Percutaneous Coronary Intervention



Percutaneous Coronary Intervention


Olabisi Akanbi

David Lee



HISTORY OF PERCUTANEOUS CORONARY INTERVENTION

Dotter performed the first angioplasty using sequential catheter dilation of a femoral arterial stenosis in 1964, and with advancement in catheter technology, Andreas Gruentzig performed the first balloon coronary angioplasty in 1977.1 The high acute success rate and relatively low risk for percutaneous transcatheter coronary angioplasty (PTCA) allowed it to gain popularity over the next decade as a number of clinical trials confirmed its safety and utility in relieving angina. However, PTCA was limited by acute complications with abrupt closure of the vessel in 3% to 11% of procedures and restenosis, in which endothelial damage from the balloon procedure instigated a chain of events leading to a re-narrowing of the artery at the site of the injury in up to 50% of lesions weeks to months after the procedure.


Emergence of Coronary Stents

As the scientific understanding of restenosis grew, coronary stents were developed. The Cook Inc (Bloomington, Ind.) Gianturco-Roubin Flex-Stent was approved by the Food and Drug Administration (FDA) in May 1993 for the treatment of acute and threatened closure following balloon angioplasty. Designed as a balloon expandable stainless steel linear backbone with a series of coils soldered along its length, it provided mechanical scaffolding to support the vessel architecture after balloon injury and treat acute closure due to recoil and/or local vascular dissection.2 In 1994, the Palmaz-Schatz stent (Johnson & Johnson), a mesh stent design based on a previously approved Palmaz stent for the iliac arteries, was also approved by the FDA. The impact on restenosis was quite remarkable, with the 202 subjects Stent Restenosis Study (STRESS) showing a target lesion revascularization rate of 10.2% in the stent group versus 18.4% in a balloon angioplasty-only group, a relative reduction of 45%. Despite these successes, the specter of acute and subacute stent thrombosis became a new important clinical problem. A landmark study, the Stent Anticoagulation Restenosis Study (STARS) trial,3 established that dual antiplatelet therapy (DAPT) with aspirin and ticlopidine was the best choice for the prevention of stent thrombosis. In this trial of 1653 patients, patients treated with aspirin and ticlopidine had a stent thrombosis rate of 0.5% versus 3.6% for aspirin alone and 2.7% for aspirin and warfarin.

As the stent market grew, the number of available stents also grew. Multiple competitive stent designs became readily available with most clinically compared to previously FDA-approved stents in order to gain market approval. Despite modifications—decreasing stent bulk, improving deliverability to the target lesion, and changing cell design—the rates of restenosis and stent thrombosis remained relatively static.


Drug-Eluting Stents

The next era of coronary stenting began in April 2003 with the introduction of the Cypher stent (Cordis Corp., Santa Clara, CA, USA) in the United States. This stent incorporated the backbone of a stainless steel stent with the important additions of (1) a durable polymer coating and (2) an anti-restenosis drug (sirolimus). The coating, which consisted of a two polymer mix with sirolimus atop a base layer sprayed onto the stent surface, allowed an appreciable amount of sirolimus to be eluted into the vessel wall. The FDA pivotal Sirolimus-eluting Stents Versus Standard Stents in Patients with Stenosis in a Native Coronary Artery (SIRIUS) study4 showed a target vessel revascularization (TVR) rate of 8.0% and target lesion revascularization (TLR) rate of 4.1% (21.0% and 16.6%, respectively, in the bare metal randomized group).

In May 2004, Boston Scientific (Natick, MA, USA) introduced its TAXUS drug-eluting stent (DES). This device used an existing bare metal stent platform with a proprietary polymer base and paclitaxel as its anti-restenosis drug. The TAXUS-IV FDA pivotal trial5 yielded a TVR rate of 4.7% and TLR of 3.0%, with DES versus a bare metal control of 12% TVR and 11.3% TLR at 6 months.

The first major safety concern regarding DES arose in 2006 with the presentation of data from the Scandinavian national registry6 as well as other meta-analyses, suggesting that DES was associated with worse clinical outcomes when compared with bare metal stents, especially with end points of death and late stent thrombosis after 6 months. This led to a much greater interest in stent thrombosis and concerns about premature cessation of DAPT.7 Consequently, new guidance for duration of DAPT after DES changed to a prolonged plan of therapy, up to 1 year post-DES implantation with a bare minimum of 6 months. Subsequent data sets did not confirm the original Scandinavian findings, but concern persisted nonetheless for several years.

The next generation of DES with smaller delivery profiles, improved pharmacokinetics and greater biocompatible polymers, was delivered in 2010 and began the next wave of excitement in reducing major adverse cardiovascular events
(MACEs) related to coronary stents. As the performance of these stents improved, the interest in tackling more complex anatomies of coronary artery disease (CAD) became greater and moved the procedure forward to where we are today.


ADJUNCTIVE DEVICES

A number of adjunctive devices have been used to augment angioplasty and stenting and may be used for “vessel preparation” (ie, to allow delivery of the eventual stent). Atherectomy is used in perhaps 1% to 2% of all percutaneous coronary interventions (PCIs). This low use has been ascribed to the extra time needed for device preparation and use, cost of the devices, and general lack of data demonstrating additional clinic improvement when using atherectomy either as a primary treatment or as an adjunct to balloon angioplasty and/or coronary stenting. Atherectomy devices are the most widely used adjunctive device for vessel preparation and a variety of approaches exist. These include direct atherectomy, rotational and orbital atherectomy, excimer laser atherectomy, and, most recently, ultrasonic atherectomy.


Rotational and Orbital Atherectomy

The most widely used of atherectomy devices today are rotational and orbital atherectomy, both of which mechanistically work by plaque pulverization using a spinning diamond-tipped crown. For rotational atherectomy (Boston Scientific, Natick, MA, USA), the crown generally spins at 140 to 180,000 rpm and requires a specialized 0.009” coronary guidewire. The device is often used in calcific or densely packed lesions. As the plaque is pulverized, small 7 to 10 nm particles are created and sent downstream, increasing the risk of the no-reflow phenomenon. Several studies have shown its utility in aiding deliverability of balloons or stents but without any impact on restenosis rates or clinical outcomes.8,9

Orbital atherectomy has a similar mechanism of action but utilizes an eccentric diamond-tipped crown. It spins at a lower rpm while guided through the lesion and vessel, taking advantage of centrifugal force to enable differential cutting.10 Clinical results11 have been generally favorable but without clear improvement in TVR or clinical outcomes such as death and subsequent myocardial infarction (MI).


Excimer Laser Atherectomy

Excimer laser atherectomy involves the use of laser energy delivered to the vessel wall to vaporize plaque.12 Traditionally, it has been used in undilatable or difficult to cross lesions as well as cases involving under-expanded stents. Its main advantage is that it can use a standard 0.014” coronary guidewire and provides a novel approach to lesion modification, which is distinctly different from rotational or orbital atherectomy.


Focused Ultrasound Energy—Intravascular Lithotripsy

Focused ultrasound energy has been developed as a tool to aid in treatment of severely calcified coronary lesions. Initial concept and success of intravascular lithotripsy has been demonstrated in the peripheral vasculature. The coronary device can be used on a standard 0.014” coronary guidewire and involves the placement of a balloon with a focused ultrasound emitter at the site of the lesion and the emitter is activated, which then destabilizes calcific plaque through microvibrations created by the sound waves. Based on reports13,14,15 demonstrating safety and utility of this approach in the coronary vasculature, the FDA granted approval of the device in February 2021 for the treatment of severely calcified CAD.


INDICATIONS FOR PERCUTANEOUS CORONARY INTERVENTION


Physiologic Measurements in the Catheterization Laboratory

Pressure wire technology, most typically fractional flow reserve (FFR), has provided interventional cardiologists with a means of determining the physiologic significance of stenotic lesions during angiography. The use of coronary physiology to guide myocardial revascularization was shown to improve clinical outcomes and reduce cost in patients with CAD.4 The majority of patients are still managed based on angiographic visual estimation of a stenosis in isolation. The main premise of coronary physiology assessment is to determine the functional significance of individual stenoses at the time of clinical decision-making, providing an objective marker to identify ischemic lesions most likely to benefit from PCI.


Fractional Flow Reserve

FFR is the most widely used pressure-derived invasive physiologic index of coronary lesion assessment and considered the gold standard for clinical physiologic assessment in the catheterization laboratory. FFR is defined as the ratio of maximum achievable coronary blood flow (CBF) in the presence of an epicardial coronary stenosis and the theoretical maximum CBF in the hypothetical absence of coronary stenosis during pharmacologic vasodilation. FFR is the ratio of the mean distal coronary pressure (Pd) to the mean proximal coronary pressure (Pa) across a stenosis during maximal hyperemia. Vasodilators are used to achieve maximal hyperemia, most commonly adenosine (Table 43.1). The purpose of the hyperemia is to create conditions in which pressure (Pa and Pd) and flow are linearly related.

The concept of FFR and hyperemic pressure-derived indices of coronary stenosis severity depends on the fundamental physiologic principle that coronary pressure is directly proportional to CBF when microvascular resistance is stable, achievable with hyperemic agents like adenosine. Under these conditions, the decrease in pressure across a coronary stenosis reflects the decrease in CBF to the amount of subtended myocardium. Landmark studies have shown improved patient outcomes by selecting patients for PCI with FFR (Table 43.2). This has led to the incorporation of FFR into coronary revascularization guidelines, which currently recommend its clinical use based on a fixed 0.8 cutoff. Of note, the current evidence on the value of FFR as a clinical decision tool is based on studies

that have used two different FFR criteria for defining hemodynamically significant lesions: 0.75 or 0.80. The different choice of dichotomous cutoffs has its origin in early validation studies, which demonstrated that an FFR <0.75 has 100% specificity to identify stenosis with inducible ischemia, whereas an FFR >0.80 has a sensitivity of more than 90% to exclude stenoses that cause ischemia. Recent developments spurred by wire-based FFR include other coronary functional indexes such as instantaneous wave-free ratio (iFR) and resting distal-to-aortic coronary pressure ratio (Pd/Pa), which can be performed without hyperemic agents as well as angiography-based FFR, which utilizes computational flow dynamics to estimate FFR by contrast flow16 (Figure 43.1A-D and Table 43.3).















Irrespective of incorporation into guidelines, global adoption into clinical practice remains underutilized for a variety of reasons, including technicalities associated with FFR measurements, time consumption, inadequate reimbursement, or relative contraindications associated with hyperemia (such as severe pulmonary disease and use of adenosine).


Instantaneous Wave-Free Ratio

iFR is a pressure-based physiologic index of coronary stenosis severity that is measured under resting conditions by making use of the unique properties of baseline coronary physiology; it does not require the administration of vasodilator drugs. Consequently, it is a simpler, safe, and effective alternative to FFR to guide revascularization.

While resting Pd/Pa is the ratio of distal coronary artery pressure to aortic pressure over the entire cardiac cycle (systole and diastole), iFR is measured during a specific period of diastole known as the wave-free period, when flow is intrinsically at its highest compared with the whole cardiac cycle and there are no competing waves affecting the CBF5. The onset of diastole is identified from the dicrotic notch, and the diastolic window is calculated beginning 25% into diastole and ending 5 ms before the end of diastole. Resting blood flow is preserved across all severities of stenosis as a result of compensatory microcirculatory vasodilation in response to the stenosis at the expense of Pd, which falls even at rest. Because pressure falls at
rest with stenosis severity, a resting index should be sufficient to quantify severity, provided there is sufficient flow velocity to distinguish between stenoses. During diastole, the competing waves are quiescent, and during the wave-free period, microcirculatory resistance is at its lowest and most stable compared to the rest of the cardiac cycle. At this time, the pressure and flow velocity are linearly related, and pressure ratios can assess the flow limitation imposed by a stenosis.