Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

[Gender discrepancy: time to implement gender-based clinical management]. / Position paper ANMCO: Differenze di genere nell'approccio farmacologico cardiovascolare.

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.

Congenital Ventricular Diverticulum.

Herein, we describe a 54-year-old patient with a congenital ventricular diverticulum (CVD), referred to our emergency department for presyncope episodes and multiple re-entrant ventricular tachycardias (VT). Significantly, echocardiographic findings were not clear, and the diagnosis was made by cardiac magnetic resonance imaging (CMRI), which showed the presence of an apical accessory cavity connected to the ventricle and contracting synchronously. CMRI allowed the differential diagnosis with other outpouching cardiac defects. The patient underwent a subcutaneous implantable cardioverter defibrillator (S-ICD) implant and was referred for heart transplantation (HT). The diagnosis, treatment, and main findings of the CVD are discussed in this case report.

Clinical Utility of Three-Dimensional Echocardiography in the Evaluation of Mitral Valve Disease: Tips and Tricks.

Although real-time 3D echocardiography (RT3DE) has only been introduced in the last decades, its use still needs to be improved since it is a time-consuming and operator-dependent technique and acquiring a good quality data can be difficult. Moreover, the additive value of this important diagnostic tool still needs to be wholly appreciated in clinical practice. This review aims at explaining how, why, and when performing RT3DE is useful in clinical practice.

Patent Foramen Ovale and Cryptogenic Stroke: Integrated Management.

Patent foramen ovale (PFO) is a common cardiac abnormality with a prevalence of 25% in the general population. PFO has been associated with the paradoxical embolism causing cryptogenic stroke and systemic embolization. Results from clinical trials, meta-analyses, and position papers support percutaneous PFO device closure (PPFOC), especially if interatrial septal aneurysms coexist and in the presence of large shunts in young patients. Remarkably, accurately evaluating patients to refer to the closure strategy is extremely important. However, the selection of patients for PFO closure is still not so clear. The aim of this review is to update and clarify which patients should be considered for closure treatment.

Management of oral anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation.

Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.

[ANMCO Position paper: Choosing Wisely - ANMCO proposals for 2023]. / Position paper ANMCO: Choosing Wisely ­ le proposte dell'ANMCO nel 2023.

Nowadays, a progressive and exponential increase in the use of invasive and non-invasive instrumental diagnostics and therapeutic services has been shown. Although unnecessary, instrumental examinations are often largely prescribed, replacing clinical evaluation. Their correct use, on the contrary, would address precise epidemiological and clinical contexts. Therefore identifying whether a test or procedure is appropriate or not plays a crucial role in clinical practice. Several documents from scientific societies and expert groups indicate the most appropriate cardiovascular diagnostic and therapeutic procedures. The international Choosing Wisely campaign invited the main scientific societies to identify five techniques or treatments used in their field that are often unnecessary and may potentially damage patients. The Italian Association of Hospital Cardiologists (ANMCO) joined the project identifying the five cardiological practices in our country at greater risk of inappropriateness in 2014. This list has recently been updated. Moreover, possible solutions to this problem have been proposed.

[ANMCO Position paper: Ionizing radiation exposure and radioprotection in the cath-lab]. / Position paper ANMCO: Radioesposizione e radioprotezione nei laboratori di cardiologia interventistica.

In the last decades, because of the improvements in the percutaneous treatment of coronary heart disease, valvular heart disease, congenital heart defects, and the increasing number of cardiac resynchronization therapy and cardioverter-defibrillator implantations, the interventional cardiologists' radio-exposure has importantly risen, causing concerns for ionizing radiation-associated diseases such as cancer and neurodegenerative disorders. Consequently, the radiation exposure issue importantly affects operators' safety. However, our knowledge of this field is poor and most operators are unaware to be at risk, especially because of the absence of effective preventive measures. The aim of this ANMCO position paper is to improve the awareness of operators and identify new ways of reducing operator ionizing radiation dose and minimizing the risk.

[ANMCO/SICI-GISE/SIC/SIECVI/SIRM Consensus document: Appropriateness of multimodality imaging in cardiovascular disease]. / Documento di consenso ANMCO/SICI-GISE/SIC/SIECVI/SIRM: Appropriatezza dell'imaging multimodale nelle patologie cardiovascolari.

The complexity of cardiovascular diseases has led to an extensive use of technological instruments and the development of multimodality imaging. This extensive use of different cardiovascular imaging tests in the same patient has increased costs and waiting times.The concept of appropriateness has changed over time. Appropriateness criteria address the need for specific cardiovascular imaging tests in well-defined clinical scenarios, and define the kind of cardiovascular imaging that is appropriated for each clinical scenario in different stages of the disease. The concept of appropriateness criteria has replaced the old idea of appropriate use criteria and reflects the increasing effort of the international Scientific Societies to create and review in a critical way the management of diagnostic tests used by clinicians.The aim of this Italian consensus document is to address the use of multimodality imaging in the diagnosis and management of the major cardiovascular clinical scenarios, taking into consideration not only the international guidelines and scientific documents already published, but also the reality of Italian laws as well as the various professional profiles involved in patient management and availability of technological diagnostic instruments.

Rate of atherosclerotic plaque formation predicts cardiovascular events in ESRD.

Carotid intima media thickness (IMT) is a strong, independent predictor of cardiovascular events in both the general population and among those with end-stage renal disease (ESRD), but it is unknown whether changes in IMT or other ultrasound-measured indicators of atherosclerosis over time provide additional prognostic information. The progression of atherosclerosis with carotid ultrasound was followed in a cohort of 135 ESRD patients, 103 of whom had a repeat ultrasound after 15 mo of follow-up. The number of plaques and the proportion of patients with severe atherosclerosis increased substantially during the follow-up period, but IMT, common carotid artery diameter, common carotid artery wall-to-lumen ratio, and cross-sectional area, did not change. The rate of formation of new plaques was a strong, independent predictor of incident cardiovascular events, even after adjusting for baseline plaque burden and other potential confounders. New plaque formation over time was independently predicted by background plaque burden and serum C-reactive protein (P = 0.004 and P = 0.02, respectively). Changes in IMT and the other ultrasound-measured indicators of atherosclerosis progression did not predict cardiovascular outcomes. Therefore, monitoring IMT over time is unlikely to provide additional prognostic information compared with a single measurement, but longitudinal ultrasound monitoring of plaque formation may be useful for cardiovascular risk stratification in the ESRD population.

Left atrial volume in end-stage renal disease: a prospective cohort study.

BACKGROUND: End-stage renal disease (ESRD) is a high-risk condition and left ventricular hypertrophy (LVH) is the strongest risk factor in this population. OBJECTIVE AND METHODS: Since the prognostic value of left atrial (LA) size in ESRD is still unknown, we performed a prospective cohort study aimed at testing the prognostic value of LA volume in a cohort of 249 ESRD patients. RESULTS: Both un-indexed and indexed LA volume (LAV) was significantly higher in dialysis patients than in healthy subjects (P < 0.001). On multivariate analysis only left ventricular mass index (LVMI), LV ejection fraction (LVEF), ratio of early (E) to late atrial (A) mitral Doppler peak flow velocity (E/A ratio) and antihypertensive treatment maintained an independent association with LAV. During the follow-up 113 patients died. LAV added significant prognostic power to a multivariate Cox model of all-cause death and the model based on height provided the best data fit. Notably, this index maintained an independent predictive value for death (P = 0.03) also when LVMI and LVEF were jointly forced into the Cox's model. Neither crude nor body surface area (BSA)-adjusted LAV had an independent association with death when tested in the Cox model including LVMI and LVEF. CONCLUSIONS: In patients with ESRD, LAV indexed for height displays prognostic value beyond and above that provided by LV mass and function.

Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease.

BACKGROUND: Sympathetic tone is consistently raised in patients with end-stage renal disease (ESRD). We therefore tested the hypothesis that sympathetic activation is associated with mortality and cardiovascular events in a cohort of 228 patients undergoing chronic hemodialysis who did not have congestive heart failure at baseline and who had left ventricular ejection fraction >35%. METHODS AND RESULTS: The plasma concentration of norepinephrine (NE) was used as a measure of sympathetic activity. Plasma NE exceeded the upper limit of the normal range (cutoff 3.54 nmol/L) in 102 dialysis patients (45%). In a multivariate Cox regression model that included all univariate predictors of death as well as the use of sympathicoplegic agents and beta-blockers, plasma NE proved to be an independent predictor of this outcome (hazard ratio [1-nmol/L increase in plasma NE]: 1.07, 95% CI 1.01 to 1.14, P=0.03). Similarly, plasma NE emerged as an independent predictor of fatal and nonfatal cardiovascular events (hazard ratio [1-nmol/L increase in plasma NE] 1.08, 95% CI 1.02 to 1.15, P=0.01) in a model that included previous cardiovascular events, pulse pressure, age, diabetes, smoking, and use of sympathicoplegic agents and beta-blockers. The adjusted relative risk for cardiovascular complications in patients with plasma NE >75th percentile was 1.92 (95% CI 1.20 to 3.07) times higher than in those below this threshold (P=0.006). CONCLUSIONS: Sympathetic nerve overactivity is associated with mortality and cardiovascular outcomes in ESRD. Controlled trials with antiadrenergic drugs are needed to determine whether interference with the sympathetic system could reduce the high cardiovascular morbidity and mortality in dialysis patients.

Biomarkers of left atrial volume: a longitudinal study in patients with end stage renal disease.

Left atrial volume (LAV) has recently emerged as a useful biomarker for risk stratification and risk monitoring in patients with end stage renal disease. We investigated the relationship between cardiac natriuretic peptides (atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]) and norepinephrine (NE) with LAV and LAV changes over time in 199 end stage renal disease patients. At baseline, LAV was directly related to BNP (r=0.60), ANP (r=0.59), and NE (r=0.28; P<0.001), and these relationships held true in multiple-regression models adjusting for potential confounders (P< or =0.003). In the longitudinal study (17+/-2 months), LAV increased from 9.8+/-4.6 to 10.9+/-5.4 mL/m(2.7) (+11%). In a multiple linear regression model, BNP (beta=0.28; P=0.003), ANP (beta=0.22; P=0.03), and NE (beta=0.27; P=0.003) predicted LAV changes. The area under the receiver operating characteristic curve for predicting LAV changes (>3 mL/m(2.7) per year) of a risk score on the basis of standard risk factors was 0.72. Plasma BNP (+12%; P=0.004), ANP (+8%; P=0.03), NE (+8%; P=0.05) and midwall fraction shortening (+8%; P=0.05) increased the area under the receiver operating characteristic curve to a significant extent, whereas LV mass did not (+5%; P=0.18). Predictive models, including BNP, ANP, and NE, maintained a satisfactory discriminatory power for LAV and LAV changes also when tested by a bootstrap resampling technique. BNP and ANP are strongly related to LAV in the end stage renal disease patients and predict LAV changes over time in these patients. Because an increased LAV underlies diastolic dysfunction and/or volume overload (ie, potentially modifiable risk factors), the measurement of the plasma concentration of these compounds might be useful for risk stratification and for guiding treatment in dialysis patients.

Left atrial volume monitoring and cardiovascular risk in patients with end-stage renal disease: a prospective cohort study.

Left atrial volume (LAV), as indexed by height(2.7), has recently emerged as an useful echocardiographic measurement to refine the estimate of cardiovascular (CV) risk in ESRD. Whether progression or regression in LAV has prognostic value in patients with ESRD is still unknown. The prognostic value for CV events of changes in LAV was tested in a cohort of 191 dialysis patients. Echocardiography was performed twice, 17 +/- 2 mo apart. Changes in LAV that occurred between the second and the first echocardiographic studies were used to predict CV events during the ensuing 27 +/- 13 mo. During the follow-up, there was a significant increase in LAV (from 10.5 +/- 5.0 to 11.6 +/- 5.6 ml/m(2.7); P < 0.001). After the second echocardiographic study, 76 patients died (52 [68%] of CV causes) and 33 had nonfatal CV events. The independent association between changes in LAV and CV events was analyzed in a multiple Cox regression model taking into account a series of potential confounders, including baseline LAV and left ventricular mass and geometry. In these models, a 1-ml/m(2.7) per yr increase in LAV was associated with a 12% increase in the relative risk for fatal and nonfatal CV events (P < 0.001). Changes in LAV predict incident CV events in dialysis patients independent of the corresponding baseline measurement and of left ventricular mass. Monitoring LA size by echocardiography is useful for monitoring CV risk in patients with ESRD.

Cardiac consequences of hypertension in hemodialysis patients.

Hypertension in end-stage renal disease (ESRD) is an important risk factor for left ventricular hypertrophy (LVH), cardiac failure, coronary artery disease (CAD), and arrhythmia. LVH is generally considered an integrator of the long-term effects of hypertension and other cardiovascular (CV) risk factors and represents the strongest predictor of adverse CV outcomes in ESRD patients. The risk of heart failure is higher in patients with a history of hypertensive renal disease than in those with other diagnoses. Both coronary heart disease (CHD) and LVH predict congestive heart failure, which is often the ultimate cause of death in patients with cardiac ischemia or LVH. A history of long-standing hypertension is associated with ischemic heart disease both in cross-sectional and prospective studies in ESRD. Atrial fibrillation and ventricular arrhythmias are highly prevalent in dialysis patients and are implicated in mortality and sudden death in this population. Despite the lack of evidence from randomized controlled trials, it appears reasonable that interventions aimed at curbing the high CV mortality of ESRD should be targeted to both hypertension and LVH.

Prognostic value of ultrasonographic measurement of carotid intima media thickness in dialysis patients.

High-resolution carotid ultrasonography is considered a fundamental technique for the investigation of the vascular system. However, it is still very unclear whether ultrasonographic studies of carotid arteries are useful for the prediction of cardiovascular events in patients with end-stage renal disease. The prediction power of carotid ultrasonography for all-cause and cardiovascular mortality was tested in a cohort of 138 patients receiving chronic dialysis treatment (91 receiving hemodialysis treatment and 47 receiving continuous ambulatory peritoneal dialysis treatment; follow-up, 29.8 +/- 15.0 mo), and the relationship between this parameter and alterations in left ventricular mass (LVM) and geometry was examined. On univariate analysis, intima media thickness (IMT) was directly related to LVM as well as to the absolute and relative thicknesses of LV walls but independent of LV end-diastolic volume. Data analysis based on LV geometry patterns revealed that patients with concentric hypertrophy were those with the highest IMT. The internal diameter of the common carotid artery (DCCA) was also related to concentric hypertrophy, but the strength of this relationship was of borderline significance (P = 0.06). During the follow-up period, 63 patients died: 32 (51%) of them of cardiovascular causes. IMT was significantly higher (P = 0.006) in patients who died of cardiovascular causes (1.10 +/- 0.21 mm) than in patients who survived (0.99 +/- 0.24 mm), In a Cox regression model, this parameter turned out to be an independent predictor of cardiovascular death, and it retained an independent effect in a model that included LVM. Treatment modality failed to independently predict this outcome. The risk of cardiovascular death was progressively higher from the first IMT tertile onward. DCCA failed to predict cardiovascular outcomes. IMT in dialysis patients is associated with LV concentric hypertrophy and is an independent predictor of cardiovascular death. IMT may be usefully applied for risk stratification in the dialysis population.

Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase that has been linked to endothelial dysfunction and atherosclerosis in the general population. ADMA is also elevated in end-stage renal disease and may contribute to the high cardiovascular risk in patients with chronic renal failure. A prospective cohort study was performed to investigate the relationship between plasma ADMA, C-reactive protein (CRP), and intima-media thickness (IMT) in 90 patients undergoing hemodialysis. In the baseline study, plasma ADMA was directly related to IMT both on univariate analysis (r = 0.32, P = 0.002) and on multiple regression analysis (beta = 0.23, P = 0.01). In the follow-up study (15 mo) IMT changes were significantly related to ADMA (r = 0.51, P = 0.02) and serum CRP (r = 0.53, P = 0.01) in patients with initially normal IMT. In these patients, ADMA and CRP were strongly interrelated (r = 0.64, P = 0.002), and on multiple regression analysis the interaction between ADMA and CRP emerged as the sole independent predictor of the progression of intimal lesions. Independently of other risk factors, plasma ADMA in patients on hemodialysis is significantly related to IMT. Furthermore, in patients with initially normal IMT, ADMA and CRP are interacting factors in the progression of carotid intimal lesions. These data support the hypothesis that accumulation of this endogenous inhibitor of NO synthase is an important risk factor for cardiovascular disease in chronic renal failure and suggest a possible link between ADMA and inflammation.

Norepinephrine and concentric hypertrophy in patients with end-stage renal disease.

We have recently observed that in patients with end-stage renal disease (ESRD) raised plasma norepinephrine (NE) is an independent predictor of incident cardiovascular events but that its prognostic power is reduced when this sympathetic marker is tested in statistical models including also left ventricular mass. Because left ventricular hypertrophy (LVH) may be a mechanism whereby NE contributes to the high rate of cardiovascular events in ESRD, we examined the relationship between plasma NE and echocardiographic parameters of left ventricle mass in a large group of ESRD patients. Mean wall thickness (MWT) was higher in patients in the third NE tertile than in the other 2 tertiles (P=0.001), and such an increase was paralleled by a rise in relative wall thickness (RWT) (P=0.006). Concentric LVH was more prevalent in patients in the third NE tertile (46%) than in the second (38%) and first (25%) NE tertiles. Multivariate regression analysis confirmed that the association of plasma NE with the muscular component of left ventricle (MWT) and with RWT was independent (P< or =0.001) of other cardiovascular risk factors, and in these models, plasma NE ranked as the second correlate of MWT and RWT. Similarly, multiple logistic regression analysis showed that the association of plasma NE with concentric LVH was strong and again independent of other risk factors (P=0.003). Plasma NE is associated to concentric LVH in ESRD patients. These observations constitute a sound basis for testing the effect of anti-adrenergic drugs on left ventricle mass and on cardiovascular outcomes in patients with ESRD.

Prognostic impact of the indexation of left ventricular mass in patients undergoing dialysis.

Left ventricular hypertrophy (LVH) is exceedingly frequent in patients undergoing dialysis. Cardiac mass is proportional to body size, but the influence of various indexing methods has not been studied in patients with end-stage renal disease. The issue is important because malnutrition and volume expansion would both tend to distort the estimate of LV mass (LVM) in these patients. In a cohort of 254 patients, the prognostic impact on all-cause mortality and cardiovascular outcomes of LVH values, calculated according to two established methods of indexing, either body surface area (BSA) or height(2.7), was assessed prospectively. When LVM was analyzed as a categorical variable, the height(2.7)-based method identified a larger number of patients with LVH than the corresponding BSA-based method. One hundred and thirty-seven fatal and nonfatal cardiovascular events occurred during the follow-up period. Overall, 90 patients died, 51 of cardiovascular causes. In separate Cox models, both the LVM/height(2.7) and the LVM/BSA index independently predicted total and cardiovascular mortality (P < 0.001). However, the height(2.7)-based method coherently produced a closer-fitting model (P < or = 0.02) than did the BSA-based method. The height(2.7) index was also important for the subcategorization of patients according to the presence of concentric or eccentric LVH because the prognostic value of such subcategorization was apparent only when the height(2.7)-based criterion was applied. In conclusion, LVM is a strong and independent predictor of survival and cardiovascular events in patients undergoing dialysis. The indexing of LVM by height(2.7) provides more powerful prediction of mortality and cardiovascular outcomes than the BSA-based method, and the use of this index appears to be appropriate in patients undergoing dialysis.