Kare Tang

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI

Background Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave‐free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. Methods We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR‐guided or FFR‐guided coronary revascularization. The primary end point was the 1‐year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. Results At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, ‐0.2 percentage points; 95% confidence interval [CI], ‐2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). Conclusions Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE‐FLAIR ClinicalTrials.gov number, NCT02053038.)

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial

BACKGROUND Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. METHODS ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. FINDINGS ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. INTERPRETATION In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. FUNDING NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease: Physiology-Stratified Analysis of ORBITA

Background: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. Methods: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. Results: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], –4.0 to 45.5; P=0.100) with no interaction of FFR (Pinteraction=0.318) or iFR (Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70–1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR (Pinteraction<0.00001) and decreasing iFR (Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96–2.80; P=0.072) with no detectable evidence of interaction with FFR (Pinteraction=0.849) or iFR (Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30–4.72; P=0.006) but neither FFR (Pinteraction=0.693) nor iFR (Pinteraction=0.761) modified this effect. Conclusions: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Early targeted brain COOLing in the cardiac CATHeterisation laboratory following cardiac arrest (COOLCATH).

INTRODUCTION Trials demonstrate significant clinical benefit in patients receiving therapeutic hypothermia (TH) after cardiac arrest. However, incidence of mortality and morbidity remains high in this patient group. Rapid targeted brain hypothermia induction, together with prompt correction of the underlying cause may improve outcomes in these patients. This study investigates the efficacy of Rhinochill, an intranasal cooling device over Blanketrol, a surface cooling device in inducing TH in cardiac arrest patients within the cardiac catheter laboratory. METHODS 70 patients were randomized to TH induction with either Rhinochill or Blanketrol. Primary outcome measures were time to reach tympanic ≤34 °C from randomisation as a surrogate for brain temperature and oesophageal ≤34 °C from randomisation as a measurement of core body temperature. Secondary outcomes included first hour temperature drop, length of stay in intensive care unit, hospital stay, neurological recovery and all-cause mortality at hospital discharge. RESULTS There was no difference in time to reach ≤34 °C between Rhinochill and Blanketrol (Tympanic ≤34 °C, 75 vs. 107 mins; p=0.101; Oesophageal ≤34 °C, 85 vs. 115 mins; p=0.151). Tympanic temperature dropped significantly with Rhinochill in the first hour (1.75 vs. 0.94 °C; p<0.001). No difference was detected in any other secondary outcome measures. Catheter laboratory-based TH induction resulted in a survival to hospital discharge of 67.1%. CONCLUSION In this study, Rhinochill was not found to be more efficient than Blanketrol for TH induction, although there was a non-significant trend in favour of Rhinochill that potentially warrants further investigation with a larger trial.

23 The influence of collateral regression post coronary chronic total occlusion (cto) percutaneous coronary intervention (pci) on donor vessel coronary pressure-derived measurements

Background There is strong evidence of FFR guided treatment in multi-vessel disease. The presence of a concomitant CTO may influence the FFR measurement in donor vessel as suggested in previous studies and reports. This has an important implication on clinical decision making for complete revascularisation in patients with chronic total occlusion. We sought to investigate the influence of collateral regression after successful CTO recanalisation on donor vessel pressure-derived indices. Methods The study participants were patients with angina who had RCA CTO. 28 out of 34 consecutive patients underwent successful PCI to RCA CTOs during the study period and completed the follow study (at 3 months post CTO PCI) were included in this analysis. Coronary pressure-derived indices (resting PD/PA, iFR and FFR) were measured pre and post successful RCA CTO PCI in donor vessels and at follow up procedures. Results The mean age was 62.38 years. The mean estimated CTO duration was 238.72 weeks and CTO length was 32.44 mm. 25 patients had ischaemia and or viability in the RCA territory assessed with cardiac MRI. LAD was the major donor vessel in 24 patients and LCX was the minor donor vessel in 4 patients. Percent stenosis on QCA in the major and minor donor vessel were 40.6% and 35.1% respectively. The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI and at follow-up procedures in major donor vessel were (0.893, 0.862, 0.764), (0.907, 0.886, 0.753) and (0.918, 0.901, 0.787) respectively. The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI and at follow-up procedures in minor donor vessel were (0.979, 0.966, 0.890), (0.983, 0.979, 0.880) and (0.981, 0.974, 0.898) respectively. The changes in coronary pressure-derived indices pre and post RCA CTO PCI and at follow up procedures are summarised in table 1. In major donor vessel, there was significant changes in the difference between follow up and pre-CTO PCI values for Pd/Pa, iFR and FFR values (p values 0.006, 0.003 and 0.047 respectively). There was also significant change in the difference between follow up and post-CTO PCI FFR value (P value 0.002). FFR collateral reduced significantly at follow-up (p value 0.000). Conclusion Successful recanalisation of a RCA CTO results in increase in major donor vessel coronary pressure-derived indices at follow up procedure associated with the regression of collateral function. In patients with multi-vessel disease, the expected change and the optimal timing to perform PCI in donor vessel should be considered when planning multi-vessel revascularisation in this setting.Abstract 23 Table 1 Coronary pressure-derived indices pre and post RCA CTO PCI and at follow up procedures (FU:Follow-up, PCI:Percutaneous Coronary Intervention, FFR: Fractional Flow Reserve, CTO: Chronic Total Occlusion)

24 The physiological impact of coronary chronic total occlusion (cto) percutaneous coronary intervention (pci) on donor vessel coronary pressure-derived measurements and the influence of collateral circulation

Background There is strong evidence of FFR guided treatment in multi-vessel disease. Multi-vessel disease is present in up to 66% of patients with CTO in a large registry analysis. The presence of a concomitant CTO may influence the FFR measurement in donor vessel as suggested in previous studies and reports. This has an important implication on clinical decision making for complete revascularisation in patients with chronic total occlusions. There is a growing interest on the influence of collateral circulation, flow, amount of myocardium supplied by donor artery to a CTO and the impact of CTO revascularisation on donor vessel pressure-derived indices. We sought to investigate the physiological impact of CTO recanalisation on donor vessel pressure-derived indices. Methods The study participants were patients with angina who had RCA CTO. 34 out of 40 consecutive patients underwent successful PCI to RCA CTOs during the study period were included in the analysis. Coronary pressure-derived indices (resting Pd/Pa, iFR and FFR) were measured pre and post successful RCA CTO PCI in donor vessels. Donor vessel characteristics were graded using the Rentrop and colloateral connexion grading classification. Results The mean age was 61.76 years. The mean estimated CTO duration was 238.72 weeks and CTO length was 32.44 mm. 31 patients had ischaemia and or viability in the RCA territory assessed with cardiac MRI. LAD was the predominant donor vessel in 30 patients and LCX was the minor donor vessel in 4 patients. Percent stenosis on QCA in the predominant and minor donor vessel were 41.43% and 35.05% respectively. The angiographic details are as outlined in table 1. The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI in major donor vessel were (0.891, 0.858, 0.759) and (0.903, 0.882, 0.746) respectively. iFR in the major donor vessel increased from 0.858 to 0.882 (difference, 0.02412 (0.00573 to 0.04250); p=0.012). There were no significant difference in resting Pd/Pa and FFR pre and post CTO PCI (p=0.109 and p=0.388 respectively). The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI in minor donor vessel were (0.982, 0.969, 0.894) and (0.985, 0.979, 0.885) respectively. There were no significant difference in resting Pd/Pa, iFR and FFR pre and post CTO PCI in minor donor vessel (p=0.534, p=0.152, p=0.183 respectively). The mean collateral FFR was 0.310. The mean total ischaemic burden on baseline cardiac MRI in RCA territory was 12.6%. Conclusion Successful recanalisation of a RCA CTO results in increase in iFR but no significant difference was seen in resting Pd/Pa and FFR pre-RCA CTO PCI and immediately post recanalisation in predominant donor vessel. Complete collateral regression was not observed in all patients immediately post RCA CTO PCI and this may account for the non-significant change in FFR values.Abstract 24 Table 1 Angiographic Characteristics

32 The Impact of Haemoglobin Reduction on Short- and Long-Term Mortality Following Primary Percutaneous Coronary Intervention for St-Elevation Myocardial Infarction-analysis from a Real World Stemi Population

Introduction Mortality following ST-elevation myocardial infarction has declined significantly with the advent of primary PCI (PPCI). Concurrent use of antiplatelet agents has further decreased complication rates and mortality; however, these agents confer an increased bleeding risk, an independent risk factor for mortality. This retrospective study assesses the effect of blood loss on short- and long-term mortality and its association with clinical characteristics in a real world population of patients undergoing PPCI at a tertiary referral centre in the UK. Methods All patients accepted for PPCI within the period of September 2009 to November 2011 were eligible for inclusion in the study. Patient data were obtained from our Cardiac Services Database System (Phillips CVIS) and mortality data were gathered from the Summary Care Record (SCR) database. Statistical comparisons of continuous variables were made by one-way ANOVA. Categorical variables were compared using the chi-squared test. A P value of < 0.05 was taken to indicate statistical significance. Results 1403 patients with recorded admission and discharge haemoglobin levels were included in this analysis. Characteristics and clinical outcomes were compared in three groups according to the degree of haemoglobin reduction (Table 1). Patients with a reduction in haemoglobin were more likely to be female, slightly older and have prior history of MI. Patients with a significant reduction in haemoglobin were more likely to have received abciximab. Thirty-day mortality was significantly higher in the group with a haemoglobin drop (Table 1) as was overall mortality (hazard ratio 1.8, 95% CI 1.2–2.5) during a mean follow-up period of 2.1 years (Figure 1). Abstract 32 Figure 1 Kaplan-Meier survival curves Abstract 32 Table 1 Clinical characteristics and outcomes No change in Hb, g/dl (n = 374) Hb reduction 0.1–1 g/dl (n = 517) Hb reduction >1 g/dl (n = 512) p-value Risk factorsMean Age (+/- SD)MaleHypertensionDiabetes MellitusPrevious MIPrevious CABG 64.4 +/- 14290 (77.5%)110 (29.4%)53 (14.2%)59 (15.8%)9 (2.4%) 63.1 +/- 13383 (74%)132 (25.5%)63 (12.2%)61 (11.8%)14 (2.7%) 67.5 +/- 13355 (69.3%)140 (27.3%)64 (12.5%)51 (10%)11 (2.1%) <0.0001*0.021*0.3700.6560.031*0.843 Procedure relatedRadialAbciximab use 113 (30.2%)114 (30.5%) 147 (28.4%)161 (31.1%) 130 (25.4%)208 (40.6%) 0.2630.0001* Clinical outcome30-day mortalityOverall mortality 15 (4%)36 (9.6%) 12 (2.3%)46 (8.9%) 42 (8.2%)79 (15.4%) <0.0001*0.0019* Conclusions Our retrospective analysis in a large cohort of patients confirms recent data suggesting an adverse association between a reduction in haemoglobin following PPCI and long-term mortality. Further work is required on strategies to reduce bleeding risk and hence improve clinical outcome following PPCI.

036 COMPARISON OF CLINICAL CHARACTERISTICS AND OUTCOMES IN PATIENTS WITH LEFT BUNDLE BRANCH BLOCK VERSUS ST ELEVATION MYOCARDIAL INFARCTION REFERRED FOR PRIMARY PCI

Aims Current national and international guidelines continue to recommend activation of the primary percutaneous coronary intervention (PPCI) pathway in patients presenting with chest pain and presumed new-onset left bundle branch block (LBBB). Previous research has suggested that a lower proportion of patients presenting with LBBB require emergency intervention. In this study we have compared baseline clinical characteristics, angiographic findings and subsequent outcome in patients with LBBB versus ST-elevation myocardial infarction (STEMI) referred to our tertiary centre for PPCI. Table 1 Clinical characteristics Risk factor LBBB (n=155) STEMI (n=1720) p Value Mean age (±SD) 70.35±11.9 64.95±14.0 <0.0001 Male 87 (56.1%) 1228 (71.4%) <0.0001 Hypertension 70 (45.2%) 668 (38.8%) 0.127 Hypercholesterolaemia 52 (33.5%) 512 (29.8%) 0.327 Diabetes mellitus 26 (16.8%) 201 (11.7%) 0.063 Previous MI 36 (23.2%) 205 (11.9%) <0.0001 Previous CABG 10 (6.5%) 44 (2.6%) 0.005 Methods All patients accepted for PPCI within the period of September 2009 to November 2011 were included in the study. Patient data obtained from our Cardiac Services Database System (Phillips CVIS) were analysed and angiographic images reviewed on our Cardiac Image Database (McKesson Horizon). Mortality data were gathered from the Summary Care Record (SCR) database. Statistical comparisons of continuous variables were made by an unpaired t test. Categorical variables were compared using the χ2 test. A p value of <0.05 was considered to indicate statistical significance. Results During the study period, 1875 patients were referred for PPCI of whom 155 (8.3%) had LBBB. Compared with STEMI, patients with LBBB were significantly older, more likely to be female and have prior history of MI and CABG (table 1). Patients with LBBB had similar door-to-balloon (DTB) and call-to-balloon (CTB) times. PCI was performed in 40 (26%) patients with LBBB although an acutely occluded culprit vessel was found in only 19 (12.2%) patients (table 2). Furthermore, 85 (54.8%) patients had non-flow limiting coronary artery disease and of those with significant disease 12 (7.7%) patients required CABG (figure 1). Overall, an acute coronary syndrome (defined as ischaemic chest pain with positive troponin) was confirmed in only 67 (43.2%) of patients presenting with LBBB. 30-day mortality was similar between LBBB and STEMI patients (table 2). However, during a mean follow-up period of 2.1 years, overall mortality was significantly higher in the LBBB group compared to STEMI (HR 2.01, 95% CI 1.26 to 3.20) (figure 2). Conclusions Our study shows that, in contrast to STEMI, only a small proportion of patients presenting with chest pain and LBBB had an acutely occluded coronary artery. Although short-term mortality was similar between the two groups, long-term outcome was significantly worse in patients with LBBB. Further work is needed to identify those patients presenting with LBBB who are most likely to have an acute coronary occlusion, in order to facilitate the appropriate use of emergency coronary angiography and PPCI. Table 2 Clinical outcomes Outcome LBBB (n=155) STEMI (n=1720) p Value Door-to-balloon time (min±SD) 40±17 37±25 0.710 Call-to-balloon time (min±SD) 128±36 120±47 0.263 Acute coronary occlusion 19 (12.2%) 1096 (63%) <0.0001 PCI performed 40 (26%) 1430 (83%) <0.0001 30-day mortality (all) 8 (5.2%) 120 (6.9%) 0.391 30-day mortality (PCI) 3/40 (7.5%) 94/1430 (6.6%) 0.825 30-day mortality (no PCI) 5/115 (4.3%) 26/290 (8.9%) 0.115 Overall mortality 32 (27.8%) 240 (13.9%) 0.023 Figure 1 Clinical outcome in patients with LBBB. Figure 2 Kaplan-Meier comparison of survival curves.

PAR-1 inhibitor antiplatelet agents: performance below par?

Antiplatelet agents reduce mortality from acute coronary syndrome (ACS). Aspirin, clopidogrel, glycoprotein IIb/IIIa inhibitors and newer agents such as prasugrel or ticagrelor are now used routinely in ACS and with percutaneous coronary intervention (PCI). Although currently available antiplatelet therapies are highly effective, they cannot nullify atherothrombotic risk. Recurrent ischaemic events occur despite treatment with aspirin and/or clopidogrel, the most widely prescribed antiplatelet drugs. Breakthrough ischaemic events may reflect the inability of these agents to fully suppress the stimulus for platelet activation at sites of plaque disruption, or they may be the result of resistance to the antiplatelet effects of aspirin or clopidogrel. Aggressive risk factor profiles, genetic background and a heightened thrombotic state can all play a part in the recurrence of ischaemic events. One of the most feared complications in patients with ACS undergoing PCI is stent thrombosis (ST), which has an unacceptably high mortality rate of about 45%. The rate of stent thrombosis remains high even in the newer studies where state-of-the-art antiplatelet therapy was deployed. For instance, in the Therapeutic Outcomes by Optimizing Platelet Inhibition with PrasugreleThrombolysis in Myocardial Infarction (TRITONeTIMI) 38 trial of prasugrel, the rates of stent thrombosis in the patients treated with prasugrel and clopidogrel were 1.1% and 2.4%, respectively at 450 days follow-up. The Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trials confirmed that the