The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol.

BACKGROUND: Percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated. AIMS: The ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3. METHODS: Patients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up. RESULTS: The co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test. CONCLUSION: The feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's

Mineralocorticoid receptor antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction: The MINIMIZE STEMI trial

Background: Mineralocorticoid receptor antagonist (MRA) therapy has been shown to prevent adverse left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients with heart failure. Whether initiating MRA therapy prior to primary percutaneous coronary intervention (PPCI) accrues additional benefit of reducing myocardial infarct size and preventing adverse LV remodeling is not known. We aimed to investigate whether MRA therapy initiated prior to reperfusion reduces myocardial infarct (MI) size and prevents adverse LV remodeling in STEMI patients. Methods: STEMI patients presenting within 12 hours and with a proximal coronary artery occlusion with Thrombolysis In Myocardial Infarction flow grade 0 were consented and randomized to either an intravenous bolus of potassium canrenoate, followed by oral spironolactone for 3 months or matching placebo. The primary endpoint was MI size by cardiovascular magnetic resonance at 3 months. Results: Sixty-seven patients completed the study. There was no significant difference in the final MI size at 3 months between the 2 groups (placebo: 17 ± 11%, MRA: 16 ± 10%, P = .574). There was also no difference in acute MI size (26 ± 16% versus 23 ± 14%, P = .425) or myocardial salvage (26 ± 12% versus 24 ± 8%, P = .456). At follow-up, there was a trend towards an improvement in LVEF (placebo: 49 ± 8%, MRA: 54 ± 11%, P = .053), and the MRA group had significantly greater percentage decrease in LVEDV (mean difference: −12.2 (95% CI −20.3 to −4.4)%, P = .003) and LVESV (mean difference: −18.2 (95% CI −30.1 to −6.3)%, P = .003). Conclusion: This pilot study showed no benefit of MRA therapy in reducing MI size in STEMI patients when initiated prior to reperfusion, but there was an improvement in LV remodeling at 3 months. Adequately powered studies are warranted to confirm these findings

The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol

BackgroundPercutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated.AimsThe ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3.MethodsPatients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up.ResultsThe co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test.ConclusionThe feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's

Impact of Percutaneous Revascularization on Exercise Hemodynamics in Patients With Stable Coronary Disease

Background: Recently, the therapeutic benefits of percutaneous coronary intervention (PCI) have been challenged in patients with stable coronary artery disease (SCD). Objectives: The authors examined the impact of PCI on exercise responses in the coronary circulation, the microcirculation, and systemic hemodynamics in patients with SCD. Methods: A total of 21 patients (mean age 60.3 ± 8.4 years) with SCD and single-vessel coronary stenosis underwent cardiac catheterization. Pre-PCI, patients exercised on a supine ergometer until rate-limiting angina or exhaustion. Simultaneous trans-stenotic coronary pressure-flow measurements were made throughout exercise. Post-PCI, this process was repeated. Physiological parameters, rate-limiting symptoms, and exercise performance were compared between pre-PCI and post-PCI exercise cycles. Results: PCI reduced ischemia as documented by fractional flow reserve value (pre-PCI 0.59 ± 0.18 to post-PCI 0.91 ± 0.07), instantaneous wave-free ratio value (pre-PCI 0.61 ± 0.27 to post-PCI 0.96 ± 0.05) and coronary flow reserve value (pre-PCI 1.7 ± 0.7 to post-PCI 3.1 ± 1.0; p < 0.001 for all). PCI increased peak-exercise average peak coronary flow velocity (p < 0.0001), coronary perfusion pressure (distal coronary pressure; p < 0.0001), systolic blood pressure (p = 0.01), accelerating wave energy (p < 0.001), and myocardial workload (rate-pressure product; p < 0.01). These changes observed immediately following PCI resulted from the abolition of stenosis resistance (p < 0.0001). PCI was also associated with an immediate improvement in exercise time (+67 s; 95% confidence interval: 31 to 102 s; p < 0.0001) and a reduction in rate-limiting angina symptoms (81% reduction in rate-limiting angina symptoms post-PCI; p < 0.001). Conclusions: In patients with SCD and severe single-vessel stenosis, objective physiological responses to exercise immediately normalize following PCI. This is seen in the coronary circulation, the microcirculation, and systemic hemodynamics

Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease: Primary Results of the International Multicenter iFR GRADIENT Registry.

The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings.This article is freely available via Open Access. Please click on the Additional Link above to access the full-text via the publisher's site

Fractional Flow Reserve: Does a Cut-off Value add Value?

Fractional flow reserve (FFR) has been shown to improve outcomes when used to guide percutaneous coronary intervention (PCI). There have been two proposed cut-off points for FFR. The first was derived by comparing FFR against a series of non-invasive tests, with a value of ≤0.75 shown to predict a positive ischaemia test. It was then shown in the DEFER study that a vessel FFR value of ≥0.75 was associated with safe deferral of PCI. During the validation phase, a ‘grey zone’ for FFR values of between 0.76 and 0.80 was demonstrated, where a positive non-invasive test may still occur, but sensitivity and specificity were sub-optimal. Clinical judgement was therefore advised for values in this range. The FAME studies then moved the FFR cut-off point to ≤0.80, with a view to predicting outcomes. The ≤0.80 cut-off point has been adopted into clinical practice guidelines, whereas the lower value of ≤0.75 is no longer widely used. Here, the authors discuss the data underpinning these cut-off values and the practical implications for their use when using FFR guidance in PCI

Impact of right atrial pressure on fractional flow reserve calculation in the presence of a chronic total occlusion

Background : The aim of this study was to assess the impact of right atrial pressure (Pra) on non-CTO vessels FFR measurements in patients with a chronic total occlusion. Methods : Consecutive patients who underwent PCI for a CTO of the right coronary artery (RCA) were included. Prior to RCA recanalization, FFR and FFRmyo were measured in non-CTO vessels. FFR was calculated using the Pd/Pa equation during maximum hyperaemia and also accounting for right atrial pressure (Pd-Pra/Pa-Pra). Non-CTO vessels were characterised as major or minor donors based on angiographic assessment of provided collaterals. Results : FFR and FFRmyo were measured in 68 arteries (34 LAD and 34 Cx) in 34 consecutive patients with successful RCA CTO PCI. Patients' mean age was 62 ± 10 years old and 88% were male. Mean left ventricular ejection fraction was 51% ± 20. During maximum hyperaemia, mean Pra, Pa, and Pd were 4.1 ± 3.8 mm Hg, 82.6 ± 12.2 mm Hg, and 63.8 ± 14.3 mm Hg, respectively. In the major donor vessel, FFRmyo showed a difference of 0.007 to FFR (0.760 ± 0.113 vs. 0.767 ± 0.112, p = 0.004). In the minor donor vessel the difference was 0.004 (0.895 ± 0.067 vs. 0.899 ± 0.065, p < 0.001). There was a strong positive correlation between the FFR and FFRmyo in both the major and minor donor vessel groups (r = 0.993, p < 0.001 and r = 0.996, p < 0.001 respectively). Conclusion: In the presence of a CTO, RA pressure adjustment of FFR in the non-CTO vessels leads to trivial numerical changes, which are statistically significant but clinically negligible

Serial Fractional Flow Reserve Measurements Post Coronary Chronic Total Occlusion Percutaneous Coronary Intervention

Background: The aim of this study was to evaluate the functional result of chronic total occlusion percutaneous coronary intervention (PCI) measured by fractional flow reserve (FFR) immediately post the index procedure and at short-term follow-up. Methods and Results: This was a prospective single-center observational study. Consecutive patients with right coronary artery chronic total occlusion scheduled for elective PCI were included. FFR measurements were performed immediately after successful PCI and at 4 months follow-up. Twenty-six patients completed baseline and follow-up measurements. Mean age was 61.2±9.7 years, 88.5% of the patients were male, and 19.2% were diabetic. The mean FFR immediately after successful chronic total occlusion PCI was 0.82±0.10 and significantly increased to 0.89±0.07 at 4 months (P<0.001). The FFR increased in 77% of the patients with a mean absolute increase of 0.07±0.08. The incidence of FFR ≤0.80 immediately after PCI was significantly higher amongst patients with subintimal versus intraplaque recanalization (23% versus 12%; P=0.03). At 4 months, FFR ≤0.80 was found only in 2 patients with subintimal recanalization. At follow-up, 42.7% of the patients continued to have an FFR <0.90. Conclusions: Post chronic total occlusion PCI, FFR increased significantly at short-term follow-up compared with measurements post index procedure. Because FFR remained <0.90 in many cases, further efforts should be made to optimize procedural results

Mineralocorticoid receptor antagonist pretreatment to MINIMISE reperfusion injury after ST-elevation myocardial infarction (The MINIMISE STEMI Trial): Rationale and Study Design

Clinical Cardiology385259-26