Incidence, source, and prognostic impact of major bleeding across the spectrum of aortic stenosis.

BACKGROUND: Severe aortic stenosis (AS) has been associated with bleeding. However, there is a lack of prospective assessment of bleeding events and their clinical significance in a large population of outpatients with variable degree of AS severity. OBJECTIVES: To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with variable degree of AS severity. METHODS: Between May 2016 and December 2017, consecutive outpatients were included. Major bleeding was defined as type ≥3 bleed using the Bleeding Academic Research Consortium definition. Cumulative incidence was calculated with death as the competing event. Data was censored at time of aortic valve replacement. RESULTS: Among 2,830 patients, 46 major bleeding events occurred (0.7%/year) during a median follow-up of 2.1 years (interquartile range: 1.4-2.7). Most frequent sites of bleeding were gastrointestinal (50%) and intracranial (30.4%). Major bleeding was significantly associated with all-cause mortality (hazard ratio: 5.93 (95% confidence interval 3.64-9.65); P < .001). AS severity was associated with major bleedings (P = .041). By multivariable analysis, severe AS was an independent determinant of major bleeding (hazard ratio vs mild AS: 3.59 [95% confidence interval 1.56-8.29]; P = .003). The increased risk of bleeding associated with severe AS was significantly exacerbated in patients using oral anticoagulation. CONCLUSION: In AS patients, major bleeding is rare but a strong independent predictor of death. AS severity is a determinant of bleeding events. Severe AS and oral anticoagulation should be identified as an association at very high risk of major bleeding.

Five-Year Clinical Outcome and Valve Durability After Transcatheter Aortic Valve Replacement in High-Risk Patients.

BACKGROUND: The FRANCE-2 registry (French Aortic National Corevalve and Edwards) previously reported good early- and medium-term clinical and echocardiographic efficacy for transcatheter aortic valve replacement. We here report 5-year follow-up results from the registry. METHODS: The registry includes all consecutive patients undergoing transcatheter aortic valve replacement for severe aortic stenosis in France. Follow-up is scheduled at 30 days, 6 months, then annually from 1 to 5 years. Clinical events were defined according to the Valve Academic Research Consortium criteria, and hemodynamic structural valve deterioration (SVD) was defined according to the consensus statement by the European Association of Percutaneous Cardiovascular Interventions. RESULTS: Between January 2010 and January 2012, 4201 patients were enrolled in 34 centers. Five-year vital status was available for 95.5% of patients; 88.1% had clinical evaluation or died. Overall, at 5 years, all-cause mortality was 60.8% (n=2478; 95% CI, 59.3% to 62.3%). The majority of cardiovascular events occurred in the first month after valve implantation, and incidence remained low thereafter, at <2% per year up to 5 years, except for heart failure. The rate of heart failure was 14.3% at 1 year, then decreased over time to <5% per year. In cumulative incidence function, the rates of severe SVD and moderate/severe SVD at 5 years were 2.5% and 13.3%, respectively. Mortality did not differ between patients with or without severe SVD (hazard ratio, 0.71; 95% CI, 0.47-1.07; P=0.1). Finally, in the population of patients with severe SVD, 1 patient (1.7%) experienced a stroke, and 8 patients presented ≥1 heart failure event (13.3%). CONCLUSIONS: The 5-year follow-up results of the FRANCE-2 registry represent the largest long-term data set available in a high-risk population. In surviving patients, the low rate of clinical events and the low level of SVD after 1 year support the long-term efficacy of transcatheter aortic valve replacement in both types of transcatheter prosthesis featuring in the registry.

Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Transcatheter aortic valve implantation for paradoxical low-flow low-gradient aortic stenosis patients.

OBJECTIVES: We compared the outcomes of transcatheter aortic valve implantation (TAVI) in three different aortic stenosis syndromes: paradoxical low-flow low-gradient aortic stenosis (PLFLG), high-gradient aortic stenosis (HGAS), and low ejection fraction low-gradient severe aortic stenosis (LEF-LG). BACKGROUND: Outcomes for PLFLG patients after TAVI procedure are not well known. METHODS: Between 2010 and 2013, patients with severe (indexed aortic valve area iAVA≤0.6 cm(2)/m(2)) symptomatic aortic stenosis were consecutively referred to our institution for TAVI because of multiple comorbidities and excessive surgical risk. About 262 patients were split into three groups as following, PLFLG: mean gradient MG≤40 mm Hg, stroke volume index SVI≤35 mL/m(2), ejection fraction EF≥55%, valvuloarterial impedance Zva>4.5 mm Hg/mL/m(2), maximal aortic jet velocity MaxV<4 m/s; LEF-LG: MG≤40 mm Hg, MaxV<4 m/s, EF≤50%, SVI≤35 mL/m(2); and HGAS: MaxV>4 m/s, MG>40 mm Hg, EF>55%. The primary endpoint of our study was to evaluate mid-term global and cardiovascular mortalities; secondary endpoints included recommended VARC-2 variables. RESULTS: PLFLG (n = 31) mid-term survival was similar to HGAS (n = 172) (mean follow-up = 13.2 months [4.6-26]). Conversely LEF-LG patients (n = 59) displayed significant higher rates of all-cause (P = 0.01) and cardiovascular mortalities (P = 0.05). Postprocedural outcomes (VARC-2 criteria) were similar in the PLFLG and HGAS groups except regarding major bleeding (P = 0.02), while the LEF-LG group had more congestive heart failure and a higher BNP before discharge (both P < 0.001) than the other groups. 30-days deaths were significantly more frequent in LEF-LG and PLFLG in comparison to HGAS (P = 0.03). CONCLUSION: As opposed to LEF-LG patients, mid-term prognosis after TAVI procedure in PLFLG patients is similar to HGAS patients despite higher perioperative mortality.

Registry of transcatheter aortic-valve implantation in high-risk patients.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2. METHODS: All TAVIs performed in France, as listed in the FRANCE 2 registry, were prospectively included in the study. The primary end point was death from any cause. RESULTS: A total of 3195 patients were enrolled between January 2010 and October 2011 at 34 centers. The mean (±SD) age was 82.7±7.2 years; 49% of the patients were women. All patients were highly symptomatic and were at high surgical risk for aortic-valve replacement. Edwards SAPIEN and Medtronic CoreValve devices were implanted in 66.9% and 33.1% of patients, respectively. Approaches were either transarterial (transfemoral, 74.6%; subclavian, 5.8%; and other, 1.8%) or transapical (17.8%). The procedural success rate was 96.9%. Rates of death at 30 days and 1 year were 9.7% and 24.0%, respectively. At 1 year, the incidence of stroke was 4.1%, and the incidence of periprosthetic aortic regurgitation was 64.5%. In a multivariate model, a higher logistic risk score on the European System for Cardiac Operative Risk Evaluation (EuroSCORE), New York Heart Association functional class III or IV symptoms, the use of a transapical TAVI approach, and a higher amount of periprosthetic regurgitation were significantly associated with reduced survival. CONCLUSIONS: This prospective registry study reflected real-life TAVI experience in high-risk elderly patients with aortic stenosis, in whom TAVI appeared to be a reasonable option. (Funded by Edwards Lifesciences and Medtronic.).

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial).

BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.

Poor agreement between light transmission aggregometry, Verify Now P2Y12 and vasodilatator-stimulated phosphoprotein for clopidogrel low-response assessment: a potential explanation of negative results of recent randomized trials.

Clopidogrel low response as assessed by several different biological tests correlates with poor prognosis after percutaneous coronary intervention (PCI). However, recent randomized clinical trials (RCT) testing the strategy of individual antiplatelet therapy tailoring based on one sole test have all shown negative results. Poor correlation between the different tests may explain the difficulties of patient selection and identification of "true poor responders" to clopidogrel. In this prospective study, clopidogrel response was assessed in 100 consecutive patients between 18 and 24 hours after a 600 mg clopidogrel loading dose using three different tests: light transmission aggregometry with 10 µmol ADP (LTA, results expressed as platelet aggregation percentage: PAP), Verify Now P2Y12 (VN, results expressed as P2Y12 reaction unit: PRU) and vasodilatator-stimulated phosphoprotein (VASP, results expressed as platelet reactivity index: PRI). Patients under chronic clopidogrel therapy were excluded. The mean PAP, PRU and PRI values were 38.6%, 176.1 PRU and 52.4%, respectively. When clopidogrel response was analyzed as continuous variable, there was a good correlation between the different tests: LTA/VN (R(2 )= 0.642, p < 0.001), LTA/VASP (R(2 )= 0.409, p < 0.001) and VN/VASP (R(2 )= 0.616, p < 0.001). However, when clopidogrel response was analyzed as pre-specified cut-off points to define patients as "poor or good responders" (according to the literature: 50% PAP for LTA, 235 PRU for VN and 50% PRI for VASP), only 47% of the patients were defined as "good" or "poor responders" by the three tests. Altogether, 33% of the patients were defined as "poor responders" by only one test, 20% by two tests and only 16% by the three tests. The correlation between the different tests is good when clopidogrel response is analyzed as continuous variable. Each individual is however rarely (less than 50%) defined as "poor or good responder" by all the three tests when pre-specified cut-off values are used. A sole test might not be sufficient to manage antiplatelet therapy in an individual patient and these results may explain the results of recent RCT showing the lack of benefit of systematic antiplatelet therapy monitoring strategy.

Implantation of a Sapien XT aortic bioprosthesis through the left carotid artery.

Transcatheter aortic valve implantation (TAVI) is still under active investigation. When the femoral route is impossible for anatomic reasons, the transapical, transaxillary and direct aortic approaches have demonstrated their effectiveness. We report the successful implantation of a Sapien XT bioprosthesis with the NovaFlex catheter through a left carotid approach.

Pulmonary valve replacement in a large and tortuous right ventricle outflow tract with a 32†mm Myval valve under local anaesthesia: challenges and technical considerations: a case report.

Background: Pulmonary valve replacement in patients with congenital heart diseases and heart failure is challenging. Case summary: Here, we describe a case of a patient who had surgical fallot repair with chronic heart failure. Investigations found severe biventricular dysfunction and enlargement due to chronic pulmonary regurgitation. The right ventricle outflow tract was tortuous and large with a diameter of 35 mm. Percutaneous pulmonary valve implantation (PPVI) was done after a challenging pre-stenting. A 32 mm Myval valve over-sized to 35 mm was used for PPVI, which yielded a good result. Discussion: A 32 mm Myval valve is effective at extending the possibilities of PPVI in a large and tortuous right ventricle outflow tract not accessible for the other valves.

Transcatheter aortic valve implantation with the Evolut platform for bicuspid aortic valve stenosis: the international, multicentre, prospective BIVOLUTX registry.

BACKGROUND: Prospective data about transcatheter aortic valve implantation (TAVI) in bicuspid aortic valve (BAV) patients are limited. AIMS: We aimed to evaluate the clinical impact of the Evolut PRO and R (34 mm) self-expanding prostheses in BAV patients and explore the impact of different computed tomography (CT) sizing algorithms in a prospective registry. METHODS: A total of 149 bicuspid patients were treated in 14 countries. The primary endpoint was the intended valve performance at 30 days. Secondary endpoints were 30-day and 1-year mortality, severe patient-prosthesis mismatch (PPM) and the ellipticity index at 30 days. All study endpoints were adjudicated according to Valve Academic Research Consortium 3 criteria. RESULTS: The mean Society of Thoracic Surgeons score was 2.6% (1.7-4.2). Type I L-R BAV was observed in 72.5% of the patients. Evolut valve sizes 29 and 34 mm were utilised in 49.0% and 36.9% of the cases, respectively. The 30-day cardiac death rate was 2.6%; the 1-year cardiac death rate was 11.0%. Valve performance at 30 days was observed in 142/149 (95.3%) patients. The mean aortic valve area post-TAVI was 2.1 (1.8-2.6) cm2, and the mean aortic gradient was 7.2 (5.4-9.5) mmHg. No patient had more than moderate aortic regurgitation at 30 days. PPM was observed in 13/143 (9.1%) surviving patients and was severe in 2 patients (1.6%). Valve function was maintained at 1 year. The mean ellipticity index remained 1.3 (interquartile range 1.2-1.4). Overall, 30-day and 1-year clinical and echocardiography outcomes were similar between the two sizing strategies. CONCLUSIONS: BIVOLUTX demonstrated a favourable bioprosthetic valve performance and good clinical outcomes after TAVI with the Evolut platform in patients with bicuspid aortic stenosis. No impact from the sizing methodology could be identified.

Balloon aortic valvuloplasty for severe aortic stenosis before urgent non-cardiac surgery.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has been proposed as a therapeutic option in patients suffering from severe aortic stenosis (SAS) who need urgent non-cardiac surgery (NCS). Whether this strategy is better than medical therapy in this very specific population is unknown. AIMS: We aimed to evaluate the clinical benefit of an invasive strategy (IS) with preoperative BAV in patients with SAS requiring urgent NCS. METHODS: From 2011 to 2019, a registry conducted in two centres included 133 patients with SAS undergoing urgent NCS, of whom 93 underwent preoperative BAV (IS) and 40 a conservative strategy (CS) without BAV. All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW) (10 clinical and anatomical variables). RESULTS: The primary outcome was MACE at one-month follow-up after NCS including mortality, heart failure, and other cardiovascular outcomes. In patients managed conservatively, occurrence of MACE was 20.0% (n=8) and death was 10.0% (n=4) at 1 month. In patients undergoing BAV, the occurrence of MACE was 20.4% (n=19) and death was 5.4% (n=5) at 1 month. Among patients undergoing conservative management, all events were observed after NCS while, in patients undergoing BAV, 12.9% (n=12) had events between BAV and NCS including 3 deaths, and 7.5% (n=7) had events after NCS including 2 deaths. In IPTW propensity analyses, the incidence of the primary outcome (20.4% vs 20.0%; OR 0.93, 95% CI: 0.38-2.29) and three-month survival (89.2% vs 90.0%; IPTW-adjusted HR 0.90, 95% CI: 0.31-2.60) were similar in both groups. CONCLUSIONS: Patients with SAS managed conservatively before urgent NCS are at high risk of events. A systematic invasive strategy using BAV does not provide a significant improvement in clinical outcome.

Feasibility and safety of transfemoral transcatheter aortic valve implantation performed with a percutaneous coronary intervention-like approach.

BACKGROUND: Transfemoral percutaneous transcatheter aortic valve implantation (TF-TAVI) is a safe, reproducible and established procedure, mainly performed under local anaesthesia, which is mostly administered and monitored by a dedicated anaesthesia team (regular approach). Our centre has developed a standardized pathway of care, and eligible patients are selected for a minimalist TF-TAVI, entirely managed by operators without the presence of the anaesthesia team in the operating room, like most interventional coronary procedures ("percutaneous coronary intervention-like" approach [PCI approach]). AIM: To compare the safety and efficacy of TF-TAVI performed with the PCI approach versus the regular approach. METHODS: The analysis population comprised all patients who underwent TF-TAVI with the PCI or regular approach in our institution from November 2016 to July 2019. The two co-primary endpoints were early safety composite and early efficacy composite at 30days as defined by the Valve Academic Research Consortium-2. The PCI (n=137) and Regular (n=221) approaches were compared using the propensity score based method of inverse probability of treatment weighting. RESULTS: No differences were observed after comparison of TAVI performed with the PCI or regular approach regarding the composite safety endpoint (7.3% vs. 11.3%; odds ratio 0.63, 95% confidence interval 0.37 to 1.07; P=0.086) or the composite efficacy endpoint (4.4% vs. 6.3%; odds ratio 0.78, 95% confidence interval 0.41 to 1.49; P=0.45). CONCLUSIONS: This study suggests that the efficacy and safety of TF-TAVI entirely managed by a PCI approach for selected patients are not different to those when TF-TAVI is performed with the attendance of a full anaesthesia care team. The PCI approach appears to be a safe and efficient clinical pathway, providing an appropriate and rational utilization of anaesthesiology resources, and could be used for the majority of TF-TAVI procedures.

TAVR Patients Requiring Anticoagulation: Direct Oral Anticoagulant or Vitamin K Antagonist?

OBJECTIVES: Using French transcatheter aortic valve replacement (TAVR) registries linked with the nationwide administrative databases, the study compared the rates of long-term mortality, bleeding, and ischemic events after TAVR in patients requiring oral anticoagulation with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). BACKGROUND: The choice of optimal drug for anticoagulation after TAVR remains debated. METHODS: Data from the France-TAVI and FRANCE-2 registries were linked to the French national health single-payer claims database, from 2010 to 2017. Propensity score matching was used to reduce treatment-selection bias. Two primary endpoints were death from any cause (efficacy) and major bleeding (safety). RESULTS: A total of 24,581 patients who underwent TAVR were included and 8,962 (36.4%) were treated with OAC. Among anticoagulated patients, 2,180 (24.3%) were on DOACs. After propensity matching, at 3 years, mortality (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.12-1.67; P < 0.005) and major bleeding including hemorrhagic stroke (HR: 1.64; 95% CI: 1.17-2.29; P < 0.005) were lower in patients on DOACs compared with those on VKAs. The rates of ischemic stroke (HR: 1.32; 95% CI: 0.81-2.15; P = 0.27) and acute coronary syndrome (HR: 1.17; 95% CI: 0.68-1.99; P = 0.57) did not differ among groups. CONCLUSIONS: In these large multicenter French TAVR registries with an exhaustive clinical follow-up, the long-term mortality and major bleeding were lower with DOACs than VKAs at discharge. The present study supports preferential use of DOACs rather than VKAs in patients requiring oral anticoagulation therapy after TAVR.

Clinical significance of electrocardiographic markers of myocardial damage prior to aortic valve replacement.

BACKGROUND: Pre-operative myocardial fibrosis and remodeling impact on outcomes after aortic valve replacement (AVR). We aimed at investigating the prognostic impact of preoperative electrocardiographic (ECG) markers of left ventricular (LV) myocardial damage, i.e. bundle branch block (BBB) and ECG strain pattern after (surgical or transcatheter) AVR for severe aortic stenosis (AS). METHODS: Between April 2008 and October 2017, we explored consecutive patients referred to our Heart Valve Clinic for first AVR for severe AS. Detailed pre-operative phenotyping and ECG analysis were performed. Patients were followed-up after AVR for major cardiac events (ME), i.e. cardiovascular death, cardiac hospitalization for acute heart failure and stroke. RESULTS: BBB and ECG strain were respectively observed in 13.5 and 21% of the 1122 patients included. These ECG markers identified a subgroup of older patients, with higher NYHA class and more advanced myocardial disease as detected by echocardiography, i.e. higher LV mass and lower LV ejection fraction, global longitudinal strain and integrated backscatter, than patients without ECG strain or BBB. ME occurred in 212 (18.6%) patients during a mean follow-up of 4.4 ± 1.5 years with higher incidence in case of ECG strain or BBB (HR 1.56, 95%CI 1.13-2.14, p = 0.006; HR 1.47, 95%CI 1.02-2.13, p = 0.04 respectively). The prognostic value of ECG strain remained significant after adjustment for age, diabetes and pre-operative LVEF. CONCLUSIONS: Pre-operative ECG markers of myocardial damage identify a subgroup of AS patients at high risk of post-AVR cardiovascular complications irrespective of other prognostic factors and should help the multiparametric staging of cardiac damage to guide AVR.

Impact of high loading and maintenance dose of clopidogrel within the first 15 days after percutaneous coronary intervention on patient outcome.

BACKGROUND: An increase in clopidogrel dose results in an improved inhibition of platelet aggregation. However, whether an increase in clopidogrel dose may improve patient outcome is still debated. The aim of this study was to analyze the impact on patient outcome of an increase in clopidogrel loading and maintenance doses within the first 15 days after percutaneous coronary intervention (PCI). METHODS: Between 2003 and 2007, we included 2,954 consecutive patients who underwent PCI and stent implantation. We compared 2 historical groups. In the "low-dose" group (2003-2005, n = 1,984), patients were pretreated with a 300-mg clopidogrel loading dose followed by 75 mg/d after PCI. In the "high-dose" group (2006-2007, n = 970), patients were pretreated with a 600-mg clopidogrel loading dose followed by 150 mg/d within the first 15 days and 75 mg/d thereafter. The composite primary end point (death, myocardial infarction, stent thrombosis) and bleeding were systematically indexed during the 2-month follow-up period. RESULTS: Clinical and most of angiographic characteristics were similar between the 2 groups. By multivariate analysis, high dose of clopidogrel was associated with a decrease in the composite primary end point (hazard ratio 0.694, 95% CI 0.485-0.993, P = .046). The other predictors were age, left ventricular ejection fraction, diabetes, renal failure, and acute coronary syndrome. Major bleeding was similar in the low- and high-dose groups (2.8% vs 3.4%, respectively, P = .379). After propensity score matching, the high-dose group was still associated with a significant clinical benefit. CONCLUSION: Our results show that a 600-mg loading dose followed by a 150-mg maintenance dose of clopidogrel within the first 15 days after PCI is independently associated with a decrease in the composite death-myocardial infarction-stent thrombosis at 2 months without increase in hemorrhagic complications.

High incidence of recurrent in stent thrombosis after successful treatment of a first in stent thrombosis.

OBJECTIVES: We attempted to investigate incidence and predictors of recurrent in stent thrombosis (IST) after successful treatment of a first IST. BACKGROUND: The occurrence of recurrent IST after successful treatment of a first IST may be a decisive factor for patient clinical outcome. However, incidence and predictors of recurrent IST are currently poorly described in the literature. METHODS: Between 2003 and 2005, 2,190 patients underwent a percutaneous coronary intervention in our center. During a median follow-up of 19.4 months, 49 patients (2.24%) presented a first definite IST. Patients presenting with a first IST were followed during an additional median period of 40 months. Their baseline characteristics were listed and cardiovascular events especially recurrent IST as defined by the Academic Research Consortium definition were systematically indexed. RESULTS: Altogether 39 (80%) patients were successfully treated with an effective reperfusion after percutaneous coronary intervention. Fourteen (36%) patients presented a recurrent IST and three presented multiple recurrent IST. The median occurrence time of recurrent IST was 5 days, range between 1 and 11 days. Multivariate analysis identified history of neoplasia (HR = 11.53, 95% CI 2.32-57.37, P = 0.003), residual diameter stenosis (HR = 1.15, 95% CI 1.02-1.29, P = 0.02), and residual dissection after treatment (HR = 8.78, 95% CI 1.85-41.62, P = 0.006), as independent predictors of recurrent IST. CONCLUSION: Recurrent IST is a frequent and early event after successful treatment of a first IST. Our results suggest that mechanical factors like residual dissection and residual diameter stenosis should be carefully tracked down. In addition, patients with multiple recurrent IST and the early time course of recurrent IST also suggest a potential role of inadequate antiplatelet therapy.

Successful transcatheter aortic valve implantation for severe aortic stenosis of a bicuspid valve with situs inversus totalis guided by advanced image processing: a case report.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) can be challenging in case of complex anatomy such as bicuspid aortic valve stenosis or situs inversus. This report illustrates a successful procedure in a patient with both conditions after careful pre-operative planning and per-operative guidance by means of a novel software. CASE PRESENTATION: We report the case of a 71-year-old man that presented a type 0 bicuspid aortic valve stenosis and situs inversus. We performed transfemoral TAVI using the Edwards Sapien 3 transcatheter heart valve (THV) and a novel software that provides insight for patient anatomy through computed tomography (CT) extracted three-dimensional reconstruction before the procedure aiming at improving THV positioning during the procedure through fusion of a CT-extracted virtual aortic annulus on the fluoroscopy screen and enhancing of calcifications that can be considered as anatomical landmarks. The Edwards Sapien 3 THV was accurately implanted in a supra-annular fashion. Post-operative echocardiography showed an excellent result without any para-prosthetic leak, and the patient reported symptom improvement. DISCUSSION: During TAVI the angiographic appearance of the cusps of a bicuspid aortic valve is irregular and asymmetric, which can lead to malpositioning, paravalvular regurgitation, and increased rates of pacemaker implantation after TAVI. Furthermore, usual anatomical landmarks can be even more disturbed by the situs inversus totalis. We believe that pre-operative three-dimensional reconstruction and per-operative fluoroscopy image processing, provided by software such as the one presented in this case report, can provide precious guidance for TAVI in patients with complex and unusual anatomy.

Advanced image processing with fusion and calcification enhancement in transcatheter aortic valve implantation: impact on radiation exposure.

OBJECTIVES: Radiation exposure is a concern for both patients and operators during transcatheter aortic valve implantation (TAVI). Efforts to reduce radiation dose are warranted. We aimed at investigating if per-operative advanced image processing can reduce patient and operator irradiation use during TAVI. METHODS: We performed a prospective single-centre observational study comparing patient and operator radiation exposure using standard fluoroscopy (control group) or a novel technology of live advanced fluoroscopic image processing (test group) among consecutive patients undergoing TAVI between August 2015 and April 2016. Patient irradiation (dose-area product, effective dose and air kerma), contrast media volume and clinical outcomes were assessed. RESULTS: Among 152 elderly [median age (interquartile range): 83 (78-87)] patients (n = 76 per group) undergoing TAVI, baseline clinical characteristics were similar between the control and test groups, except for a higher median EuroSCORE II (2.8% vs 2.3%, P = 0.02) and higher rate of TAVI for failing surgical bioprosthesis (11.8% vs 2.6%, P = 0.03) in the control group. The dose-area product was reduced in the test group: mean reduction of -27.5 Gy × cm2 [95% confidence intervals (CIs): 15.9-39.1, P < 0.001]. Furthermore, effective dose [mean reduction -6.5 (95% CI: 5.9-7.2) mSv, P < 0.001] and air kerma [mean reduction -167.5 (95% CI 163.4-177.3) mGy, P < 0.001] were lower in the test group. Fluoroscopy time, contrast volume and clinical outcomes were similar. CONCLUSIONS: Patient radiation exposure was significantly reduced using a novel live advanced fluoroscopy image processing with calcification enhancement and fusion of the virtual aortic annulus without compromising patient safety.

Urgent balloon aortic valvuloplasty in patients with cardiogenic shock related to severe aortic stenosis: time matters.

AIMS: The aim of the study was to assess the outcomes of balloon aortic valvuloplasty (BAV) as a rescue therapy in patients with cardiogenic shock (CS) related to severe aortic stenosis (AS). METHODS AND RESULTS: Forty-four consecutive patients, n=31 with hypotensive CS (HCS) and n=13 with non-hypotensive CS (NHCS) due to acutely decompensated severe AS, from two centres were treated with urgent BAV. The composite primary endpoint was mortality or recurrent CS at one-year follow-up. These patients (77.3±8.1 years old; 75% male) had a mean EuroSCORE II of 41.6±13.7%. One-month mortality was 47%. Twelve patients (27%) had either a staged TAVR (n=10) or surgical aortic valve replacement (SAVR) (n=2) with a median delay of 79 days after BAV: n=6 (19%) in the HCS subgroup and n=6 (46%) in the NHCS population (p=0.06). At one year, the rate of composite all-cause death or recurrent CS was 75% and significantly higher in the HCS subgroup (83% vs. 53%; p=0.03). Overall one-year mortality was 70% (n=31) with a trend for a better prognosis in NHCS patients (54% vs. 77%; p=0.09). Univariate predictive factors of the primary endpoint included preoperative dose of dobutamine >5 microg/kg/min (100% vs. 57%; p=0.001) and delayed BAV >48 hrs (90% vs. 59%; p=0.01). CONCLUSIONS: Despite the initial success of urgent BAV, morbidity and mortality of CS related to severe AS remain high and directly related to the time of the valvuloplasty. Performing BAV before or within 48 hours of starting inotropic agents appears to be key to survival.