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Herein, we present the case of a 58 y–o Caucasian man with unremarkable cardiovascular history and a strong family history for cancer. He was diagnosed with lung adenocarcinoma IVb (pleura, pleural effusion, lymph nodes), PDL1: 2% TPS and absence of actionable driver mutations on DNA and RNA NGS (only ERBB2 mutation). Started first–line chemotherapy with cisplatin–pemetrexed regimen and immunotherapy with pembrolizumab. He developed common/superficial femoral and popliteal deep vein thrombosis (DVT) and pulmonary embolism (PE). The patient started low–molecular–weight heparin (LMWH) namely enoxaparin 1 mg/kg x 2/d (weight: 65 Kg). After 1 mo, CT showed PE resolution. Due to DVT persistence and patient’s preference for oral administration, LMWH was replaced with direct oral anticoagulant (DOAC) namely edoxaban 60 mg 1 cp/d. After 2 mo, resolution of common femoral and popliteal vein thrombosis with partial recanalization of superficial femoral DVT were detected. However, he developed brain metastases treated with WB radiotherapy. We decided for edoxaban full dose long–term anticoagulant treatment with monthly cardioncological surveillance. After 6 mo since cancer diagnosis, the patient was still adherent to DOAC therapy, although in a maintenance combined regimen pemetrexed–pembrolizumab based, without both drug–drug interactions and brain bleeding. Conclusions Thromboembolism is the second leading cause of death in malignancy. In this clinical case, a man with advanced lung cancer developed extended cancer–associated thrombosis (CAT). However, the appearance of brain metastases has posed a clinical dilemma: to continue or to withdraw the anticoagulant therapy and, also, which drug to choose between LMWH and DOAC. Literature is limited on the use of DOACs in cancer patients with brain metastases. Besides, current guidelines neither advocate contraindication to DOAC, nor suggest caution as requested for gastrointestinal and genitourinary sites of cancer. We decided to proceed with edoxaban therapy, despite chemotherapy combined to immunotherapy were still ongoing and the concurrent appearance of brain metastases, with good results in efficacy, patient’s adherence and, mostly, safety. In conclusion, in regard to our clinical experience, we point out DOAC as a reliable and manageable therapeutical choice in CAT, also in active cancer patients with brain metastases receiving chemo–immunotherapy.

The most challenging feature of heart failure (HF) still remains the evaluation of congestion. Residual congestion at discharge and the difficulties in perfectly dosing therapies in order to balance the hydration status of the patient are the most worrisome issues when dealing with HF. The use of bioimpedance vector analysis (BIVA) might promote a different approach in the general management of patients with HF. BIVA is a reliable, fast, bedside tool able to assess the congestion status. It proved to be helpful to physicians for diagnosing congestive status, managing therapies, and providing prognostic information in the setting of HF. Bioelectrical Phase Angle (PhA) – as derived from equations related to the parameters of BIVA – recently surged as a possible biomarker for patients with HF. Studies provided data about the application of PhA in the clinical management and in the overall risk stratification of HF patients. Basically, the use of PhA might be considered as a holistic evaluation of patients with HF which includes the need for a multiparametric approach able to effectively depict the clinical status of patients. There is no definite biomarker able to comprehensively describe and identify all the features of HF patient, but scores based on molecules/techniques able to explore the different pathogenetic mechanisms of HF are desirable. The aim of this review was to provide a comprehensive evaluation of literature related to PhA role in HF and the impact of this biomarker on clinical management and risk stratification of HF patients.

The impact of coronary artery disease (CAD) on all–cause mortality and overall disabilities is well–established. Percutaneous and/or surgical coronary revascularization procedures dramatically reduced the occurrence of adverse cardiovascular events in patients suffering with atherosclerosis. Specifically, guidelines from the European Society of Cardiology on the management of myocardial revascularization promoted coronary artery by–pass graft (CABG) intervention in patients with specific alterations in coronary tree due to higher beneficial effects of this procedure as compared to percutaneous one. Left internal mammary artery (LIMA) is one of the best–performing vessels in CABG procedures due to its location and its own structural characteristics. Nevertheless, non–invasive assessment of its patency is challenging. Doppler Ultrasonography (DU) might perform as a reliable technique for non–invasive evaluation of the patency of LIMA. Data from literature revealed that DU may detect severe (>70%) stenosis of the LIMA graft. In this case, pulsed–wave Doppler might show peak diastolic velocity/peak systolic velocity < 0.5 and diastolic fraction < 50%). Stress test might also be adopted for the evaluation of patency of LIMA through DU. The aim of this narrative review is to evaluate the impact of DU on the evaluation of the patency of LIMA graft in patients who undergo follow–up after CABG intervention. The aim of this narrative review is to evaluate the impact of DU on the evaluation of the patency of LIMA graft in patients who undergo follow–up after CABG intervention.

Aims We have recently proposed a new prediction model for risk mortality based on four parameters of congestion to predict mortality in patients with acute or chronic heart failure. This risk model (HYDRA Score, HS) is based on the number of parameters of congestion above significant cut–offs (range 0–4): BNP >441 pg/mL, estimated plasma volume status (ePVS) >5.3 dL/gr, bioimpedance vector analysis (BIVA) >73.8%, and BUN/creatinine ratio (BUN/Cr) >25. As bioimpedance vector analysis is a measure of peripheral congestion but it is not frequently used in clinical practice, we evaluated the performance of the risk model by including the presence of peripheral edema in place of BIVA (HYDRA Semplified Score, HSS). Methods and results We analysed data from 436 HF patients. During a one–year follow–up 81 patients died (18.6%). Discrimination for all–cause mortality was compared by Harrell‘s C–statistic. Calibration was assessed by Hosmer–Lemeshow test and global performance by Nagelkerke‘s R2. Correlation between scores was assessed by Spearman rank test. Correlation between the scores was good (rho = 0.91, p Conclusions Simplified HYDRA score seems a good and friendly model risk to predict one–year mortality in patients with heart failure and could be used as alternative to HYDRA score.

Abstract Acid sphingomyelinase deficiency (ASMD) – also known as Niemann–Pick (NP) disease – is a rare, autosomal recessive disorder which is characterized by deficiency of the lysosomal enzyme acid sphingomyelinase (ASM), thus resulting in excessive storage of lipids in organs (i.e. spleen, liver, lung, bone marrow, lymph nodes, and vascular system). Literature provided few cases of moderate–to–severe valvular heart disease due to ASMD, mostly in adulthood. We reported the case of a patient with B–subtype NP disease which was diagnosed during his adulthood. NP disease was associated to situs inversus. Specifically, a severe, symptomatic aortic stenosis was also identified and the need for surgical or percutaneous intervention was deemed. The heart team chose Trans Aortic Valvular Implantation (TAVI) which was successfully performed with no further complications at follow–up.

Background The relationship between anaemia and congestion in HF and its prognostic role are controversial. The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in HF and the impact on mortality. Methods We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin (Hb) levels < 12 g/dL in women and < 13 g/dL in men. We evaluated brain natriuretic peptide (BNP, central congestion biomarker) and Hydration Index (HI %, bioimpedance vector analysis, peripheral congestion biomarker). The endpoint was all–cause mortality. Results Anaemia occurred in 59% of patients with AHF and in 35% with CHF (p Conclusions Anaemia correlates HF status, functional class, renal function and biomarkers of central/peripheral congestion. Indeed, anaemia was not an independent predictor for mortality. Therefore, anaemia in HF seems rather a marker of disease severity in patients with high congestion burden than a predictor of death.

Background Patients discharged after acute coronary syndrome (ACS) deserve a tight follow–up in order to optimize long–term pharmacological treatments and prevent the occurrence of adverse events. The aim of the PONTE–ACS Project was to evaluate the impact of a dedicated cooperative program between hospital and outpatient structures on the persistance on recommended therapies and long–term outcome occurrence in patients discharged after ACS. Materials and Methods This was a prospective, longitudina, cohort study. We enrolled patients who were discharged after ACS and/or after coronary revascularization in the HUB centres of ASL Bari. Patients underwent cardiologic evaluation and laboratory examination at 30 days, 3–, 6–, and 12–months from the index event. The following endpoint were considered: all–cause mortality, ACS recurrence/cardiac ischemia/angina, restenosis/intrastent thrombosis, stroke/transient ischemic attack (TIA), heart failure, any bleeding. Adherence and persistence to therapies were evalauted as well as the percentage of patients who reached the recommended goals. Results We enrolled 2476 patients (77.4% male, mean age: 67.2±12.0 yrs). After one–year follow–up, 99.5% (p Conclusions The PONTE–ACS Project was able to improve the management of patients after ACS, to manage a structured follow–up protocol for patients discharged after ACS and/or coronary revascularization, thus improving adhesion to recommended therapies and keeping lower the incidence of major cardiovascular and bleeding events.

Background Circulating concentrations of parathyroid hormone (PTH) increase in heart failure (HF) patients. Plasma concentrations in PTH are related to HF severity, thus considering PTH as biomarkers of HF worsening. The aim of our study was to evaluate clinical correlations and prognostic role of PTH in patients with HF. Methods We evaluated 229 HF patients (42% acute and 58% chronic HF). Patients underwent evaluation of NYHA functional class, measurements of bioactive PTH (1–84), B–type natriuretic peptide (BNP), creatinine cleareance, and hydration status (by means of bioimpedance analysis) and all–cause mortality during follow–up. Results PTH levels were higher in acute HF as compared to chronic HF (248±180 pg/ml vs 153±133 pg/ml, p 249 (AUC=0.65; sensibility 50% and specificity 82% ). At multivariate Cox regression analysis PTH level was no longer associated with death, while BNP, hydration status, and renal function maintained an independent predictive value for mortality (HR 1.0004, HR 1.06, and HR 0.98, respectively). Conclusions Our study demonstrated that circulating concentrations of bioactive PTH are related to other biomarkers of HF worsening, i.e. creatinine clearance and hydration status. Although PTH acted as a prognostic determinants of mortality in HF, it was not an independent prognostic biomarkers at multivariate regression analysis.

Background The evaluation of congestion play a central role in the management of patients with acute heart failure (AHF).The impact of gender on congestion in patients with HF is still a matter of debate. The objective of this analysis was to evaluate the impact of gender on congestion status at admission of patients hospitalized for AHF. Methods We consecutively enrolled 487 patients with AHF (50% female). We assessed peripheral edema, jugular venous distention (>10 cm), B–type natriuretic peptide (BNP), hydration status (by means of bioimpedance analysis), and estimated plasma volume (by means of the Duarte’s formula [D–ePVS] and Kaplan–Hakim formula [KH–ePVS]). Results Home medications and body mass index were not different between women and men. Women were older (79 yrs vs 77 yrs, P = 0.005), showed better left ventricular ejection fraction (mean 50% vs 38%, P Conclusions The evaluation of congestion in AHF using physical examination and multiparametric approaches was similar between women and gender. Women rather showed higher plasma volume as compared to male individuals.

Background Dual antiplatelet therapy (DAPT) has important implications for clinical outcomes in coronary disease. Nevertheless, the risk for bleeding often impact on the long–term administration of DAPT. The aim of this study was to evaluate the determinants of bleeding risk after ACS. Methods This was a subanalysis of the PONTE ACS study. The PONTE ACS study is a prospective, longitudinal, cohort study which enrolled patients who were discharged from HUB centres of ASL BARI after coronary revascularization and/or ACS. They underwent clinical evaluation at 30 days, 3, 6 and 1 year–follow–up. The data were collected after including the data in the electronic medical record of the PONTE ACS study. Anthropometric, clinical and pharmacological parameters, instrumental and laboratory examinations were included. Data were computed in order to evaluate the major determinants of all–cause bleeding at one–year follow–up. Results We finally enrolled 2476 patients (77.4% male, mean age: 67.2±12.0 years). Pharmacological treatments were optimized during the follow–up visits. According to anti–thrombotic therapies, 92.1% of patients persisted on DAPT at one–year follow–up. The number of patients on DAPT+anticoagulant were: 4.4%. All–cause bleeding occurred in 2.2% of patients. Anthropometric characteristics (height [β: –0.04594 ± 0.01610, p = 0.0044] and weight [β: –0.03043 ± 0.01035, p = 0.033]), male gender [β: –0.7008 ± 0.2818, p = 0.0129], and age [β: 0.02535 ± 0.01219, p = 0.0376] were the major determinants of all–cause bleeding at univariate regression analysis but they were not confirmed at multivariate regression analysis (p=ns). Kaplan Meier curve points out the impact of age on all–cause bleeding (Figure 1). Nor DAPT or triple therapy remained associated with all–cause bleeding at one year follow–up. Conclusions Long–term DAPT is not a predictor of all–cause bleeding in patients who suffered ACS and/or coronary revascularization.

Background The administration of statin therapy in patients who suffered from acute coronary syndrome (ACS) is fundamental in order to avoid recurrences and adverse cardiovascular events. The long–term adherence and persistence on statin therapy is challenging. The aim of this study was to evaluate the prognostic impact of a dedicated follow–up outpatient program for patients who were discharged with the diagnosis of ACS on adherence and persistence on statin therapy. Methods This was a subanalysis of the PONTE ACS study. The PONTE ACS study is a prospective, longitudinal, cohort study which enrolled patients who were discharged from HUB centres of ASL BARI after coronary revascularization and/or ACS. They underwent clinical evaluation at 30 days, 3, 6 and 1 year–follow–up. The data were collected after including the data in the electronic medical record of the PONTE ACS study. Anthropometric, clinical and pharmacological parameters, instrumental and laboratory examinations were included. The following endpoints were considered: all cause death, ACS recurrence/cardiac ischemia/angina, restenosis/intrastent thrombosis, stroke/transient ischemic attack (TIA), heart failure, all–cause bleeding. Results We enrolled 2476 patients (mean age: 67.2±12.0 years). At 1–year follow–up optimal medical therapy was reached in most of patients: 84.1% were on beta–blockers, 63.1% on ACEi/sartans, 92.1% on dual antiplatelet therapy, 99.5% on statins, 16.1% on ezetimibe, and 9.9% on PCSK9 inhibitors. At multivariate regression analysis, heart rate, baseline creatinine values, and statin therapy were independent predictors of the composite endpoint all cause death, ACS recurrence/cardiac ischemia/angina, restenosis/intrastent thrombosis, while heart rate and statin therapy remained predictors of the composite endpoint death, ACS recurrence/cardiac ischemia/angina, restenosis/intrastent thrombosis, stroke/transient ischemic attack (TIA), heart failure (Figure 1). Conclusions Statin therapy confirmed their therapeutic role in secondary cardiovascular prevention protocols. The need for continuing long–term statin therapy after ACS is fundamental in order to ameliorate the prognosis of patients.

Background The assessment of long term mortality in acute decompensated heart failure (ADHF) is challenging. Respiratory failure and congestion play a fundamental role in risk stratification of ADHF patients. The aim of this study was to investigate the impact of arterial blood gases (ABG) and congestion on long–term mortality in patients with ADHF. Methods and Results We enrolled 252 patients with ADHF. Brain natriuretic peptide (BNP), blood urea nitrogen (BUN), phase angle as assessed by means of bioimpedance vector analysis (BIVA), and ABG analysis were collected at admission. The endpoint was all–cause mortality. At a median follow–up of 447 days, (IQR: 248–667), 72 patients died 1–840 days (median 106, IQR: 29–233) after discharge. Respiratory failure types I and II was observed in 78 (19%) and 53 (20%) patients, respectively. The ROC analyses revealed that the cut–off points for predicting death were: >441 pg/mL for BNP, >30 mg/dL for BUN, ≤ 69.7 mmHg for partial pressure in Oxygen (PaO2), and ≤4.9° for Phase Angle. Taken together, these four variables proved to be good predictors for long–term mortality in ADHF (AUC 0.78, 95% CI 0.72–0.78), thus explaining 60% of all deaths. A multiparametric score based on these variables was determined: each single–unit increase promoted a 2.2–fold augmentation of the risk for death (HR 2.2, 95% CI 1.8–2.8, P Conclusions A multiparametric approach based on measurements of BNP, BUN, PaO2, and phase angle is a reliable approach for long–term prediction of mortality risk in patients with ADHF.

Background Heart rate is able to impact on the prognosis if patients with cardiovascular diseases. The aim of this study was to evaluate the impact of heart rate at discharge of patients with ACS and/or coronary revascularization on long–term follow–up Methods This was a subanalysis of the PONTE ACS study. The PONTE ACS study is a prospective, longitudinal, cohort study which enrolled patients who were discharged from HUB centres of ASL BARI after coronary revascularization and/or ACS. They underwent clinical evaluation at 30 days, 3, 6 and 1 year–follow–up. The data were collected after including the data in the electronic medical record of the PONTE ACS study. Anthropometric, clinical and pharmacological parameters, instrumental and laboratory examinations were included. Data were computed in order to evaluate the major determinants of all–cause mortality at one–year follow–up. Results We finally enrolled 2476 patients (77.4% male, mean age: 67.2±12.0 years). Pharmacological treatments were optimized during the follow–up visits. Heart rate at discharge was 65.5 ± 11.3 bpm. At univariate regression analysis, age, systolic and diastolic arterial pressure, body mass index, smoke habit, diabetes, hypertension, high–density lipoprotein and total cholesterol, creatinine, haemoglobin, fasting glycemia, left ventricle ejection fraction, heart rate, use of ACEi/sartans, statins, dual/triple anti–thrombotics were all related to all–cause mortality. Nevertheless, at multivariate Cox regression analysis, age (β coefficient: 0.07117 ± 0.01942, p = 0.0002), history of hypertension (1.4823 ± 0.7476, p = 0.0474), and heart rate (0.04409 ± 0.01278, p = 0.0006) remained related to the primary endpoint. Conclusions Heart rate confirmed to act as a long–term predictor of all–cause death in patients with ACS.

Background Soluble suppressor of tumorigenity (sST)–2 plasma concentrations are related to atherosclerosis. The aim of the study was to assess the prognostic impact of sST2 and its membrane–associated form (ST2L) in patients with carotid atherosclerotic plaque who underwent endarterectomy (CEA). Methods 82 consecutive patients (age range: 48–86 years) who underwent CEA were enrolled. Anthropometric, clinical, instrumental, and laboratory evaluations were gathered. Thirty–seven (45%) patients were symptomatic for cerebrovascular diseases. Patients underwent a five–year follow–up. Phone calls and the analysis of national and regional databases were adopted in order to evaluate the occurrence of the primary outcome (all–cause mortality). The populations was divided according to survival status. Results Statins were administered in 81% and 87.5% of survivors and non–survivors, respectively. sST2 levels were higher in non–survivors as compared to survivors (117.0 ± 103.9 vs 38.0 ± 30.0ng/mL, p 98.44 ng/mL as the best predictor for mortality. At one year follow–up, survival rate decreased up to 20% in patients with sST2 higher than the cut–off value. At multivariate regression analysis sST2 (HR: 1.012, 95% CI: 1.008–1.016, p Conclusions sST2 may act as independent prognostic determinant of all–cause mortality and symptomatic cerebrovascular diseases in patients with carotid atherosclerotic plaque who underwent CEA.

Experimental and clinical data have been presented which support the efficacy of using a large-volume nonblood perfusate for cardiopulmonary bypass. Dogs have consistently survived hemodilution of 100 to 120 ml/kg body wt when manifest hypoxic acidosis has been ameliorated with THAM (tris [hydroxymethyl] aminomethane) or sodium bicarbonate. Fifty-eight patients have undergone total bypass with the disc oxygenator totally primed with 2,500 to 3,000 ml of buffered Ringer's or Ringer's lactate solution. Normothermia and moderate hypothermia have been employed with a hemodilution of 33 to 60 ml/kg body wt and a mean perfusion hematocrit of 24%. Despite the decrease in oxygen-carrying capacity of the blood, acidosis has not been observed during prolonged perfusions at median flow rates. Following oxygenator reinfusion, the postoperative total blood volume has been normal. However, a decrease in red cell mass was observed which necessitated the administration of "packed red cells." With this technique, the clotting time was more readily restored to normal, and kidney function was markedly improved over a comparable series of patients perfused with donor blood.