General description of procedure, equipment, technique

Tremendous strides have been made in the past few years in the management of patients presenting with acute coronary syndromes (ACS), namely unstable angina, non–ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Unstable angina and NSTEMI patients constitute approximately two thirds of all ACS patients and are classified together as non–ST-elevation ACS (NSTE-ACS).

Six-month mortality rates have decreased by approximately 33% (4.9% in 1999 to 3.3% in 2005 in the Global Registry of Acute Events [GRACE] registry) in NSTE-ACS patients over the past decade. A number of factors have been responsible for the improvement in outcomes, including procedural advances in coronary perfusion techniques, a greater number of patients receiving timely reperfusion, newer pharmacological agents and increased adherence to the use of evidence-based therapies, both at admission and at discharge.

Although earlier studies favored a more conservative approach in these patients, more recent studies and guidelines have outlined the utility of an early invasive approach (i.e., diagnostic angiography with intent to perform revascularization within 48 to 72 hours of presentation) in most patients, particularly those that are high-risk.

Indications and patient selection

Significant heterogeneity exists among NSTE-ACS patients with respect to short- and long-term risk of mortality and reinfarction. One of the key elements in the management of these patients is accurate risk stratification. Three of the commonly used clinical risk calculators are the Thrombolysis in Myocardial Infarction (TIMI) risk score, the GRACE score, and the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression using Integrilin (PURSUIT) risk score.

TIMI risk score:

  • Age
  • Known coronary artery stenosis greater than or equal to 50%
  • Three or more traditional coronary artery disease (CAD) risk factors: hypertension, diabetes mellitus, hyperlipidemia, smoking
  • Aspirin use in the prior 7 days
  • Anginal episodes within the past 24 hours
  • ST-segment deviation greater than or equal to 0.5mm on the electrocardiography (EKG) test
  • Elevated cardiac biomarkers

A value of 1 or 0 is assigned to each factor that is present or absent. The overall score is predictive of the risk of death and death/myocardial infarction (MI) at 14 days. Patients with a score of 0 to 2 are considered low-risk, 3 to 4 as intermediate risk, and 5 to 7 as high risk.

GRACE risk score:

  • Age
  • Resting heart rate
  • Systolic blood pressure (BP)
  • Creatinine
  • Killip class
  • Cardiac arrest on presentation
  • ST-segment deviation
  • Elevated cardiac biomarkers

This score uses a nomogram to predict the risk of in-hospital and 6-month death and death/MI rates. Scores less than or equal to 108 are considered low-risk (in-hospital mortality <1%) , 109 to 140 as intermediate (in-hospital mortality 1%-3%), and greater than 140 as high-risk (in-hospital mortality >3%).

PURSUIT risk score:

  • Age
  • Sex
  • Canadian Cardiovascular Society (CCS) class in the previous 6 weeks
  • Signs of congestive heart failure
  • ST-segment depression in the presenting EKG test

This score also uses a nomogram to predict the risk of death and death/MI at 30 days.

In general, an early invasive approach is indicated for symptom relief and improving prognosis in the presence of high-risk features. Current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend an early invasive approach in the following patients:

  • Refractory angina despite intensive anti-ischemic treatment
  • Hemodynamic or electrical instability
  • Elevated troponin levels
  • Dynamic ST- or T-wave changes
  • Depressed left ventricular function (<40%)
  • Recurrent angina or ischemia with congestive heart failure symptoms, S3 gallop, pulmonary edema, worsening rales, new or worsening mitral regurgitation
  • Recent percutaneous coronary intervention (PCI) (within 6 months)
  • Previous coronary artery bypass graft (CABG)
  • Post-MI angina
  • High-risk findings on noninvasive stress testing
  • Intermediate and high-risk patients according to risk score assessment

Current European Society of Cardiology (ESC) guidelines are similar for the most part. One exception is the inclusion of diabetic patients and those with renal insufficiency as high-risk. In addition, ESC guidelines advocate the use of a bleeding score (e.g., Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) or Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) scores) to further risk stratify these patients. Depending on angiographic findings, patients with one-vessel disease and multivessel disease with suitable anatomy are usually referred for PCI. Consideration for CABG is important in other patients, particularly in those with complex multivessel disease and diabetes mellitus.

In low-risk patients, most notably in troponin-negative women, a conservative approach is recommended.


Contraindications for early invasive approach in patients with NSTE-ACS:

  • Extensive comorbidities (such as liver and pulmonary failure, cancer) in which the risks of revascularization and comorbid conditions likely outweigh the benefits of revascularization
  • Patients with acute chest pain and low risk of ACS (suggesting alternative diagnoses)
  • Patients who will not consent for revascularization, irrespective of angiographic findings
  • In patients being considered for PCI; standard contraindications to PCI include severe bleeding diatheses

Details of how the procedure is performed

Procedural details are similar to those for PCI in stable angina. Access is obtained via the femoral or radial arteries, and diagnostic angiography of the right and left coronary arteries is performed. The pathophysiology of ACS involves inflammatory plaque rupture and its subsequent consequences.

Studies indicate that these lesions frequently have a large lipid core and a thin fibrous cap. Consequently, ACS lesions have variable amounts of thrombus burden. They are also usually complex lesions angiographically, with a higher risk of plaque embolization, microvascular obstruction and “no-reflow.”

Approximately 50% of these patients have multivessel disease, and approximately 20% to 30% have moderate to severe calcification of the coronary vessels. In a recent large randomized trial (ACUITY), the mean number of lesions in ACS patients was four. Despite these high-risk features, angiographic success in these patients is high (96% to 97%).

In our practice, we carefully cross these lesions with a regular workhorse 0.014-inch coronary wire. Occasionally, calcification and/or tortuosity will necessitate the need for a hydrophilic wire, but these can be associated with a higher rate of coronary dissection. Special care is necessary when traversing through ACS lesions since they are unstable and frequently subtotally occluded, and thus prone to abrupt closure.

Given the complex nature of these lesions, particularly calcification, we like to predilate the lesion(s) with a compliant balloon to ensure adequate lesion preparation prior to stenting. This also helps with stent sizing, particularly in angulated and tortuous vessels. Although variable amounts of thrombus are associated with these lesions, there is usually no role for aspiration thrombectomy for these lesions.

One exception is total occlusion of the left circumflex artery, which is often silent electrocardiographically, and manifests as a NSTEMI rather than STEMI despite total vessel occlusion. Similarly, total occlusions of distal branch vessels can present as NSTEMI, and may require aspiration thrombectomy. In almost all cases, stenting is indicated. This can be performed with either a bare-metal stent or a drug-eluting stent. As with routine PCI, we may postdilate the stent(s) with noncompliant balloons to ensure adequate stent expansion and apposition.

Fractional flow reserve (FFR) guidance: FFR assessment can be helpful in the management of these patients since the prevalence of multivessel disease is higher than in non-ACS settings. In the landmark Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial, patients who underwent FFR-guided PCI (with PCI only if FFR ≤0.8) had fewer stents placed (1.9 vs. 2.7) and superior 1-year major adverse cardiac event (MACE) rates (13.2% vs 18.3%) as compared with patients undergoing routine angiography-guided PCI. Similarly, at 2 years, rates of death/MI and repeat revascularization were lower in the FFR-guided arm. Approximately 32% of patients in the FAME trial presented with ACS.

Radial versus femoral approach:Traditionally, transfemoral access has been used for cardiac catheterization. With the routine use of 6 Fr guide catheters and better equipment, there has been a renewed interest in the utility of transradial access for all PCIs, including in NSTE-ACS. Data from randomized controlled trials indicate that transradial access has similar procedural success rates as transfemoral access, although there seems to be a steep “learning curve” for transradial access. Moreover, major bleeding (mostly access-site bleeding) is significantly reduced as compared with transfemoral access. This has been true in patients presenting with ACS as well.

Bare-metal stent versus drug-eluting stent PCI: Although no randomized controlled trials have directly compared the use of bare-metal stents and drug-eluting stents specifically in NSTE-ACS, numerous trials have compared the two stents in a wide range of patients with CAD. Unstable CAD patients (including STEMI patients) represent approximately 30% to 50% of patients in these trials.

There appears to be no difference in the risk of mortality or reinfarction between patients receiving drug-eluting or bare-metal stents, although patients receiving bare-metal stents, particularly those with diabetes, have a higher risk of restenosis and need for repeat revascularization than patients receiving drug-eluting stents. There also appears to be a slight increase in the risk of very late stent thrombosis (beyond 1 year) with the use of first generation drug-eluting stents as compared with bare-metal stents.

While this appears to be true for most patients undergoing first generation drug-eluting stent implantation, it is especially true for ACS lesions, likely due to stent implantation in an inflamed, thrombotic, and unstable environment. In ACS patients, it is recommended that dual antiplatelet therapy be continued for at least 1 year, but potentially longer.

The optimal duration of dual antiplatelet therapy use in patients undergoing drug-eluting stent implantation is an area of active investigation. A careful assessment of bleeding risk and patient adherence prior to drug-eluting stent implantation is a prerequisite for all patients. Some second generation drug-eluting stents, particularly the everolimus-eluting stent, appear to have a lower risk of stent thrombosis than first-generation drug-eluting stents and possibly even a lower risk of stent thrombosis than bare metal stents, including in ACS patients.

Timing of PCI: Although numerous studies have documented the utility of an early invasive approach in NSTE-ACS patients, particularly in those who are intermediate- to high-risk, the optimal timing of angiography is not well-defined. Early or immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy. This is also usually necessary in unstable patients.

Conversely, pretreatment with intensive antithrombotic therapy in stable patients may diminish thrombus burden and “cool down” unstable plaques, improving the safety of percutaneous revascularization and reducing the risk of periprocedural ischemic complications. It is reasonable to pursue a more urgent revascularization strategy (within 12 to 24 hours of admission) in patients who are stable but high-risk (GRACE scores >140), while a more delayed invasive strategy (24 to 72 hours of admission) can be used in lower risk stable NSTE-ACS patients.

Outcomes (applies only to therapeutic procedures)

Short- and long-term cardiovascular outcomes in patients presenting with NSTE-ACS are heterogenous, depending on patient risk, as discussed above. In the international GRACE registry, overall in-hospital mortality was 3% for troponin negative patients and 6% for troponin positive patients. Overall 6-month mortality was 4.8%. As noted above, the GRACE registry reported a decline in 6-month mortality from 4.9% in 1999 to 3.3% in 2005.

In addition, rates of adverse in-hospital outcomes fell significantly from 1999 to 2005, including congestive heart failure (13% to 6.1%), reinfarction (3.0% vs 1.7%), and cardiogenic shock (2.1% vs 1.8%). Although improvements in pharmacological management certainly contributed, these improvements coincided with a 21% increase in angiography and an 18% increase in PCI in these patients.

Current evidence from randomized controlled trials suggests a 25% reduction in all-cause mortality over 2 years of follow-up in NSTE-ACS patients who received early invasive treatment compared with a conservative approach (4.9% vs. 6.5%). Similarly, a significant reduction in reinfarction (7.6% vs. 9.1%) and repeat unstable angina (19.9% vs. 28.7%) was reported.

These benefits appear to be most apparent in troponin positive patients. These results were echoed in the large, national CRUSADE registry, a “real world” cohort of high-risk NSTE-ACS patients, in whom in-hospital mortality was 2.0% in those receiving an early invasive approach and 6.2% in those conservatively managed.

Cardiogenic shock: The percentage of patients who develop/present with cardiogenic shock following a NSTE-ACS has been more or less constant in the GRACE registry, at approximately 2% between 1999 and 2005. However, this group has a very high mortality. In the Should we Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial, which included patients with acute MI and cardiogenic shock, the 30-day mortality was 51%, and the 6-month mortality was 57%. There appeared to be a benefit with early revascularization in patients in cardiogenic shock (6-month mortality: 50.3% vs 63.1%). Current guidelines therefore strongly advocate an early invasive approach in these patients.

Gender differences:Data from randomized controlled trials suggest that gender may influence outcomes in patients with NSTE-ACS. A recent meta-analysis of eight trials comparing an invasive strategy to conservative management noted a significant reduction in death, reinfarction, or rehospitalization for ACS in men but less so in women up to 12 months of follow-up.

The response for women was heterogenous, with biomarker-positive women demonstrating significant benefit with an invasive strategy, while biomarker-negative women demonstrated a tendency toward harm. Long-term studies in patients undergoing PCI for NSTE-ACS based on gender are scant, but more recent data indicate comparable long-term mortality in men and women undergoing PCI.

Alternative and/or additional procedures to consider

Special considerations

PCI vs CABG:In patients stabilized after an episode of ACS, the choice of revascularization modality can be made as in stable CAD. In approximately one third of patients, angiography will reveal single-vessel disease, allowing ad hoc PCI in most cases.

Multivessel disease will be present in another 50%. Here the decision is more complex and the choice has to be made between culprit lesion PCI, multivessel PCI, CABG, or a combined (hybrid) revascularization in some cases.

The revascularization strategy should be based on the clinical status, as well as the severity and angiographic distribution of the CAD and the lesion characteristics. One tool to stratify patients based on angiographic complexity is the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score (www.syntaxscore.com).

SYNTAX was a landmark trial that compared outcomes between drug-eluting stent-PCI (paclitaxel-eluting stent) and CABG in patients with three-vessel disease and/or left main disease. In this trial, approximately 28% of patients presented with an ACS. At 4 years, patients with a low SYNTAX score and three-vessel disease (values between 0 and 22, indicating low angiographic complexity) had similar cardiovascular outcomes with PCI and CABG, including death, MI, and stroke.

However, there was a higher risk of repeat revascularization in the PCI arm. In patients with intermediate (23 to 32) and high (>32) SYNTAX scores, CABG was superior to PCI for cardiovascular outcomes including death, MI, and need for repeat revascularization.

Culprit vessel only versus multivessel PCI: In most patients with multivessel disease, culprit vessel PCI is usually the treatment of choice. There are no randomized controlled trials comparing these two strategies in patients undergoing PCI for NSTE-ACS. Data from national registries, such as the US National Cardiovascular Data Registry (NCDR), suggest that procedural success may be slightly lower in multivessel PCI, but outcomes tend to be similar. In certain situations, multivessel PCI is necessary. These include patients in whom the culprit vessel is not easily distinguishable, patients with simultaneous plaque rupture in multiple distributions, and cardiogenic shock patients, in whom multivessel PCI may provide benefit over culprit vessel PCI by reducing ischemia in noninfarct territories.

Complications and their management

Complications associated with PCI for NSTE-ACS are similar to those noted with PCI for any other indication. These include coronary dissection, abrupt vessel closure, “no reflow,” stent thrombosis, coronary perforation, myocardial infarction, stroke, renal failure, and death. Of these, two complications deserve special mention.

Stent thrombosis can be acute, usually due to technical factors such as dissection, plaque prolapse, or inadequate anticoagulation. The majority of patients with stent thrombosis will have evidence of ST elevation on the EKG test. Others may manifest with persistent or new chest pain and upward trending biomarkers.

Repeat cardiac catheterization demonstrates a total or subtotal occlusion in the region of the recently placed stent. Intravascular ultrasound can be helpful in determining the exact etiology of acute stent thrombosis. Thrombectomy and balloon dilation are usually adequate; repeat stenting is usually not necessary unless there is stent fracture or deformation, or an uncovered coronary dissection.

Most operators would opt to repeat intravascular ultrasound after obtaining a satisfactory angiographic result to ensure adequate stent apposition and expansion. Late thrombosis and very late stent thrombosis are different pathophysiologically than early stent thrombosis, and are a bigger concern for first generation drug-eluting stents, as detailed above, particularly in the setting of PCI for unstable lesions.

Another complication that occurs with greater frequency in ACS patients undergoing PCI is “no reflow” or slow reflow. No reflow is defined as the inability to adequately perfuse distal myocardium after temporary occlusion of an epicardial vessel, without evidence of a persistent mechanical obstruction.

Slow reflow refers to impaired blood flow into previously ischemic tissue. Although the pathophysiology is not completely understood, a significant component involves microvascular damage from capillary plugging, microthrombi formation, accumulation of leukocytes, altered calcium metabolism, and production of oxygen free radicals.

Distal occlusive thrombus formation/propagation is also a reason. No reflow manifests as reduced/absent epicardial flow, absence of myocardial blush, and new or persistent ST elevations on the EKG. Potential treatment options include intracoronary administration of medications such as verapamil, nitroprusside, nicorandil, adenosine, and abciximab.

What’s the evidence?

Jneid, H, Anderson, JL, Wright, RS. “2012 ACCF/AHA focused update on the guideline management of patients with unstable angina/non-ST-elevation myocardial infarction (Updating the 2007 guideline and replacing the 2011 focused update): A report of the ACC/AHA Task Force on Practice Guidelines”. Circulation. vol. 126. 2012. pp. 875-910. (These are the most recent ACC/AHA guidelines on the management of patients with NSTE-ACS.)

Hamm, CW, Bassand, JP, Agewall, S. “ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the ESC”. Eur Heart J. vol. 32. 2011. pp. 2999-3054. (These are the most recent ESC guidelines on the management of patients with NSTE-ACS.)

Fox, KA, Steg, PG, Eagle, KA. “Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006”. JAMA. vol. 297. 2007. pp. 1892-1900. (These are data from the international GRACE registry.)

Eagle, KA, Lim, MJ, Dabbous, OH. “A validated prediction model for all forms of acute coronary syndromes: estimating the risk of 6-month postdischarge death in an international registry”. JAMA. vol. 291. 2004. pp. 2727-33. (This is the prediction model derived from the international GRACE registry.)

Antman, EM, Cohen, M, Bernink, PJ. “The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making”. JAMA. vol. 284. 2000. pp. 835-42. (This is the prediction model derived from a TIMI trial.)

Boersma, E, Pieper, KS, Steyerberg, EW. “Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators”. Circulation. vol. 101. 2000. pp. 2557-2567. (This is the prediction model derived from the PURSUIT trial.)

Bavry, AA, Kumbhani, DJ, Rassi, AN. “Benefit of early invasive therapy in acute coronary syndromes: A meta-analysis of contemporary randomized clinical trials”. J Am Coll Cardiol. vol. 48. 2006. pp. 1319-25. (This summarizes all the data from randomized controlled trials, which favor an early invasive approach in patients with NSTE-ACS.)

Hochman, JS, Sleeper, LA, Webb, JG. “Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK investigators”. N Engl J Med. vol. 341. 1999. pp. 625-34. (These are the results of the SHOCK trial in patients with cardiogenic shock following an acute MI.)

Bhatt, DL, Roe, MT, Peterson, ED. “Utilization of early invasive management strategies for high-risk patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative”. JAMA. vol. 292. 2004. pp. 2096-104. (This summarizes national trends in the management of patients with NSTE-ACS, as reported in the CRUSADE registry.)

O’Donoghue, M, Boden, WE, Braunwald, E. “Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis”. JAMA. vol. 300. 2008. pp. 71-80. (This summarizes gender differences from randomized controlled trials comparing an early invasive approach to conservative management in patients with NSTE-ACS.)