Left Atrial Appendage Closure With a Second Generation Device

Pharmacotherapy, 2008

The temporary total artificial heart (TAH-t) has emerged as an effective bridge to transplantation for individuals with biventricular failure. Implantation of a TAH-t creates a hypercoagulable state requiring a multidrug approach that includes low-dose unfractionated heparin (UFH) in order to minimize thromboembolism. A concern with UFH is the development of heparindependent antibodies, which develop in up to 50% of patients receiving the drug as part of cardiopulmonary bypass. If UFH therapy continues postoperatively, the risk of heparin-induced thrombocytopenia approaches 3%. Small investigations have demonstrated that bivalirudin, given as a bolus of 0.75-1 mg/kg followed by an infusion at 1.75-2.5 mg/kg/hour, is an effective alternative to UFH for therapeutic anticoagulation during coronary artery bypass surgery, valve replacement, or both. We describe a series of five adults (age range 24-58 yrs) who received bivalirudin as an alternative to low-dose UFH after TAH-t implantation. None of the patients had documented heparin-induced thrombocytopenia. Treatment was started at the discretion of the treating physician, and adjustments were based principally on the results of thromboelastography. Additional general monitoring included activated partial thromboplastin time, prothrombin time, international normalized ratio, fibrinogen, D-dimer, platelet count, hemoglobin, hematocrit, and platelet aggregation studies. Bivalirudin therapy was continued until successful warfarin implementation. All five patients received bivalirudin in addition to standard antithrombotic therapy. Bivalirudin treatment started at a dosage of 0.005 or 0.01 mg/kg/hour with titration to maintain normocoagulability, which occurred (without concomitant warfarin therapy) within the dosage range of 0.01-0.02 mg/kg/hour. Duration of TAH-t implantation was a mean of 38.8 days (range 25-60 days), and bivalirudin was continued for a mean of 15.2 days (range 7-24 days). No major hemorrhagic events occurred during treatment, and all patients successfully transitioned to warfarin therapy. Low-dose bivalirudin, as an alternative to UFH, maintained normocoagulability after TAH-t implantation. Further investigation is warranted to define the role and dosing of bivalirudin in this situation.

Journal of Surgical Research, 1984

The risk of postoperative thromboembolism (PTE), anticoagulant related hemorrhage (ARH), and the influence of thromboembolic risk factors (TERF) were assessed retrospectively in 206 unselected patients undergoing mitral valve replacement (MVR) with porcine xenobioprostheses (PXBP). Other aims were to identify the "high-risk" group with respect to PTE and to assess the effectiveness of longterm anticoagulant therapy (AT) in this subset, as well as to elucidate the most adequate method of AT and ascertain if AT is strictly necessary in patients undergoing MVR with PXBP. Patients were divided in two groups: Group I (N = 115) received long-term AT, there were 22 PTE. Group II (N = 91) with only 8 weeks of AT had 2 PTE (P < 0.01). ARH was the same in both groups. Actuarially, 71.7% of the patients in group I and 96.3% of the patients in group II were free of PTE at 6 years. Long-term AT proved ineffective in preventing PTE and carried a significant incidence of ARH. ARH surpassed PTE (3S:l) in patients on short-term AT. Patients without TERF have a low incidence of PTE, and AT is not indicated. The "high-risk" group were patients in postoperative atrial fibrillation and left atria1 enlargement. One week heparin therapy and 3 months oral AT is suggested for patients with TERF. PXBP for MVR in patients with TERF is significantly thrombogenic. Early operation is advocated to avoid development of TERF that will affect patient outlook after MVR with PXBP due to the significantly increased risks of PTE and (if placed on AT) ARH.

American Heart Journal, 2009

Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2005

To describe the perioperative management in a heparin-induced thrombocytopenia (HIT) positive patient who had prosthetic valve endocarditis and an aortic root abscess. The patient underwent high-risk cardiac re-operation with the use of the alternative anticoagulant, bivalirudin. Clinical features: A 62-yr-old patient who underwent stentless tissue aortic valve replacement with a Toronto-SPV valve in 1998, was admitted to hospital with symptoms of stroke. A heparin infusion was started and further investigation revealed positive blood cultures. The patient developed HIT which was confirmed by laboratory tests. Echocardiographic examination performed one month later showed vegetations on the aortic tissue valve and a small aortic root abscess. The patient still tested positively for the presence of HIT antibodies and was treated conservatively with antibiotics. A repeat echocardiographic examination showed progression of the aortic root abscess and it was decided to proceed with urgent redo aortic valve surgery. Anticoagulation for cardiopulmonary bypass (CPB) was achieved with the use of a direct thrombin inhibitor (DTI), bivalirudin. Following an uneventful wean from CPB, hemostasis was achieved within 40 min. The postoperative course was uncomplicated and the patient was discharged from hospital on the seventh postoperative day. Conclusion: Bivalirudin is a DTI, which can be used as an alternative anticoagulant for CPB in HIT positive patients. This case report showed a favourable outcome with bivalirudin for urgent complex redo cardiac surgery requiring CPB. Objectif : Décrire la prise en charge périopératoire d'un patient atteint de TIH, victime d'une endocardite sur prothèse valvulaire et d'un abcès à la racine de l'aorte. Le patient a subi une réopération cardiaque à haut risque avec l'usage d'anticoagulant de remplacement, la bivalirudine. Éléments cliniques : Un patient de 62 ans chez qui on a remplacé le tissu de la valve aortique, sans endoprothèse, par une valve Toronto-SPV en 1998 a été admis à l'hôpital pour des symptômes d'accident vasculaire cérébral. Une perfusion d'héparine a été amorcée et un examen ultérieur a révélé des cultures sanguines positives. Une TIH s'est développée et a été confirmée par les tests de laboratoire. L'échocardiographie, réalisée un mois plus tard, a montré des végétations sur la valve tissulaire aortique et un petit abcès à la racine de l'aorte. Les résultats aux tests indiquant toujours la présence d'anticorps de TIH, le patient a reçu une antibiothérapie conservatrice. Une nouvelle échocardiographie a montré la progression de l'abcès aortique, ce qui a conduit à répéter d'urgence l'opération de la valve aortique. L'anticoagulation pour la circulation extracorporelle (CEC) a été réalisée avec un inhibiteur direct de la thrombine (IDT), la bivalirudine. Après un sevrage sans incident de la CEC, l'hémostase a été atteinte en moins de 40 min. Aucune complication n'est survenue par la suite et le patient a quitté l'hôpital au septième jour postopératoire. Conclusion : La bivalirudine est un IDT qui peut être utilisé comme anticoagulant de remplacement pendant la CEC chez des patients victimes de TIH.

The American Journal of Cardiology, 2010

Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI) for stable angina and acute coronary syndrome. This study analyzed the impact of bivalirudin-based anticoagulation strategy versus UFH-based anticoagulation strategy on long-term bleeding complications and major adverse cardiac events in patients undergoing PCI in routine clinical practice. From September 2005 to April 2009, 3,367 consecutive patients who underwent PCI for stable angina or non-STsegment elevation acute coronary syndrome at Brigham and Women's Hospital were studied. Of these patients, 2,228 patients (66%) received UFH and 1,139 (34%) received bivalirudin. Bleeding complication and major adverse cardiac event rates were compared at discharge, 30 days, and 1 year. In a propensity-score matched analysis, bivalirudin-based anticoagulation strategy was associated with lower bleeding complications at 30 days (7.0% vs 13.7%, p ‫؍‬ 0.001) and 1 year (12.7% vs 18.9%, p ‫؍‬ 0.013). Major adverse cardiac event rates were not significantly different between groups at discharge, 30 days, and 1 year (6.4% vs 8.3%, p ‫؍‬ 0.103; 9.4% vs 10.9%, p ‫؍‬ 0.449; 12.1% vs 14.8%, p ‫؍‬ 0.235, respectively). There was no difference in all-cause mortality rates between the 2 groups (0.9% vs 0.8%, p ‫؍‬ 0.808, at discharge; 1.9% vs 3.6%, p ‫؍‬ 0.112, at 30 days; 3.6% vs 5.5%, p ‫؍‬ 0.195, at 1 year). In conclusion, in a real-world cohort of patients undergoing PCI, bivalirudin-based anticoagulation strategy is associated with a significant decrease in risk of bleeding complications after 30 days and 1 year compared to a UFH-based anticoagulation strategy with no increase in risk for major adverse cardiac events.

Thrombosis Research, 2015

Introduction: Transcatheter aortic valve implantation (TAVI) is associated with bleeding that increases mortality. Dual antiplatelet therapy (DAPT) is recommended in TAVI, however little is known about pre-procedural DAPT use and its impact on hemostasis. We sought to determine the frequency, predictors and bleeding events in patients receiving DAPT before TAVI. Methods: Three-hundred-and-three (n = 303, 78.6 ± 7.6 years, 49% female, EuroScore 23.1 ± 16.9) consecutive patients undergoing TAVI were prospectively analyzed and followed for in-hospital events. According to preprocedural antiplatelet status study population was divided into 2 groups: patients receiving aspirin and clopidogrel (DAPT) and those on aspirin only or no antiplatelet therapy (noDAPT). Results: Pre-procedural DAPT was used in 139 cases (46%). Previous PCI (OR 4.8,], p b 0.0001), implantation of self-expandable prosthesis (OR 2.2, [1.2-4], p = 0.007) femoral access (OR 2.2, [1.1-4.5], p = 0.029) and platelet count (OR 1.006, [1.002-1.01], p = 0.002) were identified as independent predictors of pre-procedural DAPT. No difference was observed in the rates of any bleeding (23% in DAPT vs. 24.4% in noDAPT, p = 0.930) or major/life-threatening bleeding (12.2% in DAPT vs. 14.7% in noDAPT, p = 0.715). Propensity-score matching analysis did not alter the results. GFR b 30 ml/min was the strongest predictor of bleeding (OR 4.3, [1.9-9.9], p = 0.0005). There was a trend towards lower frequency of MI and stroke/TIA in DAPT as compared with noDAPT (3.6% vs. 9.8%, p = 0.082). Conclusions: Pre-procedural DAPT is frequent and does not increase short-term bleeding complications or need for transfusion following TAVI. Possible impact of DAPT use before TAVI on ischemic complications needs to be investigated in larger populations.

European Heart Journal, 2008

The aim of this study was to identify a subset of patients at high risk of bleeding or myocardial infarction from a percutaneous coronary intervention and to investigate whether such high-risk subsets derive preferential benefit from heparin or bivalirudin. This study included 4570 patients with coronary artery disease enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment trial and randomized to receive bivalirudin or heparin. Primary outcomes were in-hospital incidence of major bleeding and 30-day incidence of myocardial infarction. Major bleeding, myocardial infarction, and bleeding plus myocardial infarction occurred in 140, 204, and 34 patients, respectively. Older age, female sex, lower body weight, low cholesterol, multi-lesion intervention, complex lesions, and heparin therapy were independent correlates of increased risk of bleeding. Multi-lesion intervention, unstable angina, and lower body weight correlated independently with increased risks of myocardial infarction. Compared with heparin, bivalirudin was associated with a reduction in major bleeding (3.1 vs. 4.6%, P ¼ 0.008), but mostly in low-risk patients. A reduction in the bleeding risk inversely correlated with an increase in the risk of myocardial infarction with bivalirudin (R ¼ 20.61). Bivalirudin and unfractionated heparin have a differential effect on risk of bleeding and myocardial infarction across various subsets of patients.

IJC Heart & Vasculature, 2018

MitraClip is an established therapy for patients with mitral regurgitation (MR) that are considered of high-risk or inoperable. However, late bleeding events (BE) after hospital discharge and their impact on prognosis in this cohort of patients have been poorly investigated. Our purpose is to address the incidence, related factors and clinical implications of BE after hospital discharge in patients treated with MitraClip. Methods: Prospective registry of all consecutive patients (n = 80) who underwent MitraClip implantation in our Institution between June 2014 and December 2017. BE were defined according to MVARC definitions. A combined clinical end-point including admission for heart failure (HF) and all-cause mortality was established to analyze prognostic implications of BE. Results: During a median follow up of 523.5 days, 41 BE were reported in 21 patients. Atrial fibrillation (AF, HR 4.54, CI95% 1.20-17.10) and combined antithrombotic therapy at discharge (HR 3.52, CI95% 1.03-11.34) were independently associated with BE. In the study period, 15 (18.8%) patients died, 20 (25%) were admitted for HF and 29 (36.3%) presented the combined end-point. After multivariable adjustment BE remained independently associated with an adverse outcome (HR 3.80, CI 95% 1.66-8.72). In the subgroup of patients with AF, HAS-BLED score was higher among subjects with BE (3.1 ± 1.3 vs 2.1 ± 0.9, p = 0.003). HAS-BLED score had a significant discrimination power for the occurrence BE (AUC: 0.677 [0.507-0.848]) in this subgroup. Conclusions: BE are common after MitraClip and are associated with an impaired outcome. Strategies to reduce bleeding events are paramount in this cohort of patients.

Journal of the American College of Cardiology, 2016

team assessed risk of operative mortality. We plan to report the final 2-year outcomes at the meeting. METHODS The Evolut R CE Study enrolled patients at 6 sites in Australia, New Zealand and the United Kingdom and included the first use of the valve for all operators. An independent echocardiographic core laboratory was employed, and Clinical Events Committee adjudicated major adverse events according to Valve Academic Research Consortium-2 criteria. RESULTS The study cohort comprised 60 patients; all successfully implanted with the Evolut R TAV. Mean age was 82.8AE 6.1 years; 66.7% women, 68.3% with New York Heart Association (NYHA) III/IV symptoms, and mean STS PROM was 7.0%AE3.7%. The majority of patients (68.3%) were considered frail. The repositioning feature of the Evolut R was successfully used 22 times in 15 patients. At 1 year, 4 patients had died (6.7%) and 2 patients had a disabling stroke (3.4%). A new pacemaker was required in 7 patients through 30 days (11.7%), with 2 additional implanted after 30 days for a 1-year rate of 15.2%. NYHA class improved from baseline to 1 year in 89.8% of patients. Forward flow hemodynamics continued to be excellent, with mean AV gradient of 7.5 AE 2.7 mmHg and mean EOA of 1.9 AE 0.4 cm2 at 1 year. In paired analysis, none or trace paravalvular leak (PVL) was present in 19/45 patients (42.2%) post-procedure; and 28/45 (62.2%) at 1 year. Two patients (4.3%) had moderate PVL and no patients had severe. No incidence of valve thrombosis, migration, embolization, coronary obstruction, endocarditis or evidence of structural valve degeneration has been reported through 1 year follow-up. CONCLUSION The Evolut R was associated with good safety and efficacy through 1 year. We plan to report final 2-year outcomes at the time of the meeting.

Pharmacotherapy, 2007

Objective. To compare clinical outcomes and glycoprotein IIb-IIIa inhibitor use in patients undergoing percutaneous coronary intervention (PCI) who received bivalirudin or unfractionated heparin (UFH) in a real-world setting. Design. Retrospective cohort analysis. Setting. University-affiliated medical center. Patients. One thousand seventy-five adult patients who underwent PCI and received either bivalirudin (539 patients) or UFH (536 patients) from April 1, 2003-April 1, 2004. Measurement and Main Results. Patient data on demographics, comorbidities, laboratory values, and reports of radiologic examinations, cardiac catheterizations, and discharge summaries were obtained. Outcomes evaluated included rates of in-hospital mortality, myocardial infarction, revascularization, and length of stay (LOS), as well as Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) and Thrombosis in Myocardial Infarction (TIMI) bleeding categorization. Bivalirudin use was associated with a significant reduction in TIMI major (5.0% vs 9.7%, p=0.003), REPLACE-2 major (5.4% vs 12.9%, p<0.001), and TIMI minor (1.7% vs 6%, p<0.001) bleeding complications compared with UFH use. Significantly fewer patients in the bivalirudin group received glycoprotein IIb-IIIa inhibitors (27.3% vs 62.7%, p<0.001). Patients receiving bivalirudin had significantly fewer myocardial infarctions after catheterization (10.7% [40/375] vs 18.0% [51/284], p=0.007).