Effects of stent postdilatation during primary PCI for STEMI: Insights from coronary physiology and optical coherence tomography.

OBJECTIVES: This study aimed to assess the impact of stent optimization by NC-balloon postdilatation (PD) during primary-PCI for STEMI with the use of coronary physiology and intracoronary imaging. METHODS: This was a prospective observational study (ClinicalTrials.gov:NCT02788396). Optical coherence tomography (OCT) and physiological measurements were performed immediately before and after PD with the operators blinded to all measurements. The index of microcirculatory resistance (IMR), coronary flow reserve (CFR) and fractional flow reserve (FFR) were measured. OCT analysis was performed for assessment of stent expansion, malapposition, in-stent plaque-thrombus prolapse (PTP) and stent-edge dissections (SED). The change in IMR before and after PD as a measure of microvascular injury was the primary objective of the study. RESULTS: Thirty-two STEMI patients undergoing primary-PCI had physiological measurements before and after PD. All patients received second-generation DES (diameter 3.1 ± 0.5 mm, length 29.9 ± 10.7 mm) and postdilatation with NC-balloons (diameter 3.6 ± 0.6 mm, inflation pressure 19.3 ± 2.0 atm). IMR (44.9 ± 25.6 vs. 48.8 ± 34.2, p = 0.26) and CFR (1.60 ± 0.89 vs. 1.58 ± 0.71, p = 0.87) did not change, while FFR increased after PD (0.91 ± 0.08 vs. 0.93 ± 0.06, p = 0.037). At an individual patient level, IMR increased in half of the cases. PD improved significantly absolute and relative stent expansion, reduced malapposition, and increased PTP. There was no difference in clinically relevant SED. CONCLUSION: In this exploratory, hypothesis-generating study, postdilatation during primary-PCI for STEMI improved stent expansion, apposition and post-PCI FFR, without a significant effect on coronary microcirculation overall. Nevertheless, IMR increased in a group of patients and larger studies are warranted to explore predictors of microcirculatory response to postdilatation.

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

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 .).

Contemporary management of stent thrombosis: Predictors of mortality and the role of new-generation drug-eluting stents.

OBJECTIVES: We sought to evaluate mortality predictors and the role of new-generation drug-eluting stents (NG-DES) in stent thrombosis (ST) management. BACKGROUND: No data are available regarding the outcome of patients with ST after interventional management that includes exclusively NG-DES. METHODS: Patients with definite ST of DES or BMS who underwent urgent/emergent angiography between 2015 and 2018 at our institution were considered for the study. After excluding patients who achieved TIMI-flow<2 after intervention or received an old-generation stent, 131 patients were included. Management classification was stent or non-stent treatment (medical management, thromboaspiration, balloon-angioplasty). Follow-up was performed to document all-cause death (ACD) and target-lesion-revascularization (TLR) that was used for censorship. RESULTS: Mode of presentation was STEMI in 88% and UA/NSTEMI in 12%. Type of ST was early, late, and very late in 11, 4, and 85%, respectively. Eighty four patients received stent and 47 non-stent treatment. After 926 ± 34 days, 21 ACDs, 7 TLRs and no cases of definite, recurrent ST were observed. Univariate predictors of in-hospital mortality were LVEF and presentation with shock or cardiac arrest. For patients discharged alive, non-stent treatment (HR 4.2, p = .01), TIMI-2 flow (HR 7.4, p = .002) and GFR < 60 mL/min (HR 3.8, p = .01) were independent predictors of ACD. The stent-treatment group had significantly better ACD-free survival after discharge, both unadjusted (p = .022) and adjusted (p = .018). CONCLUSIONS: After ST management, different predictors were observed for in-hospital mortality and mortality in patients discharged alive. The better outcome with NG-DES treatment is a novel observation, warranting further studies to elucidate if it is associated with stent-related or patient-related factors.

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.

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.

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.

The impact of coronary chronic total occlusion percutaneous coronary intervention upon donor vessel fractional flow reserve and instantaneous wave-free ratio: Implications for physiology-guided PCI in patients with CTO.

OBJECTIVE: To investigate the immediate and short term impact of right coronary artery (RCA) chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) upon collateral donor vessel fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). BACKGROUND: CTO PCI influences collateral donor vessel physiology, making the indication and/or timing of donor vessel revascularization difficult to determine. METHODS: In patients with RCA CTO, FFR, iFR, and collateral function index (FFRcoll ) were measured in LAD and LCx pre-CTO PCI, immediately post and at 4 month follow-up. RESULTS: 34 patients underwent successful PCI. In the predominant donor vessel immediately post PCI, FFR, and FFRcoll did not change (0.76 ± 0.12 to 0.75 ± 0.13, P = 0.267 and 0.31 ± 0.10 vs. 0.34 ± 0.11, P = 0.078), but iFR increased significantly (0.86 ± 0.10 to 0.88 ± 0.10, P = 0.012). At follow-up, there was a significant increase in predominant donor FFR and iFR (0.76 ± 0.12 to 0.79 ± 0.11, P = 0.047 and 0.86 ± 0.10 to 0.90 ± 0.07, P = 0.003), accompanied by a significant reduction in FFRcoll (0.31 ± 0.10 to 0.18 ± 0.07 P < 0.0001). These changes resulted in a reclassification of the predominant donor vessel from ischemic to nonischemic in 18% (FFR) and 25% (iFR) of the cases, respectively. CONCLUSIONS: Successful recanalization of an RCA CTO resulted in a modest but statistically significant increase in the predominant donor vessel immediately post CTO PCI in the case of iFR and at 4-month follow-up for FFR and iFR compared to pre-PCI with a concomitant reduction in collateral function.

The Effect of Hydrostatic Pressure on Coronary Flow and Pressure-Based Indices of Coronary Stenosis Severity.

Background: To assess whether hydrostatic pressure gradients caused by coronary height differences in supine versus prone positioning during invasive physiological stenosis assessment affect resting and hyperaemic pressure-based indices or coronary flow. Methods: Twenty-three coronary stenoses were assessed in twenty-one patients with stable coronary artery disease. All patients had a stenosis of at least 50% visually defined on previous coronary angiography. Pd/Pa, iFR, FFR, and coronary flow velocity (APV) measured using a Doppler were recorded across the same stenosis, with the patient in the prone position, followed by repeat measurements in the standard supine position. Results: When comparing prone to supine measurements in the same stenosis, in the LAD, there was a significant change in mean Pd/Pa of 0.08 ± 0.04 (p = 0.0006), in the iFR of 0.06 ± 0.07 (p = 0.02), and in the FFR of 0.09 ± 0.07 (p = 0.003). In the Cx, there was a change in mean Pd/Pa of 0.05 ± 0.04 (p = 0.009), iFR of 0.07 ± 0.04 (p = 0.01), and FFR of 0.05 ± 0.03 (p = 0.006). In the RCA, there was a change in Pd/Pa of 0.05 ± 0.04 (p = 0.032), iFR of 0.04 ± 0.05 (p = 0.19), and FFR of 0.04+-0.03 (p = 0.004). Resting and hyperaemic coronary flow did not change significantly (resting delta APV = 1.6 cm/s, p = 0.31; hyperaemic delta APV = 0.9 cm/s, p = 0.85). Finally, 36% of iFR measurements and 26% of FFR measurements were re-classified across an ischaemic threshold when prone and supine measurements were compared across the same stenosis. Conclusions: Pd/Pa, iFR, and FFR were affected by hydrostatic pressure variations caused by coronary height differences in prone versus supine positioning. Coronary flow did not change signifying a purely pressure-based phenomenon.

Safety and Effectiveness of a Novel Microcatheter in Coronary Chronic Total Occlusions-The BIOMICS Study.

Background: Chronic total occlusion (CTO) remains the most complex anatomical subset of lesions in percutaneous coronary intervention (PCI), often requiring advanced techniques and technologies, including the use of microcatheters. Methods: The BIOMICS study is a premarket first-in-human prospective, multicenter, open-label, single-arm trial investigating the safety and efficacy of a novel coronary microcatheter (BioMC, Biosensors International) in 100 patients with symptoms of ischemia undergoing elective CTO-PCI. The primary efficacy end point of the study was device success defined according to the CTO-ARC (Chronic Total Occlusion Academic Research Consortium) criteria namely the ability of the microcatheter to successfully facilitate placement of a guide wire beyond the occluded coronary segment. The primary safety end point was the incidence of in-hospital cardiac death or myocardial infarction at hospital discharge. Results: Hundred patients were recruited between March 2022 and January 2023. The primary efficacy end point was achieved in 75% of patients (95% CI, 65.3%-83.1%; P < .0001 for superiority compared to the prespecified performance goal of 54%). The primary safety end point of in-hospital cardiac death or myocardial infarction was observed in 2% of the patients. There were no study device-related coronary perforations or device failures. Conclusions: The use of a novel coronary microcatheter during CTO-PCI was associated with a high device success and an excellent safety profile.

Comparison of bolus versus continuous thermodilution derived indices of microvascular dysfunction in revascularized coronary syndromes.

Background: The assessment of coronary microvascular dysfunction (CMD) using invasive methods is a field of growing interest, however the preferred method remains debated. Bolus and continuous thermodilution are commonly used methods, but weak agreement has been observed in patients with angina with non-obstructive coronary arteries (ANOCA). This study examined their agreement in revascularized acute coronary syndromes (ACS) and chronic coronary syndromes (CCS) patients. Objective: To compare bolus thermodilution and continuous thermodilution indices of CMD in revascularized ACS and CCS patients and assess their diagnostic agreement at pre-defined cut-off points. Methods: Patients from two centers underwent paired bolus and continuous thermodilution assessments after revascularization. CMD indices were compared between the two methods and their agreements at binary cut-off points were assessed. Results: Ninety-six patients and 116 vessels were included. The mean age was 64 ± 11 years, and 20 (21 %) were female. Overall, weak correlations were observed between the Index of Microcirculatory Resistance (IMR) and continuous thermodilution microvascular resistance (Rµ) (rho = 0.30p = 0.001). The median coronary flow reserve (CFR) from continuous thermodilution (CFRcont) and bolus thermodilution (CFRbolus) were 2.19 (1.76-2.67) and 2.55 (1.50-3.58), respectively (p < 0.001). Weak correlation and agreement were observed between CFRcont and CFRbolus (rho = 0.37, p < 0.001, ICC 0.228 [0.055-0.389]). When assessed at CFR cut-off values of 2.0 and 2.5, the methods disagreed in 41 (35 %) and 45 (39 %) of cases, respectively. Conclusions: There is a significant difference and weak agreement between bolus and continuous thermodilution-derived indices, which must be considered when diagnosing CMD in ACS and CCS patients.

N-of-1 Trial of Angina Verification Before Percutaneous Coronary Intervention.

BACKGROUND: In stable coronary artery disease, 30% to 60% of patients remain symptomatic despite successful revascularization. Perhaps not all symptoms reported by a patient with myocardial ischemia are, in fact, angina. OBJECTIVES: This study sought to determine whether independent symptom verification using a placebo-controlled ischemic stimulus could distinguish which patients achieve greatest symptom relief from percutaneous coronary intervention (PCI). METHODS: ORBITA-STAR was a multicenter, n-of-1, placebo-controlled study in patients undergoing single-vessel PCI for stable symptoms. Participants underwent 4 episodes (60 seconds each) of low-pressure balloon occlusion across their coronary stenosis, randomly paired with 4 episodes of placebo inflation. Following each episode, patients reported the similarity of the induced symptom in comparison with their usual symptom. The similarity score ranged from -10 (placebo replicated the symptom more than balloon occlusion) to +10 (balloon occlusion exactly replicated the symptom). The primary endpoint was the ability of the similarity score to predict symptom relief with PCI. RESULTS: Fifty-one patients were recruited, aged 62.9 ± 8.6 years. The median fractional flow reserve was 0.68 (Q1-Q3: 0.57-0.79), and the instantaneous wave-free ratio was 0.80 (Q1-Q3: 0.48-0.89). The median similarity score was 3 (Q1-Q3: 0.875-5.25). The similarity score was a strong predictor of symptom improvement following PCI: a patient with an upper quartile similarity score of 5.25 was significantly more likely to have lower angina frequency at follow-up (OR: 8.01; 95% credible interval: 2.39-15.86) than a patient with a lower quartile similarity score of 0.875 (OR: 1.31; 95% credible interval: 0.71-1.99), Pr(difference) >99.9%. CONCLUSIONS: Similarity score powerfully predicted symptom improvement from PCI. These data lay the foundation for independent symptom mapping to target PCI to those patients most likely to benefit. (Systematic Trial of Angina Assessment Before Revascularization [ORBITA-STAR]; NCT04280575).

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.

Changes in absolute flow, myocardial resistance and FFR after chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Randomised studies of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) have shown inconsistent outcomes, suggesting incomplete understanding of this cohort and their coronary physiology. To address this shortcoming, we designed a prospective observational study to measure the recovery of absolute coronary blood flow following successful CTO PCI Aims: We sought to identify patient and procedural characteristics associated with a favourable physiological outcome after CTO PCI. METHODS: Consecutive patients with a CTO subtending viable myocardium underwent PCI utilising contemporary techniques and the hybrid algorithm. Immediately after PCI, and at 3-month follow-up, physiological measurements were performed utilising continuous thermodilution. RESULTS: A total of 81 patients were included with a mean age of 63.6±8.9 years, and 66 (81.5%) were male. Physiological measurements of absolute coronary blood flow in the CTO vessel increased by 30% (p<0.001) and microvascular resistance reduced by 16% (p<0.001) from immediately post-CTO PCI to follow-up assessment. Fractional flow reserve increased by 0.02 (p=0.015) in the same period. Prior coronary artery bypass graft (CABG) and a higher estimated glomerular filtration rate (eGFR) were associated with a larger change in absolute flow. An extraplaque strategy was associated with a smaller change in absolute flow. CONCLUSIONS: Post-CTO PCI, there is a continued augmentation in absolute coronary blood flow and reduction in microvascular resistance from baseline to follow-up at 3 months. Prior CABG and a higher baseline eGFR were predictors of a larger change in absolute coronary flow, whilst an extraplaque final wire path strategy predicted a smaller change. Lastly, the patient characteristics and comorbidities had a larger influence than procedural factors on the observed change in absolute flow.

Stress perfusion cardiovascular magnetic resonance and serial fractional flow reserve assessment of the left anterior descending artery in patients undergoing right coronary artery chronic total occlusion revascularization.

BACKGROUND: Fractional flow reserve (FFR) assessment of remote arteries, in the context of a bystander chronic total occlusion (CTO), can lead to false positive results. Adenosine stress cardiovascular magnetic resonance (CMR) evaluates perfusion defects across the entire myocardium and may therefore be a reliable tool in the work-up of remote lesions in CTO patients. The IMPACT-CTO study investigated donor artery invasive physiology before, immediately post, and at 4 months following right coronary artery (RCA) CTO percutaneous coronary intervention (PCI). The aim of this subanalysis was to assess the concordance between baseline perfusion CMR and serial FFR evaluation of left anterior descending artery (LAD) ischemia in patients from the IMPACT-CTO study. METHODS: Baseline adenosine stress CMR examinations from 26 patients were analyzed for qualitative evidence of LAD ischemia. The results were correlated with the serial LAD FFR measurements. RESULTS: The present findings demonstrated that before RCA CTO PCI, there was 62% agreement between perfusion CMR and FFR (ischemic threshold £ 0.8) in the assessment of LAD ischemia (k = 0.29; fair concordance). At 4 months after revascularization, there was 77% agreement (k = 0.52; moderate concordance) between the index CMR assessment of LAD ischemia and the follow-up LAD FFR. Concordance was improved at a LAD FFR ischemic threshold of £ 0.75. CONCLUSIONS: In this hypothesis generating study, baseline CMR assessment of LAD ischemia correlated better with the 4 months LAD FFR data (threshold £ 0.8) as compared to the FFR measurements taken prior to RCA CTO revascularization.

Clinical effectiveness of thrombus aspiration during percutaneous coronary intervention for stent thrombosis in a contemporary setting.

OBJECTIVE: The impact of adjunctive manual thrombus aspiration (TA) in patients with stent thrombosis (ST) treated with percutaneous intervention has not been evaluated in the current era of potent P2Y12 agents and new-generation drug-eluting stents. We sought to assess the effect of TA using data from a large contemporary registry. METHODS: The study population was derived from the Essex ST Investigation Registry (ESTHIR), which contains all consecutive cases of angiographically determined definite ST undergoing interventional treatment in a tertiary cardiac centre between November 2015 and June 2018. Propensity score matching was performed to match patients who underwent TA (TA group) to those who did not (n-TA group). The study endpoints were final TIMI flow and survival free of cardiovascular death (CD) or target lesion revascularisation (TLR). RESULTS: A total of 128 ST patients were included in the present analysis. The mean age was 65 ± 11 years, and 84% were male. About 90% of the patients presented with STEMI, and 85% had very late ST. Seventy-two patients (56%) underwent TA. After propensity score matching, 30 patients were included in each study group. A higher rate of final TIMI III flow was observed in the TA group (TA vs n-TA group, 100% vs 83%), but this difference did not reach statistical significance (p = 0.052). At 1000 days of follow-up, survival free of CD or TLR was not different between the two groups (p = 0.8). CONCLUSION: In a propensity-matched population of ST patients undergoing PCI in a contemporary setting, TA was not associated with improved final TIMI flow or long-term cardiovascular outcomes.

Changes in coronary collateral function after successful chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) incorporates wire escalation and dissection/re-entry recanalisation strategies. AIMS: The purpose of the study was to investigate changes in collateral function after CTO PCI and to identify whether the mode of successful recanalisation influences collateral function regression. METHODS: Patients scheduled for elective CTO PCI with evidence of viability in the CTO territory by noninvasive imaging were included in this study. After successful CTO PCI, the aortic pressure (Pa) and distal coronary artery wedge pressure (Pw) during balloon occlusion were measured, both in a resting state and during infusion of intravenous adenosine, allowing the calculation of the pressure-derived collateral pressure index at rest and hyperaemia (CPIrest and the collateral fractional flow reserve [FFRcoll], respectively). Measurements were repeated 3 months later during angiographic follow-up. RESULTS: Eighty-one patients had physiological measurements at baseline and follow-up. In the final cohort the mean age was 64 years and 82% were male. The mean maximal stent diameter and total stent length were 3.2±0.5 mm and 68±31 mm, respectively. Successful strategies were antegrade wiring (64.2%), antegrade dissection re-entry (8.6%), and retrograde dissection re-entry (27.1%). Between the index procedure and follow-up, wedge pressure decreased from 34±11 mmHg to 21±8.5 mmHg (p<0.01), respectively. FFRcoll changed from 0.34±0.11 to 0.19±0.09 (p<0.01) at follow-up and CPIrest from 0.40±0.14 to 0.17±0.09 (p<0.01). Absolute maximum collateral flow decreased from 55±32 ml/min directly after PCI to 38±24 ml/min (p<0.01). There was no relation between the recanalisation technique and changes in FFRcoll. CONCLUSIONS: There was a significant reduction in collateral flow over time, independent of the recanalisation technique.

1-Year Outcomes of Blinded Physiological Assessment of Residual Ischemia After Successful PCI: DEFINE PCI Trial.

OBJECTIVES: The aim of this study was to identify the post-percutaneous coronary intervention (PCI) target value of instantaneous wave-free ratio (iFR) that would best discriminate clinical events at 1 year in the DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) study. BACKGROUND: The impact of residual ischemia detected by iFR post-PCI on clinical and symptom-related outcomes is unknown. METHODS: Blinded iFR pull back was performed after successful stent implantation in 500 patients. The primary endpoint was the rate of residual ischemia, defined as iFR ≤0.89, after operator-assessed angiographically successful PCI. Secondary endpoints included clinical events at 1 year and change in Seattle Angina Questionnaire angina frequency (SAQ-AF) score during follow-up. RESULTS: As reported, 24.0% of patients had residual ischemia (iFR ≤0.89) after successful PCI, with 81.6% of cases attributable to angiographically inapparent focal lesions. Post-PCI iFR ≥0.95 (present in 182 cases [39%]) was associated with a significant reduction in the composite of cardiac death, spontaneous myocardial infarction, or clinically driven target vessel revascularization compared with post-PCI iFR <0.95 (1.8% vs 5.7%; P = 0.04). Baseline SAQ-AF score was 73.3 ± 22.8. For highly symptomatic patients (baseline SAQ-AF score ≤60), SAQ-AF score increased by ≥10 points more frequently in patients with versus without post-PCI iFR ≥0.95 (100.0% vs 88.5%; P = 0.01). CONCLUSIONS: In DEFINE PCI, despite angiographically successful PCI, highly symptomatic patients at baseline without residual ischemia by post-PCI iFR had greater reductions in anginal symptoms at 1 year compared with patients with residual ischemia. Achieving post-PCI iFR ≥0.95 was also associated with improved 1-year event-free survival. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367).

Feasibility of early waking cardiac arrest patients whilst receiving therapeutic hypothermia: The therapeutic hypothermia and early waking (THAW) trial.

AIM: To determine the safety and feasibility of an early (12 h) waking and extubation protocol for out-of-hospital cardiac arrest (OHCA) patients receiving targeted temperature management (TTM). METHODS: This was a single-centre, prospective, non-randomised, observational, safety and feasibility pilot study which included successfully resuscitated OHCA patients, of presumed cardiac cause. Inclusion criteria were: OHCA patients aged over 18 years with a return of spontaneous circulation, who were going to receive TTM33 (TTM at 33 °C for 24 h and prevention of hyperthermia for 72 h) as part of their post cardiac arrest care. Clinical stability was measured against physiological and neurological parameters as well as clinical assessment. RESULTS: 50 consecutive patients were included (median age 65.5 years, 82% male) in the study. Four (8%) patients died within the first twelve hours and were excluded from the final cohort (n = 46). Twenty-three patients (46%) were considered clinically stable and suitable for early waking based on the intention to treat analysis; 12 patients were extubated early based on a variety of clinical factors (21.4 ± 8.6 h) whilst continuing to receive TTM33 with a mean core temperature of 34.2 °C when extubated. Of these, five patients were discharged from the intensive care unit (ICU) <48 h after admission with a mean ICU length of stay 1.8 ± 0.4 days. Twenty-eight patients (56%) were discharged from the ICU with a modified Rankin Score of 0-2. The overall intra-hospital mortality was 50% (n = 25). CONCLUSIONS: It is safe and feasible to wake selected comatose OHCA patients at 12 h, allowing for earlier positive neuro-prognostication and reduced ICU stay.

Impact of Intravascular Ultrasound on Chronic Total Occlusion Percutaneous Revascularization.

AIM: We sought to investigate the impact of IVUS use on chronic total occlusion (CTO) PCI using data from a contemporary registry of consecutive patients and applying a propensity score matching analysis. METHODS AND RESULTS: We evaluated 514 successful CTO-PCIs, median age: 67 years (IQR: 58-73), 83.5% males. IVUS-guided PCI was performed in 184 (35.8%) of cases. After using 1:1 propensity matching score analysis, two groups of 182 patients each (IVUS-guided vs. angiography-guided CTO-PCI group) were produced to form the study population. In the IVUS-guided group the median maximum stent diameter was larger and the median total stented segment was longer compared to the angiography-guided group [(3.5 mm, IQR: 3.0-4.0 vs. 3.2 mm, IQR: 3.0-3.5, p < 0.001) and (60.0 mm, IQR: 38.0-91.3 vs. 38.0 mm, IQR: 32.0-70.5, p < 0.001), respectively]. In the IVUS-guided group, retrograde recanalization was more frequently encountered compared to the angiography-guided PCI group (30.2% vs. 20.9%, p = 0.04). Procedural time was significantly longer in the IVUS-guided group, without any difference in fluoroscopy time, radiation dose and contrast volume. Multivariate linear regression analysis showed that IVUS use was the strongest independent factor associated with larger maximum diameter stents (p < 0.001) and a strong independent predictor for total stented segment length during CTO-PCI (p < 0.001). Up to 8 years follow-up, there was no difference in the incidence of the composite endpoint of all-cause death, cardiac death, myocardial infarction and target vessel revascularization between the IVUS-guided PCI and the angiography-guided PCI groups (hazard ratio: 13.7% vs. 15.9%, respectively, log-rank: p = 0.67, median follow-up time: 49.0 months, IQR: 33.0-67.0). CONCLUSIONS: Use of IVUS in CTO-PCI was associated with larger stent diameter and longer stented segments. Despite more frequent use of IVUS in retrograde CTO-PCI, there was no difference in long-term adverse events between IVUS and angiography CTO-PCI groups; nevertheless, the study was not powered to assess clinical outcomes.

Coronary artery height differences and their effect on fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) uses pressure-based measurements to assess the severity of a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximal aortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, may impact FFR calculation. METHODS: One hundred computed tomography coronary angiographies were used to measure height differences between the coronary ostia and points in the coronary tree. Mean heights were used to calculate the hydrostatic pressure effect in each artery, using a correction factor of 0.8 mmHg/cm. This was tested in a simulation of intermediate coronary stenosis to give the "corrected FFR" (cFFR) and percentage of values, which crossed a threshold of 0.8. RESULTS: The mean height from coronary ostium to distal left anterior descending (LAD) was +5.26 cm, distal circumflex (Cx) -3.35 cm, distal right coronary artery-posterior left ventricular artery (RCA-PLV) -5.74 cm and distal RCA-posterior descending artery (PDA) +1.83 cm. For LAD, correction resulted in a mean change in FFR of +0.042, -0.027 in the Cx, -0.046 in the PLV and +0.015 in the PDA. Using 200 random FFR values between 0.75 and 0.85, the resulting cFFR crossed the clinical treatment threshold of 0.8 in 43% of LAD, 27% of Cx, 47% of PLV and 15% of PDA cases. CONCLUSIONS: There are significant vertical height differences between the distal artery (Pd) and its point of normalization (Pa). This is likely to have a modest effect on FFR, and correcting for this results in a proportion of values crossing treatment thresholds. Operators should be mindful of this phenomenon when interpreting FFR values.