Rationale and design of the ULYSS trial: A randomized multicenter evaluation of the efficacy of early Impella CP implantation in acute coronary syndrome complicated by cardiogenic shock.

CONTEXT: Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLAⓇ CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy. DESIGN: The ULYSS trial is a prospective randomized open label, 2 parallel multicenter clinical trial that plans to enroll patients with AMICS for whom an emergent percutaneous coronary intervention (PCI) is intended. Patients will be randomized to an experimental therapeutic strategy with pre-PCI implantation of an IMPELLAⓇ CP device on top of standard medical therapy or to a control group undergoing PCI and standard medical therapy. The primary objective of this study is to compare the efficacy of this experimental strategy by a composite end point of death, need to escalate to ECMO, long-term left ventricular assist device or heart transplantation at 1 month. Among secondary objectives 1-year efficacy, safety and cost effectiveness will be assessed. CLINICAL TRIAL REGISTRATION: NCT05366452.

Impact of targeted pulmonary arterial hypertension therapies in severe pulmonary hypertension in chronic lung diseases.

Research questions: Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients. Study design and methods: We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response. Results: 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of -1.0 Wood Units (p<0.001) and -4 mmHg (p<0.001), respectively, under treatment. 18% of patients had to withdraw treatment for intolerance. Treatment duration <3 months was associated with poor survival (hazard ratio 2.75, p=0.0005). Conclusion: Oral targeted pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease, but could improve haemodynamic parameters.

FCGR2A-HH Gene Variants Encoding the Fc Gamma Receptor for the C-Reactive Protein Are Associated with Enhanced Monocyte CD32 Expression and Cardiovascular Events' Recurrence after Primary Acute Coronary Syndrome.

Fcγ receptors (FcγRs) interact with the C-reactive protein (CRP) and mediate activation of inflammation-related pathogenic mechanisms affecting cardiovascular health. Our study evaluated whether FcγRIIA and FcγRIIIA profiles are associated with the recurrence of adverse cardiovascular events during the first year after a primary acute coronary syndrome (ACS). The primary endpoint was the recurrence of cardiovascular events (RCE), identified as a composite outcome comprising acute heart failure (AHF) and major adverse cardiovascular events (MACE). We obtained blood samples of 145 ACS patients to measure hsCRP circulating levels, to identify FcγRIIA-131RH rs1801274 and FcγRIIIA-158FV rs396991 polymorphisms, to analyze circulating monocytes and NK cell subsets expressing CD16 and CD32, and to detect serum-mediated FCGR2A-HH activation by luciferase reporter assays. The hsCRP, CD32-expression, and Fc-R mediated activation levels were similar in all patients regardless of their MACE risk. In contrast, the hsCRP levels and the proportion of CD14+ circulating monocytes expressing the CD32 receptor for CRP were significantly higher in the patients who developed AHF. The FCGR2A rs1801274 HH genotype was significantly more common in patients who developed RCE and MACE than in RCE-free patients and associated with an enhanced percentage of circulating CD32+CD14+ monocytes. The FCGR2A-HH genotype was identified as an independent predictor of subsequent RCE (OR, 2.7; p = 0.048; CI, 1.01-7.44) by multivariate analysis. These findings bring preliminary evidence that host FCGR2A genetic variants can influence monocyte CD32 receptor expression and may contribute to the fine-tuning of CD32-driven chronic activating signals that affect the risk of developing RCEs following primary ACS events.

Survival and Factors Associated with Survival with Extracorporeal Life Support During Cardiac Arrest: A Systematic Review and Meta-Analysis.

The survival rate after cardiac arrest (CA) remains low. The utilization of extracorporeal life support is proposed to improve management. However, this resource-intensive tool is associated with complications and must be used in selected patients. We performed a meta-analysis to determine predictive factors of survival. Among the 81 studies included, involving 9256 patients, survival was 26.2% at discharge and 20.4% with a good neurologic outcome. Meta-regressions identified an association between survival at discharge and lower lactate values, intrahospital CA, and lower cardio pulmonary resuscitation (CPR) duration. After adjustment for age, intrahospital CA, and mean CPR duration, an initial shockable rhythm was the only remaining factor associated with survival to discharge (ß = 0.02, 95% CI: 0.007-0.02; p = 0.0004).

Impact of Platelet Reactivity in ACS Patients on Clinical Outcomes with Triple Antithrombotic Therapy.

Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients on oral anticoagulants (OAC) remains a clinical conundrum. In fact, combining an OAC with dual antiplatelet therapy (triple antithrombotic therapy, TAT) increases the risk of bleeding. Clopidogrel is the only thienopyridine recommended in TAT patients. Whether its response plays a relevant role in this setting remains uncertain. We aimed to evaluate the level of platelet reactivity inhibition (PRI) achieved by oral TAT in Acute Coronary Syndrome (ACS) patients undergoing PCI and its relationship with outcomes. We performed a multicenter prospective observational study and assessed PRI by vasodilator-stimulated phosphoprotein (VASP) index following a loading dose of clopidogrel. The primary endpoint was the incidence of major adverse cerebral or cardiovascular events (MACCE) at six months based on High on Treatment Platelet Reactivity (HTPR, VASP > 50%). The secondary endpoint was the incidence of bleeding at six months based on Low on Treatment Platelet Reactivity (LTPR, VASP < 16%). 491 patients were followed up for six months: 7.7% experienced MACCE and 17.3% experienced bleeding. There was no significant relationship between HTPR and MACCE, neither between LTPR and bleeding. Vitamin-K antagonist (VKA) treatment was associated with more MACCE and bleeding events, and the majority of events occurred within the first months. VASP index failed to predict outcomes in post-ACS patients with TAT. We confirm that direct acting OAC should be prioritized over VKA in TAT regimen.

Antithrombotic strategies in elderly patients with acute coronary syndrome.

Elderly patients represent a growing proportion of the acute coronary syndrome population in Western countries. However, their frequent atypical symptoms at presentation often lead to delays in management and to misdiagnosis. Furthermore, their prognosis is poorer than that of younger patients because of physiological changes in platelet function, haemostasis and fibrinolysis, but also a higher proportion of comorbidities and frailty, both of which increase the risk of recurrent thrombotic and bleeding events. This complex situation, with ischaemic and haemorrhagic risk factors often being intertwined, may lead to confusion about the required treatment strategy, sometimes resulting in inadequate management or even to therapeutic nihilism. It is therefore critical to provide a comprehensive overview of our understanding of the pathophysiological processes underlying acute coronary syndrome in elderly patients, and to summarise the results from the latest clinical trials to help decision making for these high-risk patients.

Impella CP Implantation during Cardiopulmonary Resuscitation for Cardiac Arrest: A Multicenter Experience.

BACKGROUND: Impella CP is a left ventricular pump which may serve as a circulatory support during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). Nevertheless, the survival rate and factors associated with survival in patients undergoing Impella insertion during CPR for CA are unknown. METHODS: We performed a retrospective multicenter international registry of patients undergoing Impella insertion during on-going CPR for in- or out-of-hospital CA. We recorded immediate and 30-day survival with and without neurologic impairment using the cerebral performance category score and evaluated the factors associated with survival. RESULTS: Thirty-five patients had an Impella CP implanted during CPR for CA. Refractory ventricular arrhythmias were the most frequent initial rhythm (65.7%). In total, 65.7% of patients immediately survived. At 30 days, 45.7% of patients were still alive. The 30-day survival rate without neurological impairment was 37.1%. In univariate analysis, survival was associated with both an age < 75 years and a time from arrest to CPR ≤ 5 min (p = 0.035 and p = 0.008, respectively). CONCLUSIONS: In our multicenter registry, Impella CP insertion during ongoing CPR for CA was associated with a 37.1% rate of 30-day survival without neurological impairment. The factors associated with survival were a young age and a time from arrest to CPR ≤ 5 min.

Acute Coronary Syndrome in the Era of SARS-CoV-2 Infection: A Registry of the French Group of Acute Cardiac Care.

BACKGROUND: In this study, we aimed to report clinical characteristics and outcomes of patients with and without SARS-CoV-2 infection who were referred for acute coronary syndrome (ACS) during the peak of the pandemic in France. METHODS: We included all consecutive patients referred for ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) during the first 3 weeks of April 2020 in 5 university hospitals (Paris, south, and north of France), all performing primary percutaneous coronary intervention. RESULTS: The study included 237 patients (67 ± 14 years old; 69% male), 116 (49%) with STEMI and 121 (51%) with NSTEMI. The prevalence of SARS-CoV-2-associated ACS was 11% (n = 26) and 11 patients had severe hypoxemia on presentation (mechanical ventilation or nasal oxygen > 6 L/min). Patients were comparable regarding medical history and risk factors, except a higher prevalence of diabetes mellitus in SARS-CoV-2 patients (53.8% vs 25.6%; P = 0.003). In SARS-CoV-2 patients, cardiac arrest on admission was more frequent (26.9% vs 6.6%; P < 0.001). The presence of significant coronary artery disease and culprit artery occlusion in SARS-CoV-2 patients respectively, was 92% and 69.4% for those with STEMI, and 50% and 15.5% for those with NSTEMI. Percutaneous coronary intervention was performed in the same percentage of STEMI (84.6%) and NSTEMI (84.8%) patients, regardless of SARS-CoV-2 infection, but no-reflow (19.2% vs 3.3%; P < 0.001) was greater in SARS-CoV-2 patients. In-hospital death occurred in 7 SARS-CoV-2 patients (5 from cardiac cause) and was higher compared with noninfected patients (26.9% vs 6.2%; P < 0.001). CONCLUSIONS: In this registry, ACS in SARS-CoV-2 patients presented with high a percentage of cardiac arrest on admission, high incidence of no-reflow, and high in-hospital mortality.

CONTEXTE: Notre étude avait pour but d'établir les caractéristiques cliniques et les résultats de patients infectés ou non par le SRAS-CoV-2 qui ont été orientés en raison d'un syndrome coronarien aigu (SCA) pendant la phase aiguë de la pandémie en France. MÉTHODOLOGIE: Nous avons inclus dans l'étude tous les patients consécutifs qui ont présenté un infarctus du myocarde avec sus-décalage du segment ST (STEMI) ou sans sus-décalage du segment ST (NSTEMI) au cours des 3 premières semaines d'avril 2020 et qui ont été orientés vers 5 hôpitaux universitaires (situés à Paris, ainsi que dans le sud et le nord de la France), tous en mesure de réaliser des interventions co-ronariennes percutanées primaires. RÉSULTATS: L'étude comprenait 237 patients (âge : 67 ± 14 ans; proportion d'hommes : 69 %); 116 (49 %) présentaient un STEMI et 121 (51 %), un NSTEMI. La prévalence d'un SCA associé à une infection par le SRAS-CoV-2 s'établissait à 11 % (n = 26), et 11 patients étaient en hypoxémie grave (nécessitant une ventilation artificielle ou l'administration d'oxygène par voie nasale à un débit de plus de 6 l/min) à leur arrivée. Les patients présentaient des antécédents médicaux et des facteurs de risque comparables, à l'exception du fait que la prévalence du diabète était plus élevée chez les patients infectés par le SRAS-CoV-2 (53,8 % vs 25,6 %; p = 0,003). Ces derniers avaient plus souvent subi un arrêt cardiaque à leur admission (26,9 % vs 6,6 %; p < 0,001). Chez les patients infectés par le SRAS-CoV-2, une coronaropathie importante et une occlusion de l'artère coupable ont été observées chez respectivement 92 % et 69,4 % des patients présentant un STEMI, et chez 50 % et 15,5 % des patients présentant un NSTEMI. Une intervention coronarienne percutanée a été effectuée dans les mêmes proportions chez les patients subissant un STEMI (84,6 %) que chez ceux présentant un NSTEMI (84,8 %), sans égard à la présence ou à l'absence d'une infection par le SRAS-CoV-2, mais les cas de non-reperfusion (no-reflow) ont été plus fréquents chez les patients infectés que chez les autres patients (19,2 % et 3,3 %, respectivement; p < 0,001). Sept patients infectés par le SRAS-CoV-2 sont morts à l'hôpital (5 de cause cardiaque), ce qui représente un taux de mortalité plus élevé que chez les patients non infectés (26,9 % vs 6,2 %; p < 0,001). CONCLUSIONS: Dans le cadre de cette étude, le SCA survenu chez les patients infectés par le SRAS-CoV-2 était associé à un fort pourcentage d'arrêt cardiaque à l'admission, à une fréquence élevée de cas de non-reperfusion et à un taux élevé de mortalité hospitalière.

On-Ticagrelor Platelet Reactivity and Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome.

BACKGROUND: A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting. OBJECTIVES: We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI. METHODS: We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction, stroke, and urgent revascularization. RESULTS: We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥2 or with MACE (p = 0.12 and p = 0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor when it was analyzed qualitatively (low on-treatment PR [LTPR] vs. no LTPR). CONCLUSION: On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.

Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis.

BACKGROUND: Myocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue. Therefore, we aimed to investigate and compare the clinical course, management and outcome of ICI-induced myocarditis patients requiring or not requiring IIST. METHODS: This case-control study included all patients consecutively admitted to The Mediterranean University Center of Cardio-Oncology (Aix-Marseille University, France) for the diagnosis of ICI-induced myocarditis according to Bonaca's criteria and treated with or without IIST. In addition, we searched PubMed and included patients from previously published case reports treated with IIST in the analysis. The clinical, biological, imaging, treatment, all-cause death and cardiovascular death data of patients who required IIST were compared with those of patients who did not. RESULTS: A total of 60 patients (69±12 years) were included (36 were treated with IIST and 24 were not). Patients requiring IIST were more likely to have received a combination of ICIs (39% vs 8%, p=0.01), and developed the first symptoms/signs of myocarditis earlier after the onset of ICI therapy (median, 18 days vs 60 days, p=0.002). They had a significantly higher prevalence of sustained ventricular arrhythmia, complete atrioventricular block, cardiogenic shock and troponin elevation. Moreover, they were more likely to have other immune-related adverse events simultaneously (p<0.0001), especially myositis (p=0.0002) and myasthenia gravis (p=0.009). Patients who required IIST were more likely to die from any cause (50% vs 21%, p=0.02). Among them, patients who received infliximab were more likely to die from cardiovascular causes (OR, 12.0; 95% CI 2.1 to 67.1; p=0.005). CONCLUSION: The need for IIST was more common in patients who developed myocarditis very early after the start of ICI therapy, as well as when hemodynamic/electrical instability or neuromuscular adverse events occurred. Treatment with infliximab might be associated with an increased risk of cardiovascular death.

Hemodynamic Profiles of Cardiogenic Shock Depending on Their Etiology.

The pathophysiology of cardiogenic shock (CS) varies depending on its etiology, which may lead to different hemodynamic profiles (HP) and may help tailor therapy. We aimed to assess the HP of CS patients according to their etiologies of acute myocardial infarction (AMI) and acute decompensated chronic heart failure (ADCHF). We included patients admitted for CS secondary to ADCHF and AMI. HP were measured before the administration of any inotrope or vasopressor. Systemic Vascular Resistances index (SVRi), Cardiac Index (CI), and Cardiac Power Index (CPI) were measured by trans-thoracic Doppler echocardiography on admission. Among 37 CS patients, 28 had CS secondary to ADCHF or AMI and were prospectively included. The two groups were similar in terms of demographic data and shock severity criteria. AMI CS was associated with lower SVRi compared to CS related to ADCHF: 2010 (interquartile range (IQR): 1895-2277) vs. 2622 (2264-2993) dynes-s·cm-5·m-2 (p = 0.002). A trend toward a higher CI was observed: respectively 2.13 (1.88-2.18) vs. 1.78 (1.65-1.96) L·min-1·m-2 (p = 0.067) in AMICS compared to ADCHF. CS patients had different HP according to their etiologies. AMICS had lower SVR and tended to have a higher CI compared to ADHF CS. These differences should be taken into account for patient selection in future research.

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial.

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Optimal Timing of Intervention in NSTE-ACS Without Pre-Treatment: The EARLY Randomized Trial.

OBJECTIVES: The aim of this study was to compare a delayed and a very early invasive strategy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) without pre-treatment. BACKGROUND: The optimal delay of the invasive strategy in patients with NSTE-ACS remains debated and has never been investigated in patients not pre-treated with P2Y12-adenosine diphosphate receptor antagonists. METHODS: A prospective, open-label, randomized controlled trial was conducted. Altogether, 741 patients presenting with intermediate- or high-risk NSTE-ACS intended for an invasive strategy were included. The modified intention-to-treat analysis was composed of 709 patients after 32 withdrew consent. Patients were randomized 1:1 to the delayed invasive group (DG) (n = 363) with coronary angiography (CA) performed 12 to 72 h after randomization or the very early invasive group (EG) (n = 346) with CA within 2 h. No pre-treatment with a loading dose of a P2Y12-adenosine diphosphate receptor antagonist was allowed before CA. The primary endpoint was the composite of cardiovascular death and recurrent ischemic events at 1 month, as determined by a blinded adjudication committee. RESULTS: Most patients had high-risk NSTE-ACS in both groups (93% in the EG vs. 92.5% in the DG). The median time between randomization and CA was 0 h (interquartile range [IQR]: 0 to 1 h) in the EG group and 18 h (IQR: 11 to 23 h) in the DG. The primary endpoint rate was significantly lower in the EG (4.4% vs. 21.3% in the DG; hazard ratio: 0.20; 95% confidence interval: 0.11 to 0.34; p < 0.001), driven by a reduction in recurrent ischemic events (19.8% vs. 2.9%; p < 0.001). No difference was observed for cardiovascular death. CONCLUSIONS: Without pre-treatment, a very early invasive strategy was associated with a significant reduction in ischemic events at the time of percutaneous coronary intervention in patients with intermediate- and high-risk NSTE-ACS. (Early or Delayed Revascularization for Intermediate and High-Risk Non ST-Elevation Acute Coronary Syndromes; NCT02750579).

Doppler echocardiography for assessment of systemic vascular resistances in cardiogenic shock patients.

OBJECTIVE: Impaired vascular tone plays an important role in cardiogenic shock. Doppler echocardiography provides a non-invasive estimation of systemic vascular resistance. The aim of the present study was to compare Doppler echocardiography with the transpulmonary thermodilution method for the assessment of systemic vascular resistance in patients with cardiogenic shock. METHODS: This prospective monocentric comparison study was conducted in a single cardiology intensive care unit (Hopital Nord, Marseille, France). We assessed the systemic vascular resistance index by both echocardiography and transpulmonary thermodilution in 28 patients admitted for cardiogenic shock, on admission and after the introduction of an inotrope or vasopressor treatment. RESULTS: A total of 35 paired echocardiographic and transpulmonary thermodilution estimations of the systemic vascular resistance index were compared. Echocardiography values ranged from 1309 to 3526 dynes.s.m2/cm5 and transpulmonary thermodilution values ranged from 1320 to 3901 dynes.s.m2/cm5. A statistically significant correlation was found between echocardiography and transpulmonary thermodilution (r=0.86, 95% confidence interval (CI) 0.74, 0.93; P<0.0001). The intraclass correlation coefficient was 0.84 (95% CI 0.72, 0.92). The mean bias was -111.95 dynes.s.m2/cm5 (95% CI -230.06, 6.16). Limits of agreement were -785.86, 561.96. CONCLUSIONS: Doppler echocardiography constitutes an accurate non-invasive alternative to transpulmonary thermodilution to provide an estimation of systemic vascular resistance in patients with cardiogenic shock.

High prevalence of mutations in perilipin 1 in patients with precocious acute coronary syndrome.

BACKGROUND AND AIMS: Genetic partial lipodystrophies are rare heterogeneous disorders characterized by abnormalities of fat distribution and associated metabolic complications including a predisposition for atherosclerotic cardiovascular disease. We hypothesized that the milder forms of these diseases might be underdiagnosed and might result in early acute coronary syndrome (ACS) as the first sign of the pathology. METHODS: We performed targeted sequencing on a panel of 8 genes involved in genetic lipodystrophy for 62 patients with premature ACS, and selected heterozygous missense variations with low frequency. To confirm those results, we analyzed a second independent group of 60 additional patients through Sanger sequencing, and compared to a control group of 120 healthy patients. RESULTS: In the first cohort, only PLIN1 exhibited variants in more than 1 patient. In PLIN1, 3 different variants were found in 6 patients. We then analyzed PLIN1 sequence in the second cohort with premature ACS and found 2 other patients. Altogether, 8 patients were carriers of 4 different mutations in PLIN1. The variant frequencies in the total cohort of 122 patients were compared to frequencies observed in a local control cohort and in 2 different public databases showing a significant difference between patient vs control group frequencies for two mutations out of 4 (c.245C > T p = 10-4; c.839G > A p = 0.014). DISCUSSION: This is the first study that identifies a high frequency of potential pathogenic mutations in PLIN1 related to early onset ACS. These findings could contribute to the prevention and care of precocious ACS in families carrying those mutations.

Etiology and Prognosis of Cardiogenic Shock in a Secondary Center without Surgical Back-Up.

BACKGROUND: Cardiogenic shock (CS) remains a major challenge in contemporary cardiology. Data regarding CS etiologies and their prognosis are limited and mainly derived from tertiary referral centers. AIMS: To investigate the current etiologies of cardiogenic shock and their associated short- and long-term outcomes in a secondary center without surgical back-up. METHODS: We performed an observational prospective monocenter study. All patients admitted for a first episode of CS related to left ventricular dysfunction were enrolled. The definition of CS was consistent with the European Society of Cardiology guidelines. Patients were followed for 6 months. Etiologies were analyzed, and survival rates derived from Kaplan-Meier estimates were compared with the log-rank test. RESULTS: Between January 2015 and January 2016, 152 patients were included. The first most common cause of CS was acute decompensation of chronic heart failure (CHF). Acute coronary syndromes (ACS) were the second most common cause of CS (35.4%). At one month, the all-cause mortality rate was 39.5% and was similar between ACS and CHF (43% vs 35%, respectively; p=0.7). In a landmark analysis between 1 and 6 months, we observed a significantly higher mortality in patients with CHF than in patients with ACS (18% vs. 0%; p=0.01). CONCLUSIONS: In the present registry, acute decompensation of chronic heart failure was the most common cause of CS, while ACS complicated by CS was the second most common cause. Of importance, acute decompensation of CHF was associated with a significantly worse outcome than ACS in the long term.

Platelet reactivity inhibition following ticagrelor loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

BACKGROUND: Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome. OBJECTIVES: We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). METHODS: We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR. RESULTS: Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis. CONCLUSION: In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.