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.

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.).

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.

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).

Myocardial ischemia and reperfusion leads to transient CD8 immune deficiency and accelerated immunosenescence in CMV-seropositive patients.

RATIONALE: There is mounting evidence of a higher incidence of coronary heart disease in cytomegalovirus-seropositive individuals. OBJECTIVE: The aim of this study was to investigate whether acute myocardial infarction triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in cytomegalovirus-seropositive patients. METHODS AND RESULTS: Thirty-four patients with acute myocardial infarction undergoing primary percutaneous coronary intervention were longitudinally studied within 3 months after reperfusion (Cohort A). In addition, 54 patients with acute myocardial infarction and chronic myocardial infarction were analyzed in a cross-sectional study (Cohort B). Cytomegalovirus-seropositive patients demonstrated a greater fall in the concentration of terminally differentiated CD8 effector memory T cells (TEMRA) in peripheral blood during the first 30 minutes of reperfusion compared with cytomegalovirus-seronegative patients (-192 versus -63 cells/µL; P=0.008), correlating with the expression of programmed cell death-1 before primary percutaneous coronary intervention (r=0.8; P=0.0002). A significant proportion of TEMRA cells remained depleted for ≥3 months in cytomegalovirus-seropositive patients. Using high-throughput 13-parameter flow cytometry and human leukocyte antigen class I cytomegalovirus-specific dextramers, we confirmed an acute and persistent depletion of terminally differentiated TEMRA and cytomegalovirus-specific CD8(+) cells in cytomegalovirus-seropositive patients. Long-term reconstitution of the TEMRA pool in chronic cytomegalovirus-seropositive postmyocardial infarction patients was associated with signs of terminal differentiation including an increase in killer cell lectin-like receptor subfamily G member 1 and shorter telomere length in CD8(+) T cells (2225 versus 3397 bp; P<0.001). CONCLUSIONS: Myocardial ischemia and reperfusion in cytomegalovirus-seropositive patients undergoing primary percutaneous coronary intervention leads to acute loss of antigen-specific, terminally differentiated CD8 T cells, possibly through programmed cell death-1-dependent programmed cell death. Our results suggest that acute myocardial infarction and reperfusion accelerate immunosenescence in cytomegalovirus-seropositive patients.

Cardiac output in patients with small annuli undergoing transcatheter aortic valve implantation with self-expanding versus balloon expandable valve (COPS-TAVI).

BACKGROUND: There is limited data on cardiac output in patients with small aortic annuli undergoing trans-catheter aortic valve implantation (TAVI) according to the implanted platform of balloon-expandable (BEV) compared to self-expanding valves (SEV). METHODS: This is a retrospective analysis of consecutive patients with severe aortic stenosis and small annuli who underwent successful TAVI. Cardiac output was measured using echocardiography within 4 weeks following TAVI. Data were recorded and analysed by an experienced operator who was not aware of the type of the implanted valve. RESULTS: 138 patients were included in the analysis, of whom 57 % underwent TAVI with BEV. Clinical and echocardiographic characteristics were comparable between the two platforms, except for more frequent previous cardiac surgery and smaller indexed aortic valve in the BEV group. There was no relationship between computed tomography-derived aortic annulus area and cardiac output post TAVI. When compared to patients who underwent TAVI with BEV, those with SEV had larger cardiac output [mean difference - 0.50 l/min, 95 % CI (-0.99, -0.01)] and cardiac index [mean difference - 0.20 l/min/m2, 95 % CI (-0.47, 0.07)], although the latter did not reach statistical significance. Unlike patients with small body surface area, in those with large body surface area both cardiac output and cardiac index were statistically larger in patients who underwent SEV compared to BEV. CONCLUSION: Cardiac output, as measured by echocardiography, was larger in patients with small annuli who underwent TAVI procedure with SEV compared to BEV. Such difference was more evident in patients with large body surface area.

Complete versus incomplete revascularization in patients with a non-ST-elevation myocardial infarction: Analysis from the e-ULTIMASTER registry.

BACKGROUND: Incomplete revascularization (ICR) has been associated with a worse prognosis after a percutaneous coronary intervention (PCI). In NSTEMI patients with multivessel disease (MVD) however, the benefit of a complete revascularization (CR) remains unclear. METHODS: Patients presenting with an NSTEMI and MVD were selected from the global e-ULTIMASTER registry and grouped according to completeness of revascularization at index hospitalization discharge. The primary endpoint was the patient oriented composite endpoint (POCE) defined as all death, any myocardial infarction, and any revascularization at 1 year. Target lesion failure (TLF) was defined as the composite of cardiac death, target vessel related myocardial infarction and clinically driven target lesion revascularization. Inverse propensity score weighting (IPSW) was performed to harmonize the patient's baseline characteristics between the groups. RESULTS: CR was achieved in 1800 patients (47.0 %) and ICR in 2032 patients (53.0 %). The incidence of POCE at 1 year was lower in the CR group compared to the ICR group: 7.0 % vs. 12.9 %, p < 0.0001. Similarly for TLF at 1 year: 3.6 % vs. 5.5 %, p < 0.01. After IPSW, the incidence of POCE was 7.7 % vs. 12.0 %, p < 0.0001, due to a lower all-cause mortality: 2.7 % vs. 4.2 %, p = 0.02 and less revascularizations: 4.9 % vs. 7.9 %, p < 0.001. The incidence of TLF was no longer statistically significant: CR 3.9 % vs. IR 5.0 %, p = 0.10. CONCLUSIONS: Patients with a NSTEMI and multi vessel disease undergoing a percutaneous coronary revascularization with a complete revascularization during index hospitalization have better 1-year clinical outcomes. Randomized studies are warranted to confirm these results.

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.

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).

Intracoronary ECG ST-segment recovery during primary percutaneous intervention for ST-segment myocardial infarction: insights from a cardiac MRI study.

BACKGROUND: ST-segment-resolution (STR) on surface electrocardiogram (ECG) is a good surrogate for myocardial reperfusion in patients with acute ST-segment-elevation-myocardial-infarction (STEMI). We sort to determine the optimal criteria of measuring STR on intracoronary-ECG (IC-ECG) for prediction of myocardial injury evaluated by cardiac MRI (CMR). METHODS: Measurements of IC-ECG ST-segments were performed at baseline, immediately after (early) and 15 min (late) after achieving TIMI-3 flow during primary-PCI. The degree of ST-segment-shift from baseline noted upon the IC-ECG was divided into four groups: (group 1) ST-segment-resolution >1 mm, (group 2) <30% resolution, (group 3) >50% resolution, (group 4) >70% resolution at both early and late time points. Patients had CMR at days 3 and 90 postprimary-PCI. RESULTS: Fifty two patients (aged 60 ± 11 years; 43 males) were evaluated. Early intracoronary-ECG ST-segment resolution (early IC-STR >1 mm) correlated with smaller scar mass (P = 0.003), nonviable myocardial mass (P < 0.001), and microvascular obstruction (MVO) (P = 0.004) on CMR at day 3. Ejection fraction (EF) was also better at day 3 (P = 0.026) and 90 (P = 0.039). Patients with poor early IC-STR (IC-STR <30%) conversely is associated with larger scar mass (P = 0.017), nonviable myocardial mass (P = 0.01), and MVO (P = 0.021) at day 3. This was also associated with worse EF at day 90 (P = 0.044). Neither group 3 or 4, or the late measurements of late IC-STR correlated with CMR markers of myocardial injury. CONCLUSION: The degree of early IC-STR (defined by IC-STR > 1 mm or <30%) successfully predicts myocardial damage following primary-PCI for an acute STEMI. Further studies are required to investigate its potential utility.

Diagnostic accuracy of adenosine stress cardiovascular magnetic resonance following acute ST-segment elevation myocardial infarction post primary angioplasty.

BACKGROUND: Adenosine stress cardiovascular magnetic resonance (CMR) has been proven an effective tool in detection of reversible ischemia. Limited evidence is available regarding its accuracy in the setting of acute coronary syndromes, particularly in evaluating the significance of non-culprit vessel ischaemia. Adenosine stress CMR and recent advances in semi-quantitative image analysis may prove effective in this area. We sought to determine the diagnostic accuracy of semi-quantitative versus visual assessment of adenosine stress CMR in detecting ischemia in non-culprit territory vessels early after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). METHODS: Patients were prospectively enrolled in a CMR imaging protocol with rest and adenosine stress perfusion, viability and cardiac functional assessment 3 days after successful primary-PCI for STEMI. Three short axis slices each divided into 6 segments on first pass adenosine perfusion were visually and semi-quantitatively analysed. Diagnostic accuracy of both methods was compared with non-culprit territory vessels utilising quantitative coronary angiography (QCA) with significant stenosis defined as ≥ 70%. RESULTS: Fifty patients (age 59 ± 12 years) admitted with STEMI were evaluated. All subjects tolerated the adenosine stress CMR imaging protocol with no significant complications. The cohort consisted of 41% anterior and 59% non anterior infarctions. There were a total of 100 non-culprit territory vessels, identified on QCA. The diagnostic accuracy of semi-quantitative analysis was 96% with sensitivity of 99%, specificity of 67%, positive predictive value (PPV) of 97% and negative predictive value (NPV) of 86%. Visual analysis had a diagnostic accuracy of 93% with sensitivity of 96%, specificity of 50%, PPV of 97% and NPV of 43%. CONCLUSION: Adenosine stress CMR allows accurate detection of non-culprit territory stenosis in patients successfully treated with primary-PCI post STEMI. Semi-quantitative analysis may be required for improved accuracy. Larger studies are however required to demonstrate that early detection of non-culprit vessel ischemia in the post STEMI setting provides a meaningful test to guide clinical decision making and ultimately improved patient outcomes.

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.

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.

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.

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.

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.

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.

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.