Thibault Lhermusier

Mechanisms of stent thrombosis analysed by optical coherence tomography: insights from the national PESTO French registry

AIMS Angiography has limited value for identifying the causes of stent thrombosis (ST). We studied a large cohort of patients by optical coherence tomography (OCT) to explore ST characteristics and mechanisms. METHODS AND RESULTS A prospective multicentre registry was screened for patients with confirmed ST. Optical coherence tomography was performed after initial intervention to the culprit lesion (in 69% of cases in a deferred procedure). Stent thrombosis was classified as acute (AST), sub-acute (SAST), late (LST), and very late (VLST). Optical coherence tomography records were analysed in a central core lab. The analysis included 120 subjects aged 61.7 [51.4-70.7]; 89% male. Very late ST was the clinical presentation in 75%, LST in 6%, SAST in 15%, and AST in 4% of patients. Bare metal stents (BMS) were used in 39%, drug-eluting stents (DES) in 59% and bioresorbable vascular scaffolds in 2% of the cases. Optical coherence tomography identified an underlying morphological abnormality in 97% of cases, including struts malapposition (34%), neoatherosclerotic lesions (22%), major stent underexpansion (11%), coronary evagination (8%), isolated uncovered struts (8%), edge-related disease progression (8%), and neointimal hyperplasia (4%). Ruptured neoatherosclerotic lesions were more frequent with BMS than with DES (36 vs. 14%, P = 0.005), whereas coronary evaginations were more frequent with DES than with BMS (12 vs. 2%, P = 0.04). LST + VLST were mainly related to malapposition (31%) and neoatherosclerosis (28%), while prominent mechanisms for AST + SAST were malapposition (48%) and underexpansion (26%). CONCLUSION In patients with confirmed ST, OCT imaging identified an underlying morphological abnormality in 97% of cases.

Are P2Y12 reaction unit (PRU) and % inhibition index equivalent for the expression of P2Y12 inhibition by the VerifyNow® assay? Role of haematocrit and haemoglobin levels

The results of the whole blood VerifyNow P2Y12 assay can be expressed as platelet reaction units (PRU) or % inhibition index (%inh), but an optimal cut-off for the assessment of high on-treatment platelet reactivity (HPR) predictive of clinical events has been validated only for PRU. The aim of the study was to study the influence of haematological variables, such as platelet and leukocyte counts or haematocrit / haemoglobin, within the limits indicated by the manufacturer for assay validity, on the results of the test. We performed a comparison of PRU and %inh in a series 186 samples obtained from a clinical trial on patients under dual antiplatelet therapy. The results show that PRU significantly decreases with increasing haematocrit / haemoglobin, whereas %inh does not, due to a parallel change in PRU and iso-TRAP baseline value. PRU and % inhibition index are not equivalent for the definition of HPR, because of their different sensitivities to haematocrit / haemoglobin.

Prognostic Indicators for Recurrent Thrombotic Events in HIV-infected Patients with Acute Coronary Syndromes: Use of Registry Data From 12 sites in Europe, South Africa and the United States

AIMS Limited data are available on prognostic indicators for HIV patients presenting with ACS. METHODS AND RESULTS Data on consecutive patients with HIV infection receiving standard highly active antiretroviral therapy (HAART) presenting with ACS between January 2001 and September 2012 were collected. Cardiac death and myocardial infarction (MI) were the primary end-points. 10,050 patients with ACS were screened, and among them a total of 201 patients (179 [89%] males and a median age of 53 [47-62] years) were included, 48% of them admitted for ST-elevation myocardial infarction and 14% having left ventricular systolic dysfunction (LVSD) at discharge. CD4+ counts less than 200 cells/mm(3) were reported in 18 patients (9%), and 136 patients (67%) were treated with nucleoside-reverse transcriptase inhibitors (NRTI). After a median of 24 months (10-41), 30 patients (15%) died, 12 (6%) for cardiac reasons, 20 (10%) suffered a MI, 29 (15%) a subsequent revascularization, and 7 (3%) a stent thrombosis. Other than LVSD (hazard ratio=6.4 [95% confidence interval [CI]: 1.6-26: p=0.009]), the only other independent predictor of cardiac death was not being treated with NRTI (hazard ratio=9.9 [95% CI: 2.1-46: p=0.03); a CD4 cell count <200 cells/mm(3) was the only predictor of MI (hazard ratio=5.9 [95% CI: 1.4-25: p=0.016]). CONCLUSIONS HIV patients presenting with ACS are at significantly increased risk for cardiac death if not treated with NRTI, and at significantly increased risk of MI if their CD4 cell count is <200 cells/mm(3), suggesting that the stage of HIV disease (and lack of NRTI treatment) may contribute to cardiovascular instability.

More on: adenosine diphosphate‐inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel

art was that thrombin generation was normal in cirrhosis [3]. Whilst our paper was undergoing peer review, Tripodi et al. described enhanced thrombin generation using both thrombomodulin [7] and Protac [8]. The use of Protac, despite being unphysiological , is important because it is used routinely in coagulation laboratories in other assays. Hence, it is readily available and much cheaper than thrombomodulin, thus making this assay more feasible for day to day use. We welcome Tripodi et al. s use of Protac in their experiments, albeit using a different thrombin generation assay [8]. Finally, we agree with the conclusions of Tripodi that in contrast to the previously held belief, patients with advanced liver disease have normal and often enhanced thrombin generation, at least in patients with an INR of £2.0.

Transcatheter heart valve selection and permanent pacemaker implantation in patients with pre-existent right bundle branch block

Background Right bundle branch block is an established predictor for new conduction disturbances and need for a permanent pacemaker (PPM) after transcatheter aortic valve replacement. The aim of the study was to evaluate the absolute rates of transcatheter aortic valve replacement related PPM implantations in patients with pre‐existent right bundle branch block and categorize for different transcatheter heart valves. Methods and Results We pooled data on 306 transcatheter aortic valve replacement patients from 4 high‐volume centers in Europe and selected those with right bundle branch block at baseline without a previously implanted PPM. Logistic regression was used to evaluate whether PPM rate differed among transcatheter heart valves after adjustment for confounders. Mean age was 83±7 years and 63% were male. Median Society of Thoracic Surgeons score was 6.3 (interquartile range, 4.1–10.2). The following transcatheter valve designs were used: Medtronic CoreValve (n=130; Medtronic, Minneapolis, MN); Edwards Sapien XT (ES‐XT; n=124) and Edwards Sapien 3 (ES‐3; n=32; Edwards Lifesciences, Irvine, CA); and Boston Scientific Lotus (n=20; Boston Scientific Corporation, Marlborough, MA). Overall permanent pacemaker implantation rate post‐transcatheter aortic valve replacement was 41%, and per valve design: 75% with Lotus, 46% with CoreValve, 32% with ES‐XT, and 34% with ES‐3. The indication for PPM implantation was total atrioventricular block in 98% of the cases. Lotus was associated with a higher PPM rate than all other valves. PPM rate did not differ between ES‐XT and ES‐3. Ventricular paced rhythm at 30‐day and 1‐year follow‐up was present in 81% at 89%, respectively. Conclusions Right bundle branch block at baseline is associated with a high incidence of PPM implantation for all transcatheter heart valves. PPM rate was highest for Lotus and lowest for ES‐XT and ES‐3. Pacemaker dependency remained high during follow‐up.

Mechanical abnormalities associated with first- and second-generation drug-eluting stent thrombosis analyzed by optical coherence tomography in the national PESTO French registry

BACKGROUND AND OBJECTIVES DES thrombosis may be triggered by different mechanisms that are difficult to identify by angiography alone. This work aimed to investigate and compare the characteristics of stent thrombosis (ST) between 1st- and 2nd-generation drug-eluting stents (DES) among a large cohort of patients explored by optical coherence tomography (OCT). METHODS AND RESULTS The PESTO study was a prospective national registry involving 29 French catheterization facilities. Patients with acute coronary syndromes were prospectively screened for presence of definite ST and analyzed by OCT after culprit lesion deocclusion. The analysis involved 71 subjects including 34 patients with 1st-generation DES (DES1G) and 35 patients with 2nd-generation DES (DES2G). Most patients (80%) presented with very late stent thrombosis. The median time between initial PCI and ST was longer in DES1G than DES2G patients (3.8 [2.6-6.5] years vs. 1.1 [0.04-2.3] years, p<0.0001). OCT identified an underlying morphological abnormality in 96% of the cases. Significant malapposition was the main abnormality observed either in DES1G (26%) or DES2G patients (35%). Ruptured neoatherosclerotic lesions were more frequently observed with DES1G than with DES2G (26% vs. 3%, p=0.008). There was no significant difference in percentage of malapposed struts and uncovered struts between groups. CONCLUSIONS In this registry, DES thrombosis mainly occurred ≥1year after initial PCI. OCT identified a mechanical abnormality in the vast majority of the cases. Similar causes were observed between DES1G and DES2G, but neoatherosclerotic lesions were more common in DES1G.

In-hospital and long-term outcomes after percutaneous coronary intervention for chronic total occlusion in elderly patients: A consecutive, prospective, single-centre study

BACKGROUND Elderly patients are increasingly referred for complex percutaneous coronary interventions (PCI), including recanalization of chronic total occlusion (CTO). AIMS To assess the feasibility, safety and clinical benefits associated with CTO-PCI in elderly patients. METHODS Consecutive patients (n=356) who underwent CTO-PCI in our institution between January 2008 and December 2011 were prospectively included. The short-term outcomes of CTO-PCI were assessed by comparing the rates of successful recanalization and postoperative complications in patients aged ≥ 75 years and those < 75 years. The clinical effect of successful recanalization was evaluated in a 20-month follow-up analysis in patients ≥ 75 years. RESULTS Although patients ≥ 75 years (n = 93) had more complex coronary artery disease, the procedural success rate was similar to that in younger patients (78.2% vs. 74.3%, respectively; P = 0.41). Postoperative complications were more frequent in older patients (5.4% vs. 0.4%; P = 0.005). Major adverse cardiac event-free survival analysis at 20 months revealed that successful revascularization was indicative of a better prognosis in older patients (hazard ratio: 0.43, 95% confidence interval: 0.19-0.96; P = 0.039). CONCLUSION Elderly patients have more complex coronary disease and are at a higher risk of postoperative complications. Nevertheless, we observed a similar success rate for CTO-PCI in elderly patients as for younger patients. Successful CTO recanalization improved the event-free survival rate at 20 months. Thus, CTO-PCI constitutes an alternative strategy for treating selected elderly patients.

Gender disparity in 48-hour mortality is limited to emergency percutaneous coronary intervention for ST-elevation myocardial infarction

BACKGROUND Previous studies indicate that mortality from acute coronary syndromes is higher in women than in men, especially in case of interventional strategy. AIM To assess whether the in-hospital mortality rate differs between genders during the first 48h after emergency percutaneous coronary intervention for ST-elevation myocardial infarction (emergency PCI-STEMI) or after non-emergency PCI. METHODS All patients treated with PCI between January 2005 and June 2008 were included. The primary endpoint was frequency of death within 48h after the PCI procedure; secondary endpoints included frequency of recurrent myocardial infarction, new PCI or coronary artery bypass graft surgery, stroke, and major vascular or renal complications. Data were analysed via logistic regression with and without propensity-score matching. RESULTS More than 9000 patients underwent PCI. In the emergency PCI-STEMI group (n=1753), 48-hour mortality occurred in 2.2% of men and 4.9% of women (p=0.004). However, gender disparity occurred only in elderly patients; the rate was significantly (p=0.02) higher in women (8.1%) than in men (3.3%) aged > or =75 years. There was no evidence of gender disparity in the non-emergency PCI group (n=7336) or in secondary endpoints for either PCI group. Similar results were obtained in pair analyses of men and women with matching propensity scores. CONCLUSIONS Elderly women have a disproportionately high in-hospital mortality rate during the first 48h after emergency PCI for treatment of STEMI; however, there is no gender discrepancy in younger patients or patients of any age who receive non-emergency procedures.

ATP-binding cassette transporter 1 (ABCA1) deficiency decreases platelet reactivity and reduces thromboxane A2 production independently of hematopoietic ABCA1.

Essentials The role of ATP‐binding cassette transporter 1 (ABCA1) in platelet functions is poorly characterized. We studied the impact of ABCA1 deficiency on platelet responses in a mouse model and two Tangier patients. ABCA1‐deficient platelets exhibit reduced positive feedback loop mechanisms. This reduced reactivity is dependent on external environment and independent of hematopoietic ABCA1.

Relation between left ventricular outflow tract obstruction and left ventricular shape in patients with hypertrophic cardiomyopathy: A cardiac magnetic resonance imaging study

BACKGROUND Hypertrophic cardiomyopathies (HCM) are often associated with left ventricular (LV) outflow tract obstruction, which can explain symptoms and impact prognosis. AIMS To better understand the mechanisms that link obstruction and LV shape in HCM. METHODS Patients with HCM who underwent cardiac magnetic resonance (CMR) imaging were included retrospectively. Obstructive HCM was defined as LV outflow gradient more than 30 mm Hg at rest by transthoracic echocardiography. The LV shape and mitral angle were assessed by CMR. Results were compared with control subjects. RESULTS Mean LV-mitral angle was smaller in patients with obstructive HCM (n=29) than in patients with non-obstructive HCM (n=15) or control subjects (n=15) (80 ± 5° vs 87 ± 7° [P=0.0002] and 89 ± 2° [P<0.0001]). Mean mitral papillary muscles angle was greater in patients with non-obstructive HCM than in patients with obstructive HCM or control subjects (136 ± 17° vs 123 ± 16° [P=0.007] and 118 ± 10° [P=0.002]). Patients with non-obstructive HCM had a greater mean LV-aortic root angle than patients with obstructive HCM or control subjects (139 ± 6° vs 135 ± 7° [P=0.04] and 133 ± 7° [P=0.03]). CONCLUSION There is a relation between morphological and functional parameters in HCM within which the mitral valve is probably part of pathophysiogenesis.