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Loeffler's endocarditis (LE) is the cardiac manifestation of hypereosinophilic syndrome, a rare systemic disease characterized by the sustained production of eosinophils leading to organ damage. Few data, principally by case reports, are available regarding the diagnostic workup in patients with suspected LE. Thus, we have performed a systematic search of the literature dealing with imaging in LE and propose an integrated multimodality imaging approach in the cardiac diagnostics of LE patients. The aim is to provide an updated state-of-the-art review focused on noninvasive and invasive imaging modalities for this rare and underdiagnosed disease. Standard and advanced echocardiography are typically the first cardiac imaging examinations when LE is suspected and they are also used later in follow-up for prognostic stratification and assessing response to treatment. Cardiac magnetic resonance provides a more detailed anatomical and functional evaluation of cardiac chambers, tissue characterization for the presence and extension of myocardial edema and fibrosis, and ventricular thrombi identification. Computed tomography scan and [18F]-fluoro-deoxy-glucose positron emission tomography may be helpful in selected cases to evaluate the cardiac involvement of LE as well as the other noncardiac manifestations of hypereosinophilic syndrome. Endomyocardial biopsy may be considered in patients with high clinical suspicion of LE if noninvasive imaging findings are confusing or not conclusive. The appropriate use of invasive and noninvasive imaging modalities, combining the available techniques with the patients' clinical features, will hopefully lead to early diagnosis, more accurate staging of disease, and timely treatment of LE that may prevent the irreversible myocardial damage of LE and adverse cardiovascular events.

Background: There is an incomplete understanding of the prevalence and predictors of attainment of low-density lipoprotein cholesterol (LDL-C) goal after myocardial infarction (MI). Aim: To evaluate the prevalence of achievement of LDL-C goal of 70 mg/dL, to identify the baseline features associated with suboptimal lipid control, and to assess the use of LDL-C-lowering drug therapies (LLT) beyond the first year after MI. Methods: The EYESHOT Post-MI was a prospective, cross-sectional, Italian registry, which enrolled patients presenting to cardiologist 1 to 3 years after MI. In this retrospective post-hoc analysis, patients were categorized in 2 groups according to the achievement or not of the LDL-C goal of 70 mg/dL. Univariable and multivariable logistic regression analyses were performed to identify the baseline features associate with LDL-C≥70 mg/dL. Results: The study population included 903 patients (mean age 65.5 ± 11.5 years). Among them, LDL-C was ≥70 mg/dL in 474 (52.5%). Male sex ( P = 0.031), hypertension ( P = 0.024), prior percutaneous coronary intervention ( P = 0.016) and high education level ( P = 0.008) were higher in the LDL-C Conclusions: In patients presenting to cardiologists 1 to 3 years from the last MI event, LDL-C is not under control in a large proportion of patients, particularly in those with a low education level or without hypertension. LLT is underused in this very-high-risk setting.

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 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.

Type A aortic dissection, according to Stanford classification, is a surgical emergency with high morbidity and carries 56% of in-hospital mortality when surgical intervention is not performed. The surgical mortality at 30 days is 10 to 20%. The therapeutic goals are to replace the diseased ascending aorta and to treat or to monitor the distal aortic patent false lumen. When the dissection involves the aortic root and the architecture of aortic valve is normal, the surgical techniques used could be multiple: reinforce the aortic root and spare the native aortic valve or replace the aortic valve and the aortic root. The Florida sleeve technique has been developed to treat the aortic aneurysm, sparing the aortic valve in patients with connective tissue disease. Some case reports have described the use of this technique to treat an acute aortic dissection. In the following case, we present a single stage repair of the ascending aorta, aortic arch, and proximal intrathoracic aorta in a patient with Type A aortic dissection through the contemporaneous use of two techniques: Florida sleeve and Vascutek “Thoraflex” hybrid prosthesis. The use of these two techniques allows the repair/replacement of the proximal intrathoracic aorta, the sparing of the native aortic valve, the employment of a hybrid prosthesis to replace the supraortic vessels, and the creation of a descending aortic landing zone for later, distal intervention.

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.

Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF (n = 23), HFmrEF (n = 23) and HFrEF (n = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-&alpha, ) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF (p &lt, 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r2 = 0.899 and r2 = 0.909, respectively), and between ACE2 activity and Sirt1 (r2 = 0.801 and r2 = 0.802, respectively). HFrEF showed the highest TNF-&alpha, levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients&rsquo, phenotypes from each other, especially HFmrEF/HFrEF from HFpEF.

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.

Background The risk of death in patients affected by ST-elevation segment myocardial infarction (STEMI) is well known, but more data are required to define the in-hospital mortality in special subsets. We sought to assess the prognostic value of indicators in patients with large anterior STEMI as a first acute coronary event, undergoing percutaneous coronary intervention (PCI) and intra-aortic balloon pump (IABP). Methods and results We evaluated 48 consecutive large anterior STEMI patients admitted as first acute coronary event, undergoing in acute phase both PCI and IABP. Patient demographics, clinical, noninvasive and invasive findings, together with in-hospital complications, were collected. Moreover, findings obtained after a 24-month follow-up were reported. The primary endpoint was in-hospital mortality, whereas the secondary endpoints were out of hospital mortality, rehospitalization for heart failure or reinfarction, and New York Heart Association (NYHA) class at least 2 at follow-up visit. The univariate analysis showed a significant association with symptom to balloon, left anterior descending coronary artery, myocardial blush grade, and wall motion score index. Results of the multivariable analysis revealed the strongest predictive power for in-hospital mortality of proximal left anterior descending coronary artery (odds ratio: 6.9; 95% confidence interval: 1.1-67.7) and of myocardial blush grade 0-1 (odds ratio: 5.5; 95% confidence interval: 1.0-38.8). In-hospital death occurred in 13 patients (27% of total cases), whereas, at follow-up, the mean of survival was 66.7 ± 7.0%. Conclusion The patients with large anterior STEMI as a first acute coronary event, undergoing PCI and IABP, had a very high in-hospital mortality, whereas the mortality rate over the follow-up period was lower. The involvement of a large territory at risk and the ineffective treatment in terms of myocardial reperfusion were the main predictors of in-hospital mortality.

Background The efficacy and safety of pharmacoinvasive strategy following fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to renal function have not been established. Methods Using patient-level data from 4 randomized controlled trials, we examined the efficacy and safety of pharmacoinvasive versus standard treatment after fibrinolysis for STEMI. Patients were stratified based on the estimated glomerular filtration rate (eGFR) on presentation ( 2 vs ≥60 mL/min/1.73 m 2 ). The primary outcome was the composite of death or reinfarction at 30 days. Results Of 2,029 patients, 457 (23%) had an eGFR 2 . Patients with eGFR 2 were older and had higher Thrombolysis in Myocardial Infarction risk scores. Compared with patients with eGFR ≥ 60 mL/min/1.73 m 2 , patients with renal dysfunction had higher rates of the primary outcome (5.3% vs 11.8%, respectively; P P heterogeneity = .73) or the rate of death or reinfarction at 1 year ( P heterogeneity = .64) in relation to eGFR. Patients with renal dysfunction had higher rates of in-hospital major bleeding compared with patients with eGFR ≥60 mL/min/1.73 m 2 (7.7% vs 4.3%, respectively; P = .004); however, there was no difference in bleeding events between treatment arms in the overall cohort or in relation to eGFR ( P heterogeneity = .67). Conclusions Renal impairment is associated with increased rates of adverse events in STEMI patients treated with fibrinolysis. However, the safety and efficacy of pharmacoinvasive strategy are preserved in patients with renal impairment on presentation.

Background: In patients with Normal Glucose Tolerance (NGT) some causes of ischemic heart disease (IHD) were not completely investigated. The role both of metabolic milieu and adipokines in IHD progression was not fully investigated. Our aim was to assess the link between adipokines plasma levels, insulin resistance (IR) and IHD in NGT patients undergoing Percutaneous Coronary Intervention (PCI). Methods: AIRE is a single-center prospective longitudinal observational study investigating the IHD outcome of NGT subjects who underwent coronary revascularization by PCI in a third level cardiology center at A.O. dei Colli Hospital, University of Campania "Luigi Vanvitelli". Six hundred seventy-nine subjects hospitalized in 2015 for coronary arteriography not suffering from Acute Coronary Syndrome (ACS) in the previous 4 weeks, as well as from all conditions could affect glycemic plasma levels and IR status, were assessed for eligibility. Fifty-four patients with neither history of diabetes nor Altered Fasting Glucose (AFG)/Impaired Fasting Glucose (IGT) after Oral Glucose Tolerance Test (OGTT) were finally enrolled. Primary endpoint was the assessment of the relationship of adipokines and HOMA-IR with the occurrence of restenosis in NGT subjects. As secondary endpoint we assessed the association of the same adipokines and IR with overall ACS events after PCI in NGT subjects. Results: The 54 NGT patients enrolled were mainly males (85%), with a median age of 60 years [IQR 58-63 years]. Only 4 patients (7.4%) experimented restenosis. Median follow-up was equal to 29.5 months [IQR 14.7-34 months]. Adiponectin levels were independently associated to restenosis (OR 0.206; 95% CI 0.053-0.796; p = 0.000). Instead HOMA-IR and adiponectin appeared independently associated both to de novo IHD (OR 9.610 13 ; 95% CI 3.026-3.0810 27 ; p = 0.042 and OR 0.206; 95% CI 0.053-0.796; p = 0.000, respectively) and overall new PCI (OR 1.510 11 ; 95% CI 2.593-8.6810 21 ; p = 0.042 and OR 0.206; 95% CI 0.053-0.796; p = 0.000, respectively). Moreover, we fixed a potential cut-off for adiponectin for risk of restenosis (≤ 8.5 μg/mL) and overall new PCI (≤ 9.5 μg/mL). Conclusion: IR and cytokines play a role in progression of any stage of IHD also in NGT subjects. Our results in this setting of patients, though the relatively small sample size, represent a novelty. Future studies on larger populations are needed to analyze more in depth adipokines and insulin resistance role on IHD progression in non-diabetic people. © 2019 The Author(s). BackgroundIn patients with Normal Glucose Tolerance (NGT) some causes of ischemic heart disease (IHD) were not completely investigated. The role both of metabolic milieu and adipokines in IHD progression was not fully investigated. Our aim was to assess the link between adipokines plasma levels, insulin resistance (IR) and IHD in NGT patients undergoing Percutaneous Coronary Intervention (PCI).MethodsAIRE is a single-center prospective longitudinal observational study investigating the IHD outcome of NGT subjects who underwent coronary revascularization by PCI in a third level cardiology center at A.O. dei Colli Hospital, University of Campania Luigi Vanvitelli. Six hundred seventy-nine subjects hospitalized in 2015 for coronary arteriography not suffering from Acute Coronary Syndrome (ACS) in the previous 4weeks, as well as from all conditions could affect glycemic plasma levels and IR status, were assessed for eligibility. Fifty-four patients with neither history of diabetes nor Altered Fasting Glucose (AFG)/Impaired Fasting Glucose (IGT) after Oral Glucose Tolerance Test (OGTT) were finally enrolled. Primary endpoint was the assessment of the relationship of adipokines and HOMA-IR with the occurrence of restenosis in NGT subjects. As secondary endpoint we assessed the association of the same adipokines and IR with overall ACS events after PCI in NGT subjects.ResultsThe 54 NGT patients enrolled were mainly males (85%), with a median age of 60years [IQR 58-63 years]. Only 4 patients (7.4%) experimented restenosis. Median follow-up was equal to 29.5months [IQR 14.7-34months]. Adiponectin levels were independently associated to restenosis (OR 0.206; 95% CI 0.053-0.796; p=0.000). Instead HOMA-IR and adiponectin appeared independently associated both to de novo IHD (OR 9.6*10(13); 95% CI 3.026-3.08*10(27); p=0.042 and OR 0.206; 95% CI 0.053-0.796; p=0.000, respectively) and overall new PCI (OR 1.5*10(11); 95% CI 2.593-8.68*10(21); p=0.042 and OR 0.206; 95% CI 0.053-0.796; p=0.000, respectively). Moreover, we fixed a potential cut-off for adiponectin for risk of restenosis (8.5 mu g/mL) and overall new PCI (9.5 mu g/mL).ConclusionIR and cytokines play a role in progression of any stage of IHD also in NGT subjects. Our results in this setting of patients, though the relatively small sample size, represent a novelty. Future studies on larger populations are needed to analyze more in depth adipokines and insulin resistance role on IHD progression in non-diabetic people.

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates (ADIRs) and average daily bleeding rates (ADBRs) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low‐dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient‐days of follow‐up and assessed within different clinical phases: acute (0–3 days), subacute (4–30 days), and late (31–365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4–2.9) higher than ADBRs. ADIRs were significantly higher in the clopidogrel arm than in the low‐dose prasugrel arm in the subacute phase (P adj, See Editorial by Kinnaird

Aim: To evaluate the long-term outcome of patients with Takotsubo syndrome (TTS) and severely reduced left ventricular ejection fraction (LVEF ≤ 35%) at presentation. Methods and results: The study population included 326 patients (mean age 69.5 ± 10.7 years, 28 male) with TTS enrolled in the Takotsubo Italian Network, divided into two groups according to LVEF (≤ 35%, n = 131; > 35%, n = 195), as assessed by transthoracic echocardiography at hospital admission. In-hospital events were recorded in both groups. At long-term follow-up (median 26.5 months, interquartile range 18–33), composite major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, heart failure, and TTS recurrence) and rehospitalization were investigated. Compared to patients with LVEF > 35%, patients with LVEF ≤ 35% were older (71.2 ± 10.8 vs. 68.4 ± 10.6 years; P = 0.026) and experienced more frequently cardiogenic shock (16% vs. 4.6%; P < 0.001), acute heart failure (28.2% vs. 12.8%; P = 0.001), and intra-aortic balloon pump support (11.5% vs. 2.6%; P = 0.001) in the acute phase. At long-term follow-up, higher rates of composite MACE (25.2% vs. 10.8%; P = 0.001) and rehospitalization for cardiac causes (26% vs. 13.3%; P = 0.004) were observed in these patients. LVEF ≤ 35% at admission [hazard ratio (HR) 2.184, 95% confidence interval (CI) 1.231–3.872; P = 0.008] and age (HR 1.041, 95% CI 1.011–1.073; P = 0.006) were independent predictors of MACE. Patients with LVEF ≤ 35% also had a significant lower freedom from composite MACE during long-term follow-up (χ2 = 11.551, P = 0.001). Conclusion: Left ventricular ejection fraction ≤ 35% at presentation is a key parameter to identify TTS patients at higher risk not only in the acute phase but also at long-term follow-up.

BackgroundTo evaluate the prognostic impact of diabetes mellitus (DM) in patients with Infective Endocarditis (IE).Methods and results375 patients with diagnosis of IE referred to our Hospital between 1994-2017 were retrospectively included; diabetes was reported in 129 (34.4%). Diabetic patients were older than non-diabetic (66±1 vs. 57±2 years, pConclusionIn patients with IE, DM is associated to a higher prevalence of anatomic complications and a more impaired LVEF. Diabetic patients show a significantly lower survival both in hospital and during follow-up compared to the non-diabetic ones.

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration. PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p 0.001) and 1 month (43.4 ± 20.3% vs. 46.8 ± 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders (age, sex, diabetes, chronic kidney disease, Syntax score15), the β coefficient of smoke on PRI was -8.51 [-11.90 to -5.11, p 0.001] at baseline and -3.41 [-6.30 to -0.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80). Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.

Objective High on-treatment platelet reactivity (HPR) is a well-known risk factor for adverse events in patients undergoing percutaneous coronary intervention (PCI). However, whether reducing platelet reactivity can lead to a lower incidence of ischemic events after PCI is still controversial. Therefore, we sought to investigate this issue by a meta-regression analysis of randomized trials. Methods We collected randomized trials reporting HPR rates in patients receiving different antiplatelet therapies. ΔHPR was defined as the difference between HPR rates achieved in control vs. experimental arms, and the relationship between ΔHPR and clinical outcomes was evaluated. Results Thirty trials totalling 6683 patients with a mean follow-up of 3-month were included. Reducing platelet reactivity was associated to a decreased risk of major adverse cardiac events (MACE), with a linear relationship between ΔHPR and MACE (change in tau 2 = −2.50; p = 0.023). Particularly, achieving a 10% difference in HPR rates resulted in a parallel risk reduction in MACE of about 11% (Exp (b) = 0.98; 95% CI, 0.97–0.99). Changes in HPR predict the risk of ischemic events in patients with acute coronary syndrome (change in tau 2 = −2.52; Exp (b) = 0.98; 95% CI, 0.97–0.99; p = 0.03), but not in patients with poor response to clopidogrel (change in tau 2 = −1.44; Exp (b) = 0.98; 95% CI, 0.96–1.01; p = 0.19) or stable coronary artery disease (change in tau 2 = −0.14; Exp (b) = 0.99; 95% CI, 0.94–1.05; p = 0.89). Conclusion Reducing HPR occurrence decreases the risk of ischemic events in patients with acute coronary syndrome undergoing PCI, whereas a strategy of reducing platelet reactivity does not improve clinical outcomes in patients with poor response to clopidogrel or stable coronary artery disease.

To determine the prevalence, clinical characteristics, in-hospital course and determinants of major adverse events in a cohort of Caucasian patients with Takotsubo syndrome (TTS) and right ventricular involvement (RVi), regardless of left ventricular variant forms.The study population consisted of 424 patients (mean age 69.1±11.5years; female 92.2%) with a diagnosis of TTS divided into two groups according to the presence or absence of RVi. RVi patients (n=57; 13.4%) showed a higher prevalence of comorbidities, especially respiratory diseases (p=0.011), and a higher Charlson comorbidity index (CCI; p=0.006) than non-RVi patients. In-hospital major adverse events (acute heart failure, cardiogenic shock and death) occurred more frequently in RVi patients (p0.001). Heart rate and CCI, along with the echocardiographic parameters of wall motion score index, E/e' ratio, tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP) were associated with adverse in-hospital outcome. At multivariate analysis, CCI (HR: 1.871; 95% CI: 1.202-2.912; p=0.006), sPAP (HR: 1.059; 95% CI: 1.016-1.104; p=0.007) and TAPSE (HR: 0.728; 95% CI: 0.619-0.855; p0.001) were independent correlates of the composite outcome in patients with RVi.Patients with RVi are characterized by distinct clinical profile and should undergo closely clinical and echocardiographic monitoring. The presence of echocardiographic signs of right ventricular failure along with substantial comorbidities burden identify a cohort at higher risk of in-hospital major adverse cardiovascular events.

The predictors of outcome in patients with de novo diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF) are poorly known. All consecutive HFrEF patients admitted between October 2012 and November 2017 with their first episode of HF were scheduled for an outpatient follow-up. After 3 months, patients with confirmed HFrEF underwent Iodine-123 Meta-Iodobenzylguanidine imaging. We defined three study endpoints: HF rehospitalization, cardiac death and all-cause death. Eighty-four patients were enrolled. During follow-up (39.9 ± 18.6 months) HF rehospitalization occurred in 33 cases, cardiac death in 18 and all-cause death in 24. At multivariate analysis, systolic pulmonary arterial pressure (sPAP; HR: 1.047; p = .027) and Late lung to heart ratio (L/H; HR: 1.341; p

Background The prognostic predictors of outcome in patients with functional mitral regurgitation (FMR) undergoing MitraClip implantation (MCi) are still poorly known. The aim of our study is to identify the baseline predictors of outcome in FMR patients candidate to MCi. Methods All patients with symptomatic moderate-to-severe or severe FMR undergoing MCi at our institution were consecutively and prospectively enrolled. Baseline clinical and instrumental data were collected. Primary endpoint was the occurrence of cardiac death; secondary endpoints were all-cause death and the composite of cardiac death or rehospitalization for heart failure. Results 74 patients (mean 71.6 ± 8.3 years) were enrolled. During follow-up (median 416.0 days), the primary endpoint occurred in 15 (20.3%), all-cause death in 26 (35.1%) and the composite endpoint in 25 (33.8%). At multivariate analysis, the left atrial volume index (LAVi; HR:1.02; P = 0.048) and the low peak oxygen uptake (peak VO2; HR:0.73; P = 0.018) increased the risk of cardiac death at follow-up; atrial fibrillation (AF; HR:2.69; P = 0.027) was independently associated to all-cause death and the low level of peak VO2 was an independent predictor of overall mortality (HR:0.70; P The ROC analysis identified a peak VO2 cut-off of 10.0 mL/kg/min as the best predictor for the three study endpoints; the best LAVi cut-off for cardiac death was 67 mL/m2. Kaplan-Meier analysis for the individual and combined outcome predictors confirmed their significant stratification ability during follow-up. Conclusions Peak VO2, along with LAVi and AF, identify FMR patients with the worst prognosis after MCi.

Acute coronary syndromes (ACS) may represent an intriguing clinical scenario for implantation of bioresorbable vascular scaffold (BRS). Nevertheless, the knowledge about the performance of these devices in patients with ACS is limited. Therefore, we performed a meta-analysis of clinical studies aiming to assess the safety and efficacy of everolimus-eluting-BRS versus everolimus-eluting-metallic stents (EES) in ACS patients undergoing percutaneous coronary intervention. Six studies enrolling 2,318 patients were included and analyzed for the risk of primary safety outcome (stent or scaffold thrombosis [ST/ScT]), primary efficacy outcome (target lesion revascularisation [TLR]), and secondary outcomes (myocardial infarction, cardiac death, all-cause death). Median follow-up was 9.5 (6 to 19.5) months. Patients treated with BRS had a significantly higher risk of definite ST/ScT compared with those receiving EES (2.3% vs 1.08%, odds ratio [OR] 2.22, 95% confidence interval [CI] 1.10 to 4.45, p = 0.03, I2 = 0%). Similarly, the risk of TLR was significantly higher in the BRS compared with EES group (3.5% vs 2.5%, OR 1.79, 95% CI 1.02 to 3.16, p = 0.04, I2 = 0%). When TLRs due to thrombosis were excluded, the difference in risk estimates between the 2 groups was no longer significant (OR 1.19, 95% CI 0.48 to 2.98, p = 0.71, I2 = 25%). Risk for secondary endpoints did not differ between the 2 groups. Results were confirmed when clinical and procedural variables were tested as potential effect modifiers in the meta-regression analysis for both primary endpoints. In conclusion, compared with those receiving EES, patients with ACS treated with BRS had increased risk of definite device thrombosis and TLR at mid-term follow-up.

Background: Elderly treated with dual antiplatelet therapy after percutaneous coronary intervention (PCI) represent a challenging population because of increased risk of both ischemic and bleeding events. We aimed to investigate the association between high on-treatment platelet reactivity (HPR) and long-term outcome in elderly with non-ST-elevated acute coronary syndromes (NSTE-ACS) undergoing PCI.Methods: Platelet reactivity was measured by vasodilator-stimulated phosphoprotein (VASP) assay at three time points (baseline, discharge, 1 month after PCI) in 1053 NSTE-ACS patients (311 elderly) treated with clopidogrel. Major adverse cardiac events (MACE) were assessed up to 1 year-follow-up.Results: Elderly with HPR at discharge showed a significantly higher incidence of overall MACE (13 vs 4%, p=.006), cardiac death (6 vs 0.7%, p=.020), myocardial infarction (MI, 12 vs 4%, p=.031) and a trend for higher stent-thrombosis (5 vs 0.7%, p=.068). Similarly, elderly with 1-month-HPR showed between 1 month and 1 year significantly higher incidence of MACE (10 vs 4%, p=.012), cardiac death (6 vs 0.7%, p=.019) and composite cardiac death/MI (11 vs 4%, p=.014). Up to 1 year, elderly with HPR showed a 4-fold increased risk of MACE compared to both elderly without HPR (for discharge-HPR: p =. 005; for 1-month-HPR: p =. 01) and non-elderly with HPR (for discharge-HPR: p

AIMS: To describe the contemporary management by cardiologists of patients after an episode of myocardial infarction (MI). METHODS: The EYESHOT Post-MI was a prospective, observational, nationwide study aimed to evaluate the management of patients referring to cardiologists 1 to 3 years from the last MI event. RESULTS: Over a 3-month period, 1633 consecutive patients [median 22 (IQR 15-28) months from MI] were enrolled: 1028 (63.0%) at the second and 605 (37.0%) at the third year from MI. During the 12 months prior to enrolment, the majority of patients received a transthoracic echocardiogram (60% and 54%), followed by coronary angiography (24% and 16%, in the second and third year from MI groups, respectively). At the time of enrolment, the majority of patients were prescribed on statins (93%) and beta-blockers (82%), without significant differences between the 2 groups. A dual antiplatelet therapy (DAPT) was used more frequently among patients presenting during the second compared to the third year from MI (40% vs 24%; p

BACKGROUND The aim of this study was to investigate long-term survival, clinical status, and echocardiographic findings of patients with severe functional mitral regurgitation (FMR) undergoing MitraClip (MC) treatment and to explore the role of baseline features on outcome. Methods and Results: Randomized and observational studies of FMR patients undergoing MC treatment were collected to evaluate the overall survival, New York Heart Association (NYHA) class and echocardiographic changes after MC treatment. Baseline parameters associated with mortality and echocardiographic changes were also investigated. Across 23 studies enrolling 3,253 patients, the inhospital death rate was 2.31%, whereas the mortality rate was 5.37% at 1 month, 11.87% at 6 months, 18.47% at 1 year and 31.08% at 2 years. Mitral regurgitation Grade

Although Takotsubo syndrome (TTS) is most prevalent among postmenopausal women, the number of cases reported in premenopausal and even peripartum patients has increased [(1)][1]. We systematically reviewed papers published (PubMed, OVID Medline, EMBASE, and Cochrane Library) from January 1990 to

Dual antiplatelet therapy (DAPT) is a cornerstone of treatment for patients with acute coronary syndromes (ACS). Mounting evidences have opened the debate about the optimal DAPT duration. Considering the ACS-pathophysiology, the most recent guidelines recommend DAPT in all ACS patients for at least 12 months unless there are contraindications such as excessive risk of bleeding. Thus, it can be considered acceptable earlier discontinuation if the risk of morbidity from bleeding outweighs the anticipated benefit. On the other hand, several studies have clearly indicated that a significant burden of platelet related-events, such as stroke and new ACS might occur after this period, suggesting that potential benefits might derive by prolonging DAPT beyond 12 months (Long DAPT). Indeed, although current guidelines give some indications about patients eligible for Long DAPT, they do not embrace several real-life clinical scenarios. Thus, in such scenarios, how to decide whether a patient is eligible for Long DAPT or not might be still challenging for clinicians. This position paper presents and discusses various “real-life” clinical scenarios in ACS patients, in order to propose several possible recommendations to overcome guidelines potential limitations.

Background Many ST-segment elevation myocardial infarction (STEMI) patients have a multivessel disease that initially require percutaneous coronary intervention (PCI) of the culprit vessel but subsequently may require coronary artery bypass graft (CABG) of nonculprit vessels. Evidence supports staged revascularization, but the identification of optimal strategies (percutaneous or surgical), the timing and the management of antiplatelet therapy after recent PCI with stenting are matters of great controversies. Methods In our retrospective registry, we have enrolled 21 patients presenting with STEMI and multivessel disease, who underwent PCI of the culprit vessel only and then CABG of nonculprit vessels. Demographic, clinical, echocardiographic, angiographic findings, preoperative score, surgical data and postoperative complications were collected. At 21.6 ± 15.6 months follow-up death, reinfarction and/or cardiovascular and noncardiovascular events were recorded. Results Patients were 62 ± 9 years old and had in the most cases a good ejection fraction. At angiography, the culprit lesion was right coronary artery in 16 patients (76%). Angiographic characteristics excluded a staged PCI (SYNTAX score = 31.6 ± 7.4) and European System for Cardiac Operative Risk Evaluation II resulted low (1.46 ± 1.01). Following the indication to cardiac surgery after Heart Team discussion, the withdrawal of oral P2Y12 inhibitor was planned and tirofiban intravenous was started. Off-pump CABG was performed after 7.2 ± 3.2 days. No death, reinfarction and/or cardiovascular and noncardiovascular events occurred at follow-up. Conclusion We can conclude that a careful preoperative selection is mandatory for a good postoperative course and long-term survival and that early-staged CABG can, however, be performed using bridge therapy, also after STEMI.

Background Lower extremity peripheral arterial disease (LE-PAD) reduces walking capacity and is associated with an increased cardiovascular risk. Endovascular revascularization of LE-PAD improves walking performance and quality of life. In the present study, we determined whether successful lower limbs revascularization also impacts cardiovascular outcome in LE-PAD patients. Methods 479 consecutive LE-PAD patients at stage II of Fontaine's classification, with ankle/brachial index ≤0.90 and one or more stenosis >50% in at least one leg artery, were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 264 (55.1%) underwent percutaneous lower extremity angioplasty (PTA group), while 215 (44.9%) were managed with conservative therapy (MT group). The incidence of major cardiovascular events (including cardiovascular death, myocardial infarction, ischemic stroke, coronary and carotid revascularizations) was prospectively analyzed by Kaplan–Meier curves. Crude and adjusted HRs (95% CI) of developing a cardiovascular event were calculated by Cox analysis. Results No baseline differences were observed among the groups, except for a lower maximum walking distance in the PTA group. During a median follow-up of 21months (12.0–29.0), the incidence of cardiovascular events was markedly lower in PTA compared to MT patients (6.4% vs. 16.3%; p=0.003), and patients in the MT group showed a 4.1-fold increased cardiovascular risk compared to patients in the PTA group, after adjustment for potential confounders (95% CI 1.22–13.57, p=0.023). Conclusions This study shows that successful revascularization of LE-PAD patients affected by intermittent claudication, in addition to improving functional status, reduces the occurrence of future major cardiovascular events.

Spontaneous coronary artery rupture is a rare disorder that may develop early into a sudden death due to the abrupt evolution of the associated cardiac tamponade. In some cases the rupture is contained and a false aneurysm develops with slower evolution of clinical signs. The correct diagnosis of spontaneous coronary artery rupture deserves a high level of suspicion; frequently it may be missed because the time window of its evolution seems to be very short or signs of acute coronary syndrome sometimes can prevail, leading to delays in diagnosis or to misdiagnosis. We report the case of a patient presenting a giant pseudoaneurysm of the right coronary artery due to spontaneous coronary artery rupture without any underlying disease. Moreover we present a review of the few cases in the literature, offering a pathophysiological hypothesis linking the site of rupture and clinical presentation.

Background: Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients.Objectives: To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI).Methods: Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up.Results: Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26-0.99; p = 0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26-1.20; p = 0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07-0.99; p = 0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n = 2574).Conclusions: In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial. (C) 2015 Elsevier Inc. All rights reserved.

Background BCL-2-associated athanogene 3 (BAG3) is a protein implicated in the cardiomyocyte stress response and genesis of cardiomyopathy. Extracellular BAG3 is measurable in patients with heart failure (HF), but the relationship of BAG3 with HF prognosis is unclear. Methods BAG3 plasma concentrations were measured in 39 acutely decompensated HF patients; the primary endpoint was death at 1 year. Baseline characteristics were compared by vital status and median BAG3 concentration. Correlation of BAG3 with left ventricular ejection fraction (LVEF) and other biomarkers was performed. Prognostic value was assessed using Cox proportional hazards regression and Kaplan–Meier analysis. Results At baseline, median BAG3 was significantly higher in decedents (N = 11) than survivors (N = 28; 1489 ng/mL versus 50 ng/mL; P = 0.04); decedents also had worse renal function and higher median natriuretic peptide (NP) and sST2. BAG3 was not significantly correlated with NPs, mid-regional pro-adrenomedullin, sST2, or eGFR, however. Mortality was increased in patients with supra-median BAG3 (> 336 ng/mL; 42.1% versus 15.0%, P = 0.06). In age and LVEF-adjusted Cox proportional hazards, BAG3 remained a significant mortality predictor (HR = 3.20; 95% CI = 1.34–7.65; P = 0.02); those with supra-median BAG3 had significantly shorter time-to-death (P = 0.04). Conclusion The stress response protein BAG3 is measurable in patients with ADHF and may be prognostic for death.

Aortic dissection (AD) is the most common life-threatening disease involving the aorta. It is rarely associated with systemic disorders such as Autosomal Dominant Polycystic Kidney Disease (ADPKD), a genetic syndrome characterized by cystic degeneration of kidneys, possible presence of cysts in other organs and extra-renal manifestations, including cardiovascular disorders. We performed a systematic literature search focused on the occurrence of AD associated with ADPKD (25 cases identified), and reported two cases from our experience. We selected data on sex, age, family history of ADPKD and/or AD, habitus, hypertension, renal function, presence of hepatic/pancreatic/splenic cysts, clinical presentation of AD, AD type according to the Stanford classification, treatment and outcome. Furthermore we compared this dataset with the data of the overall population with AD from the International Registry of Acute Aortic Dissection (IRAD). Stanford A type AD was documented in 62% of patients. As expected, the initial manifestation of AD was most commonly chest and back pain (80%). The mean age of AD occurrence appears significantly reduced in ADPKD patients compared to the general population with AD (49 ± 12 vs 62 ± 14, P