Ruby anniversary: The key revolutions of the past 40 years

Giuliana Capretti and Alaide Chieffo

Advances in materials and techniques over the past 40 years have led to a substantial reduction in major adverse cardiovascular events. Giuliana Capretti and Alaide Chieffo review these key advances, or revolutions, and also look at how leading female interventional cardiologists have helped to shape the field.

Following the pivotal first in-human coronary angioplasty, performed by Andreas Grüntzig, the first revolution in the history of coronary angioplasty was the introduction of a new catheter system with the steerable guidewire (John Simpson, USA, 1981) and the invention of a rapid exchange catheter known as the “monorail” catheter (Tassilo Bonzel, Germany, 1984). Occlusive dissections and restenosis after angioplasty were identified as the main limits of the procedure. Therefore, the second revolution was the introduction of intraluminal stent—metal scaffolding designed to enhance procedural success, avoiding vessel closure from dissections.

Jacques Puel in France implanted the first coronary Wallstent in 1986 and the Palmaz-Schatz stent was approved by FDA, after the results of two randomised trials demonstrating its efficacy in reducing restenosis: BENESTENT (Belgium–Netherlands Stent) presented by Patrick  Serruys and STRESS (Stent Restenosis Study) reported by David L Fishman, in 1994.

After the introduction of the bare metal stent, the initial enthusiasm was tempered by reports of acute and subacute stent thrombosis. Initially, anticoagulation therapy with heparin administration in the cath labs and subsequent oral anticoagulation, then with warfarin in combination with single antiplatelet therapy with aspirin, was used to prevent stent thrombosis. However, the regimen was associated with 2.7% rate of stent thrombosis and an excess of bleeding and vascular access site complications.1

In 1995, Antonio Colombo tested the hypothesis that oral anticoagulation therapy was not necessary when stent expansion was optimal, accomplished by using intravascular ultrasound (IVUS) and high pressures stent implantation, as well as when dual antiplatelet therapy (DAPT) with aspirin and ticlopidine was given. He suggested that restenosis and subacute stent thrombosis might be the result of stent under-deployment and inadequate sizing, and that platelets—rather than coagulation factors—had a role in stent thrombosis.2

However, despite DAPT and optimal implantation, restenosis remained a main limitation of bare metal stent implantation. In 1996, in attempt to minimise this phenomenon, Robert Falotico developed a device eluting an antiproliferative drug during stent deployment. Therefore, the third revolution in the history of coronary angioplasty was the drug-eluting stent—approved by FDA in 2003 after the results of large clinical trials demonstrated a significant reduction of in-stent restenosis compared to BMS (RAVEL, TAXUS II). Drug-eluting stents were more effective in preventing in-stent restenosis. Without any doubt, the forth revolution in the history of coronary angioplasty has been bioresorbable scaffolds—but there are technical issues still to resolve.

Women in interventional cardiology

Although women have been always under-represented in interventional cardiology, female cardiologists have made significant contributions to the field. Since the beginning, women were part of the history of angioplasty. Andreas Grüntzig was the first to perform angioplasty, but his breakthrough was possible because of the work of his assistant Maria Schlumpf who collaborated in fashioning the hand-made balloon catheters on the kitchen table in Grüntzig’s apartment.

In the last two decades, other female interventional cardiologists worked on ways to improve current angioplasty practices. Many of the developments have been led by female pioneers conducting large randomised trials. Firstly, Marie-Claude Morice (France) who contributed to the therapeutic revolution brought about by stents validating the concept of DAPT for prevention of stent thrombosis in the French study in 1996. She had also a central role in pivotal trials; she was the principal investigator of the RAVEL (Randomised comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization) trial, the first worldwide randomised study on drug-eluting stent showed that they improved prevention of restenosis and associated clinical events compared with bare metal stent.3 Most recently, she was in the executive committee of the SYNTAX (Synergy between PCI with Taxus and cardiac surgery) and EXCEL (Evaluation of Xience versus coronary artery bypass surgery for effectiveness of left main revascularization) trials have led to significant changes in guidelines for the treatment of coronary left main disease. She is also the president and medical director of the European Center for Cardiovascular Research (CERC) founded in 2008.

Next in line is Cindy Grines (USA), who is one of the true pioneers of primary percutaneous coronary intervention (PCI). She was the principal investigator of PAMI trial, the first randomised trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction.4 The results of this trial converted the world into using primary angioplasty instead of thrombolytic revolutionising the management of ST elevation myocardial infarction. Actually, she is the only female editor of an interventional cardiology journal (Journal of Interventional Cardiology).

Another female pioneer, Lilian Grinfeld (Argentina), played a particular role as she was the first female cardiologist to perform angioplasty in Argentina. She was also the first female president of both the Argentina Society of Cardiology and the Argentine College of Interventional Cardiologists Association. She actively participated in many research trials and collaborations and she was a founding member of Women in Innovations (WIN) initiative founded by Roxana Mehran (USA) to address gender disparities in treatment and outcomes and to advocate for greater inclusion of women in clinical trials.

In addition to the WIN initiative, Roxana Mehran  is recognised for her experience and expertise as a clinical trial specialist and for her research interests expanding from mechanisms of restenosis to treatment,5 developing a score model for acute kidney injury after PCI6 and several studies evaluating the optimal antithrombotic regimen in PCI and transcatheter aortic valve implantation (TAVI).

Recent years have seen rapid development in the catheter-based treatment of structural heart disease. Therefore, focusing on the early female pioneers of cardiac intervention, it is important to cite Helene Eltchaninoff (France) who was at Alain Cribier’s side for the first human TAVI case and with him or alone for subsequent implantations.7

In summary, angioplasty has revolutionised the way heart disease and we have to be grateful for the pioneering work of Andreas Grüntzig and the other forefathers and foremothers that have to be an inspiration for the future. We have to look ahead to the future of angioplasty continually working on ways to improve current materials and technique and also motivate new generation of cardiologists in order to give them the possibility to become the pioneers of the new era of interventional cardiology.


  1. Leon et al. N Engl J Med. 1998; 339 (23): 1665–71.
  2. Colombo et al. Circulation 1995; 91 (6): 1676–88.
  3. Morice et al. N Engl J Med 2002; 346 (23): 1773–80.
  4. Grines et al. J Am Coll Cardiol 2002; 39 (11): 1713–19.
  5. Mehran et al. Circulation 1999; 100 (18): 1872–78.
  6. Mehran et al. J Am Coll Cardiol 2004; 44 (7): 1393–99.
  7. Cribier et al. Circulation 2002; 106 (24): 3006–08.

Giuliana Capretti and Alaide Chieffo are both at Interventional Cardiology Unit, San Raffaele Scientific Institute, Milan, Italy


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