Sebastien Hess

The extent of P2Y12 inhibition by clopidogrel in diabetes mellitus patients with acute coronary syndrome is not related to glycaemic control: Roles of white blood cell count and body weight

It was the study objective to determine whether glycaemic control affects the extent of platelet inhibition by thienopyridines as assessed by vasodilator-stimulated phosphoprotein flow cytometry (VASP-FCT) in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) during acute coronary syndrome (ACS). Although the proportion of high on-treatment residual platelet reactivity is higher in DM, the contributions of glycaemic control and other factors associated with DM, such as excess body weight and inflammation, to this impaired platelet inhibition by thienopyridines have not yet been fully characterised. In this study, the extent of P2Y12 ADP receptor pathway inhibition was evaluated by the VASP-FCT. Platelet activation was expressed as the platelet reactivity index (PRI). Low response to clopidogrel (LR) was defined as a PRI of >61%. Four hundred forty-five consecutive ACS patients (DM = 160, NDM = 285) were enrolled. The proportion of LR was higher in DM patients (50 vs. 37.5%). In DM, PRI was not correlated with glycosylated haemoglobin (HbA1c) or glycaemia. In a univariate analysis, LR was associated with age, male sex, overweight, and white blood cell count (WBC). In a multivariate analysis, WBC >10,000 and body weight >80 kg were the sole independent predictors of LR to clopidogrel (hazard ratio (HR) 3.02 [1.36-6.68], p=0.006 and HR 2.47 [1.14-5.35], p = 0.021, respectively). Conversely, in non-DM patients, ST-elevation myocardial infarction was the sole independent predictor of LR. In conclusion, in ACS DM patients undergoing PCI, the extent of P2Y12 inhibition by clopidogrel is not related to glycaemic control but is related to body weight and inflammatory status as assessed by the WBC.

Impact of Malignancies in the Early and Late Time Course of Takotsubo Cardiomyopathy

BACKGROUND Although the relationship between malignancies and catecholamine-induced myocardial stunning remains largely speculative, it has been suggested that the presence of cancer may lower the threshold for stress stimuli and/or may aggravate cardiac adrenoreceptor sensitivity. We sought to investigate whether associations exist between a previous or current diagnosis of malignancy, diagnostic parameters during hospitalization and death in takotsubo. METHODSANDRESULTS The 154 takotsubo patients were retrospectively identified between May 2008 and December 2014. Previous history of malignancy was identified in 44 patients (28.5%). Cardiac arrest was present at admission in 13 patients (8.4%). Intra-aortic balloon pump was inserted in 16 patients (10.4%). In patients with malignancy, higher B-type natriuretic peptide (BNP), leukocyte and C-reactive protein (CRP) peaks could be observed during the hospital phase. Initial impairment of left ventricular ejection fraction was negatively related to BNP, leukocyte, and CRP peaks. At a median follow-up of 364 days, all-cause death occurred in 41 patients (26.6%) and cardiac death in 12 patients (7.7%). Multivariate Cox regression analysis identified malignancy (hazard ratio 4.77 (1.02-22.17), leukocyte peak and age as independent predictors of cardiac death. Malignancy (2.62 (1.26-5.44), leukocyte peak (1.05 (1.01-1.08) and initial cardiac arrest (6.68 (2.47-18.01) were identified as independent predictors of overall mortality. CONCLUSIONS In the present takotsubo patients, the prevalence of malignancy was high and may have affected cardiovascular outcomes through the activation of inflammatory and neurohormonal mechanisms. (Circ J 2016; 80: 2192-2198).

Takotsubo and Takotsubo-like syndrome: A common neurogenic myocardial stunning pathway?

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Out-of-hospital cardiac arrest survivors sent for emergency angiography: a clinical score for predicting acute myocardial infarction

Background: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue. Emergency coronary angiography and percutaneous coronary intervention might improve survival, especially when cardiac arrest is caused by acute myocardial infarction (AMI). However, identifying patients with AMI after OHCA remains challenging. The aim of this study was to determine the clinical and ECG criteria in OHCA that may help to identify better the patients with AMI. Methods: Consecutive OHCA patients who underwent emergency coronary angiography in our centre between 2009 and 2013 were included in this retrospective single-centre observational study. Results: A total of 177 patients with complete datasets were included. Significant coronary artery disease was found in 71% of the patients, and 43% presented with AMI. The independent predictors of AMI were ST elevation in any lead including aVR (odds ratio (OR) 18.06; 95% confidence interval (CI) 6.6–49.38), chest pain before cardiac arrest (OR 4.05; 95% CI 1.55–10.54) and an initial shockable rhythm (OR 2.99; 95% CI 1.34–6.45). An additive score that included these three predictors yielded a sensitivity and a specificity for detecting AMI of 93% and 63%, respectively. Conclusions: These data suggest that fewer than half of patients with OHCA undergoing emergency coronary angiography present with AMI. The identification of OHCA patients with AMI might be improved by a simple score using post-resuscitation ECG and simple clinical criteria.

Impact of manual thrombectomy on myocardial reperfusion as assessed by ST-segment resolution in STEMI patients treated by primary PCI

BACKGROUND In STEMI patients treated by primary PCI, damage of the microvascular circulation caused by distal embolization of thrombotic material affects the quality of myocardial reperfusion. Important controversies remain concerning the usefulness of the manual thrombectomy to improve myocardial perfusion. The aim of this study is to evaluate the impact of manual thrombectomy on ST resolution as a surrogate of reperfusion extent. METHODS Two hundred and thirty-nine consecutive STEMI patients with an <12 hours onset of symptoms, were enrolled in an observational registry. Patients were divided into two cohorts according to the reperfusion strategy: manual thrombectomy before primary PCI (n=102) or conventional-PCI (n=137). The primary endpoint was the post procedural frequency of complete (>70%) resolution of ST segment elevation. RESULTS A complete resolution of ST segment elevation occurred in 51.4% of patients in the thrombectomy group and in 35,6% of those in the conventional-PCI group (P=0.018). Thrombectomy strategy was associated with a lower use of stents. Multivariate analysis identified manual thrombectomy (HR=2.08 IC 95% (1.01-4.26); P=0.046), inferior location and short ischemic delay (<180 min) as independent predictors of ST resolution. The cumulative Kaplan-Meier estimate of MACE was not significantly different between the two groups at one, three years follow-up. CONCLUSION In STEMI patients, manual thrombectomy improves myocardial reperfusion as assessed by the percentage of ST segment resolution and a lower use of stents. However, in this cohort of limited size, this strategy did not translate into an improved cardiovascular outcome at one year follow-up.

Antiplatelet Therapy in ACS Patients: Comparing Appropriate P2Y12 Inhibition by Clopidogrel to the Use of New P2Y12 Inhibitors

Aim: In percutaneous coronary intervention (PCI)-treated acute coronary syndrome (ACS) patients on clopidogrel therapy, high on-treatment platelet adenosine diphosphate (ADP) reactivity was observed in numerous studies, with significant increases in non-fatal myocardial infarction, definite/probable stent thrombosis, or cardiovascular mortality. Compared to clopidogrel, prasugrel and ticagrelor provide more potent platelet inhibition. Whether new P2Y12 inhibitors reduce thrombotic events in a similar manner compared to the rate observed with appropriate P2Y12 inhibition by clopidogrel must still be determined. This study sought to compare longterm outcomes between clopidogrel responders (platelet reactivity index [PRI] vasodilator-stimulated phosphoprotein [VASP] < 61%) and patients under prasugrel or ticagrelor therapy following PCI-treated ACS. Methods: 730 ACS patients undergoing urgent PCI were prospectively enrolled into two groups: clopidogrel responders (n = 448) and those under ticagrelor or prasugrel therapy (n = 282). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stent thrombosis, and stroke; the secondary endpoint comprised major hemorrhagic events. Results: The median follow-up was 260 ± 186 days. Clopidogrel patients were older and more likely to present non-ST segment elevation myocardial infarction, cardiovascular risk factors, atrial fibrillation, or prior vascular disease. After propensity score matching, the primary endpoint was met in 7.1% of the clopidogrel group and 4.1% of the prasugrel/ticagrelor group (p = 0.43). Minor bleeding events were significantly reduced in the clopidogrel group (1.1% vs. 3%; p = 0.03). In a multivariate analysis, the antiplatelet treatment strategy was not an independent primary endpoint predictor. Conclusion: In PCI-treated ACS patients, clopidogrel therapy and PRI VASP < 61% were not associated with increased risks of thrombotic events compared to prasugrel or ticagrelor therapy.

0258: Comparison of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement in very high risk patients, monocentric registry of an early experience

Introduction The PARTNER trial has shown that TAVI is not inferior to surgical aortic valve replacement (AVR) in high-risk aortic stenosis. However, real life registry comparing TAVI and surgery are lacking. Methods monocentric registry of high-risk patients (lEUROSCORE1 ≥15%) undergoing TAVI (114 patients) or AVR (81 patients) between 2009 and 2013 in our institution. Results Mean age was 84,4 and 83,6 yo (p=NS). TAVI patients had higher EUROSCORE1 (31 vs 24.5%, p Conclusion The present registry results confirm that TAVI is a real alternative to surgery in patients with at high surgical risk. Longer follow up is required to confirm these results. Abstract 0258 – Table. AVR TAVI p n 81 114 Age 83.6 84.4 0.21 Euroscore1 (%) 24.5 31 FEV (%) 57.1 48.5 DTVG (mm) 51 54 0.086 Mean Gradient (mmHg) 53 46 0.008 Creatinin pre (microM/L) 111 138 0.003 Hemoglobin pre (g/100) 12.6 11.6 Death (%) 17.3 9.6 0.12 Vascular complication (%) 0 11.4 0.001 Infection (%) 19 11 0.008 Dialysis (%) 13.6 11.4 0.65 AFIB post (%) 41 20 0.002 Pericardial effusion (% ) 2.5 8.8 0.13 Stroke (%) 4.9 1.8 0.23 Pace Maker (%) 4.9 24.6 Transfusions (%) 80 25

0228: Aortic annulus sizing strategy in TAVI, comparison of echocardiography and CT, impact on aortic regurgitation incidence and patients prognosis

Background Aortic regurgitation (AR) after TAVI is the main limitation of this procedure. The aim of this study was to evaluate i) aortic annulus sizing by CT and/or echocardiography (TTE or TEE) ii) the incidence of AR and its determinism iii) the prognostic impact of AR and other survival predictors. Methods 136 consecutive patients undergoing TAVI were included between 2010 and 2013. The aortic annulus sizing for prosthesis choice was done by TEE in 29 patients and by CT in 107 patients. Aortic valve calcium volume was measured by the volume technique in 67% of patients who have got CT. Follow-up was performed at 1, 6, 12 and 24 months. Results Aortic annulus sizing by TTE and TEE echocardiography (TEE) were well correlated (r=0,73, p=0,0001, n=51) but were significantly lower than CT sizing (p 25%, aortic regurgitation ≥ 2/4, renal failure with creatinin> 130μmol/l, anemia after TAVI Conclusion This study showed that aortic annulus sizing by echocardiography is significantly lower than sizing by CT. AR have an independent prognostic on survival. Prevention of aortic regurgitation is an important issue for the future of this technique.

Reply to the letter by Ando et al.

We would like to thank Ando and coworkers for their interesting comment [1] on our paper entitled «Takotsubo and Takotsubo-like syndrome: a common neurogenic myocardial stunning pathway»[2]. In our clinical experience, stress-induced cardiomyopathy detected by the specific scintigraphic signature associating severe 123I-MIBG and 18FDG defects contrasting with normal 99mTc-Tetrofosmin perfusion could be assessed in a large variety of clinical settings, including the classical stress-induced catecholamine stunning (Takotsubo syndrome), epinephrine treatment or overdosing, trauma, acute medical or surgical illness including shock, intracranial bleeding and pheochromocytoma [3,4]. Other groups share similar experience, emotional cause being evidenced in a minority of cases, whereas physical stress owing to acutemedical illness or surgical procedure now represents the vastmajority of triggers.Whatever the triggering eventmight be, recent analysis clearly depicted a common pathophysiological underlying mechanism [5,6]. In the outstanding paper published by Paur and coworkers, biased agonism of epinephrine for β [2] Adrenoreceptor (AR)-G(s) at low concentrations and for G(i) at high concentrations underpins the acute apical cardiodepression observed in Takotsubo cardiomyopathy, the apical–basal gradient in β [2] AR accounting for the differential regional responses. Although we recognize that some issues remain to be addressed such as the high prevalence of postmenopausal women, the spatial distribution of beta adrenergic receptors, the potential involvement of microvascular dysfunction, it is now thoroughly demonstrated that endogenous or exogenous epinephrine activation of β[2] Adrenoreceptor G(i) protein pathway represents the common underlying mechanism for catecholamine induced myocardial stunning. Activation of this pathway was found to be antiapoptotic and cardioprotective whereas its inhibition triggered cardiac death [6]. In this animal model, the inability of norepinephrine at equivalent or higher doses to initiate acute apical dysfunction excludes coronary vasospasm or β1AR-mediated signaling as a primary effector, in agreementwith clinical observations showing that the apical dysfunction in Takotsubo cardiomyopathy extends beyond the territory of a single coronary bed [6]. Therefore, we do not believe that the exclusion of pheochromocytoma or intracranial bleeding as suggested by thewidespread criteria is still pathophysiologically relevant. Because a common underlying pathophysiological pathway has been evidenced, we propose that the term «catecholamine induced myocardial stunning» could be used in the future to refer to stress cardiomyopathy.