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For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

A broad spectrum of concomitant disorders may complicate heart failure adding further morbidity and mortality risk. Comorbidities may be subdivided into cardiovascular and noncardiovascular. The first group includes hypertension, coronary artery disease, peripheral artery disease, cerebrovascular disease, arrhythmias and valvular heart disease. Noncardiovascular comorbidities include respiratory, endocrine, metabolic, nutritional, renal, hematopoietic, neurological as well as musculoskeletal conditions. In recent years, advances in the treatment of heart failure have not been attended by important changes in management of its comorbidities. They now seem to be major causes of the poor prognosis of heart failure patients. In this review we provide an updated summary of the epidemiological, pathophysiological and clinical characteristics of comorbidities as well as their potential impact for heart failure treatment.

Aims To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). Conclusion Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities’ effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in “fight against heart failure.”

Aims: To evaluate endothelial function in subjects with left ventricular assist devices (LVADs), comparing them with subjects with chronic heart failure with reduced ejection fraction on the list for heart transplant (HT) and with HT patients with a normal systolic cardiac function to identify any differences. Methods: We enrolled 28 subjects with LVAD, 55 subjects with HT, and 42 subjects with heart failure on the transplant list. The subjects underwent a general physical examination, assessment of laboratory blood parameters, and assessment of endothelial function through flow-mediated dilation (FMD) of brachial artery. Results: The three groups were homogeneous as regards age, gender, smoke abuse, C-reactive protein (CRP) and FMD parameters (P=ns). In LVAD group percentage of FMD change showed an inverse correlation with CRP (rho: −0.5, P: 0.003), a well-known marker of inflammation and tissue damage. Conclusions: Continuous flow related to LVAD seems to not worsen endothelial function. Endothelial function was not affected by cardiovascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, and tobacco habit), by the functional status expressed by New York Heart Association class, by the left ventricular systolic function and by the presence or absence of ischaemic heart disease in all the populations analysed. CRP was the only factor able to influence percentage of FMD change in patient with LVAD, reinforcing the hypothesis that inflammation is the main determinant of endothelial function.

Purpose:. The final diagnosis of myocarditis is challenging. The aim of our study was to provide the D.A.M.E. (Diagnosis of Acute Myocarditis in Emergency) Score for the fast identification of patients suffering from myocarditis at Emergency Department (ED). Methods:. This was a multicenter, retrospective study involving three centers. All medical records from January 2010 to December 2014 reporting a final discharge diagnosis of myocarditis were considered. One hundred-four patients (mean age: 40.2±16.5 years) were enrolled. Clinical, biochemical and instrumental data were gathered. Data were analysed by means of logistic regression model and factorial analysis. A validation cohort from a fourth center was enrolled. Results:. The final determinants of the DAME score were six: fever, chest pain, erythrocyte sedimentation rate (ESR) > 20 mm/h, C-reactive protein (hs-CRP) >3 mg/L, troponin serum levels >3 ng/L, and left ventricle ejection fraction < 50%. All of them received a specified score ranging from 0 to 4. A score > 4 was related to 75% probability of myocarditis; a final score ranging between 1 and 4 was related to 57% probability of myocarditis. ROC curve on the validation cohort (289 patients, 27 with myocarditis) demonstrated the best cut-off to be 7: AUC 0.958 (p< 0.001), sensibility: 100%, specificity: 85.11%, PPV: 40.9%, NPV: 100% (LR+: 6.72; LR-: 0.00). Logistic regression analysis revealed Odds Ratio equal to 2.83 (95% CI 1.90 – 4.20, p < 0.0001). Conclusions:. DAME score can offer a reliable tool in ED setting for the evaluation of patients suffering from suspected myocarditis.

We aimed to examine biomechanical and neuroautonomic adaptation to blood volume displacement induced by tilt test in patients with previous inferoapical/inferolateral (IA-IL) or basal/apical septal (BS-AS) myocardial infarction (MI). Twenty-four patients with heart failure (HF) and previous IA-IL MI and 30 patients with HF and previous BS-AS MI were enrolled. All patients underwent head-up tilt test, radionuclide ventricular function monitoring (VEST), sympathovagal balance evaluation, and chronotropic 25-dose isoproterenol infusion test (CD25). Physiopathological reactions to stress-tests were assessed in both groups. Follow-up lasted 36 mo. IA-IL patients showed lower stroke volume (SV), cardiac output (CO), and left ventricle ejection fraction (LVEF) compared with BS-AS. End-diastolic volume decreased in IA-IL group (F = 3.1, P = 0.043) more than in BS-AS group during tilt test. The time trend of end-systolic volume, SV, CO, LVEF, and peak filling rate were similar in the two groups. Norepinephrine (IA-IL supine→tilting 499.5 (SD:28.8)→719.3 (SD:41.5) pg/mL vs. BS-AS supine→tilting 533.9 (SD:33.3)→768.8 (SD:47.9) pg/mL; P < 0.001) and epinephrine plasma concentrations (IA-IL supine→ tilting 125.7 (SD:9.8)→193.7 (SD:9.6) pg/mL vs. BS-AS supine→ tilting 118.8 (SD:8.9)→191.7 (SD:10.2) pg/mL; P < 0.001) increased in both groups. Low-to-high frequencies ratio significantly increased in IA-IL and decreased in BS-AS patients. CD25 was similar in IA-IL and BS-AS patients (IA-IL = 4.6 (SD:0.94), BS-AS = 5.0 (SD:1.06) mg; P = 0.79). CD25 predicted all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.32–1.67; P < 0.0001) after adjusting for age/heart rate. In conclusion, patients with ischemic HF show abnormal biomechanical adaptation to volume displacement and compensatory sympathetic overdrive. The association of reduced b-adrenergic sensitivity and sympathetic denervation in such patients warrants for careful therapeutic choices. NEW & NOTEWORTHY The adaptation to volume displacement induced by tilt test was assessed in patients with heart failure and previous inferoapical/inferolateral or basal/apical septal myocardial infarction. The responsiveness of cardiac muscle to sympathetic nervous system stimulation predicts the mortality in patients with ischemic heart failure and may represent a useful tool for clinicians in the general assessment of this kind of patients.

Arterial hypertension, a widespread disease, whose prevalence increases with age, represents a major risk factor for cardiovascular events, causing damage in several organs, including the heart. In this context, echocardiography has a clear and pivotal role, being able to assess cardiac morphology and detect haemodynamic changes induced by this disease. 2018 European Society of Cardiology/European Society of Hypertension guidelines on AH identified main echo parameters such as left ventricular mass, relative wall thickness and left atrial volume, for detecting cardiac organ damage. The present review highlights the advantage of additional echocardiographic parameters such as diastolic measurement and both thoracic and abdominal aortic dimensions. An overlook on aortic valve should also be suggested to detect aortic regurgitation and stenosis, both frequent complications in hypertensive patients. In this kind of comprehensive assessment, the combination of standard and advanced echocardiography (speckle tracking echocardiography and, with a lesser extent, three-dimensional echocardiography) could be considered to improve the diagnostic accuracy, stratify prognosis and address management in arterial hypertension.

Cardiovascular diseases represent a major health problem, being one of the leading causes of morbidity and mortality worldwide. Therefore, in this scenario, cardiovascular prevention plays an essential role although it is difficult to establish when promoting and implementing preventive strategies. However, there is growing evidence that prevention should start even before birth, during pregnancy, aiming to avoid the onset of cardiovascular risk factors, since events that occur early in life have a great impact on the cardiovascular risk profile of an adult. The two pillars of this early preventive strategy are nutrition and physical exercise, together with prevention of cardio-metabolic diseases during pregnancy. This review attempts to gather the growing evidence of the benefits of antenatal, perinatal and primordial prevention, discussing also the possibility to reverse or to mitigate the cardiovascular profile developed in the initial stages of life. This could pave the way for future research, investigating the optimal time and duration of these preventing measures, their duration and maintenance in adulthood, and the most effective interventions according to the different age and guiding in the next years, the best clinical practice and the political strategies to cope with cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women.Some authors highlighted that the female risk profile consists of traditional and emerging risk factors. Despite the lower prevalence of type 2 diabetes, years of life lost owing to the disease for women are substantially higher compared with men. In addition, pregnancy complicated by gestational diabetes represents a risk factor for CVD. Women with gestational diabetes have a higher prevalence of coronary artery disease that occur at a younger age and are independent of T2DM.Hypertension is an important cardiovascular risk factor in women. Estrogens and progesterone, known to have an impact on blood pressure levels, have also been proposed to be protective against sleep-disordered breathing. It is very difficult to understand whereas obstructive sleep apnea in women is independently associated with hypertension or if many confounders acting at different stages of the woman lifespan mediate this relation.The cardioprotective effect of physical activity in women of all ages is well known. Women are generally more physically inactive than men. During and after menopause, most women tend to reduce their physical activity levels and together with the reduction in basal metabolic rate, women experience loss of skeletal muscle mass with a negative change in the ratio of fat-to-lean mass.In conclusion, sex differences in the cardiovascular system are because of dissimilarities in gene expression and sex hormones; these result in variations in prevalence and presentation of CVD and associated conditions, such as diabetes, hypertension and vascular and cardiac remodeling.Changes in lifestyle and increase in physical activity could help in prevention of cardiovascular disease in women.

Background Implantable cardioverter-defibrillators (ICDs) have a role in preventing cardiac arrest in patients at risk for life-threatening ventricular arrhythmias. Purpose To compare ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic or nonischemic cardiomyopathy. Data sources MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, and EMBASE databases, as well as several Web sites, from 1 April 1976 through 31 March 2017. Study selection Randomized controlled trials, published in any language, comparing ICD therapy with conventional care and reporting mortality outcomes (all-cause, sudden, any cardiac, or noncardiac) in the primary prevention setting. Data extraction 2 independent investigators extracted study data and assessed risk of bias. Data synthesis Included were 11 trials involving 8716 patients: 4 (1781 patients) addressed nonischemic cardiomyopathy, 6 (4414 patients) ischemic cardiomyopathy, and 1 (2521 patients) both types of cardiomyopathy. Mean follow-up was 3.2 years. An overall reduction in all-cause mortality, from 28.26% with conventional care to 21.37% with ICD therapy (hazard ratio [HR], 0.81 [95% CI, 0.70 to 0.94]; P = 0.043), was found. The magnitude of reduction was similar in the cohorts with nonischemic (HR, 0.81 [CI, 0.72 to 0.91]) and ischemic (HR, 0.82 [CI, 0.63 to 1.06]) disease, although the latter estimate did not reach statistical significance. The rate of sudden death fell from 12.15% with conventional care to 4.39% with ICD therapy (HR, 0.41 [CI, 0.30 to 0.56]), with a similar magnitude of reduction in patients with ischemic (HR, 0.39 [CI, 0.23 to 0.68]) and those with nonischemic disease (HR, 0.44 [CI, 0.17 to 1.12]). Noncardiac and any cardiac deaths did not differ significantly by treatment. Limitation Heterogeneous timing of ICD placement; heterogeneous pharmacologic and resynchronization co-interventions; trials conducted in different eras; adverse events and complications not reviewed. Conclusion Overall, primary prevention with ICD therapy versus conventional care reduced the incidence of sudden and all-cause death. Primary funding source None.

// Gian Matteo Rigolin 1 , Elena Saccenti 1,2 , Lara Rizzotto 1 , Manuela Ferracin 2 , Sara Martinelli 1 , Luca Formigaro 1 , Francesca Cibien 1 , Maurizio Cavallari 1 , Enrico Lista 1 , Giulia Daghia 1 , Olga Sofritti 1 , Maria Ciccone 1 , Francesco Cavazzini 1 , Laura Lupini 2 , Cristian Bassi 2 , Barbara Zagatti 2 , Massimo Negrini 2 , Antonio Cuneo 1 1 Hematology Section, Department of Medical Sciences, University of Ferrara, University Hospital Arcispedale S. Anna, Ferrara, Italy 2 Laboratory for Technologies of Advanced Therapies (LTTA) and Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy Correspondence: Gian Matteo Rigolin, email: // Keywords : Oncotargets, miR-125a-5p, CLL, CD38, prognosis Received : September 8, 2013 Accepted : October 28, 2013 Published : October 30, 2013 Abstract The majority of patients with chronic lymphocytic leukemia (CLL) and favorable prognostic features live for long periods without treatment. However, unexpected disease progression is observed in some cases. In a cohort of untreated CD38- CLL patients with normal FISH or isolated 13q- we found that, by fluorescence in situ hybridization (FISH), 16/28 cases presented, within immunomagnetic sorted CD38+ cells, genetic lesions undetectable in the CD38- fraction. These patients showed a shorter time to first treatment (TTFT, p=0.0162) in comparison to cases without FISH lesions in CD38+ cells. Patients with FISH abnormalities in CD38+ cells showed a distinctive microRNA profile, characterized by the down-regulation of miR-125a-5p both in the CD38- and CD38+ populations. In an independent cohort of 71 consecutive untreated CD38- CLL with normal FISH or isolated 13q-, a lower miR125a-5p expression was associated with a shorter TTFT both in univariate and multivariate analysis (p=0.003 and 0.016, respectively) and with a higher prevalence of mutations (7/12 vs 0/8, p=0.015) as assessed by next-generation sequencing. In conclusion, our data showed previously unrecognized subclonal heterogeneity within the CD38+ fraction of CD38- CLL patients with low-risk FISH findings and suggested an association between down-regulated miR-125a-5p expression, genetic complexity and worse outcome.

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with “normal” FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic features.

To better define the significance of proliferation centers (PCs), the morphological hallmark of chronic lymphocytic leukemia (CLL), lymph node biopsies taken from 183 patients were submitted to histopathologic and fluorescence in situ hybridization (FISH) studies using a 5-probe panel on tissue microarrays. Seventy-five cases (40.9%) with confluent PCs were classified as 'PCs-rich' and 108 cases (59.1%) with scattered PCs were classified as 'typical'. Complete FISH data were obtained in 101 cases (55.1%), 79 of which (78.2%) displayed at least one chromosomal aberration. The incidence of each aberration was: 13q- 36,7%, 14q32 translocations 30.8%, 11q- 24.7%, trisomy 12 19.5% and 17p- 15.6%. Five cases showed extra copies of the 14q32 region. The 'PCs-rich' group was associated with 17p-, 14q32/IgH translocation, +12, Ki-67>30%. The median survival from the time of tissue biopsy for PCs-rich and typical groups was 11 and 64 months, respectively (P=0.00001). The PCs-rich pattern was the only predictive factor of an inferior survival at multivariate analysis (P=0.022). These findings establish an association between cytogenetic profile and the amount of PC in CLL, and show that this histopathologic characteristic is of value for risk assessment in patients with clinically significant adenopathy.