Search

Risk stratification of cardiovascular death and treatment strategies in patients with heart failure (HF), the optimal timing for valve replacement, and the selection of patients for implantable cardioverter defibrillators are based on an echocardiographic calculation of left ventricular ejection fraction (LVEF) in most guidelines. As a marker of systolic function, LVEF has important limitations being affected by loading conditions and cavity geometry, as well as image quality, thus impacting inter- and intra-observer measurement variability. LVEF is a product of shortening of the three components of myocardial fibres: longitudinal, circumferential, and oblique. It is therefore a marker of global ejection performance based on cavity volume changes, rather than directly reflecting myocardial contractile function, hence may be normal even when myofibril's systolic function is impaired. Sub-endocardial longitudinal fibers are the most sensitive layers to ischemia, so when dysfunctional, the circumferential fibers may compensate for it and maintain the overall LVEF. Likewise, in patients with HF, LVEF is used to stratify subgroups, an approach that has prognostic implications but without a direct relationship. HF is a dynamic disease that may worsen or improve over time according to the underlying pathology. Such dynamicity impacts LVEF and its use to guide treatment. The same applies to changes in LVEF following interventional procedures. In this review, we analyze the clinical, pathophysiological, and technical limitations of LVEF across a wide range of cardiovascular pathologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Vancheri, Longo and Henein.)

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy., Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website., Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and ≥40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity ( P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001)., Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)

Background: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand better how different echocardiographic modalities are used and accessed in Italy., Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved via an electronic survey based on a structured questionnaire, uploaded on the SIECVI website., Results: Data were obtained from 228 echocardiographic laboratories: 112 centers (49%) in the northern, 43 centers (19%) in the central, and 73 (32%) in the southern regions. During the month of observation, we collected 101,050 transthoracic echocardiography (TTE) examinations performed in all centers. As concern other modalities there were performed 5497 transesophageal echocardiography (TEE) examinations in 161/228 centers (71%); 4057 stress echocardiography (SE) examinations in 179/228 centers (79%); and examinations with ultrasound contrast agents (UCAs) in 151/228 centers (66%). We did not find significant regional variations between the different modalities. The usage of picture archiving and communication system (PACS) was significantly higher in the northern (84%) versus central (49%) and southern (45%) centers ( P < 0.001). Lung ultrasound (LUS) was performed in 154 centers (66%), without difference between cardiology and noncardiology centers. The evaluation of left ventricular (LV) ejection fraction was evaluated mainly using the qualitative method in 223 centers (94%), occasionally with the Simpson method in 193 centers (85%), and with selective use of the three-dimensional (3D) method in only 23 centers (10%). 3D TTE was present in 137 centers (70%), and 3D TEE in all centers where TEE was done (71%). The assessment of LV diastolic function was done routinely in 80% of the centers. Right ventricular function was evaluated using tricuspid annular plane systolic excursion in all centers, using tricuspid valve annular systolic velocity by tissue Doppler imaging in 53% of the centers, and using fractional area change in 33% of the centers. When we divided into cardiology (179, 78%) and noncardiology (49, 22%) centers, we found significant differences in the SE (93% vs. 26%, P < 0.001), TEE (85% vs. 18%), UCA (67% vs. 43%, P < 0001), and STE (87% vs. 20%, P < 0.001). The incidence of LUS evaluation was similar between the cardiology and noncardiology centers (69% vs. 61%, P = NS)., Conclusions: This nationwide survey demonstrated that digital infrastructures and advanced echocardiography modalities, such as 3D and STE, are widely available in Italy with a notable diffuse uptake of LUS in the core TTE examination, a suboptimal diffusion of PACS recording, and conservative use of UCA, 3D, and strain. There are significant differences between northern and central-southern regions and echocardiographic laboratories that pertain to the cardiac unit. This inhomogeneous distribution of technology represents one of the main issues that must be solved to standardize the practice of echocardiography., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)

Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1β, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

Endothelial dysfunction is one of the earliest manifestations of atherosclerosis, contributing to its development and progression. Mental stress induces endothelial dysfunction through increased activity of the sympathetic nervous system, release of corticotropin-releasing hormone from the hypothalamus, inhibition of nitric oxide (NO) synthesis by cortisol, and increased levels of pro-inflammatory cytokines. Mental-stress-induced increased output of the sympathetic nervous system and concomitant withdrawal of the parasympathetic inflammatory reflex results in systemic inflammation and activation of a neural-hematopoietic-arterial axis. This includes the brainstem and subcortical regions network, bone marrow activation, release of leukocytes into the circulation and their migration to the arterial wall and atherosclerotic plaques. Low-grade, sterile inflammation is involved in all steps of atherogenesis, from coronary plaque formation to destabilisation and rupture. Increased sympathetic tone may cause arterial smooth-muscle-cell proliferation, resulting in vascular hypertrophy, thus contributing to the development of hypertension. Emotional events also cause instability of cardiac repolarisation due to brain lateralised imbalance of cardiac autonomic nervous stimulation, which may lead to asymmetric repolarisation and arrhythmia. Acute emotional stress can also provoke severe catecholamine release, leading to direct myocyte injury due to calcium overload, known as myocytolysis, coronary microvascular vasoconstriction, and an increase in left ventricular afterload. These changes can trigger a heart failure syndrome mimicking acute myocardial infarction, characterised by transient left ventricular dysfunction and apical ballooning, known as stress (Takotsubo) cardiomyopathy. Women are more prone than men to develop mental-stress-induced myocardial ischemia (MSIMI), probably reflecting gender differences in brain activation patterns during mental stress. Although guidelines on CV prevention recognise psychosocial factors as risk modifiers to improve risk prediction and decision making, the evidence that their assessment and treatment will prevent CAD needs further evaluation.

Epidemiological studies have shown that a substantial proportion of acute coronary events occur in individuals who lack the traditional high-risk cardiovascular (CV) profile. Mental stress is an emerging risk and prognostic factor for coronary artery disease and stroke, independently of conventional risk factors. It is associated with an increased rate of CV events. Acute mental stress may develop as a result of anger, fear, or job strain, as well as consequence of earthquakes or hurricanes. Chronic stress may develop as a result of long-term or repetitive stress exposure, such as job-related stress, low socioeconomic status, financial problems, depression, and type A and type D personality. While the response to acute mental stress may result in acute coronary events, the relationship of chronic stress with increased risk of coronary artery disease (CAD) is mainly due to acceleration of atherosclerosis. Emotionally stressful stimuli are processed by a network of cortical and subcortical brain regions, including the prefrontal cortex, insula, amygdala, hypothalamus, and hippocampus. This system is involved in the interpretation of relevance of environmental stimuli, according to individual's memory, past experience, and current context. The brain transduces the cognitive process of emotional stimuli into hemodynamic, neuroendocrine, and immune changes, called fight or flight response, through the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. These changes may induce transient myocardial ischemia, defined as mental stress-induced myocardial ischemia (MSIMI) in patients with and without significant coronary obstruction. The clinical consequences may be angina, myocardial infarction, arrhythmias, and left ventricular dysfunction. Although MSIMI is associated with a substantial increase in CV mortality, it is usually underestimated because it arises without pain in most cases. MSIMI occurs at lower levels of cardiac work than exercise-induced ischemia, suggesting that the impairment of myocardial blood flow is mainly due to paradoxical coronary vasoconstriction and microvascular dysfunction.

Aims: To investigate and compare changes in the rates of ischaemic heart disease (IHD) incidence and mortality between 1990 and 2019 in 20 high-income Western European countries with similar public health systems and low cardiovascular risk., Methods and Results: The 2020 updated version of the Global Burden of Disease database was searched. Variability and differences in IHD incidence and mortality rates (per 100 000) between countries over time, were calculated. A piecewise linear (join point) regression model was used to identify the slopes of these trends and the points in time at which significant changes in the trends occur. Ischaemic heart disease incidence and mortality rates varied widely between countries but decreased for all between 1990 and 2019. The relative change was greater for mortality than for incidence. Ischaemic heart disease incidence rates declined by approximately 36% between 1990 and 2019, while mortality declined by approximately 60%. Breakpoint analysis showed that the largest decreases in incidence and mortality occurred between 1990 and 2009 (-32%, -52%, respectively), with a much slower decrease after that (-5.9%, -17.6%, respectively), and even a slight increase for some countries in recent years. The decline in both incidence and mortality was lower in the Mediterranean European countries compared to the Nordic and Central European regions., Conclusions: In the Western European countries studied, the decline in age-standardized IHD incidence over three decades was slower than the decline in age-standardized IHD mortality. Decreasing trends of both IHD incidence and mortality has substantially slowed, and for some countries flattened, in more recent years., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19., Methods: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE)., Results: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan-Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001)., Conclusions: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.

Background and Aims: The Coptic clergy, due to their specific work involving interaction with many people, could be subjected to increased risk of infection from COVID-19. The aim of this study, a sub-study of the COVID-19-CVD international study of the impact of the pandemic on the cardiovascular system, was to assess the prevalence of COVID-19 among Coptic priests and to identify predictors of clinical adverse events., Methods: Participants were geographically divided into three groups: Group-I: Europe and USA, Group II: Northern Egypt, and Group III: Southern Egypt. Participants' demographic indices, cardiovascular risk factors, possible source of infection, number of liturgies, infection management, and major adverse events (MAEs), comprising death, or mechanical ventilation, were assessed., Results: Out of the 1570 clergy serving in 25 dioceses, 255 (16.2%) were infected. Their mean age was 49.5 ± 12 years and mean weekly number of liturgies was 3.44 ± 1.0. The overall prevalence rate was 16.2% and did not differ between Egypt as a whole and overseas ( p = 0.23). Disease prevalence was higher in Northern Egypt clergy compared with Europe and USA combined (18.4% vs. 12.1%, p = 0.03) and tended to be higher than in Southern Egypt (18.4% vs. 13.6%, p = 0.09). Ten priests (3.92%) died of COVID-19-related complications, and 26 (10.2) suffered a MAE. The clergy from Southern Egypt were more obese, but the remaining risk factors were less prevalent compared with those in Europe and USA ( p = 0.01). In multivariate analysis, obesity (OR = 4.180; 2.479 to 12.15; p = 0.01), age (OR = 1.055; 0.024 to 1.141; p = 0.02), and systemic hypertension (OR = 1.931; 1.169 to 2.004; p = 0.007) predicted MAEs. Obesity was the most powerful independent predictor of MAE in Southern Egypt and systemic hypertension in Northern Egypt ( p < 0.05 for both)., Conclusion: Obesity is very prevalent among Coptic clergy and seems to be the most powerful independent predictor of major COVID-19-related adverse events. Coptic clergy should be encouraged to follow the WHO recommendations for cardiovascular disease and COVID-19 prevention.

Background and Aims: The clinical adverse events of COVID-19 among clergy worldwide have been found to be higher than among ordinary communities, probably because of the nature of their work. The aim of this study was to assess the impact of cardiac risk factors on COVID-19-related mortality and the need for mechanical ventilation in Coptic clergy., Methods: Of 1570 Coptic clergy participating in the COVID-19-Clergy study, serving in Egypt, USA and Europe, 213 had the infection and were included in this analysis. Based on the presence of systemic arterial hypertension (AH), participants were divided into two groups: Group-I, clergy with AH ( n = 77) and Group-II, without AH ( n = 136). Participants' demographic indices, cardiovascular risk factors, COVID-19 management details and related mortality were assessed., Results: Clergy with AH were older ( p < 0.001), more obese ( p = 0.04), had frequent type 2 diabetes (DM) ( p = 0.001), dyslipidemia ( p = 0.001) and coronary heart disease (CHD) ( p = 0.04) compared to those without AH. COVID-19 treatment at home, hospital or in intensive care did not differ between the patient groups ( p > 0.05 for all). Clergy serving in Northern and Southern Egypt had a higher mortality rate compared to those from Europe and the USA combined (5.22%, 6.38%, 0%; p = 0.001). The impact of AH on mortality was significant only in Southern Egypt (10% vs. 3.7%; p = 0.01) but not in Northern Egypt (4.88% vs. 5.81%; p = 0.43). In multivariate analysis, CHD OR 1.607 ((0.982 to 3.051); p = 0.02) and obesity, OR 3.403 ((1.902 to 4.694); p = 0.04) predicted COVID-19 related mortality. A model combining cardiac risk factors (systolic blood pressure (SBP) ≥ 160 mmHg, DM, obesity and history of CHD) was the most powerful independent predictor of COVID-19-related mortality, OR 3.991 ((1.919 to 6.844); p = 0.002). Almost the same model also proved the best independent multivariate predictor of mechanical ventilation OR 1.501 ((0.809 to 6.108); p = 0.001)., Conclusion: In Coptic clergy, the cumulative impact of risk factors was the most powerful predictor of mortality and the need for mechanical ventilation.

Background: Atherosclerosis is a multi-system pathology with heterogeneous involvement. We aimed to investigate the relationship between the presence and severity of carotid and coronary calcification in a group of patients with coronary artery disease., Methods: Sixty-three patients presenting with unstable angina or positive stress test for myocardial ischaemia were enrolled in this study. All patients underwent CT scanning of the carotid and coronary arteries using the conventional protocol and Agatston scoring system. Risk factors for atherosclerosis were also analyzed for correlation with the extent of arterial calcification., Results: Total coronary artery calcium score (CAC) was several times higher than total carotid calcium score (1274 (1018) vs 6 (124), p = 0·0001, respectively). The left carotid calcium score correlated strongly with the right carotid calcium score (rho = 0·69, p < 0·0001). The total CAC score correlated modestly with the total carotid calcium score (rho = 0·34, p = 0·007), in particular with left carotid score (rho = 0·38, p = 0·002), but not with the right carotid score. The left coronary calcium score correlated with the right coronary calcium score (rho = 0·35, p = 0·004), left carotid calcium score (rho = 0·33, p = 0·007) and left carotid calcium score at the bifurcation (rho = 0·34, p = 0·006). While hypertension correlated with carotid calcium score, diabetes and dyslipidaemia correlated with left CAC score., Conclusion: In patients with coronary disease, the carotid calcification pattern appeared to be similar between the right and left system in contrast to that of the coronary arteries. CAC correlated only modestly with the carotid score, despite being significantly higher. Hypertension was related to carotid calcium score while diabetes and dyslipidaemia correlated with coronary calcification., (© 2021 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Inflammation has a central role in atherosclerotic plaque formation and rupture. Intense macrophage inflammatory activity results in microcalcifications which are strongly associated with plaque vulnerability. Microcalcifications with specific critical size between 5 and 65 μ, located in the fibrous cap producing local mechanical stress on the plaque surface and may directly contribute to plaque rupture. Hence, accurate assessment of microcalcifications size and dimension has significant clinical importance. Current invasive and noninvasive plaque imaging has limited spatial resolution which limits accurate definition of microcalcifications in the atherosclerotic plaques. We describe a new imaging technique with high spatial resolution, based on confocal microscopic analysis, using a dedicated software which allows automatic characterization of microcalcifications and quantitative assessment of their extent and localization.

Many patients with chest pain undergoing coronary angiography do not show significant obstructive coronary lesions. A substantial proportion of these patients have abnormalities in the function and structure of coronary microcirculation due to endothelial and smooth muscle cell dysfunction. The coronary microcirculation has a fundamental role in the regulation of coronary blood flow in response to cardiac oxygen requirements. Impairment of this mechanism, defined as coronary microvascular dysfunction (CMD), carries an increased risk of adverse cardiovascular clinical outcomes. Coronary endothelial dysfunction accounts for approximately two-thirds of clinical conditions presenting with symptoms and signs of myocardial ischemia without obstructive coronary disease, termed "ischemia with non-obstructive coronary artery disease" (INOCA) and for a small proportion of "myocardial infarction with non-obstructive coronary artery disease" (MINOCA). More frequently, the clinical presentation of INOCA is microvascular angina due to CMD, while some patients present vasospastic angina due to epicardial spasm, and mixed epicardial and microvascular forms. CMD may be associated with focal and diffuse epicardial coronary atherosclerosis, which may reinforce each other. Both INOCA and MINOCA are more common in females. Clinical classification of CMD includes the association with conditions in which atherosclerosis has limited relevance, with non-obstructive atherosclerosis, and with obstructive atherosclerosis. Several studies already exist which support the evidence that CMD is part of systemic microvascular disease involving multiple organs, such as brain and kidney. Moreover, CMD is strongly associated with the development of heart failure with preserved ejection fraction (HFpEF), diabetes, hypertensive heart disease, and also chronic inflammatory and autoimmune diseases. Since coronary microcirculation is not visible on invasive angiography or computed tomographic coronary angiography (CTCA), the diagnosis of CMD is usually based on functional assessment of microcirculation, which can be performed by both invasive and non-invasive methods, including the assessment of delayed flow of contrast during angiography, measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), evaluation of angina induced by intracoronary acetylcholine infusion, and assessment of myocardial perfusion by positron emission tomography (PET) and magnetic resonance (CMR).

Identifying patients at increased risk of coronary artery disease, before the atherosclerotic complications become clinically evident, is the aim of cardiovascular prevention. Imaging techniques provide direct assessment of coronary atherosclerotic burden and pathological characteristics of atherosclerotic lesions which may predict the progression of disease. Atherosclerosis imaging has been traditionally based on the evaluation of coronary luminal narrowing and stenosis. However, the degree of arterial obstruction is a poor predictor of subsequent acute events. More recent techniques focus on the high-resolution visualization of the arterial wall and the coronary plaques. Most acute coronary events are triggered by plaque rupture or erosion. Hence, atherosclerotic plaque imaging has generally focused on the detection of vulnerable plaque prone to rupture. However, atherosclerosis is a dynamic process and the plaque morphology and composition may change over time. Most vulnerable plaques undergo progressive transformation from high-risk to more stable and heavily calcified lesions, while others undergo subclinical rupture and healing. Although extensive plaque calcification is often associated with stable atherosclerosis, the extent of coronary artery calcification strongly correlates with the degree of atherosclerosis and with the rate of future cardiac events. Inflammation has a central role in atherogenesis, from plaque formation to rupture, hence in the development of acute coronary events. Morphologic plaque assessment, both invasive and non-invasive, gives limited information as to the current activity of the atherosclerotic disease. The addition of nuclear imaging, based on radioactive tracers targeted to the inflammatory components of the plaques, provides a highly sensitive assessment of coronary disease activity, thus distinguishing those patients who have stable disease from those with active plaque inflammation., Competing Interests: The authors declare no conflict of interest.

Strategies to prevent acute coronary and cerebrovascular events are based on accurate identification of patients at increased cardiovascular (CV) risk who may benefit from intensive preventive measures. The majority of acute CV events are precipitated by the rupture of the thin cap overlying the necrotic core of an atherosclerotic plaque. Hence, identification of vulnerable coronary lesions is essential for CV prevention. Atherosclerosis is a highly dynamic process involving cell migration, apoptosis, inflammation, osteogenesis, and intimal calcification, progressing from early lesions to advanced plaques. Coronary artery calcification (CAC) is a marker of coronary atherosclerosis, correlates with clinically significant coronary artery disease (CAD), predicts future CV events and improves the risk prediction of conventional risk factors. The relative importance of coronary calcification, whether it has a protective effect as a stabilizing force of high-risk atherosclerotic plaque has been debated until recently. The extent of calcium in coronary arteries has different clinical implications. Extensive plaque calcification is often a feature of advanced and stable atherosclerosis, which only rarely results in rupture. These macroscopic vascular calcifications can be detected by computed tomography (CT). The resulting CAC scoring, although a good marker of overall coronary plaque burden, is not useful to identify vulnerable lesions prone to rupture. Unlike macrocalcifications, spotty microcalcifications assessed by intravascular ultrasound or optical coherence tomography strongly correlate with plaque instability. However, they are below the resolution of CT due to limited spatial resolution. Microcalcifications develop in the earliest stages of coronary intimal calcification and directly contribute to plaque rupture producing local mechanical stress on the plaque surface. They result from a healing response to intense local macrophage inflammatory activity. Most of them show a progressive calcification transforming the early stage high-risk microcalcification into the stable end-stage macroscopic calcification. In recent years, new developments in noninvasive cardiovascular imaging technology have shifted the study of vulnerable plaques from morphology to the assessment of disease activity of the atherosclerotic lesions. Increased disease activity, detected by positron emission tomography (PET) and magnetic resonance (MR), has been shown to be associated with more microcalcification, larger necrotic core and greater rates of events. In this context, the paradox of increased coronary artery calcification observed in statin trials, despite reduced CV events, can be explained by the reduction of coronary inflammation induced by statin which results in more stable macrocalcification.

Background and Aim: Whether aging affects left ventricular (LV) filling and ejection and the LV electric function is not well established. We investigated the effect of normal aging on echocardiographic measurements of LV morphology and function, LV electric function and the relationship between LV electric and mechanical function in asymptomatic individuals., Methods: As part of a cross-sectional survey for the prevalence of coronary risk factors in the general population in Caltanissetta, Italy, individuals without signs or symptoms of coronary artery disease or heart failure were randomly selected and underwent electrocardiographic and echocardiographic examination. QRS duration and amplitude, PR, QT and QTc intervals, were automatically measured. Echocardiographic examination included the measurement of LV systolic and diastolic dimensions, volumes and ejection fraction (EF). From the spectral Doppler flow LV early diastolic (E wave) and atrial systolic (A wave) velocities, isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT) were measured. Global LV dyssynchrony was assessed using the total isovolumic time (T-IVT) and the Tei index., Results: Aging reduced LV long-axis function, LV filling time and E wave velocity and prolonged T-IVT, IVRT and Tei index. It did not affect LV dimensions, ejection fraction, IVCT or QRS amplitude and duration. QRS duration correlated with LV dimensions, wall thickness and left atrial area. QRS amplitude and QTc interval correlated with the markers of LV dyssynchrony T-IVT and Tei index., Conclusions: Overall, systolic and electric LV function are not affected by age, whereas subendocardial function, diastolic and synchronous function are significantly influenced., (© 2018 Wiley Periodicals, Inc.)

Background and Aim: QRS amplitude and duration are associated with increased left ventricular (LV) volume, mass and dysfunction. However, the diagnostic concordance between QRS measurements and LV morphology and function, as shown by Doppler echocardiography, is not well established. We investigated the relationships of QRS duration and amplitude with echocardiographic measurements of LV morphology and systolic and diastolic function in normal individuals., Methods: Individuals without signs or symptoms of coronary artery disease or heart failure, who underwent clinical examination as a part of a cross-sectional survey for the prevalence of coronary risk factors, randomly selected from the population list in Caltanissetta, Italy, were included in the study. QRS duration and amplitude were automatically measured using inbuilt software. LV ejection and filling patterns were studied using Doppler echocardiography., Results: We studied 184 individuals (96 men and 88 women), mean age 55.9 (11.3). QRS duration increased by 5.4 ms for every 100 g increase in LV mass, and by 4.6 ms for each 10 mm increase in LV end-diastolic diameter. The amplitude increased by 0.8 mm for every 100 g increase in LV mass. There was no relationship with LV dimensions. A nonlinear correlation was found between QRS amplitude and indexes of global dyssynchrony. The time-voltage QRS area correlated with LV mass, dimensions and indexes of dyssynchrony. There was no relationship between QRS measurements and ejection fraction., Conclusions: QRS prolongation and increase in amplitude are strongly influenced by LV increased mass and volume, as well as by dyssynchrony, independently of ejection fraction., (© 2017, Wiley Periodicals, Inc.)

Background and Aim: Left ventricular (LV) segmental dyssynchrony is common in patients with heart failure or myocardial activation abnormalities and is associated with increased cardiovascular risk. Total isovolumic time (t-IVT) and Tei index are sensitive indexes of global ventricular dyssynchrony. The aim of this study was to investigate the effect of age on t-IVT and Tei index., Methods: We evaluated 410 individuals with no evidence for coronary heart disease or activation abnormalities. T-IVT was calculated as 60 - (total ejection time + total filling time) and Tei index as t-IVT/total ejection time. The relationship between age, LV systolic and diastolic function parameters as well as t-IVT and Tei index was studied., Results: Ejection fraction and stroke volume did not change with age, whereas early diastolic filling velocity fell and atrial systolic velocity increased, reducing the E/A ratio. Isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) lengthened. With every 10 years of age, total LV ejection time shortened by 1.5 sec/min and total filling time by 2.1 sec/min. T-IVT and Tei index increased with age and strongly correlated with IVCT and E/A, but not with ejection fraction or QRS duration., Conclusion: Normal aging is associated with worsening of LV global dyssynchrony shown by prolongation of isovolumic times resulting in shortening of filling and ejection times. Age also affects diastolic function as shown by E/A but not systolic function parameters, ejection fraction or stroke volume. Worsening of global dyssynchrony correlates with that of diastolic function but not with QRS duration., (© 2016, Wiley Periodicals, Inc.)

Objectives: To determine whether there is a relation between statin utilisation and coronary heart disease (CHD) mortality in populations with different levels of coronary risk, and whether the relation changes over time., Design: Ecological study using national databases of dispensed medicines and mortality rates., Setting: Western European countries with similar public health systems., Main Outcome Measures: Population CHD mortality rates (rate/100,000) as a proxy for population coronary risk level, and statin utilisation expressed as Defined Daily Dose per one Thousand Inhabitants per Day (DDD/TID), in each country, for each year between 2000 and 2012. Spearman's correlation coefficients between CHD mortality and statin utilisation were calculated. Linear regression analysis was used to assess the relation between changes in CHD mortality and statin utilisation over the years., Results: 12 countries were included in the study. There was a wide range of CHD mortality reduction between the years 2000 and 2012 (from 25.9% in Italy to 57.9% in Denmark) and statin utilisation increase (from 121% in Belgium to 1263% in Denmark). No statistically significant relations were found between CHD mortality rates and statin utilisation, nor between changes in CHD and changes in statin utilisation in the countries over the years 2000 and 2012., Conclusions: Among the Western European countries studied, the large increase in statin utilisation between 2000 and 2012 was not associated with CHD mortality, nor with its rate of change over the years. Factors different from the individual coronary risk, such as population ageing, health authority programmes, guidelines, media attention and pharmaceutical industry marketing, may have influenced the large increase in statin utilisation. These need to be re-examined with a greater emphasis on prevention strategies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aim: We investigated whether the risk estimates of General Practitioners (GPs) and their treatment decisions mutually influence each other and whether factors not related to the patient's risk, such as the gender and length in clinical practice, interact., Background: The quantitative assessment of the absolute risk of developing coronary heart disease (CHD) and the decision to start treatment with lipid-lowering drugs are crucial tasks in the primary prevention of CHD., Methods: Nine clinical vignettes, four rated high-risk and five rated low-risk according to the Framingham equation, were mailed to three groups of 90 randomly selected GPs in Stockholm. One group (R) was asked to estimate the risk of CHD within 10 years on a visual analogue scale. A second group (R1D) was asked to estimate the risk and to specify whether they would recommend a pharmacological lipid-lowering treatment. A third group (D) only to indicate whether they would recommend treatment., Results: Response rate ranged from 42.2% to 45.6%. The median risk estimates were higher in the R group than in the R1D group (difference not statistically significant). R1D group showed higher proportions of correct decisions to start treatment compared with the R group (86.2% versus 77.5%, P50.19). More correct decisions were made by female doctors (OR 1.77, 95% CI 1.19-2.61, P50.004) and by less experienced doctors (OR 0.97, 95% CI 0.95-0.99, P50.016)., Conclusions: The task of making CHD risk estimates and the task of making decisions whether to start lipid-lowering treatment do not seem to influence each other. The gender of physicians and the length of clinical experience seem to affect treatment decisions. Female GPs and less experienced GPs are more likely to make correct decisions. However, the relatively low response rate to the questionnaires may limit the generalizability of these results.

Background: Quantitative assessment of an individual's absolute cardiovascular risk is essential for primary prevention. Although risk-scoring tools have been developed for this task, risk estimates are usually made subjectively. We investigated whether general practitioners (GPs), internists and cardiologists differ in their quantitative estimates of cardiovascular risk and their recommendations about lipid-lowering treatment for the same set of patients., Methods: Mail survey. Nine written clinical vignettes, four rated high-risk and five rated low-risk according to the Framingham equation, were mailed to 90 randomly selected GPs and to the same number of internists and cardiologists in Sicily. The doctors were then asked to estimate the 10-year coronary risk in each case and to decide whether they would recommend a lipid-lowering treatment., Results: In the majority of the nine cases, the cardiologists' risk estimates were significantly lower than those of the other two groups. A higher proportion of internists (mean value 0.68) decided to start treatment than GPs (0.54) or cardiologists (0.57). In all three groups, the doctors' willingness to begin treatment was over 90% when their risk estimate was above 20%, and less than 50% when it fell below this level. Internists were more prone to treat than the other two groups even when their patients' estimated risk was below 20%., Conclusion: When presented with the same set of clinical cases, GPs, internists and cardiologists make different quantitative risk estimates and come to different conclusions about the need for lipid-lowering treatment. This may result in over- or under-prescription of lipid-lowering drugs and inconsistencies in the care provided by different categories of doctors.

Metformin is a biguanide commonly used in type 2 diabetes mellitus (DM). Lactic acidosis, a potentially life-threatening metabolic disorder, may be due to a number of different causes, including metformin therapy. We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM, admitted to the emergency department with a history of dehydration due to diarrhoea and complicated by acute renal failure. Patient complained malaise and severe weakness and was tachypneic (Kussmaul's respiration), agitated and confused, with a Glasgow Coma Scale score of 13/15. Heart rate was 75 b/min and blood pressure 110/80 mmHg. The pH was 6.87, HCO3- 3 mmol/l, lactate 15 mmol/l, potassium 6.9 mEq/l. The renal function was markedly impaired with a creatinine of 9.75 mg/dl, and pancreatic enzymes, amylase and lipase, were also increased in absence of abdominal pain. Patient was treated with intravenous fluids, bicarbonate infusion and haemodialysis with bicarbonate buffered replacement fluid. Clinical conditions improved rapidly, with a progressive normalization of the acid-base balance and the other laboratory data. Authors discuss the pathophysiologic mechanisms of these alterations with particular regard to the role played by metformin as potential cause of lactic acidosis.

The metabolic syndrome denotes a clustering of specific risk factors for both cardiovascular disease and type 2 diabetes, whose underlying pathophysiology is believed to include insulin resistance. It has been widely reported that the syndrome is a simple clinical tool to identify people at high long term risk of cardiovascular disease and diabetes. However, its clinical importance is under debate. There are substantial uncertainties about the clinical definition of the syndrome, as to whether the risk factors clustering indicates a single unifying disorder, whether the risk conferred by the condition as a whole is higher risk than its individual components, and whether its predictive value of future cardiovascular events or diabetes is greater than established predicting models such as the Framingham Risk Score and the Diabetes Risk Score. We undertook an extensive review of the literature. Our analysis indicates that current definitions of the syndrome are incomplete or ambiguous, more than one pathophysiological process underlies the syndrome, although the combination of insulin resistance and hyperinsulinemia are related to most cases; the risk associated with the syndrome is no greater than that explained by the presence of its components, and the syndrome is less effective in predicting the future development of cardiovascular events and diabetes than established predicting models. Although the syndrome has some importance in understanding the pathophysiology of cardiovascular and diabetes risk factors clustering, its use as a clinical syndrome is not justified by current data.

Background: The Italian register of cardiovascular diseases is a surveillance system of fatal and nonfatal cardiovascular events in the general population aged 35-74 years. It was launched in Italy at the end of the 1990 s with the aim of estimating periodically the occurrence and case fatality rate of coronary and cerebrovascular events in the different geographical areas of the country. This paper presents data for cerebrovascular events., Methods: Current events were assessed through record linkage between two sources of information: death certificates and hospital discharge diagnosis records. Events were identified through the ICD codes and duration. To calculate the number of estimated events, current events were multiplied by the positive predictive value of each specific mortality or discharge code derived from the validation of a sample of suspected events. Attack rates were calculated by dividing estimated events by resident population, and case fatality rate at 28 days was determined from the ratio of estimated fatal to total events., Results: Attack rates were found to be higher in men than in women: mean age-standardized attack rate was 21.9/10,000 in men and 12.5/10,000 in women; age-standardized 28-day case fatality rate was higher in women (17.1%) than in men (14.5%). Significant geographical differences were found in attack rates of both men and women. Case fatality was significantly heterogeneous in both men and women., Conclusions: Differences still exist in the geographical distribution of attack and case fatality rates of cerebrovascular events, regardless of the north-south gradient. These data show the feasibility of implementing a population-based register using a validated routine database, necessary for monitoring cardiovascular diseases., ((c) 2007 S. Karger AG, Basel.)

Primary antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis. However, a small number of patients present with visceral aneurysms. Although such aneurysms are rare, their presence in patients who are usually treated with lifelong anticoagulation raises important therapeutic problems, in view of the risk of aneurysm rupture and acute abdominal hemorrhage. We report the case of a young woman with APS who presented with abdominal bleeding due to ruptured common hepatic artery aneurysm. She was successfully treated by proximal ligation. The features of such aneurysms are discussed.