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The severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID-19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off-label for the treatment of COVID-19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune-checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death-1 (PD-1)/PD ligand-1 (PD-L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID-19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T-cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti-tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T-cell exhaustion, which is also observed following SARS-CoV-2 infection. Importantly, when treated with anti-PD-1 and anti-PD-L1 antibodies, they restore their T-cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti-PD-1 antibody administration to both cancer and non-cancer individuals affected by COVID-19. The results may prove the hypothesis that restoring exhausted T-cells may be a winning strategy to beat SARS-CoV-2 infection.

When diabetes mellitus is not properly controlled with drugs and a healthy lifestyle, it exposes patients with advanced peripheral arterial disease or critical limb ischaemia (CLI) to the most serious complications, in particular lower limb ulcers. Surgical or endovascular treatments represent the first line of intervention; in addition, the adequate management of ulcers can guarantee not only a faster wound healing but also the improvement of the patient's prognosis. To speed up this process, negative pressure wound therapy (NPWT), platelet‐rich plasma (PRP), and other advanced moist wound dressing have been proposed. During Coronavirus disease 2019 (COVID‐19) pandemic, many patients with CLI and diabetes mellitus had difficult access to advanced treatments with a significant reduction in life expectancy. We report the cases of patients with non‐healing ulcers and CLI treated with an empiric multistage approach after successful endovascular revascularisation; the postoperative course was eventful in all patients, and foot ulcers are currently in an advanced state of healing. The association between adequate revascularisation, systemic anti‐inflammatory, and antibiotic therapy with the multistage advanced medications ensures healing of ulcers, limb salvage, and improvement of patient prognosis.

Cardiovascular disease and cancer are responsible for the majority of deaths in the Western world. These two entities share common risk factors and their intersection will be more and more frequent in future due to general population aging and long-term cancer control. Clinical presentation, management and outcome of acute coronary syndromes (ACS) in cancer patients could differ from noncancer ones. Cancer patients were frequently excluded from clinical trials and so the paucity of data further complicates the scenario. The management of ACS in cancer patients represents a unique setting in which the risk/benefit ratio of invasive treatment should be carefully evaluated. This review focused on the available evidence of all aspects of ACS in cancer patients providing a guide to a multidisciplinary approach.

Adult patients with simple congenital heart disease (sACHD) represent an expanding population vulnerable to atrial arrhythmias (AA). CHA2DS2-VASc score estimates thromboembolic risk in non-valvular atrial fibrillation patients. We investigated the prognostic role of CHA2DS2-VASc score in a non-selected sACHD population regardless of cardiac rhythm. Between November 2009 and June 2018, 427 sACHD patients (377 in sinus rhythm, 50 in AA) were consecutively referred to our ACHD service. Cardiovascular hospitalization and/or all-cause death were considered as composite primary end-point. Patients were divided into group A with CHA2DS2-VASc score = 0 or 1 point, and group B with a score greater than 1 point. Group B included 197 patients (46%) who were older with larger prevalence of cardiovascular risk factors than group A. During a mean follow-up of 70 months (IQR 40–93), primary end-point occurred in 94 patients (22%): 72 (37%) in group B and 22 (10%, p < 0.001) in group A. Rate of death for all causes was also significantly higher in the group B than A (22% vs 2%, respectively, p < 0.001). Multivariable Cox regression analysis revealed that CHA2DS2-VASc score was independently related to the primary end-point (HR 1.84 [1.22–2.77], p = 0.004) together with retrospective AA, stroke/TIA/peripheral thromboembolism and diabetes. Furthermore, CHA2DS2-VASc score independently predicted primary end-point in the large subgroup of 377 patients with sinus rhythm (HR 2.79 [1.54–5.07], p = 0.01). In conclusion, CHA2DS2-VASc score accurately stratifies sACHD patients with different risk for adverse clinical events in the long term regardless of cardiac rhythm.

The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of these populations. Indeed, not only a higher risk of contracting the infection has been reported but also an increased occurrence of a more severe course and unfavourable outcome. Beyond the direct consequences of COVID-19 infection, the pandemic has an enormous impact on global health systems. Screening programmes and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in STEMI accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the ‘rebound effect’ that will likely show a relative increase in the short- and medium-term incidence of diseases such as heart failure, myocardial infarction, arrhythmias, and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavourable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this document is to evaluate the impact of the pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19) in order to optimize medical strategies during and after the pandemic.

Aims: Cardio-oncology has achieved a pivotal role in science, but real world data on its clinical impact are still limited.Methods: A questionnaire was sent out to all cardio-oncology services across Italy (n = 120). The questionnaire was made up of 28 questions divided into four blocks: (A) general information on hospitals and service, (B) the inner organization of cardio-oncology and its relationships with out-of-hospital cardiologists and general practitioners, (C) educational needs and referral guidelines, and (D) activities/specific workload.Results: Ninety-six out of 120 (80%) completed the questionnaire; 9.4% were cancer centers while 90.6% were general hospitals. A cardio-oncology team was present in 56% of the cancer centers and in 20% only of general hospitals, and a cardio-oncology pathway was active in 55% of cancer centers and in just 14% of the general hospitals. Relationships with out-of-hospital cardiologists and general practitioners were lacking. The guidelines of reference were ESC and ANMCO/AIOM. Patients receiving anthracycline chemotherapy underwent scheduled monitoring by means of echocardiography in 58% of cases. Routine use of cardiac damage biomarkers was overall low, ranging from 22 to 33% while the use of global longitudinal strain reached 44%.Conclusions: Italian cardio-oncology showed a growing influence on clinical practice but still has room for improvement. Cardio-oncology teams are still scarce, and the application of dedicated paths is poor. The need for specific training has been highlighted.

Background To date, only a few comparisons between subcutaneous implantable cardioverter-defibrillator (S-ICD) patients undergoing and those not undergoing defibrillation testing (DT) at implantation (DT+ vs DT–) have been reported. Objective The purpose of this study was to compare long-term clinical outcomes of 2 propensity-matched cohorts of DT+ and DT– patients. Methods Among consecutive S-ICD patients implanted across 17 centers from January 2015 to October 2020, DT– patients were 1:1 propensity-matched for baseline characteristics with DT+ patients. The primary outcome was a composite of ineffective shocks and cardiovascular mortality. Appropriate and inappropriate shock rates were deemed secondary outcomes. Results Among 1290 patients, a total of 566 propensity-matched patients (283 DT+; 283 DT–) served as study population. Over median follow-up of 25.3 months, no significant differences in primary outcome event rates were found (10 DT+ vs 14 DT–; P = .404) as well as for ineffective shocks (5 DT– vs 3 DT+; P = .725). At multivariable Cox regression analysis, DT performance was associated with a reduction of neither the primary combined outcome nor ineffective shocks at follow-up. A high PRAETORIAN score was positively associated with both the primary outcome (hazard ratio 3.976; confidence interval 1.339–11.802; P = .013) and ineffective shocks alone at follow-up (hazard ratio 19.030; confidence interval 4.752–76.203; P = .003). Conclusion In 2 cohorts of strictly propensity-matched patients, DT performance was not associated with significant differences in cardiovascular mortality and ineffective shocks. The PRAETORIAN score is capable of correctly identifying a large percentage of patients at risk for ineffective shock conversion in both cohorts.

The open abdomen (OA) procedure as part of damage control surgery represents a significant surgical advance in severe intra-abdominal infections. Major techniques used for OA are negative pressure wound therapy (NPWT) and non-NPWT. The aim of this retrospective study is to evaluate the effects of different abdominal closure methods and their outcomes in patients presenting with abdominal sepsis treated with OA. We retrospectively analyzed clinical outcomes of patients affected by severe intra-abdominal sepsis treated with OA. Demographic features, mortality prediction score, abdominal closure methods, length of hospital stay, complications and mortality rates of patients were determined and compared. This study included 106 patients, of whom 77 underwent OA with NPWT and 29 with non-NPWT. OA duration was longer in NPWT patients (p = 0.007). In-hospital mortality rates in NPWT and in non-NPWT patients were 40.3% and 51.7%, respectively (p = 0.126), with an overall 30-day mortality rate of 18.2% and 51.7%, respectively (p = 0.0002). After emergency colorectal surgery, patients who underwent OA with NPWT had a lower rate of colostomy (p = 0.025). NPWT is the best temporary abdominal closure technique to decrease mortality and colostomy rates in patients managed with OA for severe intra-abdominal infections.

Since its introduction, transanal endoscopic microsurgery (TEM) has become the treatment of choice for rectal benign lesions not amenable to flexible endoscopic excision and for early rectal cancer. Disposable soft devices as the Trans-anal Minimally Invasive Surgery (TAMIS) are a valid alternative to non-disposable rigid trans-anal endoscopic microsurgery (TEM) platforms. The aim of the present study is to compare TEM and TAMIS in terms of incidence of R1 resection and lesion fragmentation which were combined in a composite outcome called quality resection. Perioperative complication and operative time were also investigated. A total of 132 patients were eligible for this study of whom 63 (47.7%) underwent TAMIS and 69 (52.3%) underwent TEM. Patients were extracted for from a prospective maintained database and groups resulted homogenous after matching using propensity score in terms of size of the lesion, height from the anal verge, position within the rectal lumen, preoperative histology, neoadjuvant treatment. A multivariate logistic and linear regression analysis was carried out using those variables that have significant independent relationship with the quality of surgical resection and operative time. The incidence of R0 resection and lesion fragmentation was similar between groups. No differences were found in terms of perioperative complication. TAMIS was associated with less setup time and less operative time compared with TEM. Variables influencing quality resection at the multivariate analysis were larger lesion (> 5 cm) and ≥ T2 stage. Variables influencing operative time were surgical procedure (TEM vs TAMIS), height from the anal verge and size of the lesion. The present study shows that TEM and TAMIS are equally effective in terms of quality of local excision and perioperative complication. TAMIS resulted less operative time consuming compared to TEM.

Background High diagnostic accuracy for pneumonia, absence of radiation exposure and repeatability are intrinsic features of lung ultrasonography making it an attractive tool in the assessment of patients with COVID-19 pneumonia. The aim of our prospective, observational study was to detect COVID-19-associated sonographic features and assess the potential value of LUS in predicting adverse events. Methods From March 12th to April 20th 2020 patients admitted to two medium-intensive wards with a discharge diagnosis of COVID-19 pneumonia were enrolled and underwent lung ultrasonography. The prognostic value of several ultrasonographic scores at admission and after 72 hours from the first examination (the total score, the anterolateral score, the number of positive region and the presence of consolidation) were analysed with logistic regression along with other potential prognostic factors. The primary outcome was a composite of death and transfer to Intensive Care Unit (ICU), while the secondary was continuous positive airways pressure (CPAP) support. Results 190 patients were enrolled in the study. The primary outcome was seen in 25 patients (13%), the secondary outcome in 36 (22%). At multivariate regression no sonographic score at admission was independently correlated with the primary outcome while the total score, the anterolateral score, the number of positive regions were associated with CPAP support. When considering the subgroup of patients undergoing lung ultrasonography after 72 hours (128 patients) the total score was independently associated with both the primary and secondary outcome. Conclusion Lung ultrasonography can be a promising prognostic tool in patients admitted to non-ICU units for COVID-19 pneumonia.

Cardiovascular disease and cancer are leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system. The above considerations have led to the development of a new branch of clinical cardiology based on the principles of multidisciplinary collaboration between cardiologists and oncologists: Cardio-oncology, which aims to find solutions to the prevention, monitoring, diagnosis and treatment of heart damage induced by cancer care in order to pursue, in the individual patient, the best possible care for cancer while minimizing the risk of cardiac toxicity. In this consensus document we provide practical recommendations on how to assess, monitor, treat and supervise the candidate or patient treated with potentially cardiotoxic cancer therapy in order to treat cancer and protect the heart at all stages of the oncological disease. Cardiovascular diseases and cancer often share the same risk factors and can coexist in the same individual. Such possibility is amplified by the deleterious effects of cancer treatment on the heart. The above considerations have led to the development of a new branch of clinical cardiology, based on multidisciplinary collaboration between cardiologist and oncologist: the cardio-oncology. It aims to prevent, monitor, and treat heart damages induced by cancer therapies in order to achieve the most effective cancer treatment, while minimizing the risk of cardiac toxicity. In this paper, we provide practical recommendations on how to assess, monitor, treat and supervise patients treated with potential cardiotoxic cancer therapies.

Patient: Male, 72-year-old Final Diagnosis: Metastatic squamous cell carcinoma Symptoms: None Medication:— Clinical Procedure: — Specialty: Cardiology Objective: Rare disease Background: Cardiac metastases of head and neck tumors are extremely rare, and antemortem diagnosis is even rarer. In most cases, patients show symptoms or electrocardiographic abnormalities and expected survival is considerably low. Case Report: A 72-year-old man was admitted to our cardiology ward with suspected endocarditis 2 months after a right hemiglossectomy for a squamous cell carcinoma. He was asymptomatic and showed no electrocardiogram abnormalities. Echocardiography showed an iso-ipoechogenic round-shaped formation at the right ventricle apex that was suspected to be a metastasis owing to 2 cardiac magnetic resonance imaging examinations showing a significant increase in its volume over 14 days. The patient was evaluated by a multidisciplinary team and referred for first-line chemotherapy with carboplatin, 5-fluoruracil, and cetuximab. He died after almost 4 months of follow-up. Conclusions: This case presents a very rare diagnosis as well as some unique features, including the intramyocardial localization, the absence of symptoms, and electrocardiogram abnormalities. Our report shows the relevance of imaging techniques in defining even the most unusual clinical findings, and it emphasizes the significance of early recognition of cardiac masses in order to identify the appropriate medical or surgical therapy for patients.

INTRODUCTION AND OBJECTIVES Cardiologists' work distress has been seldom studied. The ItAliaN cardiologists' Undetected distress Study survey was designed to assess prevalence of work distress and satisfaction, and to gain insight into associations among these constructs and socio-demographics and job description. METHODS We invited members of our national cardiological society (Associazione Nazionale Medici Cardiologi Ospedalieri) to participate in an anonymous, self-report, exclusively web-based survey, posted on the Associazione Nazionale Medici Cardiologi Ospedalieri website. ItAliaN cardiologists' Undetected distress Study included socio-demographics, job description and a 15-item questionnaire on job-related distress and work satisfaction. RESULTS Of 7393 invited cardiologists, 1064 completed the survey. Organizational problems and worries about medico-legal controversies were reported by 71% and 49% of participants, respectively; over one-third reported loss of enthusiasm, helplessness, work-life imbalance and lack of control over work. Conversely, 86% felt competent at work, 67% rewarded by the moral/human meaning of their work and 52% satisfied with their professional fulfilment. Factor analysis revealed a meaningful underlying structure including four factors: job strain, positive meaning, emotional fatigue and relational difficulties. Relational difficulties were more frequent in cardiologists working in primary-level than in secondary and tertiary care hospitals (P = 0.017 and P = 0.013, respectively). Interventional cardiologists reported higher positive meaning than those in the clinical inpatients area and outpatient diagnostic settings (P = 0.007 and P = 0.025, respectively) and lower emotional fatigue than subjects in the clinical inpatients area (P = 0.0005). CONCLUSION Cardiologists' work distress should be interpreted integrating job-related negative aspects with a reappraisal of protective personal and relational resources, which should be fostered to promote physicians' wellbeing at the individual, collective and organizational levels.

Objectives The aim of this study was to assess the relationship between gait speed and the risk for death and/or hospital admission in older patients with heart failure (HF). Background Gait speed is a reliable single marker of frailty in older people and can predict falls, disability, hospital admissions, and mortality. Methods In total, 331 community-living patients ≥70 years of age (mean age 78 ± 6 years, 43% women, mean ejection fraction 35 ± 11%, mean New York Heart Association functional class 2.7 ± 0.6) in stable condition and receiving optimized therapy for chronic HF were prospectively enrolled and followed for 1 year. Gait speed was measured at the usual pace over 4 m, and cutoffs were defined by tertiles: ≤0.65, 0.66 to 0.99, and ≥1.0 m/s. Results There was a significant association between gait speed tertiles and 1-year mortality: 38.3%, 21.9%, and 9.1% (p Conclusions Gait speed is independently associated with death, hospitalization for HF, and all-cause hospitalization and improves risk stratification in older patients with HF evaluated using the Cardiac and Comorbid Conditions Heart Failure score. Assessment of frailty using gait speed is simple and should be part of the clinical evaluation process.

Cancer patients have an increased risk of severe COVID-19 infection due to the suppression of the immune system and the development of cytokine release syndrome (CRS) that favor respiratory syndromes and interstitial pneumonia. However, substantial differences exist between patients treated with chemotherapy and patients treated with immune checkpoint inhibitors (ICIs), for which the risk of COVID-19 infection and the immunologic and cytokine profile in case of infection have not yet been well characterized. The administration of ICIs for the treatment of severe COVID-19 infection has been recently suggested. However, no conclusive data have been generated on this matter. To recognize the therapeutic potential of ICIs administration in COVID-19 patients with or without cancer, the Universal Immune System Simulator (UISS) prediction model was used to simulate the immunologic response of COVID-19 patients after ICIs administration. Briefly, UISS represents an appropriate computational modeling infrastructure able to simulate the dynamics of every single entity of the immune system after a stimulus or a therapeutic intervention by using an agent-based methodology. Therefore, the UISS platform, already used for the prediction of the efficacy of specific SARS-CoV-2 candidate vaccines, was here adopted to characterize the immunologic behavior in both COVID-19 and cancer patients and to predict the effects of ICIs in these patients. The computational results allowed us to identify key inflammatory and immune-related factors responsible for severe respiratory syndromes in COVID-19 infected patients with and without cancer. UISS results suggest that the administration of ICIs modulates the immune system and the inflammatory status in both groups of patients with COVID-19 infection, reducing the risk of severe symptoms. Although the results of the present study are still under validation in peripheral blood samples obtained from COVID-19 patients and from cancer patients after two cycles of treatment with ICIs, we can speculate that ICIs may be a good therapeutic approach for the treatment of COVID-19 severe respiratory syndrome even with a concomitant cancer diagnosis. If this is the case, the lower expression levels of inflammatory biomarkers can result in the drop-down of the viral load, assessed by droplet digital PCR in COVID-19 patients. Citation Format: Giulia Russo, Luca Falzone, Bruno Cacopardo, Giuseppe Nunnari, Francesco Torino, Giuseppa Scandurra, Stefania Stefani, Francesco Pappalardo, Massimo Libra. Computational modeling of immunologic response to immune checkpoint inhibitors in COVID-19 patients with and without cancer [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-050.

Background Patients who underwent a successful repair of the aortic coarctation (CoA) show high risk for cardiovascular (CV) events. Mechanical and structural abnormalities in the ascending aorta (Ao) might have a role in the prognosis of CoA patients. We analyzed the elastic properties of Ao measured as aortic stiffness index (AoSI) in CoA patients in the long-term period and we compared AoSI with a cohort of 38 patients with rheumatoid arthritis (RA) and 38 non-RA matched controls. Methods Data from 19 CoA patients were analyzed 28 ± 13 years after surgery. Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation. Results CoA patients showed more than two-fold higher AoSI compared to RA and controls (9.8 ± 12.6 vs 4.8 ± 2.5% and 3.1 ± 2.0%, respectively; all p

Background and Aims Patients who underwent a successful repair of the aortic coarctation show chronic hyperdynamic state and normal left ventricular (LV) geometry; however, there are few data regarding the LV systolic function in the long term. Accordingly, we assessed LV systolic mechanics and factors associated with LV systolic dysfunction (LVSD) in patients with repaired CoA. Methods Clinical and echocardiographic data from 19 repaired CoA were analyzed 28 ± 13 years after surgery. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S′) were analyzed as indexes of LV circumferential and longitudinal systolic function, respectively. Echocardiographic data of CoA patients were compared with 19 patients matched for age and hypertension and 38 healthy controls. Sc-MS was considered impaired if

OBJECTIVES: Due to the chronic inflammatory status, specific neuro-hormones and progression of arterial stiffness, patients with rheumatoid arthritis (RA) are exposed to the development of excessive left ventricular mass disproportionate to the need to compensate left ventricular load. This condition, named inappropriately high left ventricular mass (iLVM), is associated with unfavorable prognosis in patients with hypertension, aortic stenosis or diabetes. In this study, we assessed prevalence and factors associated with iLVM in a large cohort of patients with RA and tested the hypothesis that RA per se is a condition related to iLVM. METHODS: We prospectively analyzed 235 RA patients without overt cardiac disease recruited between January and December 2014, who were compared with 235 controls matched for age, sex, BMI, prevalence of hypertension and diabetes. iLVM was defined as measured/predicted LVM ratio above 123%. LVM was predicted in each individual by using a simple equation considering height, sex and left ventricular work. RESULTS: iLVM was detected in 150 RA patients (64%) and in 30 controls (15%; P

The CKD-EPI equation is more accurate than the MDRD equation in the general population. We performed this study to establish whether chronic kidney disease (CKD) is commonly recognized by clinicians and whether the CKD-EPI equation improves prognosis estimation in patients with chronic cardiovascular disease (CVD). We analyzed data on 12394 CVD patients consecutively examined at the Cardiovascular Center of Trieste (Italy) between November 2009 and October 2013. The outcomes were all-cause death and a composite outcome of death/hospitalization for CV events (D+cvH). CKD-EPI formula reclassified 1786 (14.4 %) patients between KDIGO categories compared to the MDRD: 2.3 % (n = 280) placed in a lower risk and 12.1 % (n = 1506) into a higher risk group. CKD, defined as eGFR-CKD-EPI formula 60 but eGFR-CKD-EPI formula

Aims Unplanned readmissions early after a discharge from acute heart failure hospitalization are common and have become a reimbursement benchmark and marker of hospital quality. However, the competing risk of short-term post-discharge mortality is substantial. Methods and results Using data from the prospective, nationwide Registry IN-HF Outcome, we analysed the incidence and predictors of 30-day mortality or readmissions and associated days-alive-out-of-hospital (DAOH) in 1520 patients discharged alive after admission for acute heart failure. Within 30 days after discharge, 94 patients (6.2%) were readmitted (91% for cardiovascular causes; 60% recurrent heart failure) and 42 (2.8%) died, 10 of which occurred during readmission. Overall, 126 patients (8.3%) met the combined endpoint. By multivariable logistic regression, worsening chronic heart failure as clinical presentation [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.21–2.77, P = 0.005), inotropes during admission (OR 2.19, 95% CI 1.40–3.43, P = 0.0006), length of stay (OR 1.02, 95% CI 1.01–1.04, P = 0.002) and renin–angiotensin system inhibitors at discharge (OR 0.52, 95%CI 0.35–0.77, P = 0.001) independently predicted 30-day all-cause mortality and/or readmission (c-statistic = 0.695). Per cent 30-day DAOH was lower in patients with in-hospital inotrope use, no renin–angiotensin system inhibitors prescription at discharge, New York Heart Association III–IV class at discharge, and correlated inversely with length of stay and age. Conclusion A clinical and biohumoral profile consistent with chronic advanced heart failure and end-organ damage identifies acute heart failure patients discharged home from cardiology units, who are at highest risk of early death and/or readmission. These findings have practical implications for tailoring specific follow-up.

Background The CHA2DS2-VASc score well stratifies the risk for thromboembolic events in non-valvular atrial fibrillation (NVAF) patients. This score may also predict thromboembolic events in sinus rhythm populations. Purpose The purpose of this study was to assess the prognostic role of CHA2DS2-VASc in a Caucasian community population of patients with arterial hypertension and sinus rhythm. Methods A total of 12,599 arterial hypertension residents not receiving anticoagulation were selected from a community population in Trieste between November 2009 and October 2014: 11,159 sinus rhythm and 1440 NVAF patients. We considered thromboembolic events, cardiovascular hospitalisation and all-cause death in all patients divided according to CHA2DS2-VASc. Results Sinus rhythm patients were 74 (interquartile range 65-81) years old, 50% were women, 32% with CAD, mean CHA2DS2-VASc 3.68 ± 1.47 points, significantly lower than NVAF patients (4.26 ± 1.50, P

Chronic inflammation, a condition frequently associated with several pathologies, is characterized by angiogenic and fibrogenic responses that may account for the development of granulomatous tissue. We previously demonstrated that the chymase, rat mast cell protease-5 (rMCP-5), exhibits pro-inflammatory and pro-angiogenic properties in a model of chronic inflammation sustained by mast cells (MCs), granuloma induced by the subcutaneous carrageenan-soaked sponge implant in rat. In this study, we investigated the effects of palmitoylethanolamide (PEA), an anti-inflammatory and analgesic endogenous compound, on rMCP-5 mRNA expression and Microphtalmia-associated Transcription Factor (MITF) activation in the same model of chronic inflammation. The levels of rMCP-5 mRNA were detected using semi-quantitative RT-PCR; the protein expression of chymase and extracellular signal-regulated kinases (ERK) were analyzed by western blot; MITF/DNA binding activity and MITF phosphorylation were assessed by electrophoretic mobility shift assay (EMSA) and immunoprecipitation, respectively. The administration of PEA (200, 400 and 800 µg/ml) significantly decreased rMCP-5 mRNA and chymase protein expression induced by λ-carrageenan. These effects were associated with a significant decrease of MITF/DNA binding activity and phosphorylated MITF as well as phosphorylated ERK levels. In conclusion, our results, showing the ability of PEA to inhibit MITF activation and chymase expression in granulomatous tissue, may yield new insights into the understanding of the signaling pathways leading to MITF activation controlled by PEA.

The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser227 following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders.

Background A proper prognostic stratification is crucial for organizing an effective clinical management and treatment decision-making in patients with chronic heart failure (CHF). In this study, we selected and characterized a sub-group of CHF patients at very low risk for death aiming to assess predictors of death in subjects with an expected probability of 1-year mortality near to 5%. Methods We used the Cardiac and Comorbid Conditions HF (3C-HF) Score to identify CHF patients with the best mid-term prognosis. We selected patients belonging to the lowest quartile of 3C-HF score (≤9 points). Results We recruited 1777 consecutive CHF patients at 3 Italian Cardiology Units (age 76±10years, 43% female, 32% with preserved ejection fraction). Subjects belonging to the lowest quartile of 3C-HF score were 609. During a median follow-up of 21 [12–40] months, 48 of these patients (8%) died, and 561 (92%) survived. The variables that contributed to death prediction by Cox regression multivariate analysis were older age (HR 1.03[CI 1.00–1.07]; p =0.04), male gender (HR 2.93[CI 1.50–5.51]; p =0.002) and a higher degree of renal dysfunction (HR 0.96[CI 0.94–0.98]; p Conclusions The prognostic stratification of CHF patients by 3C-HF score allows one to select patients at different outcome and to identify the factors associated with death in outliers with a very low mortality risk at mid-term follow-up. The reasons why these patients do not outlive the matching part of subjects who expectedly survive are related to a declined renal function and unmodifiable conditions including older age and male gender.

BACKGROUND: Tissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk. METHODS: Two hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise. RESULTS: ExSEcho classified 168 (83.6 %) patients as non-ischemic and 33 (16,4 %) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S') was significantly lower in ischemic than non-ischemic patients (8.7 ± 2.1 vs 9.7 ± 2.7 cm/sec, p = 0.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S', higher LV circumferential end-systolic stress and LASF. CONCLUSIONS: In asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

Anthracyclines, taxanes and trastuzumab are used for therapy in early breast cancer (EBC) overexpressing Human Epidermal Growth Factor 2 (HER2+). These drugs, considered alone, do not present potential nephrotoxicity. However, renal dysfunction (RD) may increase the myocardial sensibility to the insult of these chemotherapies used in combination. The aim of the study is to assess the role of RD on the development of cardiotoxicity associated with trastuzumab-based adjuvant therapy (aTrastC) for EBC. Clinical and echocardiographic data of 499 women with ERB2+ EBC were analyzed. At 12-month evaluation, any symptoms of heart failure or decrease in left ventricular ejection fraction (LVEF) were recorded. Patients who had cardiotoxicity (n = 130, 26 %) were older (57 ± 11 vs. 55 ± 11 years; p = 0.03), had lower glomerular filtration rate (GFR) (76 ± 15 vs. 83 ± 19 ml/min/1.73 m(2); p = 0.003), higher LVEF (69 ± 6 vs. 63 ± 5 %; p < 0.001) and received more frequent doses of doxorubicin (18 vs. 9 %; p = 0.01) than those who did not. In patients with GFR 60-90 and

In the year 2006 the Italian Association of Hospital Cardiologists (ANMCO) promoted a Consensus Conference among professional Scientific Societies in order to redefine the role and core responsibilities of each health professionals involved in heart failure management in a novel integrated network. Five years later, a questionnaire has been proposed to each Italian Regional President of the Association, in order to assess the implementation of the proposed management strategies in the different clinical scenarios of the Italian Regions. Although the Document utilization is not homogeneous through Italy, it is still considered a valuable tool of work.

Background: The authors have applied the selective embolization of thyroid arteries in the treatment of voluminous cervicomediastinal goiters, especially in patients at high surgical risk or reluctant to undergo surgical intervention and radioiodine therapy. Method: Selective arteriography was used to embolize the thyroid arteries in 2 patients with voluminous hyperfunctioning cervicomediastinal goiters and mediastinal compressive symptoms. The first patient had already undergone unsuccessful radioiodine metabolic therapy and had severe left ventricular insufficiency contraindicating surgery. The second patient, despite having no contraindications, declined surgery and radioiodine metabolic therapy. Results: Radiological embolization markedly reduced the goiters in volume, resolved the compressive symptoms, and also normalized thyroid hyperfunction. The second patient needed a second embolization procedure because the embolized arterial branches had partly recanalized. Conclusion: Selective embolization of thyroid arteries can be successfully used to treat selected patients as a preoperative procedure and as an alternative to thyroid resection. Embolization can be repeated to achieve the required therapeutic aims.

Background and purpose: Chronic inflammatory conditions, such as granulomas, are associated with angiogenesis. Mast cells represent the main cell type orchestrating angiogenesis, through the release of their granule content. Therefore, compounds able to modulate mast cell behaviour may be considered as a new pharmacological approach to treat angiogenesis-dependent events. Here, we tested the effect of selective cannabinoid (CB) receptor agonists in a model of angiogenesis-dependent granuloma formation induced by λ-carrageenin in rats. Experimental approach: Granulomas were induced by λ-carrageenin-soaked sponges implanted subcutaneously on the back of male Wistar rats. After 96 h, implants were removed and granuloma formation was measured (wet weight); angiogenesis was evaluated by histological analysis and by the measurement of haemoglobin content. Mast cells in the granulomas were evaluated histologically and by RT-PCR and immunoblotting analysis for mast cell-derived proteins (rat mast cell protease-5 (rMCP-5) and nerve growth factor). Selective CB1 and CB2 receptor agonists, ACEA and JWH-015 (0.001–0.1 mg mL−1), were given locally only once, at the time of implantation. Key results: The CB1 and CB2 receptor agonists decreased the weight and vascularization of granulomas after 96 h. This treatment also reduced mast cell number and activation in granulomatous tissue. Specifically, these compounds prevented the transcription and expression of rMCP-5, a protein involved in sprouting and advance of new blood vessels. Conclusion and implications: Modulation of mast cell function by cannabinoids reduced granuloma formation and associated angiogenesis. Therefore cannabinoid-related drugs may be useful in the management of granulomatous diseases accompanied by angiogenesis. British Journal of Pharmacology (2008) 154, 1672–1679; doi:10.1038/bjp.2008.211; published online 16 June 2008

Noninvasive imaging plays a pivotal role in the diagnosis and management of congenital heart disease (CHD). Despite cardiac magnetic resonance (MRI) and computed tomography (CT) have gained particular importance, 2D transthoracic echocardiogram (TEE) and 3D trans- esophageal echocardiogram (TOE) still remain the work- houses of imaging routinely used in all and CHD patients; however 3D images could be challenging in some CHD patients and not being so informative. 3D printing tech- nology improvements have been tremendous over the last few years and several different 3D printing processes have been invented in Medicine

Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective.

Objectives Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a cardiac disease characterised by myocardial necrosis followed by fibro-fatty substitution leading to the onset of ventricular arrhythmias. The aim of the present study was to analyse pregnancy in women affected by this condition. Study design Six women affected by ARVC/D who underwent a pregnancy were studied with a follow-up programme, consisting of 12-lead ECG, signal-averaged ECG, 24-h ECG and two-dimensional and Doppler echocardiogram performed before the beginning of the pregnancy, at 3rd and 7th month of gestation and after the delivery. Results All women were on antiarrhythmic therapy during pregnancy; two complained of palpitations in the last 3 months. Delivery was performed at full terms in all, with caesarean section and epidural anaesthesia in four. Mean weight at birth was 3490 g. No adverse reactions on the newborns were detected. All patients were advised against breast-feeding. No significant morphological changes were detected. During the period following the delivery (1–6 years, mean 2,6 years) one subject experienced a sustained ventricular tachycardia. Conclusions Pregnancy seems to be well tolerated in patients affected by ARVC/D, but a programmed clinical protocol is mandatory particularly in the last trimester and puerperium, due to increased risk of ventricular arrhythmias.

A bidirectional relationship between kidney and heart function is present in all stages of cardiac and renal disease, from the asymptomatic phase of left ventricular systolic dysfunction to overt heart failure, as well as from the initial reduction of glomerular filtration rate to end-stage kidney disease, respectively. The simultaneous presence of both diseases has a significant impact on prognosis and requires specific therapeutic strategies. The early recognition of abnormalities of renal and myocardial function may have a relevant influence on management of combination of these conditions.

Severe ventricular arrhythmias represent one of the main causes of mortality after repair of tetralogy of Fallot. Their appearance is primarily caused by the large ventricular scar created by surgical intervention. However, the role of autonomic activity as a modulating factor should be considered. The aim of our study was to evaluate this activity in a low-risk group of patients operated on for TOF and its correlation with the occurrence of sustained ventricular tachycardia.The study group included 38 patients with a mean age of 31 +/- 10 years, selected out of 76 subjects operated on for total correction of tetralogy of Fallot. After a mean interval of 21.9 +/- 6 years from surgical procedure, they underwent electrocardiography, echocardiography, and time domain heart rate variability (HRV) analysis obtained by 24-hour Holter monitoring. Thirty-five healthy subjects comprised the control group for HRV analysis. During a mean follow-up of 6.2 +/- 3 years, 8 patients experienced episodes of sustained ventricular tachycardia. Among different HRV parameters, the standard deviation of all normal beat intervals showed a significant reduction in this group of patients (91.7 +/- 19 versus 133.4 +/- 46, P.02). Echocardiographic examination demonstrated an increased left ventricular end diastolic volume (85.6 +/- 55 versus 61.3 +/- 13 mL/m(2), P.05) and a reduced left ventricle ejection fraction (53.9 +/- 9 versus 61.0 +/- 6 %, P.01) in arrhythmic patients. QRS duration was similar in patients with or without sustained ventricular tachycardia.Patients after surgical correction of tetralogy of Fallot, considered to be at low risk, showed a significant incidence of severe ventricular arrhythmias. HRV analysis seems to be a useful method for identifying arrhythmic patients, and the standard deviation of all normal beat intervals appears to be the more helpful index.

In the English literature there is no single definition that identifies elderly patients. In our retrospective study, we divided total thyroidectomized patients operated on from 2000 to 2010 in the Department of Surgical Sciences of the “Sapienza” University of Rome, in two groups: group 1 consists of 448 patients over 65 years and group 2 consists of 1275 patients under 65 years. We compared both groups in terms of indications for surgery, histological diagnoses, postoperative complications (laryngeal nerv palsy, hypocalcemia, bleeding and seroma) and mortality. The results showed no statistically significant differences between the two groups with respect to the type of surgical indication, the type of comorbidities, the incidence of postoperative complications and perioperative mortality. The only data discordant with those in the international literature was the incidence of neoplastic disease that is found to be slightly greater in group 2. In conclusion, total thyroidectomy in patients over 65 years is a safe procedure and is not burdened with a higher percentage of postoperative complications, even if requires a careful preoperative assessment of risk factors related to comorbidity.

Wanting to find a way of identifying patients suitable for early discharge after thyroidectomy, we set out to establish whether ionized calcium concentration is a better predictor of post-surgical hypocalcemia than total serum calcium. Data were analyzed to establish whether serum ionized calcium concentrations are correlated with total serum calcium levels and symptomatic hypocalcemia after thyroidectomy. Sixty-two patients undergoing total thyroidectomy at the Department of Surgical Sciences of the "Sapienza" University of Rome, Italy, in 2010. Ionized calcium was measured before (day 0) and after surgery (days 1, 2 and 60) in all the patients. These measurements were compared with preoperative (day 0) and postoperative total serum calcium levels (days 1, 2 and 60). The preoperative ionized calcium levels differed from the ionized calcium levels recorded on days 1 and 2; this pattern was not observed for the total calcium concentrations. Conversely, total calcium on days I and II correlated significantly with the various ionized calcium measurements. The presence of parathyroid glands in the surgical specimen did not seem to affect suitability for discharge. The statistical analysis showed that ionized calcium measurements are more reliable than total calcium measurements in the immediate and long-term follow-up of total thyroidectomy patients. Applying a 95% confidence interval we established reference values for both total serum calcium and ionized calcium, below which all patients develop postoperative symptomatic hypocalcemia. In conclusion, measurement of ionized calcium, as opposed to total calcium, should be strongly recommended in the immediate and longterm follow-up of total thyroidectomy patients.

Background An accurate prognostic stratification is essential for optimizing the clinical management and treatment decision-making of patients with chronic heart failure (HF). Among the best available models, we used the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause mortality in patients with CHF. Methods: we selected and characterized the subgroup of patients at very high risk with the worst mid-term prognosis belonging to the highest decile of 3C-HF score with the aim to assess predictors of survival in subjects with an expected probability of 1-year mortality near to 45%. Methods and results We recruited 1777 consecutive chronic HF patients at 3 Italian Cardiology Units. Median age was 76±10years, 43% were female, and 32% had preserved ejection fraction. Subjects belonging to the highest decile of 3C-HF score were 246 (13.8% of total population). During a median follow-up of 21 [12–40] months, 110 of these patients (45%) survived and 136 (55%) died. The variables that contributed to survival prediction emerged by Cox regression multivariate analysis were the lower degree of renal dysfunction and higher body mass index. Conclusions The prognostic stratification of chronic HF patients allows in daily practice to select patients at different risk for death and identify prognosticators of survival in outliers at very high risk of death. The reasons why these patients outlive the matching part of subjects who expectedly die are related to the maintenance of a satisfactory renal function and body mass index.

Left atrial appendage thrombi in neonates are uncommon. We describe a neonate with a large thrombus in the left atrial appendage detected by echocardiography after a paroxystic sustained supraventricular tachycardia associated with intermittent Wolff–Parkinson–White syndrome. Mechanisms and therapy of atrial thrombosis in neonates are briefly discussed.

Radial pseudoaneurysm (PA) is a rare complication of the transradial approach for the arterial catheterization.

Background The well established correlation between intima-media thickness (IMT) and the risk of cardiovascular and cerebrovascular events and death is usually measured in subjects with multiple vascular risk factors, which makes it difficult, after application of the usual analysis-of-variance linear combination of effects model, to establish whether each cardiovascular risk factor has, per se, an effect on IMT. Method and results In this study we investigated five “pure” groups of patients (865), i.e. each presenting only one of the following risk factors: hypertension, obesity, overweight, smoking, hypercholesterolaemia and a control group of 37 healthy subjects. We measured, both as discrete and as continuous variables, the following indices: intima-media thickening of the common carotid artery (IMTC) and of the common femoral artery (IMTF) and the ankle-brachial index (ABI). Descriptive statistics were used to analyse the prevalence of pathological values for the three indices in the different groups. Subsequently the entire group of 902 subjects was included in a correlation analysis in which the Pearson correlation coefficient for each pair of variables was computed. In order to assign the risk factors a continuous ranking, and obtain a more general idea of the correlation structure, principal component analysis (PCA) was used. The scores obtained from PCA made it possible to build a scale of severity of the vascular risk factors considered. All the risk factors considered were demonstrated to strongly affect the studied indices. Overweight was shown to be the least important risk factor with regard to intima-media thickening, followed by smoking, hypercholesterolaemia, hypertension and finally obesity, which emerged as the greatest risk factor. Conclusions The strong correlation between the indices made it possible to compute a composite general score, which provides an univocal risk estimation at single-patient level. IMTF was demonstrated to be the most sensitive descriptor. The construction of this risk scale has implications for preventive treatment and the frequency of instrumental examinations, allowing clear quantitative definition of the extent of the damage.

Valve ring abscess complication of infective endocarditis increases the expected morbidity and mortality rates of patients, but is seldom recognized by available noninvasive techniques. In our study, two-dimensional echocardiography successfully detected valve ring abscesses in eight patients with infective endocarditis affecting aortic valve prosthesis. Echocardiography showed the perivalvular abscess as an echo-free space in all patients. Prosthetic vegetations were seen in the only patient who had a biological prosthesis and excessive prosthetic rocking was observed in cases with severe aortic regurgitation. In two patients, the first echocardiographic examination showed an echo-free space without evident clinical signs of endocarditis or significant valve regurgitation. Severe aortic insufficiency and congestive heart failure followed the enlargement of the echo-free space. Valve replacement was required in all but one patient. The echocardiographic findings were confirmed at surgery. In one patient, the extension of the abscess to the interventricular septum was not detected by the echocardiography.

One of the most important mechanisms proposed in the pathogenesis of neurally mediated syncope considers the stimulation of myocardial mechanoreceptors as the final trigger leading to reflex hypotension and bradycardia. The aim of our study was to analyze the modifications of systolic and diastolic velocities of the left ventricle by tissue Doppler echocardiography, during the upright tilt test, to confirm the presence of an increased ventricular contractility before syncope. We evaluated 47 patients (mean age 43 years) with unexplained syncope and 13 healthy subjects. Three echocardiographic recordings were collected: at baseline, during the initial 5 minutes of the test, and after 15 minutes of tilt. The upright tilt test was positive in 28 patients. During the test, all of them had a similar, significant, progressive reduction of left ventricular end-diastolic volume, left atrial area, and left atrial volume. In contrast, the left ventricular ejection fraction showed an early, more pronounced decrease in those with positive tests. By tissue Doppler echocardiography, the systolic waves remained almost unchanged, and the early filling waves decreased similarly in those with positive or negative findings and the controls. In contrast, the atrial filling waves showed a significant decrease only in patients with positive tests. In conclusion, our study did not find increased ventricular contractility before syncope. In contrast, a decreased atrial contribution to ventricular filling characterized patients with positive upright tilt test results, which, we postulate, may be an important contributory factor to vasovagal syncope.

SAECG in Tetralogy of Fallot. Introduction: Surgical repair of tetralogy of Fallot is complicated by the occurrence of ventricular tachycardia (VT). Among different indexes proposed to assess prognosis of these patients, the study of QRS and repolarization provided useful information. Controversial results come from the analysis of signal-averaging ECG (SAECG). The aim of our study was to identify patients operated for tetralogy of Fallot at higher risk of sudden death by means of SAECG. Methods and Results: Sixty-six consecutive patients, mean age 26 ′ 10 years, were studied 17.7 ′ 5.8 years after total correction for tetralogy of Fallot using standard ECG, 24-hour Holter recordings, SAECG, and echocardiography. The following variables were measured: standard QRS duration, filtered QRS duration (fQRS), high-frequency and low-amplitude signal duration (HFLA), root mean square of the mean voltage in the terminal portion of filtered QRS (RMS), left and right end-diastolic volumes, and ejection fractions. During a mean follow-up period of 7.3 ′ 3.1 years, 12 patients had episodes of sustained VT and two of them suddenly died. All patients had complete right bundle branch block. Patients with VT were characterized by a significantly longer fQRS duration at all filter settings. On the contrary, there was no difference in standard QRS duration in patients with or without VT. At a multivariate analysis, left ventricular ejection fraction and fQRS were independent predictors for VT. Conclusions: A longer fQRS duration is associated with an increased risk in developing malignant ventricular arrhythmias in asymptomatic patients after total correction of tetralogy of Fallot.

Objective: To assess the health related quality of life of patients who were operated on during childhood for total correction of tetralogy of Fallot, focusing on the psychosocial and cognitive outcomes. Patients: 54 patients (24 men and 30 women, mean (SD) age 32 (4) years), operated on for total correction of tetralogy of Fallot at mean age of 8.2 years, underwent a cardiological examination, psychological assessment (semistructured interview, Minnesota multiphasic personality inventory), evaluation of quality of life (36 item short form health survey), and neuropsychological assessment with an extensive neuropsychological battery of tests. Results: Psychological characteristics—(1) a lower than normal academic level, (2) a job inadequate for educational level, (3) a preference for an overprotective familiar setting, and (4) a difficulty communicating own corporal image. Denial of the cardiopathy was found to be a common behaviour to normalise functioning. Very few patients had a deficit in memory, learning, or attention functions; rather, patients had a deficit in the executive functions, problem solving, and planning strategies. Conclusions: Despite a satisfactory health related quality of life, there are residual psychological and social problems in addition to impaired cognitive outcomes in the presence of a normal intelligence quotient.

Current methods used to investigate pulmonary hypertension in rat models of the disease allow for only one to two measurements of pulmonary artery (PA) pressure in the life of a rat. We investigated whether transthoracic echocardiography can be used to assess the progression of pulmonary hypertension in rats at multiple time points. Serial echocardiographic measurements were performed over a 6-wk period on rats injected with monocrotaline (MCT) or placebo. Development of a midsystolic notch in the PA waveform, a decrease in the PA flow acceleration time (PAAT), an increase in right ventricular (RV) free-wall thickness, and the development of tricuspid regurgitation (TR) were observed as pulmonary hypertension developed. Changes in the PA waveform and PAAT began in week 3 of disease development as the PA systolic pressure (PASP) reached 25–30 mmHg according to right heart catheterization. The RV free-wall thickness increased significantly by week 5 (PASPs 40–50 mmHg). Development of quantifiable TR occurred in week 6 or at PASPs > 65 mmHg. A linear correlation was found between the PAAT and PASP in the range of 30–65 mmHg and between the RV-right atrial pressure gradient (derived from TR velocity) and PASP at pressures >65 mmHg, which enabled a noninvasive estimate of the PASP over a wide range of pressures based on these parameters. These data indicate that transthoracic echocardiography can be used for monitoring the progress of pulmonary hypertension in a rat model.

E-mail: antonella.cherubini@ass1.sanita.fvg.it Background: From the literature we know that less than 50% of patients with coronary artery disease (CAD) reaches the target LDL cholesterol 75 yo 42% vs 46%, p=0,002), had more cardiovascular (CV) risk factors, comorbidities (Charlson index >5) and statins prescription (70% vs 61%), but less frequent stroke or TIA. In the group with LDL available, CARDIOVASCULAR PREVENTION and REHABILITATION

e11556 Background: Adjuvant trastuzumab therapy improves survival of Human Epidermal growth factor Receptor 2 (HER2)-positive women with early breast cancer (EBC). Trastuzumab-induced cardiotoxicity is not uncommon, occurring prevalently asymptomatic in the first three months of therapy. In the setting of community patients, the incidence, timing and phenotype of new onset congestive heart failure (CHF) is unknown. Methods: 499 consecutive HER2-positive women (mean age 55+11) with EBC treated with Trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed-up for 1 year. We evaluated incidence, time of occurrence, clinical features associated with CHF. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and 3-6-9-12 months during Trastuzumab therapy. Results: CHF occurred in 16 patients (3.2%), who were older and had a higher prevalence and higher degree of hypertension in comparison with patients who had not CHF. All CHF patients had a significant reduction in LVEF with a mean peak of – 12 points % detected at 3-month follow up. CHF occurred in 7 patients (44%) within 3-month follow-up, 4 patients (25%) between 3-6 months, 3 patients (19%) between 6-9 months and 2 patients (12%) between 9-12 months. Trastuzumab was discontinued in 10 of 16 patients and re-started in 5 after LVEF recovery. New onset CHF was predicted by the presence of hypertension (OR 2.9 [CI 1.1 – 7.9]. Conclusions: In clinical practice new onset CHF occurs seldom in HER-positive women with EBC, prevalently in the first six months of therapy. CHF is invariably associated with a significant reduction in LVEF and is predicted by a history of hypertension.