Percutaneous transluminal coronary angioplasty (PTCA) was first described by Andreas Gruentzig in 1976, when he reported the successful application of the new technique in canine coronary experiments. Dr. Gruentzig designed and assembled balloon dilation catheters in his own kitchen. He performed the first coronary angioplasty in a conscious human patient in September 1977 in Zurich, Switzerland. The dilation catheter consisted of a balloon attached to a long shaft and a short wire attached to its tip. Soon after, balloon catheters were designed with a central guidewire lumen. Since the introduction of balloon angioplasty, major advancements have taken place in the field of percutaneous coronary interventions, but the majority of cases still require dilatation of the lesion with a balloon catheter even when a stent or other devices are used. In many instances, lesion preparation is crucial prior to stent deployment.

Coronary Balloon Material

Challenging lesions require a balloon with optimal performance in terms of:

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  Catheter pushability in order to transmit the force applied by the interventionalist’s hand to the distal end of the catheter, especially when guiding support is not adequate;

  
  
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  Catheter trackability over the guidewire through tortuous segments; and

  
  
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  Lesion crossability, especially in cases of calcified lesions with severe stenosis.

Therefore, despite the fact that standalone “plain old balloon angioplasty” (POBA) is mostly a thing of the past, there is an ongoing effort to manufacture more user-friendly balloon catheters that can address preparation of complex lesions to complement newer percutaneous technology. Several balloon catheter characteristics are considered in the manufacturing process.

Over-the-Wire and Rapid Exchange Systems

In an over-the-wire (OTW) system, the balloon catheter has a central lumen permitting free guidewire movement. This system is helpful when crossing difficult anatomy such as a chronic total occlusion, where balloon support is helpful and wire exchange is anticipated. On the other hand, the rapid exchange (RX) balloon catheter system is preferred by most single operators. The lesion is crossed with a standard-length guidewire. The wire is then fixed with one hand while the balloon catheter is advanced with the other. The wire exits a few centimeters from the distal end of the balloon catheter rather than its proximal end. The main disadvantage is that the wire cannot be pulled out for reshaping and cannot be exchanged for another wire without taking the entire system out. Balloon support may not be as good as with a full-length OTW system, since the balloon catheter is tracking over a relatively short distance of the wire. Therefore, the shaft design plays a fundamental role in balancing several characteristics for optimal catheter performance. These include pushability of the proximal shaft and flexibility as well as trackability of the distal shaft. Other important characteristics are lubricity, torque transmission and kink resistance. Factors that improve crossability include a smooth transition from the distal shaft to the balloon and a low profile of the very distal catheter tip.

Balloon Material

The first balloon catheter used by Andreas Gruentzig was made of polyvinylchloride, a low compliance plastic polymer. Most balloon catheters available on the market today are derived from 1 of 4 families of balloon materials: polyolefin, nylon, polyester, and urethane. It is the type of balloon material derived from these categories of plastic that largely determine the characteristics that differentiate dilatation catheters. Noncompliant balloons are usually made of polyethylene terephthalate, a widely used resin in plastic soda bottles. The strength of the material allows the balloon to be used in calcified lesions at high pressures. The maximum recommended pressure is provided by the manufacturer. Relatively high-pressure balloons can be made out of nylon, although the strength of the material is somewhat less than that of polyethylene terephthalate; therefore, nylon balloons are characterized as semicompliant. Compliant balloons are made out of polyethylene or polyolefin copolymer, allowing for lower profile, more flexibility, and a lower tendency to “wing” after deflation. This allows for more effective rewrapping of semicompliant as compared to noncompliant balloons. The disadvantage of a compliant balloon is the reduced ability to dilate hard lesions with a greater tendency to “dog-bone” since the distending force may stretch the balloon longitudinally rather than concentrating the force circumferentially on the atherosclerotic plaque. Manufacturers also use hydrophilic surface coating for better crossability, however this is balanced against creating slippage during balloon inflation especially in hard lesions.

Each balloon comes with a compliance chart that correlates the balloon diameter to the inflation pressure. The nominal pressure is the atmospheric pressure at which the balloon reaches its nominal preset diameter as tested in vitro. Because of their stretching properties, compliant balloons attain a larger diameter with higher pressures compared to non-compliant balloons. The rated burst pressure is the maximum allowed pressure below which there is a high confidence that 99.9% of balloons will not rupture. Balloon rupture can be caused by specific lesion morphology^{1, 2} such as the sharp edge of a calcium spicule. Most commonly, however, a rupture takes place at pressures exceeding the burst pressure in the form of a pinhole or a longitudinal tear in the balloon. Balloon rupture can cause dye staining which is usually benign or can cause an intramural hematoma and, very rarely, vessel perforation.

Cutting Balloons

The cutting balloon was first described by Barath in 1991³. It consists of a balloon catheter with 3 or 4 microtomes—sharp metal blades mounted longitudinally on the surface of the balloon. The balloon is inflated slowly, allowing the blades to “cut” into the lesion before actual balloon dilation (Fig. 28-1). It is felt that these controlled microsurgical incisions may limit overall vessel stretch and vascular injury,⁴ therefore reducing the balloon dissection rate and possibly also the elastic recoil. The balloon uses lower inflation pressure than conventional balloons and achieves a trend toward larger lumen gain with increased plaque reduction.⁵ The cutting balloon has gained popularity for angioplasty of in-stent restenosis. In these situations, it has the advantage of preventing “watermelon seeding” of the balloon and may result in better dilatation.⁶ It is not felt to reduce the rate of angiographic restenosis compared to conventional balloons.^6-8 It is important to keep in mind that the device is stiff and has a high crossing profile. Some anatomic situations, such as lesions in very tortuous segments, may be out of reach with the cutting balloon.

Scoring Balloons

The AngioSculpt Scoring Balloon Catheter (Angio-Score, Inc., Fremont, CA) consists of a minimally compliant balloon housed in 3 low-profile spirally arranged nitinol wires (Fig. 28-2). In theory, during balloon expansion, the dilating force is concentrated focally in the wires resulting in the scoring effect on the vessel lumen surface. This mechanism can result in a controlled expansion of the lumen with reduced barotrauma and lower dissection rates. As with cutting balloon angioplasty, device slippage is reduced, especially in in-stent restenosis.⁹ Optical coherence tomography (OCT) images show lumen expansion and imprints caused by the scoring elements of the nitinol wire cage (Fig. 28-3).¹⁰ The scoring balloon is lower in profile and more deliverable than the cutting balloon. It has been proposed for lesion preparation prior to stent delivery. In an observational study, predilation with the AngioSculpt balloon, compared with either direct stenting or conventional balloon predilation, resulted in better stent expansion by intravascular ultrasound (IVUS) measurements, irrespective of plaque morphology.¹¹ This technology has also been proposed in complex bifurcation lesions with dilatation of the side branch with the scoring balloon prior to implantation of a drug-eluting stent in the main vessel. In a prospective clinical trial that enrolled 93 patients,¹² this strategy was associated with a favorable procedure success rate of 91.4%. Dissections were observed in 8.2% of cases in the main branch and 6% in the side branch post scoring balloon angioplasty. Bailout stenting in the side branch was required in 10.8% of cases. At 9 months, the composite major adverse cardiac events (MACE) rate was 5.4%. A similar “simple provisional” strategy in true bifurcation lesions was tested in a pooled analysis of the Nordic Bifurcation and the British Bifurcation Coronary randomized trials.¹³ Both trials compared provisional T-stenting versus a complex strategy of bifurcating drug-eluting stents. In the simple strategy group (n = 457), stenting the main vessel was performed first, followed by provisional dilatation of the side branch with a conventional balloon, then stenting if necessary. This strategy resulted in 128 patients (28%) undergoing ballooning of the side branch, and 16 patients (3.5%) requiring a T-stent. At 9 months—the composite endpoint of all-cause death—myocardial infarction and target vessel revascularization occurred in 10.1% of the simple strategy group versus 17.3% of the complex group (P = 0.001). While most evidence supports the simple strategy approach in bifurcating lesions, it is difficult to properly evaluate the place of the scoring balloon compared to the conventional balloon in the absence of a randomized clinical trial.

Drug-coated scoring balloon catheters are discussed in Chapter 32.

The mechanism of coronary angioplasty is intriguing. In the original 1964 publication describing the transluminal treatment of arteriosclerotic peripheral artery obstructions with serial dilating catheters, Charles Dotter and Melvin Judkins speculated the following mechanism: “relatively non-traumatic remodeling and lateral displacement of the encircling atheromatous material.”¹⁴ However, soon after the inception of coronary balloon angioplasty, the theory of vessel injury gained momentum. In one of his publications, Andreas Gruentzig wrote: “the atherosclerotic material is compressed and pressed into the vessel wall, thereby partly disrupting and dissecting the intima and overstretching the media.”¹⁵ Gruentzig refers to this as “controlled injury.” The notion of plaque compression has since been largely refuted for lack of experimental evidence. Human coronary arteries studied postmortem after successful angioplasty demonstrated splitting of the atheromatous plaque at the point of least resistance.^16-19 Morphologic studies are never conclusive, primarily because atherosclerotic plaques differ in their composition. In acute coronary syndrome for example, the plaque may have already ruptured and may have varying degrees of superimposed thrombotic material. These types of plaques may respond differently to balloon angioplasty than those in stable coronary artery disease situations where fibrosis and calcifications usually prevail.²⁰ Nevertheless, the body of evidence, especially from IVUS data, supports the mechanism of lumen enlargement with balloon angioplasty to be largely the result of endothelial desquamation, plaque fissuring and arterial wall dissection, stretching of the vessel wall through the elasticity of both the media and adventitia, and axial plaque redistribution.^21-25 Recent work addressed the dissection mechanisms triggered during the early stages of angioplasty in an atherosclerotic coronary artery 2-dimensional geometric-based computational model.²⁶ The study showed that the onset of dissection damage occurs very early. Plaque detachment at the shoulder region results in an intimal flap or partial dissection of the plaque from the media, but what is interesting is the occurrence, very early on during balloon inflation, of damage within the wall of the media layer itself. This again stresses the probability of several injury mechanisms at different locations. The degree to which each of these various mechanisms play a role varies with each lesion morphology and atherosclerotic plaque composition as well as with balloon pressure and sizing.

Procedural Complications

Intimal tears and arterial wall dissections are commonly identified by IVUS following balloon angioplasty. Some form of plaque disruption is seen in 50% to 75% of cases.²² Intramural hematomas have also been described by IVUS.²⁷ These can result from a medial dissection with blood accumulating in the medial space and extending into the contiguous normal arterial wall, especially in the absence of a clear re-entry point. Coronary dissections pose a risk for acute or subacute vessel closure, one of the most dreaded complications of balloon angioplasty. In particular, intramural hematomas predict a high rate of non–Q-wave myocardial infarction, need for repeat revascularization, and sudden death. By providing scaffolding to “tack up” dissections, coronary stents have largely resolved the problem of acute vessel closure that is caused by a coronary dissection with or without intramural hematoma. However, before the stent era, PTCA resulted in a significant complication rate. In the first 1500 patients enrolled in the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry (1977-1981), major complications occurred in 9.2% of patients and were in the form of myocardial infarction, urgent revascularization, or in-hospital death.²⁸ Emergency surgery was required in 6.8%. It is interesting to note that in this very early experience, success rate was reported in only 63% of cases. Despite refinement in balloon technology, the incidence of periprocedural vessel occlusion after angioplasty remained relatively high at 6.8% through 1985 to 1986, with roughly two-thirds of the vessel occlusions occurring in the cardiac catheterization laboratory.²⁹ Acute vessel closure was associated with a high risk of major complications, including bypass surgery in 35% and mortality in 5%, which was substantially higher than the 1% mortality reported in PTCA patients without vessel closure.

Acute vessel closure with balloon angioplasty is primarily caused by severe coronary dissections.³⁰ Less common reasons include thrombus formation and coronary spasm. Acute closure occurring in a proximal location of a large vessel can result in ST-segment elevation and significant hemodynamic compromise, especially if the area of myocardium supplied by the vessel is substantial and/or collaterals are absent. If the wire is still across the lesion, redilatation with a properly sized balloon was the only thing that could be tried in the vessel before the availability of stents. In the early era of coronary angioplasty, heparin was administered generously (10,000 units at the beginning of the procedure and 5000 units every hour). Automatic coagulation timer (ACT) machines were not widely available in cardiac catheterization laboratories, and a weight-based heparin approach was not routine. Prolonged balloon inflations were the norm as long as the hemodynamic situation allowed. Intra-aortic balloon pumps were frequently used. A fully staffed operating room was kept on standby and the surgery and anesthesia teams were alerted as soon as a major complication took place.³¹ Even now, recrossing a lesion during acute vessel closure when the wire is no longer across the lesion remains potentially very challenging, as the wire may inadvertently advance through the false lumen, resulting in propagation of the dissection. In the very early period of balloon angioplasty, the rate of emergency bypass surgery was high, either as a result of procedure failure or due to acute vessel closure.

In 1988, Stack RS et al described the coronary perfusion balloon that allows passive myocardial perfusion during balloon inflation.³² Perfusion holes are distributed on the catheter shaft proximal to the balloon. Blood enters through the holes and exits distally from the wire lumen, perfusing the distal artery bed beyond the inflated balloon. Early results were encouraging in terms of improving the hemodynamic condition of the patient or reducing the angiographic severity of the dissection.^33,34

The laser balloon was another modality that was proposed for sealing severe coronary dissections and reversing abrupt closure.³⁵ It works by heating tissues with an Nd:YAG laser during balloon inflation and welding plaque-arterial wall separation.^36-38 However, restenosis following successful treatment with the laser balloon was relatively high. The experimental device was discontinued before entering the clinical market.

Significant improvement in clinical outcome and reduction in major complications were not seen until coronary stents were introduced to clinical practice. This was shown when 1559 consecutive patients in the 1997–1998 Dynamic Registry who were having percutaneous interventions including use of stents in de novo lesions were compared to 2431 patients in the 1985–1986 National Heart, Lung, and Blood Institute (NHLBI) Registry of patients undergoing PTCA in the prestent era.³⁹ Patients in the Dynamic Registry were on average older, clinical presentation was more unstable and lesions were more complex than patients in the NHLBI PTCA registry. Coronary stents were used in 70.5% of patients in this early era. Procedural success was higher in the Dynamic Registry (92.0% vs 81.8%; P < 0.001) and the rate of major in-hospital complications was lower (4.9% vs 7.9%; P = 0.001) compared to the NHLBI registry. Similarly, the 1-year rate for coronary artery bypass grafting (CABG) was nearly cut in half in the early stent era (6.9% vs 12.6%; P = < 0.001) compared to the prestent era.

In contemporary percutaneous coronary interventions, the in-hospital major cardiac event rate is very low compared to that of the balloon angioplasty era.

Predictors of Procedural Complications with Balloon Angioplasty

Several angiographic and clinical predictors have been found to be associated with balloon angioplasty procedural complications. In 1988, new American College of Cardiology/American Heart Association guidelines on PTCA emerged.⁴⁰ The guidelines described lesion morphologies that can affect both the success and complication rates with PTCA. These angiographic characteristics were grouped into three types: A, B, and C reflecting an anticipated low, moderate, or high procedural risk (Table 28-1). Ellis et al assessed the procedural outcome in patients with multivessel disease undergoing PTCA.⁴¹ Three hundred and fifty consecutive patients (1100 stenoses) from 4 clinical sites were analyzed. A modified ACC/AHA score was applied whereby type B lesions were sub-grouped into type B₁ (having 1 type B characteristic) and type B₂ (having ≥2 type B characteristics). The distribution was as follows: type A, 28.7%; type B₁, 34.1%; type B₂, 26.6%; and type C, 10.6%. The influence of lesion characteristics according to the modified score on the procedural success and complication rates are shown in Figures 28-4 and 28-5.

In-hospital mortality was 1.1% in this study. Major ischemic complications (death, myocardial infarction, or emergency bypass surgery) occurred in 30 patients (8.6%). The only variables that were independently predictive of procedural outcome were the modified scoring system and the presence of diabetes mellitus. Consequently, this modified ACC/AHA score became widely applicable. However, as experience matured, there was practically less reliance on a scoring system and more on lesion-specific morphologic characteristics to predict clinical outcome with angioplasty.⁴²

In a review of databases of patients undergoing PTCA, Kleiman et al⁴³ reported the multivariate predictors of complications. It was evident that clinical factors such as acute coronary syndrome presentation played an important role in increasing the complication risk by creating a thrombogenic milieu. Other clinical factors included female gender, age, diabetes, chronic renal failure, low ejection fraction, and jeopardy score.

Restenosis

Occurrence of Restenosis with Balloon Angioplasty

Since the early days of PTCA, it became readily apparent that longterm efficacy after a successful procedure was primarily limited by recurrence of the original lesion. The definition of angiographic restenosis evolved over time. In one of the early reports of the PTCA registry,⁴⁴ Holmes et al applied the definition of an increase of at least 30% from the immediate post-PTCA stenosis to the follow-up stenosis or a loss of at least 50% of the gain achieved at PTCA. In 557 patients with successful PTCA and follow-up angiography in 84%, the restenosis rate was reported as 33.6% of patients. In another study of patients who underwent elective PTCA to native coronary arteries between July 1980 and July 1984⁴⁵ and angiographic follow-up in 57%, angiographic restenosis was seen in 302 patients (30.3%), according to the more traditional definition of luminal narrowing greater than 50% at the time of follow-up angiography. A more complete angiographic follow-up rate of 90% was achieved in the CAVEAT trial that randomized 1012 patients to directional coronary atherectomy versus percutaneous balloon angioplasty.⁴⁶ Based on the classic definition of greater than 50% diameter stenosis 6 months after an initially successful procedure, the restenosis rate was 57% in the balloon angioplasty group. This rate was viewed as surprisingly high at the time of study publication, but it was probably more reflective of the true incidence of angiographic restenosis with balloon angioplasty.

The clinical relevance of angiographic restenosis is measured in terms of associated anginal symptoms, demonstration of ischemia and/or the need for target lesion revascularization (TLR). Binary restenosis according to the classic definition of lesion recurrence ≥50% in diameter stenosis does not always result in TLR. Hemodynamically significant lesions usually correlate with a diameter stenosis ≥70%. We analyzed 3363 patients who had a successful elective balloon angioplasty procedure at Emory University Hospitals between 1980 and 1990 and who had a repeat angiographic evaluation for different indications at 4 to 12 months.⁴⁷ Angiographic restenosis was seen in 1570 patients (47%). In patients with restenosis, 71% had angina versus 39% in patients without restenosis (P < 0.0001). At 6 years, the survival in patients with and without restenosis was not statistically different (93% vs 95% respectively P = 0.16). These data support the well-accepted notion that restenosis after PTCA does not increase short- or long-term mortality.

Pathophysiology of Restenosis

Our understanding of restenosis following coronary interventions continues to evolve. Indeed, despite the fact that many mechanisms have been elucidated, many others remain obscure or incompletely understood. The most accepted theory is that coronary arteries dilated with a balloon are prone to restenosis through acute lumen loss from elastic recoil⁴⁸ and through late loss from intimal hyperplasia and negative vessel remodeling. IVUS technology has also helped shed some light on the different patterns of remodeling that can occur after angioplasty and the complex nature of the restenotic process.^49,50

Restenosis occurs in response to deep arterial wall injury to the intima and media which often creates a strong thrombogenic response. Lesion-specific characteristics as well as regional flow dynamics and wall shear stress contribute to the extent of injury.⁵¹ Longitudinal plaque fissures that commonly occur with balloon angioplasty expose the subendothelial and medial components including collagen, elastin, and smooth muscle cells to the circulating blood.⁵² Platelets deposit and aggregate at the site of balloon injury and release various cytokines, chemokines, and growth factors.^53-57 Thromboxane A2, a very powerful platelet aggregator and vasoconstrictor, is released. Platelets also release platelet-derived growth factor, transforming growth factor-b1, and insulin-like growth factor 1. Inflammatory cells also release a wide variety of mitogens. Thrombin, which is the most potent known platelet activator, plays a key role following balloon injury and endothelial denudation. Thrombin activity and thrombin receptor expression are upregulated.⁵⁸ Thrombin facilitates several biologic responses that can induce vascular lesion formation, including being a direct smooth muscle mitogenesis.⁵⁹ Growth factors and mitogens, in turn, will stimulate cell migration and proliferation. Vascular smooth muscle cells will migrate from the media to the intima and deposit extracellular connective tissue matrix proteins. This results in what is referred to as intimal hyperplasia.