Strategies for diagnosis: functional testing and imaging

Exercise testing and cardiac imaging are used to confirm the diagnosis of CAD, to document ischaemia in patients with stable symptoms, to risk-stratify patients, and to help choose treatment options and evaluate their efficacy. Another indication for non-invasive imaging before revascularization is the detection of myocardial viability in patients with poor LV function.

When noninvasive stress imaging is contraindicated, non-diagnostic, or unavailable, the measurement of fractional flow reserve (FFR) or coronary flow reserve is helpful during diagnostic coronary angiography. Deferral of PCI or CABG in patients with FFR .0.80 appears safe.Fractional flow reserve measurement is indicated for the assessment of the functional consequences of moderate coronary stenoses FFR-guided PCI with medical therapy has been shown to decrease the need for urgent revascularization compared with the best available medical therapy alone.

Indications for diagnostic testing in patients with suspected CAD and stable symptoms

Screening for silent (asymptomatic) myocardial ischaemia may be considered in selected high-risk patients, such as those with diabetes mellitus.
CT is considered to perform best in the lower range of pre-test probability (15—50%).

Detection of myocardial viability
Multiple imaging techniques, including PET, SPECT, and dobutamine stress echocardiography, have been evaluated for assessment of viability and prediction of clinical outcome after myocardial revascularization. In general, nuclear imaging techniques have a high sensitivity, whereas techniques evaluating contractile reserve have a somewhat lower sensitivity but higher specificity. MRI has a high diagnostic accuracy for assessing the transmural extent of myocardial scar tissue and can also assess contractile reserve, but its ability to detect viability and predict recovery of wall motion is no better than other imaging techniques.

Revascularization for stable coronary artery disease

Rationale for revascularization

Prior to revascularization, patients with SCAD must receive guideline-recommended medical treatment, due to its established benefits in terms of prognosis and symptom relief. The indications for revascularization in patients with SCAD are persistence of symptoms despite medical treatment and/or improvement of prognosis. Ischaemia is of prognostic importance in patients with SCAD, particularly when occurring at low workload. Revascularization relieves myocardial ischaemia more effectively than medical treatment alone. The extent, location, and severity of coronary artery obstruction as assessed by coronary angiography or coronary computed tomography (CT) angiography are important prognostic factors in addition to ischaemia and left ventricular function.

Evidence basis for revascularization

Most meta-analyses comparing a strategy of PCI against initial medical therapy found no evidence in favour of an invasive strategy, in terms of survival or myocardial infarction. Two reported a small survival benefit for PCI over medical therapy, although this might have been influenced by the inclusion of a subset of patients who had had a recent myocardial infarction.
It is important to consider that the best current revascularization results achieved with PCI are with new-generation DES and for CABG with maximal use of arterial grafts.
Meta-analysis demonstrated a survival benefit from CABG in patients with LM or three-vessel SCAD, particularly when the proximal LAD coronary artery was involved. The MASS II trial randomly compared medical therapy with PCI and CABG. At 10 years, compared with medical therapy, CABG was associated with reduced rates of cardiac mortality, myocardial infarction and angina. In the Surgical Treatment Ischemic Heart failure (STICH) trial, 1212 patients with CAD and a left ventricular ejection fraction (LVEF) of =35% were randomized to medical therapy or CABG. Patients with LM disease were excluded, and 17% of patients on medical therapy underwent CABG and 6% of patients underwent PCI by the end of the follow-up period. In the intention-to-treat analysis, all-cause mortality was not significantly lower with CABG than with medical therapy; however, all-cause mortality or hospitalization for cardiovascular causes occurred less frequently among patients undergoing CABG. The results with respect to all other secondary clinical outcomes also favoured CABG.

Indications for revascularization in patients with stable angina or silent ischaemia



Left main coronary artery disease: It has been suggested that two important pathophysiological features mitigate against the success of PCI in LM lesions (i) up to 80% of LM disease involves the bifurcation, which is known to be at higher risk of restenosis and (ii) up to 80% of LM patients also have multivessel SCAD, where CABG offers a survival advantage independent of the presence of LM disease. More recent evidence suggests, however, that PCI provides at least equivalent results to CABG for lower-severity LM lesions at up to 5 years of follow-up.
The SYNTAX trial included a pre-specified subgroup analysis of limited power in 705 patients with predominant distal LM disease, who were randomly assigned to CABG or PCI. At 5 years' follow-up, rates of death and myocardial infarction were not significantly different, whereas CABG was associated with a higher rate of stroke (4.3% vs. 1.5%) and a lower risk of repeat revascularization (15.5% vs. 26.7%) with no significant difference in the overall MACCE rates (31.0% vs. 36.9%). MACCE outcomes were comparable for PCI and CABG in the lower (022) and intermediate (2332) SYNTAX score tertiles. In patients with SYNTAX scores .32, CABG was associated with numerically lower mortality (14.1% vs. 20.9%) and a significantly reduced need for repeat revascularization (11.6% vs. 34.1%) albeit at a numerically higher risk of stroke (4.9% vs. 1.6%).
The Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease (PRECOMBAT) trial randomized 600 patients with LM disease to PCI or CABG. All patients had newly diagnosed ULMCA stenosis (more than 50% diameter stenosis by visual angiographic estimation) and had been judged to be suitable candidates for either PCI or CABG. At baseline, the patients had a mean age of 62. One-third had diabetes and one-half had stable angina. On average, they had a normal ejection fraction (61%) and a EuroSCORE of about 2.7. About 70% had left main artery stenosis with two-vessel or three-vessel disease. The SYNTAX score was around 25 in both groups. The lack of significant differences between the two groups was maintained over 2 years from randomization. As a result of low event rates, however, the study was underpowered and the study authors have noted that these findings should not be clinically directive.

Three-vessel coronary artery disease: SYNTAX randomly assigned 1800 patients with LM and/or three vessel CAD to either an early-generation paclitaxel-eluting stent or CABG. At 5 years, CABG, as compared with PCI, significantly reduced overall MACCE. In the 1095 patients with three-vessel CAD, in comparison with PCI, CABG resulted in lower total death, cardiac death, myocardial infarction and repeat revascularization. In these patients with low SYNTAX score, rates of MACCE were similar for CABG and PCI. Conversely, when compared with PCI in patients with intermediate and high SYNTAX scores, CABG showed lower rates of MACCE.
In observational study based on the New York State registry, a lower risk of death was noted in all subgroups (CABG), except for those with two-vessel CAD without proximal LAD lesions. Two main findings can be highlighted from this study: (i) the presence of LAD disease conferred a survival benefit to CABG and (ii) the survival benefit with CABG became evident only during the second half of the 5-year follow-up. There is notable consistency in the findings on the survival advantage of CABG over PCI for more severe three-vessel CAD.



Revascularization in non-ST-segment elevation acute coronary syndromes (NSTE-ACS)

Patients in cardiogenic shock, or after resuscitation, should undergo immediate angiography (within 2 hours) because of the high likelihood of critical CAD, but it is equally important to identify patients at low risk, in whom invasive and medical treatments provide little benefit or may even cause harm.

Early invasive vs. conservative strategy

A more recent meta-analysis, based on individual patient data from three studies that compared a routine invasive against a selective invasive strategy, revealed lower rates of death and myocardial infarction at 5-year follow-up, with the most pronounced difference in high-risk patients.184 Age, diabetes, previous myocardial infarction, ST-segment depression, hypertension, body mass index (<25 kg/m2 or >35 kg/m2), and treatment strategy were found to be independent predictors of death and myocardial infarction during follow-up. All results supported a routine invasive strategy but highlight the importance of risk stratification in the decision-making process management.


Timing of angiography and intervention

The timing of angiography and revascularization should be based on patient risk profile. Patients at very high risk (i.e. those with refractory angina, severe heart failure or cardiogenic shock, life-threatening ventricular arrhythmias, or haemodynamic instability) should be considered for urgent coronary angiography (in less than 2 hours), regardless of ECG or biomarker findings. In patients at high risk, with at least one primary high-risk criterion, an early invasive strategy within 24 hours appears to be the reasonable timescale. In lower-risk subsets, with a GRACE risk score of <140 but with at least one secondary high-risk criterion, the invasive evaluation can be delayed without increased risk but should be performed during the same hospital stay, preferably within 72 hours of admission. In other low-risk patients without recurrent symptoms, a noninvasive assessment of inducible ischaemia should be performed before hospital discharge.


Type of revascularization

In stabilized patients, the choice of revascularization modality can be made in analogy to patients with SCAD. In multivessel disease the decision is more complex and the choice has to be made between culprit-lesion PCI, multivessel PCI,CABG, or a hybrid revascularization.

Culprit-lesion PCI is usually the first choice in most patients with NSTE-ACS and multivessel disease; however, there are no prospective studies comparing culprit-lesion PCI with early CABG. In stabilized patients with multivessel disease and a high SYNTAX score (>22), particularly when there is no clearly identified culprit lesion, a strategy of urgent CABG should be preferred. In a large database including 105 866 multivessel CAD patients with NSTE-ACS, multivessel PCI was compared with single-vessel PCI and was associated with lower procedural success but similar in-hospital mortality and morbidity. However, incomplete revascularization appears to be associated with more 1-year adverse event rates.

After culprit-lesion PCI, patients with scores in the two higher terciles of the SYNTAX score should be discussed by the Heart Team, in the context of functional evaluation of the remaining lesions. This also includes the assessment of patients' comorbidities and individual characteristics.

As there is no randomized study comparing an early with a delayed CABG strategy, the general consensus is to wait 48–72 hours in patients who had culprit-lesion PCI and have residual severe CAD. When there is continuing or recurrent ischaemia, ventricular arrhythmias, or haemodynamic instability, CABG should be performed immediately. Patients with LM or three-vessel CAD involving the proximal LAD should undergo surgery during the same hospital stay. Pre-treatment with a dual antiplatelet regimen should be considered only as a relative contraindication to early CABG.

New generation DES are preferred over BMS as the default option. Dual antiplatelet therapy (DAPT) should be maintained for 12 months, irrespective of stent type.

According to 2014 ESC/EACTS Guidelines on myocardial revascularization.