Emmanuel Sorbets

Update on the need for a permanent pacemaker after transcatheter aortic valve implantation using the CoreValve® Accutrak™ system.

AIMS High rates of permanent pacemaker (PPM) implantation are reported after transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve® system. The Accutrak™ catheter is designed to allow a more predictable landing zone. Little is known about the real clinical impact of this catheter. The aims of this paper were to describe the potential impact of the Accutrak™ catheter on the accuracy of positioning a 26 or 29 mm CoreValve® across the aortic annulus and its impact on the need for a pacemaker. METHODS AND RESULTS A total of 134 patients were treated with the CoreValve® Accutrak™ system at two French centres (Lille and Toulouse). Mean age was 82.4 ± 4.7 years; logistic EuroSCORE was 24.3 ± 9.5%. Procedural success rate was 99.2%; mean depth of implantation was 4.9 mm. A final position between 0 and 6 mm was achieved in 85.8% of the patients. All-cause mortality at 30 days was 6%. The PPM implantation rate was 10.6%. Due to a limited number of events, we could not identify any predictor of need for a PPM: pre-existing right bundle branch block (RBBB) (OR 2.72 [0.63-11.87], p=ns), use of a 29 mm prosthesis (OR 2.73 [0.33-22.90], p=ns) and left ventricular septal hypertrophy (OR 2.63 [0.08-83.32], p=ns). CONCLUSIONS In this cohort of patients treated with the CoreValve® Accutrak™ system, the incidence of permanent pacemaker implantation was low, which may be a consequence of an average small implantation depth. The Accutrak™ catheter seems to be helpful in achieving higher and more predictable implants. Operators could standardise their technique to place the CoreValve® prostheses less than 6 mm below the aortic annulus.

NSAID Use and Association with Cardiovascular Outcomes in Outpatients with Stable Atherothrombotic Disease

BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin have been linked to heart failure, salt retention, adverse ventricular remodeling, and thrombosis. We therefore sought to assess their impact on cardiovascular events in outpatients with stable atherothrombotic disease. METHODS We analyzed 44,095 patients in the REduction of Atherothrombosis for Continued Health (REACH) registry with information on NSAID use and 4-year follow-up. Cox proportional hazard models, including NSAID use as a time-dependent covariate, were constructed and adjusted for key baseline characteristics. End points of interest included multivariate adjusted: cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations; cardiovascular death/myocardial infarction/stroke; hospitalization for heart failure; and individual components of the composite end points. RESULTS Compared with NSAID nonusers (n = 39,675), NSAID users (n = 4420) were older (70 vs 68 years), more frequently female and white, and had more baseline heart failure and atherosclerotic risk factors (hypertension, dyslipidemia, diabetes, reduced creatinine clearance) (all P < .001). NSAID use was associated with an increased hazard for cardiovascular death/myocardial infarction/stroke/ischemic hospitalizations (adjusted hazard ratio [adj. HR] 1.12; 95% confidence interval [CI], 1.04-1.21; P = .003) and for cardiovascular death/myocardial infarction/stroke (adj. HR 1.16; 95% CI, 1.03-1.30; P = .02). There also was a higher risk of myocardial infarction (adj. HR 1.37; 95% CI, 1.12-1.68; P = .002), stroke (adj. HR 1.21; 95% CI, 1.00-1.45; P = .048), heart failure hospitalizations (adj. HR 1.18; 95% CI, 1.03-1.34; P = .013), and ischemic hospitalizations (adj. HR 1.17; 95% CI, 1.07-1.27; P = .001). CONCLUSION Among patients with stable atherothrombosis, NSAID use is associated with a higher risk of myocardial infarction, stroke, and hospitalizations for both ischemia and heart failure.

Association of spontaneous and procedure-related bleeds with short- and long-term mortality after acute coronary syndromes: an analysis from the PLATO trial

AIMS We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity. METHODS AND RESULTS The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2±123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions. CONCLUSIONS Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding.

Renin-angiotensin system antagonists and clinical outcomes in stable coronary artery disease without heart failure

AIMS The aim of this study was to determine whether angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB) use is associated with lower rates of cardiovascular events in patients with stable coronary artery disease (CAD) but without heart failure (HF) receiving contemporary medical management. METHODS AND RESULTS Using data from the Reduction of Atherothrombosis for Continued Health (REACH) registry, we examined, using propensity score approaches, relationships between cardiovascular outcomes and ACEI/ARB use (64.1% users) in 20 909 outpatients with stable CAD and free of HF at baseline. As internal control, we assessed the relation between statin use and outcomes. At 4-year follow-up, the risk of cardiovascular death, MI, or stroke (primary outcome) was similar in ACEI/ARB users compared with non-users (hazard ratio, 1.03; 95% confidence interval [CI], 0.91-1.16; P = 0.66). Similarly, the risk of the primary outcome and cardiovascular hospitalization for atherothrombotic events (secondary outcome) was not reduced in ACEI/ARB users (hazard ratio, 1.08; 95% CI, 1.01-1.16; P = 0.04), nor were the rates of any of its components. Analyses using propensity score matching yielded similar results, as did sensitivity analyses accounting for missing covariates, changes in medications over time, or analysing separately ACEI and ARB use. In contrast, in the same cohort, statin use was associated with lower rates for all outcomes. CONCLUSIONS Use of ACEI/ARB was not associated with better outcomes in stable CAD outpatients without HF. The benefit of ACEI/ARB seen in randomized clinical trials was not replicated in this large contemporary cohort, which questions their value in this specific subset.

Residual Ischemic Risk and Its Determinants in Patients With Previous Myocardial Infarction and Without Prior Stroke or TIA: Insights From the REACH Registry

Although the rate of in‐hospital ischemic events after myocardial infarction (MI) has dramatically decreased, long‐term residual risk may remain substantial. However, most of the information on current residual risk is derived from highly selected randomized trials.

Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes

Background Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality. Methods In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time‐dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events. Results A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short‐ and long‐term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short‐ and long‐term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98‐2.19) and 0.92 (0.52‐1.62) (PLATO major); 1.26 (0.80‐1.96) and 1.19 (0.58‐2.24) (TIMI major), 0.72 (0.47‐1.10) and 0.83 (0.38‐1.79) (GUSTO severe) (all P > 0.05) Conclusions In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem “prognostically equivalent” to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

A single value of high-sensitive troponin T below the limit of detection is not enough for ruling out non ST elevation myocardial infarction in the emergency department

BACKGROUND Recent 2015 ESC recommendations for the management of patients with suspected acute myocardial infarction (AMI) support that a single value of high-sensitivity cardiac troponin (HS-cTn) measured at presentation could rule out AMI if below the limit of blank (LoB) or detection (LoD). OBJECTIVES We aimed to evaluate whether an undetectable HS-cTnT at presentation safely rules out NSTEMI in unselected patients with chest pain. PATIENTS AND METHODS This is a post hoc analysis of two prospective cohorts with similar design that included patients suspected of AMI at three French university hospitals. Patients were followed-up during one month, before the adjudication of a final diagnosis. RESULTS 413 patients (mean age 58±17years) were analyzed; 45 (11%) had a final diagnosis of NSTEMI, and 26 (6%) had STEMI. The sensitivity of HS-cTnT value at 3ng/L (LoB) for NSTEMI was 97.8% [95% CI: 86.8-99.9], yielding a negative predictive value (NPV) of 99.3% [95% CI: 95.4-100.0]. Proportion of patients ruled out for NSTEMI was 32% when applying the LoB. The sensitivity of HS-cTnT value at 5ng/L (LoD) was 97.8% [95% CI: 86.8-99.9] yielding a NPV of 99.5% [95% CI: 96.5-100.0]. Proportion of patients ruled out for NSTEMI was 43% when applying the LoD. One patient (delay between onset of chest pain and presentation <3h) had NSTEMI and HS-cTnT <LoB at presentation. CONCLUSION The NPV of a single measurement of HS-cTnT below the LoD is high in unselected patients, but not enough to rule out safely NSTEMI for very early presenters.

Impact of diabetes mellitus and metabolic syndrome on acute and chronic on-clopidogrel platelet reactivity in patients with stable coronary artery disease undergoing drug-eluting stent placement.

BACKGROUND Previous studies, which compared the prevalence of high on-clopidogrel platelet reactivity (HCPR) in type 2 diabetes mellitus (T2DM) versus non-T2DM and obese versus nonobese patients provided conflicting results. METHODS We compared the prevalence of HCPR in patients with T2DM, metabolic syndrome (MS), or neither T2DM nor MS undergoing drug-eluting stent implantation for stable coronary artery disease. Platelet functions were measured after a 600-mg clopidogrel loading dose and after 4 months on clopidogrel 75 mg/d. RESULTS The prevalence of HCPR was significantly higher in 63 T2DM and 50 MS patients than in 43 patients with neither T2DM nor MS (46.0% and 52.0% vs 20.9%) after clopidogrel loading dose, whereas, at 4 months, only T2DM patients had a significantly higher prevalence of HCPR (50.8% and 31.3% vs 23.8%). By multivariable analysis, T2DM (odds ratio [OR] 3.62, 95% CI, 1.34-9.80, P = .011), MS (OR 4.00, 95% CI 1.39-11.46, P = .010), and previous chronic treatment with clopidogrel (OR 0.22, 95% CI 0.09-0.49; P < .001) were the main independent predictors of HCPR after clopidogrel loading dose, whereas only T2DM (OR 2.98, 95% CI 1.20-7.41, P = .017) was an important independent predictor of HCPR at 4 months. CONCLUSIONS Both MS and T2DM were independent predictors of HCPR after clopidogrel loading dose. On clopidogrel maintenance therapy, only T2DM remained an independent predictor. This observation may be clinically relevant in the current era of antiplatelet therapy.

Comparison of hospital mortality during ST-segment elevation myocardial infarction in the era of reperfusion therapy in women versus men and in older versus younger patients.

There is intense interest in examining hospital mortality in relation to gender in ST-segment elevation myocardial infarction. The aim of the present study was to determine whether gender influences outcomes in men and women treated with the same patency-oriented reperfusion strategy. The influence of gender on hospital mortality was tested using multivariate analysis and local regression. The influence of age was tested as a continuous and as a categorical variable. In the overall population of 2,600 consecutive patients, gender was not correlated with hospital mortality except in the subgroup of women aged ≥65 years. The risk for death increased linearly in logit scale for men. Up to the age of 65 years, the risk also increased linearly in women but thereafter increased faster than in men. Testing age as a categorical variable, hospital mortality was higher in women than in men aged ≥75 years but was similar between the genders in the younger age categories. In conclusion, despite following an equal patency-oriented management strategy in men and women with ST-segment elevation myocardial infarctions, the risk for hospital death increased linearly with age but with an interaction between age and gender such that older women had an independent increase in hospital mortality. Longer time to presentation and worse baseline characteristics probably contributed to determine a high-risk subset but reinforce the need to apply, as recommended in the international guidelines in the management of patients with ST-segment elevation myocardial infarctions, the same strategy of acute reperfusion in men and women.

Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry

Patients with symptomatic peripheral artery disease (PAD) are at high risk of ischemic events. However, data about predictors of this risk are limited.