Giuseppe Ambrosio
Università degli Studi di Perugia, Medicina, Faculty Member
In the postischemic heart, coronary vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function. Although the eNOS cofactor tetrahydrobiopterin (BH4) is depleted, its repletion only partially restores... more
In the postischemic heart, coronary vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function. Although the eNOS cofactor tetrahydrobiopterin (BH4) is depleted, its repletion only partially restores eNOS-mediated coronary vasodilation, indicating that other critical factors trigger endothelial dysfunction. Therefore, studies were performed to characterize the unidentified factor(s) that trigger endothelial dysfunction in the postischemic heart. We observed that depletion of the eNOS substrate NADPH occurs in the postischemic heart with near total depletion from the endothelium, triggering impaired eNOS function and limiting BH4 rescue through NADPH-dependent salvage pathways. In isolated rat hearts subjected to 30 min of ischemia and reperfusion (I/R), depletion of the NADP(H) pool occurred and was most marked in the endothelium, with >85% depletion. Repletion of NADPH after I/R increased NOS-dependent coronary flow well above that with BH4 alone. ...
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We investigated the relationship between the day-night blood pressure (BP) dip and the early morning BP surge in an cohort of 3012 initially untreated subjects with essential hypertension. The day-night reduction in systolic BP showed a... more
We investigated the relationship between the day-night blood pressure (BP) dip and the early morning BP surge in an cohort of 3012 initially untreated subjects with essential hypertension. The day-night reduction in systolic BP showed a direct association with the sleep trough ( r =0.564; P <0.0001) and the preawakening ( r =0.554; P <0.0001) systolic BP surge. Over a mean follow-up period of 8.44 years, 268 subjects developed a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and heart failure requiring hospitalization) and 220 subjects died. In a Cox model, after adjustment for predictive covariates, including age, sex, diabetes mellitus, cigarette smoking, total cholesterol, left ventricular hypertrophy on ECG, estimated glomerular filtration rate, and average 24-hour systolic BP, a blunted sleep trough (≤19.5 mm Hg; quartile 1) and preawakening (≤9.5 mm Hg; quartile 1) BP surge was associated with an excess ris...
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Research Interests: Cardiology, Medicine, Echocardiography, Humans, Left Ventricular Assist Device, and 13 moreFemale, Male, Myocardial Revascularization, Left Ventricular Dysfunction, Dilated cardiomyopathy, Aged, Middle Aged, Prognosis, Myocardial Ischemia, Diastole, Left Ventricular, systole, and Cardiovascular medicine and haematology
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Stable angina (SA) is a chronic condition reducing physical activity and quality of life (QoL). Physicians treating patients with SA in Italy, Germany, Spain, and United Kingdom completed a web-based survey. The objective was to assess... more
Stable angina (SA) is a chronic condition reducing physical activity and quality of life (QoL). Physicians treating patients with SA in Italy, Germany, Spain, and United Kingdom completed a web-based survey. The objective was to assess physician perceptions of patient needs, the impact of SA on QoL, and evaluate SA management. Overall, 659 physicians (cardiologists and general practitioners) entered data from 1965 eligible patients. The perceived importance of everyday activities for patients with a recent diagnosis (≤2 years) was higher than for patients with a longer diagnosis (>2 years), while severity of limitations for those activities were rated similarly for both groups. Gender-based analyses revealed that physicians documented more severe SA, more symptoms and more angina attacks in women, yet they rated the patients’ condition as similar for both sexes. Women also received less medical and interventional treatment. Patients who have previously had a percutaneous coronary...
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To assess the characteristics and prognosis of patients with myocardial infarction and non-obstructed coronary arteries (MINOCA). MINOCA was defined as acute myocardial infarction (AMI) with angiographic coronary stenosis... more
To assess the characteristics and prognosis of patients with myocardial infarction and non-obstructed coronary arteries (MINOCA). MINOCA was defined as acute myocardial infarction (AMI) with angiographic coronary stenosis <50%.Cardiomyopathies and myocarditis were - a priori - excluded from the study. Stenoses <30% were considered normal coronary arteries (NCA); stenoses ≥30% but <50% were considered mild coronary artery disease (MCAD). Patients were subdivided in 3 groups: I) NCA (0 vessels; stenosis <30%); II) 1-2 vessels showing MCAD and III) MCAD in 3 vessels or the left main stem (LMS). From January 2006 to December 2014, 7935 consecutive AMI patients were entered into our institutional database;150 (2%) were diagnosed as having MINOCA. At a median follow-up of 7.1 years the composite end-point (cardiovascular death, AMI or acute coronary syndrome, heart failure, stroke) occurred in 23 patients (17.4%). Survival analysis showed no differences between NCA versus MCAD...
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Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical... more
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained ov...
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Despite the availability of anti-hypertensive medications with proven efficacy and good tolerability, many hypertensive patients have blood pressure levels(BP) not at the goals set by international societies. Some of these patients are... more
Despite the availability of anti-hypertensive medications with proven efficacy and good tolerability, many hypertensive patients have blood pressure levels(BP) not at the goals set by international societies. Some of these patients are either non-adherent to the prescribed drugs or not optimally treated. However, a proportion, despite adequate treatment, has resistant hypertension(RH) defined as office BP above goal despite the use of ≥3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic). Diagnosis of RH based upon office measurements, however, needs confirmation through 24-h BP monitoring to exclude "white coat" RH since cardiovascular events and mortality rates follow mean ambulatory BPs. Although several studies have approached the issue of the prevalence of RH in the hypertensive population, its prevalence is by and large based upon reasonable but approximate estimates for reasons detailed in the text. Standardized combination ther...
Although transcatheter aortic valve implantation (TAVI) is a steadily expanding treatment for the pathology of the aortic valve, its role in the replacement of native aortic valves following valve-sparing surgery has not been... more
Although transcatheter aortic valve implantation (TAVI) is a steadily expanding treatment for the pathology of the aortic valve, its role in the replacement of native aortic valves following valve-sparing surgery has not been investigated. Among 150 patients who underwent TAVI at the authors' institution, three (2%) had a failed valve-sparing operation. The in-hospital outcome, mid-term mortality, and valvular function of the three patients were evaluated retrospectively. These patients, who were deemed at high surgical risk by the heart team, underwent TAVI for predominant severe aortic stenosis (n = 2) or pure severe aortic regurgitation (AR) (n = 1). A self-expandable CoreValve prosthesis was inserted via femoral access in all three patients. Based on the Valve Academic Research Consortium 2 criteria (VARC-2), implantation was successful in all cases, with only one major access site complication and no more than mild residual AR. At a follow up of 13 ± 6 months there were no ...
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: Structural changes in left and right cardiac chambers that occur in arterial hypertension (AH) may lead to an increased risk of atrial fibrillation. Considering that AH is currently the most common cardiovascular disease in the general... more
: Structural changes in left and right cardiac chambers that occur in arterial hypertension (AH) may lead to an increased risk of atrial fibrillation. Considering that AH is currently the most common cardiovascular disease in the general population, it represents a major risk factor for atrial fibrillation development. This review explores the complex relationship between atrial fibrillation and AH, starting from its pathophysiological basis. It focuses on the role of echocardiography in the management of hypertensive and atrial fibrillation patients, with emphasis on what should be evaluated about left ventricular remodeling, diastolic and systolic function, left atrial (LA) size and function and right ventricular deformation in patients with AH.
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Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure... more
Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. The most important studies published in the literature on LA size, function and diastolic dysfunction in patie...
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Trancatheter heart valve (THV) thrombosis is effectively treated with anticoagulation but alternative therapies are required when a faster gradient reduction is needed. Open heart surgery has been rarely performed due to the high... more
Trancatheter heart valve (THV) thrombosis is effectively treated with anticoagulation but alternative therapies are required when a faster gradient reduction is needed. Open heart surgery has been rarely performed due to the high perioperative mortality and only five cases have been described so far. Here we describe a case of emergent surgical explantation for THV thrombosis after a valve-in-valve. A 67years old man underwent transcatheter aortic valve implantation for a failed surgical bioprosthesis Epic 21mm (St. Jude Medical; St. Paul, Minnesota, US). A CoreValve 23mm (Medtronic, Minneapolis, Minnesota, US) was implanted through femoral access under conscious sedation without complications. Mean transvalvular gradient was effectively reduced (33mmHg vs 16mmHg) with no more than mild residual aortic regurgitation. After 8days the patient was discharged on dual antiplatelet therapy but was readmitted to the intensive care unit for pulmonary oedema 13days later. Echocardiography sh...
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The prevalence of chronic heart failure (CHF) is steadily increasing. Both sexes are affected, with significant differences in etiology, epidemiology and clinical presentation, prognosis, comorbidities, and response to treatment. Women... more
The prevalence of chronic heart failure (CHF) is steadily increasing. Both sexes are affected, with significant differences in etiology, epidemiology and clinical presentation, prognosis, comorbidities, and response to treatment. Women tend to develop CHF at a more advanced age, present more often with HF with preserved ejection fraction, are more symptomatic, and have a worse quality of life than men, but also a better prognosis. In women, CHF has more frequently a non-ischemic etiology, and arterial hypertension and diabetes mellitus are leading comorbidities. Furthermore, many sex-related differences have been detected in the response to treatment, for example a greater prognostic benefit from angiotensin-receptor blockers in women, a higher incidence of complications after defibrillator implantation, and a greater response to cardiac resynchronization therapy. Furthermore, women are less likely to receive defibrillator therapy or heart transplantation. The significant underrepre...
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T-wave abnormalities are common during the acute phase of non-ST-segment elevation acute coronary syndromes, but mechanisms underlying their occurrence are unclear. We hypothesized that T-wave abnormalities in the presentation of... more
T-wave abnormalities are common during the acute phase of non-ST-segment elevation acute coronary syndromes, but mechanisms underlying their occurrence are unclear. We hypothesized that T-wave abnormalities in the presentation of non-ST-segment elevation acute coronary syndromes correspond to the presence of myocardial edema. Secondary analysis of a previously enrolled prospective cohort of patients presenting with non-ST-segment elevation acute coronary syndromes was conducted. Twelve-lead electrocardiography (ECG) and cardiac magnetic resonance with T2-weighted imaging were acquired before invasive coronary angiography. ECGs were classified dichotomously (ie, ischemic versus normal/nonischemic) and nominally according to patterns of presentation: no ST- or T-wave abnormalities, isolated T-wave abnormality, isolated ST depression, ST depression+T-wave abnormality. Myocardial edema was determined by expert review of T2-weighted images. Of 86 subjects (65% male, 59.4 years), 36 showe...
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Pericardial cysts (PCs) are very rare, often congenital, mediastinal masses. Usually, they are located in the right cardiophrenic angle and only in 8% of cases in the anterior or posterior mediastinum. Computed tomography and/or magnetic... more
Pericardial cysts (PCs) are very rare, often congenital, mediastinal masses. Usually, they are located in the right cardiophrenic angle and only in 8% of cases in the anterior or posterior mediastinum. Computed tomography and/or magnetic resonance imaging are accurate tools for the diagnosis and characterization of mediastinal masses. However, echocardiography is, in many cases, a good screening technique. If asymptomatic, they do not require surgical excision. The authors describe a case of posterior mediastinum PC; in these cases, echocardiography cannot see the mass and three-dimensional imaging techniques are required. The clinical management of this case is discussed.
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Contradictory findings have been reported regarding the safety and efficacy of digitalis in patients recovering from acute myocardial infarction (MI). We studied the association of digitalis use with long-term and short-term prognosis in... more
Contradictory findings have been reported regarding the safety and efficacy of digitalis in patients recovering from acute myocardial infarction (MI). We studied the association of digitalis use with long-term and short-term prognosis in patients presenting with an acute MI complicated with heart failure (HF), left ventricular dysfunction, or both. Using the High-Risk MI Database Initiative combining data from 4 major clinical trials, totaling 27,673 patients, we investigated the association between digitalis use at baseline (3093 patients with digitalis and 24,580 without) with the rate of all-cause death, sudden cardiac death, cardiovascular death, HF hospitalization and the combination of the latter two, over a mean follow-up time of 2.7 years. Patients with and without atrial fibrillation (AF) were studied separately. After a propensity score-based analysis, among patients without AF, those receiving digitalis experienced a higher rate of all-cause [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.42-1.67] and sudden cardiac death (HR 1.65, 95% CI 1.44-1.89), compared to those not receiving digitalis; similar results were found for the other 3 endpoints (all HR around 1.6). In contrast, in AF patients, digitalis had a milder effect on all outcomes (all HR ≤ 1.12), with significant association only for the composite endpoint (HR 1.10, 95% CI 1.00-1.21, p = 0.049); comparable results were obtained at 30 days. Finally, the detrimental effect associated with digitalis use appeared to be more pronounced in patients with ejection fraction ≥ 40%. In MI survivors with HF and/or systolic dysfunction, digitalis was associated with a significant increased risk of death in patients without AF with mild to neutral associations for patients with AF. These findings raise concerns regarding the safety of digitalis in MI survivors with HF, especially for those without AF.
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Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) explored the impact of gender, risk factors and anticoagulant (AC) treatment on 1-year outcomes in patients with non-valvular atrial fibrillation (NVAF).... more
Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) explored the impact of gender, risk factors and anticoagulant (AC) treatment on 1-year outcomes in patients with non-valvular atrial fibrillation (NVAF). GARFIELD-AF is a prospective non-interventional registry. Investigator sites (n=1048) are representative of the care settings/locations in each of the 35 countries. Patients ≥18yrs with newly diagnosed (≤6 weeks' duration) NVAF and ≥1 investigator-determined stroke risk factors. Event rates per 100 person-years were estimated from the Poisson model and HRs and 95% CIs calculated. Of 28 624 patients (women 44.4%; men 55.6%) enrolled, there were more elderly (≥75 years) women (46.9%) than men (30.4%). All-cause mortality rates per 100 person-years (95% CI) for women and men were 4.48 (4.12 to 4.87) and 4.04 (3.74 to 4.38), respectively, stroke/systemic embolism (SE) (1.62 (1.41 to 1.87) and 1.17 (1.01 to 1.36)) and major bleeding (0.93 (0.78 to 1.13) and...
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Administrative healthcare databases can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions and use of healthcare resources, thus providing answers to a wide... more
Administrative healthcare databases can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions and use of healthcare resources, thus providing answers to a wide spectrum of research questions. However, a crucial issue is the reliability of information gathered. Aim of this protocol is to validate International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) codes for major cardiovascular diseases, including acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF) and stroke. Data from the centralised administrative database of the entire Umbria Region (910 000 residents, located in Central Italy) will be considered. Patients with a first hospital discharge for AMI, HF, AF or stroke, between 2012 and 2014, will be identified in the administrative database using the following groups of ICD-9-CM codes located in primary position: (1) 410.x for AMI; (2) 427.31 for ...
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Global peak systolic longitudinal strain (PLS) derived from speckle tracking echocardiography (STE) is a widely used left ventricular deformation parameter. Modern ultrasound systems with improved temporal resolution and new software now... more
Global peak systolic longitudinal strain (PLS) derived from speckle tracking echocardiography (STE) is a widely used left ventricular deformation parameter. Modern ultrasound systems with improved temporal resolution and new software now allow automated multilayer analysis; however, there is limited evidence regarding its reproducibility. We performed intra- and inter-observer analyses within a population-based cohort study using conventional quantitative strain analysis (GE Healthcare). Fifty patients (49 ± 14 years) were randomly selected among the fourth visit of the STANISLAS Cohort. Multilayer PLS (transmural, subendocardial, and subepicardial), and strain rate (peak systolic, early and late diastolic) were evaluated. Peak systolic shortening (PSS) and early positive systolic strain (EPS) were calculated, as well as post-systolic index (PSI) and pre-stretch index (PST), two additional strain-derived parameters. Intra-observer intraclass correlation coefficients (ICC) were >0...
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This was a propensity score analysis of the prospective, randomized, double-blind Survival of Myocardial Infarction Long-term Evaluation (SMILE) 4 study in which one-year treatment with zofenopril 60 mg plus acetylsalicylic acid (ASA) 100... more
This was a propensity score analysis of the prospective, randomized, double-blind Survival of Myocardial Infarction Long-term Evaluation (SMILE) 4 study in which one-year treatment with zofenopril 60 mg plus acetylsalicylic acid (ASA) 100 mg gave superior results compared to ramipril 10 mg plus ASA in terms of death or hospitalization for cardiovascular causes in patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction (LVD). A total of 716 patients of the intention-to-treat population were divided into homogeneous propensity quintiles (Q) using a logistic regression model (QI: best risk profile; QV: worst risk profile). Treatment was associated with a similar low rate of major cardiovascular events in any Q. However, the efficacy of zofenopril was better than that of ramipril in QII, QV, and particularly QIII (odds ratio (OR) and 95% confidence interval: 0.43 (0.21-0.87), p<0.05]. This result was primarily attributed to a decrease in the risk o...
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Pulmonary congestion assessed at discharge by lung ultrasonography predicts poor prognosis in heart failure (HF) patients. We investigated the association of B-lines with indices of hemodynamic congestion [BNP, E/e’, pulmonary systolic... more
Pulmonary congestion assessed at discharge by lung ultrasonography predicts poor prognosis in heart failure (HF) patients. We investigated the association of B-lines with indices of hemodynamic congestion [BNP, E/e’, pulmonary systolic arterial pressure (PAPs)] in HF patients, and their prognostic value overall and according to concomitant atrial fibrillation (AF), reduced (≤40%) ejection fraction (EF), and timing of quantification during hospitalisation for heart failure (HHF). In 110 HHF patients, B-lines were highly discriminative of BNP >400 pg/ml (AUC ≥ 0.80 for all), and moderately discriminative of PAPs >50 mmHg (AUC = 0.68, 0.56 to 0.80); conversely, B-lines poorly discriminated average E/e’ ≥ 15, except at discharge. B-line count significantly predicted mid-term recurrent HHF or death (overall and in subgroups), regardless of AF status, EF, and timing of quantification during HHF (all p for interaction >0.10). regardless, B-lines ≥30 at discharge were most predicti...
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To determine the influence of baseline beta-blocker use on long-term prognosis of myocardial infarction (MI) survivors complicated with heart failure (HF) or with left ventricular dysfunction and with history of chronic obstructive... more
To determine the influence of baseline beta-blocker use on long-term prognosis of myocardial infarction (MI) survivors complicated with heart failure (HF) or with left ventricular dysfunction and with history of chronic obstructive pulmonary disease (COPD). Among the 28 771 patients from the High-Risk MI Database Initiative we identified 1573 patients with a baseline history of COPD. We evaluated the association between beta-blocker use at baseline (822 with beta-blocker and 751 without) on the rates of all-cause and cardiovascular mortality. On univariable Cox analysis, beta-blocker use was found to be associated with lower rates of both all-cause [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.51-0.75, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001] and cardiovascular mortality (HR = 0.63, 95% CI 0.51-0.78, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). After extensive adjustment for confounding, including 24 baseline covariates, COPD patients still benefited from beta-blocker usage (HR = 0.73, 95% CI 0.60-0.90, P = 0.002 for all-cause mortality; HR = 0.77, 95% CI 0.61-0.97, P = 0.025 for cardiovascular mortality). Adjusting for propensity scores (PS) constructed from the 24 aforementioned baseline characteristics provided similar results. In a cohort of 561 pairs of patients taking or not taking beta-blocker matched on PS using a 1:1 nearest-neighbour matching method, patients treated with beta-blocker experienced fewer all-cause deaths (HR = 0.71, 95% CI 0.56-0.89, P = 0.003) and cardiovascular deaths (HR = 0.76, 95% CI 0.59-0.97, P = 0.032). In the specific setting of a well-treated cohort of high-risk MI survivors, beta-blockers were associated with better outcomes in patients with COPD.
Research Interests: Mortality, Medicine, Heart Failure, Humans, Female, and 14 moreMale, Propensity Score, Left Ventricular Dysfunction, Aged, Middle Aged, Myocardial Infarction, Prognosis, Protective factors, Chronic obstructive pulmonary disease, Cardiovascular Diseases, Proportional Hazards Models, Cohort Studies, Cause of death, and Cardiovascular medicine and haematology
We studied evolving antithrombotic therapy patterns in patients with newly diagnosed non-valvular atrial fibrillation (AF) and ≥1 additional stroke risk factor between 2010 and 2015. 39 670 patients were prospectively enrolled in four... more
We studied evolving antithrombotic therapy patterns in patients with newly diagnosed non-valvular atrial fibrillation (AF) and ≥1 additional stroke risk factor between 2010 and 2015. 39 670 patients were prospectively enrolled in four sequential cohorts in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF): cohort C1 (2010-2011), n=5500; C2 (2011-2013), n=11 662; C3 (2013-2014), n=11 462; C4 (2014-2015), n=11 046. Baseline characteristics and antithrombotic therapy initiated at diagnosis were analysed by cohort. Baseline characteristics were similar across cohorts. Median CHA2DS2-VASc (cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)) score was 3 in all four cohorts. From C1 to C4, the proportion of patients on anticoagulant (AC) therapy increased by almost 15% (C1 57.4%; C4 71.1%). Use of vitamin K antagonist (VKA)±antiplatelet (AP) (C1 53.2%; C4 34.0%) and AP monotherapy...
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In 2013 the European Society of Cardiology (ESC) released new guidelines on the management of stable coronary artery disease. These guidelines update and replace the previous ESC guidelines on the management of stable angina pectoris,... more
In 2013 the European Society of Cardiology (ESC) released new guidelines on the management of stable coronary artery disease. These guidelines update and replace the previous ESC guidelines on the management of stable angina pectoris, issued in 2006. There are several new aspects in the 2013 ESC guidelines compared with the 2006 version. This opinion paper provides an in-depth interpretation of the ESC guidelines with regard to these issues, to help physicians in making evidence-based therapeutic choices in their routine clinical practice. The first new element is the definition of stable coronary artery disease itself, which has now broadened from a 'simple' symptom, angina pectoris, to a more complex disease that can even be asymptomatic. In the first-line setting, the major changes in the new guidelines are the upgrading of calcium channel blockers, the distinction between dihydropyridines and non-dihydropyridine calcium channel blockers, and the presence of important sta...
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A national study group has been established by the Italian Federation of Cardiology to investigate the role of stem/progenitor cell therapy in the treatment of cardiovascular diseases. This article is aimed to point out the challenges and... more
A national study group has been established by the Italian Federation of Cardiology to investigate the role of stem/progenitor cell therapy in the treatment of cardiovascular diseases. This article is aimed to point out the challenges and debated issues in the conduction of clinical trials, focusing on the Italian clinical and regulatory existing situation.
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We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drankad libitumregular cola (C,n=12) or tap water (W,n=12).Measures.Body... more
We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drankad libitumregular cola (C,n=12) or tap water (W,n=12).Measures.Body weight, nutritional data, plasma glucose, cholesterol fractions, TG, urea, creatinine, coenzyme Q10, SBP, and echocardiograms (0 mo and 6 mo). At 6 months euthanasia was performed. Kidneys were processed for histopathology and immunohistochemistry (semiquantitative). Compared with W, C rats showed (I) overweight (+8%,p<0.05), hyperglycemia (+11%,p<0.05), hypertriglyceridemia (2-fold,p<0.001), higher AIP (2-fold,p<0.01), and lower Q10level (−55%,p<0.05); (II) increased LV diastolic diameter (+9%,p<0.05) and volume (systolic +24%,p<0.05), posterior wall thinning (−8%,p<0.05), and larger cardiac output (+24%,p<0.05); (III) glomerulosclerosis (+21%,p<0.05), histopathology (+13%,p<0.05), higher tubular expression of IL-6 (7-fo...
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Pulmonary embolism is a common disease with significant mortality. Anticoagulant and thrombolytic therapies are a mainstay in the management of acute pulmonary embolism, especially with hemodynamic compromise. However, systemic drugs... more
Pulmonary embolism is a common disease with significant mortality. Anticoagulant and thrombolytic therapies are a mainstay in the management of acute pulmonary embolism, especially with hemodynamic compromise. However, systemic drugs cannot achieve timely and effective treatment of acute pulmonary embolism in all patients. Recently, rheolytic thrombectomy has been proven to be effective in the treatment of massive thrombosis in vein grafts. The purpose of this study was to describe the rheolytic thrombectomy procedure and to evaluate the efficacy of thrombus removal using the AngioJet catheter in patients with acute massive and submassive pulmonary embolism. Thirty consecutive patients (16 men, 14 women, mean age 67.9 +/- 13.5 years) with massive or submassive pulmonary embolism were treated with rheolytic thrombectomy. The Miller index and the systolic pulmonary pressure were evaluated pre- and post-rheolytic thrombectomy. In-hospital results were analyzed according to the learning curve of operators. Technical success was achieved in 93.3% of patients. Eleven patients received adjunctive loco-regional thrombolytic agent (alteplase) or abciximab. A significant improvement in the obstruction, perfusion and Miller indexes and in the systolic pulmonary pressure was observed after rheolytic thrombectomy (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) in all patients. The achievement of a larger experience by the operators was associated with a less procedural complication rate (i.e. post-procedural increase in creatinine, cardiac arrest during the procedure, post-procedural hemoptysis, and in-hospital mortality). Total in-hospital mortality occurred in 5 patients (16.7%), 60% of them presented with cardiogenic shock. All patients were alive at the 12-month follow-up, except one who died after 3 months for myocardial infarction. Percutaneous rheolytic thrombectomy using the AngioJet catheter may be a valid treatment option for patients with massive or submassive pulmonary embolism with rapid and significant hemodynamic improvement and encouraging results at early and long-term follow-up. Greater laboratory and operator experience yield better clinical results.
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This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats. Forty-eight Wistar rats were randomly assigned to 4 groups depending on a) beverage consumption ad... more
This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats. Forty-eight Wistar rats were randomly assigned to 4 groups depending on a) beverage consumption ad libitum, water (W) or cola beverage (C), and b) physical activity, sedentary (S) or treadmill running (R). Accordingly, 4 groups were studied: WS (water sedentary), WR (water runner), CS (cola sedentary) and CR (cola runner). Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry), and systolic blood pressure (plethysmography) were measured. After 6 months, euthanasia was performed (overdose sodium thiopental). Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations. The effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001) rather than si...
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Myocardial reflectivity, as assessed by calibrated integrated backscatter (cIB) analysis, is a non-invasive surrogate for the amount of left ventricular (LV) fibrosis. The aim of this study was to assess the myocardial reflectivity... more
Myocardial reflectivity, as assessed by calibrated integrated backscatter (cIB) analysis, is a non-invasive surrogate for the amount of left ventricular (LV) fibrosis. The aim of this study was to assess the myocardial reflectivity pattern in patients with heart failure and preserved ejection fraction (HFpEF), and to evaluate its relationship with longitudinal systolic deformation of LV by 2D-speckle tracking echocardiography, and degree of diastolic dysfunction. Transthoracic echocardiography, myocardial Doppler-derived systolic (Sm) and early diastolic velocity (E&amp;amp;amp;amp;amp;amp;amp;amp;#39;), global longitudinal strain (GLS), and tissue characterization by cIB, were obtained in 86 subjects, 46 with HFpEF, and 40 controls. GLS was significantly impaired in HFpEF patients (-15.4 ± 3.5 % vs -21.5 ± 2.9 % in controls; P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Increased myocardial reflectivity, as evidenced by less negative values of cIB, was also found in HFpEF compared to controls (-21.2 ± 4.4 dB vs -25.3 ± 3.9 dB, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). In HFpEF patients, myocardial reflectivity was positively related to GLS (r = 0.68, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), E/E&amp;amp;amp;amp;amp;amp;amp;amp;#39; ratio (r = 0.38, P = 0.009), and Tau (r = 0.43, P = 0.002), and inversely related to E&amp;amp;amp;amp;amp;amp;amp;amp;#39; velocity (r = -0.46, P = 0.0012). These associations remained significant after adjustment for age, preload and afterload indices. Patients with HFpEF show changes of LV structure consistent with enhanced fibrosis-as evidenced by increased myocardial reflectivity- which parallel the degree of diastolic dysfunction, and of longitudinal systolic dysfunction.
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Mediastinal irradiation can induce coronary artery disease characterized by fibrous lesions developing in the absence of lipid/foam cell accumulation. We document several consecutive cases of acute coronary artery occlusion developing... more
Mediastinal irradiation can induce coronary artery disease characterized by fibrous lesions developing in the absence of lipid/foam cell accumulation. We document several consecutive cases of acute coronary artery occlusion developing over radiation-induced lesions in patients who were relatively young, without evidence of classical risk factors for atherosclerosis, and in whom the coronary vasculature was otherwise apparently free of disease. The finding of acute coronary artery occlusion at the site of a fibrous lesion lends further support to the hypothesis that acute coronary syndromes may not necessarily be identifiable with ulceration/disruption of the atherosclerotic plaque as the underlying mechanism of acute thrombus formation.
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Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We... more
Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care. We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications. Only 1513 patients (11.7%) were rece...