Jason C Kovacic

Cardiovascular Research Foundation, New York City, New York, United States

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Publications (72)510.56 Total impact

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    ABSTRACT: Veins grafted into an arterial environment undergo a complex vascular remodeling process. Pathologic vascular remodeling often results in stenosed or occluded conduit grafts. Understanding this complex process is important for improving the outcome of patients with coronary and peripheral artery disease undergoing surgical revascularization. Using in vivo murine cell lineage-tracing models, we show that endothelial-derived cells contribute to neointimal formation through endothelial-to-mesenchymal transition (EndMT), which is dependent on early activation of the Smad2/3-Slug signaling pathway. Antagonism of transforming growth factor-β (TGF-β) signaling by TGF-β neutralizing antibody, short hairpin RNA-mediated Smad3 or Smad2 knockdown, Smad3 haploinsufficiency, or endothelial cell-specific Smad2 deletion resulted in decreased EndMT and less neointimal formation compared to controls. Histological examination of postmortem human vein graft tissue corroborated the changes observed in our mouse vein graft model, suggesting that EndMT is operative during human vein graft remodeling. These data establish that EndMT is an important mechanism underlying neointimal formation in interpositional vein grafts, and identifies the TGF-β-Smad2/3-Slug signaling pathway as a potential therapeutic target to prevent clinical vein graft stenosis.
    Science translational medicine 03/2014; 6(227):227ra34. · 10.76 Impact Factor
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    ABSTRACT: There is a looming global epidemic of obesity and diabetes. Of all the end-organ effects caused by diabetes, the cardiovascular system is particularly susceptible to the biologic perturbations caused by this disease, and many patients may die from diabetes-related cardiovascular complications. Substantial progress has been made in understanding the pathobiology of the diabetic vasculature and heart. Clinical studies have illuminated the optimal way to treat patients with cardiovascular manifestations of this disease. This article reviews these aspects of diabetes and the cardiovascular system, broadly classified into diabetic vascular disease, diabetic cardiomyopathy, and the clinical management of the diabetic cardiovascular disease patient.
    Endocrinology and metabolism clinics of North America 03/2014; 43(1):41-57. · 3.56 Impact Factor
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    ABSTRACT: Pluripotent stem cells (PSCs) represent an appealing source from which to develop cell replacement therapies. Different initiatives have been launched to promote their development toward clinical applications. This article will review the main questions that should be considered before translating PSC-derived cardiomyocytes into clinical investigations, including the development of good manufacturing practice-level PSC lines, the development of efficient protocols to generate pure populations of cardiac myocytes, and the development of techniques to improve the retention and survival rate of transplanted cells.
    Stem Cell Research & Therapy 01/2014; 5(1):1. · 3.65 Impact Factor
  • Matthew I. Tomey, Jagat Narula, Jason C. Kovacic
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    ABSTRACT: Atherosclerosis research has classically followed two intertwining lines of investigation concerning atherosclerosis as a local process (the “high-risk plaque”) and as a systemic disease (the “high-risk patient”). Over time, the weight of attention has swung, like a pendulum, between these two related foci. With optimal medical therapy and attention to risk factors firmly established as fundamental aspects of management, in the past year, we have nevertheless perceived a shift in the pendulum toward renewed focus on the local plaque. We contend that this shift results from a convergence of major advances in understanding the biology of plaque progression, novel sophisticated invasive and noninvasive imaging modalities for the in vivo characterization of plaque composition and inflammation, and emerging data and technologies which have renewed interest in locally targeted interventions. Here, we review the dynamic and exciting progress that has occurred over the last 12 months in this arena, while acknowledging future work that remains to be done to refine and validate new imaging modalities and therapies.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
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    ABSTRACT: Aims: We sought to assess if bivalirudin use during balloon aortic valvuloplasty (BAV) would affect clinical outcomes compared with heparin. Methods and results: We compared the outcomes of consecutive patients who underwent elective or urgent BAV with intraprocedural use of bivalirudin or heparin at two high-volume centres. All in-hospital events post BAV were adjudicated by an independent, blinded clinical events committee. Of 427 patients, 223 patients (52.2%) received bivalirudin and 204 (47.8%) received heparin. Compared with patients who received heparin, patients who received bivalirudin had significantly less major bleeding (4.9% vs. 13.2%, p=0.003). Net adverse clinical events (NACE, major bleeding or major adverse cardiovascular events [MACE]) were also reduced (11.2% vs. 20.1%, p=0.01). There was no significant difference in the rates of MACE (mortality, myocardial infarction or stroke, 6.7% vs. 11.3%, p=0.1), or vascular complications (major, 2.7% vs. 2.0%; minor, 4.5% vs. 4.9%; p=0.83). After multivariate analysis controlling for vascular preclosure, the use of bivalirudin remained independently associated with reduced major bleeding (OR 0.37; 95% CI: 0.16 to 0.84; p=0.02) while the association was attenuated in propensity-adjusted analysis (OR 0.44, 95% CI: 0.18 to 1.07, p=0.08). Conclusions: In this registry of patients with severe aortic stenosis, bivalirudin as compared to heparin resulted in improved in-hospital outcomes post BAV in terms of reduced major bleeding, similar MACE and reduced NACE. If verified in a randomised study and extended to the transcatheter aortic valve implantation (TAVI) population, these results might indicate a potential benefit for patients undergoing such procedures.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 11/2013; · 3.17 Impact Factor
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    ABSTRACT: Introduction:Generic clopidogrel recently became available in the United States and was rapidly adopted as a cost-effective alternative to the brand name formulation. However, unlike other medications, subtle differences in clopidogrel bioavailability may lead to acute consequences including stent thrombosis (ST).Materials and METHODS: We studied the incidence of acute and subacute ST during the initial period of generic clopidogrel use (June 18, 2012-September 6, 2012 [80 days]) at a single percutaneous coronary intervention (PCI) center. There were 4 definite ST cases within 30 days of successful PCI in patients receiving generic clopidogrel, which were compared to historic control ST cases from 80 days prior to generic clopidogrel use and for 3 years from June 18, 2009 to June 17, 2012. During generic clopidogrel administration, 1054 PCIs were performed, giving a definite 30-day ST incidence of 0.38% (4 of 1054) among these patients. By comparison, there were 2 episodes of definite 30-day ST during the 80 days immediately preceding generic clopidogrel use (2 of 1114), while 3-year historic data indicated a definite 30-day ST incidence of 0.14% (20 of 14 432), representing a 2.7-fold increase in definite 30-day ST with generic clopidogrel use (P = .076). Exclusion of 3 historic controls with a defined reason for ST (noncompliance, marked thrombocytosis) gave a 3.2-fold increase in 30-day ST with generic clopidogrel (P = .050). An ST-predictive algorithm revealed no difference in the likelihood of ST between patients receiving generic clopidogrel and historic controls. We observed an unexpected >2-fold increase in ST coincident with generic clopidogrel use. Although we cannot ascribe causality, this observation warrants increased vigilance and close monitoring of patients receiving generic clopidogrel.
    Journal of Cardiovascular Pharmacology and Therapeutics 11/2013; · 2.38 Impact Factor
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    ABSTRACT: Phenotypic modulation or switching of Vascular Smooth Muscle Cells (VSMC) from contractile/quiescent to a proliferative/synthetic phenotype plays a key role in vascular proliferative disorders, such as atherosclerosis and restenosis. Although several calcium handling proteins that control differentiation of SMCs have been identified, the role of protein phosphatase inhibitor 1 (I-1) in the acquisition and/or maintenance of the contractile phenotype modulation remain unknown. In human coronary arteries, I-1 and Sarco/endoplasmic Reticulum Ca(2+)-ATPase (SERCA2a) expression is specific to contractile VSMCs. In synthetic cultured human coronary artery SMC (hCASMCs), protein phosphatase inhibitor 1 (PP1; I-1 target) is highly expressed, leading to a decrease in Phospholamban (PLB) phosphorylation, SERCA2 and cAMP Responsive Element Binding (CREB) activity. I-1 knock-out mice lack PLB phosphorylation and exhibit VSMC arrest in the synthetic state with excessive neointimal proliferation following carotid injury, and significant modifications of contractile properties and relaxant response to acetylcholine (ACh) of femoral artery in vivo. Constitutively active I-1 (I-1c) gene transfer decreased neointimal formation in an angioplasty rat model by preventing VSMC contractile to synthetic phenotype change CONCLUSIONS: I-1 and SERCA2a synergistically induce the VSMC contractile phenotype. Gene transfer of I-1c is a promising therapeutic strategy for preventing vascular proliferative disorders.
    Circulation 11/2013; · 15.20 Impact Factor
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    ABSTRACT: BACKGROUND: RE-ENDOTHELIALIZATION IS DELAYED AFTER DRUG-ELUTING STENT (DES) IMPLANTATION. IN THIS SETTING, NEOINTIMA IS MORE PRONE TO BECOME LIPID LADEN AND DEVELOP NEOATHEROSCLEROSIS (NA), POTENTIALLY INCREASING PLAQUE VULNERABILITY.METHODS AND RESULTS: OPTICAL COHERENCE TOMOGRAPHY AND NEAR-INFRARED SPECTROSCOPY WITH INTRAVASCULAR ULTRASOUND WERE USED TO CHARACTERIZE NA IN 65 (51 DES AND 14 BARE-METAL STENTS) CONSECUTIVE SYMPTOMATIC PATIENTS WITH IN-STENT RESTENOSIS. MEDIAN DURATION POSTSTENT IMPLANTATION WAS 33 MONTHS. OPTICAL COHERENCE TOMOGRAPHYVERIFIED NA WAS OBSERVED IN 40 STENTS WITH IN-STENT RESTENOSIS (62%), WAS MORE PREVALENT IN DES THAN BARE-METAL STENTS (68% VERSUS 36%; P=0.02), AND DEMONSTRATED SIGNIFICANTLY HIGHER PREVALENCE OF THIN-CAP NEOATHEROMA (47% VERSUS 7%; P=0.01) IN DES. NEAR-INFRARED SPECTROSCOPY ASSESSMENT DEMONSTRATED THAT THE TOTAL LIPID CORE BURDEN INDEX (34 [INTERQUARTILE RANGE, 1292] VERSUS 9 [INTERQUARTILE RANGE, 032]; P0.001) AND THE DENSITY OF LIPID CORE BURDEN INDEX (LIPID CORE BURDEN INDEX/4 MM, 144 [INTERQUARTILE RANGE, 60285] VERSUS 26 [INTERQUARTILE RANGE, 086]; P0.001) WERE HIGHER IN DES COMPARED WITH BARE-METAL STENTS. TOPOGRAPHICALLY, NA WAS CLASSIFIED AS I (THIN-CAP NA), II (THICK-CAP NA), AND III (PERI-STRUT NA). TYPE I THIN-CAP NEOATHEROMA WAS MORE COMMON IN DES (20% VERSUS 3%; P=0.01) AND IN AREAS OF THE STENTED SEGMENT WITHOUT SIGNIFICANT IN-STENT RESTENOSIS (71%). PERIPROCEDURAL MYOCARDIAL INFARCTION OCCURRED ONLY IN DES (11 VERSUS 0; P =0.05), OF WHICH 6 (55%) COULD BE ATTRIBUTED TO SEGMENTS WITH 70% IN-STENT RESTENOSIS. BY LOGISTIC REGRESSION, PRIOR DES WAS THE ONLY INDEPENDENT PREDICTOR OF BOTH NA (ODDS RATIO, 7.0; 95% CONFIDENCE INTERVAL, 1.727; P=0.006) AND PERIPROCEDURAL MYOCARDIAL INFARCTION (ODDS RATIO, 1.8; 95% CONFIDENCE INTERVAL, 1.12.4; P=0.05).CONCLUSIONS: In-stent thin-cap neoatheroma is more prevalent, is distributed more diffusely across the stented segment, and is associated with increased periprocedural myocardial infarction in DES compared with bare-metal stents. These findings support NA as a mechanism for late DES failure.
    Circulation Cardiovascular Interventions 09/2013; · 6.54 Impact Factor
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    ABSTRACT: To investigate the use of the GuideLiner "mother-and-child" guide catheter extension system as a simple solution to facilitate initial device delivery in balloon uncrossable chronic total occlusions (CTOs) undergoing percutaneous coronary intervention (PCI). During PCIs for CTO lesions, an important reason for procedural failure is the inability to deliver a balloon or microcatheter across the lesion. We retrospectively accessed our interventional registry for 07/01/2010 to 03/21/2012 and extracted data on all CTO lesions involving GuideLiner catheter use. Cine review was performed to identify cases where a guidewire had crossed the CTO and the use of a GuideLiner catheter facilitated initial device delivery. We identified 28 patients that underwent PCI for CTO with a GuideLiner catheter used to assist initial balloon or microcatheter advancement across the culprit lesion. Mean overall CTO length was 26.3 ± 18.1 mm. The GuideLiner catheter was successful in delivering a small balloon to the CTO lesion in 85.7% of cases (24/28). A single CTO PCI resulted in a distal guidewire perforation, but there was no hemodynamic compromise or pericardial effusion and the patient was discharged the next day. Overall procedural success in these selected cases (where a guidewire had already crossed the CTO) was 89.3% (25/28). The GuideLiner mother-and-child catheter is a simple, safe and efficacious adjunctive device for difficult CTO PCIs where despite standard measures it is not possible to deliver an initial balloon or microcatheter across the occluded segment.
    Journal of Interventional Cardiology 08/2013; 26(4):343-50. · 1.50 Impact Factor
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    ABSTRACT: Emerging data have indicated unexpected complexity in the regulation of vascular and bone calcification. In particular, several recent studies have challenged the concept of a universally positive relationship between body morphology [weight, height, body mass index (BMI), body surface area (BSA)] and the extent of vascular calcification. We sought to clarify these discrepancies and investigated the relationship between index lesion coronary artery calcification (CAC) and body morphology in patients undergoing percutaneous coronary intervention (PCI) using three-dimensional intravascular ultrasound (IVUS). We analysed CAC in patients who underwent PCI with pre-intervention IVUS imaging. The main outcome measure was the calcium index (CalcIndex); a three-dimensional IVUS-derived measure of total calcification per obstructive coronary lesion. A total of 346 patients (65.3 ± 10.6 years; 29.5% females) underwent PCI with IVUS-based CAC assessment. CalcIndex was categorized as zero-low (0-0.1399; n = 152) or intermediate-high (0.1400-1.2541; n = 194). All measures of body morphology were lower in patients with intermediate-high CalcIndex (height, P = 0.024; weight, P = 0.008; BMI, P = 0.064; BSA, P = 0.005). In adjusted multivariable models, weight and BSA were independent inverse predictors of intermediate-high CalcIndex [weight: odds ratio (OR) 0.986, P = 0.017; BSA: OR 0.323, P = 0.012] while CalcIndex also trended towards an inverse association with both height (P = 0.068) and BMI (P = 0.064). These independent inverse associations were consistent across multiple clinical subgroups, including stratification by age, race, gender, diabetes, and renal impairment. Using three-dimensional IVUS to assess vascular calcification, these data confirm an independent, inverse relationship between body size and index lesion CAC in patients with obstructive coronary artery disease.
    European heart journal cardiovascular Imaging. 07/2013;
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    ABSTRACT: Objectives This study sought to determine the impact of short-term intensive statin therapy on intracoronary plaque lipid content.Background Statin therapy significantly reduces the risk for thrombotic events. Whether or not these benefits are attributable to reduction in plaque lipid content remains to be properly documented in human obstructive coronary artery disease (CAD).Methods We randomized 87 patients with multivessel CAD undergoing percutaneous coronary intervention and at least 1 other severely obstructive (fractional flow reserve [FFR] ≤0.8) nontarget lesion (NTL) to intensive (rosuvastatin 40 mg daily) or standard-of-care lipid-lowering therapy. NTLs were evaluated at baseline and after 7 weeks of therapy with FFR, near-infrared spectroscopy, and intravascular ultrasound. The primary endpoint was the change in lipid-core burden index at the 4-mm maximal segment (LCBI4mm max), wherever this occurred within the lesion.Results Upon follow-up, median reduction (95% confidence interval) in LCBI4mm max was significantly greater in the intensive versus standard group (−149.1 [−210.9 to −42.9] vs. 2.4 [−36.1 to 44.7]; p = 0.01). Results remained consistent after adjustment for baseline differences in LCBI between groups and use of change in LCBI across the entire lesion as the dependent outcome.Conclusions Short-term intensive statin therapy may reduce lipid content in obstructive lesions. These hypothesis-generating findings warrant confirmation in larger studies with longer follow-up. (Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy [YELLOW]); NCT01567826)
    Journal of the American College of Cardiology 07/2013; 62(1):21-29. · 14.09 Impact Factor
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    ABSTRACT: Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, that efficiently induces endothelial-like precursor cells, with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1, and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent hematopoietic stem cell gene-expression profiles and cell-surface phenotypes. After transgene silencing and reaggregation culture, the specified cells generate hematopoietic colonies in vitro. Thus, we show that a simple combination of transcription factors is sufficient to induce a complex, dynamic, and multistep developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem and progenitor cells, as well as more-differentiated blood products.
    Cell stem cell 06/2013; · 23.56 Impact Factor
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    ABSTRACT: OBJECTIVE: Mice genetically deficient in endothelial nitric oxide synthase (eNOS(-/-)) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. Although the current paradigm holds that this bioactivity derives specifically from the expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. APPROACH AND RESULTS: To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted wild-type and eNOS(-/-) mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate l-arginine and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert (14)C-arginine into (14)C-citrulline in an NOS-dependent fashion. CONCLUSIONS: These are the first studies to definitively establish a role for a blood-borne eNOS, using cross-transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2013; · 6.34 Impact Factor
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    ABSTRACT: Objectives: To compare the discriminatory value of differing risk scores for predicting clinical outcomes following PCI in routine practice. Background: Various risk scores predict outcomes after PCI. However, these scores consider markedly different factors, from purely anatomical (SYNTAX risk score [SRS]) to purely clinical (ACEF, modified ACEF [ACEFmod], NCDR), while other scores combine both elements (Clinical SYNTAX score [CSS], NY State Risk Score [NYSRS]). Methods: Patients with triple vessel and/or LM disease with 12 month follow-up were studied from a single center PCI registry. Exclusion criteria included STEMI presentation, prior revascularization and shock. Clinical events at 12 months were compared to baseline risk scores, according to score tertiles and area under receiver-operating-characteristic curves (AUC). Results: We identified 584 eligible patients (69.8±12.3yrs, 405 males). All scores were predictive of mortality, with the SRS being least predictive (AUC=0.66). The most accurate scores for mortality were the CSS and ACEF (AUC=0.76 for both: p=0.019 and 0.08 vs. SRS, respectively). For TLR, while the SRS trended toward being positively predictive (p=0.075), several scores trended towards a negative association, which reached significance for the NCDR (p=0.045). The SRS and CSS were the only scores predictive of MI (both p<0.05). No score was particularly accurate for predicting MACE (death+MI+TLR), with AUCs ranging from 0.53 (NCDR) to 0.63 (SRS). Conclusions: Competing factors influence mortality, MI and TLR after PCI. An increasing burden of comorbidities is associated with mortality, whereas anatomical complexity predicts MI. By combining these outcomes to predict MACE, all scores show reduced utility. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 05/2013; · 2.51 Impact Factor
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    ABSTRACT: Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4-6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 - 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.
    Thrombosis and Haemostasis 05/2013; 110(1). · 6.09 Impact Factor
  • Arteriosclerosis Thrombosis and Vascular Biology 05/2013; · 6.34 Impact Factor
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    ABSTRACT: Objective: To determine the impact of suture-mediated vascular closure devices on net adverse clinical events (NACE) after balloon aortic valvuloplasty (BAV). Background: Ischemic and bleeding complications are common following transfemoral BAV however; previous studies have been single center and limited by varying definitions of major bleeding. Methods: The Effect of Bivalirudin on Aortic Valve Intervention Outcomes (BRAVO) study was a retrospective observational study conducted at two high-volume academic centers over a 6-year period designed to compare the effect of bivalirudin versus unfractionated heparin. This is a sub-analysis of 428 consecutive patients who underwent BAV (with 10-13 French sheaths) to compare the effect of hemostasis with vascular closure devices versus manual compression utilizing standardized definitions. NACE was defined as the composite of major bleeding and major adverse clinical events (MACE). All events were adjudicated by an independent clinical events committee who were blinded to antithrombin use. Results: Pre-closure was performed in 269 (62.8%) of patients. While bivalirudin was used more frequently in those with pre-closure (60.6% vs. 37.7%, p<0.001), a history of prior BAV (11.1% vs. 3.6%, p=0.04) and peripheral vascular disease (30.7% vs. 19.7%, p=0.01) was more common in those not undergoing pre-closure (n=159, 37%). Other clinical and demographic features were well balanced between groups. Vascular closure was associated with a significant reduction in NACE (24.5% vs 10.0% p<0.001). Results remained significant after adjusting for baseline differences and bivalirudin use (OR 0.38, 95% CI: 0.21 - 0.68; p=0.001). Conclusions: Our study suggests that suture-mediated vascular closure is associated with a substantial reduction in NACE after transfemoral BAV. Large randomized clinical trials should be conducted to confirm our results. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 02/2013; · 2.51 Impact Factor
  • Heart (British Cardiac Society) 01/2013; · 5.01 Impact Factor
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    ABSTRACT: Patients with ST-segment elevation myocardial infarction (STEMI) admitted during nonregular working hours (off-hours) have been reported to have greater mortality than those admitted during regular working hours (on-hours), perhaps because of the lower availability of catheterization laboratory services and longer door-to-balloon times. This might not be the case, however, for hospital centers in which primary percutaneous coronary intervention (PCI) is invariably performed. We conducted a substudy using the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction study data to determine whether the STEMI arrival time was associated with differing clinical outcomes. We identified all patients with STEMI admitted to a PCI-capable hospital who underwent primary PCI. Patients presenting during on-hours were compared to those presenting during off-hours. The primary outcome of death, major adverse cardiovascular events, and net adverse clinical events was examined. We identified 2,440 patients (1,205 [49%] on-hours and 1,235 [51%] off-hours). Similar baseline characteristics were observed. The off-hour patients had a significantly longer door-to-balloon time (92 vs 75 minutes; p <0.0001) and total ischemic time (209 vs 194 minutes; p <0.0001). Despite these differences, the risk-adjusted all-cause mortality, major adverse cardiovascular events, and net adverse clinical events rates were similar for both groups during the in-hospital, 1-year, and 3-year follow-up. In conclusion, patients with STEMI presenting to primary PCI hospitals during off-hours might have slightly longer delays to revascularization; however, they experienced similar short- and long-term survival and clinical outcomes as those arriving during on-hours.
    The American journal of cardiology 01/2013; · 3.58 Impact Factor
  • Jason C Kovacic, Valentin Fuster
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    ABSTRACT: There are very few things in medicine which are simple. Birth and mortality are relatively straightforward to define... but after that the trouble begins. To the casual observer the etiology of myocardial infarction (MI) is relatively obvious: prolonged myocardial ischemia. However, as Aldrovandi et al(1) have taught us in this edition of Circulation, we still have a lot to learn about this disease. Indeed, earlier this year the updated Third Universal Definitions of Myocardial Infarction were published.(2) Of course, the tacit fact underlying this publication is that even the definition of an MI remains a major "work in progress."
    Circulation 11/2012; · 15.20 Impact Factor

Publication Stats

432 Citations
92 Downloads
510.56 Total Impact Points

Institutions

  • 2013
    • Cardiovascular Research Foundation
      New York City, New York, United States
  • 2011–2013
    • Mount Sinai Medical Center
      New York City, New York, United States
    • Mount Sinai School of Medicine
      Manhattan, New York, United States
  • 2012
    • Albert Einstein College of Medicine
      New York City, New York, United States
  • 2010–2012
    • Mount Sinai Hospital
      New York City, New York, United States
  • 2004–2011
    • Victor Chang Cardiac Research Institute
      Darlinghurst, New South Wales, Australia
  • 2008–2010
    • National Heart, Lung, and Blood Institute
      • Translational Medicine Branch
      Maryland, United States
    • National Human Genome Research Institute
      Maryland, United States
  • 2004–2006
    • St. Vincent's Hospital Sydney
      • Department of Cardiology
      Sydney, New South Wales, Australia
  • 2003–2005
    • Saint Vincent Hospital
      Worcester, Massachusetts, United States