Prasugrel and ticagrelor are similarly effective during the first year after MI. Economically motivated early post-discharge switches to clopidogrel were not associated with an increased risk of ischemic events. (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction [PRAGUE-18]; NCT02808767).

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used for circulatory support in cardiogenic shock patients, although the evidence supporting its use in this context remains insufficient. The aim of the Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock (ECMO-CS) trial was to compare immediate implementation of VA-ECMO vs. an initially conservative therapy (allowing downstream use of VA-ECMO) in patients with rapidly deteriorating or severe cardiogenic shock. Methods: This multicenter, randomized, investigator-initiated, academic clinical trial included patients with either rapidly deteriorating or severe cardiogenic shock. Patients were randomly assigned to immediate VA-ECMO or no immediate VA-ECMO. Other diagnostic and therapeutic procedures were performed as per current standard(s) of care. In the early conservative group, VA-ECMO could be used downstream in case of worsening hemodynamic status. The primary endpoint was the composite of death from any cause, resuscitated circulatory arrest, and implementation of another mechanical circulatory support device at 30 days. Results: A total of 122 patients were randomized; after excluding 5 patients due to the absence of informed consent, 117 subjects were included in the analysis, of whom 58 randomized to immediate VA-ECMO and 59 to no immediate VA-ECMO. The composite primary endpoint occurred in 37 (63.8%) and 42 (71.2%) of patients in the immediate VA-ECMO and the no early VA-ECMO groups, respectively (hazard ratio, 0.72; 95% confidence intervals [CI], 0.46 to 1.12; P=0.21). VA-ECMO was used in 23 (39%) of no early VA-ECMO patients. The 30-day incidence of resuscitated cardiac arrest (10.3. % vs. 13.6%; risk difference [RD], -3.2; 95% CI, -15.0 to 8.5), all-cause mortality (50.0% versus 47.5%; RD, 2.5; 95% CI, -15.6 to 20.7), serious adverse events (60.3% vs. 61.0%; RD, -0.7; 95% CI, -18.4 to 17.0), sepsis, pneumonia, stroke, leg ischemia, and bleeding was not statistically different between the immediate VA-ECMO and the no immediate VA-ECMO groups. Conclusions: Immediate implementation of VA-ECMO in patients with rapidly deteriorating or severe cardiogenic shock did not improve clinical outcomes compared with an early conservative strategy that permitted downstream use of VA-ECMO in case of worsening hemodynamic status. Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT02301819.

clinicaltrials.gov Identifier: NCT00091637.

Acute heart failure and/or cardiogenic shock are frequently triggered by ischemic coronary events. Yet, there is a paucity of randomized data on the management of patients with heart failure complicating acute coronary syndrome, as acute coronary syndrome and cardiogenic shock have frequently been defined as exclusion criteria in trials and registries. As a consequence, guideline recommendations are mostly driven by observational studies, even though these patients have a particularly poor prognosis compared to heart failure patients without signs of coronary artery disease. In acute heart failure, and especially in cardiogenic shock related to ischemic conditions, vasopressors and inotropes are used. However, both pathophysiological considerations and available clinical data suggest that these treatments may have disadvantageous effects. The inodilator levosimendan offers potential benefits due to a range of distinct effects including positive inotropy, restoration of ventriculo-arterial coupling, increases in tissue perfusion, and anti-stunning and anti-inflammatory effects. In clinical trials levosimendan improves symptoms, cardiac function, hemodynamics, and end-organ function. Adverse effects are generally less common than with other inotropic and vasoactive therapies, with the notable exception of hypotension. The decision to use levosimendan, in terms of timing and dosing, is influenced by the presence of pulmonary congestion, and blood pressure measurements. Levosimendan should be preferred over adrenergic inotropes as a first line therapy for all ACS-AHF patients who are under beta-blockade and/or when urinary output is insufficient after diuretics. Levosimendan can be used alone or in combination with other inotropic or vasopressor agents, but requires monitoring due to the risk of hypotension.

Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions. The default mode network of the brain has an important role in the representation of introspective mental activities and therefore can be considered as a nodal point, common for both chronic pain and depression. Neuroplasticity which involves molecular, cellular and synaptic processes modifying connectivity between neurons and neuronal circuits can also be affected by pathological states such as chronic pain or depression. We suppose that pathogenesis of depression and chronic pain shares common negative neuroplastic changes in the central nervous system (CNS). The positive impact of antidepressants would result in a reduction of these pathological cellular/molecular processes and in the amelioration of symptoms, but it may also increase survival times and quality of life of patients with chronic cancer pain.

Background: Oral factor XIa (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without significantly increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6–2 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on factor XIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% were women, 51% had ST-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10, 20, 50 mg, and placebo (pooled asundexian vs. placebo: HR 0.98, 90% CI 0.71–1.35). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10, 20, 50 mg, and placebo (pooled asundexian 20 and 50 mg vs. placebo: HR 1.05, 90% CI 0.69–1.61). Conclusions: : In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients following acute MI.

Acute cardiovascular care has progressed considerably since the last position paper was published 10 years ago. It is now a well-defined, complex field with demanding multidisciplinary teamworking. The Acute Cardiovascular Care Association has provided this update of the 2005 position paper on acute cardiovascular care organisation, using a multinational working group. The patient population has changed, and intensive cardiovascular care units now manage a large range of conditions from those simply requiring specialised monitoring, to critical cardiovascular diseases with associated multi-organ failure. To describe better intensive cardiovascular care units case mix, acuity of care has been divided into three levels, and then defining intensive cardiovascular care unit functional organisation. For each level of intensive cardiovascular care unit, this document presents the aims of the units, the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region/area. This update emphasises cardiologist training, referring to the recently updated Acute Cardiovascular Care Association core curriculum on acute cardiovascular care. The training of nurses in acute cardiovascular care is additionally addressed. Intensive cardiovascular care unit expertise is not limited to within the unit's geographical boundaries, extending to different specialties and subspecialties of cardiology and other specialties in order to optimally manage the wide scope of acute cardiovascular conditions in frequently highly complex patients. This position paper therefore addresses the need for the inclusion of acute cardiac care and intensive cardiovascular care units within a hospital network, linking university medical centres, large community hospitals, and smaller hospitals with more limited capabilities.

Theta burst stimulation (TBS) is a modified form of high-frequency repetitive transcranial magnetic stimulation (rTMS) with promising effect in chronic pain. The aim of our double-blind, sham-controlled, parallel-group, randomized study was to assess an efficacy of intermittent TBS (iTBS) in the treatment of patients with chronic orofacial pain. Nineteen patients (twelve females) with chronic orofacial pain were prospectively included and randomly assigned to single session of an active (iTBS) or sham (intermediate TBS; imTBS) stimulation delivered to the primary motor cortex (M1) contralateral to painful side. The primary outcome was pain relief assessed using a visual analogue scale (VAS) after stimulation and at the end of two-week follow- up. The secondary outcomes were changes in the quantitative sensory testing (QST). QST set the threshold for thermal and tactile (touch) sensation in the affected facial area. Intermittent TBS, compared with the sham, showed significant improvement in VAS after stimulation, but not at the end of two-week follow-up. Regarding the secondary outcomes (QST), we failed to find any significant difference between iTBS and sham. Our findings demonstrate that iTBS of M1 transiently provides transient and modest subjective pain relief in chronic orofacial pain.