Chronic coronary syndromes — structured viva

Stem

Practice viva. You are the cardiology registrar in a chest-pain clinic. The examiner works through suspected and established chronic coronary syndromes: estimating the likelihood of obstructive CAD, choosing the first test, high-risk anatomy and revascularisation, the ISCHEMIA and ORBITA-2 evidence, first-line antianginal therapy, and vasospastic angina. Answer under the 2024 ESC guideline unless asked for AHA/ACC.

Branch A — Estimating the likelihood

Examiner: A 70-year-old woman with four coronary risk factors describes breathlessness on exertion. Her resting ECG and echocardiogram are normal. How likely is obstructive CAD?^[1]

Strong answer:

• In the initial diagnostic management of individuals with suspected CCS, ESC 2024 recommends estimating the pre-test likelihood of obstructive epicardial CAD with the Risk Factor-weighted Clinical Likelihood (RF-CL) model (Class I, Level B), which includes sex, age, angina symptoms and the number of risk factors.^[1]
• The risk factors counted (0–5) are family history, smoking, dyslipidaemia, hypertension and diabetes.^[1]
• The main symptom is scored either as chest pain (0–3 points: 1 point each for constricting discomfort retrosternally or in the neck, jaw, shoulder or arm; aggravation by physical or emotional stress; and relief by rest or nitrates within 5 min) or as dyspnoea (2 points: shortness of breath and/or trouble catching breath aggravated by physical exertion).^[1]
• In ESC 2024 Figure 4, a woman aged 70–80 with a symptom score of 2 points and 4–5 risk factors has an RF-CL of 16%; ESC 2024 Figure 8 uses exactly this patient (a 70-year-old woman with four coronary risk factors and exertional dyspnoea, pre-test likelihood 16%).^[1]
• That is a moderate likelihood (more than 15% to 50%), and ESC 2024 encourages patients with moderate, high or very high likelihood to undergo further diagnostic testing.^[1]

Follow-up: Her referral letter calls the breathlessness atypical. Why does that label not help?^[1]

• ESC 2024 says the typical/atypical terminology no longer aligns with current concepts of CCS and should be replaced by a detailed description of symptoms; patients with “typical” vs “atypical” angina in the PRECISE study had similar 1-year outcomes.^[1]
• The Figure 4 symptom score replaces that potentially misleading terminology: three chest pain characteristics, formerly “typical” angina, score 3 points; two, formerly “atypical”, score 2 points; and none or one, formerly “non-cardiac/non-anginal”, score 0–1 point.^[1]
• Sex-stratified analyses cited by ESC 2024 indicate that, women with suspected angina are usually older and have a heavier cardiovascular risk-factor burden, more frequent comorbidities, non-anginal symptoms such as dyspnoea and fatigue, and a greater prevalence of MVA than men.^[1]
• AHA/ACC 2021 recommends that chest pain not be described as atypical, because the term is not helpful in determining the cause and can be misinterpreted as benign; chest pain should instead be described as cardiac, possibly cardiac or noncardiac (COR 1, LOE C-LD).^[3]

Branch B — Choosing the first test

Examiner: Which test do you request first for her, and why?

Strong answer:

• In symptomatic individuals with suspected CCS whose pre-test likelihood of obstructive CAD by clinical assessment is above 5%, ESC 2024 recommends CCTA or non-invasive functional imaging for myocardial ischaemia as the initial diagnostic test (Class I, Level B).^[1]
• In individuals with suspected CCS, ESC 2024 recommends choosing between them on the pre-test likelihood, patient characteristics that influence test performance (ability to exercise, likelihood of good image quality, expected radiation exposure, and risks or contraindications), and local expertise and availability (Class I, Level C).^[1]
• At her likelihood, both routes have Class I rows: in individuals with suspected CCS and low or moderate (more than 5% to 50%) pre-test likelihood of obstructive CAD, ESC 2024 recommends CCTA to diagnose obstructive CAD and to estimate the risk of MACE (Class I, Level A; Recommendation Table 8 is scoped to CCTA if available and supported by local expertise) and as the preferred modality to rule out obstructive CAD (Class I, Level B).^[1]
• In individuals with suspected CCS and moderate or high (more than 15% to 85%) pre-test likelihood of obstructive CAD, ESC 2024 recommends stress echocardiography (to diagnose myocardial ischaemia and estimate the risk of MACE), stress SPECT or, preferably, PET perfusion imaging, and stress CMR perfusion imaging (each to diagnose and quantify ischaemia and/or scar and estimate the risk of MACE; PET also to quantify myocardial blood flow), if available and supported by local expertise (each Class I, Level B).^[1]
• ESC 2024 reasoning: there is growing support for CCTA as a first-line test in the low or moderate (15%–50%) likelihood group; given the low prevalence of CAD in this group and its high negative predictive value, CCTA is the most effective diagnostic method to rule out obstructive CAD.^[1]
• Tests for ischaemia have better rule-in power than CCTA and should be selected if there is a moderate–high (more than 15% to 85%) likelihood; functional imaging also overcomes the limitations of CCTA in groups that include older patients with more extensive coronary calcification.^[1]
• ESC 2024 notes that temporal and spatial resolution remain technical limitations of CCTA that can hinder precision in adjudicating coronary stenosis severity, and that this is most problematic in older patients with heavily calcified coronary arteries, in whom functional testing may be more appropriate than CCTA.^[1]

Follow-up: What does the AHA/ACC 2021 chest pain guideline recommend for intermediate-high risk patients, and when would you not use CCTA?^[3][1]

• For intermediate-high risk patients with stable chest pain and no known CAD, AHA/ACC 2021 states that CCTA is effective for diagnosis of CAD, for risk stratification and for guiding treatment decisions (COR 1, LOE A), and that stress imaging (stress echocardiography, PET/SPECT MPI or CMR) is effective for diagnosis of myocardial ischaemia and for estimating the risk of MACE (COR 1, LOE B-R).^[3]
• Its text adds that, in intermediate-high risk patients with stable chest pain and no known CAD, CCTA is preferable in those under 65 years of age and not on optimal preventive therapies, while stress testing may be advantageous in those 65 years or older, because they have a higher likelihood of ischaemia and obstructive CAD.^[3]
• In the initial diagnostic management of individuals with suspected CCS, ESC 2024 does not recommend CCTA in severe renal failure (eGFR below 30 mL/min/1.73 m2), decompensated heart failure, extensive coronary calcification, fast irregular heart rate, severe obesity, inability to cooperate with breath-hold commands, or any other condition that can make good image quality unlikely (Class III, Level C; Recommendation Table 8 is scoped to CCTA if available and supported by local expertise).^[1]

Follow-up: Her CCTA is normal. What now?^[1]

• In ESC 2024 Figure 8, a normal CCTA almost completely rules out obstructive CAD in this patient, with a very low negative post-test likelihood (2%); the post-test likelihoods in that figure were calculated using likelihood ratios from recent meta-analyses.^[1]
• The likelihood models do not include ANOCA/INOCA, which always needs to be considered if symptoms persist after diagnostic testing that excludes obstructive CAD.^[1]

Branch C — High-risk anatomy

Examiner: A different patient: a 64-year-old man without diabetes has exertional angina despite a beta-blocker and a DHP-CCB. His LVEF is 60%. CCTA shows stenoses of 70% or more in the proximal segments of all three main coronary arteries; the left main stem is not stenosed. What next?

Strong answer:

• This is high event risk on CCTA: ESC 2024 Recommendation Table 14 recommends using test results to identify individuals at high risk of adverse events, and for CCTA these are left main disease with 50% or more stenosis, three-vessel disease with 70% or more stenosis, two-vessel disease with 70% or more stenosis including the proximal LAD, or one-vessel disease of the proximal LAD with 70% or more stenosis and FFR-CT of 0.8 or less (Class I, Level B).^[1]
• ESC 2024 defines high event risk, from large registries and historical RCTs, as a cardiac mortality rate above 3% per year.^[1]
• In individuals at high risk of adverse events (regardless of symptoms), ICA, complemented by invasive coronary pressure (FFR/iFR) when appropriate, is recommended with the aim of refining risk stratification and improving symptoms and cardiovascular outcomes by revascularisation (ESC 2024 Class I, Level A).^[1]
• In the diagnostic management of individuals with suspected CCS, when ICA is indicated, ESC 2024 recommends radial artery access as the preferred access site (Class I, Level A).^[1]

Follow-up: At ICA, the circumflex lesion looks 60%. Do you treat it on appearance?^[1]

• No. Haemodynamic relevance (FFR 0.80 or less, or iFR 0.89 or less) correlates poorly with visual diameter stenosis: in the PRIME-FFR and FAME data cited by ESC 2024, 31% of 40%–49% stenoses were haemodynamically significant, only 35% of 50%–70% stenoses were, and 20% of 71%–90% stenoses were not; only an estimated diameter stenosis above 90% predicted haemodynamic relevance with high accuracy (96% correct classification).^[1]
• During ICA, selective assessment of the functional severity of intermediate stenoses (typically around 40%–90% for non-left main stem or 40%–70% for left main stem by visual estimate) is recommended to guide the decision to revascularise, using FFR/iFR (significant at 0.8 or less or 0.89 or less, respectively; Class I, Level A) or QFR (significant at 0.8 or less; Class I, Level B).^[1]
• In CCS patients with multivessel disease, ESC 2024 recommends intracoronary pressure measurement (FFR or iFR) or computation (QFR) to guide lesion selection for intervention (Class I, Level A), but during ICA systematic and routine wire-based coronary pressure assessment of all coronary vessels is not recommended (Class III, Level A).^[1]

Follow-up: All three lesions are functionally significant. How do you decide between CABG and PCI?^[1]

• In CCS patients with LVEF above 35%, ESC 2024 recommends myocardial revascularisation, in addition to GDMT, for functionally significant three-vessel disease to improve long-term survival and to reduce long-term cardiovascular mortality and the risk of spontaneous MI (Class I, Level A).^[1]
• In CCS patients with significant three-vessel disease, preserved LVEF, no diabetes and insufficient response to GDMT, ESC 2024 recommends CABG over medical therapy alone to improve symptoms, survival and other outcomes (Class I, Level A).^[1]
• In CCS patients with preserved LVEF, no diabetes, insufficient response to GDMT and significant three-vessel disease of low-to-intermediate anatomic complexity in whom PCI can provide similar completeness of revascularisation to that of CABG, ESC 2024 recommends PCI, given its lower invasiveness and generally non-inferior survival (Class I, Level A).^[1]
• In CCS patients with multivessel obstructive CAD, ESC 2024 recommends calculating the SYNTAX score to assess the anatomical complexity of disease (Class I, Level B).^[1]
• In patients with CCS, for complex clinical cases, in particular when CABG and PCI hold the same level of recommendation, ESC 2024 recommends a Heart Team discussion (interventional cardiology, cardiac surgery, non-interventional cardiology and other specialties if indicated) to define the optimal treatment strategy, aimed at selecting the most appropriate treatment to improve patient outcomes and quality of life (Class I, Level C).^[1]
• ESC 2024 recommends that CCS patients scheduled for percutaneous or surgical revascularisation receive complete information about the benefits, risks, therapeutic consequences and alternatives to revascularisation, as part of shared clinical decision-making (Class I, Level C).^[1]
• AHA/ACC 2023: in CCD with complex 3-vessel disease or when the optimal treatment strategy is unclear, a Heart Team approach that includes interventional cardiology and cardiac surgery is recommended to improve patient outcomes (COR 1, LOE B-NR); in patients with CCD who require revascularisation for multivessel CAD with complex and diffuse CAD (eg, SYNTAX score above 33), it is reasonable to choose CABG over PCI to improve survival (COR 2a, LOE B-R).^[2]

Branch D — ISCHEMIA and ORBITA-2

Examiner: A third patient, aged 60, has CCS with an LVEF of 60%. CCTA showed two-vessel disease not involving the left main stem or the proximal LAD, and stress echocardiography shows stress-induced hypokinesia in 2 of 16 segments. He has no angina on a beta-blocker. He asks whether a stent would help him live longer.

Strong answer:

• He does not meet the ESC 2024 Recommendation Table 14 high-risk results: on stress echocardiography the threshold is 3 or more of 16 segments with stress-induced hypokinesia or akinesia, and the CCTA criterion for two-vessel disease is 70% or more stenosis including the proximal LAD (Class I, Level B).^[1]
• AHA/ACC 2023 adds that, in CCD, ICA for risk stratification is not routinely recommended in patients without LV systolic dysfunction, heart failure, stable chest pain refractory to GDMT, and/or noninvasive testing suggestive of significant (more than 50%) left main disease (COR 3: No benefit, LOE A).^[2]
• ISCHEMIA randomised 5179 patients with moderate or severe ischaemia to an initial invasive strategy (angiography and revascularisation when feasible) plus medical therapy or to an initial conservative strategy of medical therapy alone, with angiography if medical therapy failed; the primary outcome was a composite of cardiovascular death, MI, or hospitalisation for unstable angina, heart failure or resuscitated cardiac arrest.^[4]
• Over a median of 3.2 years there were 318 primary-outcome events in the invasive group and 352 in the conservative group; the cumulative event rate was 5.3% vs 3.4% at 6 months (difference 1.9 percentage points; 95% CI 0.8 to 3.0) and 16.4% vs 18.2% at 5 years (difference −1.8 percentage points; 95% CI −4.7 to 1.0).^[4]
• Results were similar for the key secondary outcome (cardiovascular death or MI); the incidence of the primary outcome was sensitive to the definition of MI, and a secondary analysis yielded more procedural MIs of uncertain clinical importance.^[4]
• Among patients with stable coronary disease and moderate or severe ischaemia, the investigators did not find evidence that an initial invasive strategy, compared with an initial conservative strategy, reduced the risk of ischaemic cardiovascular events or death from any cause over a median of 3.2 years; they note that the trial findings were sensitive to the definition of MI used.^[4]
• ESC 2024 reads ISCHEMIA (patients without left main disease nor reduced LVEF, with moderate-severe ischaemia at non-invasive testing) as showing no short-term survival benefit from early revascularisation, suggesting that most such patients should initially be treated conservatively with optimised GDMT.^[1]
• It also notes that patients assigned to the invasive strategy had significantly lower rates of spontaneous MI and greater improvement in angina-related health status than those assigned to the conservative strategy.^[1]
• In ISCHEMIA-EXTEND (follow-up up to 7 years), ESC 2024 reports a significant 2.2% absolute decrease in cardiovascular mortality favouring the initial invasive strategy (adjusted HR 0.78; 95% CI 0.63–0.96), most marked in multivessel CAD (70% or more diameter stenosis on CCTA; adjusted HR 0.68; 95% CI 0.48–0.97), but offset by a significant 1.2% absolute increase in non-cardiac mortality, without a significant difference in all-cause mortality (absolute decrease of −0.7%).^[1]

Follow-up: Six months later he has angina limiting his walking despite two antianginal drugs. What changes?^[1]

• In CCS patients with persistent angina or anginal equivalent despite guideline-directed medical treatment, ESC 2024 recommends myocardial revascularisation of functionally significant obstructive CAD to improve symptoms (Class I, Level A).^[1]
• In symptomatic CCS patients with significant single- or double-vessel disease not involving the proximal LAD and with insufficient response to GDMT, PCI is recommended to improve symptoms (ESC 2024 Class I, Level B).^[1]
• ESC 2024 text: for patients with obstructive CAD and refractory symptoms despite optimised GDMT, a referral for ICA may be considered to improve symptoms through revascularisation; optimisation by combining two or more antianginal drugs can safely be obtained over 6 weeks in almost all patients and should be awaited before referral to ICA.^[1]
• ORBITA-2 was a double-blind, placebo-controlled trial: patients with stable angina stopped all antianginal medications, had a 2-week symptom assessment phase, and 301 were then randomised 1:1 to PCI (151) or a placebo procedure (150) and followed for 12 weeks.^[8]
• The primary end point was the angina symptom score (range 0 to 79, higher scores indicating worse health status with respect to angina); at 12 weeks it was 2.9 with PCI and 5.6 with placebo (odds ratio 2.21; 95% CI 1.41 to 3.47; P below 0.001).^[8]
• The investigators concluded that, among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischaemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina.^[8]
• ESC 2024 notes that in the ORBITA trial (Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina), PCI did not provide short-term advantages compared with GDMT in reducing anginal frequency or physical limitations.^[1]

Branch E — First-line antianginal therapy

Examiner: A 66-year-old man with newly confirmed obstructive CCS, LVEF 55% and no heart failure has exertional angina. His resting heart rate is 78 b.p.m. Start his antianginal treatment.

Strong answer:

• In patients with CCS, ESC 2024 recommends tailoring the selection of antianginal drugs to the patient’s characteristics, comorbidities, concomitant medications, treatment tolerability and underlying pathophysiology of angina, also considering local drug availability and cost (Class I, Level C).^[1]
• In patients with CCS, ESC 2024 recommends short-acting nitrates for immediate relief of angina (Class I, Level B).^[1]
• Initial treatment with beta-blockers and/or CCBs to control heart rate and symptoms is recommended for most patients with CCS (ESC 2024 Class I, Level B); the table footnote warns that these drugs may require caution or may be contraindicated in certain patients with low BP (beta-blockers and DHP-CCB), DM (beta-blockers), atrioventricular conduction disorders (beta-blockers and non-DHP-CCB) and chronic obstructive pulmonary disease (non-cardioselective beta-blockers).^[1]
• The ESC text adds that the empirical approach of starting with a beta-blocker can be recommended in many patients with CCS, unless there are contraindications or other drugs are more suitable (e.g. patients with low heart rate and/or BP).^[1]
• If a beta-blocker is used for antianginal purposes, the aim should be to lower resting heart rate to 55–60 b.p.m.^[1]
• In patients with CCS, ESC 2024 says that, regardless of the initial strategy, response to initial antianginal therapy should be reassessed, and treatment adapted if adequate angina control is not achieved or if the initial treatment is poorly tolerated.^[1]
• AHA/ACC 2023: in patients with CCD and angina, antianginal therapy with either a beta blocker, CCB or long-acting nitrate is recommended for relief of angina or equivalent symptoms (COR 1, LOE B-R), and sublingual nitroglycerin or nitroglycerin spray is recommended for immediate short-term relief (COR 1, LOE B-NR).^[2]

Follow-up: Would you add ivabradine?^[1]

• Not in him. ESC 2024 does not recommend ivabradine as add-on therapy in patients with CCS, LVEF above 40% and no clinical heart failure (Class III, Level B).^[1]
• In patients with CCS, ESC 2024 says ivabradine should be considered as add-on antianginal therapy in those with LV systolic dysfunction (LVEF below 40%) and inadequate control of symptoms, or as part of initial treatment in properly selected patients (Class IIa, Level B).^[1]
• In patients with CCS, ESC 2024 does not recommend combining ivabradine with a non-DHP-CCB or other strong CYP3A4 inhibitors (Class III, Level B).^[1]
• AHA/ACC 2023: in patients with CCD and normal LV function, adding ivabradine to standard antianginal therapy is potentially harmful (COR 3: Harm, LOE B-R).^[2]

Branch F — Vasospastic angina

Examiner: A 48-year-old woman has episodes of chest pain at rest. An ECG recorded during one episode shows transient ST-segment elevation that resolves after sublingual nitrate. How do you confirm and treat vasospastic angina?

Strong answer:

• ESC 2024: VSA should be suspected when typical transient ST-segment elevations or depressions with U-wave changes are seen during an angina attack at rest, and in suspected VSA a resting 12-lead ECG recorded during angina is recommended (Class I, Level C).^[1]
• With suspected VSA and frequent symptoms, ambulatory ST-segment monitoring should be considered to identify ST-segment deviation during angina (ESC 2024 Class IIa, Level B).^[1]
• With suspected VSA and repetitive episodes of rest angina associated with ST-segment changes that resolve with nitrates and/or calcium antagonists, invasive coronary functional testing is recommended to confirm the diagnosis and to determine the severity of underlying atherosclerotic disease (ESC 2024 Class I, Level C).^[1]
• Acetylcholine is given by intracoronary bolus or graded infusion, first at a low dose or grade to assess endothelial dysfunction and then at a higher dose or grade to eventually induce microvascular and/or epicardial spasm.^[1]
• The test is positive for macrovascular spasm if symptoms occur with ischaemic ECG changes and an angiographic lumen reduction of 90% or more; with symptoms and ischaemic ECG changes but a lumen reduction below 90%, microvascular spasm is diagnosed.^[1]
• In patients with ANOCA/INOCA, for isolated VSA, calcium channel blockers are recommended to control symptoms and to prevent ischaemia and potentially fatal complications (ESC 2024 Class I, Level A), and nitrates should be considered to prevent recurrent episodes (ESC 2024 Class IIa, Level B).^[1]
• In severe VSA it may be necessary to give unusually high doses of calcium antagonist (diltiazem 2 × 200 mg daily or higher, up to 960 mg daily) or even a combination of a non-dihydropyridine (such as diltiazem) with a dihydropyridine calcium blocker (such as amlodipine).^[1]
• In patients with ANOCA/INOCA and evidence of overlapping endotypes, combination therapy with nitrates, calcium channel blockers and other vasodilators may be considered (ESC 2024 Class IIb, Level B).^[1]

Follow-up: Why does the diagnosis matter?^[1]

• ESC 2024 states that VSA is associated with major adverse events, including sudden cardiac death, acute MI and syncope, and that coexisting microvascular angina and epicardial VSA is associated with a worse prognosis.^[1]