RIGHT, LEFT HEART AND CORONARY CATHETERIZATION
The year 1929, arguably, marks the dawn of modern interventional cardiology. Standing on the shoulders of earlier visionaries, Werner Forsmann, a young surgical resident, inserted 65 cm of a ureteral catheter through basilic vein and documented its position in the right atrium by chest X-ray. Although he envisaged this as a procedure for intracardiac injection of drugs and for “central bloodletting”, it paved the way for accessing the right heart for pressure measurements, oximetry, angiography and interventional catheterization. In parallel, by 1947, polyethylene replaced rubber as the material for catheters and subsequently by a radiopaque variant in 1956. The other major advance which helped usher in the era of modern catheterization was the development of the image intensifier in the 1950s which allowed for the recording of cineangiograms as roll films (as opposed to single plate angiograms and series of “cut-films”).
Catheterization of the left heart took a different route to progress. Perhaps because it is counterintuitive to traverse retrograde through the peripheral arteries into the left sided chambers, most initial attempts to catheterize the left heart involved direct puncture of the thoracic aorta, left atrium and left ventricle, often with disastrous results. Though Farinas had demonstrated that it was possible to access the left heart through the femoral arteries in 1941, it was not until Seldinger devised his simple, safe and elegant technique in 1953 that left-heart catheterization became mainstream in catheterization laboratories.
The next great landmark in the evolution of interventions is the serendipitous catheterization of the right coronary by Mason Sones in 1958 during an ascending aortogram. Hitherto, 2direct contrast injection into the right coronaries was thought to be fatal. It is worth noting that Sones did not formally publish his work until he had carefully worked to improve the technique of coronary arteriography. Further refinements to the technique ensued over the subsequent years through the work of several people most notably, Judkins and Amplatz.
BALLOON ANGIOPLASTY
Although Dotter was using balloon-tipped catheters for angiography since the early 50s, it was not until 1963 that he, again serendipitously, recognized their therapeutic value while inadvertently crossing an occluded iliac artery while performing an aortogram. Dotter and his fellow Judkins performed the first intentional dilatation of a popliteal artery in an 82-year-old woman with gangrene. Though this technique of relieving obstruction (subsequently called “Dottering”) had been practiced centuries ago for relieving urethral strictures (Egypt, 500 BC), it failed to gain popularity because of the need to introduce rigid, wide-bore catheters and the hazard to side branches due to the “snow-plough effect”.
The next courageous step was taken by Andreas Gruentzig, an epidemiologist by training, who worked to reduce the bore of the catheters and used polyvinyl chloride for his balloons (which were less compliant than balloons made of latex). Gruentzig and Myler performed the first angioplasties retrogradely through the distal left anterior descending artery, in operating rooms after thoracotomy on patients who were undergoing coronary artery bypass grafting. Gruentzig performed the first coronary angioplasty on an awake patient in 1977 at Zurich and published the results of his first 5 patients in the Lancet. Of note, the subsequent cases also involved the left main in 1 patient and multiple vessels in another. Improvements to the technique and material (such as the introduction of the over-the-wire balloon by Simpson) followed. Gruentzig was planning a randomized trial of angioplasty compared to surgery at the time of his death in 1985 in a plane crash at the age of 46 (this was later funded as the Emory Angioplasty versus Surgery Trial).
ANGIOPLASTY BEYOND THE BALLOON
The limitations of plain balloon dilatation were recognized early on, and Dotter and Judkins speculated in the early 60s that silastic or plastic stents could maintain vessel patency after dilatation. But the main focus of investigators remained the mechanical removal of atherosclerotic material in the years after coronary angioplasty. Simpson developed the first atherectomy device which received US FDA approval in 1991. Other techniques such as rotational and laser atherectomy followed. The idea of stents in coronary arteries received a fillip through the work of Sigwart and colleagues who deployed the first self-expanding (Wallstent) in human coronary arteries 3in 1987. Subsequently balloon-mounted slotted tube stents (Palmaz-Shatz) and coil stents (Gianturco-Rubin) were developed. The early stents were approved for use primarily in the event of acute vessel closure after balloon angioplasty. Primary stenting at the time of angioplasty was recognized to reduce restenosis only after the completion of the STRESS and Benestent trials (Table 1).
CORONARY STENTS
The use of stents brought to the fore two major problems: (1) stent thrombosis and (2) in-stent restenosis. Much of the focus in interventional cardiology has since then been on combating these two adverse consequences. Studies in the 90s recognized the central role of the platelet in causing stent thrombosis and established the need for dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. The earliest P2Y12 inhibitor (Ticlopidine) has since been replaced by newer, more potent agents which afford greater protection against stent thrombosis, but also increase the risk of bleeding in some patients. Concurrently, changes in stent design (such as thinner struts) and deployment strategies (high-pressure deployment) have been applied to reduce the risk of restenosis and stent thrombosis. The recognition that in-stent restenosis is caused by injury-induced proliferation of local smooth muscle cells prompted the use of systemic, and later, local delivery of anti-proliferative agents at the site of injury. The development of the technology for stable stent coatings, with the desired antiproliferative agent which can be reliably delivered after stent implantation, is arguably the greatest recent advance in the prevention of restenosis. Validation of this strategy came in the year 2001 with the publication of the results of the Cypher trial of the sirolimus eluting stainless steel stent which showed near-zero restenosis rates. Paclitaxel eluting stainless steel stents followed soon.
Putative reactions to the polymer vehicle for stable local drug delivery through stents and the delayed endothelialization as a result of the antiproliferative drug brought on the scourge of late stent thrombosis. While restenosis has been considered rather benign and has been referred to as the “mouse that roared”, stent thrombosis is often fatal. The occurrence of late stent thrombosis spurred the development of stents with biodegradable polymers, thinner strut platforms of alternative metal alloys, newer antiproliferative agents, and regimens of prolonged dual antiplatelet therapy. Newer generations of drug eluting stents are not only much more deliverable than their stainless steel predecessors, but also newer platforms, polymers and drugs have reduced the risk of stent thrombosis and restenosis to very low levels.
One solution to the prevention of late stent thrombosis was the biodegradable stent: if there is no stent, there is no risk of thrombosis. The absence of a stent also may theoretically restore vascular reactivity of the coronary artery.4
The idea of biodegradable stents unfortunately predated the technology needed. It is only recently that a viable biodegradable scaffold for clinical use has been developed. However, this technology is in its infancy and issues of deliverability, radial strength and thrombogenicity need to be addressed.
THE FUTURE
In his Nobel lecture in 1956, Andre Cournand pointed out that the cardiac catheter was the “key in the lock” to unravelling the mysteries of the heart. The invention of cardiac catheterization undoubtedly triggered the cascade of developments which have brought us to this era of coronary intervention which would have been unimaginable even a few decades ago. If we can learn anything from the past, it may be to remember that this dizzying progress was possible only because of the genius and hard work of courageous and prescient individuals working together, guided by the scientific method.
SUGGESTED READINGS
- Dotter CT, Judkins MP. Transluminal treatment of arteriosclerotic obstruction: description of a new technic and a preliminary report of its application. Circulation. 1964;30:654–70.
- Gruentzig AR, Myler RK, Hanna ES, Turina MI. Coronary transluminal angioplasty [Abstract]. Circulation. 1977;55–5684.
- Seldinger SI. Catheter replacement of the needle in percutaneous arteriography: a new technique. Acta Radiol. 1953;39:368–76.
- Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316:701–6.
- Sones FM Jr, Shirey EK, Proudfit WL, Westcott RN. Cine-coronary arteriography [Abstract). Circulation 1959;20:773.
- Warren JV. Fifty years of invasive cardiology: Werner Forssmann (1904–1979). Am J Med. 1980;69:10–2.