Ticagrelor vs Clopidogrel in Clopidogrel-Naive Patients With Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.

Serum lactate in refractory out-of-hospital cardiac arrest: Post-hoc analysis of the Prague OHCA study.

BACKGROUND: The severity of tissue hypoxia is routinely assessed by serum lactate. We aimed to determine whether early lactate levels predict outcomes in refractory out-of-hospital cardiac arrest (OHCA) treated by conventional and extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This study is a post-hoc analysis of a randomized Prague OHCA study (NCT01511666) assessing serum lactate levels in refractory OHCA treated by ECPR (the ECPR group) or conventional resuscitation with prehospital achieved return of spontaneous circulation (the ROSC group). Lactate concentrations measured on admission and every 4 hours (h) during the first 24 h were used to determine their relationship with the neurological outcome (the best Cerebral Performance Category score within 180 days post-cardiac arrest). RESULTS: In the ECPR group (92 patients, median age 58.5 years, 83% male) 26% attained a favorable neurological outcome. In the ROSC group (82 patients, median age 55 years, 83% male) 59% achieved a favorable neurological outcome. In ECPR patients lactate concentrations could discriminate favorable outcome patients, but not consistently in the ROSC group. On admission, serum lactate >14.0 mmol/L for ECPR (specificity 87.5%, sensitivity 54.4%) and >10.8 mmol/L for the ROSC group (specificity 83%, sensitivity 41.2%) predicted an unfavorable outcome. CONCLUSION: In refractory OHCA serum lactate concentrations measured anytime during the first 24 h after admission to the hospital were found to correlate with the outcome in patients treated by ECPR but not in patients with prehospital ROSC. A single lactate measurement is not enough for a reliable outcome prediction and cannot be used alone to guide treatment.

Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock: Results of the ECMO-CS Randomized Clinical Trial.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used for circulatory support in patients with cardiogenic shock, although the evidence supporting its use in this context remains insufficient. The ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) aimed to compare immediate implementation of VA-ECMO versus 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 standards of care. In the early conservative group, VA-ECMO could be used downstream in case of worsening hemodynamic status. The primary end point 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 because of the absence of informed consent, 117 subjects were included in the analysis, of whom 58 were randomized to immediate VA-ECMO and 59 to no immediate VA-ECMO. The composite primary end point occurred in 37 (63.8%) and 42 (71.2%) patients in the immediate VA-ECMO and the no early VA-ECMO groups, respectively (hazard ratio, 0.72 [95% CI, 0.46-1.12]; 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.% versus 13.6%; risk difference, -3.2 [95% CI, -15.0 to 8.5]), all-cause mortality (50.0% versus 47.5%; risk difference, 2.5 [95% CI, -15.6 to 20.7]), serious adverse events (60.3% versus 61.0%; risk difference, -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. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02301819.

CPR-related injuries after non-traumatic out-of-hospital cardiac arrest: Survivors versus non-survivors.

AIM: There have been no direct comparisons of cardiopulmonary resuscitation (CPR)-related injuries between those who die during CPR and those who survive to intensive care unit (ICU) admission. This study aimed to compare the incidence, severity, and impact on survival rate of these injuries and potential influencing factors. METHOD: This retrospective multicenter study analyzed autopsy reports of patients who experienced out-of-hospital cardiac arrest (OHCA) and were not admitted to hospital. CPR-related injuries were compared to OHCA patients with clinical suspicion of CPR-related injury confirmed on imaging when admitted to the ICU. RESULTS: A total of 859 out-of-hospital cardiac arrests (OHCA) were divided into 2 groups: those who died during CPR and underwent autopsy (DEAD [n = 628]); and those who experienced return of spontaneous circulation and admitted to the ICU (ICU [n = 231]). Multivariable analyses revealed that independent factors of 30-day mortality included no bystander arrest, cardiac etiology, no shockable rhythm, and CPR-related injury. Trauma was independently associated with older age, bystander CPR, cardiac etiology, duration of CPR, and no defibrillation. CPR-related injury occurred in 30 (13%) patients in the ICU group and 547 (87%) in the DEAD group (p < 0.0001). Comparison of injuries revealed that those in the DEAD group experienced more thoracic injuries, rib(s) and sternal fractures, and fewer liver injuries compared to those in the ICU group, without differences in injury severity. CONCLUSION: CPR-related injuries were observed more frequently in those who died compared with those who survived to ICU admission. Injury was an independent factor of 30-day mortality.

Bypassing out-of-hospital cardiac arrest patients to a regional cardiac center: Impact on hemodynamic parameters and outcomes.

INTRODUCTION: Current guidelines recommend systematic care for patients who experience out-of-hospital cardiac arrest (OHCA) and the development of cardiac arrest centers (CACs). However, data regarding prolonged transport time of these often hemodynamically unstable patients are limited. METHODS: Data from a prospective OHCA registry of a regional CAC collected between 2013 and 2017, when all OHCA patients from the district were required to be transferred directly to the CAC, were analyzed. Patients were divided into two subgroups: CAC, when the CAC was the nearest hospital; and bypass, when OHCA occurred in a region of another local hospital but the subject was transferred directly to the CAC (7 hospitals in the district). Data included transport time, baseline characteristics, hemodynamic and laboratory parameters on admission (systolic blood pressure, lactate, pH, oxygen saturation, body temperature, and initial doses of vasopressors and inotropes), and final outcomes (30-day in-hospital mortality, intensive care unit stay, days on artificial ventilation, and cerebral performance capacity at 1 year). RESULTS: A total of 258 subjects experienced OHCA in the study period; however, 27 were excluded due to insufficient data and 17 for secondary transfer to CAC. As such, 214 patients were analyzed, 111 in the CAC group and 103 in the bypass group. The median transport time was significantly longer for the bypass group than the CAC group (40.5 min [IQR 28.3-55.0 min] versus 20.0 min [IQR 13.0-34.0], respectively; p˂0.0001). There were no differences in 30-day in-hospital mortality, 1-year neurological outcome, or median length of mechanical ventilation. There were no differences in baseline characteristics, initial hemodynamic parameters on admission, catecholamine dosage(s). CONCLUSION: Individuals who experienced OHCA and taken to a CAC incurred significantly prolonged transport times; however, hemodynamic parameters and/or outcomes were not affected. These findings shows the safety of bypassing local hospitals for a CAC.

LUCAS II Device for Cardiopulmonary Resuscitation in a Nonselective Out-of-Hospital Cardiac Arrest Population Leads to Worse 30-Day Survival Rate Than Manual Chest Compressions.

BACKGROUND: The LUCAS (Lund University Cardiopulmonary Assist System; Physio-Control Inc./Jolife AB, Lund, Sweden) was developed for automatic chest compressions during cardiopulmonary resuscitation (CPR). Evidence on the use of this device in out-of-hospital cardiac arrest (OHCA) suggests that it should not be used routinely because it has no superior effects. OBJECTIVE: The aim of this study was to compare the effect of CPR for OHCA with and without LUCAS via a regional nonurban emergency medical service (EMS) physician-present prehospital medical system. METHODS: We analyzed a prospective registry of all consecutive OHCA patients in four EMS stations. Two of them used a LUCAS device in all CPR, and the EMS crews in the other two stations used manual CPR. Individuals with contraindication to LUCAS or with EMS-witnessed arrest were excluded. RESULTS: Data from 278 patients were included in the analysis, 144 with LUCAS and 134 with manual CPR. There were more witnessed arrests in the LUCAS group (79.17% vs. 64.18%; p = 0.0074) and patients in the LUCAS group were older (p = 0.03). We found no significant difference in return of spontaneous circulation (30.6% in non-LUCAS vs. 25% in LUCAS; p = 0.35). In the LUCAS group, we observed significantly more conversions from nonshockable to shockable rhythm (20.7% vs. 10.10%; p = 0.04). The 30-day survival rate was significantly lower in the LUCAS group (5.07% vs. 16.31% in the non-LUCAS group; p = 0.044). At 180-day follow-up, we observed no significant difference (5.45% in non-LUCAS vs. 9.42% in LUCAS; p = 0.25). CONCLUSIONS: Use of the LUCAS system decreased survival rate in OHCA patients. Significantly higher 30-day mortality was seen in LUCAS-treated patients.

Acute heart failure registry from high-volume university hospital ED: comparing European and US data.

BACKGROUND: Acute heart failure (AHF) is associated with a poor prognosis. OBJECTIVES: The objectives of this study are to describe mechanisms of AHF and to identify the predictors for all-cause mortality by patients admitted for hospitalization by emergency departments (EDs) as well as to compare European and American data. METHODS: We designed a prospective registry of consecutively admitted patients for AHF to a high-volume university hospital ED during a 1-year period (n=202; age, 75±11 years; 51% men; ejection fraction, 38%±15%). RESULTS: The major causes of AHF were coronary artery disease, often with concomitant mitral regurgitation, hypertension, or atrial fibrillation (>90% of cases). At admission, 24.9% of patients had preserved ejection fractions (>50%); and only 7.7% fulfilled the definition of diastolic AHF. The 30-day and long-term mortality (median follow-up, 793 days) were 20.3% and 31.0%, respectively. A low systolic blood pressure (P=.006), reduced ejection fraction (P=.044), and low serum hemoglobin level (P<.01) emerged as the strongest predictors of all-cause mortality. In patients with AHF without acute myocardial infarction (MI) (63.9%), prescription, at discharge, of statins (P<.05) was independently associated with all-cause mortality. CONCLUSIONS: The patient's blood pressure, ejection fraction, and hemoglobin values, at admission, were identified as the strongest predictors of all-cause mortality. In AHF not triggered by acute MI, long-term use of statins may be associated with reduced survival. The prevalence of diastolic AHF is low. The American AHF population had similar baseline characteristics; needed fewer intensive care unit admissions; had a better 30 days of prognosis, lower incidence of MI, and de novo AHF diagnoses. In a similar subgroup, we observed similar incidences of inotropic support and mechanical ventilation. Our results could not be generalized to all patients with AHF admitted to US EDs.

Heart failure with preserved ejection fraction in outpatients with unexplained dyspnea: a pressure-volume loop analysis.

OBJECTIVES: The aim of the present study was to diagnose heart failure with preserved ejection fraction (HFPEF) in outpatients with unexplained chronic dyspnea and to elucidate its underlying mechanisms in this population using invasive pressure-volume loop analysis. BACKGROUND: The diagnosis of HFPEF in stable outpatients with unexplained dyspnea is difficult. METHODS: Thirty patients (age 67 +/- 8.6 years, 27% males) with preserved left ventricular (LV) ejection fraction (>50%) and unexplained chronic New York Heart Association functional class II to III dyspnea underwent heart catheterization. Patients with significant coronary artery stenosis (>50%) were excluded. Pressure-volume loops were assessed using a conductance catheter at rest, hand-grip exercise, leg lifting, and nitroprusside and dobutamine infusion. RESULTS: Twenty (66%) patients showed LV end-diastolic pressure >16 mm Hg (HFPEF), whereas the remaining 10 patients served as controls. Patients with HFPEF had significantly higher end-diastolic stiffness (0.205 +/- 0.074 vs. 0.102 +/- 0.017, p < 0.001) at rest, and their end-diastolic pressure-volume relationship showed a consistent upward and leftward shift during all hemodynamic interventions compared with controls. Regarding the underlying mechanism of HFPEF, 14 (70%) patients had markedly increased end-diastolic stiffness, which was considered a sufficient single pathology to induce increased LV end-diastolic pressure. Four (20%) patients showed a concomitant presence of moderately increased stiffness and severe LV dyssynchrony, and the remaining 2 (10%) patients, with normal stiffness, showed significant exercise-induced mitral regurgitation at hand-grip exercise. If the invasive pressure measurements were absent, only 5 (25%) of the outpatients with HFPEF fulfilled the European Society of Cardiology definition of HFPEF. CONCLUSIONS: A significant proportion of stable outpatients with unexplained chronic dyspnea may have HFPEF. In the patients whom we studied, increased LV stiffness, dyssynchrony, and dynamic mitral regurgitation were the major mechanisms underlying development of HFPEF.

Tissue Doppler predicts long-term clinical outcome after cardiac resynchronization therapy.

BACKGROUND: Pulsed-wave tissue Doppler imaging (TDI) was shown to predict short-term left ventricular functional recovery after cardiac resynchronization therapy (CRT). However, few data are available regarding the baseline cardiac asynchrony and clinical outcome after CRT. Therefore, we aimed to investigate the prognostic value of pre-CRT cardiac asynchrony on clinical outcome after CRT. METHODS: The study population consisted of 48 consecutive patients with moderate to severe heart failure and a wide QRS complex undergoing implantation of biventricular pacemaker. Cardiac asynchrony was assessed at pulsed-wave TDI from measurements of regional electromechanical coupling times in basal segments of both ventricles (Sum asynchrony). Clinical end-points were cardiac mortality and hospitalization for worsening heart failure. RESULTS: During a follow-up period of 970+/-319 days, clinical end-point (9 deaths, 15 hospitalizations) occurred in 24 patients (clinical nonresponders). At baseline, responders showed higher asynchrony than nonresponders (153+/-57 ms vs. 103+/-58 ms, p<0.01). Sum asynchrony of >98 ms showed the highest accuracy (AUC=0.80, sensitivity 92%, specificity 67%) to identify responders. In contrast, baseline NYHA class, conventional echo-Doppler indices and QRS complex duration were similar in both groups. Eight end-point events (3 deaths) occurred in 30 patients with significant Sum asynchrony (>98 ms) as compared to 16 events (6 deaths) in 18 patients with smaller Sum asynchrony (27% vs. 89%; HR 0.14; 95% CI 0.04 to 0.46; p<0.001). Favorable clinical outcome was associated with larger left ventricular functional recovery at 2 years follow-up (p<0.001). CONCLUSIONS: TDI-derived index of baseline intra- and interventricular asynchrony appears to predict long-term clinical outcome after CRT.