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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.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.We included in our analysis 1364 patients, divided in quartiles of Hb values (lt;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.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.

To date, non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease, affecting up to 70% of patients with diabetes. Currently, there are no specific drugs available for its treatment. Beyond their anti-hyperglycemic effect and the surprising role of cardio- and nephroprotection, GLP-1 receptor agonists (GLP-1 RAs) have shown a significant impact on body weight and clinical, biochemical and histological markers of fatty liver and fibrosis in patients with NAFLD. Therefore, GLP-1 RAs could be a weapon for the treatment of both diabetes mellitus and NAFLD. The aim of this review is to summarize the evidence currently available on the role of GLP-1 RAs in the treatment of NAFLD and to hypothesize potential future scenarios.

Atrial fibrillation (AF) is a major cause of cerebral ischemia, and its early detection may impact on health. Both invasive and non-invasive devices can be used for the diagnosis of AF. The aim of our study was to estimate the prevalence of AF using a single-lead ECG device (MyDiagnostickTM) on an adult, asymptomatic population during a screening campaign.A total of 2547 subjects underwent AF screening.The device detected an arrhythmia in 42 subjects (1.65%), and AF was confirmed on 12-lead ECG in 14 (0.55%) of them. The prevalence of confirmed AF increased in subjects over 65 years of age (1.21%) or with a CHA2DS2-VASc score ≥2 in males or ≥3 in females (1.33%). Furthermore, heart failure (odds ratio [OR] 8.62, 95% confidence interval [CI] 1.87-39.6, p=0.006) and diabetes (OR 4.55, 95% CI 1.25-16.5, p=0.021) significantly increased the risk of AF.During a screening campaign, the diagnosis of AF increases when subjects with a high thromboembolic risk are selected.

Background: Contemporary guidelines advocate for early invasive strategy with coronary angiography in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Still, the impact of an invasive strategy in older patients remains controversial and may be challenging in spoke hospitals with no catheterization laboratory (cath-lab) facility. Purpose: The purpose of this study was to analyse the characteristics and outcomes of patients ≥80 years old with NSTE-ACS admitted to spoke hospitals. Methods: Observational–retrospective study of all consecutive NSTE-ACS patients admitted to two spoke hospitals of our cardiology network, where a service strategy (same-day transfer between a spoke hospital and a hub centre with a cath-lab facility in order to perform coronary angiography) was available. Patients were followed up for 1 year after the admission date. Results: From 2013 to 2017, 639 patients were admitted for NSTE-ACS; of these, 181 (28%) were ≥80 years old (median 84, IQR 82–89) and represented the study cohort. When the invasive strategy was chosen (in 105 patients, or 58%), 98 patients (93%) were initially managed with a service strategy, whereas the remainder of the patients were transferred from the spoke hospital to the hub centre where they completed their hospital stay. Of the patients managed with the service strategy, a shift of strategy after the invasive procedure was necessary for 10 (10%). These patients remained in the hub centre, while the rest of the patients were sent back to the spoke hospitals, with no adverse events observed during the back transfer. The median time to access the cath-lab was 50 h (IQR 25–87), with 73 patients (70%) reaching the invasive procedure

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. Résumé: 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.

Elderly patients are under-represented in clinical trials and registries, and a gap of evidence exists for clinical decision making in the setting of acute coronary syndromes (ACS). We aimed to assess the prevalence and independent prognostic impact of valvular heart disease (VHD) diagnosed during the index hospitalization on clinical outcomes among elderly patients with ACS. Included VHDs were moderate-to-severe mitral regurgitation (MR), moderate-to-severe aortic stenosis (AS), or both combined.We explored the Elderly-ACS 2 dataset, which includes patients older than 74 years of age diagnosed with ACS and managed invasively. The primary endpoint was a composite of all-cause death, myocardial infarction, disabling stroke, and rehospitalization for heart failure at 1 year; the secondary endpoint was death for cardiovascular causes. Patients were stratified into 4 groups: no VHD, moderate-to-severe MR, moderate-to-severe AS, and both moderate-to-severe MR and AS.Of the 1443 subjects enrolled, 190 (13.2%) had moderate-to-severe MR, 26 (1.8%) had moderate-to-severe AS, and 13 (0.9%) had both moderate-to-severe MR and AS. When compared with those with no VHD, patients with moderate-to-severe MR had hazard ratios (HRs) for the primary endpoint of 2.04 (95% confidence interval [CI], 1.36-3.07], those with moderate-to-severe AS had HRs of 3.10 (95% CI, 1.39-6.93), and those with both moderate-to-severe MR and AS had HRs of 4.00 (95% CI, 1.65-9.73] (all P0.01). Patients with moderate-to-severe MR also had increased risks of cardiovascular death (HR 3.17; 95% CI, 1.57-6.42; P0.01), whereas in those with moderate-to-severe AS or both moderate-to-severe MR and AS, a nonsignificant increased risk was observed.In a contemporary cohort of elderly patients admitted for ACS, VHD was found in 1 of 5 subjects and had an independent, consistent impact on prognosis.

Background prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. Methods data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. Results there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P Conclusions statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients.

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.

Background Tailoring Dual Antiplatelet Therapy (DAPT) to each patient bleeding and ischemic risk profile is a majopr challenge in everyday clinical practice. As the elderlies were underrepresented in validation cohorts of bleeding risk scores, their generalizability in this context is uncertain. Purpose We sought to assess the clinical utility of the PRECISE-DAPT and PARIS bleeding risk scores to elderly patients suffering from ACS and undergoing invasive management. Methods Our external validation cohort included 1,883 patients older >74 years admitted for ACS and treated with PCI from 3 multicenter, randomized trials. Bleeding risk scores were calculated on a patient-level and subjects were stratified into risk categories according to each risk score definition. Results After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3–5 bleedings (log rank p=0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (log rank p=0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all χ2>0.05), but PARIS risk score was associated to a greater overestimation of the risk (mean D observed-predicted probability = −0.65 for PRECISE DAPT and −4.62 for PARIS, p=0.02; Figure 1). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%. A sensitivity showed that calibration and discrimination power was moderate for both risk scores also after including BARC 2 events. Conclusion In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance and a higher net benefit. Figure 1 Funding Acknowledgement Type of funding source: None

Background We sought to assess and compare the prediction power of the PRECISE-DAPT and PARIS risk scores with regards to bleeding events in elderly patients suffering from acute coronary syndromes (ACS) and undergoing invasive management. Methods Our external validation cohort included 1883 patients older >74 years admitted for ACS and treated with PCI from 3 prospective, multicenter trials. Results After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3–5 bleedings (p = 0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (p = 0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all χ2 > 0.05), but PARIS risk score was associated to a greater overestimation of the risk (p = 0.02). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%. Conclusions In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance.

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

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

Background Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. Results Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. Conclusions Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.

Background: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. Methods: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. Results: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78–1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13–1.00; P =0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85–3.16; P =0.18). Conclusions: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01777503.

Among pregnant women, SCAD is the most frequent etiology of non-atherosclerotic acute coronary syndrome. SCAD related to pregnancy is more frequent within the first month (especially first week) of puerperium or last trimester, or is otherwise anecdotal. The concomitance of SCAD and pregnancy poses many issues regarding diagnosis and treatment in respect to maternal and fetal safety and requires tailored intervention with close interaction between clinical cardiologists, interventional cardiologists, cardiothoracic surgeons, and obstetricians. We report the case of a patient, pregnant in the second trimester with a life-threatening SCAD, successfully treated with percutaneous coronary intervention with excellent outcome for mother and baby.

The prognostic role of previous coronary artery bypass (CABG) in elderly patients admitted to hospital for an acute coronary syndrome (ACS) is unclear. Therefore, the aim of this study was to compare the prognosis of patients aged ≥75 years admitted for an ACS with or without previous history of CABG. The primary outcome of the study was a composite of overall mortality, recurrent nonfatal myocardial infarction, nonfatal stroke, and rehospitalization for heart failure at 1-year follow-up. We included 2,253 ACS patients, aged 81 (78 to 85) years enrolled in 3 multicenter studies (the Italian Elderly ACS study, the LADIES ACS study, and the Elderly ACS 2 randomised trial) – 178 (7.9%) with previous CABG, 2,075 (92.1%) without. Patients with previous CABG had a higher burden of cardiovascular risk factors, lower ejection fraction, and higher creatinine values on admission. However, both at univariate analysis and after adjustment for the most relevant covariates (sex, age, previous myocardial infarction, type of ACS, left ventricular ejection fraction, and serum creatinine on admission), previous CABG did not show any statistically significant association with 1-year outcome (adjusted hazard ratio 0.85; 95% confidence interval 0.61 to 1.19; p = 0.353). In conclusion, our study suggests that elderly ACS patients with previous CABG have worse basal clinical characteristics. Nevertheless, in a broad cohort of patients mostly treated with percutaneous coronary intervention during the index event, previous CABG did not confer independent additional risk of major adverse cardiovascular events at 1-year follow-up.

Background Chronic kidney disease is common in patients admitted with acute coronary syndrome and its prevalence dramatically increases with age. Understanding the determinants of adverse outcomes in this extremely high-risk population may be useful for the development of specific treatment strategies and planning of secondary prevention modalities. Aim The aim of this study was to assess the impact of baseline renal function and acute kidney injury on one-year outcome of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Methods Patients aged 75 years and older with acute coronary syndrome undergoing successful percutaneous coronary intervention were selected among those enrolled in three Italian multicentre studies. Based on the baseline estimated glomerular filtration rate (eGFR) calculated using the Cockcroft–Gault formula ([(140–age) × body weight × 0.85 if female]/(72 × serum creatinine)* 1.73 m2 of body surface area), patients were classified as having none or mild (eGFR ≥60 ml/min/1.73 m2), moderate (eGFR 30–59 ml/min/1.73 m2) or severe (eGFR Results A total of 1904 patients were included. Of these, 57% had moderate and 11% severe renal dysfunction. At 12 months, patients with renal dysfunction had higher rates (P Conclusions Baseline renal dysfunction is highly prevalent and is associated with higher mortality in elderly acute coronary syndrome patients undergoing percutaneous coronary intervention. Acute kidney injury occurs more frequently among ST-elevation myocardial infarction patients and those with pre-existing renal dysfunction and is independently associated with one-year mortality.

Background Prasugrel was superior to clopidogrel in the setting of acute coronary syndromes (ACS) and recent data highlighted its possible role in the setting of complex percutaneous coronary intervention (PCI). Nonetheless, evidence supporting its use in high bleeding risk population are lacking. Purpose The aim of this post-hoc subgroup analysis was to evaluate the impact of prasugrel administration in elderly patients undergoing complex PCI for ACS. A primary composite endpoint of composite of mortality, myocardial infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year and secondary endpoints of all-cause mortality and any bleeding at 1 year were analyzed. Methods In the multicenter Elderly ACS 2 Study 1,443 patients aged >74 y were randomly assigned to receive low-dose prasugrel (5 mg) or clopidogrel (75 mg) and were prospectively followed for 1 year (Table 1). Complex PCI was defined if ≥3 lesions were treated, if ≥3 stents were deployed, or if any bifurcation, trifurcation, chronic total obstruction or moderate-to-severe calcified lesions were treated. Results Patients undergoing complex PCI (n=607) did not experience worse outcome, as compared to those with simpler PCI, in terms of primary endpoint (p=0.21, Figure 1A). Furthermore, in this subgroup, no significant difference was observed with prasugrel vs clopidogrel with regard to the primary endpoint (HR 1.17; CI 0.819–1.67; p=0.39, Figure 1A), all-cause death and bleeding (Figure 1C and 1D). No significant interaction was observed between treatment and PCI complexity (interaction p=0.34). Table 1 Overall Non-complex PCI Complex PCI p value Age (y) 80.60±4.46 80.00 [77.00, 84.00] 80.00 [77.00, 83.00] 0.215 STE-ACS 595 (41.2) 272 (32.5) 323 (53.4) Figure 1 Conclusions In elderly patients presenting with ACS low-dose prasugrel was comparable to clopidogrel in terms of all-cause mortality and any bleeding at 1 year. Acknowledgement/Funding None

Background Elderly patients with acute coronary syndromes (ACS) represent a group seldom included in clinical trials and in whom robust data regarding mid-term impact of significant concomitant valvular heart disease are lacking. Purpose Our aim was to evaluate the impact of moderate-to-severe mitral regurgitation (MR), moderate-to-severe aortic stenosis (AS), or both conditions combined on a primary composite endpoint of mortality, myocardial infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year in a population of ACS patients included in the Elderly ACS 2 trial. Methods In the multicenter Elderly II ACS Study, 1,443 patients aged >74 y undergoing percutaneous coronary intervention (PCI) for ACS, were randomly assigned to receive prasugrel (5 mg) or clopidogrel (75 mg) and were prospectively followed for 1 year. Amongst these, 1,102 patients received full echocardiographic assessment and were included in the post-hoc analysis (Table 1). Results Survival analysis showed that patients presenting with moderate-to-severe MR, AS or both (Figure 1A), had worse outcome in terms of primary endpoint (p Table 1 Overall No residual valvular heart disease Moderate-to-severe MR Moderate-to-severe AS Both Age (y) 80.68±4.50 80.40±4.42 81.47±4.45 82.92±5.42 83.23±5.42 Male gender 652 (59.2) 538 (61.6) 92 (48.4) 19 (73.1) 3 (23.1) STE-ACS 420 (38.1) 319 (36.5) 91 (47.9) 6 (23.1) 4 (30.8) Diabetes mellitus 203 (18.4) 158 (18.1) 35 (18.4) 5 (19.2) 5 (38.5) LVEF (%) 48.30±9.58 49.26±9.27 44.61±9.45 48.50±11.22 38.31±10.87 History of cancer 32 (2.9) 26 (3.0) 3 (1.6) 2 (7.7) 1 (7.7) Tot number of diseased vessel 2.31±1.05 2.28±1.04 2.49±1.05 2.04±0.87 2.54±1.13 Data are expressed as mean ± SD or count (valid %). Figure 1 Conclusions Moderate-to-severe MR and AS represent significant predictors of 1-year outcome in elderly patients hospitalized for ACS, even when other well-established prognostic factors are taken into account and after revascularization with PCI. Therefore, these patients should be carefully screened for the presence of valvular heart disease at the time of presentation and the need for surgical or percutaneous correction should be assessed accordingly. Acknowledgement/Funding None

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.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 (or ≥ 25.7 kg/m2). BMI was associated with hypertension, diabetes, hypercholesterolemia, estimated glomerular filtration rate and hemoglobin (p 0.001), and inversely with age (p = 0.005). Overweight patients displayed larger use of diuretics at admission (p = 0.03), aspirin pre-randomization (p = 0.01) and radial access (p = 0.04). At a median follow-up of 367 [337-378] days, BMI did not affect CV mortality in the overall population 4% vs 3.8%; adjusted HR [95%CI] = 2.3 [0.8-6.5], p = 0.12. Similar findings were observed for our secondary efficacy and safety endpoints. Results did not change when considering separately higher risk subsets of patients, (female gender, diabetics, ST-segment elevation myocardial infarction or the type of DAPT treatment allocation), with no significant interaction between these population characteristics and BMI.Among elderly patients with ACS, BMI did not condition the survival or the risk of major cardiovascular and bleeding complications. The results were consistent across several patient risk categories.

Background Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5 mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding. Study design The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75 mg in patients older than 74 years with ACS (either ST- or non–ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score). Conclusion The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503 ).

Because of the aging of the population, the proportion of elderly patients admitted to the coronary care unit for an acute coronary syndrome (ACS) is increasing. Until a decade ago, treatment of elderly patients was based on poor scientific evidence, as older patients were commonly excluded from randomized controlled trials. In the last years, real-world registries and randomized controlled trials specifically addressing the older population have been published and provided clear evidence. Primary percutaneous angioplasty has become the standard of care for the treatment of ST-elevation myocardial infarction also in the elderly population, whereas the Italian Elderly ACS and the After Eighty randomized trials have demonstrated the superiority of an invasive strategy over an initial conservative strategy also in elderly patients affected by non-ST-elevation myocardial infarction. Moreover, real-world registries have shown that an increased use of early revascularization was associated with a progressive reduction in mortality after ACS: these findings have been confirmed also in a clinical context characterized by high mortality rates such as that of cardiogenic shock. As 80% of deaths after an ACS have been shown to be due to cardiovascular causes also in the elderly, the focus has been shifted to secondary prevention. Data regarding the use of both ticagrelor or low-dose prasugrel, as compared to clopidogrel, showed that a reduction of ischemic events was counterbalanced by an increase in bleeding events. In perspective, it might be interesting to explore the superiority of a strategy that limits the duration of dual antiplatelet therapy to a short period after an ACS (when the ischemic event rate is higher) in elderly patients, and to explore other endpoints such as mid-term quality of life outcome after ACS in elderly patients.

Background Psoriasis has been associated with a higher prevalence of cardiovascular disease risk factors. However, there is inadequate quantification on the association between psoriasis and acute coronary syndrome (ACS), particularly in the elderly. Therefore, the aim of the present study was to assess the risk of ACS according to history of psoriasis in subjects aged 75 years and older. Methods We carried out a case control study based on 1455 cases and 1108 controls. Cases were all the patients admitted in the randomized Elderly ACS 2 trial. Controls were selected from subjects aged ≥75 years included in the Prevalence of Actinic Keratoses in the Italian Population Study (PraKtis), based on a representative sample of the general Italian population. Odds ratios (OR) of ACS according to history of psoriasis were obtained using a multiple logistic regression model including terms for age, sex and smoking. Results The prevalence of psoriasis was lower among cases (12/1455, 0.8%) than among controls (18/1108, 1.6%). The multivariate OR of ACS according to history of psoriasis was 0.51 (95% confidence interval: 0.23–1.09). Conclusions Our data does not support an association between psoriasis and risk of ACS in the elderly.

In this prospective observational single-center study, 55 patients with essential thrombocythemia who were candidates for second line treatment with anagrelide (ANA) received a preliminary cardiovascular (CV) clinical, instrumental and biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure, heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in-depth CV screening, 54 out of 55 patients were deemed to be fit for ANA treatment. Thirty-eight of the 55 patients received ANA treatment for a median of 36 months (range 3-48), and were monitored using the same CV evaluation. Fourteen of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2 arterial hypertension, 2 acute myocardial infarction) that were not predicted by the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non-cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did not appear to be necessary in ET patients to evaluate their suitability for ANA treatment, and, moreover, was not able to predict the occurrence of CV adverse events during ANA treatment. Nevertheless, the CV adverse events (mostly palpitations and edema) were easily managed by the hematologists, and required the cardiologist involvement in very few selected cases.

Lymph node (LN) metastasis in canine cutaneous mast cell tumours (cMCTs) is a well-known negative prognostic factor. The role of lymphadenectomy in the treatment of stage II disease remains controversial because of its uncertain therapeutic benefit. Aim of this retrospective study was to investigate the impact of lymphadenectomy on tumour control and survival for dogs with stage II cMCTs. Dogs with firstly occurring, histologically confirmed cMCT with LN metastasis undergoing resection of the primary tumour and medical treatment thereafter were retrospectively enrolled. Dogs were classified into two groups: LN sampling (LNS; diagnosis of metastasis obtained by cytology) and regional LN dissection (LND; diagnosis obtained by histopathology). To determine the therapeutic value of lymphadenectomy, the characteristics of recurrence (local, nodal and distant) and survival were compared between groups. Evaluated outcome variables included signalment, anatomic location, diameter, ulceration, substage, surgical margins, Patnaik grading, Kiupel grading and medical treatment. Overall, 152 dogs were included: 81 underwent LND as part of primary surgery and 71 LNS. The median follow-up time was 409 days for LND group and 620 days for LNS group. On univariable analysis, the risk of developing local, nodal or distant relapse was significantly higher in the LNS group compared with LND (P < 0.001). On multivariable analysis, the risk of tumour progression and tumour-related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001). Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II cMCTs undergoing surgical removal of the primary tumour and medical treatment.

Background Recurrent ST-segment elevations in acute coronary syndromes have been attributed to coronary cyclic flow variations (CCFVs) possibly due to coronary vasospasm and unstable platelet aggregation in partially occluded arteries. Methods We describe the case of a patient with an acute myocardial infarction, recurrent ST-segment elevations and diffuse disease of the left anterior descending artery. Results The post-angiography 12-lead continuous ECG monitoring revealed cyclic anterior ST-segment elevations that were completely abolished with continuous intravenous infusion of low-dose isosorbide-dinitrate. Conclusion The complete and sustained response to low-dose nitrate suggests that vasoconstriction plays a crucial role to provoke CCFVs. This case underlines the importance of continuous 12-lead ECG monitoring with ST-segment trend analysis in the CCU.

A 20-yr-old African fur seal (Arctocephalus pusillus) presented with a slowly growing mass located on the dorsum at the level of the last thoracic vertebrae. The mass was hard, 10 cm in diameter, and not adherent to the underlying tissues. Multiple biopsies were collected for histopathology and revealed extensive areas of necrosis, small nodules of malignant mesenchymal proliferation with areas of chondroid metaplasia, and atypical cells in vessel walls. The morphologic diagnosis was suggestive of malignant mesenchymal neoplasia originating from the vascular wall. The mass was removed 1 mo later due to ulceration and infection. Histologically, based on the World Health Organization's classification of neoplastic processes in domestic animals, the tumor was consistent with malignant mesenchymoma. The margins of resection revealed the presence of neoplastic cells. Based on these results, the particular species involved, the high local invasiveness, and the high metastatic index of this malignant tumor in domestic mammals and humans, the prognosis was poor. The animal died 6 mo later with metatastic disease.

Ponatinib (Iclusig, ARIAD Pharmaceuticals-Incyte Co.) is a third-generation structure-guided tyrosine kinase inhibitor that is approved for treatment of Philadelphia chromosome-positive leukaemias resistant or intolerant to other inhibitors. The clinical use of ponatinib is complicated by the possible development of cardiovascular events, primarily hypertension and arterial or venous thrombotic events. The US Food and Drug Administration and the European Medicine Agency recommend that the cardiovascular profile of patients candidate for ponatinib should be carefully evaluated. For patients deemed to carry a high risk of cardiovascular events, other life-saving therapeutic options should be considered. When alternative options are not available, treatment with ponatinib is indicated but requires that haematologists and cardiologists collaborate and identify modalities of surveillance and risk mitigation in the best interest of the patient. This article reports on the expert opinion provided by a panel of Italian haematologists, cardiologists and clinical pharmacologists. It summarises suggestions that may help to improve the therapeutic index of ponatinib, primarily in the settings of chronic-phase chronic myeloid leukaemia.

Maximal oxygen consumption (VO2max) and oxygen consumption at anaerobic threshold (VO2AT) are commonly measured parameters to test elite soccer players; however, studies relating metabolic parameters of professional soccer players with performance and best fitting to the field role are scarce. Our aim was to study the relations of VO2max and VO2AT with the field role of elite soccer players to generate a robust dataset with a solid statistical analysis. Over a 12-year period we performed 953 field evaluation tests of VO2 max and VO2AT on 450 elite soccer players of 13 professional teams by incremental, continuous and exhausting test modified from Conconi’s test. Statistical analysis was performed by one-way ANOVA followed—when appropriate—by Tukey post hoc test. Effect size was evaluated by the Cohen D test and η partial squared test. Statistical significance was set for p

The 2011 edition of the ESC guidelines on non-ST-segment elevation acute coronary syndromes (NSTE-ACS) maintains the approach strongly based upon risk stratification, following the concept that "the higher the risk of ischemic events, the larger will be the benefit of an aggressive pharmaco-interventional approach". This concept applies both to the indication and timing of angiography/revascularization and to the choice of concomitant pharmacological therapies. The proofs of efficacy of the most recent drug treatments are solid, but the choice among the several available options and the evaluation of the efficacy/safety ratios in patient subsets require clinical wisdom, especially for the management of the most complex and frail patients. The indication for performing coronary angiography within 24h in high-risk patients would imply extending to NSTE-ACS patients the networks already in place for primary percutaneous coronary intervention in ST-elevation myocardial infarction.

Spongy or noncompacted myocardium is a rare congenital cardiomyopathy characterized by parietal myocardial structural alterations secondary to intrauterine arrest of myocardial fiber compaction. It can be associated with other congenital cardiovascular malformations or manifest as an isolated disease. It is characterized by a wide variety of clinical presentations that range from complete absence of symptoms to thromboembolic manifestations, ventricular arrhythmias and congestive heart failure; the short- and mid-term prognosis is quite severe. We here describe a casual finding of an advanced form of noncompacted myocardium associated with patent ductus arteriosus in a young asymptomatic athlete during a routine visit for agonistic sports eligibility. Although the patient had a normal functional capacity, transthoracic echocardiography showed left ventricular dilation with a moderately depressed contractile function and the presence of numerous prominent trabeculae and deep intertrabecular recesses which communicated with the left ventricular cavity. These findings which were confirmed by further echocardiographic examinations, and the absence of other cardiovascular disorders associated with this disease, led us to the diagnosis of noncompacted myocardium. The patient was not allowed to perform sports activities and underwent percutaneous closure of the patient ductus arteriosus. He was asymptomatic and because in the recent literature there are no data regarding pharmacological therapy in these patients, the subject was submitted to routine clinical follow-up evaluation with no medical therapy.

The relationships between cell metabolism and both hemodynamics and oxygen transport/utilization (VO2/DO2) pattern were evaluated intra and postoperatively in eight patients undergoing major valvular heart surgery with the aid of moderately hypothermic cardiopulmonary bypass (CPB). Quadriceps femoris specimens were obtained by the needle biopsy technique for muscle ATP, ADP, AMP, phosphocreatine (PCr), creatine and lactate determination at anesthesia induction, after CPB, as well as in the ICU 18 h after surgery. Moreover, hemodynamic variables, oxygen transport and utilization indices, and plasma lactate were measured at the same intervals and throughout the CPB period. After CPB, muscle ATP and PCr contents were reduced (p less than .05) as compared to those of both pre-CPB patients and healthy control subjects; muscle and plasma lactate levels were increased (p less than .05). Mean VO2 and DO2 values measured during CPB significantly decreased (p less than .05), but VO2 reduction was proportionally greater than that of DO2 (-62% vs. -41%). No correlation was found between VO2 and DO2 at that time, but a significant relationship (p less than .05) was found at the end of CPB. A further decrease in muscle ATP and PCr levels was measured in the ICU, as muscle and plasma lactate levels were still elevated. At that time, VO2 and DO2 were not significantly different from pre-CPB values, but were significantly (p less than .05) correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Anagrelide treatment is considered potentially responsible of cardiovascular toxicity and side effects. For this reason, we have retrospectively evaluated 130 patients (pts) with Essential Thrombocythemia (ET) treated with Anagrelide in 10 Italian Hematological Centres belonging to the GIMEMA Group. The pts, 55 males and 75 females, had at diagnosis a mean age of 43 years (range 13–82) and a mean platelet (PLT) count of 1086x10(e)9/L. The Anagrelide treatment was started after a mean of 47 months from diagnosis(range 0–196). A previous treatment with cytoreductive drugs (mainly HU and IFN) and antiplatelet agents (mainly ASA), was performed in 65% and 98% of cases, respectively. The mean Anagrelide dose was 1 mg/day at start and 1.7 mg/day in the maintenance phase (mean PLT count below 500x10(e)9/L). Twenty-five patients (19%) discontinued the treatment after a mean of 27 months (range 1–85) for the following reasons: compliance loss (n8), no satisfactory response (n7), palpitations and tachycardia (n6), other side effects (n4), anemia (n1), renal toxicity (n1), thromboembolism (n1). During the follow-up (median 28 months) 4 thrombotic complications (1.15/100 pt-yrs) and 2 minor hemorrhages (0.57/100 pt-yrs) were registered. Moreover, 15 pts showed non lethal cardiovascular events: angina (n6), cardiomiopathy (n4), arrhythmia (n3), AMI (n2). An instrumental cardiovascular evaluation with Echocardiography (ECHO) and ECG was performed at Anagrelide start in 58 pts: the Ejection Fraction (EF) was abnormal in only one pt (EF 47%). The instrumental monitoring was done in 28 pts every 6–12 months. Four out of these 28 pts showed a decrease of the EF below the level of 50% (43%,45%,47%, and 49%), and only 1 pt discontinued Anagrelide for this reason (see table). The clinical and instrumental cardiovascular evaluation in ET patients receiving Anagrelide is becaming of routinary application and an observational prospective study of the Registro Italiano Trombocitemia (RIT) is now in progress. | CASES | AGE | EF % BASELINE | EF % 1ST YEAR | EF% 2ND YEAR | |:---------------------------------------------------------- | --- | ------------- | ------------- | ------------ | | *Anagrelide discontinuation because tachycardia and EF