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

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

Reference invasive tests of microvascular injury in myocardial infarction

No abstract available

Novel insights into the assessment and therapeutics of microcirculatory injury in acute myocardial infarction

Introduction: Microvascular injury in acute ST-segment elevation myocardial infarction (STEMI) is an important predictor of adverse prognosis. However, persistent microvascular injury typically passes undetected after primary percutaneous coronary intervention (PCI), and is a problem of unmet therapeutic need. The aim of this work was to gain greater insight into the invasive assessment of acute microvascular injury following primary PCI, for risk-stratification, and to provide mechanistic insights into the effects of intracoronary alteplase on the microcirculation. Methods: The first part of the thesis sought to establish the influence of coronary flow on the effects of adjunctive intracoronary alteplase, and to investigate the effects of intracoronary alteplase on invasive physiology measures of microvascular function. Through a multi-centre, prospective, randomised controlled trial (T-TIME, NCT02257294), alteplase 10mg, and alteplase 20mg were compared to placebo, in patients undergoing primary PCI. Eligible participants presented within 6 hours from STEMI onset, and the study drug was administered before stent implantation. In 421 patients, TIMI (thrombolysis in myocardial infarction) flow grade was determined in the infarct-related artery immediately before study drug administration. In a subset of 144 patients, invasive physiology parameters were measured in the infarct-related artery at the end of the primary PCI procedure (the prespecified T-TIME physiology sub-study). These invasive physiology parameters included index of microcirculatory resistance (IMR), coronary flow reserve (CFR) and resistive reserve ratio (RRR). Microvascular obstruction (MVO) and myocardial haemorrhage were assessed on cardiovascular magnetic resonance (CMR) imaging at 2 to 7 days post-STEMI, and CMR imaging was repeated at 3 months. The second part of the thesis sought to prospectively compare IMR, CFR, RRR, myocardial perfusion grade (MPG) and TIMI frame count (TFC), for predicting MVO and myocardial haemorrhage, and clinical outcomes at 1 year, in the T-TIME physiology sub-study. The following adjudicated clinical outcomes were assessed: major adverse cardiac events, heart failure hospitalisations, and all-cause death/ heart failure hospitalisations. Furthermore, a retrospective analysis was performed in 271 acute STEMI patients from a single-centre observational study (MR-MI, NCT02072850), for the derivation of a newly conceived invasive physiology parameter termed temperature recovery time (TRT). The associations between TRT and MVO (on 2 to 7 day CMR imaging) and clinical outcomes, were assessed in the MR-MI cohort, and were prospectively validated in the T-TIME physiology sub-study population. Results: The main findings are summarised as follows: - Low-dose intracoronary alteplase given early during primary PCI, was associated with increased occurrence of MVO and myocardial haemorrhage in participants who had TIMI flow ≤2 immediately preceding drug administration. - In participants with TIMI 3 flow immediately preceding drug administration, there was no difference in MVO or myocardial haemorrhage with intracoronary alteplase compared to placebo. - There was overall no difference in microvascular function, measured by IMR, CFR and RRR, between intracoronary alteplase and placebo groups. - In patients with ischaemic time <2 hours, CFR and RRR were higher with alteplase 20mg vs. placebo, whereas in patients with ischaemic times ≥4 hours, MVO extent was higher with alteplase 20mg vs. placebo. - In acute STEMI patients, lower RRR, IMR >40, and MPG ≤1 were associated with more MVO, myocardial haemorrhage presence and adverse clinical outcomes, whereas CFR ≤2 was not. - In acute STEMI patients, TFC >27 was associated with adverse clinical outcomes, but was not associated with MVO or myocardial haemorrhage. - Higher TRT independently predicted more MVO and adverse clinical outcomes, in two independent acute STEMI cohorts. Conclusions: The findings from this PhD are novel and clinically relevant. Invasive measures of microvascular injury during primary PCI allows potential for early administration of targeted adjunctive therapies to the highest risk patients. The data support IMR in conjunction with RRR instead of CFR, to select patients for adjunctive therapies. Moreover, TRT was found to detect failed microvascular perfusion and may have potential to refine risk stratification in acute STEMI. The findings raise a question as to the safety of intracoronary administration of alteplase in the context of STEMI when there is <TIMI 3 flow. Finally, the data suggest that future studies evaluating the effects of intracoronary fibrinolysis should limit recruitment to patients with short ischaemic time

The ischaemic constellation: an alternative to the ischaemic cascade—implications for the validation of new ischaemic tests

The ischaemic cascade is the concept that progressive myocardial oxygen supply–demand mismatch causes a consistent sequence of events, starting with metabolic alterations and followed sequentially by myocardial perfusion abnormalities, wall motion abnormalities, ECG changes, and angina. This concept would suggest that investigations that detect expressions of ischaemia earlier in the cascade should be more sensitive tests of ischaemia than those that detect expressions appearing later in the cascade. However, careful review of the studies on which the ischaemic cascade is based suggests that the ischaemic cascade concept may be less well supported by the literature than assumed. In this review we explore this, discuss an alternative method for conceptualising ischaemia, and discuss the potential implications of this new approach to clinical studies and clinical practice

A propensity matched comparison of return to work and quality of life after stenting or coronary artery bypass surgery

Objectives: We sought to determine (1) return to work (RTW) rates, (2) long-term employment (&gt;12 months postprocedure), (3) time taken to RTW, and (4) quality of life (QoL), in patients treated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Methods: Questionnaires regarding RTW were sent to 689 PCI and 169 CABG patients who underwent PCI or CABG at University Hospitals of Leicester Trust, UK, from May 2012 to May 2013. QoL was also measured using the European QoL 5-dimensions questionnaire (EQ-5D). Responses from patients employed preprocedure were analysed using multivariate logistic regression. Propensity score-matching was further used to compare similar patient populations receiving PCI or CABG. Results: The response rate was 38% (235 PCI and 88 CABG patients). 241 respondents (75%) were employed preprocedure. Of these 162 (93%) PCI and 51 (77%) CABG patients returned to work, whereas 147 (85%) PCI and 41 (62%) CABG patients were still employed at &gt;12 months postprocedure. After propensity analysis, there was no significant difference between PCI and CABG patients in RTW, long-term employment, nor QoL. The median time taken to RTW was 6 weeks after PCI and 13 weeks after CABG (p=0.001). The effect remained significant after multivariate analysis (p=0.001) and propensity analysis (p=0.001). Conclusions: In this first propensity score-matched study comparing RTW and QoL after PCI or CABG strict propensity matching indicates that RTW or QoL, is similar for PCI or CABG, albeit the number of matched pairs was small. There are differences, however, in delay in RTW

Sex-based associations with microvascular injury and outcomes after ST-segment elevation myocardial infarction

Objectives: We aimed to assess for sex differences in invasive parameters of acute microvascular reperfusion injury and infarct characteristics on cardiac MRI after ST-segment elevation myocardial infarction (STEMI). Methods: Patients with STEMI undergoing emergency percutaneous coronary intervention (PCI) were prospectively enrolled. Index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured in the culprit artery post-PCI. Contrast-enhanced MRI was used to assess infarct characteristics, microvascular obstruction and myocardial haemorrhage, 2 days and 6 months post-STEMI. Prespecified outcomes were as follows: (i) all-cause death/first heart failure hospitalisation and (ii) cardiac death/non-fatal myocardial infarction/urgent coronary revascularisation (major adverse cardiovascular event, MACE) during 5- year median follow-up. Results: In 324 patients with STEMI (87 women, mean age: 61 ± 12.19 years; 237 men, mean age: 59 ± 11.17 years), women had anterior STEMI less often, fewer prescriptions of beta-blockers at discharge and higher baseline N-terminal pro-B-type natriuretic peptide levels (all p &lt; 0.05). Following emergency PCI, fewer women than men had Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grades ≤ 1 (20% vs 32%, p = 0.027) and women had lower corrected TIMI frame counts (12.94 vs 17.65, p = 0.003). However, IMR, CFR, microvascular obstruction, myocardial haemorrhage, infarct size, myocardial salvage index, left ventricular remodelling and ejection fraction did not differ significantly between sexes. Female sex was not associated with MACE or all-cause death/first heart failure hospitalisation. Conclusion: There were no sex differences in microvascular pathology in patients with acute STEMI. Women had less anterior infarcts than men, and beta-blocker therapy at discharge was prescribed less often in women

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&gt;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&gt;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

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 &gt;0%) evident in 39%. Only logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) independently predicted a PVS &gt;0% (OR 1.85, p=0.002). On Cox analyses, a PVS &gt;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 &gt;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

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 (&lt;2 h, n = 107; ≥2 h but &lt;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