In 1975 at a meeting in Frankfurt, Professor Paul Lichtlen, a key European opinion leader, quipped that a significant coronary lesion with a thin fibrous cap and a large atheromatous core (vulnerable plaque) could not be stretched with a balloon without the risk of major distal embolization as proposed by Dr Andreas Grüntzig, a young radiologist. During the meeting, Andreas Grüntzig’s poster described the creation of an artificial stenosis by tying catgut around canine coronary arteries, followed by the use of a balloon to open this artificial stenosis. Honestly, foreseeing its future was challenging.

On September 17, 1977, in Zurich, Grüntzig performed successful dilatation of an 85% narrowing in the left anterior descending coronary artery of a 38-year-old man with severe angina using his percutaneous transluminal coronary angioplasty (PTCA) catheter (Figure). Without doubt this was a pivotal moment in the history of cardiovascular medicine. A few weeks later in a letter to the Lancet he reported the results of PTCA in 5 additional patients,¹ and in 1979 he published his astounding work as a case series of 50 patients. He showed that PTCA successfully reduced coronary stenoses in 32 of 50 patients from a mean of 84% to 34% and a reduction in the mean translesion gradient from 58 to 19 mmHg. Twenty-nine patients had improvements in functional class during follow-up, while 6 had restenosis. His PTCA catheter initially consisted of a balloon with 2 small channels in the catheter shaft, one to inflate the balloon with contrast medium and the other to record pressure at the distal tip of the balloon to detect the reduction in pressure gradient across the lesion after dilatation of the stenosis; at the balloon tip was a short flexible 2-cm wire. Debate over the sustainability of PTCA as a modality of revascularization continued for at least 5 years after Grüntzig’s first case.

Figure. Major milestones in percutaneous coronary intervention. The first coronary angioplasty was performed by Andreas Grüntzig in 1977. The first human coronary stent implantation was performed in 1986. The first human coronary bioresorbable scaffold implantation was performed in 1998 and the first human coronary drug eluting stent implantation was performed in 1999.

An important technical development was the introduction of the steerable, movable, guide wire by John Simpson in 1982, which allowed operators to both maintain access across the lesion in case of inadequate results requiring further dilatation and access distal stenoses or those in branch vessels with acute angulations.

The primary PTCA journey began in the early 1980s when Geoffrey O. Hartzler had the foresight to use PTCA to treat acute myocardial infarction (MI), publishing his experiences in 41 patients in 1983. Based on his knowledge of pathophysiology, William C. Roberts endorsed Hartzler’s findings in a 1984 letter published with the title “When I Have an Acute MI Take Me to the Hospital That Has a Cardiac Catheterization Laboratory and Open Cardiac Surgical Facilities.”² Exactly 4 decades later primary PCI is now the standard-of-care treatment for ST-elevation MI and has saved millions of lives worldwide.

In the early days of PTCA, acute and subacute occlusion were major hurdles. In 1986, the so-called perfusion balloon was introduced to handle acute coronary dissections and impending occlusion.

In 1988, the National Heart, Lung, and Blood Institute PTCA Registry report indicated that the rate of incidence for coronary spasm, coronary occlusion, coronary dissection, and emergency CABG increased to 5%, 4.5%, 5%, and 5.8%, respectively, between 1978 and 1981, and 1.3%, 4.9%, 4.8%, and 3.5%, respectively, between 1985 and 1986. With percutaneous old balloon angioplasty, the rate of restenosis was 30% to 60% at 6 months—mainly driven by recoil and proliferative remodeling.

By the mid-80s, engineers and interventional cardiologists were testing devices using various sources of energy to treat atherosclerotic plaque with the goal of decreasing risk for restenosis. In 1981, Lee reported “laser dissolution” of cadaveric coronary atherosclerotic obstruction. An era of “new devices” was ushered in with directional atherectomy (John Simpson, 1985); argon laser (Choy, 1983), which was successfully used to recanalize 3 totally occluded right coronary arteries in vivo during coronary artery bypass surgery (CABG) in 1986; high-speed rotational atherectomy (David C. Auth, 1987); percutaneous excimer laser coronary angioplasty (Frank Litvak, 1990), which was used as an adjunct or alternative to conventional PTCA; and transluminal extraction atherectomy (Robert Stack, 1991).

Intracoronary brachytherapy was another attempt to reduce restenosis with gamma and beta radiation explored after the first patient had been treated by Jose Condado in 1996. In 1999 our group described a new phenomenon in interventional cardiology: late and sudden thrombosis after PTCA and intracoronary brachytherapy. At the time, another pioneer in that field, Ron Waksman, concluded that with brachytherapy, late thrombosis after radiation could be like “sitting on a time bomb.” Except for the rotational atherectomy, none of these devices have stood the test of time; they were largely abandoned after the advent of stents.

Despite the golden era of new innovative technologies, coronary angioplasty still faced 2 major challenges: periprocedural acute occlusion necessitating emergency CABG and the vexing problem of late restenosis. Bare metal stents (BMS) were initially developed as a “bailout” to scaffold the dissection flap and obviate recoil, but the price to pay was subacute thrombosis of the metallic foreign body in the hours and days after treatment. Naively, it was believed that the strut mesh could act as a sieve by preventing the intraluminal migration of proliferating cells; this was wrongly perceived to be a potential antirestenotic treatment.

In 1986, Ulrich Sigwart and Jaques Puel reported use of their self-expanding stent in 19 patients with coronary artery restenosis after balloon angioplasty (Figure) as the first used in humans. Between 1986 and 1991, balloon-expandable and self-expanding stents struggled to address multiple technical and clinical problems, including poor crimping of the stent on the balloon, incomplete expansion of the balloon-expandable stent, inaccurate deployment of the self-expanding “endoprosthesis,” bulkiness, stiffness, and the thrombogenic nature of this foreign body in the coronary bloodstream. The presence of metal struts was a nidus for platelet aggregation and thrombosis leading to early occlusions with significant morbidity. The whole armamentarium of combined anticoagulation and antiplatelet treatment to prevent these thrombotic events led to catastrophic bleeding. The results from the early experience of the Wallstent in the first 105 patients treated worldwide are sobering.³ Meanwhile, a number of new stents were proposed: the Palmaz–Schatz, Wiktor, and Gianturco–Roubin.

The next milestones were the BENESTENT I and II (Belgian–Netherlands STENT Study) and STRESS (Stent Restenosis Study) trials conducted in Europe and the United States,⁴ respectively, which firmly established that BMS could markedly reduce restenosis and improve clinical outcomes. Moreover, they demonstrated that the mechanism of restenosis was at least as much dependent on constrictive remodeling as on neointimal proliferation.

Although BMS reduced restenosis rates compared with balloon angioplasty alone, in-stent restenosis (Achilles heel of BMS) due to neointimal proliferation became a new iatrogenic syndrome (16–44% of cases). In July 1999, exposure to a possible savior occurred through Cordis Corporation at their facilities in New Jersey—the drug-eluting stent (DES). Previously, Elizabeth Nabel had drawn my attention to the fact that rapamune, a cytostatic drug discovered on Rapa Nui Island (Easter Island) upregulates p27—a cell-cycle inhibitor. On that day, we designed a trial with early evaluation of DES at 4 or 6 months by quantitative coronary angiography and quantitative motorized intravascular ultrasound pullback. Eduardo Sousa, in Sao Paolo, Brazil, and I, in Rotterdam, tested them for the first time in December 1999 (Figure). At the European Society of Cardiology Andreas Grüntzig Lecture in Interventional Cardiology in August 2000, we reported the impeccable results: zero restenosis in the first 33 patients,⁵ an outcome definitively confirmed by the landmark, double-blind, randomized controlled trial—RAVEL (A Randomized Comparison of a Sirolimus-Eluting Stent With a Standard Stent for Coronary Revascularization).

Shortly after the hype of these early results, new safety issues emerged, including the new Damocles’ sword late (1–12 month) and very late (≥1 year) stent thrombosis, long-term dependence on dual antiplatelet therapy, and intrastent neoatherosclerosis. Today’s stents have ultrathin struts that are made from alloys different from the initial bulky stainless steel, with sophisticated platforms and bioresorbable or biostable coatings that have dramatically mitigated the problems of restenosis and thrombosis.

Implantation of a permanent metallic prosthesis was viewed as a major drawback in the treatment of coronary artery stenosis. Engineer Keiji Igaki and cardiologist Hideo Tamai designed a polylactide thermoexpandable scaffold, which was tested in Europe in 2000 (Figure); however, dislodgment and poor retention of the device on the balloon, together with the thermolabile nature of the scaffold, precluded its clinical use—at least in Europe. In 2006, we, along with John Ormiston, introduced the first fully biodegradable, drug-eluting scaffolds, which eliminated the long-term presence of a foreign body in the coronary circulation.⁶ The first-in-human registry was followed by a family of randomized controlled trials in Europe, China, Japan, and the United States (ABSORB [A Bioresorbable Everolimus-Eluting Scaffold Versus a Metallic Everolimus-Eluting Stent for Ischaemic Heart Disease Caused by De-Novo Native Coronary Artery Lesions] I through IV). In ABSORB II, asymptomatic patients who were tested annually with maximal exercise, suddenly thrombosed their scaffolds at the end of the third year of follow-up, and this proved to be their death knell. Most recently, the 5-year results of ABSORB IV showed that despite improved implantation techniques, rates of target lesion failure remain 3% greater with BRS than with DES. A glimmer of hope comes from the last 2 years of follow-up, wherein the safety and efficiency of BRS was comparable to DES. With more efficient and reliable iterations, the dream of “leaving nothing behind” with BRS may one day come true. Recently, Haude et al⁷ have shown that the newer generation magnesium scaffold has a late loss of 0.24±0.36 mm and clinically driven target lesion revascularization rates of 2.6% in 116 patients at 1 year.

It will be interesting to see if the old dream of eliminating flow-limiting lesions via balloon dilatation while simultaneously inhibiting constrictive remodeling and neointimal proliferation without “leaving anything behind” will be realized in future with drug-coated balloons (DCB). The paclitaxel drug-coated balloon works by passive vessel wall transfer of lipophilic cytotoxic drug; with the Sirolimus drug-coated balloon, there is active penetration into the vessel wall with electrostatic attachment and long-term residency of microspheres or even nanospheres containing hydrophilic cytostatic sirolimus, such that the vessel wall itself serves as a natural drug reservoir with a duration of elution almost comparable to DES. Beyond the treatment of restenosis, native vessels are now the current and future target of this technology.

In the last 2 decades, the transradial approach has revolutionized the practice of interventional cardiology, with its widespread adoption of PCI for reducing mortality and bleeding-related complications, and improving patient comfort and quality of life compared with femoral access. Slender PCI with a “stent on the wire” remains on the horizon.

Chronic total occlusions (CTOs) are a common anatomic entity in patients with coronary artery disease (CAD), however they have been seriously undertreated with PCI, primarily due to inferior success rates compared with non-CTO PCI. During the past decade, there has been exponential progress in CTO PCI, with dramatic improvements in materials such as guidewires and microcatheters, techniques, and success rates. Patients with increasing comorbidities and lesion complexity are currently treated with success rates of >90%.

At 3-years follow-up in EuroCTO (A Randomized Multicentre Trial Comparing Revascularization and Optimal Medical Therapy for Chronic Total Coronary Occlusions), there was no difference in the rate of cardiovascular death or MI between PCI or optimal guideline-directed medical therapy among patients with a single remaining coronary CTO. The higher rate of major adverse cardiovascular events in the guideline-directed medical therapy group was largely due to ischemia-driven revascularizations (PCI arm crossover).

The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial showed that in patients with multivessel CAD, PCI guided by pressure wire–derived fractional flow reserve is associated with lower rates of major adverse cardiovascular events and resource utilization compared with angiography-guided PCI. The FAVOR III China Study (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) randomized controlled trial showed that among patients undergoing PCI, a noninvasive quantitative flow ratio–guided strategy of lesion selection improved 1-year clinical outcomes compared with standard angiography guidance. Recently, RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) showed that among patients with complex CAD undergoing PCI, intravascular imaging guidance improves clinical outcomes when compared with angiography guidance alone. SYNTAX II (Synergy Between PCI with Taxus and Cardiac Surgery) showed quite amazing results. It employed the best contemporary PCI practice: a combination of physiology, intravascular imaging, and use of thin-strut, biodegradable-polymer, newer-generation DES, along with the mandatory use of guideline-directed medical therapy and patient selection based on SYNTAX Score II, which looks at clinical characteristics, comorbidities, and physiology.

Because incomplete revascularization (residual SYNTAX score >8) is associated with increased risk for mortality, it is hypothesized that functional completeness of revascularization after PCI may further improve prognosis. Physicians, therefore, should strive to achieve this. In fact, contemporary data have now established the prognostic benefit of complete revascularization in patients with acute or chronic coronary syndromes and multivessel disease, especially with PCI. Individualized decision-making tools like the SYNTAX Score II 2020, which has been well validated, should and will be used more often in the selection of an optimal revascularization strategy (ie, PCI vs CABG) in patients with complex CAD. Notably these tools need to be periodically recalibrated.

Another facet of physiologic assessment (pressure pullback gradient index, delta fractional flow reserve, and index of microcirculatory resistance) gaining increased attention is the detection of diffuse disease pre-PCI, which can predict poor hemodynamic outcomes post-PCI (post-PCI fractional flow reserve ≤0.90). Reliable detection of microvascular dysfunction—invasively or noninvasively—in patients with obstructive and nonobstructive CAD may become standard before treating the epicardial conductance vessel.

The DISCHARGE (Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease) trial showed that patients with stable chest pain and an intermediate pretest probability of CAD had significantly lower (74% relative risk reduction) risk for major procedure-related complications with an initial strategy of coronary computer tomography angiography (CCTA) compared to invasive coronary angiography. CCTA instead of invasive coronary angiography may be a game-changer, impacting the traditional gatekeeper relationship between the noninvasive cardiologist, invasive cardiologist, radiologist, and surgeon. In patients with significant epicardial obstruction, CCTA can assist in planning revascularization by determining disease complexity, vessel size, lesion length, and tissue composition of atherosclerotic plaque, as well as the best fluoroscopic viewing angle; it may also help in selecting adjunctive percutaneous devices (eg, rotational atherectomy) and determining the best landing zone for stents or bypass grafts. As a first-in-human trial, FASTTRACK CABG ([Safety and Feasibility Evaluation of Planning and Execution of Surgical Revascularization Solely Based on Coronary CTA and FFRCT in Patients With Complex Coronary Artery Disease] URL: https://www.clinicaltrials.gov; Unique identifier: NCT04142021) has shown exceptional feasibility and acceptable safety in surgical decision-making, planning, and execution of CABG, solely based on CCTA. The next step is to randomize an invasive coronary angiography versus CCTA strategy for treatment planning (PCI and CABG).

The decade of 2020 to 2030 will probably witness the emergence and combination of metabolic and antiinflammatory interventions targeting PCSK9 (proprotein convertase subtilisin/kexin type 9), lipoprotein(a), IL-1 (interleukin-1), IL-6, inflammasome, and many other molecular pathways, thereby curbing the need for mechanical revascularization. Gene editing with CRISPR will, with a single subcutaneous injection, permanently affect the patient’s genome with gain- or loss-of-function; this is currently being tested in familial hypercholesterolemia.

During the next 5 decades, we should not be surprised if PCI and CABG are replaced by an intelligent primordial prevention guided by the early detection of the ominous -omics, which, combined with noninvasive imaging, will identify the early stage of the diseased phenotype. It is then that the era of “imagomics” will have arrived. Time will tell.

None.

Disclosures Dr Serruys reports institutional grants from Sinomedical Sciences Technology, Sahajanand Medical Technologies, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work.

Dr Revaiah reports no conflicts.

The American Heart Association celebrates its 100th anniversary in 2024. This article is part of a series across the entire AHA Journal portfolio written by international thought leaders on the past, present, and future of cardiovascular and cerebrovascular research and care. To explore the full Centennial Collection, visit https://www.ahajournals.org/centennial

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

For Sources of Funding and Disclosures, see page 977.

Circulation is available at www.ahajournals.org/journal/circ