Procedural Results and Long-term Outcome of Chronic Total Occlusion Percutaneous Coronary Intervention in a UK Non-surgical Centre.

Background: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has evolved a great deal over recent years, with increased procedural success and lower complication rates being reported. This study aims to evaluate the feasibility, safety and success of a dedicated CTO programme in a large UK PCI centre without on-site cardiothoracic surgery facilities. Methods: Clinical and procedural data were retrospectively collected for consecutive unselected patients undergoing CTO PCI between 2015 and 2019 from the local database and regional electronic patient records. In-hospital outcomes and long-term major adverse cardiovascular events (all-cause mortality, MI, stroke and target vessel revascularisation) were recorded. Results: A total of 170 patients underwent 191 CTO procedures during the study period. The mean age was 63 ± 10 years and 80.6% of patients were male (n=137). The clinical indications were: stable chronic coronary syndromes in 88.5% (n=169) of patients; staged procedures in the context of acute coronary syndromes in 1.6% (n=3); and presentation with acute coronary syndrome in 9.9% (n=19). The procedural success rate was 50.0% (n=25) for general interventional cardiologists and 90.1% (n=127) for dedicated CTO operators. In-hospital major adverse cardiovascular events occurred once (0.5%) and interhospital transfer for emergency salvage cardiac surgery was not required. Long-term follow-up data at a median duration of 3.8 years revealed 4 (2.4%) cardiac deaths, 14 (8.3%) spontaneous MI events and 10 (5.9%) target vessel revascularisations. Conclusion: These data suggest CTO PCI using contemporary techniques is both safe and effective when undertaken in a high-volume non-surgical centre by experienced operators.

Sex-Specific Differences in Upstream Cardiac Damage in Patients With Aortic Stenosis Undergoing TAVR.

BACKGROUND: Cardiac damage caused by aortic stenosis (AS) can be categorized into stages, which are associated with a progressively increasing risk of death after transcatheter aortic valve replacement (TAVR). OBJECTIVES: The authors investigated sex-related differences in cardiac damage among patients with symptomatic AS and the prognostic value of cardiac damage classification in women and men undergoing TAVR. METHODS: In a prospective registry, pre-TAVR echocardiograms were used to categorize patients into 5 stages of cardiac damage caused by AS. Differences in the extent of cardiac damage were compared according to sex, and its implications on clinical outcomes after TAVR were explored. RESULTS: Among 2,026 patients undergoing TAVR between August 2007 and June 2022 (995 [49.1%] women and 1,031 [50.9%] men), we observed sex-specific differences in the pattern of cardiac damage (women vs men; stage 0: 2.6% vs 3.1%, stage 1: 13.4% vs 10.1%, stage 2: 37.1% vs 39.5%, stage 3: 27.5% vs 15.6%, and stage 4: 19.4% vs 31.7%). There was a stepwise increase in 5-year all-cause mortality according to stage in women (HRadjusted: 1.43; 95% CI: 1.28-1.60, for linear trend) and men (HRadjusted: 1.26; 95% CI: 1.14-1.38, for linear trend). Female sex was associated with a lower 5-year mortality in early stages (stage 0, 1, or 2) but not in advanced stages (stage 3 or 4). CONCLUSIONS: The pattern of cardiac damage secondary to AS differed by sex. In early stages of cardiac damage, women had a lower 5-year mortality than men, whereas in more advanced stages, mortality was comparable between sexes. (SwissTAVI Registry; NCT01368250).

The limited antegrade subintimal tracking technique to retrieve a trapped rotablator burr: a case report.

Background: Burr entrapment is a rare, but potentially serious complication of rotablation. This report describes the percutaneous options available for Rota burr retrieval. Case summary: A 62-year-old Caucasian man with stable angina presented for percutaneous coronary intervention. Attempted rotablation with a 1.75 mm burr resulted in Rota burr entrapment, in the heavily calcified proximal right coronary artery. A chronic total occlusion angioplasty technique (limited antegrade subintimal tracking) was successfully used to remove the trapped Rota burr, by enabling subintimal dilatation to externally crush plaque and dislodge the burr. The angioplasty procedure was then completed using the wire that had a short subintimal passage, before re-entering the true lumen. Discussion: The mechanism for Rota burr entrapment, in this case, was initiating rotablation on the heavily calcified lesion and not more proximal to allow a pecking motion. The learning points are (i) to start the rotablator several millimetres proximal to the actual lesion, and (ii) if unable to wire alongside a trapped Rota burr in the true lumen, then subintimal crossing and balloon dilatation in the subintimal space may work to dislodge the burr.

Antithrombotic Treatment After Transcatheter Valve Interventions: Current Status and Future Directions.

PURPOSE: The optimal antithrombotic strategy after transcatheter valve interventions is a subject of ongoing debate. Although there is evidence from randomized trials in patients undergoing transcatheter aortic valve replacement (TAVR), current evidence on optimal antithrombotic management after transcatheter mitral or tricuspid valve interventions is sparse. This article appraises the current evidence on this topic. METHODS: This narrative review presents key research findings and guideline recommendations, as well as highlights areas for future research. FINDINGS: After TAVR, randomized trial evidence suggests that single antiplatelet therapy is reasonable for patients without pre-existing indications for oral anticoagulation (OAC). If there is a concurrent indication for OAC, the addition of antiplatelet therapy increases bleeding risk. Whether direct oral anticoagulants achieve better outcomes than vitamin K antagonists is uncertain in this setting. Although OAC has been shown to reduce subclinical leaflet thrombosis (which may progress to structural valve degeneration), bleeding events are unacceptably high. There is a lack of randomized trial data comparing antithrombotic strategies after transcatheter mitral or tricuspid valve replacement or after mitral or tricuspid transcatheter edge-to-edge repair. Single antiplatelet therapy after mitral or tricuspid transcatheter edge-to-edge repair may be appropriate, whereas at least 3 months of OAC is suggested after transcatheter mitral valve replacement or transcatheter tricuspid valve replacement. IMPLICATIONS: Randomized studies are warranted to address the knowledge gaps in antithrombotic therapy after transcatheter valve interventions and to optimize outcomes.

Follow-up optical coherence tomography to evaluate circumflex ostium after fenestration of left main Papyrus covered stent: a case report.

Background: Left main (LM) perforations necessitating a covered stent risk sacrificing the side branch. The lost side branch can be promptly recovered by fenestration of the covered stent, using a stiff wire. However, it is unclear whether subsequent balloon angioplasty of the recovered side branch ostium is sufficient to preserve side branch patency. We report the longer-term patency of the circumflex (LCx) ostium after LM covered stenting. Case summary: A 78-year-old lady, with stable angina, presented for elective angiography. Percutaneous coronary intervention of the left anterior descending (LAD) artery to LM was complicated by a distal LM perforation. A covered stent across the LM sealed the perforation but resulted in acute occlusion of the LCx. The LCx was rescued by fenestration of the covered stent with a stiff wire, followed by balloon angioplasty to the LCx ostium. At follow-up, the angina had resolved. However, follow-up angiography demonstrated a new severe stenosis at the LCx ostium, with remnants of the polyurethane membrane seen protruding into the LCx ostium on optical coherence tomography. Therefore, the LCx ostium was stented, using the reverse Culotte technique. Conclusion: This case demonstrates that stenting the LCx ostium should be considered after covered stent implantation from LM to LAD, because balloon angioplasty of the LCx ostium may not provide a durable result in this scenario.

Bifurcation left main stenting with or without intracoronary imaging: Outcomes from the EBC MAIN trial.

BACKGROUND: The impact of intracoronary imaging on outcomes, after provisional versus dual-stenting for bifurcation left main (LM) lesions, is unknown. OBJECTIVES: We investigated the effect of intracoronary imaging in the EBC MAIN trial (European Bifurcation Club LM Coronary Stent study). METHODS: Four hundred and sixty-seven patients were randomized to dual-stenting or a stepwise provisional strategy. Four hundred and fifty-five patients were included. Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was undertaken at the operator's discretion. The primary endpoint was death, myocardial infarction or target vessel revascularization at 1-year. RESULTS: Intracoronary imaging was undertaken in 179 patients (39%; IVUS = 151, OCT = 28). As a result of IVUS findings, operators reintervened in 42 procedures. The primary outcome did not differ with intracoronary imaging versus angiographic-guidance (17% vs. 16%; odds ratio [OR]: 0.92 (95% confidence interval [CI]: 0.51-1.63) p = 0.767), nor for reintervention based on IVUS versus none (14% vs. 16%; OR: 0.88 [95% CI: 0.32-2.43] p = 0.803), adjusted for syntax score, lesion calcification and ischemic symptoms. With angiographic-guidance, primary outcome events were more frequent with dual versus provisional stenting (21% vs. 10%; adjusted OR: 2.11 [95% CI: 1.04-4.30] p = 0.039). With intracoronary imaging, there were numerically fewer primary outcome events with dual versus provisional stenting (13% vs. 21%; adjusted OR: 0.56 [95% CI: 0.22-1.46] p = 0.220). CONCLUSIONS: In EBC MAIN, the primary outcome did not differ with intracoronary imaging versus none. However, in patients with angiographic-guidance, outcomes were worse with a dual-stent than provisional strategy When intracoronary imaging was used, there was a trend toward better outcomes with the dual-stent than provisional strategy.

A Contemporary Review of Antiplatelet Therapies in Current Clinical Practice.

Antiplatelet therapy plays a crucial role in a number of cardiovascular disorders. We currently have a range of antiplatelet agents in our armamentarium. In this review, we aim to summarise the common antiplatelet agents currently available, and their use in clinic practice. We not only highlight recent trials exploring antiplatelet therapy in atherosclerotic cardiovascular disease, but also in trials related to transcatheter aortic valve implantation and coronavirus disease 2019. Inevitably, the antithrombotic benefits of these drugs are accompanied by an increase in bleeding complications. Therefore, an individualised approach to weighing each patient's thrombotic risk versus bleeding risk is imperative, in order to improve clinical outcomes.

Fractional Flow Reserve versus Angiography-Guided Management of Coronary Artery Disease: A Meta-Analysis of Contemporary Randomised Controlled Trials.

Background and Aims: Randomised controlled trials (RCTs) comparing outcomes after fractional flow reserve (FFR)-guided versus angiography-guided management for obstructive coronary artery disease (CAD) have produced conflicting results. We investigated the efficacy and safety of an FFR-guided versus angiography-guided management strategy among patients with obstructive CAD. Methods: A systematic electronic search of the major databases was performed from inception to September 2022. We included studies of patients presenting with angina or myocardial infarction (MI), managed with medications, percutaneous coronary intervention, or bypass graft surgery. A meta-analysis was performed by pooling the risk ratio (RR) using a random-effects model. The endpoints of interest were all-cause mortality, MI and unplanned revascularisation. Results: Eight RCTs, with outcome data from 5077 patients, were included. The weighted mean follow up was 22 months. When FFR-guided management was compared to angiography-guided management, there was no difference in all-cause mortality [3.5% vs. 3.7%, RR: 0.99 (95% confidence interval (CI) 0.62−1.60), p = 0.98, heterogeneity (I2) 43%], MI [5.3% vs. 5.9%, RR: 0.93 (95%CI 0.66−1.32), p = 0.69, I2 42%], or unplanned revascularisation [7.4% vs. 7.9%, RR: 0.92 (95%CI 0.76−1.11), p = 0.37, I2 0%]. However, the number patients undergoing planned revascularisation by either stent or surgery was significantly lower with an FFR-guided strategy [weighted mean difference: 14 (95% CI 3 to 25)%, p =< 0.001]. Conclusion: In patients with obstructive CAD, an FFR-guided management strategy did not impact on all-cause mortality, MI and unplanned revascularisation, when compared to an angiography-guided management strategy, but led to up to a quarter less patients needing revascularisation.

Effect of coronary tortuosity on invasive physiology.

We present a case of angina, where extreme coronary tortuosity affected invasive physiology interpretation. Extreme coronary tortuosity may lower fractional flow reserve and instantaneous wave-free ratio. Therefore, invasive physiology can be misleading in this setting, when used to evaluate stenosis significance, or when used post-percutaneous coronary (PCI) intervention for physiology guided stent optimisation.

A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: This study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure. BACKGROUND: A cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score. RESULTS: There were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score. CONCLUSIONS: This noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).

Impact of paramedic education on door-to-balloon times and appropriate use of the primary PCI pathway in ST-elevation myocardial infarction.

OBJECTIVE: Evidence supports improved outcomes and reduced mortality with rapid reperfusion through primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI). UK national audit data (Myocardial Ischaemia National Audit Project [MINAP]) demonstrates minor improvements in door-to-balloon times (DTB) of <90 min but increasing call-to-balloon times (CTB). We evaluate the effect of a regional Cardiologist delivered paramedic education programme (PEP) on DTB times and appropriate use of the PPCI pathway. METHODS: This was a prospective single-centre study of patients with STEMI brought directly to hospital via ambulance services. Data sources included ambulance charts, in-patient notes, British Cardiovascular Interventional Society (BCIS) database and local MINAP data. All DTB breaches were investigated. A local PEP was implemented with focus on ECG interpretation, STEMI diagnosis and appropriate use of the PPCI pathway. Non-parametric Wilcoxon rank test was used for comparisons of DTB and CTB times between direct versus ED-associated cath lab transfer. RESULTS: A total of 728 patients with STEMI were admitted directly to our centre via ambulance, 66% (n=484) directly to the Catheterisation Laboratory (Cath Lab) and 34% (n=244) via the Emergency Department (ED). There was a significant increase in median DTB, 83 vs 37 min (p<0.001) and median CTB 144 vs 97.5 min (p<0.001) when transfer to the Cath Lab occurred via the ED versus direct transfer. The PEP increased direct cath lab transfers (52%-85%) and generated annual reductions in median DTB times, with sustained improvement seen throughout the 7-year study period. CONCLUSIONS: Paramedic education increases direct transfer of STEMI patients to the Cath Lab, and reduces DTB times. This is an effective and reproducible intervention to facilitate timely reperfusion in STEMI.

Adjunctive Intracoronary Fibrinolytic Therapy During Primary Percutaneous Coronary Intervention.

Despite routinely restoring epicardial coronary patency, with primary percutaneous coronary intervention (PCI), microvascular obstruction affects approximately half of patients and confers an adverse prognosis. There are no evidence-based treatments for microvascular obstruction. A key contributor to microvascular obstruction is distal embolisation and microvascular thrombi. Adjunctive intracoronary fibrinolytic therapy may reduce thrombotic burden, potentially reducing distal embolisation of atherothrombotic debris to the microcirculation. In this review, the evidence from published randomised trials on the effects of adjunctive intracoronary fibrinolytic therapy during primary PCI is critically appraised, the ongoing randomised trials are described, and conclusions are made from the available evidence. Clinical uncertainties, to be addressed by future research, are highlighted.

Risk Stratification Guided by the Index of Microcirculatory Resistance and Left Ventricular End-Diastolic Pressure in Acute Myocardial Infarction.

BACKGROUND: The index of microcirculatory resistance (IMR) of the infarct-related artery and left ventricular end-diastolic pressure (LVEDP) are acute, prognostic biomarkers in patients undergoing primary percutaneous coronary intervention. The clinical significance of IMR and LVEDP in combination is unknown. METHODS: IMR and LVEDP were prospectively measured in a prespecified substudy of the T-TIME clinical trial (Trial of Low Dose Adjunctive Alteplase During Primary PCI). IMR was measured using a pressure- and temperature-sensing guidewire following percutaneous coronary intervention. Prognostically established thresholds for IMR (>32) and LVEDP (>18 mm Hg) were predefined. Contrast-enhanced cardiovascular magnetic resonance imaging (1.5 Tesla) was acquired 2 to 7 days and 3 months postmyocardial infarction. The primary end point was major adverse cardiac events, defined as cardiac death/nonfatal myocardial infarction/heart failure hospitalization at 1 year. RESULTS: IMR and LVEDP were both measured in 131 patients (mean age 59±10.7 years, 103 [78.6%] male, 48 [36.6%] with anterior myocardial infarction). The median IMR was 29 (interquartile range, 17-55), the median LVEDP was 17 mm Hg (interquartile range, 12-21), and the correlation between them was not statistically significant (r=0.15; P=0.087). Fifty-three patients (40%) had low IMR (≤32) and low LVEDP (≤18), 18 (14%) had low IMR and high LVEDP, 31 (24%) had high IMR and low LVEDP, while 29 (22%) had high IMR and high LVEDP. Infarct size (% LV mass), LV ejection fraction, final myocardial perfusion grade ≤1, TIMI (Thrombolysis In Myocardial Infarction) flow grade ≤2, and coronary flow reserve were associated with LVEDP/IMR group, as was hospitalization for heart failure (n=18 events; P=0.045) and major adverse cardiac events (n=21 events; P=0.051). LVEDP>18 and IMR>32 combined was associated with major adverse cardiac events, independent of age, estimated glomerular filtration rate, and infarct-related artery (odds ratio, 5.80 [95% CI, 1.60-21.22] P=0.008). The net reclassification improvement for detecting major adverse cardiac events was 50.6% (95% CI, 2.7-98.2; P=0.033) when LVEDP>18 was added to IMR>32. CONCLUSIONS: IMR and LVEDP in combination have incremental value for risk stratification following primary percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02257294.

Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial.

OBJECTIVES: Persistently impaired culprit artery flow (

Thermodilution-derived temperature recovery time: a novel predictor of microvascular reperfusion and prognosis after myocardial infarction.

BACKGROUND: Novel parameters that detect failed microvascular reperfusion might identify better the patients likely to benefit from adjunctive treatments during primary percutaneous coronary intervention (PCI). AIMS: The aim of this study was to test the hypothesis that a novel invasive parameter, the thermodilution-derived temperature recovery time (TRT), would be associated with microvascular obstruction (MVO) and prognosis. METHODS: TRT was derived and validated in two independent ST-elevation myocardial infarction populations and was measured immediately post PCI. TRT was defined as the duration (seconds) from the nadir of the hyperaemic thermodilution curve to 20% from baseline body temperature. MVO extent (% left ventricular mass) was assessed by cardiovascular magnetic resonance imaging at 2-7 days. RESULTS: In the retrospective derivation cohort (n=271, mean age 60±12 years, 72% male), higher TRT was associated with more MVO (coefficient: 4.09 [95% CI: 2.70-5.48], p<0.001), independently of IMR >32, CFR ≤2, hyperaemic Tmn >median, thermodilution waveform, age and ischaemic time. At five years, higher TRT was multivariably associated with all-cause death/heart failure hospitalisation (OR 4.14 [95% CI: 2.08-8.25], p<0.001) and major adverse cardiac events (OR 4.05 [95% CI: 2.00-8.21], p<0.001). In the validation population (n=144, mean age 59±11 years, 80% male), the findings were confirmed prospectively. CONCLUSIONS: TRT represents a novel diagnostic advance for predicting MVO and prognosis. ClinicalTrials.gov Identifiers: NCT02072850 & NCT02257294 Visual summary. Thermodilution-derived temperature recovery time (TRT): a novel predictor of microvascular reperfusion & prognosis after STEMI. CMR: cardiovascular magnetic resonance; MACE: major adverse cardiac events; MVO: microvascular obstruction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction.

Calculated plasma volume status predicts outcomes after transcatheter aortic valve implantation.

OBJECTIVES: Congestion can worsen outcomes after transcatheter aortic valve implantation (TAVI), but can be difficult to quantify non-invasively. We hypothesised that preprocedural plasma volume status (PVS), estimated using a validated formula that enumerates percentage change from ideal PV, would provide prognostic utility post-TAVI. METHODS: This retrospective cohort study identified patients who underwent TAVI (2007-2017) from a prospectively collected database. Actual ([1-haematocrit] × [a + (b × weight (Kg))] and ideal (c × weight (Kg)) PV were quantified from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual - ideal PV)/ideal PV]). RESULTS: In 564 patients (mean age 82±7 years, 49% male), mean PVS was -2.7±10.2%, with PV expansion (PVS >0%) evident in 39%. Only logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) independently predicted a PVS >0% (OR 1.85, p=0.002). On Cox analyses, a PVS >0% was associated with greater mortality at 3 (HR 2.29, 95% CI 1.11 to 4.74, p=0.03) and 12 months (HR 2.00, 95% CI 1.23 to 3.26, p=0.006) after TAVI, independently of, and incremental to, the EuroSCORE and New York Heart Association class. A PVS >0% was also independently associated with more days in intensive care (coefficient: 0.41, 95% CI 0.04 to 0.78, p=0.03) and in hospital (coefficient: 1.95, 95% CI 0.48 to 3.41, p=0.009). CONCLUSION: Higher PVS values, calculated simply from weight and haematocrit, are associated with greater mortality and longer hospitalisation post-TAVI. PVS could help refine risk stratification and further investigations into the utility of PVS-guided management in TAVI patients is warranted.

Comparative Significance of Invasive Measures of Microvascular Injury in Acute Myocardial Infarction.

BACKGROUND: The resistive reserve ratio (RRR) expresses the ratio between basal and hyperemic microvascular resistance. RRR measures the vasodilatory capacity of the microcirculation. We compared RRR, index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) for predicting microvascular obstruction (MVO), myocardial hemorrhage, infarct size, and clinical outcomes, after ST-segment-elevation myocardial infarction. METHODS: In the T-TIME trial (Trial of Low-Dose Adjunctive Alteplase During Primary PCI), 440 patients with acute ST-segment-elevation myocardial infarction from 11 UK hospitals were prospectively enrolled. In a subset of 144 patients, IMR, CFR, and RRR were measured post-primary percutaneous coronary intervention. MVO extent (% left ventricular mass) was determined by cardiovascular magnetic resonance imaging at 2 to 7 days. Infarct size was determined at 3 months. One-year major adverse cardiac events, heart failure hospitalizations, and all-cause death/heart failure hospitalizations were assessed. RESULTS: In these 144 patients (mean age, 59±11 years, 80% male), median IMR was 29.5 (interquartile range: 17.0-55.0), CFR was 1.4 (1.1-2.0), and RRR was 1.7 (1.3-2.3). MVO occurred in 41% of patients. IMR>40 was multivariably associated with more MVO (coefficient, 0.53 [95% CI, 0.05-1.02]; P=0.031), myocardial hemorrhage presence (odds ratio [OR], 3.20 [95% CI, 1.25-8.24]; P=0.016), and infarct size (coefficient, 5.05 [95% CI, 0.84-9.26]; P=0.019), independently of CFR≤2.0, RRR≤1.7, myocardial perfusion grade≤1, and Thrombolysis in Myocardial Infarction frame count. RRR was multivariably associated with MVO extent (coefficient, -0.60 [95% CI, -0.97 to -0.23]; P=0.002), myocardial hemorrhage presence (OR, 0.34 [95% CI, 0.15-0.75]; P=0.008), and infarct size (coefficient, -3.41 [95% CI, -6.76 to -0.06]; P=0.046). IMR>40 was associated with heart failure hospitalization (OR, 5.34 [95% CI, 1.80-15.81] P=0.002), major adverse cardiac events (OR, 4.46 [95% CI, 1.70-11.70] P=0.002), and all-cause death/ heart failure hospitalization (OR, 4.08 [95% CI, 1.55-10.79] P=0.005). RRR was associated with heart failure hospitalization (OR, 0.44 [95% CI, 0.19-0.99] P=0.047). CFR was not associated with infarct characteristics or clinical outcomes. CONCLUSIONS: In acute ST-segment-elevationl infarction, IMR and RRR, but not CFR, were associated with MVO, myocardial hemorrhage, infarct size, and clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02257294.

Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time.

BACKGROUND: Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis. OBJECTIVES: This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time. METHODS: This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440). RESULTS: Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018). CONCLUSION: In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294).