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.

Relationship between beta-blocker and angiotensin-converting enzyme inhibitor dose and clinical outcome following acute myocardial infarction.

BACKGROUND: Benefit of ß-blockers (BB) and angiotensin-converting-enzyme inhibitors (ACEI) on mortality following acute myocardial infarction (MI) is well demonstrated. This study assessed the impact of BB and ACEI doses administered following ST-elevation MI on mortality and outcome up to 1 year. METHODS AND RESULTS: The French prospective observational cohort "RIMA" included 1,461 MI patients. Dosing of BB and ACEI given at 24 h and at time of discharge was assessed as follows: no treatment; <50% of target dose; or ≥50% of target dose. For in-hospital mortality, after MI, the use of BB in the first 24 h, but not ACEI, was associated with significantly lower event rate on multivariate analysis (OR, 5.78; 95% CI: 2.62-12.76, P<0.001). In contrast at 1 year, use of higher doses of ACEI, but not BB, was associated with significantly lower CV mortality, readmission for heart failure and the composite of CV mortality and readmission for heart failure (HR, 2.65; 95% CI: 1.32-5.31, P=0.006 for absence of ACEI at discharge). CONCLUSIONS: Prescription of BB in the first 24 h was independently associated with a lower in-hospital mortality following MI. There appeared to be a significant dose effect on outcome with regard to <50% vs. ≥50% of target dose, which requires confirmation in further large-scale clinical studies.

The RIPOST-MI study, assessing remote ischemic perconditioning alone or in combination with local ischemic postconditioning in ST-segment elevation myocardial infarction.

Local ischemic postconditioning (IPost) and remote ischemic perconditioning (RIPer) are promising cardioprotective therapies in ST-elevation myocardial infarction (STEMI). We aimed: (1) to investigate whether RIPer initiated at the catheterization laboratory would reduce infarct size, as measured using serum creatine kinase-MB isoenzyme (CK-MB) release as a surrogate marker; (2) to assess if the combination of RIPer and IPost would provide an additional reduction. Patients (n = 151) were randomly allocated to one of the following groups: (1) control group, percutaneous transluminal coronary angioplasty (PTCA) alone; (2) RIPer group, PTCA combined with RIPer, consisting of three cycles of 5-min inflation and 5-min deflation of an upper-arm blood-pressure cuff initiated before reperfusion; (3) RIPer+IPost group, PTCA combined with RIPer and IPost, consisting of four cycles of 1-min inflation and 1-min deflation of the angioplasty balloon. The CK-MB area under the curve (AUC) over 72 h was reduced in RIPer, and RIPer+IPost groups, by 31 and 29 %, respectively, compared to the Control group; however, CK-MB AUC differences between the three groups were not statistically significant (p = 0.06). Peak CK-MB, CK-MB AUC to area at risk (AAR) ratio, and peak CK-MB level to AAR ratio were all significantly reduced in the RIPer and RIPer+IPost groups, compared to the Control group. On the contrary, none of these parameters was significantly different between RIPer+IPost and RIPer groups. To conclude, starting RIPer therapy immediately prior to revascularization was shown to reduce infarct size in STEMI patients, yet combining this therapy with an IPost strategy did not lead to further decrease in infarct size.

Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial.

BACKGROUND: Preclinical studies and pilot clinical trials have shown that high-dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) would limit infarct size. METHODS: A total of 110 patients undergoing successful primary coronary intervention for a first STEMI was randomized to receive standard care either alone (n = 57) or combined with intravenous administration of 1,000 U/kg of epoetin ß immediately after reperfusion (n = 53). The primary end point was infarct size assessed by gadolinium-enhanced cardiac magnetic resonance after 3 months. Secondary end points included left ventricular (LV) volume and function at 5-day and 3-month follow-up, incidence of microvascular obstruction (MVO), and safety. RESULTS: Erythropoietin significantly decreased the incidence of MVO (43.4% vs 65.3% in the control group, P = .03) and reduced LV volume, mass, and function impairment at 5-day follow-up (all P < .05). After 3 months, median infarct size (interquartile range) was 17.5 g (7.6-26.1 g) in the EPO group and 16.0 g (9.4-28.2 g) in the control group (P = .64); LV mass, volume, and function were not significantly different between the 2 groups. The same number of major adverse cardiac events occurred in both groups. CONCLUSIONS: Single high-dose EPO administered immediately after successful reperfusion in patients with STEMI did not reduce infarct size at 3-month follow-up. However, this regimen decreased the incidence of MVO and was associated with transient favorable effects on LV volume and function.

Delayed thrombocytopenia following administration of abciximab: Pharmacovigilance survey and literature review.

BACKGROUND: Abciximab (ABX) is used for acute coronary syndrome and unstable angina. Thrombocytopenia is a frequent adverse effect described as occurring in the first 24hours. The aim of this study was to evaluate, in a context of pharmacovigilance survey, the occurrence of delayed thrombocytopenia following ABX infusion in pharmacovigilance database reports and in the literature. METHODS: Individual case safety reports (ICSRs) of delayed thrombocytopenia-between 3 and 30 days - with ABX presented as a single suspect were selected in VigiBase®, the WHO global database of ICSRs. The French cases were then extracted from the French national pharmacovigilance database. In addition, a literature review of published cases was performed using PubMed. RESULTS: Among the 84 ICSRs selected from VigiBase®, 43 were also reported in the FPVD. Mean age was 60.1±12.3 years with a majority of male patients (77.4%). The average time to onset (TTO) was 8.9±5.2 days. Thrombocytopenia regressed in 5.1±2.7 days. Haemorrhagic complications were reported in 15% of ICSRs. In the French cases, the median nadir of platelet count was 28×109/L (range 1-110) with a majority of grade 4 thrombocytopenia (39.5%). The literature review identified 42 cases and provided additional information on administered therapies, which include platelet units, corticosteroids, and IV immunoglobulins. GPIIb/IIIa-ABX complex antibodies were described in 26 published cases. CONCLUSION: Delayed thrombocytopenia, probably due to immune reaction, is a possible life-threatening adverse effect of ABX with a mean TTO of 9 days, supporting the recommendation of a platelet count monitoring during at least two weeks. This recommendation was added to the abcximab SmPC in 2019.

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.

Coronary blood flow assessment after successful angioplasty for acute myocardial infarction predicts the risk of long-term cardiac events.

BACKGROUND: Analysis of coronary flow velocity (CFV) in the recanalized infarct-related coronary artery (IRA) with a Doppler guidewire is useful for predicting recovery of regional left ventricular function, in-hospital complications, and survival. We postulated that the CFV pattern after IRA reperfusion for acute myocardial infarction (AMI) would predict long-term adverse cardiac events. METHODS AND RESULTS: Sixty-eight consecutive patients with a first AMI underwent CFV measurement with a Doppler guidewire after successful reopening of the IRA by coronary angioplasty. At the end of follow-up, 3.8+/-1.7 years after AMI, 44 of the 65 surviving patients (67.7%) were free of long-term cardiac events. Univariate analysis showed that the following factors were predictive of an end point combining cardiac death, recurrent MI, and congestive heart failure: hypertension, age > or =65 years, time from onset of chest pain to PTCA > or =6 hours, peak creatine kinase >4000 IU/L, ejection fraction < or =50%, proximal left anterior descending artery occlusion, resting average peak velocity < or =10 cm/s, average systolic peak velocity < or =5 cm/s, a rapid diastolic deceleration time (< or =600 ms), and early retrograde systolic flow. In the final multivariate model, only age > or =65 years (OR, 3.6; 95% CI, 1.1 to 11.8; P=0.03), time to PTCA > or =6 hours (OR, 2.9; 95% CI, 1.0 to 8.3; P=0.04), and a rapid diastolic deceleration time (OR, 5.4; 95% CI, 1.5 to 19.3; P=0.01) were independent predictors. CONCLUSIONS: The CFV pattern appears to be an accurate predictor of long-term cardiac events in patients having undergone successful reopening of the IRA after AMI, identifying a subset of at-risk patients.

Comparison between isoproterenol and nitroglycerin sensitized head-upright tilt in patients with unexplained syncope and negative or positive passive head-up tilt response.

It is unknown if the head-upright tilt test in patients who receive isoproterenol and nitroglycerin can identify different populations with vasovagal syncope. The aim of this study was to compare the positive or negative responses to passive tilt between isoproterenol- and nitroglycerin-sensitized upright tilt. Ninety-six patients referred for unexplained recurrent syncope underwent passive tilt (45 minutes at 70 degrees angle), which was then systematically followed, within the same session and in a random order, by a 20-minute tilt at a 70 degrees angle after administration of nitroglycerin (NTG-tilt) and 10-minute tilt at a 70 degrees angle with a continuous infusion of isoproterenol (ISO-tilt). NTG-tilt led to significantly more positive responses than passive tilt or ISO-tilt (55% vs 34% vs 42%, respectively). In the subgroup of patients with a positive response during passive tilt, the percentage of positive responses with NTG-tilt was significantly higher than with ISO-tilt (94% vs 67%). The agreement between NTG-tilt and ISO-tilt was very weak (Kappa coefficient 0.06). In the subgroup of patients with a negative response during passive tilt, the percentage of positive responses between NTG-tilt and ISO-tilt was similar (35% vs 29%). The agreement between NTG-tilt and ISO-tilt was good (Kappa coefficient 0.34). NTG-tilt led to a higher number of positive responses than ISO-tilt, especially when passive tilt outcome was positive. These 2 pharmacologic agents may identify 2 different subpopulations of patients because of their specific pharmacologic actions.

Assessment of biventricular remodeling by magnetic resonance imaging after successful primary stenting for acute myocardial infarction.

Inferior acute myocardial infarction (AMI) is associated with a better outcome compared with anterior AMI, even in the presence of comparable infarct size. Whether left ventricular remodeling, a major predictor of poor outcome, and right ventricular (RV) remodeling depend on the site of an AMI remains unknown. Biventricular volumes were assessed by magnetic resonance imaging 7 +/- 2 days and 3.4 +/- 0.3 months after successful primary stenting in 51 consecutive patients with inferior or anterior AMI. This study documents RV involvement and biventricular reverse remodeling in patients with inferior AMI in the absence of RV infarction, as opposed to those with anterior AMI who show progressive biventricular remodeling.

CMR assessment after a transapical-transcatheter aortic valve implantation.

AIMS: To describe the time course of myocardial scarring after transapical-transcatheter aortic valve implantation (TA-TAVI) with the Edwards SAPIEN XT™ and the Edwards SAPIEN™ prosthesis in a 3-month follow-up study using cardiac magnetic resonance imaging (CMR). METHODS: In 20 TA-TAVI patients, CMR was performed at discharge and 3 months (3M). Cine-MRI was used for left ventricular (LV) functional assessment, and late gadolinium enhancement (LGE) imaging was employed for detecting the presence of myocardial scarring. Special attention was given to any artifacts caused by the prosthesis, which were consequently defined using a three-grade artifact scale. RESULTS: We systematically reported the presence of small LGE hyperintensity relating to the apical segment, with no variation found between discharge and 3M (2.8±1.6g vs. 2.35±1.1g). LV ejection fraction, end-diastolic, and end-systolic volumes did not significantly vary. A small area of apical akinesia was observed, with no improvement at follow-up. Whereas the Edwards SAPIEN XT™ prosthesis and the Edwards SAPIEN™ prosthesis are both constituted by metallic stenting structure, the Edwards SAPIEN™ was responsible for a larger signal void, thus potentially limiting the diagnostic performance of CMR. CONCLUSIONS: CMR may be performed safely in the context of TA-TAVI. The presence of a very small apical infarction correlating with focal akinesia was observed. As expected, the Edwards SAPIEN XT™ prosthesis was shown to be particularly suitable for CMR assessment.

Three-dimensional MRI assessment of regional wall stress after acute myocardial infarction predicts postdischarge cardiac events.

PURPOSE: To determine the prognostic significance of systolic wall stress (SWS) after reperfused acute myocardial infarction (AMI) using MRI. MATERIALS AND METHODS: A total of 105 patients underwent MRI 7.8 +/- 4.2 days after AMI reperfusion. SWS was calculated by using a three-dimensional (3D) MRI approach to left ventricular (LV) wall thickness and to the radius of curvature. Between hospital discharge and the end of follow-up, an average of 4.1 +/- 1.7 years after AMI, 19 patients experienced a major cardiac event, including cardiac death, nonfatal reinfarction or heart failure (18.3%). RESULTS: The results were mainly driven by heart failure outcome. In univariate analysis the following factors were predictive of postdischarge major adverse cardiac events: 1) at the time of AMI: higher heart rate, previous calcium antagonist treatment, in-hospital congestive heart failure, proximal left anterior descending artery (LAD) occlusion, a lower ejection fraction, higher maximal ST segment elevation before reperfusion, and ST segment reduction lower than 50% after reperfusion; 2) MRI parameters: higher LV end-systolic volume, lower ejection fraction, higher global SWS, higher SWS in the infarcted area (SWS MI) and higher SWS in the remote myocardium (SWS remote). In the final multivariate model, only SWS MI (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.01-2.60; P = 0.046) and SWS remote (OR: 2.17; 95% CI: 1.02-4.65; P = 0.046) were independent predictors. CONCLUSION: Regional SWS assessed by means of MRI a few days after AMI appears to be strong predictor of postdischarge cardiac events, identifying a subset of at risk patients who could qualify for more aggressive management.

Routine breath-hold gradient echo MRI-derived right ventricular mass, volumes and function: accuracy, reproducibility and coherence study.

Right ventricular (RV) dysfunction is a predictor of poor outcome in patients with heart disease. Conventional imaging modalities fail to assess RV volumes accurately. We sought to assess the accuracy and reproducibility of routine breath-hold gradient echo magnetic resonance imaging (MRI)-derived RV mass, volumes and function. We assessed: (1) The accuracy of in vivo MRI-derived RV mass in comparison to the RV weight in 9 minipigs. (2) Intra- and inter-observer reproducibility of RV mass, end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fraction (EF) in 15 normal volunteers and 10 patients with heart disease. (3) Inter-study reproducibility of the former parameters in 25 coronary artery disease patients. (4) The correlation between right and left ventricular stroke volumes in the total population. Strong statistically significant correlations were found between: (1) MRI-derived RV mass and RV weight (r = 0.98, bias = 2.5 g), (2) Intra-observer measurements of RV mass (r = 0.96, bias = 0.5 g), EDV (r = 0.99, bias = -1.5 ml), ESV (r = 0.98, bias = 0.1 ml) and EF (r = 0.92, bias = -1.4%), (3) Inter-observer measurements of RV mass (r = 0.95, bias = 1.1 g), EDV (r = 0.98, bias = -1.1 ml), ESV (r = 0.98, bias = 1.2 ml) and EF (r = 0.87, bias = -1.9%), (4) Inter-study measurements of RV mass (r = 0.91, bias = -0.1 g), EDV (r = 0.96, bias = 3.8 ml), ESV (r = 0.98, bias = 0.3 ml) and EF (r = 0.90, bias = 0.9%), (5) MRI-derived right and left ventricular stroke volumes (r = 0.87). The assessment of the RV mass, volumes and function by routine breath-hold gradient echo MRI is accurate and highly reproducible. The correlation between left and RV MRI-derived stroke volumes indicates excellent coherence of simultaneous bi-ventricular volume measurements.

3-D MRI assessment of regional left ventricular systolic wall stress in patients with reperfused MI.

The goal of this study was to assess the regional variations of end-systolic wall stress in patients with reperfused Q wave acute myocardial infarction (AMI), with the use of a three-dimensional (3-D) approach. Fifteen normal volunteers and fifty patients with reperfused AMI underwent cardiac MRI that used a short-axis fast-gradient-echo sequence. The end-systolic wall stress was calculated with the use of the Grossman formula with the radius and the wall thickness defined with a 3-D approach using the tridimensional curvature. The mean wall stress was significantly increased at each level of the short-axis plane only in patients with anterior AMI. When calculated at a regional level in patients with anterior AMI, wall stress significantly increased in anterior sector as well as normal sector. In patients with inferior AMI, wall stress significantly increased only in inferior and lateral sectors. In conclusion, the quantification of regional wall stress by cardiac MRI is better with the 3D approach than other methods for precise evaluation in patients with AMI. Despite early reperfusion, the wall stress remained high in patients with anterior AMI.