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Few studies have characterized recent population trends in the incidence and outcomes of myocardial infarction.We identified patients 30 years of age or older in a large, diverse, community-based population who were hospitalized for incident myocardial infarction between 1999 and 2008. Age- and sex-adjusted incidence rates were calculated for myocardial infarction overall and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction. Patient characteristics, outpatient medications, and cardiac biomarker levels during hospitalization were identified from health plan databases, and 30-day mortality was ascertained from administrative databases, state death data, and Social Security Administration files.We identified 46,086 hospitalizations for myocardial infarctions during 18,691,131 person-years of follow-up from 1999 to 2008. The age- and sex-adjusted incidence of myocardial infarction increased from 274 cases per 100,000 person-years in 1999 to 287 cases per 100,000 person-years in 2000, and it decreased each year thereafter, to 208 cases per 100,000 person-years in 2008, representing a 24% relative decrease over the study period. The age- and sex-adjusted incidence of ST-segment elevation myocardial infarction decreased throughout the study period (from 133 cases per 100,000 person-years in 1999 to 50 cases per 100,000 person-years in 2008, P0.001 for linear trend). Thirty-day mortality was significantly lower in 2008 than in 1999 (adjusted odds ratio, 0.76; 95% confidence interval, 0.65 to 0.89).Within a large community-based population, the incidence of myocardial infarction decreased significantly after 2000, and the incidence of ST-segment elevation myocardial infarction decreased markedly after 1999. Reductions in short-term case fatality rates for myocardial infarction appear to be driven, in part, by a decrease in the incidence of ST-segment elevation myocardial infarction and a lower rate of death after non-ST-segment elevation myocardial infarction.

To the Editor: There has been growing interest in the use of the transradial approach for percutaneous coronary intervention (PCI), supported by randomized clinical trials involving experienced transradial operators [(1,2)][1]. However, the assessment of transradial PCI in routine practice has

Objectives: This study examined the efficacy and safety of the direct thrombin inhibitor argatroban in patients presenting with acute coronary syndromes undergoing cardiac catheterization. Background: Argatroban is a direct-thrombin inhibitor approved for use in percutaneous coronary intervention in patients with heparin-induced thrombocytopenia. Few studies have examined its use in patients undergoing cardiac catheterization for acute coronary syndromes. We performed a retrospective cohort study of patients presenting with acute coronary syndromes who received argatroban anticoagulation during cardiac catheterization. Methods: Consecutive patients presenting with acute coronary syndromes who received argatroban while undergoing cardiac catheterization from 2002 to 2005 were included. Patient characteristics and in-hospital outcomes were examined retrospectively via detailed chart review. The primary endpoints of the study were combined death, myocardial infarction or urgent revascularization, and major bleeding during the index hospitalization. Results: A total of 144 patients presenting with an acute coronary syndrome received argatroban during cardiac catheterization within the study period: 25% presented with ST-elevation myocardial infarction and 75% presented with non-ST-elevation acute coronary syndrome. The combined endpoint of death, myocardial infarction or urgent revascularization occurred in 13.2% of patients during the hospitalization. Major bleeding occurred in 2.1% of patients. Conclusions: In this cohort of patients presenting with acute coronary syndromes, patients receiving argatroban during cardiac catheterization had a moderate rate of adverse cardiac events and a very low rate of major bleeding. © 2009 Wiley-Liss, Inc.

Objectives: This study aimed to evaluate the efficacy and safety of argatroban during percutaneous interventions for peripheral arterial disease (PAD). Background: Endovascular interventions are commonly used in patients with peripheral arterial disease. Heparin is routinely administered during these procedures, but cannot be used in patients with a history of heparin-induced thrombocytopenia (HIT). Argatroban is an approved direct thrombin inhibitor for treatment of patients with HIT. There are currently few data on the efficacy and safety of argatroban during endovascular interventions for PAD. Methods: Patients who underwent endovascular interventions for PAD on argatroban between 2002 and 2005 were identified from out database. Efficacy was evaluated using a composite of death, urgent revascularization, and amputation, while safety was assessed by TIMI major bleeding during the index hospitalization. Results: A total of 48 patients undergoing lower extremity revascularization on argatroban were identified. Thirty two of these patients (67%) had antibody-confirmed HIT and the other 16 (33%) had suspected HIT. A mean dose of argatroban was 173.5 ± 143 μg/kg bolus, followed by a 10.7 ± 9.64 μg/kg/min infusion during the procedure. Twelve patients (25%) met the composite end point (two deaths, one urgent revascularization, nine amputations because of progressive peripheral arterial disease). TIMI major bleeding occurred in three (6%) patients. Conclusion: In patients with confirmed or suspected HIT undergoing endovascular intervention for PAD, argatroban appears to be effective and safe. A larger study is warranted to confirm these findings from a single center. © 2008 Wiley-Liss, Inc.

m A b a t t c v i u. ase summary 67-year-old woman with a history of sick sinus syndrome nderwent placement of a dual-chamber pacemaker in 1993 nd generator change in 2001 (Integrity AFx DR 5342, St. ude Medical, Inc., St. Paul, MN, USA). Pacing was prorammed to DDDR mode with a lower rate limit of 70 ppm, pper rate limit of 120 ppm, and AV delay of 300 ms. While ospitalized for other reasons, she complained of palpitaions that correlated to periods of ventricular pacing. The nset is shown in Figure 1, and the termination is shown in igure 2. What is the explanation for the ventricular pacing? s the pacemaker malfunctioning? What reprogramming can e performed to prevent this rhythm, which is causing the alpitations?

Thrombocytopenia is associated with an increased risk for adverse cardiac events and bleeding in patients presenting with acute coronary syndromes (ACS) treated with unfractionated heparin (UFH). Enoxaparin has been shown to improve outcomes in ACS; however, its effect on the development of thrombocytopenia in this population is not well documented. This study was conducted to examine the incidence and clinical importance of thrombocytopenia in patients presenting with non-ST-elevation ACS randomized to treatment with enoxaparin or UFH. Thrombocytopenia was defined as a platelet count100 x 10(9)/L or a50% decrease from baseline. Thrombocytopenia developed in a total of 93 of 3,910 patients during the follow-up period of 14 days; the incidence was similar between study arms. The development of thrombocytopenia was associated with more frequent death, nonfatal myocardial infarction, and urgent revascularization during the study period (odds ratio 2.96, p = 0.001). This association was independent of assignment to treatment with enoxaparin or UFH (p for interaction = 0.47). Major bleeding was also more common in patients with thrombocytopenia regardless of treatment. In conclusion, thrombocytopenia is a significant correlate of adverse events in patients presenting with non-ST-elevation ACS treated with either enoxaparin or UFH.

We thank Dr. Ganeshan and colleagues for their interest in our paper [(1)][1]. In our subgroup analysis of the DAPT Study (Dual Antiplatelet Therapy Study) [(1)][1], continued thienopyridine therapy beyond 12 months after coronary stent placement provided consistent reductions in ischemic endpoints

We sought to describe contemporary guidewire utilization for antegrade wire escalation during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We examined guidewire and microcatheter utilization during antegrade wire escalation attempts among 1097 CTO PCIs performed at 13

Unfractionated heparin has historically been used as the anticoagulant of choice in the management of a number of thrombotic diseases. Recognition of the limitations of heparin has led to the development of a newer class of anticoagulants, the direct thrombin inhibitors. Argatroban is a synthetic small molecule that selectively inhibits thrombin at its active site. In preclinical studies, argatroban has been shown to be more effective than heparin in preventing arterial thrombosis and in promoting vessel patency in conjunction with thrombolysis in a number of animal models. In clinical trials, argatroban has been shown to be as effective as heparin in the management of ST-segment elevation myocardial infarction in conjunction with thrombolysis. It has been shown to be an effective anticoagulant in patients undergoing percutaneous coronary interventions. In patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia complicated by thrombosis, argatroban significantly decreases the risk of thrombotic events. Small studies have demonstrated a potential role for its use in ischemic stroke and hemodialysis. Additional studies are warranted to confirm argatroban's efficacy in a wide variety of clinical settings.

Twelve months duration of dual antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES) is recommended to decrease risk of stent thrombosis (ST). Controversies surround the optimal duration of DAPT for reducing risk of thrombosis and whether DAPT should be individualized

To the Editor: After coronary stent placement, the vascular response to injury includes re-endothelialization by resident and circulating bone marrow–derived endothelial progenitor cells ([1][1]). Delayed re-endothelialization after drug-eluting stent (DES) implantation may lead to uncovered

Nuclear myocardial perfusion imaging (MPI) accounted for much of the rapid growth in cardiac imaging that occurred from the 1990s through the middle 2000s.1,2 Factors potentially discouraging use (including publication of appropriate use criteria) have since emerged,3 and recent data reveal modest declines in MPI use in the Medicare fee-for-service population.4 We investigated temporal trends in MPI use within a large, community-based population that included persons younger than 65 years and explored whether increasing use of other noninvasive imaging modalities potentially offset declining MPI use.

Dr Hawn and colleagues1 evaluated the risk of undergoing noncardiac surgery following coronary stent placement. The analysis, which examines the outcomes of 28 029 veterans undergoing noncardiac surgery within 24 months of coronary stent implantation, found that emergency surgery and severity of cardiac disease were the principal factors associated with postoperative major adverse cardiovascular events (MACE).

To assess genotype stability in Mycobacterium tuberculosis, DNA genotypes were compared in sequential isolates from 49 patients who had sputum cultures separated by at least 90 days that grew M. tuberculosis. By use of IS6110 and the polymorphic GC-rich sequence (PGRS) as markers, it was found that paired isolates from 14 (29%) of 49 patients showed changes in their DNA genotypes between isolates (12 in IS6110 genotypes and 2 in PGRS genotypes). Changed IS6110 genotypes were confined to strains with 8-14 bands and were not related to the bacterial drug susceptibility, the patients' human immunodeficiency virus serostatus, or adherence to therapy. Although this rate of change complicates the interpretation of molecular epidemiologic studies, it can be exploited to gain additional insight into disease transmission. Furthermore, IS6110-related mutations may be a major source of genetic plasticity in M. tuberculosis and provide insights into the organism's evolution and virulence.

2534 Background: We have initiated phase I clinical trials treating patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) (IRB #06-138) and relapsed acute lymphoblastic leukemia ...

Background During the previous decade, many strategies for preventing acute myocardial infarction found to be efficacious in randomized controlled trials have been adopted by physicians in the community. Although evaluations of quality improvement typically focus on process measures at the hospital, practice, or clinician level, assessment of improvements in health outcomes remains the true test for the successful translation of evidence into practice. Methods We performed a review of the current literature examining trends in the incidence of myocardial infarction in communities. We focused specifically on the group of population-based studies that have examined trends in myocardial infarction incidence. Results Few population-based studies have examined recent temporal trends in the incidence of myocardial infarction, overall and by type. Existing studies have been largely limited by modest sample sizes, limited diversity within the study populations, the use of composite end points that combine disparate outcomes, and the inability to characterize the effect of long-term outpatient medication use on observed trends in incidence and severity of myocardial infarction. Conclusion More contemporary assessments of community-wide changes in the epidemiology of myocardial infarction are needed to help assess the effectiveness of primary prevention and to identify areas for potential improvement.

Heparin is ubiquitously used in cardiac catheterization but predisposes to the development of heparin-induced thrombocytopenia. The objective was to examine prospectively the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies and heparin-induced thrombocytopenia in the population undergoing cardiac catheterization.This is a prospective study of 500 consecutive patients presenting for cardiac catheterization at our institution who were enrolled over the course of 1 year. Anti-PF4/heparin antibodies and concurrent platelet counts were measured at catheterization and 5 days thereafter. Thrombotic complications were assessed 30 days after the procedure via telephone interview. All patients presenting for cardiac catheterization at our institution were screened. Inclusion criteria were (a) males and nonpregnant females with age18 years and (b) patients scheduled to undergo cardiac catheterization. Patients with a known history of heparin-induced thrombocytopenia, with documented bleeding or hypercoagulability, and those at high risk for bleeding were excluded.Of 500 patients, 15 (3%) had anti-PF4/heparin antibodies before catheterization. After catheterization, the prevalence of anti-PF4/heparin antibodies increased to 10.1% (36 of 357) of the patients. Overall rates of thrombotic complications were low (4 of 445, 0.9%) and did not correlate with anti-PF4/heparin antibody status. Patients with an initial positive test for anti-PF4/heparin antibodies were more likely to have prior coronary disease (73.3% vs 45.2%; P.05). Patients who developed anti-PF4/heparin antibodies after catheterization were more likely to have increased length of stay (3.7 vs 2.4 days; P = .02). The platelet count at the time of catheterization was lower in the cohort of patients who developed the second positive anti-PF4/heparin antibody test versus patients without a second positive antibody test (mean values of 191,800/microL vs 222,300/microL; P = .008).The prevalence of antibodies to PF4/heparin is low in the population presenting for cardiac catheterization. However, a significant proportion of patients develop antibodies to PF4/heparin after a small exposure to heparin during catheterization. Clinically significant thrombotic complications were rare and did not correlate with antibody status.

SummaryCowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and redirect CPMV particles to cells of interest, we attached a folic acid-PEG conjugate by using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moiety allowed CPMV-specific recognition of tumor cells bearing the folate receptor. In addition, by testing CPMV formulations with different amounts of the PEG-FA moiety displayed on the surface, we show that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells. These studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors.

A hybrid approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) prioritizing and combining all available crossing techniques was developed to optimize procedural efficacy, efficiency, and safety, but there is limited published data on its outcomes.We examined the procedural techniques and outcomes of 1036 consecutive CTO PCIs performed using a hybrid approach between 2012 and 2015 at 11 US centers.Mean age was 65 ± 10 years and 86% of the patients were men, with a high prevalence of diabetes mellitus (43%) and prior coronary artery bypass graft surgery (34%). Most target CTOs were located in the right coronary artery (59%), followed by the left anterior descending artery (23%) and the circumflex (19%). Dual injection was used in 71%. Technical success was achieved in 91% and a major procedural complication occurred in 1.7% of cases. The final successful crossing technique was antegrade wire escalation in 46%, antegrade dissection/re-entry in 26%, and retrograde in 28%. The initial crossing strategy was successful in 58% of the lesions, whereas 39% required an additional approach. Overall, antegrade wire escalation was used in 71%, antegrade dissection/re-entry in 36%, and the retrograde approach in 42% of procedures. Median contrast volume, fluoroscopy time, and air kerma radiation dose were 260 (200-360) ml, 44 (27-72) min, and 3.4 (2.0-5.4) Gray, respectively.Application of a hybrid approach to CTO crossing resulted in high success and low complication rates across a varied group of operators and hospital practice structures, supporting its expanding use in CTO PCI.

A variety of different stents and embolic protection devices (EPD) are used for carotid artery stenting (CAS). Little is known about current usage patterns and differences in outcomes with these devices. We analyzed 9863 consecutive carotid stent procedures in the NCDRR CARER registry performed

In patients with acute coronary syndromes (ACS), the use of emergency medical services (EMS) may allow for earlier diagnosis, stabilization and triage to a percutaneous coronary intervention (PCI) facility. Thus, use of EMS may lead to improvement in outcomes, particularly in those patients at

Safety concerns surrounding drug-eluting stents (DES) in 2006 led to questions about the potential bleeding risk of prolonged dual antiplatelet therapy for very elderly patients. We evaluated whether treatment selection strategy (DES vs. bare-metal stents [BMS]) for patients aged ≥ 85 changed