Drug-Eluting Stents and Cooled Ablation Catheters
A stent is a metal tube or “scaffold” that is inserted in a coronary artery to prevent abrupt closure of an artery after angioplasty. It was first conceptualized to complement angioplasty balloons since coronary artery walls sometimes weaken after dilatation. Stents were designed to prevent the collapse of artery walls after removing the balloon used to dilate the artery. Before stents were invented, 30% of all coronary arteries close up after balloon angioplasty which is corrected by an emergency bypass surgery. With the successful use of stents in 1986 by Jacques Puel and Ulrich Sigwart, this redundant procedure was avoided. While stents provided temporary solution for abrupt artery closure, restenosis persisted nonetheless. Restenosis or reblocking is the growth of smooth muscle cells over the metal tube fibers of a stent and is considered as a reaction to angioplasty like a scar forming over an injury. Drug-eluting stents were developed in 2002 as a solution to the persistence of restenosis in patients who underwent angioplasty. Recent advances in medicine enabled physicians to deliver therapy to target areas through the human body “highway” called the circulatory system which signified a general trend towards using less intrusive pharmacological solution in the place of the commonly used mechanical devices. After the discovery of drugs capable of disrupting biological processes that lead to restenosis, scientist looked for ways to put these drugs in stents. Stents were coated with anti-restenosis drugs which are eluted in the surrounding cells after surgery. At times, these drugs are placed inside thin fibers to facilitate the timing of the release (Angioplasty.org).
Currently only two drug-eluting stents have the approval of the Food and Drug Administration of the United States. The Cordis CYPHER™ is a sirolimus-eluting stent, approved in April 2003, and the Boston Scientific TAXUS™ is a paclitaxel-eluting stent system, approved in March 2004. In Europe, Medtronic’s Endeavor stent which delivers a drug called ABT-578 was approved in April 2005. Drug-eluting stents were found to be remarkably successful in lowering the incidence of restenosis to single digits which previously occurred in 20-30% of angioplasty cases. Furthermore, drug-eluting stents like TAXUS and CYPHER were also found to reduce reintervention in patients suffering from diabetes, a group known to be highly susceptible to restenosis. On the other hand, drug-eluting stents necessitate extended intake of expensive anti-clotting medications, which can have side effects (FDA).
In October 2003, the Food and Drug Administration warned of the risks of developing sub-acute thrombosis or blood clotting associated with the use of CYPHER stent, resulting in some deaths although additional research indicated that the incidence of blood clotting was lower or just equal to that associated with bare metal stents. However, it was also discovered that drug-eluting stents can cause a condition called “late stent thrombosis.” This condition is characterized by blood-clotting inside the stent several years after the insertion of the device. It is fatal in more than one third of cases but has been noted to be rare in Taxus and Cypher stents. According to the FDA, a small but relevant rise in the rate of death and heart attack in patients was observed after 18 months to 3 years of drug-eluted stent implantation (Feder).
There has been ongoing discontent in the efficiency and manner of use of drug-eluting stents in the United States. There are suggestions to go back to using bare metal stents for particular cases and needs. A study in Germany revealed that drug eluting-stents has almost the same effect as bare metal stents on a vessel greater than 2.8mm in diameter. This is particularly important since in the United States, patients receive drug eluting stents irrespective of their vessel sizes (FDA).
Late stent thrombosis occurred in patients implanted with drug-eluting stents due to the lack of long-term research on the device. Long-term effects are naturally hard to detect and study in such cases since these are gradual and incremental changes in the affected organ which may even take 3 years before diagnosis. Moreover, there appeared to be a lack of an extensive study detailing the effects of the anti-restenosis drugs when delivered through the stent. These are fundamental research areas that may have been truncated due to the flurry of activities between competing drug-eluting stent manufacturers which was also labeled as the “Stent Wars” to release the first commercially available device to the detriment of the paying public. Deaths due to this problem could have been prevented if only research was given enough time and importance before marketing the said products.
The impractical use of drug-eluting stents in patients with vessels greater than 2.8mm in diameter is a clear indication of inadequate product research and information dissemination. Due to the variability of patients that are obviously going to receive the drug-eluting stents, different reactions are expected. Efficiency in different vessel sizes and other patient characteristics were not considered in designing and prescribing the use of such device. Again, it takes time to determine the efficiency and appropriateness of a particular device in variable sets of patients. If the above research parameters were not considered in the development of drug-eluting stents, what more can be expected regarding allergic reactions and other side-effects?
To summarize, the occurrence of late thrombosis, related deaths and futile use of stents in patients with large vessels are all caused by a lack of extensive research. These problems could have been prevented by following the due course of scientific research. All contributing factors should have been evaluated including patient profiles and allergic reactions. In addition, both makers and physicians should have played a more responsible role of selecting patients who will clearly benefit from using drug-eluting stents.
The detection and therapy of supraventricular tachycardia (SVT) in children has been significantly aided with the use of electrophysiology researches and catheter ablation technology. SVT varies with age in children. Approximately 75% of SVT in babies and young children and 45% in adults are caused by an accessory connection. Atrioventricular node reentry tachycardia is more common in adults than in young children. Primary atrial tachycardia is found in 10-15% of the cases of SVT at all ages. The incidence of intraatrial reentry tachycardia (IART) or atrial flutter on the other hand increases with age (Zimmerman 6).
An “ablation catheter” is a catheter or a hollow, slender, flexible tube used to obliterate or ablate abnormal tissue. A heart ablation catheter includes wires placed inside the hollow of the tube. The wires are connected to an electrical system that permits a physician to visualize the movements of a heart on a monitor. Heart ablation catheters are also wired to a generator that provides energy in the form of radiofrequency or RF waves to the end of the catheter inside the heart. The RF waves produce heat that obliterates abnormal heart tissue which causes tachycardia or irregular heart beats (PR News).
The procedure of using a heart ablation catheter involves the following steps. First, the catheter is inserted into a vein adjacent to the groin called the femoral vein. The catheter is then directed through the vessel towards the heart chambers. The other end of the catheter is then wired to the electrical apparatus that permits the physician to visualize the movement of the heart on a monitor. With the aid of the monitor, the physician can position the catheter in the desired area to set the abnormal beat of the heart right. When the catheter is in position, the physician switches on the power from the generator to heat up the end of the catheter. Ablation occurs when the heat comes in contact with the tissue responsible for the irregular heart beat (Zimmerman 6).
Radiofrequency energy application through catheter ablation encounters problems due to excessive heating of the catheter tip which causes coagulum formation. It occurs in regions of the heart where blood flow is minimal and tip cooling is insufficient as observed after a Fontan operation. New ablation catheters have been recently designed to solve this problem. An example is the Chilli Cooled Ablation System which utilizes an internal fluid cooling system during activation of RF energy. The fluid circulates in the catheter which cools the tip permitting increased energy delivery without the development of coagulum. Through this technique, greater lesion depression can be obtained unlike conventional ablation techniques. This cardiovascular device was approved on August 31, 2005. Its closed-loop design eradicates the need to supplement fluid and to keep track flow rates throughout the procedure, thus lowering the probability for fluid overflow (Devicelink.com).
These new generation ablation technologies recently approved by the FDA continue to be hounded by problems such as damage beyond the myocardium resulting to injury to adjacent tissue, potentially causing adverse events and the persistence of bacterial infection in the catheter. Death of a patient in Germany on May 6, 2006 due to esophageal fistula pushed ProRhythm to recall its ProRhythm 25mm HIFU Ablation Catheter and the ProRhythm 30mm HIFU Ablation Catheter from the market. These ablation catheters where found to have focal zones with depths exceeding that of the 20mm size. The focal zone dictates the depth of the ablation lesion. This means that the mentioned HIFU catheters can cause injury beyond the myocardium and other adjacent tissues as well, leading to potentially serious effects to the patient (Sciencenews.com).
These problems are not encountered in Chilli Cooled Ablation Catheters. There are even studies extolling the cost-effectiveness of using Chilli Cooled Ablation Catheters as an alternative for treating ventricular tachycardia. This type of ablation catheter has high success rate of application but there are no definitive reports on incidence of bacterial infection commonly detected in conventional ablation catheters and believed to be the cause of the death of 23,000 patients in the United States. Myocardium injury reported in HIFU Ablation Catheters which resulted to a recall of these brands of catheters are also not reported in Chilli Catheters at the present. While these good indications boost the Chilli’s efficiency and safety, there is still no assurance that such failures and defects will not surface in the future.
Long-term research is needed to assure that similar incidents will not be encountered in cooled ablation catheters. Strict compliance to the standards according to the Food and Drug Administration can increase the probability of success of a particular device like an ablation catheter. Following the scientific methodologies for the evaluation of the safety and efficiency of cooling ablation catheter can lower risks if all possible factors are considered in the testing of the product. Factors such as patient profiles, differential system reactions of recipients, applicability and practicality should all be considered to predict possible problem areas for a cardiovascular device. Therefore, in the case of cooled ablation catheters, not only higher efficiency in destroying tissue due to the cooling properties of the device was achieved, problems regarding myocardium injury, bacterial infections and other defects were avoided through extensive research for the design and development of the product. Moreover, information dissemination and physician involvement in assessing the need and practicality of the operation could have helped in the overall efficiency of the product.
Angioplasty.org. “Drug-Eluting Stents.” 30 October 2006. 8 April 8, 2007 <http://www.ptca.org/ des.html>.
Devicelink.com. “Chilli II™ Cooled Ablation Catheter.” 8 April 2007 <www.devicelink.com>.
Fackelman, Kathleen. “Condition Critical: Is the right-heart catheter dangerous? Science News. 14 December 1996 Vol. 150 No. 24 p. 376. 8 April 2007 <http://www.sciencenews.org/ pages/ pdfs/data/1996/150-24/15024-12.pdf>.
Feder, Barnaby. “Risks of Drug-Coated Stents Divide Federal Review Panel” New York Times 8 December 2006. 8 April 2007 <http://www.nytimes.com/2006/12/08/health/08stent. html>.
Food and Drug Administration. “Electrophysiology Ablation Catheter Cardiac Ablation Generator (RF).” 8 April 2007 <http://www.fda.gov/cdrh/PDF4/p040042b.pdf>.
Food and Drug Administration. “FDA Statement on Coronary Drug-Eluting Stents.” 14 September 2006. 8 April 2007 <http://www.fda.gov/cdrh/pdf2/P020026.html>.
PR Newswire. “Stereotaxis Announces FDA Approval of Partnered 8mm Ablation Catheter.” 8 April 2007 <http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY>.
Zimmerman, Frank. “Advances in Catheter Ablation for the Treatment of Arrhythmias in Children.” Pediatric Electrophysiology. University of Chicago Medical Center. 8 April 2007.