Bicuspid Aortic Valve Disease: Classifications, Treatments, and Emerging Transcatheter Paradigms.

Bicuspid aortic valve (BAV) is a common congenital valvular malformation, which may lead to early aortic valve disease and bicuspid-associated aortopathy. A novel BAV classification system was recently proposed to coincide with transcatheter aortic valve replacement being increasingly considered in younger patients with symptomatic BAV, with good clinical results, yet without randomized trial evidence. Procedural technique, along with clinical outcomes, have considerably improved in BAV patients compared with tricuspid aortic stenosis patients undergoing transcatheter aortic valve replacement. The present review summarizes the novel BAV classification systems and examines contemporary surgical and transcatheter approaches.

Low Transvalvular Flow Rate in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI) Is a Predictor of Mortality: The TFR-TAVI Study.

BACKGROUND: Transvalvular flow rate (TFR) represents a better reflection of transvalvular flow than the stroke volume index (SVi), and has recently emerged as a useful prognostic tool in patients undergoing surgical aortic valve replacement. There is a paucity of data investigating the role of TFR and its relationship with other clinical or echocardiographic factors in patients undergoing transcatheter aortic valve implantation (TAVI). METHOD: This was a retrospective single-centre study of 629 consecutive patients who underwent TAVI between March 2009 and September 2020. Pre-TAVI low TFR was defined as <200 c/s. The primary study end point was all-cause mortality. RESULTS: Low TFR was observed in 41.8% (263/629) of included patients and was associated with increasing age, low body surface area, hypertension, diabetes, atrial fibrillation, left ventricular (LV) dysfunction, and significant mitral regurgitation. LV function status and severity of aortic valve disease were independent predictors of low TFR. Low TFR was significantly associated with long-term all-cause mortality even after adjustment for other risk factors (adjusted hazard ratio [aHR] 1.44; 95% confidence interval [CI] 1.02-2.03; p=0.038). When data were stratified according to SVi, low TFR was an independent predictor of long-term all-cause mortality in patients with normal SVi (aHR 1.98; 95% CI 1.06-3.69; p=0.032) but not in patients with low SVi (HR 1.23; 95% CI 0.71-2.11; p=0.46; p=0.016 for interaction). CONCLUSIONS: Low TFR is common in patients undergoing TAVI and is an independent predictor of all-cause mortality, particularly in patients with normal SVi.

Empty stomach together with menstrual bleeding as predictors of committed suicides among women of reproductive age: What a primary physician must know.

Background: Women of reproductive age group (WoRAG) are among the most vulnerable groups to suicide in India. The present study intended to develop a mathematical model to differentiate suicides from homicides among WoRAG. Methods: It was a cross-sectional study based on a record review of autopsy at Patna, India, from 2016 to 2021. The cause of deaths was ascertained by autopsies and other records independently by two investigators to reduce the interobserver bias. Independent variables were tested with confirmed suicides to calculate statistically significant association. These variables were further used for developing prediction models for the suicides by multivariate logistic regression analysis. Results: Out of total of 520 autopsies of WoRAG performed by investigators, the cause of death has been confirmed for 62. Of them, 30 were confirmed as suicides. In univariate analysis, suicides were associated with the menstrual bleed (OR 35 CI 6.9,179), gastric emptying (OR 3.9 CI 1.2,12.8), hanging, poisoning, and drowning as mode of death (OR 435 CI 37.4,5061.9). By logistic regression, three prediction models were built to predict suicide; Model I: gastric emptying, Model II: menstrual bleed, and Model III: including both. The area under the curve (AUC) for Models I, II, and III was 0.67 (95%CI 0.34,0.99), 0.92 (95%CI 0.75,1.00), and 0.94 (95%CI 0.82,1.00), respectively. The AUC of Model III differs significantly from that of Model I (P value 0.03) but not with Model II (P value 0.11). Conclusion: Menstrual bleed, gastric emptying, and mode of death may be used as a supplement tool in ascertaining the cause of death among WoRAG in medical and legal proceedings.

A Systematic Review and Meta-Analysis of the Clinical Outcomes of Isolated Tricuspid Valve Surgery.

Patients with isolated tricuspid valve (TV) disease have poor prognosis with no consensus on their management. Transcatheter TV intervention is emerging as a valid option in patients with prohibitive surgical risk. We analyzed studies of patients who underwent isolated TV surgery to identify the features associated with successful clinical outcomes. We performed a systematic review and meta-analysis of studies reporting clinical outcomes of isolated surgical TV intervention, namely TV repair, TV replacement with a bioprosthetic valve (TVR-B), or TV replacement with a mechanical valve (TVR-M). Twenty-seven studies involving 10,478 patients (4,931 TV repair, 3,821 TVR-B, and 1,713 TVR-M) were included. Early mortality occurred in 9% and did not differ between TV surgical approaches. Late mortality was 27% at a median follow-up of 4 (3 to 6) years and was significantly higher for all-TVR (30% vs 25%, rate ratio 1.18, 95% confidence interval 1.05 to 1.31, p = 0.004) and TVR-B (28% vs 24%, rate ratio 1.15, 95% confidence interval 1.02 to 1.30, p = 0.02) compared with TV repair. Late mortality did not differ between TVR-B and TVR-M. Across all studies, early complications included bleeding (7.4%), acute kidney injury (18.7%), permanent pacemaker (13.7%), cerebrovascular accidents (1.2%), and infection (8.9%). Late clinical outcomes included reintervention (3.7%), structural valve deterioration (2.4%), valve thrombosis (2.6%), and TV regurgitation recurrence after 1 year (15.0%). In conclusion, in isolated TV surgeries, TV repair has favorable long-term mortality compared with TV replacement. This supports the development and refinement of transcatheter TV repair approaches. Future research is recommended to provide comparative data for various transcatheter TV interventions.

Abbreviated or Standard Antiplatelet Therapy in HBR Patients: Final 15-Month Results of the MASTER-DAPT Trial.

BACKGROUND: Clinical outcomes and treatment selection after completing the randomized phase of modern trials, investigating antiplatelet therapy (APT) after percutaneous coronary intervention (PCI), are unknown. OBJECTIVES: The authors sought to investigate cumulative 15-month and 12-to-15-month outcomes after PCI during routine care in the MASTER DAPT trial. METHODS: The MASTER DAPT trial randomized 4,579 high bleeding risk patients to abbreviated (n = 2,295) or standard (n = 2,284) APT regimens. Coprimary outcomes were net adverse clinical outcomes (NACE) (all-cause death, myocardial infarction, stroke, and BARC 3 or 5 bleeding); major adverse cardiac and cerebral events (MACCE) (all-cause death, myocardial infarction, and stroke); and BARC type 2, 3, or 5 bleeding. RESULTS: At 15 months, prior allocation to a standard APT regimen was associated with greater use of intensified APT; NACE and MACCE did not differ between abbreviated vs standard APT (HR: 0.92 [95% CI: 0.76-1.12]; P = 0.399 and HR: 0.94 [95% CI: 0.76-1.17]; P = 0.579; respectively), as during the routine care period (HR: 0.81 [95% CI: 0.50-1.30]; P = 0.387 and HR: 0.74 [95% CI: 0.43-1.26]; P = 0.268; respectively). BARC 2, 3, or 5 was lower with abbreviated APT at 15 months (HR: 0.68 [95% CI: 0.56-0.83]; P = 0.0001) and did not differ during the routine care period. The treatment effects during routine care were consistent with those observed within 12 months after PCI. CONCLUSIONS: At 15 months, NACE and MACCE did not differ in the 2 study groups, whereas the risk of major or clinically relevant nonmajor bleeding remained lower with abbreviated compared with standard APT. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Aspirin Versus Dual Antiplatelet Therapy in Patients Undergoing Trans-Catheter Aortic Valve Implantation, Updated Meta-Analysis.

BACKGROUND: The Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic-Valve Implantation (POPular TAVI) trial reported comparable composite endpoints of ischemic events using aspirin compared to dual antiplatelet therapy (DAPT). However, this trial was not powered to detect individual differences in ischemic events. We sought to conduct a meta-analysis to compare aspirin to DAPT on ischemic and bleeding events following TAVI. METHODS: The MEDLINE database was searched from inception until September 2020 and only randomized clinical trials of patients receiving antiplatelet therapy following TAVI were included. The treatment effect was reported as rate ratios (RRs) with 95% confidence intervals. RESULTS: Four randomized clinical trials of 1086 TAVI patients were included. There was a 51% reduction in major or life-threatening bleeding with aspirin compared with DAPT [RR 0.49, (95%CI 0.31 to 0.78)]. Aspirin was not associated with an increased risk of death [RR 1.01, (95%CI 0.62 to 1.65)], cardiovascular death [RR 1.15, (95%CI 0.56 to 2.36)], ischemic stroke [RR 0.93, (95%CI 0.51 to 1.70)], or MI [RR 0.53, (95%CI 0.18 to 1.57)]. CONCLUSIONS: This meta-analysis supports the use of aspirin as the optimal antiplatelet strategy following TAVI procedures in reducing bleeding without an increase in ischemic events compared with dual antiplatelet therapy.

Role of coronary angiogram before transcatheter aortic valve implantation.

BACKGROUND: Coexistent coronary artery disease is commonly seen in patients undergoing transcatheter aortic valve implantation (TAVI). Previous studies showed that pre-TAVI coronary revascularisation was not associated with improved outcomes, challenging the clinical value of routine coronary angiogram (CA). AIM: To assess whether a selective approach to perform pre-TAVI CA is safe and feasible. METHODS: This was a retrospective non-randomised single-centre analysis of consecutive patients undergoing TAVI. A selective approach for performing CA tailored to patient clinical need was developed. Clinical outcomes were compared based on whether patients underwent CA. The primary endpoint was a composite of all-cause mortality, myocardial infraction, repeat CA, and re-admission with heart failure. RESULTS: Of 348 patients (average age 81 ± 7 and 57% male) were included with a median follow up of 19 (9-31) mo. One hundred and fifty-four (44%) patients, underwent CA before TAVI procedure. Patients who underwent CA were more likely to have previous myocardial infarction (MI) and previous percutaneous revascularisation. The primary endpoint was comparable between the two group (22.6% vs 22.2%; hazard ratio 1.05, 95%CI: 0.67-1.64, P = 0.82). Patients who had CA were less likely to be readmitted with heart failure (P = 0.022), but more likely to have repeat CA (P = 0.002) and MI (P = 0.007). In those who underwent CA, the presence of flow limiting lesions did not affect the incidence of primary endpoint, or its components, except for increased rate of repeat CA. CONCLUSION: Selective CA is a feasible and safe approach. The clinical value of routine CA should be challenged in future randomised trials.

Effect of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size in anterior STEMI: PiCSO in ACS study.

BACKGROUND: The aim of this clinical research was to investigate the effects of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size at 5 days after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: This comparative study was carried out in four UK hospitals. Forty-five patients with anterior STEMI presenting within 12 h of symptom onset received pPCI plus PiCSO (initiated after reperfusion; n = 45) and were compared with a propensity score-matched control cohort from INFUSE-AMI (n = 80). Infarct size (% of LV mass, median [interquartile range]) measured by cardiac magnetic resonance (CMR) at day 5 was significantly lower in the PiCSO group (14.3% [95% CI 9.2-19.4%] vs. 21.2% [95% CI 18.0-24.4%]; p = 0.023). There were no major adverse cardiac events (MACE) related to the PiCSO intervention. CONCLUSIONS: PiCSO, as an adjunct to pPCI, was associated with a lower infarct size at 5 days after anterior STEMI in a propensity score-matched population.

Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction.

AIMS: Following a favourable pilot trial using a single bolus of ciclosporin, it has been unclear why 2 large studies (CYCLE and CIRCUS) failed to prevent reperfusion injury and reduce infarct size in STEMI (ST elevation myocardial infarction). The purpose of this study was to assess the effect of ciclosporin on myocardial injury, left ventricular remodelling and lymphocyte kinetics in patients with acute STEMI undergoing primary percutaneous coronary intervention. METHODS: In this double-blind, single centre trial, we randomly assigned 52 acute STEMI patients with an onset of pain of <6 hours and blocked culprit artery to a single bolus of ciclosporin (n = 26) or placebo (n = 26, control group) prior to reperfusion by stent percutaneous coronary intervention. The primary endpoint was infarct size at 12 weeks. RESULTS: Mean infarct size at 12 weeks was identical in both groups (9.1% [standard deviation= 7.0] vs 9.1% [standard deviation = 7.0], P = .99; 95% confidence interval for difference: -4.0 to 4.1). CD3 T-lymphocytes dropped to similar levels at 90 minutes (867 vs 852 cells/µL, control vs ciclosporin) and increased to 1454 vs 1650 cells/µL at 24 hours. CONCLUSION: In our pilot trial, a single ciclosporin bolus did not affect infarct size or left ventricular remodelling, matching the results from CYCLE and CIRCUS. Our study suggests that ciclosporin does either not reach ischaemic cardiomyocytes, or requires earlier application during first medical contact. Finally, 1 bolus of ciclosporin is not sufficient to inhibit CD4 T-lymphocyte proliferation during remodelling. We therefore believe that further studies are warranted. (Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary percutaneous coronary intervention [CAPRI]; NCT02390674).

An Optimized Approach for Transfemoral Transcatheter Aortic Valve Implantation: A Comprehensive Review and Current Evidence.

Device iterations and technical refinements have enabled transcatheter aortic valve implantation (TAVI) to be offered as a routine interventional procedure in many centers with high reproducibility and success. The concept of a streamlined procedure with appropriate procedural optimization, namely "optimized approach," has become increasingly relevant, aimed at minimizing perioperative burden and promoting early recovery. Relatively high device costs may be mitigated by reducing length of hospital stay and resource utilization. This review summarizes current evidence of components related to the optimization process during transfemoral TAVI. It is important to customize the procedure specific to each patient for its optimization.

Outcomes of Direct Flow Medical vs Sapien 3 Transcatheter Aortic Valve Devices.

This retrospective study was aimed to compare the safety and efficacy of the Direct Flow Medical (DFM) valve with the more established Sapien 3 (S3) valve in transfemoral TAVI in high-risk aortic stenosis (AS) patients. Between February 2014 and August 2016, 99 and 68 patients had the S3 and DFM valves at our center, respectively. The device success rate was statistically similar among the S3 and DFM groups (p = 0.15). The overall post-procedural complication rate was similar between the two groups (p = 0.4). The procedural time was significantly shorter in the S3 group (p < 0.001) and the post-procedure peak pressure gradient (p < 0.001) was significantly higher in the DFM group. However, the frequency of valvular or paravalvular leaks was similar between both valve groups. We found no significant differences in terms of safety between the DFM and S3 valves. This study confirms the safety and efficacy of the DFM valve in high-risk AS patients.

Magnetic Resonance Perfusion or Fractional Flow Reserve in Coronary Disease.

BACKGROUND: In patients with stable angina, two strategies are often used to guide revascularization: one involves myocardial-perfusion cardiovascular magnetic resonance imaging (MRI), and the other involves invasive angiography and measurement of fractional flow reserve (FFR). Whether a cardiovascular MRI-based strategy is noninferior to an FFR-based strategy with respect to major adverse cardiac events has not been established. METHODS: We performed an unblinded, multicenter, clinical-effectiveness trial by randomly assigning 918 patients with typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test to a cardiovascular MRI-based strategy or an FFR-based strategy. Revascularization was recommended for patients in the cardiovascular-MRI group with ischemia in at least 6% of the myocardium or in the FFR group with an FFR of 0.8 or less. The composite primary outcome was death, nonfatal myocardial infarction, or target-vessel revascularization within 1 year. The noninferiority margin was a risk difference of 6 percentage points. RESULTS: A total of 184 of 454 patients (40.5%) in the cardiovascular-MRI group and 213 of 464 patients (45.9%) in the FFR group met criteria to recommend revascularization (P = 0.11). Fewer patients in the cardiovascular-MRI group than in the FFR group underwent index revascularization (162 [35.7%] vs. 209 [45.0%], P = 0.005). The primary outcome occurred in 15 of 421 patients (3.6%) in the cardiovascular-MRI group and 16 of 430 patients (3.7%) in the FFR group (risk difference, -0.2 percentage points; 95% confidence interval, -2.7 to 2.4), findings that met the noninferiority threshold. The percentage of patients free from angina at 12 months did not differ significantly between the two groups (49.2% in the cardiovascular-MRI group and 43.8% in the FFR group, P = 0.21). CONCLUSIONS: Among patients with stable angina and risk factors for coronary artery disease, myocardial-perfusion cardiovascular MRI was associated with a lower incidence of coronary revascularization than FFR and was noninferior to FFR with respect to major adverse cardiac events. (Funded by the Guy's and St. Thomas' Biomedical Research Centre of the National Institute for Health Research and others; MR-INFORM ClinicalTrials.gov number, NCT01236807.).

Transcatheter Treatment of Bicuspid Aortic Valve Disease: Imaging and Interventional Considerations.

Patients with bicuspid aortic valve disease have systematically been excluded from large randomized clinical trials investigating transcatheter aortic valve implantation (TAVI) due to their younger age, lower surgical risk and complex aortic anatomy. The asymmetric nature of the bicuspid valve orifice often accompanied by heavy regional calcification has led to concerns regarding valve positioning and expansion. Bicuspid aortic valve disease patients are at heightened risk of TAVI-related complications including coronary occlusion, aortic dissection and annular rupture, as well as the known risks of progressive aortopathy in these patients. These unique anatomical characteristics pose challenges for TAVI operators. However, with recent and ongoing refinements in implantation technique, improvements in pre-procedural imaging and iterations in device design, TAVI is emerging as a safe and feasible treatment option in this population. Paravalvular aortic regurgitation and high pacemaker rates have been the Achilles Heel for TAVI in bicuspid valve patients, yet newer generation devices are yielding promising results. Further studies are required before TAVI ultimately emerges as a viable option in low and intermediate surgical-risk patients with bicuspid valve disease. This review comprehensively summarizes the epidemiology, pathology and current evidence for TAVI in patients with bicuspid aortic valve disease. We also outline some practical tips for performing TAVI in these patients.

Overcoming Heparin-Associated RT-qPCR Inhibition and Normalization Issues for microRNA Quantification in Patients with Acute Myocardial Infarction.

BACKGROUND: Cardiac-enriched micro ribonucleic acids (miRNAs) are released into the circulation following ST-elevation myocardial infarction (STEMI). Lack of standardized approaches for reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) data normalization and presence of RT-qPCR inhibitors (e.g. heparin) in patient blood samples have prevented reproducible miRNA quantification in this cohort and subsequent translation of these biomarkers to clinical practice. MATERIALS AND METHODS: Using a RT-qPCR miRNA screening platform, we identified and validated an endogenous circulating miRNA as a normalization control. In addition, we assessed the effects of in vivo and in vitro anticoagulant drugs administration (heparin and bivalirudin) on three RT-qPCR normalization strategies (global miRNA mean, exogenous spike-in control [cel-miR-39] and endogenous miRNA control). Finally, we evaluated the effect of heparin and its in vitro inhibition with heparinase on the quantification of cardiac-enriched miRNAs in STEMI patients. RESULTS: miR-425-5p was validated as an endogenous miRNA control. Heparin administration in vitro and in vivo inhibited all RT-qPCR normalization strategies. In contrast, bivalirudin had no effects on cel-miR-39 or miR-425-5p quantification. In vitro RNA sample treatment with 0.3 U of heparinase overcame heparin-induced over-estimation of cardiac-enriched miRNA levels and improved their correlation with high-sensitivity troponin T. CONCLUSION: miRNA quantification in STEMI patients receiving heparin is jeopardized by its effect on all RT-qPCR normalization approaches. Use of samples from bivalirudin-treated patients or in vitro treatment of heparin-contaminated samples with heparinase are suitable alternatives for miRNA quantification in this cohort. Finally, we reinforce the evidence that cardiac-enriched miRNAs early after myocardial reperfusion reflect the severity of cardiac injury.

Safety and Efficacy of Delayed-Release Dimethyl Fumarate in Pediatric Patients With Relapsing Multiple Sclerosis (FOCUS).

BACKGROUND: No therapies have been formally approved by the Food and Drug Administration for use in pediatric multiple sclerosis, a rare disease. OBJECTIVE: We evaluated the safety, efficacy, and pharmacokinetics of dimethyl fumarate in pediatric patients with multiple sclerosis. METHODS: FOCUS, a phase 2, multicenter study of patients aged 10 to 17 years with relapsing-remitting multiple sclerosis, comprised an eight-week baseline and 24-week treatment period; during treatment, patients received dimethyl fumarate (120 mg twice daily on days one to seven; 240 mg twice a day thereafter). Magnetic resonance imaging scans were obtained at week -8, day 0, week 16, and week 24. The primary end point was the change in T2 hyperintense lesion incidence from the baseline period to the final 8 weeks of treatment. Secondary end points were pharmacokinetic parameters and adverse event incidence. RESULTS: Twenty of 22 enrolled patients completed the study. There was a significant reduction in T2 hyperintense lesion incidence from baseline to the final eight weeks of treatment (P = 0.009). Adverse events (most commonly gastrointestinal events and flushing) and pharmacokinetic parameters were consistent with adult findings. No serious adverse events were considered dimethyl fumarate related. CONCLUSIONS: Dimethyl fumarate treatment was associated with a reduction in magnetic resonance imaging activity in pediatric patients; pharmacokinetic and safety profiles were consistent with those in adults. Dimethyl fumarate is a potential treatment for pediatric multiple sclerosis.

Local Versus General Anesthesia in Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is conventionally performed under general anesthesia (GA) allowing intraoperative transoesophageal echocardiogram imaging. We present our experience in patients having the procedure under local anesthesia (LA), who were subsequently transferred to a low dependency unit postprocedure, to assess safety and length of hospital stay. We retrospectively assessed all the transfemoral TAVR procedures conducted at our center from January 03, 2011. Of 216 patients, 145 had the procedure under GA and 71 under LA. Both groups were similar with respect to age, co-morbidities, Euro Score, and the severity of the aortic stenosis. The procedure time was significantly shorter in the LA group measured from time in room to skin closure (108 vs 143 minutes, p <0.001). Skin open to skin closure time were the same in both groups (78 vs 79.4 minutes, p = 0.57). There was no difference in 30 days: aortic regurgitation > mild (2.1% in GA and 2.8% in LA, p = 0.67), need for permanent pacing (3.4% in GA and 1.4% in LA, p = 0.32), and disabling cerebrovascular accidents (1.4% and 1.4%, p = 1.0). The 30-day survival was not significantly different (95.9% in GA and 100% in LA, p = 0.17), whereas the median number of days in hospital was shorter in the LA group (4 in GA and 2 in LA, p <0.001). No emergency conversions to GA were performed in the LA group and only 1 patient needed admission to a high dependency (HD) unit. In conclusion, performing a TAVR under LA is at least as safe as GA. In addition, there is a reduced procedural time and length of hospital stay. LA is a safe and cost-effective alternative to GA and patients can be safely transferred to a low dependency unit.

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention.

OBJECTIVE: We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. METHODS: In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. RESULTS: From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. CONCLUSIONS: Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar.

T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion injury in patients.

BACKGROUND: Lymphocytes contribute to ischemia/reperfusion (I/R) injury in several organ systems, but their relevance in ST elevation myocardial infarction (STEMI) is unknown. Our goal was to characterize lymphocyte dynamics in individuals after primary percutaneous coronary intervention (PPCI), assess the prognostic relevance of these cells, and explore mechanisms of lymphocyte-associated injury. METHODS: Lymphocyte counts were retrospectively analyzed in 1,377 STEMI patients, and the prognostic relevance of post-PPCI lymphopenia was assessed by Cox proportional hazards regression. Blood from 59 prospectively recruited STEMI patients undergoing PPCI was sampled, and leukocyte subpopulations were quantified. Microvascular obstruction (MVO), a component of I/R injury, was assessed using MRI. RESULTS: In the retrospective cohort, lymphopenia was associated with a lower rate of survival at 3 years (82.8% vs. 96.3%, lowest vs. highest tertile; hazard ratio 2.42). In the prospective cohort, lymphocyte counts fell 90 minutes after reperfusion, primarily due to loss of T cells. CD8+ T cells decreased more than CD4+ T cells, and effector subsets exhibited the largest decline. The early decrease in effector T cell levels was greater in individuals that developed substantial MVO. The drop in T cell subsets correlated with expression of the fractalkine receptor CX3CR1 (r2 = 0.99, P = 0.006). Serum fractalkine concentration peaked at 90 minutes after reperfusion, coinciding with the T cell count nadir. CONCLUSIONS: Lymphopenia following PPCI is associated with poor prognosis. Our data suggest that fractalkine contributes to lymphocyte shifts, which may influence development of MVO through the action of effector T cells. TRIAL REGISTRATION: Not applicable. FUNDING: British Heart Foundation (FS/12/31/29533) and National Institute of Health Research (NIHR) Newcastle Biomedical Research Centre.