Search

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls.We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique.Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group.Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. Patients with stable CAD who were regularly taking aspirin (75–100 mg qd) for at least 1 month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. Five hundred three patients with CAD were included in this study, and 88 were treated with CCBs. Mean age (67.9±9.7 in the CCB group vs. 66.5±11.4 in the control group), gender (77.3 male vs. 82.9%), rates of diabetes mellitus (34.7 vs. 36.9%), rates of CKD (23.5 vs. 23.5%), dyslipidemia (85.1 vs. 85.3%), and statin therapy (89.5 vs. 90.7%) were similar. The mean ARU was 465.4±70.0 for patients treated with CCBs versus 445.2±60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). The administration of CCBs was independently associated with HAPR in a multivariate analysis (OR 1.72, 95% CI: 1.04–8.91, p=0.047) as well as in propensity score matched analysis (OR 1.56; CI: 1.22–1.93; p

Patients who present to the emergency department with chest pain during an episode of atrial fibrillation (AF) impose a clinical challenge regarding the source of pain - being coronary artery disease (CAD) or AF in origin. The aim of this study was to identify clinical, imaging or laboratory markers which can predict significant CAD among patients with an AF episode and chest pain.We included 57 consecutive patients admitted to our hospital with AF and chest pain. All patients underwent coronary evaluation. Significant CAD was defined as50% stenosis in a major coronary artery by coronary angiography or cardiac CT. We compared CAD and non-CAD groups and analyzed risk factorsby regression analysis.Twenty-four patients (42%) were diagnosed with- and 33 patients (58%) without obstructive CAD. In a multivariate analysis of regional wall motion abnormality (RWMA), elevated troponin and hypertension were found to be predictors for CAD [odds ratio (OR), 22.4 (confidence interval (CI), 1.8-272.4; P = 0.02); OR, 5.6 (CI, 1-31.0; P = 0.05) and OR, 21.4 (CI, 1.6-284.6; P = 0.02), respectively]. There were no significant differences regarding the rate of typical chest pain at presentation in the CAD vs. the non-CAD group [13 (54%) vs. 20 (60%), P = 0.374], or in ECG ST-changes [12 (50%) vs.9 (27%), respectively; P = 0.08].In patients who present acutely with chest pain and AF, troponin elevation and RWMA appear to be highly predictive of obstructive CAD, whereas clinical symptoms and ECG changes are not predictive. These findings may be helpful for guiding the management of patients admitted with AF and chest pain.

Coronavirus disease 2019 (Covid-19) is associated with a high incidence of venous and arterial thromboembolic events. Currently, there are no clinical or laboratory markers that predict thrombotic risk. Circulating immature platelets are hyper-reactive platelets, which are associated with arterial thrombotic events. The aim of this study was to assess whether the proportion of circulating immature platelets is associated with disease severity in Covid-19 patients. Patients admitted with Covid-19 disease were prospectively assessed. Immature platelet count (IPC) and immature platelet fraction (IPF) were measured at admission and at additional time points during the hospital course using the Sysmex XN-3000 auto-analyzer. A total of 136 consecutive patients with Covid-19 were recruited [mean age 60 ± 19 years, 49% woman, 56 (41%) had mild-moderate disease and 80 (59%) had severe disease at presentation]. The median IPF% was higher in patients with severe compared to mild-moderate disease [5.8 (3.9–8.7) vs. 4.2 (2.73–6.45), respectively, p = 0.01]. The maximal IPC value was also higher in patients with severe disease [15 (10.03–21.56), vs 10.9 (IQR 6.79–15.62), respectively, p = 0.001]. Increased IPC was associated with increased length of hospital stay. Patients with severe Covid-19 have higher levels of IPF than patients with mild-moderate disease. IPF may serve as a prognostic marker for disease severity in Covid-19 patients.

Multi-vessel coronary artery disease (MV-CAD) is correlated with worse clinical outcomes compared with single-vessel CAD (SV-CAD). The aim of this study was to evaluate the association between MV-CAD and high on-aspirin platelet reactivity (HAPR) in patients with stable CAD treated with aspirin.The current study is an analysis of prospectively enrolled randomly selected patients with known stable CAD, who were taking aspirin (75-100 mg qd) regularly for at least one month, and had undergone coronary angiography at least 3 months prior to the enrollment to the study.acute coronary syndrome at the time of platelet function testing, active malignancy, acute infection, active inflammatory/rheumatic disease, major surgery in the past 6 months, chronic liver failure, treatment with oral anticoagulation, non-adherence with Aspirin and thrombocytopenia (100 K/micl). Blood was drawn from the participants and sent for platelet function testing (VerifyNow, Instrumentation Laboratory Company, Bedford, Massachusetts, United States). MV-CAD was defined as50% stenosis in ≥2 separate major coronary territories per coronary angiography. HAPR was defined as aspirin reaction units (ARU)550.Overall, 507 patients were analyzed; age 66.7 ± 11.2, 17.9% women, 223 (44%) had MV-CAD. The rate of HAPR was significantly higher among patients with MV-CAD vs. SV-CAD (14.8% vs. 3.5%, p 0.001, respectively). Furthermore, a "dose response"-like association was found between the number of stenotic coronary arteries and the rate of HAPR (3.5%, 13.5 and 17.3% for SV-CAD, 2-vessel and 3-vessel disease, respectively). In a multivariate analysis adjusted for potential confounders, MV-CAD was found to be a strong independent predictor of HAPR [OR = 1.8 (95%CI: 1.05-4.7), p = 0.014].A significant association between MV-CAD and HAPR was found. Additional studies designed to investigate the mechanisms of HAPR and different therapeutic options for this subset of patients are warranted.

Circulating endothelial progenitor cells (cEPCs) are vital to vascular repair by re-endothelialization. We aimed to explore the effect of proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) on cEPCs hypothesizing a possible pleiotropic effect. Patients with cardiovascular disease (CVD) were sampled for cEPCs at baseline and following the initiation of PCSK9i. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+), and by the formation of colony-forming units (CFUs) and production of VEGF. Our cohort included 26 patients (median age 68 (IQR 63, 73) years; 69% male). Following 3 months of treatment with PCSK9i and a decline in low-density lipoprotein cholesterol levels (153 (IQR 116, 176) to 56 (IQR 28, 72) mg/dl), p

Introduction Cannabis use is known to be associated with significant cardiovascular morbidity. We describe three cases of cannabis-related malignant arrhythmias, who presented to the cardiac department at our institution within the last 2 years. All three patients were known to smoke cannabis on daily basis. Case summaries Case 1: A 30-year-old male, presented with recent onset of palpitations. A 12-lead electrocardiogram (ECG), transthoracic echocardiogram (TTE), and blood tests were all normal. During an inpatient exercise treadmill test (ETT) he developed polymorphic ventricular tachycardia (VT), which converted spontaneously to supraventricular tachycardia (SVT) in the recovery phase of the test. Subsequent risk stratification with cardiac magnetic resonance imaging and coronary angiography showed no abnormalities and an electrophysiological study was negative for sustained VT, however, SVT was easily induced with rapid conversion to atrial fibrillation. The patient successfully stopped smoking all tobacco products including cannabis and was treated with beta-blockers, with no further episodes of arrhythmia. Case 2: A 30-year-old male presented to the Emergency Department with palpitations, chest pain, and dizziness that improved during exertion. His initial ECG demonstrated complete atrioventricular block (AVB). Subsequent traces showed Mobitz Type I and second-degree AVB, which converted to atrial flutter after exertion. Routine blood tests, TTE, and an ETT were all normal and he was discharged home with no conduction abnormalities. Case 3: A 24-year-old male presented with two episodes of syncope. Baseline examination was normal, with an ECG showing a low atrial rhythm. Interrogation of his implantable loop recorder showed episodes of early morning bradycardia episodes with no associated symptoms. Discussion Cannabis-related arrhythmia can be multiform regarding their presentation. Therefore, ambiguous combinations of arrhythmia should raise suspicion of underlying cannabis abuse, where clinically appropriate. Although causality with regards to cannabis use cannot be proven definitively in these cases, the temporal relationship between drug use and the onset of symptoms suggests a strong association.

Serum albumin (SA) level is a powerful cardiovascular prognostic marker, suggested to be involved in regulation of platelet function. High on-aspirin platelet reactivity (HAPR) is associated with increased risk for deleterious cardiovascular events. The aim of the present study was to evaluate the association between HAPR and albumin levels in patients with stable coronary artery disease (CAD) treated with aspirin. Patients with known stable CAD, who were taking aspirin (75 to 100 mg qd) regularly for at least 1 month, were screened for the present study. Exclusion criteria: cancer, sepsis or acute infection, active inflammatory/rheumatic disease, recent major surgery, chronic liver failure, the administration of other antiplatelet drugs, nonadherence with aspirin and thrombocytopenia. Blood was drawn from the participants and sent for SA level and platelet function test (VerifyNow). HAPR was defined as aspirin reaction units (ARU)550. Overall 116 patients were analyzed; age 69 ± 10, 28% women. Twenty (17%) were hypoalbuminemic (≤3.5 g/dl). Hypoalbuminemic patients had similar characteristics to the normal albumin group except mildly higher creatinine in the former. SA levels were significantly lower in the hypoalbuminemic group (3.2 ± 0.2 g/dl vs 4.2 ± 0.4 g/dl, respectively, p0.001) whereas mean ARU was significantly higher compared with the normal albumin group (548 ± 45 vs 444 ± 66 ARU, respectively, p0.001). A significant inverse association was observed between SA and ARU with (R

Background Intravascular leiomyomatosis (IVL) with intracardiac extension is a rare benign tumour seen exclusively in women, characterized by proliferation of uterine smooth muscle cells through the venous circulation into the inferior vena cava (IVC) and the right heart chambers. Case summary A 47 years old women with history of previous hysterectomy due to myomatosis, presented with nausea, anorexia, and bilateral lower limb swelling over the preceding 2 months. An outpatient abdominal ultrasound discovered a mass in the IVC. Echocardiogram and computed tomography demonstrated a large intravascular mass extending from the pelvis to the right heart chambers. The tumour was completely removed in a concomitant open-heart surgery and laparotomy. Post-operative course was uncomplicated. A month later, the patient was feeling well and in good clinical condition. The histological analysis consisted with IVL. Discussion Intracardiac leiomyomatosis is a rare clinical condition which requires high index of suspicion. Multimodality imaging is usually required to establish the preoperative diagnosis, although the final diagnosis is achieved with tissue investigation. Complete surgical resection of the tumour is curative and associated with good long-term prognosis.

Background Coronavirus disease 2019 (Covid-19) is associated with a high incidence of thromboembolic events, both venous and arterial. Currently, there are no clinical or laboratory markers to guide risk-stratification or antithrombotic therapy in Covid-19 patients. Circulating immature platelets represent a population of hyper-reactive platelets, which are associated with arterial thrombotic events. Objectives To assess whether the proportion of immature platelets in the circulation is associated with disease severity in patients with Covid-19 Methods This prospective study evaluated consecutive patients with COVID-19 admitted with various degrees of disease severity, as determined by the standard Covid-19 severity Score. Disease severity was evaluated during hospitalization. Immature platelet fraction (IPF) absolute number and percentage were measured on admission and at additional time points during the hospital course using the SysmexXN-3000 auto-analyzer. The maximal values of IPF% and absolute IPF was analyzed according to disease severity. Results A total of 136 consecutive patients with Covid-19 were recruited. Mean age was 60±19 years for patients with mild and moderate disease and 69±14 years for patients with severe disease, 52% with mild and moderate disease and 48% with severe disease were woman, 11% with mild and moderate disease and 20% with severe disease with concurrent cardiovascular disease The median of IPF% was higher in the severe COVID-19 group compared to patients with mild or moderate disease [4.2 (IQR 2.73–6.45) vs 5.8 (IQR 3.9–8.7), P=0.01, Figure 1)]. The median of IPF absolute number was also significantly higher in patients with severe disease comparing to patients with mild or moderate disease (4.2 (2.85–6.1) vs 5.1 (IQR 3.65–7.35), P Conclusions Patients with severe Covid-19 have a higher level of IPF in the circulation than patients with mild or moderate disease. IPF may serve as a reliable prognostic marker for in-hospital disease severity in patients with Covid-19 Funding Acknowledgement Type of funding sources: None. Figure 1. IPF% (median, 95% confidence interval)Figure 2. IPF# (median, 95% confidence interval)

Recently we developed and internally-validated the Soroka Acute Myocardial Infarction (SAMI) Score for prediction of all-cause long-term mortality (c-statistic 0.83-0.94) among hospital-survivors of AMI. We aimed to perform an external-validation of the SAMI score for long-term risk-stratification of STEMI patients undergoing PCI.A prospective registry of 1273 STEMI patients treated using primary PCI and discharged alive from Rabin Medical Center in Israel between 2004 and 2014 (age 60.8 ± 12.5 years, 83% males) was utilized for the validation. Chi-square test and logistic regression were used for calibration, and c-statistic (ROC procedure) for discrimination assessment of the SAMI score.All-cause mortality following one- and 5-years post-discharge was 3.8% and 8.1%, respectively. SAMI score values ranged between (-5) and (+15) points (median 2-points). In a univariate analysis the SAMI score variables were significantly associated with 1- and 5-years mortality. Higher SAMI score was associated with increased risk for dying: a one-point increase was associated with OR of 1.33 (95%CI: 1.24-1.42, p 0.001) and 1.37 (95%CI: 1.29-1.44, p 0.001) for 1- and 5-years mortality respectively. No statistically significant difference was found in the currently observed mortality rates by groups of SAMI score and the expected mortality rates as per the SAMI score index. The c-statistics were 0.82 and 0.83 for 1- and 5-year mortality, respectively.The SAMI score is a simple, robust and now also externally-validated prognostic tool for prediction of long-term all-cause mortality in hospital survivors of STEMI.

International audience; BACKGROUND THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n ¼ 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n ¼ 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA 1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention. OBJECTIVES In these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction-defined major bleeding) and net clinical benefit varied with diabetes-related factors. METHODS Outcomes were analyzed across baseline diabetes duration, HbA 1c , and antihyperglycemic medications. RESULTS In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for #5 years, 11.1% for >20 years) and HbA 1c (6.4% for #6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p ¼ 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA 1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA 1c , and antihyperglycemic medications. CONCLUSION Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetesrelated factors in THEMIS-PCI but not in the overall THEMIS population.

Background Multi-vessel coronary artery disease (MV-CAD) is correlated with worse outcomes compared with single-vessel CAD (SV-CAD), potentially attributed to more advanced atherosclerotic disease in other vascular beds, greater endothelial dysfunction, thrombin activation and possibly greater platelet reactivity. Objectives The aim of the current study was to evaluate the association between MV-CAD and high on-aspirin platelet reactivity (HAPR) in patients with stable CAD treated with aspirin. Methods Patients with known stable CAD, who were taking aspirin (75–100 mg qd) regularly for at least one month, and had undergone coronary angiography at least 3 months prior to the test, were enrolled. Blood was drawn from the participants and sent for platelet function testing. MV-CAD was defined as >50% stenosis in ≥2 separate major coronary territories per coronary angiography. HAPR was defined as aspirin reaction units (ARU) >550. Results Overall 507 patients were analyzed; age 66.7±11.2, 17.9% women, 223 (44%) had MV-CAD. Mean ARU was significantly higher among patients with MV-CAD vs. SV-CAD (460±68 vs. 440±55, p Conclusions MV-CAD is significantly associated with HAPR. This could potentially explain, in part, the increased risk and/or worse outcomes in patients with MV-CAD and implies considering intensive anti-thrombotic therapy among these patients. Funding Acknowledgement Type of funding source: None

Coronavirus disease 2019 (Covid-19) is associated with high incidence of venous and arterial thromboembolic events. Currently, there are no markers to guide antithrombotic therapy in Covid-19. Immature platelets represent a population of hyper-reactive platelets associated with arterial events. This prospective study compared consecutive Covid-19 patients (n = 47, median age = 56 years) to patients with acute myocardial infarction (AMI, n = 100, median age = 59 years) and a group of stable patients with cardiovascular risk factors (n = 64, median age = 68 years). Immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points. IPF% on admission was higher in Covid-19 than the stable group and similar to the AMI group (4.8% [IQR 3.4-6.9], 3.5% [2.7-5.1], 4.55% [3.0-6.75], respectively, p = 0.0053). IPC on admission was also higher in Covid-19 than the stable group and similar to the AMI group (10.8 × 109/L [8.3-18.1], 7.35 × 109/L [5.3-10.5], 10.7 × 109/L [7.7-16.8], respectively, P < 0.0001). The maximal IPF% among the Covid-19 group was higher than the stable group and similar to the AMI group. The maximal IPC in Covid-19 was higher than the maximal IPC in both the stable and AMI groups (COVID-19: 14.4 × 109/L [9.4-20.9], AMI: 10.9 × 109/L [7.6-15.2], P = 0.0035, Stable: 7.55 × 109/L [5.55-10.5], P < 0.0001). Patients with Covid-19 have increased immature platelets indices compared to stable patients with cardiovascular risk factors, and as the disease progresses also compared to AMI patients. The enhanced platelet turnover and reactivity may have a role in the development of thrombotic events in Covid-19 patients.

Our aim was to investigate trends in prognosis among survivors of acute coronary syndrome according to left ventricular ejection fraction during a 16-year period.Data were derived from the Acute Coronary Syndrome Israeli Survey during the years 2000-2016. Patients aged 18 years and older were included in the analysis (N=11,725). Patients were classified into two groups based on their left ventricular ejection fraction: preserved (≥50%) and reduced (50%) and also according to their acute coronary syndrome onset (2000-2006 early period vs. 2008-2016 late period). Endpoints were all-cause mortality rates at one and three years after the index event.Preserved left ventricular ejection fraction was present in 5047/11,725 (43%) of patients. As expected, patients with preserved left ventricular ejection fraction had lower 1 and 3-year mortality rates as compared with reduced left ventricular ejection fraction regardless of the acute coronary syndrome period onset (6% vs. 19%, p0.001). Nevertheless, in the late period the prevalence of reduced left ventricular ejection fraction decreased significantly, becoming equal to preserved left ventricular ejection fraction [2761 (50.5%) vs. 2713 (49.5%) respectively, p=0.3]. Moreover, prognosis during the late period as compared with the early period was improved only in patients with reduced left ventricular ejection fraction (HR 0.79; 95% CI 0.70-0.89, p=0.0001).The prevalence of reduced left ventricular ejection fraction has decreased and prognosis has improved during the past several years but is still much worse than the prognosis of preserved left ventricular ejection fraction.

To assess the effect of cessation of dual antiplatelet therapy (DAPT) regimens containing 2nd generation P2Y12 inhibitors on platelet reactivity, in patients who completed 12 months of DAPT following an acute myocardial infarction. Clinical data has shown an increased cardiovascular risk in the 90 days following cessation of DAPT. One possible explanation is a transient platelet hyper-reactivity after cessation of treatment. Data from patients treated with 2nd generation P2Y12 inhibitors is scarce. Patients who completed 12 month DAPT with prasugrel/ticagrelor underwent serial assessment of platelet reactivity (on DAPT and 1, 4 and 12 weeks post cessation). The primary outcome was platelet reactivity, expressed as platelet reactivity units (PRU) at each time point. 41 participants were included in this study, (23 ticagrelor, 18 prasugrel). There was no statistically significant differences in baseline characteristics between prasugrel/ticagrelor treated patients . The pattern of platelet reactivity recovery after DAPT cessation differed between the ticagrelor and prasugrel: with ticagrelor, after the initial PRU increase from baseline, the PRU remained stable, while with prasugrel, there was a further increase in PRU between 1 and 4 weeks, with a return to the 1 week level by 12 weeks (p = 0.034 for the time × treatment interaction between ticagrelor and prasugrel). Our results suggest there is a transient platelet hyper-reactivity after cessation of ADP receptor blockers therapy with prasugrel, but not ticagrelor. Further research is required to elucidate the pathophysiologic mechanisms behind these findings and to evaluate potential strategies to prevent or overcome this “rebound” effect.

BACKGROUND Cancer patients are mostly excluded from percutaneous coronary intervention (PCI) clinical trials and oncologic history is lacking from most PCI registries. Thus, little is known about the clinical outcomes following PCI among cancer survivors. Our aim was to examine the prevalence and long-term outcome of cancer survivors among a large PCI patient cohort. METHODS We retrospectively integrated and analyzed cardiovascular and oncologic data of 12 785 consecutive patients who underwent PCI between April 2004 and October 2014. Cancer survivors were compared with pair-matched cancer-naive patients. RESULTS Cancer survivors constituted 7.8% (1005) of the patients. The mean cancer diagnosis-to-PCI interval was 3.6±3.4 years and the mean post-PCI follow-up was 6.4±5.9 years. Postmatching baseline characteristics were similar between the groups. Cancer survivors were referred to the catheterization laboratory because of acute coronary syndrome and were treated with bare-metal stents more often than cancer-naive patients. Cancer survivors to cancer-naive patients' hazard ratio and 95% confidence interval were 1.46 (1.24-1.72), P value less than 0.001 for all-cause mortality and 1.41 (1.23-1.63), P value less than 0.001 for the composite of death, nonfatal myocardial infarction, target vessel revascularization, and coronary bypass surgery. Cardiac death was the leading cause of mortality in our hospital during follow-up in both groups, although more cancer survivors died of malignancy (25 vs. 5%, P

Coronary artery calcium (CAC) is associated with poor angiographic results and higher rates of complications after percutaneous coronary intervention (PCI). Limited data are available regarding the impact of angiographically evident CAC on long-term outcomes after primary PCI in patients presenting with ST-segment elevation myocardial infarction (STEMI). In this single-center, registry-based retrospective cohort analysis, we analyzed 2,143 consecutive patients presenting with STEMI who underwent primary PCI within 12 hours of symptom onset. Patients were divided based on degree of CAC (determined by visual inspection of angiograms) as follows: (1) moderate-to-severe CAC (n = 306; 14.3%) and (2) minimal-to-none CAC (n = 1,837; 85.7%). The primary end point was all-cause mortality at 1-year after PCI. Patients with moderate-to-severe CAC were older, women, and had higher rates of hypertension, chronic kidney disease, and peripheral vascular disease. Moderate-to-severe CAC was associated with higher rates of anterior myocardial infarction, advanced Killip class, and poor final angiographic results. At 1-year follow-up, rates of all-cause mortality were higher in the moderate-to-severe CAC cohort than those in the minimal-to-none CAC cohort (8.5% vs 4.7%; p = 0.008). However, after accounting for major clinical and angiographic characteristics, moderate-to-severe CAC on presenting STEMI angiogram was no longer predictive of 1-year all-cause mortality. In conclusion, advanced CAC burden occurs in ∼15% of patients undergoing primary PCI for STEMI and reflects a marker of adverse prognosis late into follow-up after PCI.

OBJECTIVES To estimate the prevalence, identify predictors, and assess the prognostic implications of left ventricular ejection fraction (LVEF) changes after an elective percutaneous coronary intervention (PCI). METHODS We included all consecutive patients who underwent elective PCI in our institution and were evaluated with echocardiography before and within 1 year of the procedure. Patients were grouped in terms of baseline LVEF. Hazard ratios (HRs) for all-cause mortality and acute myocardial infarction were calculated for baseline LVEF groups and in terms of LVEF normalization or decline. RESULTS A total of 974 patients were included. Patients with moderately impaired (HR 1.41, P=0.01) and poor LVEF (HR 2.44, P

Adiponectin is a key component in multiple metabolic pathways. Studies evaluating associations of adiponectin with clinical outcomes in older adults have reported conflicting results. We investigated the association of adiponectin with mortality and cardiovascular disease (CVD) morbidity in a young, multiethnic adult population. We analyzed data from participants in the Dallas Heart Study without baseline CVD who underwent assessment of total adiponectin from 2000 to 2002. The primary outcome of all-cause mortality was assessed over median 10.4 years of follow-up using multivariable-adjusted Cox proportional hazards models. Secondary outcomes included CVD mortality, major adverse cardiovascular and cerebrovascular events (MACCE), and heart failure (HF). The study cohort included 3,263 participants, mean age 43.4 years, 44% women, and 50% black. There were 184 deaths (63 CVD), 207 MACCE, and 46 HF events. In multivariable models adjusted for age, gender, race, hypertension, diabetes, smoking, high-density lipoprotein cholesterol-C, hyperlipidemia, high-sensitivity C-reactive protein level, estimated glomerular filtration rate, and body mass index, increasing adiponectin quartiles were positively associated with all-cause mortality Q4 versus Q1 (hazard ratio [HR] = 2.27; 95% confidence interval [CI] 1.47, 3.50); CVD mortality Q4 versus Q1 (HR = 2.43; 95% CI 1.15, 5.15); MACCE Q4 versus Q1 (HR = 1.71; 95% CI 1.13, 2.60); and HF Q4 versus Q1 (HR = 2.95; 95% CI 1.14, 7.67). Findings were similar with adiponectin as a continuous variable and consistent across subgroups defined by age, gender, race, obesity, diabetes, metabolic syndrome, or elevated high-sensitivity C-reactive protein. In conclusion, higher adiponectin was associated with increased mortality and CVD morbidity in a young, multiethnic population. These findings may have implications for strategies aimed at lowering adiponectin to prevent adverse outcomes.

BackgroundWhile ‘plaque rupture’ is the paradigm of type 1 myocardial infarction (T1MI), T2MI is myocardial necrosis secondary to oxygen supply-demand mismatch. Being a heterogeneous and rather newly defined group, data are lacking about T2MI.MethodsA retrospective review of medical records of patients diagnosed with T2MI in the Rabin Cardiology Center, Israel between the years 2007 and 2012 was performed. Following a descriptive analysis, we used multivariate time dependent models to estimate the association of T2MI with the risk for 30-day, 1-year, and 5-year all-cause-mortality and major adverse cardiovascular events (MACE), and compared it to a T1MI group matched for age, gender and electrocardiographic changes.ResultsThe study included 107 T2MI (and 107 T1MI) patients. Sepsis, anemia, and atrial fibrillation were the most common etiologies. Triple anti-thrombotic therapy was given to 22% of T2MI patients (vs. 82% of T1MI patients, p

The new oral anticoagulants (NOACs) reduce stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but dabigatran may increase risk of coronary ischemic events for unclear reasons. Thus, this study assessed the effects of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers in patients with non-valvular AF. Patients with non-valvular AF planned to begin treatment with NOACs were included. Seventeen patients were prescribed dabigatran and ten rivaroxaban. Platelet function (as assessed by multiple-electrode aggregometry, Impact-R shear-induced platelet deposition, P-selectin expression and plasma RANTES levels) and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (prior to initiation of NOAC treatment) and at least 7 days into treatment with either dabigratran or rivaroxaban. Seventeen patients treated with dabigatran (mean age 69 ± 7 years, 35 % women, mean CHADS2 score 2.6 ± 1.2), and ten patients treated with rivaroxaban (mean age 73 ± 9 years, 20 % women, mean CHADS2 score 2.7 ± 1.6) completed the study. In both groups, there were no significant differences in platelet reactivity between the baseline and on-anticoagulant treatment time-points, as measured by each of the platelet-specific assays. There was a trend towards increased platelet reactivity in response to arachidonic acid from baseline to on-treatment in both groups, probably as a result of aspirin discontinuation in 33 % of patients. No significant differences were noted between baseline and on-treatment in hs-CRP in both anticoagulant groups. Treatment with dabigatran and rivaroxaban does not appear to be associated with changes in markers of platelet reactivity or systemic inflammation.

Objective To broaden the data supporting the use of the residual SYNTAX score (rSS) to define “reasonable” incomplete coronary revascularization (ICR) in order to improve the allocation of patients with severe coronary artery disease (CAD) to surgical/percutaneous revascularization and long-term clinical outcomes. Introduction ICR is associated with a worse prognosis in patients with severe CAD, yet no consensus exists regarding its definition. Methods We studied 148 consecutive patients with triple vessel/left main (3VD/LM) CVD treated by percutaneous coronary interventions (PCI). Clinical outcomes at 3 years were collected; the SS and rSS were calculated. We used various definitions of “reasonable” ICR:no post-PCI total occlusion, single vs. mutivessel residual post-PCI disease, and the rSS at a cutoff value determined according to ROC curve fitted for 3 years major adverse cardiovascular and cerebrovascular adverse events (MACCE) in order to determine which definition has the strongest correlation with long-term outcomes. Results rSS ≤ 8 was associated with significant reductions in 3 year MACCE (19.4 vs. 51.1%, HR = 3.62, P = 0.014) Death/MI/CVA (13.7 vs. 28.8%, HR = 6.01, P = 0.030) and repeat revascularization (8.6 vs. 28.9%, HR = 3.44, P = 0.033) using a Cox proportional hazard ratio model adjusted to baseline characteristics, whereas single vessel residual disease and absence of total occlusion were not. Conclusions “Reasonable” ICR as determined by rSS carries better long-term prognosis in terms of clinical outcomes vs. more extensive residual coronary disease in patients with 3VD/LM coronary artery disease treated by PCI. The rSS may improve the allocation of coronary patients to the optimal mode of revascularization. © 2015 Wiley Periodicals, Inc.

Given the vicissitudes of percutaneous coronary intervention (PCI) technology, epidemiology, and mode of practice, the aim of this study was to define contemporary outcome predictors in a very large consecutive patient cohort. Data from 11,441 consecutive patients who underwent PCI at a tertiary medical center from April 2004 to September 2013 are presented. A comprehensive database was built using various data sources, with outcome end points defined as all-cause mortality and as a composite of death or nonfatal myocardial infarction during follow-up. Candidate variables to influence outcome were chosen a priori and were tested using multivariate time-dependent models to estimate each interaction. Mean follow-up was 5.5 years (range 3 months to 9.5 years). The cohort consisted of 75% men, 42% patients with diabetes, and 61% patients who underwent PCI in acute coronary syndrome settings and 7.8% for ST-elevation myocardial infarction. Drug-eluting stents were used in 43.4% of patients, bare-metal stents in 52%, and balloon angioplasty alone in 4.6%. In multivariate analysis, in addition to already well-recognized predictors of death or myocardial infarction such as advanced age (hazard ratio [HR] 1.031, p0.001), female gender (HR 1.23, p0.001), urgent setting (HR 1.23, p0.001) and diabetes mellitus (HR 1.28, p0.001), we particularly noted previous anemia (HR 1.55 p0.001), previous chronic kidney injury (HR 1.93, p0.001) and previous moderate to severe left ventricular dysfunction (HR 2.29, p0.001). Drug-eluting stent placement was associated with better outcomes (HR 0.70, p0.001). In conclusion, this analysis confirms the effect of some known predictors of PCI outcomes. However, the extent of their effect is modest, while other predictors may have a greater influence on outcomes. Risk stratification of PCI patients should take into account kidney injury, anemia, and left ventricular function. Drug-eluting stents provide sustained benefit.

Antiplatelet responses to clopidogrel and prasugrel are highly variable and subject to significant rates of high on-treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI). The proportion of circulating young reticulated platelets (RPs) inversely correlates with responsiveness to both agents. We aimed to determine the relationship between RPs and on-treatment platelet reactivity in ticagrelor-treated patients. Patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with PCI and ticagrelor were tested for platelet reactivity using the VerifyNow P2Y12 assay and multiplate aggregometry. RPs levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2–4 and 30 days post-PCI. Fifty three patients were included (mean age 62.6 ± 9.8 years, 18.9 % women, 35.8 % diabetes), of which 41 patients (77 %) completed follow-up. Variability in response to ticagrelor was very low according to both assays with no identified cases of HTPR at either time-point. In addition, there were no differences in platelet reactivity, as analyzed by the VerifyNow P2Y12 assay, or in the proportion of RPs between the two time points (p > 0.5). With the multiplate assay, platelet reactivity increased between the two time-points (8.6 ± 6.0 vs. 15.5 ± 11 AU*min; p = 0.0007). There was no significant correlation between RPs and platelet reactivity at both time-points and using both assays (p > 0.5). There were no cases of HTPR up to 30-days post-PCI in patients with NSTE-ACS treated with ticagrelor. In this cohort, no correlation between % RPs and platelet reactivity was observed. Attenuation of RP-induced platelet reactivity as a novel mechanism for ticagrelor’s benefit requires further investigation.

Recent literature shows a greater risk for adverse clinical outcomes following acute coronary syndrome (ACS) events in women undergoing a percutaneous coronary intervention (PCI), especially in young and diabetic patients. We aimed to assess the impact of sex on clinical results following ACS.From our database of all-comer PCI patients, between 1 April 2004 and 31 December 2011, the procedural and angiographic results and clinical outcomes up to 5 years of 5819 patients with ACS undergoing emergent PCI were analyzed and compared according to sex.A total of 1425 (24.5%) of the patients were women. They presented at an older age (72.7±11.3 vs. 65.2±12.3 years, P0.001), and more had diabetes mellitus (46.7 vs. 40.0%, P0.001) and previous heart failure (12.1 vs. 7.26%, P=0.001). Mortality (21.63 vs. 13.22% at 5 years, P0.001) and combined endpoints of death, myocardial infarction, and target-vessel revascularization (30.72 vs. 24.65% at 5 years, P0.001) were higher in women. In a multivariate analysis using age, previous diabetes, heart failure, coronary artery bypass graft surgery, baseline glomerular filtration rate, presentation with ST-elevation myocardial infarction, and proximal left anterior descending artery disease, female sex was no longer an independent predictor of outcomes. No sex differences in mortality or major adverse cardiac events were observed in young or diabetic patients.Our results show no sex differences in clinical endpoints among ACS patients undergoing PCI after correction for advanced age and comorbidities. Importantly, no differences were found in patients with diabetes mellitus or those younger than 60 years of age. This may reflect the importance of the administration of evidence-based therapeutics in women.

Reticulated platelets (RPs) are immature platelets with high dense granules content and a residual amount of megakaryocyte-derived of mRNA. Increased level of RPs has been found to be an independent predictor of cardiovascular ischemic events, and has been associated with impaired response to various anti-platelet drugs. The study aimed to characterize and compare the surface antigenic properties of reticulated versus mature platelets. Platelets from healthy individuals and diabetic patients were tested at rest and after activation with adenosine diphosphate (ADP). For each patient, we calculated the proportion of RPs and mature platelets using flow cytometry analysis with thiazole orange staining (for RPs) and CD42b platelet-specific antibody. We also tested the surface expression of P-selectin and Annexin V, by double staining flow cytometry in RPs versus mature platelets. A total of 20 subjects were recruited (10 healthy individuals, 10 diabetics). Activation with ADP did not cause a significant change in the proportion of RPs. Following activation, RPs demonstrated a significant increase in the expression of both P-selectin and Annexin V, while mature platelets exhibited a non-significant increase in both markers. These findings were consistent in both healthy subjects and patients with diabetes. In conclusion, RPs have a significantly higher capacity to increase the expression of platelet activation markers compared with mature platelets.

Objectives Patients with acute myocardial infarction pretreated with prasugrel or ticagrelor may require urgent coronary artery bypass grafting (CABG). However, prasugrel and ticagrelor withdrawal period is recommended for 5-7 days before planned CABG to enable full platelet recovery. We hypothesized that monitoring sequential platelet reactivity (PR) could identify patients with early platelet recovery who may benefit from earlier surgery before the guideline-recommended 5-7 day delay. Patients and methods We performed preoperative PR assays in 35 patients with acute myocardial infarction who received prasugrel (60%) or ticagrelor (40%) and required an urgent CABG. When platelet inhibition levels were favorable, on the basis of the VerifyNow assay, surgery was endorsed. CABG-related bleeding parameters were collected and compared with two matched control groups composed of patients who received fewer potent antiplatelet regimens. Results On the basis of platelet function monitoring, we identified 21 (56.7%) patients with a relatively earlier platelet recovery who underwent CABG before the end of the conventional washout period (5-7 days). For these patients, the washout periods were shortened to an average time of 2.6±1.0 days for ticagrelor and 3.8±1.5 days for prasugrel. CABG-related bleeding parameters were comparable with the two matched control groups. Conclusion A strategy of performing preoperative PR assays can identify patients who recover platelet function in less than 5-7 days after ticagrelor or prasugrel discontinuation. This strategy may provide the basis for performing urgent CABGs earlier than the currently recommended delay. Future, larger studies are required to establish these preliminary findings.

BACKGROUND Limited contemporary data exist regarding the incidence, predictors, and outcomes of failure of primary percutaneous coronary intervention (PCI) in the treatment of ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS In this registry-based retrospective cohort study, all consecutive unselected patients (n=1725) who were hospitalized for STEMI and underwent primary PCI from January 2001 to December 2010 were included. PCI failure was defined as a final diameter stenosis greater than 30% or postdilatation Thrombolysis in Myocardial Infarction (TIMI) flow grade of 2 or less. We examined the predictors and survival among patients who failed primary PCI. RESULTS The overall PCI failure rate was 5.4% (94 of 1725 procedures). After adjusting for prespecified baseline characteristics, independent predictors of PCI failure included age greater than 65 years (P=0.02), procedure date between 2001 and 2005 (P=0.05), night-time PCI (P=0.008), calcific lesion (P=0.008), and lower preprocedural TIMI flow grade (P=0.006). Failed PCI was associated with a 1-year mortality rate of 22% as compared with 4.2% in the successful PCI group (P

Objectives The aim of this study was to determine whether response to prasugrel is associated with the proportion of circulating reticulated platelets (RPs) in patients with ST-segment elevation myocardial infarction (STEMI). Background Despite better pharmacodynamic properties and clinical efficacy of prasugrel compared with clopidogrel, antiplatelet responses to prasugrel are not uniform. The mechanism of this variability in response is not clear. RPs, young hyperactive forms, are increased during situations of enhanced platelet turnover. Methods Patients with STEMI treated with primary percutaneous intervention (PCI) and prasugrel were tested for platelet reactivity using purinergic receptor P2Y, G-protein coupled, 12 (P2Y12) assay and multiple electrode aggregometry (MEA). RP levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2 to 4 days and 30 days post-PCI. Platelet function was compared by varying levels of RPs, analyzed as continuous (regression analysis) and categorical (tertiles) variables. Results Sixty-two patients were included (mean age: 57.5 � 8 years; 21.2% women; 27.7% diabetes). At the early time point, RP levels were strongly correlated with platelet reactivity when evaluated by the P2Y12 assay (Spearman’s correlation coefficient: 0.55 for P2Y12 reaction units, –0.49 for percent inhibition) and MEA (Spearman’s: 0.50). The upper tertile of RPs displayed higher platelet reactivity compared with the middle and lower tertiles, according to P2Y12 assay and MEA. Similar results with strong correlations between RP and platelet reactivity were noted at 30 days post-PCI. Conclusions The proportion of circulating RPs strongly correlates with response to prasugrel in patients with STEMI treated with PCI. High levels of RPs are associated with increased platelet reactivity despite prasugrel treatment. (J Am Coll Cardiol 2014;63:513–7) a 2014 by the American College of Cardiology Foundation

Recent studies have suggested that clopidogrel response may vary significantly with age. Limited data are available exploring the age dependency of ex vivo aspirin response in young and old patients with stable coronary artery disease. Patients with stable coronary artery disease (n = 583) who had been treated with aspirin 75 to 325 mg/day for ≥1 week were recruited from a general cardiology practice. The study cohort was divided into 2 groups: patients aged75 years (n = 438) and patients aged ≥75 years (n = 145). Aspirin response was determined using the VerifyNow Aspirin Test, and resistance was defined as ≥500 or 550 aspirin reaction units (ARU). The independent predictive value of age on VerifyNow score (as a continuous function) was determined using multivariate linear regression, adjusted for gender, body mass index, and diabetes mellitus. Younger and older patients had similar baseline clinical profiles, including relative doses of aspirin therapy. The mean VerifyNow Aspirin Test score was significantly higher in patients aged ≥75 years: 450 ± 54 versus 434 ± 53 ARU (p = 0.0007). After accounting for the primary covariates, age remained a predictor of VerifyNow score (p = 0.007). Aspirin resistance on the basis of the 500-ARU cutoff was higher in older patients (19% vs 11%, p = 0.009), but there was no difference when the 550-ARU cutoff was used (7% vs 5%, p = 0.40). In conclusion, aspirin response differs significantly by age in patients with stable CAD.

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. However, in patients with diabetes, EPC number and function are markedly reduced. It is unclear whether intensive glycaemic control can modify EPC properties in diabetic patients. We aimed to examine whether glycaemic control can improve EPC number and function in patients with long-standing uncontrolled type 2 diabetes.Thirty-five patients with treated type 2 diabetes and HgA1c ≥ 8.5% were included. Patients were tested at baseline and after 3-4 months of an intensive glycaemic control programme, with the aim of achieving HgA1c of 7%. The diabetes group was compared to 20 patients without diabetes (control). Circulating EPC levels were assessed by flow cytometry for expression of VEGFR2, CD133, and CD34. The capacity of the cells to form colony-forming units (CFUs), and their migration and viability were quantified after 1 week of culture. Patients with diabetes (mean age 61.1 ± 7 years, 28.6% women, disease duration of 19.2 ± 8 years) had a baseline HgA1c of 9.4 ± 0.8%. After the glycaemic control period, HgA1c decreased to 8 ± 0.8%. Circulating EPC levels increased significantly after the intensive control period and reached a level similar to the control group. The number of EPC CFUs also increased significantly after glycaemic control but remained lower than the control group. All EPC functional assays improved following the glycaemic control.In patients with uncontrolled long-standing type 2 diabetes, intensive glycaemic control was associated with an increase in the levels of circulating EPCs, and improvement in their functional properties.

Mean platelet volume (MPV) is a value that is available from standard blood count. Increased MPV is associated with increased platelet reactivity and it has been correlated with adverse cardiac outcomes in patients with acute coronary syndromes (ACS). However, there is limited information about the prognostic value of baseline MPV in a large heterogenous patient population which undergoes percutaneous coronary intervention (PCI). To examine whether baseline MPV is predictive of clinical outcomes in patients who undergo PCI. Included were consecutive patients who underwent PCI during 2004–2010 (n = 7,585, mean age 67.7 ± 12.1 years, 76.0 % males) with a median follow-up period of 4 years. Baseline MPV before angiography and long-term clinical outcomes were assessed. The mean MPV was higher in women as compared to men (8.6 ± 1.2 vs. 8.5 ± 1.1 fL, p = 0.02), in diabetic versus non-diabetic patients (8.6 ± 1.2 vs. 8.4 ± 1.1 fL, p

Background: Retroperitoneal bleeding (RPB) is an unusual but potentially fatal vascular complication occurring after cardiac catheterization (CC). Contemporary data of RPB in the era of dual antiplatelet therapy and vascular closure devices are lacking. Methods: We retrospectively examined all RPB cases that occurred after CC in the Rabin Medical Center between the years 2005 and 2011. Results: Of 26,487 patients who underwent CC, a total of 48 patients (mean age 60.9 ± 13.8 years, 52.1% female) with RPB were identified (0.18%). The indication for CC was acute coronary syndrome (43.7%), myocardial infarction (35.4%), stable angina pectoris (8.3%), hemodynamic studies for valvular heart disease (10.4%) and others (2.1%). Coronary intervention was performed in 34 patients (70.9%) and a vascular closure device (VCD) was used in 16 patients (33.3%). Seventy-seven percent of patients were treated with clopidogrel, 20.8% with glycoprotein IIb-IIIa inhibitors and 85.4% with anticoagulation during CC. Median time to diagnosis of bleeding was 9.0 h, while the median time to bleeding differed between patients with and without a VCD (12 vs. 5 h, respectively). The clinical presentation of RPB was hemorrhagic shock in 39.6% of patients and 50.0% required at least one blood transfusion. Patients were managed either with conservative treatment (79.2%), angiography stenting (14.6%) or vascular surgery (6.2%). A total of 3 patients died during hospitalization, of which RPB was the etiology in 2 (4.2%). Conclusions: RPB which is a rare complication of CC is associated with younger age and female gender, as compared to patients without RPB. Onset of bleeding can be delayed in patients with VCDs. With careful and early diagnosis, most patients with RPB after CC can be managed conservatively.

Endothelial progenitor cells (EPCs) are attenuated, both in number and functionality, in animal models of chronic cardiovascular and metabolic disorders. This effect has subsequently been linked to the aggravation of long-term morbidity and mortality associated with such disorders. The objective was to examine EPC number and survival in chronic diabetic vs nondiabetic patients in conjunction with the examination of their redox, inflammatory, and antioxidant defense system (Nrf2 genes) status in serum and visceral fat.Visceral adipose tissue from diabetic and nondiabetic patients undergoing coronary artery bypass graft surgery was analyzed for Nrf2-dependent genes. Oxidative stress was evaluated using thiobarbituric acid-reactive substance assay (TBARS). Peripheral blood, collected 1 day prior to surgery, was evaluated for inflammatory cytokines and EPCs.When compared with controls (P0.05), results of the thiobarbituric acid-reactive substance assay were higher in diabetic patients. Although Nrf2-dependent antioxidant proteins (thioredoxin-1 [Trx-1], nicotinamide adenine dinucleotide phosphate [NAD(P)H] quinone oxidoreductase [NQO1], glutathione S-transferase [GST]) were upregulated, heme oxygenase (HO-1) and adiponectin protein expression were lower in the diabetic group (P0.05). Serum levels of bilirubin were lower (P0.005) while the levels of inflammatory cytokines were higher in diabetic patients (P0.05). EPC levels and their colony forming units were significantly lower (P0.05) with reduced viability in diabetic patients as compared with nondiabetic patients.These results demonstrate for the first time that in diabetic patients, there is an inadequate heme oxygenase-adiponectin axis response, which could compromise the compensatory antioxidant and anti-inflammatory effects consequently contributing toward EPC dysfunction in these patients.

High on-treatment platelet reactivity (HTPR) despite clopidogrel therapy is associated with adverse cardiac events after acute myocardial infarction (AMI). Most studies to date have assessed clopidogrel response at a single time point before or after percutaneous coronary intervention (PCI). It is unclear, however, whether the HTPR phenotype is stable over time. Therefore, we aimed to examine response to clopidogrel in patients with AMI treated with PCI over a 6-month period. Patients (n = 57) with AMI treated with PCI were assessed for response to clopidogrel at 3 time points: in hospital, 30 days, and 6 months after index hospitalization. Response to clopidogrel was determined by the VerifyNow P2Y12 assay (reported as P2Y12 response units) and multiple electrode aggregometry (MEA; reported as aggregation units). HTPR was defined as ≥235 P2Y12 response units or ≥47 aggregation units. Patients' mean age was 54.5 ± 10.9 years, 91% were men, 19% had diabetes, and 74% were admitted with ST-segment elevation MI. HTPR based on MEA was observed in 22.8% of patients in hospital, 26.3% at 30 days, and 17.5% at 6 months (p = NS). HTPR based on the VerifyNow assay was observed in 38.6% of patients in hospital, 28.1% at 30 days, and 33.3% at 6 months (p = NS). Individual HTPR phenotypic assignment at baseline was stable in 73.7% (based on MEA) and 70.2% (based on VerifyNow) of patients at 6-month follow-up. In conclusion, this is the first study evaluating the stability of clopidogrel response over time after AMI. Rates of HTPR to clopidogrel therapy appear to be relatively stable up to 6 months after AMI.

Clinical trial data have supported the safety and efficacy of drug-eluting stents (DES) in the treatment of patients with ST-segment elevation myocardial infarctions (STEMIs), but contemporary "real-world" registry data regarding the late safety profiles of DES are limited. This prospective registry-based study included 1,569 consecutive unselected patients with STEMIs who underwent emergency primary percutaneous coronary intervention from January 2001 to December 2009. Of the study cohort, 200 patients (12.7%) received DES, while 1,369 patients (87.3%) underwent bare-metal stent (BMS) placement. The primary end points of the study were all-cause mortality and target vessel revascularization at 1, 2, and 3 years. Survival status was assessed by municipal civil registries. Repeat revascularization procedures were prospectively collected in the hospital database. All-cause mortality was significantly lower in the DES group at 3 years (4.2% vs 13.5%, p = 0.007) compared to BMS-treated patients, but DES use was not an independent predictor of all-cause mortality (adjusted odds ratio 0.5, 95% confidence interval 0.2 to 1.2, p = 0.10). Target vessel revascularization was significantly lower in the DES group compared to the BMS group at 3 years (10.5% vs 21%, p = 0.001). DES use was an independent predictor of reduced target vessel revascularization (adjusted odds ratio 0.44, 95% confidence interval 0.25 to 0.77, p = 0.004). Late definite stent thrombosis occurring after 1 year occurred in 4 (2.5%) patients in the DES group compared to 6 (0.7%) in the BMS group (p = 0.05). DES use was an independent predictor of late stent thrombosis (adjusted odds ratio 8.6, 95% confidence interval 1.9 to 38, p = 0.004). In conclusion, this contemporary registry-based study of patients who underwent primary percutaneous coronary intervention for STEMI demonstrated improved revascularization rates without increased 3-year hazard of adverse clinical outcomes in DES-treated patients.

AIMS To conduct a risk-adjusted gender-based analysis of clinical outcomes following drug-eluting stent (DES) versus bare metal stent (BMS) implantation in patients with coronary artery disease. METHODS AND RESULTS We compared risk-adjusted total mortality rate, myocardial infarction, and event-free survival (defined as freedom from death, myocardial infarction and/or repeat revascularisation) in a consecutive cohort of 7,662 patients undergoing percutaneous coronary intervention at our institution, including 1,835 (25.4%) women. Follow-up was six months to 6.2 years (mean: 3.5 years; median: 3.6 years). The women were older than men and more likely to suffer from diabetes, hypertension or congestive heart failure. Smokers were more often men, and men were more likely to have had prior coronary bypass surgery compared to women. A DES was used in 39.9% of males and 39.5% of females. Both genders derived a significant long-term clinical benefit from DES compared to BMS; advantages were observed for mortality (men: HR=0.78, 95% CI: 0.64-0.96, p=0.016; women: HR=0.62, 95% CI: 0.45-0.85, p=0.003) and major adverse cardiac events (men: HR=0.73, 95% CI: 0.63-0.84, p

Objectives: Patients with antiphospholipid antibody syndrome (APS) have an increased risk of atherothrombotic complications. There are limited data regarding the outcome of patients with APS who undergo percutaneous coronary intervention (PCI). Accordingly, we aimed to assess the long-term outcomes of these patients. Methods: Nineteen APS patients who underwent PCI between the years 2003 and 2008 were compared to 380 patients who had undergone PCI during the same period (PCI group) and were matched by age (±5 years), gender, diabetes and hypertension. In addition, APS patients were compared to 1,458 patients with ST segment elevation myocardial infarction (MI) who were treated with PCI during the same period. Six-month to 4-year clinical outcomes were evaluated. Results: The indication for PCI in the APS group was acute coronary syndrome in 52.6% of patients. After 1 year of follow-up, patients with APS had higher rates of target vessel revascularization than the other two groups, which translated to higher rates of major adverse cardiac events. There were no differences in MI or mortality rates between the groups. Conclusions: Patients with APS who undergo PCI have worse long-term clinical outcomes, driven by higher rates of revascularization, than other patients undergoing PCI. Further study is warranted to examine the mechanisms underlying these findings.

Objectives: We aim to explore the clinical outcome of drug-eluting stents (DES) versus bare-metal stents (BMS) implantation in diabetics versus nondiabetic patients. Background: Diabetic patients sustain worse long-term clinical outcomes after percutaneous coronary interventions (PCI) when compared with nondiabetics. The use of DES decreases the rate of repeat revascularization in this population but data concerning long-term clinical benefits, such as myocardial infarction (MI) or mortality is scant. Methods: We analyzed data from a comprehensive registry of 6,583 consecutive patients undergoing PCI at our center. A propensity score was used for analysis of outcomes and for matching (DES vs. BMS). Outcome parameters were total mortality, MI, repeat target vessel revascularization (TVR) rates, and risk-adjusted event-free survival. Within this cohort, we identified 2,571 nondiabetic patients and these were compared with 1,826 diabetic coronary patients. Results: Mean and median follow up time was 3 and 3.25 years, respectively. Overall, diabetics had higher rates of major-adverse cardiovascular events (MACE) at 4 years compared with nondiabetics (23.03 vs. 31.96 P > 0.001). DES use was associated with lower rates of TVR in both groups [diabetics hazard ratio (HR) = 0.56, 95% confidence interval (CI): 0.42–0.76, P < 0.001, nondiabetics HR = 0.73, 95% CI: 0.55–0.97, P = 0.03] while sustained decreased rates of both mortality and MI were evident solely among diabetics (HR = 0.71, 95% CI: 0.56–0.89, P = 0.004 in diabetic vs. HR = 0.88, 95% CI: 0.69–1.13, P = 0.3). Conclusions: In a “real-world,” unselected population and extended clinical use, DES in diabetics was associated with sustained decreased rates of MI, death, TVR, and MACE while this benefit was attenuated in the nondiabetic population. © 2011 Wiley-Liss, Inc.

Clinical data from observational as well as prospective randomized trials has shown an increased risk for ischemic events in the 90 days following cessation of dual antiplatelet therapy (DAPT). A possible explanation for this finding is a “rebound” effect of DAPT cessation on platelet reactivity

Objectives The aim of this study was to evaluate whether addition of omega-3 fatty acids or increase in aspirin dose improves response to low-dose aspirin among patients who are aspirin resistant. Background Low response to aspirin has been associated with adverse cardiovascular events. However, there is no established therapeutic approach to overcome aspirin resistance. Omega-3 fatty acids decrease the availability of platelet arachidonic acid (AA) and indirectly thromboxane A2 formation. Methods Patients (n = 485) with stable coronary artery disease taking low-dose aspirin (75 to 162 mg) for at least 1 week were screened for aspirin response with the VerifyNow Aspirin assay (Accumetrics, San Diego, California). Further testing was performed by platelet aggregation. Aspirin resistance was defined by ≥2 of 3 criteria: VerifyNow score ≥550, 0.5-mg/ml AA-induced aggregation ≥20%, and 10-μmol/l adenosine diphosphate (ADP)-induced aggregation ≥70%. Thirty patients (6.2%) were found to be aspirin resistant and randomized to receive either low-dose aspirin + omega-3 fatty acids (4 capsules daily) or aspirin 325 mg daily. After 30 days of treatment patients were re-tested. Results Both groups (n = 15 each) had similar clinical characteristics. After treatment significant reductions in AA- and ADP-induced aggregation and the VerifyNow score were observed in both groups. Plasma levels of thromboxane B2 were also reduced in both groups (56.8% reduction in the omega-3 fatty acids group, and 39.6% decrease in the aspirin group). Twelve patients (80%) who received omega-3 fatty acids and 11 patients (73%) who received aspirin 325 mg were no longer aspirin resistant after treatment. Conclusions Treatment of aspirin-resistant patients by adding omega-3 fatty acids or increasing the aspirin dose seems to improve response to aspirin and effectively reduces platelet reactivity.