Is the duration of dual antiplatelet therapy (DAPT) excessive in post-angioplasty in chronic coronary syndrome? Data from the France-PCI registry (2014-2019).

Background: while the duration of dual antiplatelet therapy (DAPT) following coronary angioplasty for chronic coronary syndrome (CCS) recommended by the European Society of Cardiology has decreased over the last decade, little is known about the adherence to those guidelines in clinical practice in France. Aim: To analyze the real duration of DAPT post coronary angioplasty in CCS, as well as the factors affecting this duration. Methods: Between 2014 and 2019, 8.836 percutaneous coronary interventions for CCS from the France-PCI registry were evaluated, with 1 year follow up, after exclusion of patients receiving oral anticoagulants, procedures performed within one year of an acute coronary syndrome, and repeat angioplasty. Results: Post-percutaneous coronary intervention (PCI) DAPT duration was > 12 months for 53.1% of patients treated for CCS; 30.5% had a DAPT between 7 and 12 months, and 16.4% a DAPT ≤ 6 months. Patients with L-DAPT (>12 months) were at higher ischemic risk [25.0% of DAPT score ≥2 vs. 18.8% DAPT score ≥2 in S&I-DAPT group (≤12 months)]. The most commonly used P2Y12 inhibitor was clopidogrel (82.2%). The prescription of ticagrelor increased over the period. Conclusions: post-PCI DAPT duration in CCS was higher than international recommendations in the France PCI registry between 2014 and 2019. More than half of the angioplasty performed for CCS are followed by a DAPT > 12 months. Ischemic risk assessment influences the duration of DAPT. This risk is probably overestimated nowadays, leading to a prolongation of DAPT beyond the recommended durations, thus increasing the bleeding risk.

[stent thrombosis : A won battle ? (data from the France PCI registry)]. / Thrombose de stent : une bataille gagnée ? (Données du registre France PCI).

GOAL: The aim of the study is to assess the incidence, risk factors and prognosis of definite stent thrombosis (ST) at 1 year in the France PCI multicenter prospective registry. PATIENTS AND METHODS: Only patients who underwent coronary angioplasty with at least one stent implantation between 1st January 2014 and 31 December 2019 were included. The population was separated into 2 groups: the "ST" group with stent thrombosis and the "control" group without stent thrombosis. RESULTS: 35,435 patients were included. 256 patients (0.72%) presented a ST at 1 year. The rate of ST decreased significantly in acute coronary syndrome (1.5% in 2014 vs. 0.73% in 2019; p = 0.05) but not in chronic coronary syndrome (0.46% in 2014 vs 0.40%; p = 0.98). The risk factors are young age (65.8 years vs 68.2; p = 0.002), clinical context (35.27% vs 16.68%; p = 0.0001), diabetes (35.2 % vs 26.4%; p = 0.002), renal failure (11.7% vs 8%; p = 0.009) and history of coronary angioplasty (28.63% vs 21.86%; p = 0.009) and peripheral arterial disease (14.5% vs 10.1%; p = 0.021), LV dysfunction (37% vs 27.5%; p = 0.003), mean length (39.6 mm vs 31, 7mm; p <0.0001) and the mean number of stents per procedure (1.9 vs 1.6; p <0.0001), a TIMI flow ≤1 pre procedure (21.5% vs 12.4%; p <0.0001) and an intrastent restenosis (11% vs 6%; p <0.0001). The 1-year mortality of the ST group was significantly higher than that of the control group (19.14% vs 5.82%; p <0.0001). CONCLUSION: Since 2014, the incidence of ST at 1 year has been decreasing but remains stuck at a floor level of 0.54% in 2019. The battle for ST seems to have been partly won and its risk factors well identified, but its mortality is still high.

Aspirin and clopidogrel resistance: should we worry about?

Antiplatelet therapy is a cornerstone of coronary artery disease treatment and prevention. Aspirin and clopidogrel has emerged as the gold standard combination for patients receiving coronary stent and/or suffering from acute coronary syndrome. Despite their efficacy, recurrent events still occur and resistance to antiplatelet drugs might be one of the responsible factors. Aspirin and clopidogrel resistance are emerging entities primarily defined in biological studies by inability of the drug to achieve expected antiplatelet effect based on platelet function tests. Mechanisms of this variability of response remain complex and partially unknown. Moreover, clinical papers linked this biological entity with worse clinical outcomes, and therefore, tailored therapy based on platelet tests has been proposed. Mean while, new antiplatelet drugs will soon change the field while achieving homogeneous degree of platelet inhibition. The present review aims to summarize biological and clinical data about resistance to antiplatelet therapy, and try to estimate how much this might change our prescription in daily clinical practice.

6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding.

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance.

[Which patient for TAVI in 2019?] / À quel patient proposer un TAVI en 2019 ?

The therapeutic management of aortic stenosis has been drastically changed by the advent of percutaneous valve replacement (TAVI). Since the first implantation, the indications have progressively been extended from the inoperable patient to the patient at low surgical risk. The main objective of this review is to describe the currently recommended main indications of TAVI depending on an individualized assessment of each patient's risk, technical characteristics and anatomical valvular criteria.

Long-term effectiveness and side effects of mandibular advancement devices on dental and skeletal parameters.

INTRODUCTION: Continuous positive airways pressure, generally used to treat obstructive sleep apnea-hypopnea syndrome (OSAHS), is not tolerated well by many patients. An alternative is to treat OSAHS with mandibular advancement devices (MAD). This research assesses the long term (> 2 years) effectiveness and the side effects on dental and skeletal parameters of these devices. MATERIAL AND METHODS: We selected 24 patients with moderate to severe OSAHS. All were treated with MADs for at least 2 years. We gathered cephalometric teleradiographs in centric relation and sleep recordings before and after the patients were treated. We evaluated the patients' apnea-hypopnea indexes (AHI) as well as their Epworth sleepiness scale (ESS) scores. We measured the inclination of the central incisors and the positions of the upper and lower jaws. RESULTS: Mandibular advancement devices were used for more than 2 years (3.9 ± 1.9 years). We observed a statistically significant decrease of the patients' AHI and their ESS scores. We also observed a modification of the inclination of the lower central incisors (+0.521; P = 0.047) and of the position of the maxilla (-0.287; P = 0.039). DISCUSSION: We demonstrated the clinical effectiveness of mandibular advancement devices for treating OSAHS, with a very low rate of side effects on dental and skeletal positions.

[C-reactive protein (CRP) after revascularized STEMI: is CRP a prognostic factor?]. / Intérêt de la C-reactive protein (CRP) dans l'évaluation pronostique de l'infarctus du myocarde revascularisé

PURPOSE: During myocardial infarction (MI), numerous biomarkers increase, such as troponin (necrosis), BNP, and high sensibility C-reactive protein (hsCRP) (inflammation). The objectives of the study were to study kinetics of hsCRP after a revascularized MI, and correlations between hsCRP and clinical outcomes or biological markers, and prognostic value of CRP. PATIENTS AND METHODS: Fifty-two patients were admitted for STEMI (ST segment Elevation MI). Primary coronarography interventions (PCI) were performed for urgent reperfusion. Patients were included only in case of success (TIMI 3). Clinical examination was completed by a biological follow-up of BNP, troponin-I (before and after PCI, days 1, 2, 3, 6) and hsCRP (days 0, 1, 2, 3, 6). Clinical outcomes follow-up was performed during hospitalization, on the first month, and the sixth month. RESULTS: hsCRP increases during the first days (peak on day 3: 46.1mg/L), and decreases between the third and the seventh day. Clinical outcomes were correlated with CRP: door-to-balloon time, age, creatinin level on admission. During follow-up, there were clinical events in 13/49 (26%) of the patients. Among them, hsCRP on day 2 was higher (p < 0.0001), compared to other patients. Compared to other biological markers, hsCRP was correlated with BNP on days 2 and 3 (p = 0.008). CONCLUSION: hsCRP increases after revascularized STEMI, in accordance to the infarct size, in the first days. hsCRP is correlated with cardiovascular pronostic biomarkers. hsCRP could play an active role, and could be used as a pronostic biomarker after revascularized STEMI, which are usually considered as a low-risk population.

[Daily management of acute pericarditis: clinical and paraclinical outcomes, etiological diagnosis]. / Prise en charge au quotidien des péricardites aiguës: présentation clinique, paraclinique, diagnostic étiologique.

INTRODUCTION: Acute pericarditis is a frequent hospitalization cause. A prospective, bicentric study aimed at different goals: population description, aetiologies screening, and evaluation of the interest of a coordinated and combined management between cardiologists and internists. PATIENTS AND METHODS: Between May 2005 and September 2007, all patients admitted for acute pericarditis were prospectively enrolled. Physical examination, ECG, echocardiography, biological screening were performed. Patients were asked to consult both cardiologist and internist, one month later. RESULTS: Hundred and three patients were enrolled (mean age 43 years). Clinical outcome was classical in 60% of cases. ECG was typical in 59%. Troponin elevation was noted in 30% of patients. CRP was normal at diagnosis in 27% of patients, and increased significantly at first day (P=0.002). Possible cause was identified in 44 patients. In 26 patients (24.3%), precise diagnosis was performed: six cancers, one hemopathy, three connectivities, one EBV and one parvovirus B19 seroconversions, two untreated HIV patients, four inflammatory diseases, three endocrinology troubles, one oesophagitis, one dental sepsis, one amyloidosis, one acute pancreatitis, one declined dialysis indication. Eighteen de novo diagnoses (16.5%) were performed, out of them at least 12 benefited from specific management. CONCLUSION: Population of patients admitted for acute pericarditis are very heterogeneous. Our co-management between internists and cardiologists aims to diagnose earlier and easier curable diseases. Long-term follow-up remains of great interest, in order to diagnose later other disorders, which remained hidden, and to follow evolution of the population.

Reliability of hemostasis biomarkers is affected by time-dependent intra-patient variability.

Essentials Nucleosomes and free DNA are two newly described biomarkers in venous thromboembolism (VTE). Reliability of nucleosomes, plasma free DNA and conventional hemostasis markers were studied. Hemostasis biological parameters vary over a short time-frame in VTE patients. Hemostasis biological parameters also vary over a short time-frame in healthy controls. SUMMARY: Background Previous studies have associated neutrophil-derived circulating nucleosomes and plasma free DNA with venous thromboembolism (VTE). However, there are few data concerning these two biomarkers and no studies have compared the reliability of nucleosomes and plasma free DNA against that of conventional hemostasis markers. Objectives We performed a 3-year prospective study of nucleosomes and plasma free DNA levels in comparison with conventional hemostatic biomarkers and blood cells. Patients/Methods Fifteen healthy controls and 22 randomly selected patients with a history of VTE were followed monthly for 6 months. The reliability of these markers was evaluated by the intraclass correlation coefficient (ICCs). Results and Conclusions In healthy controls and patients, we found a low reliability for nucleosomes and plasma free DNA, with ICCs at 0.538 (95% confidence interval [CI], 0.334-0.764) and 0.091 (95% CI, -0.026-0.328), respectively, in the healthy controls, and at 0.213 (95% CI, 0.042-0.463) and 0.161 (CI 95%, 0.008-0.398) in the patient group. For the conventional hemostasis biomarkers and for blood cells, reliability ranged from poor to good in the healthy volunteers and from poor to acceptable in the patient group. Our study shows for the first time that hemostasis biological parameters spontaneously vary over a short time-frame in VTE patients and, more surprisingly, in normal individuals. The clinical value of such intra-individual variations is currently unknown. This variability might mean reinterpreting diagnostic or prognostic models based on static evaluation of individuals. Studying the intrinsic value of individual patterns of markers' variability is warranted.

Position paper of French Interventional Group (GACI) for TAVI in France in 2018.

Aortic stenosis is a frequent disease in the elderly. Its prevalence is 0.4% with a sharp increase after the age of 65, and its outcome is very poor when the patient becomes symptomatic. The interventional procedure known as TAVI (trans-catheter aortic valve implantation), which was developed in France and carried out for the first time in Rouen by Prof. Alain Cribier and his team in 2002, has proven to be a valid alternative to surgical aortic valve replacement. At first, this technique was shown to be efficient in patients with contra-indications to surgical treatment or deemed to be at high surgical risk. Given the very promising outcomes achieved as a result of close heart team collaboration, appropriate patient selection, simplified procedures and reduced complication rates, transfemoral (TF) TAVI is now preferred in symptomatic intermediate risk patients>75 years old according to the latest ESC guidelines. In 2017, in France, TAVI is currently performed in 50 centers with on-site cardiac surgery. The 2016 TAVI outcomes recorded in the French national TAVI registry (France TAVI) are very encouraging and show that for 7133 patients treated (age 83.4±7 years, logistic Euroscore 14%), 87% of whom via the TF approach, cross-over to surgery was very low (0.5%) with a 3.0% in-hospital mortality rate. The substantial increase in TAVI indications and the improvement of its outcomes may in the near future call for a reconsideration of the number of high volume centers authorized to carry out this technique.

[Intra-cardiac lymphoma with right heart failure: a therapeutic emergency in two patients]. / Lymphome intracardiaque avec insuffisance cardiaque droite: à propos de deux cas.

We report the cases of two patients admitted to the Emergency Department with a clinical picture of right heart failure. An emergency echocardiograph suggested an intra-cardiac tumor which turned out to be a primary intra-cardiac lymphoma in one case, and a diffuse lymphoma principally localised in the heart in the other. Echocardiographic, CT and MRI investigations clarified the sites, as well as anatomical relations and extensions. Histology confirmed the diagnosis, and allowed classification of the lymphoma in order to decide on treatment. A PET scan performed in one patient illustrated the response to treatment. The respective significance of each of these investigations is discussed, in addition to the management. While transthoracic echocardiography remains the key element in the acute management, MRI and PET scans are being used more and more often for determining the character of these lesions, as well as for assisting with therapeutic decisions and for follow-up.

Assessment of Patient's Peak Skin Dose Using Gafchromic Films During Interventional Cardiology Procedures: Routine Experience Feedback.

To assess the interest of Gafchromic films in detection of patient's peak skin dose (PSD) in interventional cardiology. A prospective study of 112 patients was conducted (July-December 2015). Three diagnostic and therapeutic procedures were evaluated: coronary angiography (CA), coronary angiography and coronary angioplasty for one or two vessels disease (CA-PTCA) and coronary angioplasty of complex chronic total occlusion (CTO). Dosimetric indicators (DIs) were collected and PSD were measured with Gafchromic films. Dose distribution was evaluated within 10 'Thorax Body-zone' defined by the system. Correlations between PSD and DI or dose distribution were computed. Delivered dose increased in complex procedures. The PSD were 0.121 ± 0.063 Gy for CA, 0.256 ± 0.142 Gy for CA-PTCA and 1.116 ± 0.721 Gy for CTO. High correlations were observed for PSD and DI as well for dose distribution within the 'Thorax Body-zone'. Film dosimetry is suggested for CTO procedures since the threshold of 2 Gy for skin injuries is likely to be exceeded.

Assessment of peak skin dose in interventional cardiology: A comparison between Gafchromic film and dosimetric software em.dose.

OBJECTIVE: To compare the use of a dose mapping software to Gafchromic film measurement for a simplified peak skin dose (PSD) estimation in interventional cardiology procedure. METHODS: The study was conducted on a total of 40 cardiac procedures (20 complex coronary angioplasty of chronic total occlusion (CTO) and 20 coronary angiography and coronary angioplasty (CA-PTCA)) conducted between January 2014 to December 2015. PSD measurement (PSDFilm) was obtained by placing XR-RV3 Gafchromic under the patient's back for each procedure. PSD (PSDem.dose) was computed with the software em.dose©. The calculation was performed on the dose metrics collected from the private dose report of each procedure. Two calculation methods (method A: fluoroscopic kerma equally spread on cine acquisition and B: fluoroscopic kerma is added to one air Kerma cine acquisition that contributes to the PSD) were used to calculate the fluoroscopic dose contribution as fluoroscopic data were not recorded in our interventional room. Statistical analyses were carried out to compare PSDFilm and PSDem.dose. RESULTS: The PSDFilm median (1st quartile; 3rd quartile) was 0.251(0.190;0.336)Gy for CA-PTCA and 1.453(0.767;2.011)Gy for CTO. For method-A, the PSDem.dose was 0.248(0.182;0.369)Gy for CA-PTCA and 1.601(0.892;2.178)Gy for CTO, and 0.267(0.223;0.446)Gy and 1.75 (0.912;2.584)Gy for method-B, respectively. For the two methods, the correlation between PSDFilm and PSDem.dose was strong. For all cardiology procedures investigated, the mean deviation between PSDFilm and PSDem.dose was 3.4±21.1% for method-A and 17.3%±23.9% for method-B. CONCLUSION: The dose mapping software is convenient to calculate peak skin dose in interventional cardiology.

[Sodium ion inhibits angiogenesis of cultured rat aortic and coronary rings]. / L'ion sodium inhibe les capacités angiogéniques in vitro d'explants d'aorte et d'artère coronaire de rat.

High sodium intake is associated with the development of cardiac hypertrophy in man and rats independently of the rise of blood pressure. In addition, the reduced capillary density observed in striated muscle of rats fed a high salt diet suggests that angiogenesis is altered. The aim of the present experiments was to investigate the angiogenic capacities of vascular rings isolated from the aorta and the coronary artery of rats. Vascular rings (external diameter of 1 669 +/- 9 and 323 +/- 26 microm for aorta and coronary artery. respectively) are cultured in a three-dimensional collagen type I lattice and a standard medium (DMEM+HAMF12) containing 152 mM of sodium. Sodium ion associated with chloride or citrate is added to the standard medium to achieve a final concentration of sodium of 160 and 176 mM. The role of sodium-proton exchanger is evaluated through the addition of amiloride to the culture medium. Sprouts formed from vascular explants are counted every second day until days 8 to 10. Kinetics of new vessels formation and the number of sprouts were similar in aortic and coronary rings (83 +/- 5 and 95 +/- 5 sprouts, respectively). Elevation of sodium chloride concentration inhibits by 50 to 80% the neo-vessels formation in both the aorta and the coronary artery. Anti-angiogenic effect of the high sodium medium was not affected when citrate was substituted to chloride. Amiloride (3.10(-5) M) reduced the number of sprouts formed in the standard medium; however, it counteracted the anti-angiogenic effect of elevated sodium concentration. These results indicate that high extracellular concentration of sodium and not chloride anion is accompanied by a deleterious effect on angiogenic capacities of cultured aortic and coronary artery rings through modifications of trans-membrane sodium exchanges.

[What is the place of bioresorbable vascular scaffolds in setting of ST-segment elevation myocardial infarction?]. / Quelle place pour les stents biorésorbables dans la prise en charge du syndrome coronarien aigu avec sus-décalage du segment ST ?

A 50-year-old woman was admitted for an inferior ST-segment elevation myocardial infarction; immediate coronary angiogram revealed a subocclusive stenosis of the right coronary artery. After optimal antithrombotic treatment, the type of stent could be discussed. The latest generation of drug-eluting stents showed excellent efficacy and safety in the long-term but has limitations such as potential chronic inflammation of the arterial wall and no recovery of vasoactive function. Bioresorbable vascular scaffolds, with complete resorption within several months, may reduce these limitations. Implantation of bioresorbable scaffold in the context of myocardial infarction may be interesting. However, very few studies are currently available in this setting. Preliminary results and perspectives are presented in this review.

Optimal time for catheterization in NSTE-ACS patients with impaired renal function: insights from the ABOARD Study.

BACKGROUND: To assess the impact of impaired renal function (IRF) and timing of catheterization (immediate versus delayed intervention) on outcomes in intermediate/high risk NSTE-ACS patients. METHODS: We performed a post-hoc analysis of the randomized ABOARD population to compare 1) patients with vs. without IRF and 2) the two intervention strategies in patients with IRF. A creatinine clearance <60 mL/min defined IRF. The primary endpoint was the in-hospital peak troponin I value; the secondary endpoints were a) the composite of death, myocardial infarction, urgent revascularization or recurrent ischemia (death/MI/UR/RI) and b) STEEPLE major bleeding (MB) at 1-month follow-up. RESULTS: Among the 345 patients, 75 (21.7%) had IRF. Patients with IRF were older, had more comorbidities and were at higher cardiovascular risk. Radial catheterization was predominant (84%). Among IRF patients, 37 (49%) and 38 (51%) patients were randomized to an immediate and delayed strategy, respectively. The primary and secondary endpoints rates were not different for the two comparisons. IRF was associated with more death (5.3% vs. 1.1%, p=0.043) and non-CABG MB (9.3% vs. 2.2%, p=0.001). In patients with IRF, a delayed strategy was associated with more recurrent ischemia (28.9% vs. 8.1%, p=0.021). Absence of clopidogrel pretreatment, insulin therapy and left main culprit lesion were independently associated with death/MI/UR/RI, while age and CABG surgery were related with MB. CONCLUSION: IRF is associated with worse outcomes in NSTE-ACS patients. The primary results of the ABOARD study apply also to patients with IRF in which the timing of catheterization does not impact hard outcomes.

Current antiplatelet options for NSTE-ACS patients.

Non-ST elevation (NSTE) myocardial infarction and unstable angina are the most common clinical presentations of acute coronary syndrome (ACS). Platelet activation is central to the pathogenesis of NSTE-ACS and consensus guidelines that advocate early revascularization supported by intensive antiplatelet therapy. This review examines the drugs used concurrently with aspirin as dual antiplatelet therapy in the NSTE-ACS setting. Clopidogrel represented an important therapeutic advance. However, variations in platelet response and a relatively slow onset of action compromise outcomes with clopidogrel. Evidence reviewed in this article shows that in NSTE-ACS patients, ticagrelor and prasugrel are more effective than clopidogrel and are relatively well tolerated, with an acceptable and manageable bleeding risk. The literature suggests several differences between ticagrelor and prasugrel that should allow clinicians to better tailor treatment to the patient. Head-to-head comparisons are now needed to compare directly the risks and benefits of ticagrelor and prasugrel in NSTE-ACS. Further studies also need to address other outstanding issues such as the benefits and risks of prasugrel pre-treatment and to stratify efficacy and tolerability according to diabetes mellitus (DM) and other co-morbidities. In the meantime, the issues discussed in this review should enhance clinicians' ability to optimize and individualize NSTE-ACS treatment, thereby further reducing the morbidity and mortality associated with this common cardiovascular condition.

[Management of ST-elevation myocardial infarction in 2012]. / Prise en charge de l'infarctus du myocarde en 2012.

Improvement of myocardial reperfusion with a greater use of primary percutaneous coronary intervention, adjunctive pharmacological and mechanical therapies have contributed to a spectacular decrease in mortality of patients presenting with ST-elevation myocardial infarction.