Paul Rocchiccioli

Discordance between Resting and Hyperemic Indices of Coronary Stenosis Severity: The VERIFY 2 Study (A Comparative Study of Resting Coronary Pressure Gradient, Instantaneous Wave-Free Ratio and Fractional Flow Reserve in an Unselected Population Referred for Invasive Angiography)

Background—Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR).We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement. Methods and Results—This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ⩽0.80 was calculated using binary cutoff values of ⩽0.90 for iFR and ⩽0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 21% versus 20.2% (P=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (P=0.55). Conclusions—Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02377310.

Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Angina CorMicA) stratified medicine clinical trial

Background Coronary angiography is performed to assess for obstructive coronary artery disease (CAD), but “nonobstructive CAD” is a common finding. Microvascular or vasospastic angina may be relevant, but routine confirmatory testing is not evidence based and thus rarely performed. Aim The aim was to assess the effect of stratified medicine guided by coronary function testing on the diagnosis, treatment, and well-being of patients with angina and nonobstructive CAD. Design The BHF CorMicA trial is a prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03193294). All-comers referred for elective coronary angiography for investigation of suspected CAD will be screened. Following informed consent, eligible patients with angina and nonobstructive CAD will be randomized 1:1 immediately in the catheter laboratory to either coronary artery function–guided diagnosis and treatment (intervention group) or not (control group). Coronary function will be assessed using a pressure-temperature–sensitive guidewire and adenosine followed by pharmacological testing with intracoronary acetylcholine. Patients will be stratified into endotypes with linked therapy. The primary outcome is change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and diagnostic certainty), and clinical utility (impact on treatment and investigations). Health status is a key secondary outcome assessed according to the following domains: quality of life, treatment satisfaction, illness perception, physical activity, and anxiety-depression score. Patients with obstructive disease who are not randomized will form a registry group who will be followed up as a comparator for secondary outcomes including health status. Health and economic outcomes will be evaluated in the longer term using electronic health record linkage. Value CorMicA is a proof-of-concept clinical trial of a disruptive stratified intervention with potential benefits to patients and health care providers.

A keen eye for risk

A 56 year old woman was referred to the rapid access chest pain clinic with stable angina pectoris. Her only cardiovascular risk factor was a family history of atherosclerosis, with her mother suffering from myocardial infarction at 50. Her body mass index was 20 kg/m2 and the main abnormality on examination was the eye sign shown in fig 1. Fasting serum cholesterol and low density lipoprotein were both markedly raised at 12.2 mmol/L and 9.3 mmol/L, respectively. Triglyceride levels were relatively normal at 1.9 mmol/L. Given the history, examination, and lipid abnormality, what further blood test would confirm the underlying diagnosis? Fig 1 Eye signs in cardiovascular disease: when the patient looks upward, a symmetrical abnormality is visible in both eyes Genetic blood testing for low density lipoprotein receptor mutation to confirm the diagnosis of …

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov).

29 Verify 2 (Final Results): A Comparison of FFR vs Resting Indices of Stenosis Severity for Decision Making in the cath lab. nct02377310

Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are resting indices of the functional significance of a coronary stenosis measured without inducing hyperaemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when both are compared to FFR. Hypotheses In comparison to an FFR for all strategy, revascularisation decisions based on either binary cut-off values for iFR or Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement. Methods A prospective study in consecutive patients undergoing FFR assessment for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR and hyperaemic iFR (HiFR). Diagnostic accuracy vs FFR was calculated firstly using binary cut-off values of <0.90 for iFR and ≤0.92 for Pd/Pa and again using the adenosine zones for iFR of 0.86–0.93 and Pd/Pa of 0.87–0.94 in the hybrid strategy. The pre-determined sample size established prior to the start of the study was 254 vessels. Results 197 patients with 257 moderate stenoses (mean DS 48%) were studied. 127 (49.4%) vessels were in patients with stable angina and 79 (31%) vessels in patients with recent (>72 h) acute coronary syndromes. Using binary cut-off values diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 20.6% vs 19.8%, p = 0.86. In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outwith the adenosine zone. Rates of misclassification were 9.4% vs 11.9%, p = 0.55. Sensitivity analyses showed no impact of a variety of angiographic measures of stenosis severity or myocardial area at risk. Comparing proximal stenoses (Syntax segments 1, 11, 5 and 6) to all other lesions and using the RESOLVE cutoff of ≤0.90 for iFR the level of misclassification was 27.7% vs 15.2%, p = 0.014 (Table 1). Using the iFR cutoff of <0.90 the level of misclassification was 26.3% vs 16.2%, p = 0.05.Abstract 29 Table 1 Sensitivity analyses for iFr in proximal vs distal segments using ≤ 0.9 cut-off compared with FFR. Proximal vs Distal – comparision of 2 proportions: 95% CI = (0.0248, 0.225), Pearson Chi-sq test of assoc: p = 0.014 Fisher’s exact test: p = 0.021 Conclusion When compared to FFR, binary cut-offs for iFR and Pd/Pa results in misclassification of 1 in 5 lesions. Using a hybrid strategy approximately half of the patient do not receive adenosine but 1 in 10 lesions is still misclassified. Neither resting index or strategy can be recommended for decision making in the cath lab. Operators wishing to use resting indices of stenosis severity should be particularly cautious when interpreting data from proximal stenoses in prognostically important vessels.Abstract 29 Figure 1 Receiver operator characteristic curves demonstrating diagnostic accuracy of iFR, Pd/Pa and HiFR in reference to FFR <0.80 Delong’s test p-values for 2 correlated ROC curves: IFR vs iFR: 0.0001, HiFR vs Pd/Pa: 0.0003Abstract 29 Figure 2 Total number of inappropriate PCI’s and incomplete revascularisations when binary cut-offs are utilised for Pd/Pa and iFR. Numbers shown are % of total, n = 257