Where Cardiac Surgery and Interventional Cardiology Merge ...
The Heart Surgery Forum #2001-4325 Online address: www.hsforum.com/vol4/issue4/2001-4325.html4 (4):290–296, 2001Where Cardiac Surgery and Interventional Cardiology Merge:The Future of Catheter-based Interventions for CardiovascularDisease(#2001-4325)Stephen N. Oesterle, MDAssociate Professor of Medicine, Harvard Medical School; Director of Invasive Cardiology Services, Dr. OesterleMassachusetts General Hospital, Boston, MAINTRODUCTION B AC KG R O U N D Although angioplasty and coronary stenting are now used The success of catheter-based interventions for cardiovas-for more than 800,000 patients in the United States each cular disease has been demonstrated foryear, a wide array of patients with coronary disease stillrequire surgical revascularization. Surgery remains the only • Discrete stenoses in native coronary artery vessels ofoption for many patients with heart failure and valvular dis- greater than 2.5 mm sizeease. New technology, with an emphasis on bioengineering, • Discrete stenoses in vein grafts, particularly at anasto-may expand catheter-based interventions for hundreds of motic sitesthousands of patients. Cardiologists and cardiac surgeons • Angioplasty for acute MIhave an unusual opportunity to join forces and develop a newgeneration of endovascular cardiovascular specialists. Although restenosis has hampered the durability of angio- In the first 25 years of catheter-based cardiac interven- plasty, the routine use of intracoronary stents has substantial-tions, endovascular technology has swiftly evolved from the ly reduced the need for repeat procedures. The advent oforiginal, fixed wire, wide-profile, non-steerable Gruentzig brachytherapy and drug eluting stents in 2001 leaves mostDG catheter to an expansive selection of intracoronary cardiologists with a conviction that restenosis can be eitherdevices that include: successfully treated or primarily prevented. Randomized trials of coronary surgery versus angioplasty • Flexible, low-proﬁle, compliant and non-compliant coro- where diabetics are excluded have not demonstrated superiori- nary dilatation catheters ty for either therapy when mortality and myocardial infarction • Intra-coronary steerable guide wires are used as outcomes, but patients having aorto-coronary • Balloon expandable and self-expanding stents bypass experience fewer symptoms in follow-up [King 1994, • Cut and retrieval catheters (Directional Coronary Pocock 2001, Serruys 2001]. The introduction of stent coat- Atherectomy—DCA™) ings [Sousa 2001] may favorably slant outcomes towards • High speed rotational atherectomy devices (Rotablator™) angioplasty in the coming years. The ability to manipulate • Thrombus extraction devices (POSSIS AngioJet™) vascular biology has made great advances in recent years, and • Excimer and Ho:YAG laser catheters bioengineering is likely to be a common component of • Cutting balloons endovascular device development in the next decade. • Gamma- and beta-emitting brachytherapy catheters Over the last 15 years, catheter-based technology has been • Percutaneous transmyocardial laser revascularization applied in a myriad of diverse diagnostic and therapeutic appli- devices (PMR) cations with substantial success, replacing surgical approaches • Distal protection/emboli containment devices for many patients. These percutaneous successes include: This expanding collection of intra-coronary devices has pro- • Mitral valvuloplasty or balloon valvotomy for mitralpelled the growth of catheter-based revascularization procedures stenosisfrom less than 1,000 cases in 1980 to the present level of more • Atrial septal defect and patent foramen ovale closuresthan 850,000 in the U.S. and nearly two million worldwide. • Pericardial windows for effusions • Alcohol ablation for obstructive cardiomyopathies due toPresented at the Minimally Invasive Cardiac Surgery (MICS) Symposium, asymmetric septal hypertrophyKey West, Florida, May 27, 2001. • Aortic aneurysm repair • Aortic dissection repairAddress correspondence and reprint requests to: Stephen N. Oesterle, MD, • Carotid angioplasty and stentingMassachusetts General Hospital, Bulfinch 105, 55 Fruit Street, Boston, • Renal angioplasty and stentingMA 02114, Email: email@example.com • Patent ductus arteriosus closure 290
The Heart Surgery Forum #2001-4325that allogenic fetal cardiomyocytes could be engrafted intopartially infarcted myocardium and achieve an improvement inejection fraction and cardiac output [Scorsin 1997]. Theseﬁndings were compared to ﬁndings for control rats that hadonly culture medium injected into their infarct zones. Li et al., at the University of Toronto, reported that trans-plantation of cultured fetal cardiomyocytes into myocardialscar tissue of rats could improve heart function while limitingscar expansion or aneurysm formation [Li 1996]. Theseinvestigators used a technique of cryo-injury to effect homo-geneous myocardial injury in the recipient rats. Allogenicfetal cardiomyocytes were injected into scar tissue four weeksafter injury, and the animals were sacriﬁced at eight weeks.Histological studies were performed to quantify the extent ofscar formation and the presence of transplanted cells. Func-tion in both transplant and control hearts was assessed using aLangendorff preparation. Gojo and colleagues extended the work of Menasché andWeisel by demonstrating that fetal cardiomyocytes can begenetically marked or modiﬁed before being grafted to theheart [Gojo 1997]. They used a replication-defective recom-binant adenovirus that carried the -galactosidase reportergene, and delivered it to cultured murine fetal cardiomy-ocytes. These cells were then transplanted to the myocardi- Figure 1.um of syngeneic adult recipient mice. Gene expression wasmanifest from 7 days to 12 weeks after cell transfer. Thisstudy also highlighted the potential for cell transfer as a vehi-cle for therapeutic gene delivery. Additionally, survival and ferred the cells using direct injection techniques, the poten-proliferation of cardiomyocytes after transplantation may rely tial for cell transfer by catheter-based technology is vigorous-on the presence of adjunct growth factors or oncogenes that ly being investigated at several institutions, including Massa-could be introduced in the cell line prior to transplantation. chusetts General Hospital. Extensive animal experimentation Nearly all investigations of cardiomyocyte and myocardial will be required before broad-based application is undertak-tissue transfer have used rodents. The experiments employed en, but a 10-year window for this type of therapy is reason-an open-chest procedure because engraftment requires direct able. Figure 1 ( ) outlines the fundamental steps that willapplication, in most cases by injection. However, percuta- require validation prior to human application.neous catheter-based techniques have been developed forstimulating angiogenesis, either by gene therapy or transmy- Degenerative Vein Graft Diseaseocardial laser. These minimally invasive therapies have been Although distal emboli containment devices have reducedsuccessfully applied in a variety of animal models and are now the complications of vein graft intervention [Oesterle 1999,being investigated in human trials with variable success [Kim Webb 1999], it is widely acknowledged that angioplasty and1997, Henry 1998, Knopf 1998, Oesterle 2000]. It is likely stenting of badly degenerated vein grafts suffer from highthat the same catheter systems used for gene transfer and per- complication rates [Mathew 2000]. Furthermore, degenera-cutaneous transmyocardial laser revascularization (PMR) tive vein graft disease is rarely discrete but tends to be dif-could be modiﬁed and used as delivery systems for myocar- fusely spread throughout the vein graft. Spot-stenting ofdial cell and tissue transplantation. short segments usually offers only short-term beneﬁt; hence, The development of a percutaneous catheter system for degenerative vein graft disease is a frequent reason for surgi-cardiomyocyte delivery would be viewed as a major advance. cal referral. Redo surgeries also have a higher incidence ofThis less invasive approach should diminish morbidity while complications and are frequently compromised by inadequateexpanding the application of these therapies to a broad spec- availability of conduits. Several catheter-based approaches aretrum of patients. The development of appropriate devices is currently being tested, including long stent grafts usinginextricably linked to choice of cells, biodegradable matrices, ePTFE that could reline the vein graft while entrappinggrowth factors, and means of quantifying success of imple- debris. Concern over long-term biocompatibility of the syn-mentation, differentiation, and functional restoration. thetic covering has led to several tissue engineering projects Several companies are already pursuing cellular cardiomy- focused on the development of small vessel conduits that areoplasty, most notably Bio-Heart™ (Weston, FL). The ﬁrst tissue-engineered using the patient’s own cells and thenuse of cell transfer for heart failure in a human was reported deployed as replacement conduits [L’Heureux 1998, Niklasonin late 2000 [Menasché 2001], and it is clear that more cases 1999]. Delivery of these tissue-engineered small vessel stentwill soon follow. Although the surgeons in that case trans- grafts seems to be feasible. 292
The Heart Surgery Forum #2001-4325 replacement. The primary cause of failure for aortic valvulo- plasty has been recoil of the diseased valve. The possibility of mechanically holding the valve open with a catheter- deployed stent graft has been envisioned and explored in prototypes. The “aortic valve stent” would incorporate a pli- able tissue or synthetic valve that would be supported by the stent structure. Clearly, this is an approach that may only apply to a select group of patients, but it is not unreasonable to anticipate such catheter-based treatment for aortic valve stenosis by the year 2010. A similar concept may have a more obvious application to patients with aortic valve insufﬁciency. A catheter-deployed stent graft with composite valve could be placed across the leak- ing valve to restore diastolic competence. The practicality of this application will require extensive pre-clinical investigation. Mitral Insufﬁciency Figure 4. Inﬁltrator Catheter Although mitral stenosis has been extensively treated using catheter-based strategies, the challenges of correcting mitral insufﬁciency with percutaneous techniques are formi- dable. A composite valve stent graft is conceivable; butstrategies for passivating plaque, rendering it less vulnerable secure placement in the endocardial cushion would not beto rupture. easy. Redundant leaflets potentially could be plicated with It is probable that the primary preventive beneﬁts of the catheter technology but it is unlikely that chordae and papil-statin class of lipid-lowering drugs are related to plaque passi- lary muscle ruptures will disappear from the surgeon’svation. In contrast to this systemic approach, the most domain in the near future.promising catheter strategies include modulation of local vas-cular biology by arterial wall gene transfer. The Massachu- Atrial Fibrillationsetts General Hospital and its partner Harvard hospitals have Atrial fibrillation (AF) will ultimately afflict up to one-recently initiated a trial of local gene delivery using an inﬁl- third of the adult population. However, its treatment hastrating catheter (Inﬁltrator™, see Figure 4, ) to distribute a been limited to pharmacological therapy of dubious beneﬁt.gene encoded for inducible nitric oxide synthetase (iNOS) to Moreover, the surgical Maze procedure that has been popu-the vessel wall. Nitric oxide (NO) is secreted by healthy larized by Cox et al. [Cox 1995] requires a lengthy operationendothelium and is recognized to be a potent endogenous time while on cardiopulmonary bypass. Attempts to duplicateinhibitor of vascular lesion formation, inhibiting platelet the surgical Maze procedure by creating linear lines of abla-adhesion, leukocyte activation, and vascular smooth muscle tion with radio frequency (RF) catheters has met with limitedproliferation and migration. The Harvard-initiated success. Recently, cardiologists in France have demonstratedREGENT trial is focused on developing NO donors NO to that isolation of the triggers of AF in and around the pul-inhibit restenosis. It is envisioned that a similar transfection monary veins may prove to be highly effective in abortingstrategy could be used to treat longer segments of arterial paroxysmal AF [Jais 1997, Haissaguerre 1998, Kuck 1998].wall with diffuse atherosclerosis, rendering the vessel less sus- Several companies are now pursuing RF and cryoablationceptible to acute thrombotic occlusion. strategies. The use of MR guidance offers the hope that these Investigators at Stanford University have begun a multi- procedures can be completed expeditiously and effectively.center trial of photo-activated local drug therapy for prevent-ing restenosis [Rockson 2000]. Pharmacylics, Inc. has devel- C O N C LU S I O Noped a porphyrin derivative, Antrin, which is selectivelyabsorbed by plaque. After systemic administration of the It is clear that many of these novel strategies for catheter-drug, a ﬁber optic device is transported by a catheter to the based intervention are still years in the making. Cardiac sur-areas of treatment in the coronary artery and red light is geons will have plenty of work for the foreseeable future.locally delivered, activating the drug and initiating a local This is not instigation for competition or confrontation but,release of oxygen radicals that are believed to inhibit prolifer- rather, an unusual opportunity for collaboration. Cardiolo-ation. A variant of this strategy may have the potential to pas- gists and cardiovascular surgeons alike have a common objec-sivate diffuse areas of atherosclerosis. tive in the treatment of cardiovascular disease. The parallel pursuits of percutaneous therapies and minimally invasiveAortic Valve Stenosis/Aortic Valve Insufﬁciency surgery merge with the common goal of better care for Although many patients with mitral stenosis have been patients. The next generation of cardiologists and heart sur-successfully treated with catheter-based balloon valvotomy geons will likely share many similar training experiences and[Palacios 1998], valvuloplasty for aortic stenosis has been less increasingly sophisticated technology: a new endovascular-effective and largely abandoned except as a bridge to valve cardiovascular specialist will likely emerge in the process. 294
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