GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history. METHODS AND RESULTS: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63-0.98; HF: HR = 1.00, 95% CI 0.82-1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71-0.92; HF: HR = 0.97, 95% CI 0.81-1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72-0.89; HF: HR = 1.00 95% CI 0.88-1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78-0.96; HF: HR = 0.83, 95% CI 0.72-0.95, pinteraction = 0.69). CONCLUSION: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264).

Differences between cardiogenic shock related to acute decompensated heart failure and acute myocardial infarction.

AIMS: The present analysis from the multicentre prospective Altshock-2 registry aims to better define clinical features, in-hospital course, and management of cardiogenic shock complicating acutely decompensated heart failure (ADHF-CS) as compared with that complicating acute myocardial infarction (AMI-CS). METHODS AND RESULTS: All patients with AMI-CS or ADHF-CS enrolled in the Altshock-2 registry between March 2020 and February 2022 were selected. The primary objective was the characterization of ADHF-CS patients as compared with AMI-CS. In-hospital length of stay and mortality were secondary endpoints. One-hundred-ninety of the 238 CS patients enrolled in the aforementioned period were considered for the present analysis: 101 AMI-CS (80% ST-elevated myocardial infarction and 20% non-ST-elevated myocardial infarction) and 89 ADHF-CS. As compared with AMI-CS, ADHF-CS patients were younger [63 (IQR 59-76) vs. 67 (IQR 54-73) years, P = 0.01], but presented with higher creatinine [1.6 (IQR 1.0-2.6) vs. 1.2 (IQR 1.0-1.4) mg/dL, P < 0.001], bilirubin [1.3 (IQR 0.9-2.3) vs. 0.6 (IQR 0.4-1.1) mg/dL, P = 0.01], and central venous pressure values [14 mmHg (IQR 8-12) vs. 10 mmHg (IQR 7-14),P = 0.01]. Norepinephrine was the most common catecholamine used in AMI-CS (79.3%), whereas epinephrine was used more commonly in ADHF-CS (65.5%); 75.8% vs. 46.6% received a temporary mechanical support in AMI-CS and ADHF-CS, respectively (P < 0.001). Length of hospital stay was longer in the latter [28 (IQR 13-48) vs. 17 (IQR 9-29) days, P = 0.001]. Heart replacement therapies were more frequently used in the ADHF-CS group (heart transplantation 13.5% vs. 0% and left ventricular assist device 11% vs. 2%, P < 0.01 and 0.01, respectively). In-hospital mortality was 41.1% (38.6% AMI-CS vs. 43.8% ADHF-CS, P = 0.5). CONCLUSIONS: ADHF-CS is characterized by a higher prevalence of end-organ and biventricular dysfunction at presentation, a longer hospital length of stay, and higher need of heart replacement therapies when compared with AMI-CS. In-hospital mortality was similar between the two aetiologies. Our data warrant development of new management protocols focused on CS aetiology.

SCAI stage reclassification at 24 h predicts outcome of cardiogenic shock: Insights from the Altshock-2 registry.

BACKGROUND: Cardiogenic shock (CS) includes several phenotypes with heterogenous hemodynamic features. Timely prognostication is warranted to identify patients requiring treatment escalation. We explored the association of the updated Society for Cardiovascular Angiography and Interventions (SCAI) stages classification with in-hospital mortality using a prospective national registry. METHODS: Between March 2020 and February 2022 the Altshock-2 Registry has included 237 patients with CS of all etiologies at 11 Italian Centers. Patients were classified according to their admission SCAI stage (assigned prospectively and independently updated according to the recently released version). In-hospital mortality was evaluated for association with both admission and 24-h SCAI stages. RESULTS: The overall in-hospital mortality was 38%. Of the 237 patients included and staged according to the updated SCAI classification, 20 (8%) had SCAI shock stage B, 131 (55%) SCAI stage C, 61 (26%) SCAI stage D and 25 (11%) SCAI stage E. In-hospital mortality stratified according to the SCAI classification at 24 h was 18% for patients in SCAI stage B, 27% for SCAI stage C, 63% for SCAI stage D and 100% for SCAI stage E. Both the revised SCAI stages on admission and at 24 h were associated with in-hospital mortality, but the classification potential slightly increased at 24-h. After adjusting for age, sex, lactate level, eGFR, CVP, inotropic score and mechanical circulatory support [MCS], SCAI classification at 24 h was an independent predictor of in-hospital mortality. CONCLUSIONS: In the Altshock-2 registry the utility of SCAI shock stages to identify risk of in-hospital mortality increased at 24 h after admission. Escalation of treatment (either pharmacological or with MCS) should be tailored to achieve prompt clinical improvement within the first 24 h after admission. Registration: http://www. CLINICALTRIALS: gov; Unique identifier: NCT04295252.

Impact of hemoglobin levels at admission on outcomes among elderly patients with acute coronary syndrome treated with low-dose Prasugrel or clopidogrel: A sub-study of the ELDERLY ACS 2 trial.

Hemoglobin (Hb) levels have emerged as a useful tool for risk stratification and the prediction of outcome after myocardial infarction. We aimed at evaluating the prognostic impact of this parameter among patients in advanced age, where the larger prevalence of anemia and the higher rate of comorbidities could directly impact on the cardiovascular risk. METHODS: All the patients in the ELDERLY-2 trial, were included in this analysis and stratified according to the values of hemoglobin at admission. The primary endpoint of this study was cardiovascular mortality within one year. The secondary endpoints were all-cause mortality, MI, Bleeding Academic Research Consortium (BARC) type 2-3 or 5 bleeding, any stroke, re-hospitalization for cardiovascular event or stent thrombosis (probable or definite) within 12 months after index admission. RESULTS: We included in our analysis 1364 patients, divided in quartiles of Hb values (<12.2; 12.2-13.39; 13.44-14.49; ≥ 4.5 g/dl). At a mean follow- up of 330.4 ± 99.9 days cardiovascular mortality was increased in patients with lower Hb (HR[95%CI] = 0.76 [0.59-0.97], p = 0.03). Results were no more significant after correction for baseline differences (adjusted HR[95%CI] = 1.22 [0.41-3.6], p = 0.16). Similar results were observed for overall mortality. At subgroup analysis, (according to Hb median values) a significant interaction was observed only with the type of antiplatelet therapy, but not with major high-risk subsets of patients. CONCLUSIONS: Among elderly patients with acute coronary syndrome managed invasively, lower hemoglobin at admission is associated with higher cardiovascular and all-cause mortality and major ischemic events, mainly explained by the higher risk profile.

Association of Sex with Outcome in Elderly Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Worse outcomes have been reported for women, compared with men, after an acute coronary syndrome (ACS). Whether this difference persists in elderly patients undergoing similar invasive treatment has not been studied. We investigated sex-related differences in 1-year outcome of elderly acute coronary syndrome patients treated by percutaneous coronary intervention (PCI). METHODS: Patients 75 years and older successfully treated with PCI were selected among those enrolled in 3 Italian multicenter studies. Cox regression analysis was used to assess the independent predictive value of sex on outcome at 12-month follow-up. RESULTS: A total of 2035 patients (44% women) were included. Women were older and most likely to present with ST-elevation myocardial infarction (STEMI), diabetes, hypertension, and renal dysfunction; men were more frequently overweight, with multivessel coronary disease, prior myocardial infarction, and revascularizations. Overall, no sex disparity was found about all-cause (8.3% vs 7%, P = .305) and cardiovascular mortality (5.7% vs 4.1%, P = .113). Higher cardiovascular mortality was observed in women after STEMI (8.8%) vs 5%, P = .041), but not after non ST-elevation-ACS (3.5% vs 3.7%, P = .999). A sensitivity analysis excluding patients with prior coronary events (N = 1324, 48% women) showed a significantly higher cardiovascular death in women (5.4% vs 2.9%, P = .025). After adjustment for baseline clinical variables, female sex did not predict adverse outcome. CONCLUSIONS: Elderly men and women with ACS show different clinical presentation and baseline risk profile. After successful PCI, unadjusted 1-year cardiovascular mortality was significantly higher in women with STEMI and in those with a first coronary event. However, female sex did not predict cardiovascular mortality after adjustment for the different baseline variables.

[Percutaneous mitral valve repair in acute mitral regurgitation]. / Plastica mitralica transcatetere per il trattamento dell'insufficienza mitralica acuta.

Acute mitral regurgitation is a life-threatening pathology. Nowadays, percutaneous mitral valve repair with the MitraClip device offers, in selected patients, a safe and effective therapeutic alternative to open surgery. Hereby, we report the case of an 82-year-old woman with lateral ST-elevation myocardial infarction determining severe acute mitral regurgitation, who was treated with an urgent MitraClip procedure. Moreover, we discuss echocardiographic assessment of acute mitral regurgitation and we review available literature and possible management of this complex scenario.

Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.

BACKGROUND: Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap. METHODS AND DESIGN: The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients. IMPLICATIONS: The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.

Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Although oral P2Y12 inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined. OBJECTIVES: The purpose of this study was to compare downstream and upstream oral P2Y12 inhibitors administration strategies in patients with non-ST-segment elevation acute coronary syndrome undergoing invasive treatment. METHODS: We performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit). RESULTS: We randomized 1,449 patients to downstream or upstream oral P2Y12 inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: -0.46; 95% repeated confidence interval: -2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment). CONCLUSIONS: Downstream and upstream oral P2Y12 inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y12 Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837).

Early detection of elevated cardiac biomarkers to optimise risk stratification in patients with COVID-19.

OBJECTIVE: Risk stratification is crucial to optimise treatment strategies in patients with COVID-19. We aimed to evaluate the impact on mortality of an early assessment of cardiac biomarkers in patients with COVID-19. METHODS: Humanitas Clinical and Research Hospital (Rozzano-Milan, Lombardy, Italy) is a tertiary centre that has been converted to the management of COVID-19. Patients with confirmed COVID-19 were entered in a dedicated database for cohort observational analyses. Outcomes were stratified according to elevated levels (ie, above the upper level of normal) of high-sensitivity cardiac troponin I (hs-TnI), B-type natriuretic peptide (BNP) or both measured within 24 hours after hospital admission. The primary outcome was all-cause mortality. RESULTS: A total of 397 consecutive patients with COVID-19 were included up to 1 April 2020. At the time of hospital admission, 208 patients (52.4%) had normal values for cardiac biomarkers, 90 (22.7%) had elevated both hs-TnI and BNP, 59 (14.9%) had elevated only BNP and 40 (10.1%) had elevated only hs-TnI. The rate of mortality was higher in patients with elevated hs-TnI (22.5%, OR 4.35, 95% CI 1.72 to 11.04), BNP (33.9%, OR 7.37, 95% CI 3.53 to 16.75) or both (55.6%, OR 18.75, 95% CI 9.32 to 37.71) as compared with those without elevated cardiac biomarkers (6.25%). A multivariate analysis identified concomitant elevation of both hs-TnI and BNP as a strong independent predictor of all-cause mortality (OR 3.24, 95% CI 1.06 to 9.93). CONCLUSIONS: An early detection of elevated hs-TnI and BNP predicts mortality in patients with COVID-19. Cardiac biomarkers should be systematically assessed in patients with COVID-19 at the time of hospital admission in order to optimise risk stratification.

Residual SYNTAX Score and One-Year Outcome in Elderly Patients With Acute Coronary Syndrome.

BACKGROUND: The residual burden of coronary artery disease after percutaneous coronary intervention (PCI) has been associated with worse ischemic outcome. However, data are conflicting in elderly patients. The aim of our study was to verify the incremental value of the residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (rSS) over clinical variables and baseline SYNTAX score (bSS) in predicting 1-year mortality or cardiovascular events. METHODS: A post hoc analysis of data collected in the Elderly-ACS 2 multicenter randomized trial was performed. We included 630 patients aged > 75 years with multivessel coronary disease undergoing PCI for acute coronary syndrome (ACS). The primary outcome was a composite of death, recurrent myocardial infarction, and stroke at 1-year follow up. Change in c-statistic and standardized net benefit were used to evaluate the incremental value of the rSS. RESULTS: Event rates were significantly higher in patients with incomplete revascularization (rSS > 8). When the rSS was included in a core Cox regression model containing age, previous myocardial infarction, and ACS type, the hazard ratio for patients with score values > 8 was 2.47 (95% confidence interval, 1.51-4.06). However, the core model with rSS did not increase the c-statistic compared with the core model with the bSS (from 0.69 to 0.70) and gave little incremental value in the standardized net benefit. CONCLUSIONS: In elderly patients with ACS with multivessel disease undergoing PCI, incomplete revascularization was associated with worse outcome at 1-year follow-up. However, there was no clear incremental value of the rSS in the prediction of 1-year adverse outcome compared with a model including clinical variables and bSS.

CONTEXTE: Le fardeau résiduel de la coronaropathie après une intervention coronarienne percutanée (ICP) a été associé à de moins bons résultats sur le plan ischémique. Les données recueillies chez les patients âgés sont toutefois contradictoires. Cette étude avait donc pour objectif de valider la valeur ajoutée du score SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) résiduel (SSr) par rapport aux paramètres cliniques et au score SYNTAX initial (SSi) pour prédire la mortalité à 1 an et les manifestations cardiovasculaires. MÉTHODOLOGIE: Une analyse a posteriori des données de l'étude multicentrique avec répartition aléatoire Elderly-ACS 2 a été effectuée. Pour ce faire, 630 patients âgés de plus de 75 ans, atteints d'une coronaropathie multitronculaire et ayant subi une ICP pour traiter un syndrome coronarien aigu (SCA) ont été retenus. Le critère d'évaluation principal était composé du décès, de l'infarctus du myocarde récurrent et de l'accident vasculaire cérébral (AVC) au moment du suivi à 1 an. La variation de la statistique C et le bénéfice net normalisé ont servi à évaluer la valeur ajoutée du SSr. RÉSULTATS: Les manifestations étaient significativement plus fréquentes chez les patients dont la revascularisation était incomplète (SSr > 8). Lorsque le SSr a été pris en compte dans un modèle de régression de Cox de base ayant pour facteurs l'âge, les antécédents d'infarctus du myocarde et le type de SCA, le rapport des risques instantanés pour les patients ayant un score > 8 était de 2,47 (intervalle de confiance à 95 % : 1,51-4,06). L'intégration du SSr dans le modèle de base n'a toutefois pas donné lieu à une statistique C plus élevée que celle du SSi (0,70 vs 0,69) et conférait peu de valeur ajoutée sur le plan du bénéfice net normalisé. CONCLUSIONS: Chez les patients âgés présentant un SCA et une atteinte multitronculaire, et subissant une ICP, la revascularisation incomplète a été associée à de moins bons résultats au moment du suivi à 1 an. Le SSr n'a toutefois pas été clairement associé à une valeur ajoutée pour prédire une issue défavorable à 1 an comparativement à un modèle reposant sur des paramètres cliniques et le SSi.

Impact of diabetes on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: insights from the ELDERLY ACS 2 trial.

BACKGROUND: Despite recent improvements in percutaneous coronary revascularization and antithrombotic therapies for the treatment of acute coronary syndromes, the outcome is still unsatisfactory in high-risk patients, such as the elderly and patients with diabetes. The aim of the current study was to investigate the prognostic impact of diabetes on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study carried out at 32 centers in Italy. METHODS: Our population is represented by 1443 patients included in the Elderly-ACS 2 trial. Diabetes was defined as known history of diabetes at admission. The primary endpoint of this analysis was cardiovascular mortality, while secondary endpoints were all-cause death, recurrent myocardial infarction, Bleeding Academic Research Consortium type 2 or 3 bleeding, and rehospitalization for cardiovascular event or stent thrombosis within 12 months after index admission. RESULTS: Diabetes was present in 419 (29%) out of 1443 patients. Diabetic status was significantly associated with major cardiovascular risk factors and history of previous coronary disease, presentation with non-ST segment elevation myocardial infarction (P = 0.01) more extensive coronary disease (P = 0.02), more advanced Killip class at presentation (P = 0.003), use at admission of statins (P = 0.004) and diuretics at discharge (P < 0.001). Median follow-up was 367 days (interquartile range: 337-378 days). Diabetic status was associated with an absolute increase in the rate of cardiovascular mortality as compared with patients without diabetes [5.5 vs. 3.3%, hazard ratio (HR) 1.7 (0.99-2.8), P = 0.054], particularly among those treated with clopidogrel [HR (95% confidence interval (CI)) = 1.89 (0.93-3.87), P = 0.08]. However, this difference disappeared after correction for baseline differences [Adjusted HR (95% CI) 1.1(0.4-2.9), P = 0.86]. Similar findings were observed for other secondary endpoints, except for bleeding complications, significantly more frequent in diabetic patients [HR (95% CI) 2.02 (1.14-3.6), P = 0.02; adjusted HR (95% CI) = 2.1 (1.01-4.3), P = 0.05]. No significant interaction was observed between type of dual antiplatelet therapy, diabetic status and outcome. CONCLUSION: Among elderly patients with acute coronary syndromes, diabetic status was associated with higher rates of comorbidities, more severe cardiovascular risk profile and major bleeding complications fully accounting for the absolute increase in mortality. In fact, diabetes mellitus did not emerge as an independent predictor of survival in advanced age.

Impact of body mass index on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: Insights from the ELDERLY ACS 2 trial.

BACKGROUND AND AIM: Elderly patients are at increased risk of hemorrhagic and thrombotic complications after an acute coronary syndrome (ACS). Frailty, comorbidities and low body weight have emerged as conditioning the prognostic impact of dual antiplatelet therapy (DAPT). The aim of the present study was to investigate the prognostic impact of body mass index (BMI) on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study comparing low-dose (5 mg) prasugrel vs clopidogrel among elderly patients with ACS. METHODS AND RESULTS: Our population is represented by 1408 patients enrolled in the Elderly-ACS 2 trial. BMI was calculated at admission. The primary endpoint of this analysis was cardiovascular (CV) mortality. Secondary endpoints were all-cause death, recurrent MI, Bleeding Academic Research Consortium (BARC) type 2 or 3 bleeding, and re-hospitalization for cardiovascular reasons or stent thrombosis within 12 months after index admission. Patients were grouped according to median values of BMI (

Healthcare professionals' knowledge on cardiopulmonary resuscitation correlated with return of spontaneous circulation rates after in-hospital cardiac arrests: A multicentric study between university hospitals in 12 European countries.

BACKGROUND: In-hospital cardiac arrest is a major cause of death in European countries, and survival of patients remains low ranging from 20% to 25%. AIMS: The purpose of this study was to assess healthcare professionals' knowledge on cardiopulmonary resuscitation among university hospitals in 12 European countries and correlate it with the return of spontaneous circulation rates of their patients after in-hospital cardiac arrest. METHODS AND RESULTS: A total of 570 healthcare professionals from cardiology, anaesthesiology and intensive care medicine departments of European university hospitals in Italy, Poland, Hungary, Belgium, Spain, Slovakia, Germany, Finland, The Netherlands, Switzerland, France and Greece completed a questionnaire. The questionnaire consisted of 12 questions based on epidemiology data and cardiopulmonary resuscitation training and 26 multiple choice questions on cardiopulmonary resuscitation knowledge. Hospitals in Switzerland scored highest on basic life support (P=0.005) while Belgium hospitals scored highest on advanced life support (P<0.001) and total score in cardiopulmonary resuscitation knowledge (P=0.01). The Swiss hospitals scored highest in cardiopulmonary resuscitation training (P<0.001). Correlation between cardiopulmonary resuscitation knowledge and return of spontaneous circulation rates of patients with in-hospital cardiac arrest demonstrated that each additional correct answer on the advanced life support score results in a further increase in return of spontaneous circulation rates (odds ratio 3.94; 95% confidence interval 2.78 to 5.57; P<0.001). CONCLUSION: Differences in knowledge about resuscitation and course attendance were found between university hospitals in 12 European countries. Education in cardiopulmonary resuscitation is considered to be vital for patients' return of spontaneous circulation rates after in-hospital cardiac arrest. A higher level of knowledge in advanced life support results in higher return of spontaneous circulation rates.

G-CSF for Extensive STEMI.

RATIONALE: In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term. OBJECTIVE: The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain. METHODS AND RESULTS: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006). CONCLUSIONS: Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.

Mitral Valve Stenosis after Transcatheter Aortic Valve Replacement: Case Report and Review of the Literature.

Mitral stenosis is a rare and potentially severe complication of transcatheter aortic valve replacement (TAVR). Given the anatomic coupling and interdependence of the aortic and mitral valves, it comes by itself that procedures (either surgical or percutaneous) involving the aortic valve imply the risk of altering mitral valve function. Indeed, transcatheter aortic prostheses may impair adequate anterior mitral leaflet (AML) opening, especially when implanted in a "low" position, thus resulting in high transvalvular gradients. Hereby, we report the case of a 71-year-old male with symptomatic severe aortic stenosis and a history of previous surgical mitral valve repair who underwent TAVR with a self-expandable prosthesis. Notwithstanding an acceptable angiographic position, the prosthetic frame was shown to interfere with the AML, as evidenced by augmented transmitral gradients; nonetheless, pulmonary artery pressures remained unchanged, and the patient experienced symptomatic improvement. Therefore, a conservative approach was chosen and the patient was discharged home after medical therapy optimization. Moreover, we provide a review of the available literature regarding the incidence, predictors and possible management of this infrequent complication.

Outcomes of Elderly Patients with ST-Elevation or Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

INTRODUCTION: Acute coronary syndromes (ACS) have been classified according to the finding of ST-segment elevation on the presenting electrocardiogram, with different treatment strategies and practice guidelines. However, a comparative description of the clinical characteristics and outcomes of acute coronary syndrome elderly patients undergoing percutaneous coronary intervention during index admission has not been published so far. METHODS: Retrospective cohort study of patients enrolled in the Elderly ACS-2 multicenter randomized trial. Main outcome measures were crude cumulative incidence and cause-specific hazard ratio (cHR) of cardiovascular death, noncardiovascular death, reinfarction, and stroke. RESULTS: Of 1443 ACS patients aged >75 years (median age 80 years, interquartile range 77-84), 41% were classified as ST-elevation myocardial infarction (STEMI), and 59% had non-ST-elevation ACS (NSTEACS) (48% NSTEMI and 11% unstable angina). As compared with those with NSTEACS, STEMI patients had more favorable baseline risk factors, fewer prior cardiovascular events, and less severe coronary disease, but lower ejection fraction (45% vs 50%, P < .001). At a median follow-up of 12 months, 51 (8.6%) STEMI patients had died, vs 39 (4.6%) NSTEACS patients. After adjusting for sex, age, and previous myocardial infarction, the hazard among the STEMI group was significantly higher for cardiovascular death (cHR 1.85; 95% confidence interval [CI], 1.02-3.36), noncardiovascular death (cHR 2.10; 95% CI, 1.01-4.38), and stroke (cHR 4.8; 95% CI, 1.7-13.7). CONCLUSIONS: Despite more favorable baseline characteristics, elderly STEMI patients have worse survival and a higher risk of stroke compared with NSTEACS patients after percutaneous coronary intervention.

Age at menopause, extent of coronary artery disease and outcome among postmenopausal women with acute coronary syndromes.

BACKGROUND: Early menopause has been associated with increased cardiovascular mortality, but prospective studies investigating outcomes of postmenopausal women with acute coronary syndromes (ACS) in relation to menopausal age are lacking. METHODS: We analyzed the 1-year outcome of 373 women with acute myocardial infarction enrolled in the Ladies ACS study. All patients underwent coronary angiography, with corelab analysis. Menopause questionnaires were administered during admission. Menopausal age below the median of the study population (50 years) was defined as "early menopause". The composite 1-year outcome included all-cause mortality, recurrent myocardial infarction and stroke. RESULTS: The mean age at index ACS was 73 years (IQR 65-83) for women with early menopause, and 74 (IQR 65-80) for those with late menopause. Patients with early menopause had more prevalent chronic kidney disease (12.8% vs 5.9%, p = 0.03), whereas there were no differences in all other clinical characteristics, extent of coronary disease at angiography (as assessed by Gensini and SYNTAX scores), as well as interventional treatments. Within 1 year, women with late menopause had significantly better outcome as compared with those with early menopause (6.5% vs 15.3%, p = 0.007). At logistic regression analysis, late menopause was independently associated with better outcome (OR 0.28; 95% CI 0.12-0.67; p = 0.004). With each year's delay in the menopause the adjusted risk decreased by 12% (OR 0.88, 0.77-0.99, p = 0.040). CONCLUSION: Despite comparable clinical and angiographic characteristics, women with late menopausal age experience better outcomes after an ACS as compared with those with early menopause.

History of vasomotor symptoms, extent of coronary artery disease, and clinical outcomes after acute coronary syndrome in postmenopausal women.

OBJECTIVE: Vasomotor symptoms (VMS) during menopausal transition have been linked to a higher burden of cardiovascular risk factors, subclinical vascular disease, and subsequent vascular events. We aim to investigate the association of VMS with the extent of coronary disease and their prognostic role after an acute coronary syndrome. METHODS: The Ladies Acute Coronary Syndrome study enrolled consecutive women with an acute coronary syndrome undergoing coronary angiography. A menopause questionnaire was administered during admission. Angiographic data underwent corelab analysis. Six out of 10 enrolling centers participated in 1-year follow-up. Outcome data included the composite endpoint of all-cause mortality, recurrent myocardial infarction, stroke, and rehospitalization for cardiovascular causes within 1 year. RESULTS: Of the 415 women with available angiographic corelab analysis, 373 (90%) had complete 1-year follow-up. Among them, 202 women had had VMS during menopausal transition. These women had the same mean age at menopause as those without VMS (50 years in both groups), but were younger at presentation (median age 71 vs 76 years; P < 0.001), despite a more favorable cardiovascular risk profile (chronic kidney dysfunction 4.5% vs 15.9%; P = 0.001; prior cerebrovascular disease 4.5 vs 12.2%; P = 0.018). Extent of coronary disease at angiography was similar between groups (mean Gensini score 49 vs 51; P = 0.6; mean SYNTAX score 14 vs 16; P = 0.3). Overall cardiovascular events at 1 year did not differ between groups (19% vs 22%; P = 0.5). CONCLUSIONS: In postmenopausal women with an acute coronary syndrome, a history of VMS was associated with younger age at presentation, despite a lower vascular disease burden and similar angiographically defined coronary disease as compared with women without VMS. No difference could be found in terms of overall clinical outcomes. These results should be interpreted cautiously as all analyses were unadjusted and did not account for risk factor differences between women with and without a history of VMS.