Papers by Maria Angela Losi
Diagnostics, 2022
Cardiac surgery is necessary in almost 50% of patients with endocarditis. Early surgery, i.e., th... more Cardiac surgery is necessary in almost 50% of patients with endocarditis. Early surgery, i.e., the surgery performed during the first hospitalization, is required in the following cases: heart failure secondary to valve regurgitation; S. aureus, fungal organism, or other highly resistant organism infection; heart block, annular or aortic abscess, or destructive penetrating lesions; evidence of persistent infection as manifested by persistent bacteremia or fevers lasting >5 days after onset of appropriate antimicrobial therapy. A 62-year-old man developed a fever (38 °C) 3 days after a transaortic electrophysiological study; blood cultures were positive for S. aureus, and were sensitive to vancomycin and ceftaroline. Antibiotic therapy was started, controlling the fever and the patient’s infective and inflammatory profiles well; however, 3 days later, acute aortic regurgitation developed. At transesophageal echocardiography (TEE), a rare condition was revealed—vegetation was attac...
European Heart Journal, 2017
The notion that women have better cardiovascular (CV) outcome than men is consolidated by strong ... more The notion that women have better cardiovascular (CV) outcome than men is consolidated by strong evidence. However whether or not this sexspecific protection persists also in the presence of hypertensive target organ damage such as left ventricular (LV) hypertrophy (LVH) is unclear. Purpose: Our objective was to assess whether the presence of LVH alters the outcome difference between men and women with treated arterial hypertension. Methods: Clinical, echocardiographic and outcome data from 5,395 women and 6,937 men free from prevalent CV disease from the prospective Campania Salute Network registry were used. Median follow-up was 49 months. LVH was identified from prognostically validated sex-specific cut-off values of LV mass index (47 g/m 2.7 for women and 50 g/m 2.7 for men). The impact of sex on incident major cardiovascular events (MACE; combined acute coronary syndromes, stroke, hospitalization for heart failure and incident atrial fibrillation) was assessed in the presence or absence of LVH, using Cox regression analysis and reported as hazard rates (HR) and 95% confidence intervals (CI). Results: Women were older, more obese, had higher systolic blood pressure (BP), total and high density lipoprotein cholesterol, and lower diastolic BP, serum triglycerides and glomerular filtration rate compared to men (all p<0.01), while the prevalence of smoking did not differ. LVH was more prevalent in women than men (43.2 vs. 32.4%, p<0.001). Incident MACE occurred in 3.5% of men and 2.8% of women during follow-up (p=0.040). In Cox regression analysis among subjects without LVH, adjusting for baseline differences in CV risk factors, women without LVH had a 32% lower HR for MACE (95% CI 0.49-0.95), p=0.025) than men without LVH (Figure, Panel A). Running the same model in subjects with LVH, women with LVH did not have a significantly lower HR for MACE (HR 0.79 [0.59-1.06], p=0.110) than men with LVH (Figure Panel B). Conclusions: In hypertension, presence of LVH attenuates the sex difference in CV risk.
Monaldi Archives for Chest Disease, 2021
Ischemic stroke represents one of the most important health problems in industrialized countries,... more Ischemic stroke represents one of the most important health problems in industrialized countries, both for epidemiological and socio-economic impact. The presence of thrombi in the aorta is rare and its treatment has not been uniquely defined. Here we report the case of an 82-years-old man with aortic thrombosis and acute ischemic stroke.
Journal of Clinical Medicine, 2021
Aims. The occurrence of ventricular arrhythmias (VAs) in ischemic heart disease (IHD) patients is... more Aims. The occurrence of ventricular arrhythmias (VAs) in ischemic heart disease (IHD) patients is related to the presence and extent of fibrotic/scar tissue. As coronary atherosclerosis is the underlying cause of myocardial ischemia and fibrosis, in IHD patients implanted with an implantable cardioverter defibrillator (ICD) we investigated the relation between the VA burden and the complexity of coronary atherosclerotic lesions. Methods and results. In IHD patients who underwent coronary angiography and ICD implant, the Syntax scores I and II (SSI-II), as index of the severity of the coronary atherosclerotic disease, and the occurrence of VA were assessed. Overall 144 patients were included (123 males). Of these 22 patients (15%) experienced at least one episode of VA (cycle length 298 ± 19 msec) that required ICD intervention. The number of episodes per patient and per year was 4 ± 6 and 2.8 ± 4, respectively. Patients that experienced a VA compared to those free from arrhythmic ev...
European Heart Journal, 2020
Background The heart failure with preserved ejection fraction (HFpEF) score is easy to use and po... more Background The heart failure with preserved ejection fraction (HFpEF) score is easy to use and potentially useful to discriminate HFpEF from noncardiac causes of dyspnea. HFpEF score may be expressed also as probability to have HFpEF. Purpose We investigated whether a high HFpEF score can identify specific cardiovascular (CV) profile in treated hypertensive patients even without dyspnea. Methods From September to December 2019, we consecutively enrolled treated hypertensive patients without dyspnea, with normal left ventricular (LV) ejection fraction (>50%), and chronic kidney disease of no more than stage III. In addition to standard echocardiographic parameters we evaluated: 1) inappropriate LV mass, identified as a percent of predicted LV mass >128%, 2) myocardial energetic efficiency as the ratio of stroke volume to heart rate normalized by LV mass (MEEi), and 3) an estimate of arterial stiffness, i.e. the ratio of pulse pressure and stroke index (by allometric normalizati...
European Heart Journal, 2020
Background Common Carotid artery (CA) cross sectional area (CCSA) is strictly related to vessel r... more Background Common Carotid artery (CA) cross sectional area (CCSA) is strictly related to vessel remodelling stimulated by mechanical stress due to arterial hypertension. Accordingly, increased CCSA might represent an early marker of vascular target organ damage independently of presence of atherosclerotic plaque. Purpose To assess early correlates and prognostic impact of CCSA in a large population of young treated HTN patients. Methods We selected 970 hypertensive patients, 18 to 40 years old (mean age 34±5 yrs; 30% women) of the Campania Salute Network registry with available CA ultrasound and follow-up data, free of overt cardiovascular (CV) disease. CCSA was computed as: CCSA = π [(CAd/2 + IMT)2 – (CAd/2)2] where CAd = CA diameter and IMT = mean intima media thickness. Participants were compared by CCSA tertiles. Results Compared to the lowest and intermediate tertiles, patients in the highest tertile were more often male, smokers, older, and had higher body mass index (BMI), di...
EP Europace, 2018
P396 Table. ROTEM data: Effect of tPA, TXA, AC/AP Sample CT (s) MCF(mm) CL (%) Control 128 55 7 t... more P396 Table. ROTEM data: Effect of tPA, TXA, AC/AP Sample CT (s) MCF(mm) CL (%) Control 128 55 7 tPA 127 55 66 tPAþTXA 123 55 9 tPAþ heparin 364 46 100 tPAþheparinþTXA 295 55 7 tPAþabciximab 123 32 72 tPAþabciximabþTXA 157 28 11 tPA-tissue plasminogen activator, TXA-tranexamic acid, CT-clot time, MCF-maximum clot firmness, ML-maximum lysis
European Heart Journal, 2018
The purpose of this study was to identify the optimal projection direction of the LAD/Dx bifurcat... more The purpose of this study was to identify the optimal projection direction of the LAD/Dx bifurcations using CCTA. Methods: We investigated a total of 300 LAD/Dx bifurcations via the CCTA results of 237 patients who had no prior histories of percutaneous coronary interventions or other cardiac surgeries. These bifurcations were categorized into three groups according to the distance between the ostial LAD and the ostial Dx. If the distance between the ostial LAD and the ostial Dx was within 15 mm, the bifurcations were classified as proximal. When the distance was 15 to 30 mm, the bifurcations were classified as mid. The bifurcations were classified as distal when the distance was more than 30 mm. There were 90 bifurcations in the proximal group, 126 bifurcations in the mid group, and 84 bifurcations in the distal group. The ideal projection direction was identified using a dedicated image viewing software. By rotating the volume-rendering images of the bifurcations around the rotary axis of a main branch in a certain direction, the largest angle between the main and side branches could be obtained (as shown in the figure; left side). This direction was defined as the ideal projection direction of the bifurcation, and was recorded on the projection direction map. Results: The distribution of the optimal projection direction of each group was indicated in the figure (right side). In the proximal group, the ideal projection direction was mainly distributed around a deep cranial view and a deep right anterior oblique caudal view. The distribution of the mid group was similar to that of the proximal group. The distribution of the distal group was different from the other two groups, as it was around the moderate to deep left anterior oblique cranial view. For most of the bifurcations, the ideal projection directions were distributed outside the observation range of the fluoroscopic apparatus. The optimal projection directions were precisely identified using CCTA, and most of them were distributed outside the observation range of the fluoroscopic apparatus. This information might enable us to treat LAD/Dx bifurcations more effectively.
Journal of human hypertension, Jan 29, 2016
Reduced myocardial mechano-energetic efficiency (MEE), estimated as stroke volume/heart rate rati... more Reduced myocardial mechano-energetic efficiency (MEE), estimated as stroke volume/heart rate ratio per g of left ventricular (LV) mass (LVM), and expressed in μl s(-1) g(-1) (MEEi), is a strong predictor of cardiovascular (CV) events, independently of LV hypertrophy and other confounders, including type II diabetes (DM). Decreased MEEi is more frequent in patients with diabetes. In the present analysis we evaluated the interrelation among MEEi, DM and metabolic syndrome (MetS) in the setting of arterial hypertension. Hypertensive patients from the Campania Salute Network, free of prevalent CV disease and with ejection fraction >50% (n=12 503), were analysed. Coexistence of MetS and DM was ordinally categorized into 4 groups: 8235 patients with neither MetS nor DM (MetS-/DM-); 502 without MetS and with DM (MetS-/DM+); 3045 with MetS and without DM (MetS+/DM-); and 721 with MetS and DM (MetS+/DM+). After controlling for sex, systolic blood pressure, body mass index, relative wall t...
Journal of the American College of Cardiology, 1998
thickness wore not mcroasod ~n dogs w'tYn 'PFYg~, mo~'p~o'~o~c and luno~on~.'~ d,I/~t ~d~',,z/('d... more thickness wore not mcroasod ~n dogs w'tYn 'PFYg~, mo~'p~o'~o~c and luno~on~.'~ d,I/~t ~d~',,z/('d (~d#~:'/m.F~ ~l~#1,'~p,~y ..?I/be .c~))~/).,~)')#,v.~), ~B ,e, hDJ4,,~ D,9)/~w," PRVP (n -6) Normnt (n = 6) % Cell Vohmm (.m 3) 30,053 i 2,549' 32,411 t 1,510 ~20 Celt Length (.m) 18,t I 5' 142 t: 2 ~20 Cstl Width (~m) 23,5 t 08 22,0 ~ 1,1 Lenoth/Widlh 8.3 t 04' 7,0 t; 0.4 ~,10 Coil Shortening (%) 4.2 t 0,fi' 7,P~ t 1,1 .... 42 Coil Rslnwstion (BSC) t O1 t 0,1' 0,71 :t 0,07 42 ;' denotes p • 0.05 v~ contrail Cenclu,~lons: 1) Cellular hypertrophy contdbufoa to venfrlcul~r remodeling in PRVPqnduood DCM in dogs, ?.) DIsproportionnl chnngos in myooyto go. omefry a!tar RVP may contribute fo incroa,os In LV wall Bfros,, 3) Increased LV chamber dimensions and dapmt~sad venfriculnr function am well reflected at the cellular level,
High blood pressure & cardiovascular prevention, Sep 22, 2020
Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Ins... more Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Insulin resistance is defined as a less than expected biologic response to a given concentration of the hormone and plays a pivotal role in the pathogenesis of diabetes. However, over the last decades, it became evident that insulin resistance is not merely a metabolic abnormality, but is a complex and multifaceted syndrome that can also affect blood pressure homeostasis. The dysregulation of neurohumoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. These mechanisms induce a chronic low grade of inflammation that interferes with insulin signalling transduction. Molecular abnormalities associated with insulin resistance include the defects of insulin receptor structure, number, binding affinity, and/or signalling capacity. For instance, hyperglycaemia impairs insulin signalling through the generation of reactive oxygen species, which abrogate insulin-induced tyrosine autophosphorylation of the insulin receptor. Additional mechanisms have been described as responsible for the inhibition of insulin signalling, including proteasome-mediated degradation of insulin receptor substrate 1/2, phosphatase-mediated dephosphorylation and kinase-mediated serine/threonine phosphorylation of both insulin receptor and insulin receptor substrates. Insulin resistance plays a key role also in the pathogenesis and progression of hypertension-induced target organ damage, like left ventricular hypertrophy, atherosclerosis and chronic kidney disease. Altogether these abnormalities significantly contribute to the increase the risk of developing type 2 diabetes.
European Heart Journal
Background Only one score for prediction of new-onset atrial fibrillation (AF) in patients with h... more Background Only one score for prediction of new-onset atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) has been developed in North America (HCM-AF North America score). Purpose To develop a new score (HCM-AF South Italy score) in an Italian derivation cohort and to test the new score with that from North America, in an Italian validation cohort. Methods A cohort of 228 patients with HCM and without history of AF, followed at referral center 1 for HCM, was used for model development. A cohort of 226 patients without history of AF, followed at referral center 2, was used for external validation. During follow-up (IQR 3–13 years, median 8 years), 59 (26%) patients developed new-onset AF. Data in the development cohort generated the HCM-AF South Italy score, a point score to predict AF probability: left atrial dimension >49 mm (+5 points), age at clinical evaluation <55 years (+2 points), the use of angiotensin-converting enzyme (ACE) or inhibitor or ang...
Biomolecules
The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification ... more The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification of pathogenic mutations of cardiomyopathies and channelopathies in more than 200 different genes. Since genes considered uncommon for a clinical phenotype are also now included in molecular testing, the detection rate of disease-causing variants has increased. Here, we report the prevalence of genetic variants detected by using a NGS custom panel in a cohort of 133 patients with inherited cardiomyopathies (n = 77) or channelopathies (n = 56). We identified 82 variants, of which 50 (61%) were identified in genes without a strong or definitive evidence of disease association according to the NIH-funded Clinical Genome Resource (ClinGen; “uncommon genes”). Among these, 35 (70%) were variants of unknown significance (VUSs), 13 (26%) were pathogenic (P) or likely pathogenic (LP) mutations, and 2 (4%) benign (B) or likely benign (LB) variants according to American College of Medical Genetics (...
Diagnostics
Background: The influence of age and gender on strain-imaging-derived myocardial work (MW) was re... more Background: The influence of age and gender on strain-imaging-derived myocardial work (MW) was recently investigated in healthy subjects. No information is available on the impact of heart rate (HR) on MW. Methods: 177 healthy subjects (47% men, mean age 42 years) underwent an echo-Doppler exam, including quantification of global longitudinal strain (GLS). Cuff blood pressure was used as a surrogate of left ventricular peak pressure to estimate global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). Statistical analyses were performed according to age and HR tertiles. Results: GWW was higher in the third HR tertile, i.e., ≥74 bpm (74.7 ± 33.6 mmHg %) than in the first HR tertile (<66 bpm) (61.0 ± 32.5 mmHg %) (p < 0.02). In the pooled population, by adjusting for systolic blood pressure, GLS, E/e’ ratio and left atrial volume index, age was independently associated with GCW (β = 0.748) and GWI (β = 0.685) (both p <...
European Heart Journal - Cardiovascular Imaging, 2021
Aims Cardiac magnetic resonance (CMR) is recommended in the diagnosis of cardiomyopathies, but i... more Aims Cardiac magnetic resonance (CMR) is recommended in the diagnosis of cardiomyopathies, but it is time-consuming, expensive, and limited in availability in some European regions. The aim of this study was to determine the use of CMR in cardiomyopathy patients enrolled into the European Society of Cardiology (ESC) cardiomyopathy registry [part of the EURObservational Research Programme (EORP)]. Methods and results Three thousand, two hundred, and eight consecutive adult patients (34.6% female; median age: 53.0 ± 15 years) with cardiomyopathy were studied: 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM), and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC). CMR scans were performed at baseline in only 29.4% of patients. CMR utilization was variable according to cardiomyopathy subtypes: from 51.1% in ARVC to 36.4% in RCM, 33.8% in HCM, and 20.6% in DCM (P < 0.001). CMR use in tertiary referral centres located in different European...
High Blood Pressure & Cardiovascular Prevention, 2020
Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Ins... more Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Insulin resistance is defined as a less than expected biologic response to a given concentration of the hormone and plays a pivotal role in the pathogenesis of diabetes. However, over the last decades, it became evident that insulin resistance is not merely a metabolic abnormality, but is a complex and multifaceted syndrome that can also affect blood pressure homeostasis. The dysregulation of neurohumoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. These mechanisms induce a chronic low grade of inflammation that interferes with insulin signalling transduction. Molecular abnormalities associated with insulin resistance include the defects of insulin receptor structure, number, binding affinity, and/or signalling capacity. For instance, hyperglycaemia impairs insulin signalling through the generation of reactive oxygen species, which abrogate insulin-induced tyrosine autophosphorylation of the insulin receptor. Additional mechanisms have been described as responsible for the inhibition of insulin signalling, including proteasome-mediated degradation of insulin receptor substrate 1/2, phosphatase-mediated dephosphorylation and kinase-mediated serine/threonine phosphorylation of both insulin receptor and insulin receptor substrates. Insulin resistance plays a key role also in the pathogenesis and progression of hypertension-induced target organ damage, like left ventricular hypertrophy, atherosclerosis and chronic kidney disease. Altogether these abnormalities significantly contribute to the increase the risk of developing type 2 diabetes.
European Heart Journal, 2020
Background Heart rate reserve (HRR) during exercise evaluates chronotropic incompetence and is a ... more Background Heart rate reserve (HRR) during exercise evaluates chronotropic incompetence and is a prognostically important marker of cardiac autonomic dysfunction, additive to regional wall motion abnormalities (RWMA) in patients with coronary artery disease. Objectives To assess determinants and prognostic value of HRR in patients with hypertrophic cardiomyopathy (HCM). Methods From 1998 to 2019, we enrolled 774 HCM patients (age = 48.8±15.9 years, 410 men) with exercise stress echocardiography (ESE) in 10 certified centres of the international stress echo network. During ESE we assessed: left ventricular outflow tract obstruction (LVOTO, significant when >50 mmHg); RWMA; HRR (peak/ rest heart rate), 344 in beta-blockers therapy (44.4%). Patients were followed for a median 49 months (IQ range, 25–78 months). The study end-point was all-cause mortality. Results During ESE, we observed stress-induced RWMA in 42 (5.4%) and LVOTO in 248 (33%); HRR was 1.92.±0.41. There were no differ...
European Journal of Preventive Cardiology, 2020
Background Determinants of changes of aortic root dimension over time are not well defined. Desig... more Background Determinants of changes of aortic root dimension over time are not well defined. Design We investigated whether specific phenotype and treatment exist predicting changes in aortic root dimension in hypertensive patients from the Campania Salute Network. Methods N = 4856 participants (age 53 ± 11 years, 44% women) were included. At first and last available echocardiograms, we measured aortic root and a z-score of aortic root (AOz) was generated as the difference between measured and predicted aortic root, derived from a healthy reference population. Aortic root dilatation (ARD) was defined as AOz >75th percentile of distribution. Results At baseline, 3642 patients (75%) exhibited normal aortic root, and 1214 (25%) ARD. After a follow-up of 6.1 years (interquartile range 3.0–8.8 years), 366 (11%) patients with initial normal aortic root exhibited ARD, whereas 457(38%) with initial ARD exhibited normal aortic root. At multivariate analysis patients with incident ARD were ...
Journal of Cardiovascular Translational Research, 2020
In the era of Next Generation Sequencing (NGS), genetic testing for inherited disorders identifie... more In the era of Next Generation Sequencing (NGS), genetic testing for inherited disorders identifies an ever-increasing number of variants whose pathogenicity remains unclear. These variants of uncertain significance (VUS) limit the reach of genetic testing in clinical practice. The VUS for Hypertrophic Cardiomyopathy (HCM), the most common familial heart disease, constitute over 60% of entries for missense variants shown in ClinVar database. We have studied a novel VUS (c.1809T>G-p.I603M) in the most frequently mutated gene in HCM, MYBPC3, which codes for cardiac myosin-binding protein C (cMyBPC). Our determinations of pathogenicity integrate bioinformatics evaluation and functional studies of RNA splicing and protein thermodynamic stability. In silico prediction and mRNA analysis indicated no alteration of RNA splicing induced by the variant. At the protein level, the p.I603M mutation maps to the C4 domain of cMyBPC. Although the mutation does not perturb much the overall structure of the C4 domain, the stability of C4 I603M is severely compromised as detected by circular dichroism and differential scanning calorimetry experiments. Taking into account the highly destabilizing effect of the mutation in the structure of C4, we propose reclassification of variant p.I603M as likely pathogenic. Looking into the future, the workflow described here can be used to refine the assignment of pathogenicity of variants of uncertain significance in MYBPC3.
European Heart Journal, 2017
Background: Obese persons have lower circulating natriuretic peptide (NP) concentrations, and it ... more Background: Obese persons have lower circulating natriuretic peptide (NP) concentrations, and it has been proposed that this "natriuretic handicap" could play a role in obesity-related hypertension. In contrast, patients with left atrial enlargement have higher circulating NP concentrations. The relationship between circulating NP concentrations and left atrial size in obese hypertensive persons is not clear. Purpose: To investigate whether obese men with hypertension have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size. Methods: We examined 103 obese men (body mass index (BMI) ≥30.0 kg/m 2) and 27 lean normotensive men (BMI 20.0-24.9 kg/m 2). All men were generally healthy and medication-free with normal left ventricular ejection fraction. We measured blood pressure using 24-hr ambulatory blood pressure (ABP) recordings. Hypertension was defined as 24-hr AMP ≥130/80 mmHg, and normotension was defined as 24-hr AMP <130/80 mmHg. We determined left atrial size using standard echocardiography (2d average of 2-chamber and 4 chamber view), and we measured fasting serum concentrations of midregional proatrial natriuretic peptide (MR-proANP). ANOVA, corrected with Tukey for multiple comparisons, was used to compare groups. Results: Of the 103 obese men, 63 had hypertension and 40 were normotensive. The table shows that there was no difference in age between the 3 groups, and that the 2 obese groups had similar BMI. The table further shows that the obese hypertensive men had lower serum MR-proANP concentrations and greater left atrial size compared with the lean normotensive men.
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Papers by Maria Angela Losi