The safety of sodium glucose transporter 2 inhibitors and trends in clinical and hemodynamic parameters in patients with left ventricular assist devices.

BACKGROUND: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2-I) in patients with left ventricular assist devices (LVAD) are unknown. METHODS: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2-I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2-I. RESULTS: SGLT2-I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2-I initiation was 108 days, IQR (26-477). Following SGLT2-I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2-38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7-4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23-11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2-I initiation (p > 0.2 for all). No adverse events were recorded during median follow-up of 354 days, IQR (206-786). CONCLUSION: SGLT2-I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP.

Outcome and safety of intraoperative defibrillation testing during device replacement: the Simpler trial.

AIMS: Intraoperative defibrillation testing (DT) during implant or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and Nordic ICD trials, and the practice of testing during new implantations has essentially been almost abandoned. Old registries demonstrated an increased incidence of significant findings in DT during replacements. The aim of the present study was to evaluate frequency of significant findings and safety of DT in subjects undergoing device replacement. METHODS AND RESULTS: A prospective observational multi-centre study included consecutive patients undergoing ICD generator replacement. The primary outcome was a failure to terminate induced ventricular fibrillation (VF) with a single shock 10 J below the maximal capacity of the device. Secondary outcomes included complications of DT. Patients were followed-up at 1- and 6-months post-procedure. A total of 92 patients were eligible, and consented to the study, of which 84 underwent DT during battery replacement. The median age was 68 years and 79.8% were males. Induction of VF was successful in 84 patients as was a successful conversion on the first attempt in all. There were no procedure-related complications. During follow up one patient had two appropriate ICD shock events. In four patients, ICD programming was changed. None suffered inappropriate shock. There was no evidence of lead malfunction. Two deaths occurred, none of which was related to arrhythmia. CONCLUSION: The present study found DT was not associated with complications in patients undergoing ICD generator replacement but produced no clinically important information.

Left atrial size predicts long-term outcome after balloon mitral valvuloplasty.

BACKGROUND: The treatment of choice for severe rheumatic mitral stenosis is balloon mitral valvuloplasty (BMV). Numerous predictors of immediate and long-term procedural success have been described. The aims of this study were to describe our experience with BMV over the last decade and to evaluate predictors of long-term event-free survival. METHODS: Medical records were retrospectively analyzed of patients who underwent BMV between 2009 and 2021. The primary outcome was a composite endpoint of all-cause mortality, mitral valve replacement (MVR), and repeat BMV. Long-term event-free survival was estimated using Kaplan-Meier curves. Logistic regression was used to create a multivariate model to assess pre-procedural predictors of the primary outcome. RESULTS: A total of 96 patients underwent BMV during the study period. The primary outcome occurred in 36 patients during 12-year follow-up: one (1%) patient underwent re-BMV, 28 (29%) underwent MVR, and eight (8%) died. Overall, event-free survival was 62% at 12 years. On multivariate analysis, pre-procedural left atrial volume index (LAVI) > 80 mL/m2 had a significant independent influence on event-free survival, as did previous mitral valve procedure and systolic pulmonary arterial pressure above 50 mmHg. CONCLUSIONS: Despite being a relatively low-volume center, excellent short and long-term results were demonstrated, with event-free survival rates consistent with previous studies from high-volume centers. LAVI independently predicted long-term event-free survival.

Hemodynamic Changes After Left Ventricular Assist Device Implantation Among Heart Failure Patients With and Without Elevated Pulmonary Vascular Resistance.

Background: Left ventricular assist devices (LVADs) may reverse elevated pulmonary vascular resistance (PVR) which is associated with worse prognosis in heart failure (HF) patients. We aim to describe the temporal changes in hemodynamic parameters before and after LVAD implantation among patients with or without elevated PVR. Methods: HF patients who received continuous-flow LVAD (HeartMate 2&3) at a tertiary medical center and underwent right heart catheterization with PVR reversibility study before and after LVAD surgery. Patients were divided into 3 groups: normal PVR (<4WU); reversible PVR (initial PVR ≥4WU with positive reversibility); and non-reversible (persistent PVR ≥4WU). Results: Overall, 85 LVAD patients with a mean age of 58 years (IQR 49-64), 65 patients (76%) were male; 60 patients had normal PVR, 20 patients with reversible and 5 patients with non-reversible PVR pre-LVAD. All patients with elevated PVR (≥4WU) had higher pulmonary pressures (PP) and increased trans-pulmonary gradient (TPG) compared to patients with normal PVR (p < 0.05). Patients with non-reversible PVR were more likely to have a significantly lower baseline cardiac output (CO) compared to all other groups (p ≤ 0.02). Hemodynamic parameters and PVR post LVAD were similar in all study groups. Patients with baseline elevated PVR (reversible and non-reversible) demonstrated a significant improvement in PP and TPG compared to patients with normal baseline PVR (p ≤ 0.05). The improvement in CO and PVR post-LVAD in the non-reversible PVR group was significantly greater compared to all other groups (p < 0.01). There were no significant differences between study groups in post LVAD and post heart transplantation course. Conclusion: Hemodynamic parameters improved after LVAD implantation, regardless of baseline PVR and reversibility, and enabled heart transplantation in patients who were ineligible due to non-reversible elevated PVR. Our findings suggest that mitigation of elevated non-reversible PVR is related to reduction in PP and increase in CO.

Clinical Outcome and Safety of Transcaval Access for Transcatheter Aortic Valve Replacement as Compared to Other Alternative Approaches.

Background: A small proportion of patients in need of transcatheter aortic valve replacement (TAVR) are not suitable for the transfemoral approach due to peripheral artery disease. Alternative TAVR approaches are associated with short- and long-term hazards. A novel technique of caval-aortic (transcaval) access for TAVR has been utilized as an alternative access technique. Aim: To compare safety and efficacy of transcaval access as compared to other alternative access (axillary or apical) for TAVR. Methods: A single-center, retrospective analysis of consecutive patients undergoing alternative access for TAVR. Events were adjudicated according to VARC-2 criteria. Results: A total of 185 patients were included in the present analysis. Mean age was 81 years with a small majority for male gender (54%). Of the entire cohort, 20 patients (12%) underwent transcaval TAVR, and 165 patients (82%) underwent TAVR using alternative access. Overall, baseline characteristics were comparable between the two groups. General anesthesia was not utilized in transcaval patients; however, it was routinely used in nearly all alternative access patients. TAVR device success was comparable between the two groups (95%). Acute kidney injury occurred significantly less frequently among transcaval patients as compared to alternative access patients (5 vs. 12%, p = 0.05). Hospital stay was shorter for transcaval patients (6.3 days vs. 14.4; p < 0.001). No difference in early or 30-day mortality (10 vs. 7.9%, p = 0.74) was noted between groups. Conclusions: In patients who cannot undergo TAVR via the trans-femoral approach due to peripheral vascular disease, transcaval access is a safe approach as compared to other alternative access techniques, with lower risk of kidney injury and shorter hospital stay.

Mitral Annulus Calcium Score.

BACKGROUND: The risk of conduction system abnormalities (CSA) after transcatheter aortic valve implantation remains high. We aimed to evaluate the impact of mitral annular calcium (MAC) score on the development of CSA after transcatheter aortic valve implantation. METHODS: Consecutive patients (n=168), with severe AoV stenosis, without prior CSA, underwent computed tomography transcatheter AoV implantation followed by device implantation; CoreValve (n=72) and SAPIEN (n=96). MAC, AoV, and left ventricular outflow tract calcium (Ca++) scores were quantitated from noncontrast ECG-gated computed tomography using Agatston method. The primary end point was a combination of complete left bundle branch block or high-degree atrioventricular block. Logistic regression was used to analyze the predictive value of Ca++ scores of different locations. RESULTS: The primary end point was documented in 62% of the fourth quartile MAC score (>2700) patients as compared with 31% of the first quartile (<140); P=0.03. Logistic regression analysis documented MAC score as an independent predictor either of primary end point as a continuous variable (odds ratio: 1.02, 95% [CI]: 1.00 - 1.03, p = 0.021) or as quartile cutoffs, whereas Q4 was a strong and independent predictor (odds ratio: 3.69, 95% [CI]: 1.37 - 9.95, p = 0.010). CONCLUSIONS: MAC score was found to be an independent predictor of CSA in patients undergoing transcatheter aortic valve implantation without preexisting CSA. Therefore, the current study suggests that patients with high MAC score category (fourth MAC score quartile) should be considered at high risk for CSA, warranting closer monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02023060.

Acute myocardial infarction occurring while on chronic clopidogrel therapy ('clopidogrel failure') is associated with high incidence of clopidogrel poor responsiveness and stent thrombosis.

OBJECTIVES: The clinical significance of the laboratory-based phenomenon of clopidogrel hypo-responsiveness and platelet reactivity associated with acute myocardial infarction, despite chronic clopidogrel therapy, is largely unknown. We aimed to determine platelet reactivity and clinical and angiographic features in 29 consecutive patients sustaining an acute myocardial infarction despite chronic (≥1 month) clopidogrel therapy. METHODS: Platelet reactivity was determined on admission using conventional aggregometry. All patients underwent coronary angiography within 24 hours of admission. Patients were matched with clopidogrel-naïve acute myocardial infarction patients. Clopidogrel-naïve patients received a 600 mg clopidogrel loading dose and 75 mg/day thereafter. RESULTS: Of the 29 study patients, 19 (66%) presented with ST-elevation myocardial infarction, and in 25% the infarction was related to angiographically-proved definite stent thrombosis. Two-thirds of these patients were poor responders to clopidogrel (adenosine diphosphate-induced platelet aggregation >50%) and dual antiplatelet poor responsiveness was found in 57% in the chronic clopidogrel therapy group. Compared with clopidogrel-naïve patients, chronic clopidogrel therapy patients were more likely to demonstrate clopidogrel poor responsiveness (66% versus 38%, p = 0.02), to be diabetic (52% versus 33%, p = 0.1) and to have multi-vessel coronary disease (79% versus 55%, p = 0.03). CONCLUSIONS: Patients sustaining acute coronary syndrome despite chronic clopidogrel therapy are more likely to exhibit inadequate platelet inhibition with clopidogrel.

Favorable Short-Term and Long-Term Outcomes Among Patients With Prior History of Malignancy Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is now the treatment of choice for high-surgical risk patients with symptomatic aortic stenosis. Little is known regarding the outcome of TAVR in patients with previous malignancy. METHODS: We investigated 477 patients who underwent TAVR in a tertiary medical center. Subjects were divided into two groups according to malignancy status: no history of malignancy (n = 386) and positive history of malignancy (n = 91). RESULTS: Mean age of the study population was 81 ± 7 years, and 52% were men. No major differences in baseline characteristics were found between groups. All-cause mortality was 24% for both malignancy and non-malignancy groups at a mean follow-up of 851 ± 629 days. Kaplan-Meier survival analysis demonstrated no difference in all-cause mortality between groups. Multivariate Cox regression analysis showed that malignancy status did not affect prognosis regarding overall mortality (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.5-1.4; P=.46). However, cancer therapy administered within 12-months of TAVR was significantly associated with increased total mortality among patients undergoing TAVR (HR, 4.38; 95% CI, 1.14-16.77; P=.03). CONCLUSIONS: Malignancy is a common comorbidity among TAVR candidates. Mere history of malignancy among elderly patients does not adversely affect short-term or long-term outcomes after TAVR; however, history of recent (<1 year) cancer-related treatment increases the risk for long-term mortality after TAVR. Decisions regarding TAVR among oncological patients should be individualized according to their malignancy status and anticipated life expectancy.

Effect of Chewing vs Swallowing Ticagrelor on Platelet Inhibition in Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Objective: To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI. Design, Setting, and Participants: A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat. Interventions: Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose. Main Outcomes and Measures: P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. Results: Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99). Conclusions and Relevance: Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT02725099.

Comparison of Outcome of Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis in 3 Age Groups (≤70; 71 to 80, and ≥81 Years).

Transcatheter aortic valve implantation (TAVI) has been widely used for the treatment of aortic stenosis. Most pivotal studies of TAVI included patients with a mean age of over 80 years old. Many young patients may also be considered for TAVI because of severe co-morbidities. We sought to describe a group of patients undergoing TAVI at an age below 70 and to compare them with older patients undergoing the procedure. This study included 1,324 consecutive patients from a 3-center TAVI registry from 2008 to 2014. Patients were divided according to age into 3 groups: patients aged 70 years and below, patients between the ages of 71 and 80, and patients 81 years and older. Patients in the younger group had higher body mass index (p <0.001), higher proportion of previous stroke (p = 0.05), peripheral vascular disease (p = 0.03), and diabetes mellitus (p <0.001). Thirty percent of patients in the younger group had functional class IV. Corticosteroids treatment was 5-fold higher in the younger group (p <0.001). Average valve area was lower in the older group (p = 0.004). Thirty-day mortality was similar between the 3 groups. We found no difference in the rate of in-hospital complications. One-year all-cause mortality rate of patients aged 70 years, 71 to 80 years, and >80 years was 7.6%, 7.5%, and 12.6%, respectively, p = 0.01. In conclusion, younger patients undergoing TAVI exhibited higher prevalence of risk factors and co-morbidities that probably explain the decision to perform TAVI rather than surgical aortic valve replacement. Nevertheless, the 1-year mortality of these patients was significantly lower than in older patients.

Addition of albumin to Traditional Risk Score Improved Prediction of Mortality in Individuals Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVES: The ability of the Society of Thoracic Surgeons (STS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE)-2 scores to predict outcomes after transcatheter aortic valve replacement (TAVR) is insufficient. Frailty and serum albumin as a frailty marker were shown to correlate with prognosis after TAVR. We sought to evaluate the additive value of serum albumin to STS and EuroSCORE-2 scores to predict mortality in individuals undergoing TAVR. DESIGN: Retrospective analysis. SETTING: Tertiary-care hospital prospective registry. PARTICIPANTS: Individuals who underwent TAVR (N = 426). MEASUREMENTS: We compared survival rates according to median baseline albumin levels (4 g/dL), STS score (4.5%), and EuroSCORE-2 (3.45%). Participants were divided into four groups according to median serum albumin and median STS and EuroSCORE-2 scores (high vs low), and 1-year survival rates were compared. A category-free net reclassification index (NRI) was calculated to compare the ability of a model of STS or EuroSCORE-2 alone to classify mortality risk with and without the addition of baseline serum albumin. RESULTS: Participants with low albumin levels had higher mortality (hazard ratio (HR) = 3.03, 95% confidence interval (CI) = 1.66-5.26, P < .001). Participants with low serum albumin and a high STS (HR = 4.55, 95% CI = 2.21-9.38, P < .001) or EuroSCORE-2 (HR = 2.72, 95% CI = 1.48-5.06, P = .001) score had higher mortality. Using NRI analysis, a model that included albumin in addition to STS correctly reclassified 42% of events (NRI = 0.58) and a model that included albumin in addition to EuroSCORE-2 correctly reclassified 44% of events (NRI = 0.64). CONCLUSION: Serum albumin, as a marker of frailty, can significantly improve the ability of STS and EuroSCORE-2 scores to predict TAVR-related mortality.

The Prognostic Effects of Coronary Disease Severity and Completeness of Revascularization on Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVES: The study sought to examine the effect of coronary artery disease (CAD) on mortality in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is common in the TAVR population. However, there are conflicting data on the prognostic significance of CAD and its treatment in this population. METHODS: The authors analyzed 1,270 consecutive patients with severe aortic stenosis (AS) undergoing TAVR at 3 Israeli centers. They investigated the association of CAD severity (no CAD, nonsevere CAD [i.e., SYNTAX score (SS) <22], severe CAD [SS >22]) and revascularization completeness ("reasonable" incomplete revascularization [ICR] [i.e., residual SS <8]; ICR [residual SS >8]) with all-cause mortality following TAVR using a Cox proportional hazards ratio model adjusted for multiple prognostic variables. RESULTS: Of the 1,270 patients, 817 (64%) had no CAD, 331 (26%) had nonsevere CAD, and 122 (10%) had severe CAD. Over a median follow-up of 1.9 years, 311 (24.5%) patients died. Mortality was higher in the severe CAD and the ICR groups, but not in the nonsevere CAD or "reasonable" ICR groups, versus no CAD. After multivariate adjustment, both severe CAD (hazard ratio: 2.091; p = 0.017) and ICR (hazard ratio: 1.720; p = 0.031) were associated with increased mortality. CONCLUSIONS: Only severe CAD was associated with increased mortality post-TAVR. More complete revascularization pre-TAVR may attenuate the association of severe CAD and mortality.

Chewing versus Swallowing Ticagrelor to Accelerate Platelet Inhibition in Acute Coronary Syndrome - the CHEERS study. For The PLATIS (Platelets and Thrombosis in Sheba) Study Group.

It was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti-platelet therapy represents standard care for treating NSTEMI patients. Ticagrelor is a direct acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Fifty NSTEMI patients were randomised to receive either a chewing loading dose of 180 mg ticagrelor or an equal standard oral dose of ticagrelor. Platelet reactivity was evaluated by VerifyNow at baseline, 1 and 4 h post-loading dose. Results are reported in P2Y12 reaction units. Patients then continued to receive standard 90 mg oral ticagrelor twice daily. Baseline characteristics did not differ between the two groups. P2Y12 reaction units in the chewing group compared with the standard group at 0, 1 and 4 h after ticagrelor loading dose were: 245 vs 239 (p=0.59), 45 vs 130 (p=0.001) and 39 vs 60 (p=0.12), respectively, corresponding to a relative inhibition of platelet aggregation of 83 % vs only 47 % at 1 h (p< 0.001), and 84 % vs 77 % (p=0.59) at 4 h. Major adverse cardiac and cardiovascular events at 30 days were low (2 %), occurring in only one patient in the standard group. In conclusion, chewing a 180 mg ticagrelor loading dose is feasible and facilitates both faster and improved early inhibition of platelet aggregation in NSTEMI patients, compared with a standard oral-loading dose.

Balloon dilatation and outcome among patients undergoing trans-femoral aortic valve replacement.

BACKGROUND: Balloon pre-dilatation before transcatheter aortic valve replacement (TAVR) is performed at the discretion of the treating physician. Clinical data assessing the implications of this step on procedural outcomes are limited. METHODS: We conducted a retrospective analysis of 1164 consecutive TAVR patients in the Israeli multicenter TAVR registry (Sheba, Rabin, and Tel Aviv Medical Centers) between the years 2008 and 2014. Patients were divided to those who underwent balloon pre-dilation (n=1026) versus those who did not (n=138). RESULTS: Rates of balloon pre-dilation decreased from 95% in 2008-2011 to 59% in 2014 (p for trend=0.002). Baseline characteristics between groups were similar except for more smoking (22% vs. 8%, p=0.008), less past CABG (18% vs. 26%, p=0.016), less diabetes mellitus (35% vs. 45%, p=0.01), and lower STS mortality scores (5.2±3.7 vs. 6.1±3.5, p=0.006) in the pre-dilatation group. The pre-dilation group included less patients with moderate to severely depressed LVEF (7% vs. 16%, p<0.001) and higher aortic peak gradients (76.9±22.7mmHg vs. 71.4±24.3mmHg, p=0.01). Stroke rates were comparable in both groups (2.5% vs. 3%, p=0.8), but pre-dilation was associated with lower rates of balloon post-dilatation (9% vs. 26%, p<0.001). On multivariate analysis, balloon pre-dilatation was not a predictor of device success or any post-procedural complications (p=0.07). CONCLUSIONS: Balloon pre-dilatation was not associated with procedural adverse events and may decrease the need for balloon post-dilatation. The results of the present study support the current practice to perform liberally balloon pre-dilatation prior to valve implantation.

Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.

Clinical impact of diabetes mellitus in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Diabetes mellitus (DM) and aortic stenosis (AS) are frequent findings in the elderly population. Data regarding the influence of DM on the outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) due to AS are limited. The aim of this study was to examine the impact of DM on TAVR outcomes. METHODS: We investigated 443 patients with severe AS undergoing TAVR. Subjects were divided into insulin-dependent diabetic mellitus (IDDM) patients (N = 44), non-dependent insulin diabetic mellitus (NIDDM) patients (N = 114) and non-diabetics (N = 285) of whom 31 (74%), 86 (79%) and 209 (76%) respectively had trans-femoral TAVR. Peri-procedural complications and outcomes were recorded according to the Valve Academic Research Consortium-2 criteria. RESULTS: Patients with IDDM as well as NIDDM demonstrated similar complication rates compared with non-diabetic patients, except for acute kidney injury (AKI) grade 3 [4 (2%) and 3 (3%) vs. 1 (0.4%) respectively, p = 0.032]. Kaplan-Meier survival analysis showed that DM, regardless of the type of treatment, was not associated with increased 2 years mortality (Log-rank p value 0.44). Multivariate cox regression analysis adjusted for age, gender, coronary artery disease, DM, AKI3, hypertension, chronic renal failure and peripheral vascular disease found that AKI3 was associated with increased risk of 2 years mortality [HR = 7.35, 95% CI 2.16-25.07, p = 0.001] whereas female gender was found as a protective factor [HR = 0.47, 95% CI 0.28-0.8, p = 0.005], and DM was not associated with increased risk. CONCLUSIONS: Following TAVR, DM patients seem to have similar peri-procedural and mid-term outcomes compared with patients without DM, while IDDM patients seem to suffer greater incidence of AKI. Further research in larger cohorts of patients is needed to validate our results.

Clopidogrel attenuates atheroma formation and induces a stable plaque phenotype in apolipoprotein E knockout mice.

AIM: Clopidogrel is a widely used anti-thrombotic for the prevention of stent thrombosis and cardiovascular events in patients with coronary atherosclerosis. Clopidogrel has been shown to exhibit anti-inflammatory effects that are related to the attenuated activation of platelets. Atherosclerosis is a complex process in which the immune system and the endothelium appear to play a prominent role. Herein, we tested the hypothesis that clopidogrel will influence plaque size and composition in the atherosclerosis prone apolipoprotein E knockout (apoE KO) mouse model. METHODS AND RESULTS: Eight week old mice were fed daily with either PBS, 1 mg or 2 mg of clopidogrel for 10 weeks. Plaque size was evaluated in the aortic sinus and cellular and humoral responses were studied as well as splenic and bone marrow endothelial progenitors by FACS. Treatment with either 1 mg and 2 mg of clopidogrel significantly reduced plaque size and augmented its stability by increasing atheromatous fibrous area. Whereas antigen specific oxLDL immune response was not influenced by clopidogrel feeding, the number of atheroprotective regulatory CD4+CD25+ T cells was significantly increased. Moreover, clopidogrel treatment resulted in a prominent rise in splenic but not bone marrow derived Sca-1+/flk-1+ endothelial progenitors. CONCLUSION: Clopidogrel significantly reduces atheroma burden and stabilizes aortic sinus plaques in apoE KO mice. These effects may partially be mediated by upregulation of the regulatory T cell pool and splenic endothelial progenitor cells. These findings may expand the potential applications of clopidogrel in human subjects.