Circulation

CENTENNIAL COLLECTION

The American Heart Association’s Centennial

and Percutaneous Coronary Intervention’s
Semi-Centennial
Patrick W. Serruys, MD, PhD; Pruthvi C. Revaiah, MD

I
n 1975 at a meeting in Frankfurt, Professor Paul Lich-
tlen, 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 dis-
tal 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. Hon-
estly, foreseeing its future was challenging.
On September 17, 1977, in Zurich, Grüntzig per-
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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 ste-
nosis; 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.
An important technical development was the intro-
duction of the steerable, movable, guide wire by John
Simpson in 1982, which allowed operators to both
maintain access across the lesion in case of inad-

formed successful dilatation of an 85% narrowing
in the left anterior descending coronary artery of a
38-year-old man with severe angina using his percuta-
neous transluminal coronary angioplasty (PTCA) cath-
eter (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
equate 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 knowl-
edge 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 pri-
mary 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 occlu-
sion were major hurdles. In 1986, the so-called perfusion

Key Words: angioplasty, balloon, coronary ■ myocardial infarction ■ percutaneous coronary intervention ■ stents

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.
Correspondence to: Patrick W. Serruys, MD, PhD, Cardiovascular Research Centre for Advanced Imaging and Core Lab Research Centre, University of Galway,
University Road, Galway, Ireland H91 TK33. Email patrick.serruys@universityofgalway.ie or patrick.w.j.c.serruys@gmail.com
For Sources of Funding and Disclosures, see page 977.
© 2024 American Heart Association, Inc.
Circulation is available at www.ahajournals.org/journal/circ

Circulation. 2024;149:973–978. DOI: 10.1161/CIRCULATIONAHA.123.064461 March 26, 2024 973

 Serruys and Revaiah History and Future of PCI
FRAME OF REFERENCE
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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.

balloon was introduced to handle acute coronary dissec-
tions and impending occlusion.
In 1988, the National Heart, Lung, and Blood Insti-
tute PTCA Registry report indicated that the rate of
incidence for coronary spasm, coronary occlusion, coro-
nary 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 bal-
loon angioplasty, the rate of restenosis was 30% to

974 March 26, 2024 Circulation. 2024;149:973–978. DOI: 10.1161/CIRCULATIONAHA.123.064461

 Serruys and Revaiah
60% at 6 months—mainly driven by recoil and prolifera-
tive remodeling.
THE DEVICE ERA
By the mid-80s, engineers and interventional cardi-
ologists 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 atheroscle-
rotic 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 ex-
traction 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
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the rotational atherectomy, none of these devices have
stood the test of time; they were largely abandoned after
the advent of stents.
BARE METAL STENTS
Despite the golden era of new innovative technologies,
coronary angioplasty still faced 2 major challenges: peri-
procedural 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 for-
eign 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 antire-
stenotic 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-
Circulation. 2024;149:973–978. DOI: 10.1161/CIRCULATIONAHA.123.064461
History and Future of PCI
expanding “endoprosthesis,” bulkiness, stiffness, and
FRAME OF REFERENCE
the thrombogenic nature of this foreign body in the cor-
onary 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 anti-
platelet 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, Wik-
tor, 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.
DRUG-ELUTING STENTS
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 cyto-
static 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 quanti-
tative motorized intravascular ultrasound pullback. Eduar-
do 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 Revas-
cularization).
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.
March 26, 2024 975
 Serruys and Revaiah
THE HYPE BEHIND BIORESORBABLE
FRAME OF REFERENCE
SCAFFOLDS
Implantation of a permanent metallic prosthesis was
viewed as a major drawback in the treatment of coro-
nary 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 pa-
tients 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
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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 scaf-
fold has a late loss of 0.24±0.36 mm and clinically driven
target lesion revascularization rates of 2.6% in 116 pa-
tients at 1 year.
DRUG-COATED BALLOONS AND THE RE-
EMERGENCE OF BALLOON ANGIOPLASTY
It will be interesting to see if the old dream of elimi-
nating flow-limiting lesions via balloon dilatation while
simultaneously inhibiting constrictive remodeling and
neointimal proliferation without “leaving anything be-
hind” will be realized in future with drug-coated bal-
loons (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 resteno-
sis, native vessels are now the current and future target
of this technology.
976 March 26, 2024 Circulation. 2024;149:973–978. DOI: 10.1161/CIRCULATIONAHA.123.064461
History and Future of PCI
THE TRANSRADIAL PERCUTANEOUS
INTERVENTION REVOLUTION
In the last 2 decades, the transradial approach has revo-
lutionized the practice of interventional cardiology, with
its widespread adoption of PCI for reducing mortality
and bleeding-related complications, and improving pa-
tient comfort and quality of life compared with femoral
access. Slender PCI with a “stent on the wire” remains
on the horizon.
INCREASING SUCCESS WITH
PERCUTANEOUS CHRONIC TOTAL
OCCLUSION INTERVENTIONS
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 im-
provements in materials such as guidewires and micro-
catheters, techniques, and success rates. Patients with
increasing comorbidities and lesion complexity are cur-
rently treated with success rates of >90%.
At 3-years follow-up in EuroCTO (A Randomized Mul-
ticentre 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 cardio-
vascular events in the guideline-directed medical therapy
group was largely due to ischemia-driven revasculariza-
tions (PCI arm crossover).
FUTURE DIRECTIONS
Physiology and Imaging-Guided PCI and
Decision-Making Tools
The FAME (Fractional Flow Reserve Versus Angiog-
raphy 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 Quan-
titative 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 selec-
tion improved 1-year clinical outcomes compared with
standard angiography guidance. Recently, RENOVATE-
COMPLEX-PCI (Randomized Controlled Trial of
 Serruys and Revaiah
Intravascular Imaging Guidance Versus Angiography-
Guidance on Clinical Outcomes After Complex Per-
cutaneous Coronary Intervention) showed that among
patients with complex CAD undergoing PCI, intravascu-
lar imaging guidance improves clinical outcomes when
compared with angiography guidance alone. SYNTAX
II (Synergy Between PCI with Taxus and Cardiac Sur-
gery) 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 com-
pleteness 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 revas-
cularization in patients with acute or chronic coronary
syndromes and multivessel disease, especially with
PCI. Individualized decision-making tools like the SYN-
TAX 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
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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 nonob-
structive CAD may become standard before treating the
epicardial conductance vessel.
Will Conventional Invasive Angiography Be
Replaced by Coronary Computer Tomography
Angiography?
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 prob-
ability of CAD had significantly lower (74% relative risk
reduction) risk for major procedure-related complica-
tions with an initial strategy of coronary computer to-
mography angiography (CCTA) compared to invasive
coronary angiography. CCTA instead of invasive coro-
nary angiography may be a game-changer, impacting
Circulation. 2024;149:973–978. DOI: 10.1161/CIRCULATIONAHA.123.064461
History and Future of PCI
the traditional gatekeeper relationship between the
FRAME OF REFERENCE
noninvasive cardiologist, invasive cardiologist, radiolo-
gist, and surgeon. In patients with significant epicardial
obstruction, CCTA can assist in planning revasculariza-
tion by determining disease complexity, vessel size, le-
sion 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 Sur-
gical 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 cor-
onary angiography versus CCTA strategy for treatment
planning (PCI and CABG).
Silencing MicroRNA and Gene Editing for
Physiologic Control of Atherosclerosis
The decade of 2020 to 2030 will probably witness the
emergence and combination of metabolic and antiin-
flammatory interventions targeting PCSK9 (propro-
tein 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.
ARTICLE INFORMATION
Affiliation
Cardiovascular Research Centre for Advanced Imaging and Core Laboratory, Uni-
versity of Galway, Ireland.
Sources of Funding
None.
Disclosures
Dr Serruys reports institutional grants from Sinomedical Sciences Technology,
Sahajanand Medical Technologies, Philips/Volcano, Xeltis, and HeartFlow, out-
side the submitted work.
Dr Revaiah reports no conflicts.
March 26, 2024 977
 Serruys and Revaiah
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