiology Today.

Concomitant advances

Stents may mark a turning point in the growth of PCI, but the development of new strategies and approaches has also moved the field forward, according to Bhatt.

“The movement toward percutaneous access many years ago was huge, and now, the increasing use of radial vs. femoral artery access has substantially decreased bleeding and vascular complications, which is another big step toward making PCI even less invasive,” he said.

Furthermore, advances in the technologies around stent use have significantly shaped the current state of PCI, Mehran said in an interview.

“We have atherectomy, scoring balloons and new wiring technologies that allow us to deal with highly calcified lesions, more complex disease and high-risk patients,” she said. “We also have hemodynamic support devices that have been central to saving lives and recovering myocardial function, as well as vascular closure devices that reduce periprocedural complications. These technologies are opening the door to early discharge, early ambulation and better patient outcomes after PCI.”

PCI technology also inspired clinicians to consider how else catheter-based procedures could benefit patients with heart disease. One area where this bore fruit was in valvular heart disease, where transcatheter aortic valve replacement, first performed in 2002 by Alain Cribier, MD, is now an accepted alterative to surgery in intermediate- to extreme-risk patients.

Revolutionizing patient care

PCI has significantly affected many aspects of patient care, but it has had the greatest impact in the area of acute MI, according to King.

“We saw a marked change in survivorship with PCI, and it eventually became the most lifesaving event for acute MI ever discovered,” he told Cardiology Today.

Bhatt also counts it as one of the major advances in medicine of the 20th century.

“We moved from having no therapy to lysis to primary PCI, which is much more efficacious and much safer in terms of intracranial bleeding,” he said. “Additionally, on the other end of the spectrum, in stable angina that’s refractory to medical therapy, PCI can significantly improve quality of life and is important in that regard as well.”

For patients with non-STEMI and unstable angina, data suggest PCI reduces important clinical CV events with appropriate risk stratification, he noted.

Importantly, as the technology evolved, so did researchers’ and physicians’ knowledge about adjunctive pharmacotherapy, according to Block. At the beginning, very little was known about what kind of anticoagulation was appropriate for patients undergoing coronary angioplasty.

This uncertainty, Bhatt noted, has changed with time.

“There are more data about different intensities and durations of dual antiplatelet therapy now, so we have a wealth of knowledge about adjunctive antithrombotic strategies as well as IV strategies showing the evolution from heparin to the use of glycoprotein IIb/IIIa inhibitors to the most recent addition of cangrelor (Kengreal, Chiesi) to our armamentarium,” he told Cardiology Today.

In some ways, the advent of PCI also revolutionized evidence-based medicine.

Christopher J. White, MD, chief of medical services at Ochsner Medical Center; professor and chairman of medicine at the Ochsner Clinical School, University of Queensland; and medical director for system service lines and system chairman for cardiology at Ochsner Medical Center in New Orleans, and Cardiology Today’s Intervention Editorial Board Member, also credited Grüntzig with the demand for data that is now common practice in cardiology.

“The discipline that interventional cardiology accepted was led by Grüntzig, who simply as the leader of this technology and the most visible person bringing PCI to patients was insistent on data to support expansion of the therapy,” he told Cardiology Today. “Many people were willing to see a quick and robust expansion of PCI, but Grüntzig’s moral leadership brought that under control and taught us lessons about the need for data.”

New paths forward

Forty years after Grüntzig performed the first PCI, interventional cardiology is faced with the question of what the next few decades will bring.

In the short term, technological refinements to stents or equipment are likely, according to experts who spoke with Cardiology Today. Investigation into optimal treatment strategies, such as complete revascularization vs. culprit lesion-only revascularization in STEMI, or the best approach for treating chronic total occlusions, is also underway.

However, Block said there may not be much of a future for PCI in the long term. New medical therapies for CAD, such as PCSK9 inhibitors, as well as the potential development of preventive drugs based on risk factors and genetics may make PCI obsolete.

“I predict that in the next 2 decades, we will look back on angioplasty and CABG as a last resort for patients who have CAD and cannot be treated with intense LDL-lowering therapies and other treatments that prevent CAD from actually occurring,” he said.

Much of the excitement surrounding percutaneous interventions has moved outside the coronary arteries, experts told Cardiology Today.

“The most rapid and, arguably, the most exciting growth has been in structural heart disease, with transcatheter aortic valve replacement becoming an almost mature specialty,” Stone said.

In addition to TAVR, other aspects of structural heart disease intervention are advancing, Meier said, noting that patent foramen ovale closure and left atrial appendage closure will likely become more common in the future. Catheter-based mitral valve and tricuspid valve therapies are also developing, albeit at a slower pace.

Endovascular intervention is entering an interesting phase as well, according to White.

“In the future, we will discover a more durable solution for lower extremity revascularization. We currently struggle with restenosis rates in the legs that approach 50% to 60% after a couple of years, so we’re going to evaluate [DES] technology that, just like in the coronary arteries, will push those restenosis rates down into single digits,” he said.

Overall, the interventional cardiology field is enthused and optimistic as it takes the next step forward, according to Stone.

“It’s a very exciting time. With 40 years of interventional cardiology behind us, it’s hard to even imagine what it’s going to look like 10 years from now, let alone 40 years in the future,” he said. – by Melissa Foster

• References:
• Berry D. Eur Heart J. 2009;doi:10.1093/eurheartj/ehp182.
• Faxon DP, et al. Circulation. 2016;doi:10.1161/CIRCULATIONAHA.116.023551.

• For more information:
• Deepak L. Bhatt, MD, MPH, can be reached at dbhatt@bwh.harvard.edu.
• Peter C. Block, MD, can be reached at peter.block@emoryhealthcare.org.
• David P. Faxon, MD, can be reached at dfaxon@partners.org.
• Spencer B. King III, MD, can be reached at spencer.king@emoryhealthcare.org.
• Martin B. Leon, MD, can be reached at ml2398@cumc.columbia.edu.
• Bernhard Meier, MD, can be reached at bernhard.meier@insel.ch.
• Roxana Mehran, MD, can be reached at roxana.mehran@mountsinai.org.
• Gregg W. Stone, MD, can be reached at gstone@crf.org.
• Christopher J. White, MD, can be reached at cwhite@ochsner.org.
• David O. Williams, MD, can be reached at dowilliams@partners.org.

Disclosures: Bhatt reports financial ties with Amarin, Amgen, AstraZeneca, Biotronik, Boston Scientific, Bristol-Myers Squibb, Cardax, Chiesi, Eisai, Eli Lilly, Ethicon, FlowCo, Forest Laboratories, Ironwood, Ischemix, Medtronic, Merck, Pfizer, PLx Pharma, Regado Biosciences, Roche, Sanofi Aventis, St. Jude Medical, Takeda and The Medicines Company. Meier reports consulting for Abbott, Medtronic and Biotronik. Stone reports consulting for Reva and Valfix and having equity in Guided Delivery Systems. Block, Faxon, King, Leon, Mehran, White and Williams report no relevant financial disclosures.