As our understanding of cardiovascular and cerebrovascular system has increased it has become more prudent to simply refer to all of them as a global vascular system and their management as global vascular therapy. Recently technical advancements in the endovascular therapy of these global vascular disorders have brought together the skills of interventional cardiologists, interventional radiologists and vascular surgeons. As a result very recently a new super specialty of global endovascular interventions has come up and formal training with input from vascular surgery, interventional radiology, vascular medicine and interventional cardiology is being given at 3 centres in United States and 1 in France. A trained global vascular interventionist has sound knowledge of the pathophysiology and natural history of these multi vascular disorders. He can provide comprehensive clinical evaluation and treatment. He can have important inputs in vascular laboratory, and also help to expand research programs and provide benefits from educational programs to population at large. Cardiologists because of the nature of their training are most suited to further train and specialize as global endovascular specialists. They have the basic coronary interventional skills, are experienced in the management of complications and have access to the catheterization laboratory. They also have ample experience in providing evidence-based medicine and control their own referrals (hence are not dependent on outside referrals). 

In the following paragraphs, we would be discussing about the advent and advancements of interventional techniques for coronary artery disease and subsequently the application of the same techniques in other vascular beds. Quite often the same patient has multiple vascular pathologies and generally all of them are treated in the same sitting by similar endovascular techniques (global revascularization strategies). 

Interventions For Coronary Artery Disease 

The pathology of atherosclerotic plaque has been known since last 30 years but the real breakthrough in the treatment occurred when Andreas Gruentzig did the first coronary angioplasty on September 16, 1977. Gruentzig inspired by the Dotter's (interventional Radiologist) technique³ for peripheral vascular disease and by Porstmann's peripheral latex balloon, further developed noncompliant low profile angioplasty balloons. This marked the beginning of the era of endovascular interventions. 

Initial angioplasty balloon catheters were over the wire and had poor steer ability and larger profile. In the 80's further refinements lead to the development of low profile monorail balloons and soft tipped guiding catheters and steerable guide wires. All these improved the immediate success of angioplasty from 83 to 93 percent. With the technical advancements in procedure, expertise and hardware, the indications broadened and soon multivessel angioplasty come in vogue. In the NHLBI PTCA registry survival rates were 79 and 78 percent for angioplasty of one and two vessels respectively. However, the restenosis rates were around 35-40 percent and rate of acute or subacute occlusion was about 6-17 percent⁴. 

Soon this technique of balloon angioplasty was extended to other arterial trees with variable success. However, two important issues viz - subacute closure and restenosis remained to be tackled. In 80's and early 90's research and technical advancements were made in these spheres. 

Various debulking devices viz DCA, Rotablator and TEC were developed. Although a lot of hype was created initially after large-scale trials they were found not to have significant benefits in reducing restenosis. However each of them do have some niche application in coronary and vascular interventions. Directional atherectomy (DCA) which was introduced by John Simpson, is presently preferred for eccentric, ostial and bifurcation lesions, while Rotablator, a device developed by David Auth is good for debulking long, calcified and fibrotic lesions. This consists of a diamond-studded burr that spins at a rate of 150,000 to 200,000 rpm and selectively pulverizes non elastic tissue to particles <3 microns in diameter. However studies like Excimer Laser, Rotablator and Angioplasty Comparison (ERBAC) trial8 and comparison of Balloon Angioplasty versus Rotational Atherectomy (COBRA)9 have not shown any better long-term outcome in preventing restenosis. Lasers can be delivered by guide wire, balloon catheter (developed by Spears) or by fluorescence-ablation technique. Although it has not shown to have any advantage in reducing restenosis, it has a niche application in improving immediate success in aorto-ostial lesions, un dilatable lesions, calcific and long lesions, SVG grafts disease, in-stent restenosis and total occlusions. 

Newer thrombectomy devices like - Posses AngioJet and Acolysis and lately Rescue and X-Sizer devices have helped in a great way in removing recent thrombus from vessels and bypass graft. Intra Vascular Ultrasound, Angioscopy and Doppler flow wire greatly facilitate catheter interventions in both coronary and other vascular trees. 

Jacques Puel at Toulourse did the first human coronary stent implantation in France in March 1986. Soon the balloon expendable stent design was introduced, the prototype being the Palmaz-Schatz stent. Present indications of stenting are a bail out procedure for acute vessel closure after PTCA, to improve the suboptimal result of balloon angioplasty and elective/de novo stenting for reducing restenosis. 

Bene stent and stress studies have emphasized the benefits of stenting over balloon angioplasty in reducing restenosis from 32 to 22 percent and 42 to 32 percent respectively in arteries. Today intracoronary stenting is carried out in majority of the angioplasty procedures. At Escorts Heart Institute And Research Centre, New Delhi where we perform close to 1900 angioplasties a year, stents are placed in about 75 percent of the cases. Besides reducing the restenosis rate from 40 percent to less than 20 percent, stents have almost avoided the need of standby coronary artery bypass surgery. Different types of stents are available for different lesion characteristics. Generally, they fall into the following categories - slotted tube stents, second-generation tubular stents, modular zigzag/hybrid stents, coil stents, self-expanding stents and biodegradable (temporary) stents. Their choice depends on the vessel size and characteristics, lesion length and position, calcification and side branch accessibility. Although stents have reduced the restenosis rates they still have not fully solved the problem of restenosis that still occurs in about 20 percent of cases. 

Even though we have different techniques like Rotational Atherectomy, Laser, Re stenting after debulking, today in stent restenosis is the greatest challenge to an Interventionist. The newer developments in preventing restenosis are drugs, endovascular radiation (brachy therapy) or gene therapy. Trapidis (Triazolopyrimidine); a platelet derived growth factor receptor blocker has shown to reduce the restenosis rate by 15.5 percent (compared to aspirin alone) (p<0.01)⁷. Probucol, an antioxidant when started one month in advance also was found to reduce restenosis in PART study (p<0.001)⁸. Endovascular radiation and brachy therapy showed very promising results in IRIS, SCRIPPS, WRIST trials. 

The future direction in preventing acute thrombosis after angioplasty and preventing restenosis and in an alternative way of revascularization by angiogenesis is directed towards Gene Therapy. Future endeavours in the gene therapy will be on stents transected with endothelial cell lining to prevent thrombosis and restenosis; and with gene encoding angiogenesis factor for promoting developments of collaterals. Antisense inhibition of genes encoding the heavy chain of non-muscle myosin also appears to be promising. 

Endovascular Interventions In Peripheral Vasculature 

Along with the advancements in coronary interventions, similar technological and therapeutic advancement have occurred in the domain of vascular interventions. Diagnostic angioplasty is complemented and in same cases even supplemented by digital subtraction techniques, duplex sonography, intravascular ultrasound and magnetic resonance imaging. Balloon angioplasty, stents, lasers, rotational and directional atherectomy, posses, axolysis, X sizer, Rescue, Hydrolyser, thrombectomy, intravascular brachy therapy and gene therapy have similarly been applied in different vascular beds. Moreover complex vasculopathies like aortic and covered endovascular stent grafts now successfully treat vascular aneurysm and aortic dissections percutaneously. Carotid artery stenosis is now routinely treated by percutaneous endovascular technique of stent-supported angioplasty with or without cerebral protection. Renal artery and mesenteric artery stenosis no longer requires a complex surgical bypass procedures and can easily be treated by stent supported angioplasty. 

Over the last 5 years most of the vascular pathologies are being treated effectively by endovascular techniques. The morbidity and mortality with these techniques is much lower than the surgical procedures. As a result many vascular surgeons are forced to learn and practice these procedures. 

In the ensuing paragraphs we would be briefly discussing the status of some of the vascular interventions and also share our experience at the Escorts Heart Institute. 

The Percutaneous Management of Renovascular Disease 

Recognition, Interventional Strategies and Future Approaches
Renal artery stenosis is currently being diagnosed more frequently because of the improved ability of ultrasonography and tomographic-densitometric techniques to recognize it and also because of a growing practice among the cardiologists to do renal angiography in patients undergoing coronary angiography. It usually presents with renovascular hypertension, (which is the most common cause of secondary hypertension) in 0.5 to 5 percent cases; renal insufficiency (present in 10 to 15% of cases); recurrent attacks of acute pulmonary edema (which is usually sudden), and deterioration of renal functions after initiation of ACE inhibitor therapy. 

There are three main etiologies of renal artery stenosis; atherosclerosis in 80 percent of the cases and fibromuscular dysplasia and Takayashu Arteritis in remaining 20 percent of the cases. The diagnosis of renal artery stenosis can be made of Colour Doppler ultrasonography, multiplane abdominal aortograms (AP, LAO 30°, and RAO 30° views), magnetic resonance imaging, computed tomography or angiography. 

The risk of progression of renal stenosis to total occlusion is high in lesions with >60% stenosis and treatment is warranted in any patient with stenosis >75%. 

The first aspect of medical treatment of this condition is to reduce systemic blood pressure. However, a lower blood pressure also lowers renal perfusion pressure and eventually this may actually worsen the renal failure. Surgical treatment has been shown to be superior to medical therapy but is associated with a mortality rate of 2 to 7 percent (mean 5.6%) and an elevated risk of deterioration of renal functions. Renal angioplasty (PTA) and stenting is currently the treatment of choice. Patients with fibromuscular dysplasia may benefit from balloon dilatation alone, with excellent results. Less favorable results are obtained in ostial atherosclerotic lesions, where stenting is warranted due to a higher incidence of recoil, disease progression and restenosis. 

The femoral approach is used in 99 percent of cases, with a 6- to 8-F. Renal guiding catheter placed directly in front of the ostium of the renal artery, enabling the passage of the guidewire. Balloon angioplasty should be performed first, and in case of an unsatisfactory result, a stent can be placed. Introducing the guiding catheter across the lesion, then slowly retracting the guide catheter, leaving the stent across the lesion, should place the stent. The stent should be deployed at high pressures (12 bars), should protrude about 1 mm into aorta, and should be dilated afterward with a larger balloon. 

Michel Henry et al have performed renal stenting in a total of 237 patients with 100 percent success rate. Majority of their cases had ostial disease and presented with hypertension. Majority of the stent were the Palmaz, AVE, and NIR stents. 

There were 3 procedural complications: 1 patient (0.4%) died, 1 patient (0.4%) had a perirenal hematoma, and stent thrombosis occurred in 1 patient (0.4%). The mean follow-up period for all patients was 29 months. Restenosis was observed in 12 percent of the ostial lesions and in 10.5 percent of the non-ostial lesions. The restenosis rate was 17.3 percent for arteries <5 mm in diameter and 10.0 percent in arteries >6 mm in diameter. Treatment of restenosis is redo renal angioplasty, which is associated with a 12 percent restenosis rate. In their series hypertension was cured in 19 percent, improved in 60 percent, and remained unchanged in 21 percent. The mean systolic blood pressure reduced from 183+/-25 mmHg before stenting to 142+/-17 mmHg after stenting. Renal functions improved in 30 percent, remained unchanged in 66 percent and deteriorated in 4 percent, which is in concordance with the current literature. The experience in Escorts Heart Institute & Research Centre is given in Table 1.

Renal functions can deteriorate after renal angioplasty in up to 22 percent of cases because of atheroemboli during the procedure, contrast material, lesion recurrence, or lesion progression. The embolic phenomena can be avoided by using distal protection devices such as the PrecuSurge device. This device was successfully used in 16 patients, non of whom had deterioration in renal function and three of whom in fact showed improvement. 

Endoluminal Stent Grafts of Exclusion of Abdominal Aortic Aneurysms and Dissection; Overview of Devices and Clinical Experiences 

The US Food and Drug Administration have recently approved some devices for the exclusion of aortic aneurysms. The diagnosis of abdominal aortic aneurysm (AAA) has been occurring with increasing frequency in the last two decades, probably because of an increase in utilization of modern imaging techniques. During the last 20 years, extensive research has been done in the field of stent grafts for the percutaneous treatment of this potentially catastrophic disease. 

Currently there are two devices on the verge of receiving FDA approval viz the AneuRx (Medtronic), made of Dacron with a metal exoskeleton; and the Ancure (Guidant), also covered with Dacron. These two devices are comparable and need longer follow-up data to assess their safety and application. Other devices that are being released include the Zenith endovascular graft (Cook); the Corvita Endovascular Graft (Corvita Corporation). The Gore Hemobahn PTFE covered graft, the Powerlink graft and the Talent device. 

Occlusion time is significantly less with the percutaneous approach than in surgical controls. Blood loss is also significantly less, about 433 mL in the percutaneous patients compared with 1500mL in the surgical group. Length of stay in ICU was 20.6 hours and total hospitalization time was 3.4+/-2.7 days, versus 9.4+/-0.8 days in the surgical arm. The Achilles heel of this procedure is endo leak at the edges of the device. Other complications include atheroembolism, limb thrombosis, hypogastric artery occlusion, colonic ischemia, and reoperation. 

Only 40 percent of the patients with aortic aneurysms are amenable to percutaneous repair, and hybrid procedures are being developed whereby a graft is placed in the aorta and communicates to one of the iliac arteries. The other iliac artery is occluded with an occluder or coil and a femoral-femoral bypass is done surgically in order to provide blood flow to the contralateral side. Endoleaks, Reintervention, Device migration, Collateralisation through Lumbar and accessory arteries, Customization of the device and large profile of the device are the present challenges in endovascular treatment of Abdominal Aortic Aneurysm. 

Stent supported carotid angioplasty 

Significant Internal Carotid artery stenosis is responsible for more than 60 percent of the strokes and is the third major cause of death. Stent supported carotid angioplasty has the potential to prevent strokes in thousand of patients and offers a number of potential advantages over conventional surgical revascularization by carotid stenting. Results of the pooled data of the global experience of carotid stenting on more than 3000 cases indicate that carotid stenting is safe and effective in reducing the incidence of stroke. The risk of cerebral embolism is reduced to less than 1 percent by the use of various techniques of cerebral protection like the Theron & Henry-Amor-Rufenach-Fried techniques. PercuSurge Guard wire system and the Angioguard Filter device. Stent placement significantly reduces the chances of acute closure, vessel recoil and restenosis. At the Escorts Heart Institute we have performed 37 carotid stenting procedures and we were one of the first few centres in the world to use PercuSurge cerebral protection during carotid stenting. Our results are shown in Table 2. 

Stenting for coarctation of aorta in adults 

Coarctation of the aorta is also one of the treatable causes of hypertension. It is also associated with high risk of cerebral hemorrhage and sudden death. Both angioplasty and surgery are viable options in childhood but until recently stenting was not carried out in adult patients of coarctation. Recent data suggests that stenting can be safely and effectively performed in these patients. However the overall world experience is very limited. We have treated 16 patients of adult coarctation and our experience is shown in Table 3. 
 
 

Conclusion

As multiple vasculopathies often coexist in a patient, a global approach of endovascular revascularization is warranted, with a view to provide complete and lasting relief at low risk and morbidity. This trend of global revascularization is becoming more and more popular and cost effective and is being adapted by leading centres all over the world. We have adapted this strategy in the last one-year and of the 1900 coronary interventions performed annually at our centre, as a part of global revascularization strategy about 10% of the patients also have endovascular interventions for carotid, renal, vertebral, subclavian, aorta-iliac or limb vessels. Fig.1 depicts one of our cases of unstable angina where coronary stenting was done along with carotid, left renal stenting, as the patient was also having recurrent TIAs and uncontrolled hypertension.
 
 

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