Clinical impact of multimodality assessment of myocardial viability.

Coronary artery disease (CAD) is a prevalent cause of left ventricular dysfunction. Nevertheless, effective elective revascularization, particularly surgical revascularization, can enhance long-term outcomes and, in selected cases, global left ventricular contractility. The assessment of myocardial viability and scars is still relevant in guiding treatment decisions and selecting patients who are likely to benefit most from blood flow restoration. Although the most recent randomized studies challenge the notion of "hibernating myocardium" and the clinical usefulness of assessing myocardial viability, the advancement of imaging techniques still renders this assessment valuable in specific situations. According to the guidelines of the European Society of Cardiology, non-invasive stress imaging may be employed to define myocardial ischemia and viability in patients with CAD and heart failure before revascularization. Currently, several non-invasive imaging techniques are available to evaluate the presence and extent of viable myocardium. The selection of the most suitable technique should be based on the patient, clinical context, and resource availability. This narrative review evaluates the characteristics of available imaging modalities for assessing myocardial viability to determine the most appropriate therapeutic strategy.

Molecular Impact of Conventional and Electronic Cigarettes on Pulmonary Surfactant.

The alveolar epithelium is covered by a non-cellular layer consisting of an aqueous hypophase topped by pulmonary surfactant, a lipo-protein mixture with surface-active properties. Exposure to cigarette smoke (CS) affects lung physiology and is linked to the development of several diseases. The macroscopic effects of CS are determined by several types of cell and molecular dysfunction, which, among other consequences, lead to surfactant alterations. The purpose of this review is to summarize the published studies aimed at uncovering the effects of CS on both the lipid and protein constituents of surfactant, discussing the molecular mechanisms involved in surfactant homeostasis that are altered by CS. Although surfactant homeostasis has been the topic of several studies and some molecular pathways can be deduced from an analysis of the literature, it remains evident that many aspects of the mechanisms of action of CS on surfactant homeostasis deserve further investigation.

Direct oral anticoagulants in patients with nonvalvular atrial fibrillation and extreme body weight.

BACKGROUND: Limited clinical data exist describing the use of direct oral anticoagulants (DOACs) in patient with extreme body weight. Thus, the International Society of Thrombosis and Haemostasis (ISTH) recommends avoiding DOACs in patients with weight >120 Kg, and on the contrary, no restrictions exist for underweight patients. OBJECTIVE: To evaluate the effects of extreme body weight on DOAC activity and to compare the clinical outcomes of patients with an extreme body weight versus patients with a normal weight (61-119 Kg) treated with DOACs. METHODS: Single tertiary care Italian centre multidisciplinary registry including nonvalvular atrial fibrillation (NVAF) patients treated with DOACs. Based on weight, three subcohorts were defined: (i) underweight patients (≤60 Kg); (ii) patients with a normal weight (61-119 Kg, as control group); and (iii) overweight patients (≥120 Kg). Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. RESULTS: 812 NVAF patients were included, 108 patients weighed ≤60 Kg (13%, underweight), 688 weighed between 61 and 119 Kg (85%, normal weight), and 16 weighed ≥120 Kg (2%, overweight). In particular, among underweight patients, dabigatran was prescribed in 26% patients, apixaban in 27%, rivaroxaban in 28% and edoxaban in 22% ones. Instead, among overweight patients, 44% were treated with dabigatran, 25% with apixaban, 25% with rivaroxaban and 4% with edoxaban. Underweight patients were older, more frequently women, with lower creatinine clearance and a history of previous strokes, resulting in higher CHA2DS2-VASc score than in both remaining groups. Up to 2 years, no statistically significant difference was observed between the three groups of weight for thromboembolic events (P = .765) and for overall bleeding (P = .125), but a trend towards decreased overall bleeding rates was noticed as weight increased (24.1% vs 16.7% vs 12.5%, respectively). CONCLUSION: In this tertiary care centre registry, 15% of patients treated with DOACs presented an extreme weight. Compared to patients with a normal weight, no significant rates of thromboembolic events were observed for underweight or overweight patients. A trend towards decreased overall bleeding frequency as weight increased was highlighted up to 2 years. The present results should be considered as preliminary and hypothesis generating.

Optimization of Fibrin Scaffolds to Study Friction in Cultured Mesothelial Cells.

To study the friction of cell monolayers avoiding damage due to stress concentration, cells can be cultured on fibrin gels, which have a structure and viscoelasticity similar to that of the extracellular matrix. In the present research, we studied different gel compositions and surface coatings in order to identify the best conditions to measure friction in vitro. We examined the adhesion and growth behavior of mesothelial cell line MET-5A on fibrin gels with different fibrinogen concentrations (15, 20, and 25 mg/mL) and with different adhesion coatings (5 µg/mL fibronectin, 10 µg/mL fibronectin, or 10 µg/mL fibronectin + 10 µg/mL collagen). We also investigated whether different substrates influenced the coefficient of friction and the ability of cells to stick to the gel during sliding. Finally, we studied the degradation rates of gels with and without cells. All substrates tested provided a suitable environment for the adherence and proliferation of mesothelial cells, and friction measurements did not cause significant cell damage or detachment. However, in gels with a lower fibrinogen concentration, cell viability was higher and cell detachment after friction measurement was lower. Fibrinolysis was negligible in all the substrates tested.

The Spectrum of ECG Abnormalities in a Large Cohort of Cardiac Masses.

BACKGROUND: Cardiac masses represent a heterogeneous clinical scenario. Potential electrocardiographic red flags of malignancy remain to be investigated. OBJECTIVES: To describe the spectrum of electrocardiographic abnormalities in a large cohort of cardiac masses and to evaluate potential red flags suggestive of malignancy. METHODS: Observational cohort study of 322 consecutive patients with a cardiac mass and available ECG at Bologna University Hospital. All masses were diagnosed by histological examination or, in the case of cardiac thrombi, by radiological resolution after proper anticoagulant therapy. Multivariable regression analysis was used to assess potential predictors of malignancy among electrocardiographic abnormalities. All-cause mortality at follow-up was evaluated. RESULTS: Of 322 patients, 98 (30.4%) had malignant tumors. Compared with patients with benign masses, those with malignant tumors exhibited a higher heart rate, right axis deviation, greater depolarization, repolarization abnormalities and bradyarrhythmia at presentation. Regarding specific ECG features, a higher heart rate on admission (p=0.014), bradyarrhythmias (p=0.009), ischemic-like repolarization abnormalities (ST-segment deviation, both depression and elevation, and negative T-wave; p<0.001), low voltages (p=0.001) and right axial deviation (0.025) were identified as independent predictors of malignancy. Considering these specific ECG alterations, a malignancy-oriented ECG was associated with higher mortality at follow up (median time of 20.7 months). CONCLUSION: ECG is frequently abnormal in case of malignant cardiac tumors. Some specific electrocardiographic changes are strongly suggestive for malignancy and type of infiltration.

Cardiac Magnetic Resonance to Predict Cardiac Mass Malignancy: The CMR Mass Score.

BACKGROUND: Multimodality imaging is currently suggested for the noninvasive diagnosis of cardiac masses. The identification of cardiac masses' malignant nature is essential to guide proper treatment. We aimed to develop a cardiac magnetic resonance (CMR)-derived model including mass localization, morphology, and tissue characterization to predict malignancy (with histology as gold standard), to compare its accuracy versus the diagnostic echocardiographic mass score, and to evaluate its prognostic ability. METHODS: Observational cohort study of 167 consecutive patients undergoing comprehensive echocardiogram and CMR within 1-month time interval for suspected cardiac mass. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, by histology or radiological resolution after adequate anticoagulation treatment. Logistic regression was performed to assess CMR-derived independent predictors of malignancy, which were included in a predictive model to derive the CMR mass score. Kaplan-Meier curves and Cox regression were used to investigate the prognostic ability of predictors. RESULTS: In CMR, mass morphological features (non-left localization, sessile, polylobate, inhomogeneity, infiltration, and pericardial effusion) and mass tissue characterization features (first-pass perfusion and heterogeneity enhancement) were independent predictors of malignancy. The CMR mass score (range, 0-8 and cutoff, ≥5), including sessile appearance, polylobate shape, infiltration, pericardial effusion, first-pass contrast perfusion, and heterogeneity enhancement, showed excellent accuracy in predicting malignancy (areas under the curve, 0.976 [95% CI, 0.96-0.99]), significantly higher than diagnostic echocardiographic mass score (areas under the curve, 0.932; P=0.040). The agreement between the diagnostic echocardiographic mass and CMR mass scores was good (κ=0.66). A CMR mass score of ≥5 predicted a higher risk of all-cause death (P<0.001; hazard ratio, 5.70) at follow-up. CONCLUSIONS: A CMR-derived model, including mass morphology and tissue characterization, showed excellent accuracy, superior to echocardiography, in predicting cardiac masses malignancy, with prognostic implications.

Myocardial infarction with nonobstructive coronary arteries: from pathophysiology to therapeutic strategies.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by clinical evidence of acute myocardial infarction (AMI) with normal or near-normal coronary arteries on coronary angiography (stenosis < 50%) and without an over the alternative diagnosis for the acute presentation. Its prevalence ranges from 6% to 11% among all patients with AMI, with a predominance of young, nonwhite females with fewer traditional risks than those with an obstructive coronary artery disease (MI-CAD). MINOCA can be due to either epicardial causes such as rupture or fissuring of unstable nonobstructive atherosclerotic plaque, coronary artery spasm, spontaneous coronary dissection and cardioembolism in-situ or microvascular causes. Besides, also type-2 AMI due to supply-demand mismatch and Takotsubo syndrome must be considered as a possible MINOCA cause. Because of the complex etiology and a limited amount of evidence, there is still some confusion around the management and treatment of these patients. Therefore, the key focus of this condition is to identify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, echocardiography, and coronary angiography represent the first-level diagnostic investigations, but coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offer additional information to understand the underlying cause of MINOCA. Although the prognosis is slightly better compared with MI-CAD patients, MINOCA is not always benign and depends on the etiopathology. This review analyzes all possible pathophysiological mechanisms that could lead to MINOCA and provides the most specific and appropriate therapeutic approach in each scenario.

Predictive value of Killip classification in MINOCA patients.

BACKGROUND: Killip classification is a practical clinical tool for risk stratification in patients with acute myocardial infarction (AMI). However, its prognostic role in myocardial infarction with non-obstructive coronary artery (MINOCA) is still poorly explored. Our purpose was to evaluate the prognostic role of high Killip class in the specific setting of MINOCA and compare the results with a cohort of patients with obstructive coronary arteries myocardial infarction (MIOCA). METHODS: This study included 2455 AMI patients of whom 255 were MINOCA. We compared the Killip classes of MINOCA with those of MIOCA and evaluated the prognostic impact of a high Killip class, defined if greater than I, on both populations' outcome. Short-term outcomes included in-hospital death, re-AMI and arrhythmias. Long-term outcomes were all-cause mortality, re-AMI, stroke, heart failure (HF) hospitalization and the composite endpoint of MACE. RESULTS: Killip class >1 occurred in 25 (9.8%) MINOCA patients compared to 327 (14.9%) MIOCA cases. In MINOCA subjects, a high Killip class was associated with a greater in-hospital mortality (p = 0.002) and, at long term follow-up, with a three-fold increased mortality (p = 0.001) and a four-fold risk of HF hospitalization (p = 0.003). Among MINOCA, a high Killip class was identified as a strong independent predictor of MACE occurrence [HR 2.66, 95% CI (1.25-5.64), p = 0.01] together with older age and worse kidney function while in MIOCA population also left ventricular ejection fraction and troponin value predicted MACE. CONCLUSIONS: Killip classification confirmed its prognostic impact on short- and long-term outcomes also in a selected MINOCA population, which still craves for a baseline risk stratification.

Safety and efficacy of direct oral anticoagulants (DOACs) in very elderly patients (≥85 years old) with non-valvular atrial fibrillation.

BACKGROUND: Limited real-world data are available regarding the comparison about safety and efficacy of DOACs prescription in very elderly patients (≥85 years) with non-valvular atrial fibrillation (NVAF). Concern about the risk of bleeding with anticoagulation in very older patients still represents an important challenge for clinicians. The aim of this study was to evaluate the different prevalence of major bleeding and thromboembolic events between very elderly NVAF patients (≥85 years) compared to those non very elderly (<85 years). METHODS: Single center multidisciplinary registry including NVAF patients treated with DOACs. Primary safety endpoint was 2-year rate of major bleeding. Primary efficacy endpoint was 2-year rate of thromboembolic events. Event-free survival curves among groups were compared using Cox-Mantel Test. RESULTS: 908 NVAF consecutive patients were included, of these, 805 patients were <85 years (89%) and 103 patients were very elderly patients with ≥85 years (11%). Compared to patients <85 years, those very elderly have higher CHA2DS2-VASc Score (P=0.001), higher rate of hypertension (P=0.001), diabetes mellitus (P=0.030), previous bleeding events (P<0.001), previous stroke/TIA/SE (P≤0.001), heart failure (P≤0.001), and lower creatinine clearance (P<0.001). In terms of safety endpoints (overall ISTH-major bleeding) no significative difference between two groups (P=0.952) were observed up to 2-year follow-up. Systemic thromboembolic event (primary efficacy endpoint) was significantly higher in patients with ≥85 years (P=0.027). The incidence of all-cause death was significantly higher in very elderly patients (P<0.001). CONCLUSIONS: This single center registry, showed that the use of DOACs in very elderly NVAF was safe and is a therapeutic option to be pursued for stroke prevention especially for those who are at high risk of ischemic events.

Sex-Related Disparities in Cardiac Masses: Clinical Features and Outcomes.

BACKGROUND: Cardiac masses (CM) represent a heterogeneous clinical scenario, and sex-related differences of these patients remain to be established. PURPOSE: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. MATERIAL AND METHODS: The study cohort included 321 consecutive patients with CM enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause mortality at follow-up was evaluated. Multivariable regression analysis assessed the potential prognostic disparities between men and women. RESULTS: Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p = 0.02) than men. Regarding CM histotypes, females were affected by benign masses more frequently (with cardiac myxoma above all), while metastatic tumours were more common in men (p < 0.001). At presentation, peripheral embolism occurred predominantly in women (p = 0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, in multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignant tumours and peripheral embolism were independent predictors of mortality. CONCLUSIONS: In a large cohort of cardiac masses, a significant sex-related difference in histotype prevalence was found: Benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex did not influence prognosis in benign and malignant masses.

[Periprocedural myocardial injury and infarction after myocardial revascularization: incidence, clinical features and prognosis]. / Infarto e danno miocardico periprocedurali dopo rivascolarizzazione miocardica: incidenza, implicazioni cliniche e prognosi.

Myocardial revascularization, either percutaneous or surgical, is the cornerstone of chronic and acute ischemic coronary artery disease therapy. Periprocedural myocardial injury and infarction are possible complications of these procedures. Several pathogenetic mechanisms have been proposed in the setting of percutaneous (distal embolism, vasospasm, obstruction of a minor vessel) or surgical revascularization (prolonged ischemic time, early graft failure, arrhythmia or severe hypotension during the procedure). High-sensitivity cardiac troponins have emerged as the recommended biomarkers due to their important prognostic implications. However, data regarding diagnostic criteria, management and prognostic implications of these complications are lacking. The present review aims to provide an overview regarding the possible diagnostic criteria, management and prognostic role of periprocedural myocardial injury and infarction.

Echocardiographic Markers in the Diagnosis of Cardiac Masses.

BACKGROUND: The echocardiographic parameters required for a comprehensive assessment of cardiac masses (CMs) are still largely unknown. The aim of this study was to identify and integrate the echocardiographic features of CMs that can accurately predict malignancy. METHODS: An observational cohort study was conducted among 286 consecutive patients who underwent standard echocardiographic assessment for suspected CM at Bologna University Hospital between 2004 and 2022. A definitive diagnosis was achieved by histologic examination or, in the case of cardiac thrombi, with radiologic evidence of thrombus resolution after appropriate anticoagulant treatment. Logistic and multivariable regression analysis was performed to confirm the ability of six echocardiographic parameters to discriminate malignant from benign masses. The unweighted count of these parameters was used as a numeric score, ranging from 0 to 6, with a cutoff of ≥3 balancing sensitivity and specificity with respect to the histologic diagnosis of malignancy. Classification tree analysis was used to determine the ability of echocardiographic parameters to discriminate subgroups of patients with differential risk for malignancy. RESULTS: Benign masses were more frequently pedunculated, mobile, and adherent to the interatrial septum (P < .001). Malignant masses showed a greater diameter and exhibited a higher frequency of irregular margins, an inhomogeneous appearance, sessile implantation, polylobate shape, and pericardial effusion (P < .001). Infiltration, moderate to severe pericardial effusion, nonleft localization, sessile implantation, polylobate shape, and inhomogeneity were confirmed to be independent predictors of malignancy in both univariate and multivariable models. The predictive ability of the unweighted score of ≥3 was very high (>0.90) and similar to that of the previously published weighted score. Classification tree analysis generated an algorithm in which infiltration was the best discriminator of malignancy, followed by nonleft localization and sessile implantation. The percentage correctly classified by classification tree analysis as malignant was 87.5%. Agreement between observer readings and CM histology ranged between 85.1% and 91.5%. The presence of at least three echocardiographic parameters was associated with lower survival. CONCLUSIONS: In the approach to CMs, some echocardiographic parameters can serve as markers to accurately predict malignancy, thereby informing the need for second-level investigations and minimizing the diagnostic delay in such a complex clinical scenario.

Sex- and age-related differences in outcomes of patients with acute myocardial infarction: MINOCA vs. MIOCA.

AIMS: The aim of the study is to evaluate the impact of sex on acute myocardial infarction (AMI) patients' clinical presentation and outcomes, comparing those with non-obstructive and obstructive coronary arteries (MINOCA vs. MIOCA). METHODS AND RESULTS: We enrolled 2455 patients with AMI undergoing coronary angiography from January 2017 to September 2021. Patients were divided according to the type of AMI and sex: male (n = 1593) and female (n = 607) in MIOCA and male (n = 87) and female (n = 168) in MINOCA. Each cohort was further stratified based on age (≤/> 70 years). The primary endpoint (MAE) was a composite of all-cause death, recurrent AMI, and hospitalization for heart failure (HF) at follow-up. Secondary outcomes included all-cause and cardiovascular death, recurrent AMI, HF re-hospitalization, and stroke. MINOCA patients were more likely to be females compared with MIOCA ones (P < 0.001). The median follow-up was 28 (15-41) months. The unadjusted incidence of MAE was significantly higher in females compared with males, both in MINOCA [45 (26.8%) vs. 12 (13.8%); P = 0.018] and MIOCA cohorts [203 (33.4%) vs. 428 (26.9%); P = 0.002]. Age was an independent predictor of MAE in both cohorts. Among MINOCA patients, females ≤70 years old had a higher incidence of MAE [18 (23.7%) vs. 4 (5.9%); P = 0.003] compared with male peers, mainly driven by a higher rate of re-hospitalization for HF (P = 0.045) and recurrence of AMI (P = 0.006). Only in this sub-group of MINOCA patients, female sex was an independent predictor of MAE (hazard ratio = 3.09; 95% confidence interval: 1.02-9.59; P = 0.040). MINOCA females ≤70 years old had worse outcomes than MIOCA female peers. CONCLUSION: MINOCA females ≤70 years old had a significantly higher incidence of MAE, compared with males and MIOCA female peers, likely due to the different pathophysiology of the ischaemic event. TRIAL REGISTRATION: Data were part of the ongoing observational study 'AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation' (ClinicalTrials.gov Identifier: NCT03883711).

Performance of Prognostic Scoring Systems in MINOCA: A Comparison among GRACE, TIMI, HEART, and ACEF Scores.

Background: the prognosis of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is not benign; thus, prompting the need to validate prognostic scoring systems for this population. Aim: to evaluate and compare the prognostic performance of GRACE, TIMI, HEART, and ACEF scores in MINOCA patients. Methods: A total of 250 MINOCA patients from January 2017 to September 2021 were included. For each patient, the four scores at admission were retrospectively calculated. The primary outcome was a composite of all-cause death and acute myocardial infarction (AMI) at 1-year follow-up. The ability to predict 1-year all-cause death was also tested. Results: Overall, the tested scores presented a sub-optimal performance in predicting the composite major adverse event in MINOCA patients, showing an AUC ranging between 0.7 and 0.8. Among them, the GRACE score appeared to be the best in predicting all-cause death, reaching high specificity with low sensitivity. The best cut-off identified for the GRACE score was 171, higher compared to the cut-off of 140 generally applied to identify high-risk patients with obstructive AMI. When the scores were tested for prediction of 1-year all-cause death, the GRACE and the ACEF score showed very good accuracy (AUC = 0.932 and 0.828, respectively). Conclusion: the prognostic scoring tools, validated in AMI cohorts, could be useful even in MINOCA patients, although their performance appeared sub-optimal, prompting the need for risk assessment tools specific to MINOCA patients.

[Cardiac masses: classification, clinical features and diagnostic approach]. / Classificazione, caratteristiche cliniche e strategie diagnostiche delle masse cardiache.

The term cardiac mass refers to benign or malignant cardiac tumors and cardiac metastases but also to pseudotumors, which is a heterogeneous group consisting of thrombi, vegetations and normal variant structures. While primitive cardiac tumors are rare, metastases and pseudotumors are relatively common. The non-invasive diagnostic approach has not been well established in the literature yet. The first-line non-invasive approach consists of echocardiography, which provides good diagnostic accuracy for masses like thrombi, vegetations and some tumors (mainly myxoma and fibroelastoma). In contrast, for other masses, it does not provide information about the potential malignancy because of poor tissue characterization. Second-line (cardiac computed tomography and cardiac magnetic resonance) or third-line (positron emission tomography-computed tomography) evaluations have been validated in the diagnostic approach to cardiac masses by many studies. In fact, a comprehensive diagnostic approach may establish the diagnosis of malignancy without histological report, which is pivotal for the subsequent therapeutic strategy.The aim of this narrative review is to describe the commonly available non-invasive diagnostic techniques for cardiac masses, their potential and limitations and to suggest a diagnostic pathway for common practice.

Effect of Chronic Kidney Disease on 5-Year Outcome in Patients With Heart Failure and Secondary Mitral Regurgitation Undergoing Percutaneous MitraClip Insertion.

Chronic kidney disease (CKD) is strongly related to outcomes in cardiovascular diseases. Limited data are available regarding the independent prognostic role of CKD after transcatheter mitral valve repair with MitraClip. We sought to evaluate the real impact of CKD in a large series of patients with heart failure (HF) and secondary mitral regurgitation (SMR) who underwent MitraClip treatment. The study included 565 patients with severe SMR from a multicenter international registry. Patients were stratified into 3 groups according to estimated glomerular filtration rate (eGFR) assessment before MitraClip implantation: normal eGFR (≥60 ml/min/1.73 m2) (n = 196), mild-to-moderate CKD (30 to 59 ml/min/1.73 m2) (n = 267), and severe CKD (<30 ml/min/1.73 m2) (n = 102). The primary end point was a composite of overall death and the first rehospitalization for HF, the secondary end points were overall death, cardiac death, and first rehospitalization for HF. CKD was present in about 2/3 of patients. At 5-year Kaplan-Meier analysis, primary clinical end point occurred in 60% of patients with normal eGFR, compared with 73% cases in patients with mild-to-moderate CKD and 91% in patients with severe CKD (p <0.001). Long-term overall death rate significantly decreased with increasing eGFR, and cardiac death and rehospitalization for HF rates. Multivariate Cox regression analysis identified severe CKD as the strongest independent predictor of adverse outcome (hazard ratio 2.136, 95% confidence interval 1.164 to 3.918, p = 0.014). In conclusion, CKD affected about 2/3 of patients who underwent MitraClip treatment for severe SMR, and it was a strong and independent predictor of 5-year adverse outcomes.

Role of MUC1 in lubrication of pleural mesothelial cells cultured on fibrine gel.

To elucidate the role of sialomucin in friction reduction, we investigated the sliding friction of pleural mesothelial cells monolayers cultured on fibrine gel. These measurements were performed on normal (4/4 RM-4) and on tumor (CARM-L1 TG3) cell lines. The effect of treatment with neuraminidase, which removes sialic acid from sialomucin, and of dexamethasone, which has shown to increase sialomucin expression, were also assessed. Furthermore, the expression of the main form of cell-surface-associated mucin (MUC1) present in the mesothelium, was assessed by western blot and immunofluorescence, under different experimental conditions. Expression of MUC1 was not significantly different in the two cell lines. Moreover, dexamethasone did not increase the expression of MUC1. Coefficient of kinetic friction (µ) was significantly higher in tumor cells than in normal cells. Neuraminidase increased µ in both cell lines. These results suggest that sialomucin may play a role in reducing the friction of pleural mesothelial cells.

Prognostic Value of Pre-operative Atrial Fibrillation in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation.

Limited data are available regarding the independent prognostic role of preoperative atrial fibrillation (AF) after transcatheter mitral valve repair with MitraClip. We sought to evaluate the impact of preoperative AF in patients with heart failure (HF) and concomitant secondary mitral regurgitation (MR) after MitraClip treatment. The study included 605 patients with significant secondary MR from a multicenter international registry. Patients were stratified into 2 groups according to the presence or absence of preoperative AF. Primary end point was 5-year overall death, secondary end points were 5-year cardiac death and first re-hospitalization for HF. To account for baseline differences, patients were propensity score matched 1:1. The overall prevalence of preoperative AF was 44%. At 5-year Kaplan-Meier analysis, compared with patients without AF, those with AF had significantly more adverse events in term of overall death (67% vs 43%; HR 1.84, log-rank p <0.001) and cardiac death (56% vs 29%; HR 2.11, log-rank p <0.001) and re-hospitalization for HF (63% vs 52%; HR 1.33, log-rank p = 0.048). Multivariate analysis identified AF as independent predictor of worse outcome in term of primary end point (HR 1.729, 95% C.I. 1.060 to 2.821; p = 0.028). After propensity score matching, patients with AF had higher rates of death and cardiac mortality but similar rates of re-hospitalization for HF. In conclusion, in patients with HF undergoing MitraClip treatment for secondary MR, preoperative AF is common and an unfavourable predictor of 5-year death and cardiac death. However, AF did not affect the frequency of re-hospitalization for HF.

Evidence for Na+-glucose cotransporter in type I alveolar epithelium.

Functional evidence of Na(+)-glucose cotransport in rat lung has been provided by Basset et al. (J. Physiol. 384:325-345, 1987). By autoradiography [(3)H]phloridzin binding has been found confined to alveolar epithelial type II cells in mouse and rabbit lungs (Boyd, J. Physiol. 422: 44P, 1990). In this research we checked by immunofluorescence whether Na(+)-glucose cotransporter (SGLT1) is also expressed in alveolar type I cells. Lungs of anesthetized rats and lambs were fixed by paraformaldehyde, perfused in pulmonary artery, or instilled into a bronchus, respectively. Tissue blocks embedded in paraffin or frozen were sectioned. Two specific anti-SGLT1 antibodies for rat recognizing aminoacid sequence 402-420, and 546-596 were used in both species. Bound primary antibody was detected by secondary antibody conjugated to fluorescein isothiocianate or Texas red, respectively. In some sections cellular nuclei were also stained. In rats alveolar type I cells were identified by fluorescent Erythrina cristagalli lectin. Sections were examined by confocal laser-scanning microscope. Both in rats and lambs alveolar epithelium was stained by either antibody; no labeling occurred in negative controls. Hence, SGLT1 appears to be also expressed in alveolar type I cells. This is functionally relevant because type I cells provide 95-97% of alveolar surface, and SGLT1, besides contributing to removal of lung liquid under some circumstances, keeps low glucose concentration in lining liquid, which is useful to prevent lung infection.

Inappropriate dose of nonvitamin-K antagonist oral anticoagulants: prevalence and impact on clinical outcome in patients with nonvalvular atrial fibrillation.

BACKGROUND: Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs). OBJECTIVE: To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription. METHODS: Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. RESULTS: A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions. CONCLUSION: Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.