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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 m 2 of body surface area), patients were classified as having none or mild (eGFR ≥60 ml/min/1.73 m 2 ), moderate (eGFR 30-59 ml/min/1.73 m 2 ) or severe (eGFR <30 ml/min/1.73 m 2 ) renal dysfunction. Acute kidney injury was defined according to the Acute Kidney Injury Network classification. All-cause and cardiovascular mortality, non-fatal myocardial infarction, rehospitalisation for cardiovascular causes, stroke and type 2, 3 and 5 Bleeding Academic Research Consortium bleedings were analysed up to 12 months., 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  < 0.001) of all-cause (4.5%, 7.5% and 17.8% in patients with none or mild, moderate and severe renal dysfunction, respectively) and cardiovascular mortality (2.8%, 5.2% and 10.2%, respectively). After multivariable adjustment, severe renal dysfunction was associated with a higher risk of all-cause (hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.52-5.37, P  = 0.001) and cardiovascular death (HR 3.11, 95% CI 1.41-6.83, P  = 0.005), whereas non-fatal events were unaffected. Acute kidney injury incidence was significantly higher in ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome patients (11.7% vs. 7.8%, P  = 0.036) and in those with reduced baseline renal function ( P  < 0.001), and it was associated with increased mortality independently from baseline renal function and clinical presentation., 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., (© The European Society of Cardiology 2020.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 <70 group. At multivariable analysis, low education level was an independent predictor of LDL-C≥70 mg/dL (OR:1.582; 95%CI, 1.156-2.165; P = 0.004). Conversely, hypertension increased the probability to achieve the LDL-C goal (OR:0.650; 95%CI, 0.443-0.954; P = 0.028). Among off-target patients, LLT was not modified in the majority of cases (67.3%), intensified in 85 (18.6%), and actually reduced in 63 patients (13.8%)., 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.

Background: The predictors of outcome in patients with de novo diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF) are poorly known., Methods and Results: 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 < .001) independently predict HF rehospitalization; left ventricular end-systolic volume (LVESV; HR: 1.016; p = .017), sPAP (HR: 1.064; p = .034) and Late L/H (HR: 1.323; p = .009) were predictors of cardiac death; LVESV (HR: 1.013; p = .018) and Late L/H (HR: 1.245; p = .012) were independent predictors of all-cause death. Kaplan-Meier analysis of the individual predictors confirmed their prognostic ability during follow-up; of note, the Late L/H cut-off of 1.1 improved the risk stratification capability of echocardiographic parameters., Conclusions: Late L/H independently predicts HF rehospitalization, cardiac death and all-cause death in patients with de novo diagnosis of HFrEF and improves the prognostic stratification capability of conventional echocardiographic parameters.

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., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF ( p < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r 2 = 0.899 and r 2 = 0.909, respectively), and between ACE2 activity and Sirt1 (r 2 = 0.801 and r 2 = 0.802, respectively). HFrEF showed the highest TNF-α 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' phenotypes from each other, especially HFmrEF/HFrEF from HFpEF.

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., Competing Interests: The authors declare no conflict of interest related to this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: To evaluate the prognostic impact of diabetes mellitus (DM) in patients with Infective Endocarditis (IE)., Methods and Results: 375 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, p<0.001) and showed a higher prevalence of comorbidities such as hypertension (75 vs. 54%, p<0.001), coronary artery disease (30 vs. 12%, p<0.001) and history of heart failure (HF; 24 vs. 13%, p = 0.021). Echocardiography showed a higher incidence of paravalvular complications (82 vs. 64%, p<0.001) and a lower left ventricular ejection fraction (LVEF; 52±11 vs. 55±10%, p = 0.001) in diabetic than in non-diabetic patients. In-hospital mortality was higher in diabetic patients (83 vs. 74%; p = 0.030). At logistic regression, history of HF (OR = 3.1, 95%CI: 1.87-5.29, p<0.001) resulted an independent predictor of in-hospital death. At long-term follow-up [median 24(7-84) months], the Kaplan-Meier analysis showed a significantly lower survival free from all-cause death in the group with diabetes (Log-rank<0.001). At the propensity score adjusted Cox multivariable analysis, DM (HR = 1.76, 95%CI: 1.18-2.6, p = 0.005), age (HR = 1.03, 95%CI: 1.02-1.05, p<0.001), intravenous drug users (HR = 5.42, 95%CI: 2.55-11.51, p<0.001) and low LVEF (HR = 0.98, 95%CI: 0.96-0.99, p = 0.013) were independently associated to a higher mortality., Conclusion: In 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., Competing Interests: The authors have declared that no competing interests exist.

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI)., Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year., Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event., Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit., Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Right ventricular (RV) dysfunction is frequently observed in patients with aortic stenosis (AS). Nevertheless, assessment of regional RV deformation is yet not performed. The aim of the study was to analyze the impact of moderate and severe AS on global and regional RV function by a multisegmental approach using tissue Doppler imaging (TDI)., Methods: In 50 patients (Group I - AS [ n = 25] and Group II - normal controls [ n = 25]), additional echocardiographic views of the RV were prospectively performed. The TDI sample volume was placed in the basal myocardial region of the anterior (RV-anterior), inferior (RV-inferior), and free RV wall (RV-free wall) to assess the following parameters: S' RV , E' RV , and A' RV waves; IVCT RV ; IVRT RV ; and myocardial performance index (MPI RV )., Results: In AS patients, left ventricular (LV) mass index, left atrial (LA) volume index, and LV end-diastolic pressure were significantly increased. Moreover, AS patients had higher systolic pulmonary artery pressure (sPAP) and lower values for PV AccT ( P < 0.0001), but TAPSE was not different between the two groups ( P = 0.062). In AS patients, IVRT RV-anterior , IVRT RV-inferior , and IVRT RV-free wall and MPI RV were statistically increased ( P < 0.0001). A significant correlation between IVRT RV (evaluated at all three regions) and the parameters including sPAP, PV AccT, and E LV /e' LV ratio was observed in AS. A strong correlation was observed between IVRT RV-free wall/inferior and AS severity by evaluation of velocities, gradient, and aortic valve area ( P < 0.0001)., Conclusions: The present study reports a correlation between the severity of AS and the increase of IVRT RV and MPI RV . Thus, a distinct analysis of RV performance is important for echocardiographic evaluation of patients with AS., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Cardiovascular Echography.)

Background: To compare cardiac magnetic resonance (CMR) qualitative and quantitative analysis methods for the noninvasive assessment of myocardial inflammation in patients with suspected acute myocarditis (AM)., Methods: A total of 61 patients with suspected AM underwent coronary angiography and CMR. Qualitative analysis was performed applying Lake-Louise Criteria (LLC), followed by quantitative analysis based on the evaluation of edema ratio (ER) and global relative enhancement (RE). Diagnostic performance was assessed for each method by measuring the area under the curves (AUC) of the receiver operating characteristic analyses. The final diagnosis of AM was based on symptoms and signs suggestive of cardiac disease, evidence of myocardial injury as defined by electrocardiogram changes, elevated troponin I, exclusion of coronary artery disease by coronary angiography, and clinical and echocardiographic follow-up at 3 months after admission to the chest pain unit., Results: In all patients, coronary angiography did not show significant coronary artery stenosis. Troponin I levels and creatine kinase were higher in patients with AM compared to those without (both P < .001). There were no significant differences among LLC, T2-weighted short inversion time inversion recovery (STIR) sequences, early (EGE), and late (LGE) gadolinium-enhancement sequences for diagnosis of AM. The AUC for qualitative (T2-weighted STIR 0.92, EGE 0.87 and LGE 0.88) and quantitative (ER 0.89 and global RE 0.80) analyses were also similar., Conclusions: Qualitative and quantitative CMR analysis methods show similar diagnostic accuracy for the diagnosis of AM. These findings suggest that a simplified approach using a shortened CMR protocol including only T2-weighted STIR sequences might be useful to rule out AM in patients with acute coronary syndrome and normal coronary angiography.

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 (χ 2 = 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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

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 VO 2 ; 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 VO 2 was an independent predictor of overall mortality (HR:0.70; P < 0.001) as well as of the composite endpoint (HR:0.73; P < 0.001). The ROC analysis identified a peak VO 2 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/m 2 . Kaplan-Meier analysis for the individual and combined outcome predictors confirmed their significant stratification ability during follow-up., Conclusions: Peak VO 2 , along with LAVi and AF, identify FMR patients with the worst prognosis after MCi., (Copyright © 2018. Published by Elsevier B.V.)

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 9.6*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 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.

With population ageing and rise of life expectancy, a progressively increasing proportion of patients presenting with an acute coronary syndrome (ACS) are older adults, including those at extreme chronological age. Increasing amounts of data, including randomized clinical trials, have shown that the benefits of an early revascularization are maintained also at very old age, resulting in improved outcome after an acute coronary event. On the contrary, the optimal antiplatelet therapy (APT) remains unclear in these patients, because of both safety and efficacy concerns. Indeed, age-related multiple organ dysfunction and high prevalence of comorbidities may on the one hand reduce the therapeutic effects of administered drugs; on the other hand, it leads to increased vulnerability to drug toxicity and side effects. Therefore, management of APT is particularly challenging in elderly patients because of higher risk of both ischemic and bleeding events. The aim of the present paper is to review the current evidence, gaps in knowledge and ongoing research regarding APT in the setting of an ACS in elderly and very elderly patients, and in those with significant comorbidities including chronic kidney disease, diabetes mellitus and frailty.

Introduction: Acute coronary syndromes (ACS) have been classified according to the finding of ST-segment elevation on the presenting electrocardiogram, with different treatment strategies and practice guidelines. However, a comparative description of the clinical characteristics and outcomes of acute coronary syndrome elderly patients undergoing percutaneous coronary intervention during index admission has not been published so far., Methods: Retrospective cohort study of patients enrolled in the Elderly ACS-2 multicenter randomized trial. Main outcome measures were crude cumulative incidence and cause-specific hazard ratio (cHR) of cardiovascular death, noncardiovascular death, reinfarction, and stroke., Results: Of 1443 ACS patients aged >75 years (median age 80 years, interquartile range 77-84), 41% were classified as ST-elevation myocardial infarction (STEMI), and 59% had non-ST-elevation ACS (NSTEACS) (48% NSTEMI and 11% unstable angina). As compared with those with NSTEACS, STEMI patients had more favorable baseline risk factors, fewer prior cardiovascular events, and less severe coronary disease, but lower ejection fraction (45% vs 50%, P < .001). At a median follow-up of 12 months, 51 (8.6%) STEMI patients had died, vs 39 (4.6%) NSTEACS patients. After adjusting for sex, age, and previous myocardial infarction, the hazard among the STEMI group was significantly higher for cardiovascular death (cHR 1.85; 95% confidence interval [CI], 1.02-3.36), noncardiovascular death (cHR 2.10; 95% CI, 1.01-4.38), and stroke (cHR 4.8; 95% CI, 1.7-13.7)., Conclusions: Despite more favorable baseline characteristics, elderly STEMI patients have worse survival and a higher risk of stroke compared with NSTEACS patients after percutaneous coronary intervention., (Copyright © 2018. Published by Elsevier Inc.)

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 <0.001) without a difference in ADBRs ( P adj =0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( P adj <0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( P adj <0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.

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 < 0.0001). At multivariable analysis, the time interval from last MI (2 vs 3 years: OR 2.27; 95% CI 1.79-2.88; p < 0.0001) and a previous percutaneous coronary intervention with multiple stents (OR 3.46; 95% CI 2.19-5.47; p < 0.0001) resulted as the major independent predictors of DAPT persistence at the time of enrolment., Conclusions: This contemporary registry provides unique insights into the current management of post-MI patients and represents an opportunity to further improve the long-term treatment of this high-risk population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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: 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 <3+ was observed in 92.76% patients at discharge and in 83.36% patients at follow-up. At follow-up, 76.63% of patients NYHA Class I-II and there were significant improvements in left ventricular (LV) volume, ejection fraction, and pulmonary pressure. Atrial fibrillation (AF) had a significant negative effect on 1-year survival (β=0.18±0.06; P=0.0047) and on the reduction in LV end-diastolic and end-systolic volumes (β=-1.05±0.47 [P=0.0248] and β=-2.60±0.53 [P=0.0024], respectively)., Conclusions: MC results in durable reductions in mitral regurgitation associated with significant clinical and echocardiographic improvements in heart failure patients. AF negatively affects LV reverse remodeling and 1-year survival after MC treatment.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (© 2018 American Heart Association, Inc.)

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 < .001; for 1-month-HPR: p < .0001). At multivariable analysis, HPR could independently predict 1-year-MACE in elderly (for discharge-HPR: HR = 3.191, CI: 1.373-7.417, p = .007; for 1-month-HPR: HR = 3.542, CI: 1.373-9.137, p = .009)., Conclusions: In elderly with NSTE-ACS undergoing PCI and treated with clopidogrel, HPR was independently associated with an increased risk of MACE up to 1 year., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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 score>15), 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.

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: 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 (<60 mL/min/1.73 m 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<60 mL/min/1.73 m 2 . Patients with eGFR<60 mL/min/1.73 m 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<.001). There was no significant heterogeneity in the treatment effect of pharmacoinvasive strategy on the primary outcome (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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). However, the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome (ACS) undergoing PCI has not been established and represents the objective of this investigation. On-treatment P2Y 12 platelet reactivity was measured using the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay before PCI, at hospital discharge, and at 1 month after PCI in ACS patients enrolled in the multicenter, prospective GEne polymorphisms, Platelet Reactivity, and Syntax Score (GEPRESS) study (n = 962). High platelet reactivity (HPR) was defined as platelet reactivity index ≥50%. Statins were prescribed at hospital discharge in 87% (n = 835) of patients. All patients were followed for 1 year. The 1-month HPR rate was lower in statin than in non-statin treated patients (39.6 vs 52%, respectively, p = 0.009). This finding was confirmed also among statin-treated patients with high Syntax score (≥15). After adjustment for differences in baseline characteristics, statin use at discharge was independently associated with 1-month HPR rate (odds ratio, 0.58, 95% confidence interval, 0.38-0.89; p = 0.015). In ACS patients undergoing PCI treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins.

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: The CHA 2 DS 2 -VASc score predicts stroke in patients with atrial fibrillation and has been reported to have a prognostic role even in acute coronary syndrome patients. The Takotsubo syndrome is a condition that mimics acute coronary syndrome and may present several complications including stroke. We sought to assess the ability of CHA 2 DS 2 -VASc score to predict adverse events in Takotsubo syndrome patients., Methods and Results: Overall, 371 Takotsubo syndrome patients were enrolled in a prospective registry. Patients were divided into 3 groups according to the CHA 2 DS 2 -VASc score: Group A (≤1), B (2-3), and C (≥4). The median CHA 2 DS 2 -VASc score was 3 (interquartile range: 2-4). Overall, 9%, 42%, and 49% were included in Group A, B, and C, respectively. Follow-up length was 26±20 months. The mortality rate was 6%, 7%, and 17% in Group A, B, and C, respectively ( P =0.011). The stroke rate was 3% and not different among the 3 groups. Estimated major adverse cardiac and cerebrovascular events (the composite of death, myocardial infarction, and stroke) rates in the 3 groups were 6%, 9%, and 17% in Group A, B, and C, respectively ( P =0.033). The CHA 2 DS 2 -VASc score resulted as a predictor of major adverse cardiac and cerebrovascular events (odds ratio 2.1, 95% confidence interval, 1.2-3.6; P =0.01) and all-cause mortality (odds ratio 1.5, 95% confidence interval, 1.2-1.9; P =0.001)., Conclusions: In Takotsubo syndrome, the CHA 2 DS 2 -VASc score allows prediction of cardiovascular events and mortality at long-term follow-up., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aim: The aim of this study was to assess preoperative determinants, prevalence, and prognostic impact of left ventricular (LV) reverse remodeling (LVRR) in patients with secondary mitral regurgitation (SMR), undergoing MitraClip implantation (MCi)., Methods: From March 2012 to January 2015, a total of 41 consecutive patients with moderate-to-severe SMR treated successfully with MCi were enrolled. All patients underwent clinical and echocardiographic follow-up after MCi. Global longitudinal strain (GLS) was obtained using two dimensional speckle tracking analysis. A reduction in LV end-systolic volume more than 10% compared with baseline was considered as a marker of LVRR. Patients were divided into two groups according to the presence or absence of LVRR. Cardiac events were defined as the occurrence of cardiac death, rehospitalization for worsening heart failure, and mitral valve surgery., Results: On univariable analysis, EuroSCORE II and GLS were associated with LVRR. On multivariable logistic regression analysis, GLS was the only independent correlate of LVRR (P = 0.004). A receiver operating characteristic curve identified a cutoff value for GLS of -9.25% (P < 0.001) associated with LVRR, with a sensitivity and specificity of 81 and 74%, respectively. New York Heart Failure Association class more than 2 after MCi, absence of LVRR after MCi, and preoperative GLS more than -9.25% were significantly correlated with adverse cardiac events at long-term follow-up. On multivariable logistic regression analysis, GLS was the only independent predictor of composite adverse cardiac events at 2-year follow-up., Conclusion: A worse preoperative GLS predicts no LVRR and is associated with adverse long-term outcome after successful MCi for SMR.

Cigarette smokers with ST-segment elevation myocardial infarction (STEMI) may present different response to potent antithrombotic therapy compared to nonsmokers. We assessed the impact of smoking status and intracoronary abciximab in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We pooled data from 5 randomized trials comparing intracoronary versus intravenous abciximab bolus in patients undergoing primary PCI. The primary end point was the composite of death or reinfarction at a mean follow-up of 292 ± 138 days. Of 3,158 participants, 1,369 (43.3%) were smokers, and they had a lower risk of the primary end point in crude, but not in adjusted analyses (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.63 to 1.21, p = 0.405). Intracoronary versus intravenous abciximab was associated with a significant reduction in the risk of primary end point among smokers (3.6% vs 8.0%; HR 0.43, 95% CI 0.26 to 0.72, p = 0.001), but not in nonsmokers (10.2% vs 9.9%; HR 0.99, 95% CI 0.72 to 1.36, p = 0.96), with a significant interaction (p = 0.009). Furthermore, intracoronary abciximab decreased the risk of reinfarction in smokers (HR 0.30, 95% CI 0.15 to 0.62, p = 0.001), with no difference in nonsmokers (HR 1.20, 95% CI 0.71 to 2.01, p = 0.50). Stent thrombosis was lowered by intracoronary abciximab in smokers (HR 0.28, 95% CI 0.06 to 0.66, p = 0.009), but was ineffective in nonsmokers (HR 1.04, 95% CI 0.54 to 2.00, p = 0.903). Interaction testing showed heterogeneity in treatment effect for reinfarction (p = 0.002) and stent thrombosis (p = 0.018) according to smoking status. In conclusion, among patients with STEMI undergoing primary PCI, smoking status did not affect the adjusted risk of clinical events. Intracoronary abciximab bolus improved clinical outcomes by reducing the risk of death or reinfarction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Transthoracic echocardiography is the first-line imaging modality for evaluating patients with Takotsubo syndrome (TTS). Beyond diagnosis, TTE enables detection of peculiar complications and is useful for risk stratification and management of patients with cardiogenic shock. Cardiac magnetic resonance can be used to detect myocardial edema typically associated with TTS and is helpful in the differential diagnosis with other disease states. Coronary computed tomography angiography can be performed as an alternative to coronary angiography to confirm coronary artery patency. Molecular imaging is a promising approach for identifying patients at increased risk of recurrence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: 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., Methods and Results: 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 (p<0.001). 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; p<0.001) were independent correlates of the composite outcome in patients with RVi., Conclusion: 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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Diabetic patients are at increased risk for future cardiovascular events after ST-segment elevation myocardial infarction (STEMI). Administration of an intracoronary abciximab bolus during primary percutaneous coronary intervention (PCI) may be beneficial in this high-risk subgroup., Objectives: This study sought to report the 1-year clinical outcomes and cardiac magnetic resonance (CMR) findings in STEMI patients with and without diabetes randomized to intracoronary or intravenous abciximab bolus at the time of primary PCI., Methods: Patient-level data from 3 randomized trials were pooled. The primary endpoint was the composite of death or reinfarction. Comprehensive CMR imaging was performed in 1 study., Results: Of 2,470 patients, 473 (19%) had diabetes and 1,997 (81%) did not. At 1 year, the primary endpoint was significantly reduced in diabetic patients randomized to intracoronary abciximab compared with those randomized to intravenous bolus (9.2% vs. 17.6%; hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.83; p = 0.009). The intracoronary abciximab bolus did not reduce the primary endpoint in patients without diabetes (7.4% vs. 7.5%; HR: 0.95; 95% CI: 0.68 to 1.33; p = 0.77), resulting in a significant interaction (p = 0.034). Among diabetic patients, intracoronary versus intravenous abciximab bolus was associated with a significantly reduced risk of death (5.8% vs. 11.2%; HR: 0.51; 95% CI: 0.26 to 0.98; p = 0.043) and definite/probable stent thrombosis (1.3% vs. 4.8%; HR: 0.27; 95% CI: 0.08 to 0.98; p = 0.046). At CMR (n = 792), the myocardial salvage index was significantly increased only in diabetic patients randomized to intracoronary compared with intravenous abciximab (54.4; interquartile range: 35.1 to 78.2 vs. 39.0, interquartile range: 24.7 to 61.7; p = 0.011; p for interaction vs. no diabetes = 0.016)., Conclusions: In diabetic patients with STEMI, the administration of intracoronary abciximab improved the effectiveness of primary PCI compared with the intravenous bolus., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: To investigate the relationship between arterial access site choice (radial versus femoral) and clinical outcomes among STEMI patients undergoing routine PCI after fibrinolysis., Methods: Patient-level data from trials of STEMI patients evaluating routine PCI after fibrinolysis were included. The primary endpoint was 30-day major bleeding; secondary endpoints included 30-day death and re-infarction., Results: 1891 patients underwent PCI (trans-radial n=338, trans-femoral n=1553). Trans-radial PCI patients were less likely to be >75years (2% vs. 8%, p=0.0001), heavier (median weight 82 [72-90] vs. 80 [70-90] kg, p=0.0013) and more likely in Killip class I at presentation (87% vs. 82%, p=0.03). At 30days, trans-radial PCI was associated with a similar unadjusted risk for major bleeding (3.7% vs. 1.2%, Odds Ratio [OR] 0.43 [95% CI 0.13-1.48], p=0.18), mortality (3.4% vs. 1.2%, OR 0.34 [0.09-1.28], p=0.11) and re-infarction (3.9% vs. 4.7%, OR 1.25 [0.60-2.58], p=0.56). In multivariable analysis, radial access was associated with similar estimates for bleeding and death/reinfarction risk., Conclusions: In STEMI patients treated with fibrinolysis and undergoing an early routine invasive strategy, radial compared to femoral PCI is chosen in younger, less ill patients and is independently associated with similar risk of bleeding, re-infarction, and mortality., Summary: This study evaluated the relationship between arterial access choice (radial versus femoral) and in-hospital and 30-day outcomes in patients undergoing routine PCI after fibrinolysis for STEMI. We included patient-level data from trials evaluating a strategy of routine PCI after fibrinolysis for STEMI. Of 1891 patients undergoing PCI, trans-radial access (n=338) was chosen in younger, lower risk patients. At 30days, trans-radial access was associated with a similar unadjusted and adjusted risk of major bleeding, re-infarction and mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: In patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with PCI, high (H) platelet reactivity (PR) significantly affects one-year outcome. The aim of this report was to analyse the relationships between HPR, the SYNTAX score (SS) and one-year major adverse cardiac events (MACE: cardiac death, myocardial infarction, stent thrombosis) according to diabetes mellitus (DM) status in patients included in the GEne Polymorphism, Platelet REactivity, and the Syntax Score (GEPRESS) study., Methods and Results: PR was measured using the vasodilator-stimulated phosphoprotein (VASP) assay at three time points (before PCI, at hospital discharge and at one month after PCI), with HPR defined as >50% PR index in 1,042 patients treated with aspirin and clopidogrel for one year after PCI. Patients with DM and an SS ≥15 had the highest MACE rate between one month and one year, further increased by the presence of HPR (16.4%). On the other hand, among all patients with an SS <15, MACE rates remained low (<3%), irrespective of DM status and PR., Conclusions: Among NSTE-ACS patients treated with PCI, the combination of DM, an SS ≥15 and HPR characterised a cohort with the highest MACE rate from one month to one year. In such high-risk patients, careful clinical monitoring and implementation of secondary prevention measures, including the use of potent P2Y12 inhibitors, are strongly advised.

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: To determine the association between baseline creatinine clearance (CrCl), coronary revascularization during index admission, and 1-year mortality in elderly patients with an acute coronary syndrome (ACS)., Methods and Results: We estimated CrCl using the Cockcroft-Gault (CG) formula in 313 patients aged ≥ 75 years enrolled in a prospective study of treatment strategies in non ST-elevation ACS (NSTEACS). Patients were stratified into four groups according to CrCl on admission (using a cutoff of 45 ml/min) and coronary revascularization versus medical management. The mean age of the study population was 81 years and the median serum creatinine level on admission was 1.0 mg/dl (interquartile range (IQR) 0.8-1.3). Patients with impaired renal function treated medically had higher in-hospital and 1-year mortality, especially if compared with patients with preserved renal function undergoing revascularization (1-year mortality 22.9% versus 4.9%). Across the spectrum of CrCl categories, coronary revascularization was independently associated with a lower risk of mortality (HR 0.405; 95% CI 0.174-0.940; p=0.035)., Conclusions: In elderly patients with NSTEACS, coronary revascularization decreases the risk of 1-year death across each CrCl category, and is one of the most powerful predictors of 1-year outcome., (© The European Society of Cardiology 2014.)

Pheochromocytoma can occur with a variety of cardiovascular signs and symptoms, and this tumor can also precipitate an acute heart failure associated with the typical clinical and instrumental findings of myocarditis. This peculiar etiology of acute myocarditis, known as “adrenergic myocarditis,” should be suspected when specific “red flags” of pheochromocytoma such as headache, palpitations, diaphoresis, hypertension, orthostatic hypotension, and left ventricular dysfunction suggesting Takotsubo syndrome are detected. In fact, its diagnosis allows a specific targeted therapy.

Background: Randomised controlled trials have demonstrated improved outcomes with an early invasive strategy compared with routine care after fibrinolysis among patients with ST-elevation myocardial infarction. However, it remains uncertain whether specific patient subsets derive differential benefit from an early invasive strategy., Methods: Using patient-level data from seven randomised trials, we studied the relationship between treatment assignment (early invasive vs standard care) and adverse cardiovascular events. The outcomes assessed were death/reinfarction at 30 days and at 1 year, as well as death/reinfarction/recurrent ischaemia, major bleeding and stroke at 30 days. The analyses were conducted in strata (age, sex, diabetes, prior infarction, Killip class, anterior infarction and time from symptom onset to fibrinolysis) to assess for an interaction between the stratifying variable and treatment assigned., Results: There were 101 deaths and 115 recurrent infarctions at 30 days in 3010 patients. There were no strata where an invasive strategy conferred a differential treatment effect. With the exception of a marginally significant interaction between Killip class and treatment for death/reinfarction at 30 days and 1 year (p values for interaction 0.044 and 0.038, respectively), no interactions between the stratifying variables and treatment assignment were observed., Conclusions: Benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is similar across patient subgroups stratified by these clinical characteristics. Therefore, prediction of risk and benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is best achieved by global risk evaluation rather than specific patient characteristics., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We examined the incidence and predictors of acute kidney injury (AKI) in elderly patients (≥75 years) enrolled in the prospective Italian Elderly acute coronary syndrome (ACS) study and explored the impact of AKI on clinical outcome. Acute kidney injury, defined according to the Acute Kidney Injury Network criteria, occurred in 128 (21%) of 615 patients. Patients submitted to coronary angiographic procedures did not present higher rate of AKI. The only baseline variables independently associated with AKI development were creatinine clearance (odds ratio [OR]: 0.98; 95% confidence interval [CI]: 0.97-0.99) and left ventricular ejection fraction (OR: 0.98; 95% CI: 0.96-0.99). Adverse clinical events were significantly higher in patients who developed AKI. After multivariable adjustment, AKI (hazard ratio: 2.73; 95% CI: 1.87-4.0) was an independent predictor of all-cause mortality within 1 year., (© The Author(s) 2015.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Although bivalirudin has been shown to reduce bleeding events in patients undergoing percutaneous coronary intervention, residual concerns remain about a possible higher risk of early (within 30 days) stent thrombosis (ST). Therefore, we performed a meta-analysis of randomised trials reporting ST events with bivalirudin compared to other antithrombotic therapies (heparins ± glycoprotein IIb/IIIa inhibitors). A systematic literature search of electronic resources was performed through May, 2014. The primary endpoint was definite early ST, according to Academic Research Consortium criteria. Secondary endpoints included: all-cause death, myocardial infarction and major bleeding. A total of 11 trials, including 16,415 patients, were accrued. Compared to other regimens, bivalirudin significantly increased the risk of early ST (odds ratio [OR]=1.80; 95 % confidence interval [CI], 1.28-2.52; p=0.0007) and reduced the risk of major bleeding (OR [95 %CI]=0.64 [0.51-0.82], p=0.0003), with a comparable risk of mortality or myocardial infarction. The higher risk of early ST was mainly attributable to acute (OR [95 % CI] =4.33 [2.33-8.05], p < 0.001) than subacute (OR [95 % CI] =0.89 [0.53-1.50], p =0.67) ST events (p for interaction < 0.001). Non-fatal myocardial infarction was the most common presentation (83 %) of early ST events, while death occurred infrequently (about 5 %). In conclusion, in patients undergoing PCI, bivalirudin compared to heparins is associated with a higher risk of early ST, which is mainly related to more frequent acute events. Further studies are required to evaluate alternative strategies to mitigate this risk, without hampering the benefits derived from the reduction in bleeding events with bivalirudin.