Search

Patients suffering from acute coronary syndrome (ACS) present a high risk of recurrence and new adverse cardiovascular events after hospital discharge. Elevated plasma LDL-cholesterol (LDL-C) levels have been shown to be a causal factor for the development of coronary heart disease, and robust clinical evidence has documented that LDL-C levels decrease linearly correlates with a reduction in cardiovascular events. Recent studies have also demonstrated the safety and efficacy of an early and significant reduction in LDL-C levels in patients with ACS. In this position paper, Italian Association of Hospital Cardiologists proposes a decision algorithm on early adoption of lipid-lowering strategies at hospital discharge and short-term follow-up of patients with ACS, in the light of the multiple evidence generated in recent years on the treatment of hypercholesterolaemia and the available therapeutic options, considering current reimbursement criteria.

In the growing therapeutic armamentarium for heart failure (HF) management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for HF. Indeed, vericiguat does not inhibit neuro-hormonal systems overactivated in HF or sodium–glucose co-transporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with HF. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with HF and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening HF. This ANMCO position paper summarises key aspects of vericiguat mechanism of action and provides a review of available clinical evidence. Furthermore, this document reports use indications based on international guideline recommendations and local regulatory authority approval at the time of writing.

Octogenarians represent the most rapidly expanding population segment in Europe. The prevalence of heart failure (HF) in this group exceeds 10%. We assessed changes in clinical characteristics, therapy, and 1-year outcomes over 2 decades in chronic HF outpatients aged ≥ 80 years enrolled in a nationwide cardiology registry.We included 2520 octogenarians with baseline echocardiographic ejection fraction measurements and available 1-year follow-up, who were recruited at 138 HF outpatient clinics (21% of national hospitals with cardiology units), across 3 enrolment periods (1999-2005, 2006-2011, 2012-2018).At recruitment, over the 3 study periods, there was an increase in age, body mass index, ejection fraction, the prevalence of obesity, diabetes, dyslipidemia, pre-existing hypertension, and atrial fibrillation history. The proportion of patients with preserved ejection fraction rose from 19.4% to 32.7% (P for trend.0001). Markers of advanced disease became less prevalent. Prescription of beta-blockers and mineralocorticoid receptor antagonists increased over time. During the 1-year follow-up, 308 patients died (12.2%) and 360 (14.3%) were admitted for cardiovascular causes; overall, 591 (23.5%) met the combined primary endpoint of all-cause mortality or cardiovascular hospitalization. On adjusted multivariable analysis, enrolment in 2006 to 2011 (HR, 0.70; 95%CI, 0.55-0.90; P=.004) and 2012 to 2018 (HR, 0.61; 95%CI, 0.47-0.79; P=.0002) carried a lower risk of the primary outcome than recruitment in 1999 to 2005.Among octogenarians, over 2 decades, risk factor prevalence increased, management strategies improved, and survival remained stable, but the proportion hospitalized for cardiovascular causes declined. Despite increasing clinical complexity, in cardiology settings the burden of hospitalizations in the oldest old with chronic HF is declining.

The appropriateness of prescribing direct oral anticoagulants [dabigatran, rivaroxaban, apixaban, and edoxaban (DOACs)] is regulated on the criteria established in Phase III trials. These criteria are reported in the summary of the product characteristics of the four DOACs. In clinical practice, prescriptions are not always in compliance with established indications. In particular, the use of lower doses than those recommended in drug data sheets is not uncommon. Literature data show that the inappropriate prescription of reduced doses causes drug underexposure and up to a three-fold increase in the risk of stroke/ischaemic transient attack, systemic thromboembolism, and hospitalization. Possible causes of the deviation between the dose that should be prescribed and that prescribed in the real world include erroneous prescription, an overstated haemorrhagic risk perception, and the presence of frail and complex patients in clinical practice who were not included in pivotal trials, which makes it difficult to apply study results to the real world. For these reasons, we summarize DOAC indications and contraindications. We also suggest the appropriate use of DOACs in common clinical scenarios, in accordance with what international guidelines and national and international health regulatory bodies recommend.

A straightforward two-step synthesis protocol affords a series of chiral amide-based bis-pyridine substituted polyether macrocycles. One ligand is particularly able to complex Terbium(III) ion spontaneously. Upon complexation, interesting chiroptical properties are observed both in absorbance (ECD) and in fluorescence (CPL). In ligand-centered electronic circular dichroism, a sign inversion coupled with a signal enhancement is measured; while an easily detectable metal-centered circularly polarized luminescence with a glum of 0.05 is obtained for the main 5D4 → 7F5 terbium transition. The coordination mode and structure of the complex was studied using different analysis methods (NMR analysis, spectrophotometric titration and solid-state elucidation).

AimsWhile several studies in the literature have reported results of catheter ablation of AF, few is known regarding outcome for more than 10 years.Methods and resultsThe complete population of patients who underwent AF ablation in the years 2002–2021 in the department of cardiology of the hospital of Reggio Emilia has been analysed. The last follow-up was made in the second half of 2022. During this period the technique of ablation remained relatively unchanged as well the physicians performing ablation. Primary endpoint was the recurrence of symptomatic AF, defined as AF that caused symptoms that were defined by the patient as able to alter their quality of life. 669 patients underwent catheter ablation and 618 were followed until 2022. Median age of the patients was 58 ± 9 years and 521 (78%) were male. There were 407 (61%) of patients with paroxysmal AF, 167 (25%) with persistent AF and 95 (14%) with long-lasting AF. A total of 838 procedures were performed, with a mean of 1.25 per patient. 163 (26%) patients had 2 procedures and 6 had 3 ablations. Periprocedural complications occurred in 4.8% of procedures. Follow-up data were available for 618 patients (92.4%). The median follow-up duration was 6.6 years (IQR 3.2–10.8). The estimated recurrence rate of symptomatic AF was 26% at 10 years, 54% at 15 years and 82% at 20 years. The recurrence rate was similar in patients who had performed one procedure and in those who had performed 2 or 3 procedures. Progression to permanent AF occurred in 112 patients (18%). The major events that occurred during the follow-up consisted of total mortality in 4.5%, heart failure in 3.1% and TIA/stroke in 2.4%.ConclusionSymptomatic AF tends to recur during long-term follow-up despite one or more procedures. Catheter ablation seems able to reduce the rate of symptomatic recurrences and to delay the time of their occurrence. These findings are consistent with the knowledge that an age-dependent progressive structural atriomiopathy is the basis for the development of AF.

Backgrounds In the recent years, two randomized controlled trials (RCTs), the PROTECT–AF trial and the PREVAIL trial demonstrated that in atrial fibrillation (AF) patients, left atrial appendage closure (LAAC) compared with oral anticoagulants (OAC), showed a non–inferiority in the prevention of stroke and even a reduction in mortality. Nevertheless, this net clinical benefit was not confirmed in the most recent RCT comparing LAAC vs OAC, the PRAGUE–17 trial. The aim of the present meta–analysis was to evaluate the efficacy and safety of LAAC compared to OAC among available high–quality studies. Methods A systematic search of electronic databases (Medline, Scopus, Embase and the Cochrane Library) was performed to identify eligible RCTs and observational studies with propensity score matching (PSM) analysis. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Outcomes of interest were the occurrence of cardiovascular death (CVD), all cause death, all–type stroke, and major bleedings. Results A total of 3 RCTs and 6 PMS studies involving 6924 patients were identified. After a median follow–up of 2.7 years (IQR 2–4.5), patients who received LAAC had a lower risk of CVD (OR=0.58; 95%CI 0.48–0.71, I2=0%), all cause death (0.59; 95% CI 0.45–0.76, I2 67%) and major bleedings (OR=0.58; 95%CI 0.43–78 I2=52%) compared with patients on OAC. No difference was found between the two groups regarding strokes incidence (OR=0.94; 95% CI 0.76–1.16, I2=0%). Conclusions According to this meta–analysis, LAAC presents a comparable efficacy in the prevention of stroke compared to OAC with a reduced risk of major bleedings, all cause death and CVD that may stand out with longer follow–up.

Introduction Cancer and CVD often share common risk factors and pathophysiological mechanisms, the relationship can be amplified by oncological treatment. In the case of aromatase inhibitors (AIs), used for a long time in breast cancer (BC) expressing the estrogen receptor there is a significant association with dyslipidemia, metabolic syndrome, ischemic heart disease and heart failure. For this reason the ESC guidelines on Cardio–oncology (LG–CO) recommend the evaluation of the baseline CV risk using SCORE2 or SCORE2–OP and aggressive control of CV risk factors (RF) to be integrated with the management of cancer. In case of suspicion of coronary artery disease (CAD), ESC LG–CO recommended the adoption of ESC 2019 guidelines for CAD. We present a case of atypical chest pain (LG 2019 ESC CAD pre–test probability < 15%) in a woman at very high CV risk and in adjuvant therapy with AI for BC Clinical case August 2022: 63–year–old female with multiple RF (premature family history of CAD, smoke, hypertension and dyslipidemia) in adjuvant treatment with Exemestane (Letrozole not tolerated) for BC (2020: T2N0M0 ER 99%, PGr– HER2– Ki67 20%) presents in ER for chest pain typical for site, character and irradiation (constricting – burdening, retrosternal radiating to the neck and shoulders) mainly at rest, in the evening, very rarely induced by rapid efforts. Statin therapy was discontinued after initiation of letrozole therapy for arthralgias – myalgias. At the most recent evaluation of blood chemistry: LDL cholesterol 185 mg/dl, Hb, glycemia and thyroid hormones were normal. ECG and rest, troponin, echocardiogram and exercise ECG were normal. Non–synchronized CT with ECG, performed for tumor staging, showed the presence of multiple calcifications on DA, CX and CD (Figure 1). The CGF confirmed the presence of a critical stenosis on the right coronary artery (Figure 2) and a non–critical stenosis on the DA (Figure 3). Successfully performed PTCA with DES implant and started DAPT + high intensity statin with Ezetimibe in addition to antihypertensive therapy obtaining asymptomaticity and optimal control of CV risk factors (FR) Conclusions Aggressive control of CV RF is mandatory in women with BC on AI therapy and high CV risk; the onset of symptoms suggestive of CAD must not be overlooked and in this context coronary CT can be a valid tool for estimating the atherosclerotic burden and to establish the diagnosis.

Background Cardiac lipomas are rare benign tumors. They carry usually a good prognosis and are often an incidental finding of cardiovascular imaging exams for cardiac evaluations. Methods We present a case of left ventricular intramyocardial lipoma detected during the work–up for a positive stress test. Results This case report involves a 55–year–old male, light smoker, with a history of glucose intolerance. Height 190 cm; weight 90 kg; BMI 24.93 kg/m2 He has always played sports and since the age of 16 he performed serial cardiological assessments and stress test for competitive fitness. Already from the first evaluation the ergometric test was markedly pathological (ST segment depression greater than 1 mm in leads V3 to V6), in absence of symptoms. The subsequent diagnostic exams performed (including an exercise myocardial scintigraphy) excluded ischemic aetiology. Competitive fitness has always been reconfirmed for many years. He also performed repeated holter–ECG in absence of any arrhythmias. He was admitted because of a routine check–up. A new stress test (ECG stress test) resulted positive for ECG changes and clinically negative (fig 1) Cardiac MRI demonstrated a small intramyocardial "round like" mass of about 7 mm, located on the middle–distal segment of the left ventricle lateral wall; MRI signals were consistent with a lipom: no evidenced of delayed enanchement (fig 2) and T1 weighted scans assessed perfusion lack of the mass (fig 3). Computed tomography confirmed this diagnosis; the coronary angiography excluded significant coronary artery stenosis. Conclusion We hypnotize that cardiac lipoma in our patient caused persistent ST changes at stress ECG since young age

A 85-year-old lady with severe dyspnea presented in emergency dept. of our institution in Reggio Emilia last July. Typical signs and symptoms of heart failure were associated with high voltage at ECG and echocardiographic findings show a reduced EF (40%) with trans-aortic mean gradient of 42 mmHg, aortic valvular area of 0.8 cm2 and moderate aortic regurgitation. At CT scan analysis, a dismorphic quadricuspid aortic valve (QAV) was detected. This is a rare congenital heart disease generally unrelated to other cardiac abnormalities and usually diagnosed incidentally. Due to QAV stenosis rarity, many considerations in Trans Aortic Valve Implantation (TAVI) in QAV are unclear. Some individuals with QAV develop aortic regurgitation and rarely other cardiovascular complications such as aortic aneurysm. Because of its infrequency, it is difficult to characterize these patients and standardize their management. Tailored therapy is more than ever necessary. Our patient also had bicameral pacemaker for grade II Mobitz 2 atrioventricular blockage. At coronarography angiography mild atheromasia was detected; AngioCT reconstructions in figure 1 panel A and B show the presence of QAV. Severe wall atheromasia along the entire course of the aorta was also detected. A few days later the patient underwent the TAVI procedure. A coronary guidewire was positioned in right coronary artery in order to protect its ostium that was slightly lower and, as known from literature, QAV has a longer leaflet height and a shallower cusp depth. After implantation of a Balloon Expandable Valve, a chimney stenting was also performed. An excellent final result was achieved with a safe deployment and a 90/10 final position (last aortography frame in Figure 2, where both coronary arteries are well visible). Post-procedural echo follow-up showed a well functioning aortic prosthesis (with mean gradient of 9 mmHg). The case presented is particularly interesting mainly for three reasons: Extreme rarity of this condition that can be challenging especially in the elderly people with calcific valve affected by stenosis and regurgitation;Paucity of procedural data in literature on QAV;It is a real life management example with subsequent successful implantation of the BEV and chimney stenting in QAV

Eosinophilic myocarditis is an inflammatory disease of the heart, even if rare, it could be a life-threatening condition, characterized by eosinophils infiltration of the myocardial tissue. First report of this type of endocarditis was reported by Löffler in 1935 and was described as an eosinophilic filling of endocardial cells with consequent myocardial fibrosis. Etiologically, viral infections are the prominent cause of myocarditis, especially the Coxsackie-B virus, drugs such as sumatriptan and canine Toxoplasma infections have been associated with eosinophilic myocarditis. Eosinophilia indeed (increase in eosinophils count in blood sample) has a similar etiology to eosinophilic myocarditis. However, as known from the literature, the relationship between myocardial damage and eosinophilia can have multiple etiologies, from hypersensitivity to autoimmune diseases but also malignancies. Clinically, its signs and symptoms present a wide spectrum of manifestations such as chest pain, dyspnea, rhythm disturbances, until sudden cardiac death. Diagnostic gold standard is endomyocardial biopsy, but cardiac magnetic resonance is a valid option in such scenarios following Lewis Lake criteria and suggestive laboratory results. We present the case of a 78-year-old lady, affected by arterial hypertension and dyslipidemia. Among her main comorbidities she complained late-onset asthma and hypothyroidism. The patient went to the emergency department of our hospital for onset of dyspnea associated with chest pain. An echocardiogram showed a dilated and diffusely hypokinetic left ventricle, severely reduced systolic function (EF 30%) and atrial fibrillation with high ventricular response. The patient presented with acute pulmonary edema and oliguria, for which non-invasive ventilation, diuretics therapy and inotropic therapy were needed. Invasive coronary angiography was negative, excluding any kind of coronary syndrome. HS-troponin peak detected was very high (73.170 ng/L). CMR was performed that showed images indicative of myocarditis (as shown in the picture A and B) with typical distribution of late gadolinium enhancement and reduced left ventricular function: The finding of hypereosinophilia was highly suspicious, so the endomyocardial biopsy performed confirmed the histotype of eosinophilic myocarditis. Hypereosinophilic myeloproliferative syndrome was ruled out after genetic testing. Therefore, a final diagnosis of eosinophilic granulomatosis with ANCA-negative polyangiotis with predominantly hematologic (peripheral hypereosinophilia), cardiac (multifocal myocarditis with inflammatory infiltrate with predominantly eosinophilic component), pulmonary (late-onset asthma) and peripheral neurologic (sciatic mononeuropathy) involvement was made. The patient underwent corticosteroid therapy, to which mepolizumab and cyclophosphamide were added. This case enlightens the rarity of this pathology, enhancing the appropriate indication of CMR in complex settings. We also remark the importance of close team collaboration with rheumatologists and CMR-expert radiologists for the resolution of the case and its proper therapeutic management.

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

Heart failure with improved ejection fraction (HFimpEF) represents a nosological entity that has recently been recognized and has little evidence from the literature. Available data indicate an increasing incidence of this patient group, consistent with the progressive improvement and implementation of medical therapy of heart failure with reduced ejection fraction (HFrEF). Furthermore, it is important to underline that the therapy itself should not be suspended after ejection fraction recovery, to avoid the recurrence of worse systolic dysfunction and patient outcomes. Only recently a randomized clinical study has been published, which enrolled also this patient subgroup, the DELIVER trial. Other data will soon become available, given the interest of the scientific community for this subgroup of patients, whose best management remains controversial. Since many studies suggest that the probability of myocardial recovery in HFrEF patients might be as high as 40%, depending on the case series taken into account, whereas the time to recovery might even be 12 months, the appropriate timing of device implantation, such as the defibrillator, in this setting deserves careful consideration.

In several clinical investigations performed in patients with type 2 diabetes mellitus and in diabetic and non-diabetic patients with heart failure or chronic kidney disease, sodium-glucose cotransporter 2 inhibitors (SGLT2i) proved their benefit on cardiac and renal adverse outcomes. Although there is clear evidence regarding the clinical benefits achieved, the pathophysiological mechanisms underlying their efficacy are still poorly understood. Some favorable mechanisms are likely related to the induced glycosuria and natriuresis. Both have been observed since the early stages of the molecule action and can drive beneficial hemodynamic changes, resulting in a decline of glomerular hyperfiltration and activation of the renin-angiotensin-aldosterone system. In addition to the improvement of cardiocirculatory regimen and renal performance, SGLT2i have an important role in cardio-renal protection by improving the metabolism of cardiomyocytes, carrying out anti-fibrotic and anti-inflammatory action and increasing the expression of cardio-protective adipokines. Further studies are needed to better understand the molecular mechanisms underlying the favorable effects of these drugs in diabetic and non-diabetic patients. The purpose of this review article is to analyze the molecular mechanisms underlying the cardiovascular benefits of SGLT2i in each of the main organs involved in the cardio-renal axis. Furthermore, the manuscript aims to analyze the extent of the beneficial effects of SGLT2i on heart failure in the different populations investigated in the most recent clinical studies.

Pharmacotherapy of chronic heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains challenging. We aimed to assess whether combined neuro-humoral modulation (NHM) (renin–angiotensin system inhibitors, betablockers, mineralocorticoid receptor antagonists) was differentially associated with outcome according to phenotype and age groups. Between 1999 and 2018 we recruited in a nationwide cardiology registry 4707 patients (HFmrEF n = 2298, HFpEF n = 2409) from three age groups: 40%, triple NHM treatment increased over time and was associated with better patient outcomes.

Telemedicine may be of benefit in patients with heart failure (HF), although virtual visits are often carried out on an ad hoc basis. Herein, we discuss a structured protocol that defines all the steps needed for virtual visits, LEAP Virtual Visit, which includes guides and support kits for clinicians and patients.A working group of clinicians was established to develop a protocol for virtual visits. The virtual model for monitoring HF patients was based on measurement and sizing of patient flows, type of services, and critical organizational points. The process of virtual visits was broken down to identify the specific activities, players, roles, and support tools needed for implementation in daily practice.In the protocol developed, sections were included on patient eligibility, exams, supportive tools, and practical organizational aspects. IT requirements were also considered and the most widely used teleconference platforms were compared according to features that were considered to be priority for virtual visits. Protocols and support kits were developed, including guides for clinicians and patients, two questionnaires to assess the level of satisfaction, patient diary, disease awareness brochure, and template to monitor key performance indicators. The phases include an enrolment phase, document sharing phase, pre-evaluation phase, the virtual visit itself, and the post-visit phase. The protocol for the virtual visit was divided into 8 sequential steps to be carried out between the clinic and patient/caregiver.The protocol described can be expected to have a number of benefits for the patient, clinic, and healthcare structure.

Atrial fibrillation (AF) is a major cause of cerebral ischemia, and its early detection may impact on health. Both invasive and non-invasive devices can be used for the diagnosis of AF. The aim of our study was to estimate the prevalence of AF using a single-lead ECG device (MyDiagnostickTM) on an adult, asymptomatic population during a screening campaign.A total of 2547 subjects underwent AF screening.The device detected an arrhythmia in 42 subjects (1.65%), and AF was confirmed on 12-lead ECG in 14 (0.55%) of them. The prevalence of confirmed AF increased in subjects over 65 years of age (1.21%) or with a CHA2DS2-VASc score ≥2 in males or ≥3 in females (1.33%). Furthermore, heart failure (odds ratio [OR] 8.62, 95% confidence interval [CI] 1.87-39.6, p=0.006) and diabetes (OR 4.55, 95% CI 1.25-16.5, p=0.021) significantly increased the risk of AF.During a screening campaign, the diagnosis of AF increases when subjects with a high thromboembolic risk are selected.

Background: Contemporary guidelines advocate for early invasive strategy with coronary angiography in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Still, the impact of an invasive strategy in older patients remains controversial and may be challenging in spoke hospitals with no catheterization laboratory (cath-lab) facility. Purpose: The purpose of this study was to analyse the characteristics and outcomes of patients ≥80 years old with NSTE-ACS admitted to spoke hospitals. Methods: Observational–retrospective study of all consecutive NSTE-ACS patients admitted to two spoke hospitals of our cardiology network, where a service strategy (same-day transfer between a spoke hospital and a hub centre with a cath-lab facility in order to perform coronary angiography) was available. Patients were followed up for 1 year after the admission date. Results: From 2013 to 2017, 639 patients were admitted for NSTE-ACS; of these, 181 (28%) were ≥80 years old (median 84, IQR 82–89) and represented the study cohort. When the invasive strategy was chosen (in 105 patients, or 58%), 98 patients (93%) were initially managed with a service strategy, whereas the remainder of the patients were transferred from the spoke hospital to the hub centre where they completed their hospital stay. Of the patients managed with the service strategy, a shift of strategy after the invasive procedure was necessary for 10 (10%). These patients remained in the hub centre, while the rest of the patients were sent back to the spoke hospitals, with no adverse events observed during the back transfer. The median time to access the cath-lab was 50 h (IQR 25–87), with 73 patients (70%) reaching the invasive procedure

Introduction Growing evidence highlight cancer and cardiovascular diseases (CVD) share common risk factors, including genetic ones, and underlying pathogenesis. Such paradigm has significant implications for cancer survivors, an exponential growing cohort of patients (Pts), due to notable improvements in survival achieved with new oncological treatments. However, many new agents of targeted– and immuno–therapy can cause cardiac damage, mainly for vascular involvement, a pathophysiological mechanism different from classic chemotherapeutic agents. We present the case of left ventricular systolic dysfunction (LVSD) in a man with metastatic papillary renal cell carcinoma (PRCC) previously exposed to anthracyclines for former peripheral T–cell lymphoma (PTCL). He came to our attention for cardiological assessment before starting immunotherapy (Nivolumab), due to the failure of Tyrosine kinase inhibitor (TKIs) (Pazopanib) treatment. Clinical case A 74–year–old Pt with hypertension, severe renal dysfunction, dyslipidemia, and exertional dyspnea (NYHA II) presented at transthoracic echocardiogram (TTE) a normal size chambers with mild concentric hypertrophy and a clinically stable moderate LVSD (LVEF 35–40%) at periodic evaluation. Pt was also performing his radiological follow–up for the estimation of metastases with CT, twice a year since 2016. A retrospective review of these non–contrast and non–ECG–gated CT highlighted an extensive increase in coronary artery calcifications during the last four years, started with the beginning of TKIs therapy. In 2018 only mild LAD calcification was detectable (Figure 1), while in 2022 a severe three–vessel coronary atherosclerosis was present (Figure 3). After multi–disciplinary discussion, an aggressive correction of multiple cardiovascular risk factors (starting Rosuvastatin and adjusting Bisoprolol) was performed and immunotherapy started without any adverse event. Conclusions Non–ECG–gated CT routinely performed for monitoring the state of the oncological disease is a useful tool for the evaluation of coronary artery calcific burden and accelerated atherosclerosis. It provides additional information beyond the traditional evaluation of CV risk and must be integrated with clinical and laboratory data.

A 59–year–old man,obese,with history of hypertension, 3 years ago underwent mitral valve (MV) replacement with a mechanical prothesis(Sorin Bicarbon 31) and preservation of the native subvalvular apparatus for severe mitral regurgitation due to anterior leaflet flail. Pre–discharge transthoracic echocardiography (TTE) showed normal prothesis function (mean pressure gradient (PG) 3,2mmHg), no valvular leaks and a normal ejection fraction (EF). Lately, the patient was admitted twice to emergency department for signs of heart failure, solved with increasing dose of oral diuretics. In both cases a TTE showed a normal EF, a trans–prosthetic mean PG of 6,5mmHg and no valvular impairment/leaks. Since the suboptimal TTE acoustic windows, a transesophageal echocardiography (TEE) was recommended. TEE showed a normal motion of both MV discs and no pannus/thrombus or leaks with the use of a 2–beat acquisition protocol. However, with longer observation a pattern of non–cyclic intermittent valve dysfunction was noted: whereas some cardiac cycles showed normal discs’ motion, other cycles demonstrated an emi–disc opening delay or blockage during diastole with significant prolongation of transmitral pressure half–time and higher transvalvular gradient, suggestive of flow impairment. A cine fluoroscopy and a CT assessment were also performed, showing the visible intermittent pattern of valve dysfunction without radiological signs of thrombosis or pannus. At this point, the interference of the MV apparatus with the emidisc was considered the most probable mechanism of dysfunction. A Heart Team decision toward reintervention was taken since the risk of a sudden worsening of the mechanical valve function, with potentially lethal consequences, was considered high. The surgeon at visual inspection confirmed the interference of the subvalvular apparatus with the posterior emidisc motion. The chronic shear stress generated on the mitral remnant likely developed a progressive fibrotic response that determined the thickening of the tissue and the periodical entrapment of the disc. MV prothesis was replaced with resection of the subvalvular apparatus. At dismissal,TTE evaluation showed normal valvular function confirmed at 6 months follow–up. Intermittent prosthetic MV dysfunction is a rare but potentially serious complication of MV replacement with subvalvular apparatus preservation. TEE, cine–fluoroscopy and CT may be useful as complementary tools to detect this rare complication.

Cardiogenic shock remains the leading cause of death in patients with acute myocardial infarction (AMICS). The IntraAortic Balloon Pump (IABP) has been the device of first choice for these patients for years, but it has not shown a mortality benefit over optimal medical therapy. The Impella (AbioMed, Danvers, Massachusetts) is an alternative circulatory support system that produces cardiac output appropriate for the needs of the patient. A 59–year–old mailman suddenly lost consciousness during his work. Basic life support was administered, and ROSC was achieved after a single effective defibrillator discharge. When the ambulance arrived, the patient presented conscious but complained of oppressive chest pain, with soreness in his left arm and head. EKG showed an ST elevation in aVR and aVL and a right bandle branch block (Fig 1). Aspirin, Heparin, and opioids were administered. During the transport, hemodynamic parameters appeared to deteriorate towards cardiogenic shock. Coronary angiography showed a total occlusion of the left main. Cangrelor was started promptly. Hemodynamic conditions dictated the application of a mechanical circulatory support device (MCSD), so IABP was applied. Primary angioplasty was performed with restoration of TIMI 3 flow. A 3.50 x 23 mm everolimus–eluting stent was implanted with a good result. Norepinephrine was ineffective in achieving satisfactory hemodynamic status with systemic arterial pressure below 50 mmHg. After volemic restoration, neither IABP nor the vasopressor could interrupt the spiral of cardiogenic shock. A coaxial pump, i.e. the Impella CP, was applied via left arterial femoral access. Despite the precise placement of this device, the parameters suggested a poor suction capacity from the pump–inlet into the left ventricle (LV) to systemic circulation in aorta. Meanwhile, echocardiogram revealed an unknown and severe hypertrophic cardiomyopathy that did not allow a proper functioning of the Impella CP device (Fig. 2). When a temporary pacemaker was applied due to reperfusion bradycardia, there were a better LV diastolic filling and Impella functioning due to right pacing. The patient was transferred to the intensive care unit, Impella was removed after 3 days, he was extubated within two weeks, no brain damage was reported but he is still hospitalised after a concomitant urinary infection, with predictable low ejection fraction (around 30%). We‘ll see: luckily, slow improvement, it is still an improvement!

Introduction Patients (Pts) with lymphoma are at high risk of cardiovascular events for the cardiotoxic effects of therapies and direct involvement of the heart. Autopsy series, indeed, indicate that cardiac localization may be observed in 10 – 25% of DLBCL Pts. The presence of cardiac mass, in DLBCL poses further complexity to the management beyond myocardial chemotherapy–related cardiotoxicity for the possible unfavorable/unpredictable evolution of the lymphoma mass (arrhythmias, AV block, myocardial ischemia, pericardial effusion and cardiac tamponade). We report the case of pt. with diffuse DLBCL, and multiple cardiac locations discovered, incidentally, on total body PET performed for disease stratification. Clinical case A 72–year–old woman with worsening asthenia and advanced stage non–GCB DLBCL presented multiple cardiac radiotracer uptake at 18FDG PET. The basal echocardiogram evidenced a roundish pedunculated mass at the level of the outflow tract of the right ventricle (24 x 22 mm) with significant obstruction of the RVOT, an oval formation at right ventricular apex with possible myocardial infiltration and a further mass in the right atrial site. Mild (< 1 mm) circumferential pericardial effusion, finally, was appreciated. No other notable alterations . After multi–disciplinary discussion, the patient underwent R–COMP based induction regimen, thus substituting conventional doxorubicin (R–CHOP) with non–pegylated liposomal doxorubicin in order to reduce the risk of acute cardiotoxicity. The first cycle was administered as inpatient under close cardiac monitoring, that was subsequently carried on before each cycle. No embolic and/or mechanical complications occurred. The response to chemotherapy was excellent: after the first cycle a substantial reduction in size of the cardiac masses was observed and after 3 cycles a complete resolution of the same was observed. Interim response evaluation by 18FDG PET after cycle 3 upheld early ultrasound observations by displaying a complete disappearance of pathological uptake. Conclusions In the case of patients with advanced DLBCL, multi–imaging evaluation enable appropriate assessment of cardiac conditions, including possible cardiac location and nature of masses. The personalized multidisciplinary management allows a tailored management of complex cases that enables both the achievement of treatment goals and the avoidance of acute complications.

Immunotherapy in recent years has revolutionized the oncology practice. ICIs targeting T lymphocyte antigen–4 (CTLA–4) and programmed death–1/ligand–1 (PD–1/PD–L1) transformed treatment landscape of many different cancers. The answers occur in a substantial fraction of patients and are often durable. ICI‘s combined block (CB) (CTLA–4 + PD–1/PD–L1) seems to improve even further clinical outcomes compared to monotherapies. However, this treatment exposes patients to the risk of immune adverse events (iAE) including cardiovascular (CV) iAE, which can be potentially fatal and, in any case, compromise the continuation of oncological treatment. Here we present the case of a young woman with advanced renal cancer (Stage IV, T3b, N0, M1) in ICI combined block therapy (Nivolumab + Ipilumab) complicated early by a pericardial effusion (PE) Clinical case Oct 2021: a 48 yrs old woman with sarcomatoid and rhabdoid renal cell cancer with liver metastases underwent left radical nephrectomy and splenectomy + cavotomy for neoplastic thrombus removal. Dec 21, she started ICIs CB (Nivolumab + Ipilumab) X 4 and sequential Nivolumab. March 2022: on CT assessment for disease restaging at the end of induction therapy with nivolumab + Ipilumab a favorable response of metastases was detected but incidental finding of G2–G3 PE was identified (figure 1). Therapy with prednisone (1 mg/kg/day) and Colchicine 0.5 mg/day was promptly started with progressive reduction of the effusion in the serial cardiological checks without recurrence although maintenance immunotherapy with Nivolumab was rechallenged. ICIs was permanently discontinued in June 2022 due to gastrointestinal G4 toxicity. At MRI evaluation after 6 months ICIs discontinuation (December 2022), liver metastases were further reduced compared to previous assessments. Conclusion This case confirms that the association between iAE side effects and efficacy of ICIs is a real possibility. Vigilant surveillance and close collaboration between oncologists and cardiologists facilitate timely capture of CV iAE and appropriate management to allow effective management.

Background Drug therapy of patients with chronic heart failure (HF) with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remains a challenge. We aimed to assess whether escalating neuro–humoral–modulation (NHM) (renin–angiotensin system inhibitors (RASI), betablockers (BB), mineralocorticoid receptor antagonists (MRA)) was differentially associated with outcome according to phenotype and age groups. Methods and Results Between 1999 and 2018 we recruited in a nationwide cardiology registry 4707 patients (HFmrEF n=2298, HFpEF n=2409) and classified them into 3 age groups: young ( Conclusions In a cardiology setting, among HF outpatient with EF>40%, prescription rates of triple NHM increased over time and were associated with better patient outcome.

Good quality echocardiographic images in the setting of critical care medicine may be difficult to obtain for many reasons. We present a case of an 85-year-old woman with acute pulmonary edema and pleural effusion, where transthoracic bedside echocardiographic examination raised a suspicion for significant aortic valve disease. However, given the orthopneic decubitus of the patients, the quality of images was poor. To increase the accuracy of diagnosis, a posterior thoracic view through the pleural effusion in the sitting position was used. This view allowed the diagnosis of mixed aortic valve disease (aortic stenosis and regurgitation) and the quantification of valve disease through multiparametric criteria as recommended by current guidelines. The posterior thoracic view, when feasible, may provide a useful option in the assessment of cardiac structures and further diagnostic information in technically difficult echocardiographic examinations.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, dapagliflozin, and empagliflozin, first developed as glucose-lowering agents for the treatment of Type 2 diabetes, have been demonstrated to improve prognosis in patients with heart failure and reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Since these drugs have only recently been included among the four pillars of HFrEF treatment, cardiologists are still unfamiliar with their use in this setting. This article provides an up-to-date practical guide for the initiation and monitoring of patients treated with SGLT2 inhibitors.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand antithrombotic therapy should reduce the risk related to recurrent ischemic events and/or stent thrombosis, on the other hand care should be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Calcium concentration must be finely tuned in all eukaryotic cells to ensure the correct performance of its signalling function. Neuronal activity is exquisitely dependent on the control of Ca

Background Cardiovascular disease and cancer have a high prevalence in Western countries, sharing many risk factors: obesity, diabetes, cigarette smoking, advanced age, diet and sedentary lifestyle. There is growing evidence that patients with ischemic heart disease (CAD) have a higher risk of developing cancer and, conversely, patients with a history of cancer are exposed to a higher incidence of CAD. In particular, cancer and its related therapies may promote the process of atherosclerosis, often with high calcific burden. Case Report This is a case of a 58 years old gentleman with a past smoking habit. Unfortunately from 2019 he was diagnosed by a stage IV lung adenocarcinoma, actually in 3rd line therapy: Carboplatin–Alimta, Atezolizumab and Paclitaxel weekly; no metastatic localizations was found at follow up CT scan. Last July, the patient complained of breath fatigue during exertion. At a complete cardiologic examination EKG was normal, and severe aortic stenosis was detected with concentric left ventricular hypertrophy, preserved ejection fraction. At CT scan, the aortic valve was confirmed as bicuspid Sievers type 0 (Figure 1, panel A). Vmax was 5.49 cm/s, max gradient was up to 120 mmHg, and medium gradient was 67 mmHg, as shown in Figure 1, panel B. Coronary angiography showed a very severe, focal, concentric calcific lesion of the left anterior descendant branch (Figure 2, Panel A). The patient was then referred to our local Heart Team and due to his oncological condition with prognosis >12 months, we decided to treat him percoutaneously. Aortic stenosis was treated Transcatheter Aortic Valve Implantation (TAVI) a few days later: predilatation, implant of a with a balloon–expandable valve Edwards Sapien 3 n°23 and post–dilatation, by femoral access (Figure 2, four steps of TAVI). Coronary lesion was uncrossable with the lowest profile balloons, so rotatripsy was perfomed: rotational atherectomy followed by 40 pulses of lithotripsy with Shockwave (Figure 2, Panel B and C). Everolimus eluting stent 3.00 x 23 mm was implanted and optimized (Figure 2, Panel D). Conclusion Recent devices and techniques in Invasive Cardiology allow percutaneous therapies for patients with time–dependent diseases, such as patients with advanced lung adenocarcinoma. Lately, oncological therapies for this type of lung cancer are very promising, allowing the combination of interventional procedures capable of further increasing the prognosis of these patients.

The study aimed to evaluate the healthcare direct costs for Italian National Health System of patients treated with lipid–lowering drugs that do not achieve the low–density lipoprotein (LDL)–cholesterol target compared to those reaching their targets, and to analyze costs according to the distance from LDL target by using real–world data. An observational analysis was performed on administrative and laboratory data from selected Italian Healthcare Departments. Patients were included if they presented at least one laboratory LDL test between 2012 and 2019 and if they were prescribed lipid–lowering drugs during 6 months prior the last LDL detection (index date). Mean annual direct costs were evaluated in the 12 months before index date in terms of all drugs prescribed, all–cause hospitalizations and all outpatient services. Distance to LDL target was calculated as difference between the index LDL level and LDL target. Total mean annual healthcare direct cost for patients that did not reach LDL target was higher compared to total cost of patients achieving LDL target (€3,678 vs €2,906). Costs were mainly driven by hospitalization (€1,330) followed by drugs expenditure (€1,012) and outpatient services (€563). Mean total annual healthcare costs increased with the distance from LDL target, specifically from €3,004 for patients with 10% distance from LDL target up to €4,823 for those 50% or more distance from LDL target. This trend was particularly evident for the cost item related to hospitalization, that went from €1,486 to €2,819 moving from 10% to ≥ 50 distance from LDL target. Results from this real–world study highlighted the higher economic burden for patients that do not reach the therapeutic LDL target, that tend to rise along with increasing distance from the LDL target. Overall, our findings could suggest that reducing the distance from LDL target could have a positive impact also on the economic outcomes for these patients.

The objective of the present real–world analysis was to evaluate the impact of adherence to lipid–lowering drugs in reaching the lipid target in settings of clinical practice in Italy. The analysis was based on administrative and laboratory database of selected Healthcare Units in Italy covering approximately 10% of Italian population. Adult patients prescribed with statin and with at least a low–density lipoprotein (LDL) determination were included between 2012 and 2019. The index date was defined as the first prescription for statin within the inclusion period. Patients fell into 4 clusters collectively exhaustive and mutually exclusive based on their characteristics assessed during the year prior index date. Patients were considered as adherent if they had a proportion of days covered (PDC)≥80%. Among overall patients prescribed statin and with a LDL determination, 1% was with familial hypercholesterolemia, 28% with previous cardiovascular events, 21% with diabetes and 50% in primary prevention. Regardless their risk profile, the increasing of adherence was related to a higher achievement of LDL–target, with an increment of + 53.2% among familial hypercholesterolemia, +43.1% in diabetes and +30% in previous cardiovascular events and primary prevention clusters while progressing from low (PDC The analysis showed adherence to be a key factor for cholesterol control. However, our findings underline a therapeutic need for patients that, although adherent, fail to achieve the lipid target, especially among patients with previous cardiovascular events (that have low level of LDL to achieve) and with familial hypercholesterolemia (that have high LDL basal level), suggesting therapeutic intensification should be applied.

Ca

The recognition of different microbe-associated molecular patterns in the rhizosphere triggers in the plant root the activation of either an immune response or an accommodation program. In both types of responses, Ca2+is a crucial intracellular messenger, mediating the early stages of the respective signalling pathways. In this work, we analysed the cytosolic and nuclear Ca2+changes activated by a set of chitin-related oligomers in different genetic backgrounds ofLotus japonicusroots by using specifically targeted aequorin-based Ca2+reporters. By means of pharmacological and genetic approaches, we dissected the Ca2+signal into two temporally distinct components: a rapid initial transient, followed by a longer and milder elevation in Ca2+concentration. Taking advantage of a complementary analysis using a cameleon-based bioassay inMedicago truncatularoot organ cultures, we showed that the second phase can be interpreted as the Ca2+spiking that is widely described in response to the perception of symbiotic signals. By contrast, the rapid first phase, critically dependent on elicitor concentration, was found to correlate with the activation of plant immunity marker genes. Overall, our study provides novel clues to a better understanding of the subtle boundaries between symbiotic and immunity responses in root-fungus interactions.HighlightIntracellular calcium changes induced inLotus japonicusroots by fungal signals were dissected in two separate phases, relying on distinct genetic programs and differentially mediating plant symbiotic or immunity responses.

Aims Our aim was to describe the electrocardiographic features of critical COVID-19 patients. Methods and results We carried out a multicentric, cross-sectional, retrospective analysis of 431 consecutive COVID-19 patients hospitalized between 10 March and 14 April 2020 who died or were treated with invasive mechanical ventilation. This project is registered on ClinicalTrials.gov (identifier: NCT04367129). Standard ECG was recorded at hospital admission. ECG was abnormal in 93% of the patients. Atrial fibrillation/flutter was detected in 22% of the patients. ECG signs suggesting acute right ventricular pressure overload (RVPO) were detected in 30% of the patients. In particular, 43 (10%) patients had the S1Q3T3 pattern, 38 (9%) had incomplete right bundle branch block (RBBB), and 49 (11%) had complete RBBB. ECG signs of acute RVPO were not statistically different between patients with (n = 104) or without (n=327) invasive mechanical ventilation during ECG recording (36% vs. 28%, P = 0.10). Non-specific repolarization abnormalities and low QRS voltage in peripheral leads were present in 176 (41%) and 23 (5%), respectively. In four patients showing ST-segment elevation, acute myocardial infarction was confirmed with coronary angiography. No ST-T abnormalities suggestive of acute myocarditis were detected. In the subgroup of 110 patients where high-sensitivity troponin I was available, ECG features were not statistically different when stratified for above or below the 5 times upper reference limit value. Conclusions The ECG is abnormal in almost all critically ill COVID-19 patients and shows a large spectrum of abnormalities, with signs of acute RVPO in 30% of the patients. Rapid and simple identification of these cases with ECG at hospital admission can facilitate classification of the patients and provide pathophysiological insights.

Hormone therapy with anti-estrogenic purposes is a cornerstone in breast cancer therapy that expresses estrogen receptors, the most frequent immunohistotype among invasive breast cancer. Hormone therapy is administered for a long time and affects the cardio-metabolic profile with possible interactions with the woman's intrinsic cardiovascular risk and the cardiotoxic effects of other treatments (chemotherapy, radiotherapy, target therapy). In this review, we analyze the pathophysiological implications and cardiovascular effects of hormone therapy providing useful elements for the creation of a personalized management program based on the "stepwise approach" as recommended by the 2021 cardiovascular disease prevention guidelines of the European Society of Cardiology and on the possible use of new antidiabetic drugs potentially useful for the management of the metabolic syndrome.

Funding Acknowledgements Type of funding sources: None. Background The elderly with non-ST-elevation coronary syndromes (NSTE-ACS) represents an high risk group and may benefit from early invasive strategy, that may be difficult to achieve in spoke hospitals with no cath-lab facility. Although a strong predictor of mortality in NSTE-ACS, the role of echocardiographically determined left ventricular ejection fraction (EF) in this setting is poorly determined. Purpose we aimed to analyze characteristics and outcomes of patients ≥80 years with NSTE-ACS admitted to spoke hospitals according to EF. Methods Observational retrospective study of all consecutive NSTE-ACS patients admitted to a spoke hospital, where a same-day transfer between spoke hospital and hub center with a cath-lab facility to perform coronary angiography was available. Patients were divided in 3 groups according to EF: normal (EF≥55%), mild-moderate (EF 35-55%) and severe reduction (FE Results from 2013-2017, 181 patients ≥80 years (median 84, IQR 82-89) were admitted for NSTE-ACS in a spoke hospital of our provincial cardiology network. Of these, 66 patients (36%) had normal EF, 79 (44%) had mild-moderate and 36 (20%) had severely EF reduction. GRACE risk score was high (>140) in the whole cohort, increasing with the lowering of EF (165 ± 27 in normal EF, 179 ± 28 in mildly-moderate and 193 ± 31 in severe reduction; p 0.1). As expected, clinical signs of heart failure presented more frequently with worsening of EF (2% in normal EF, 8% in mildly-moderate and 56% in severe reduction; p Of note, the invasive strategy was chosen less often with worsening of EF (68% in normal EF, 58% in mildly-moderate and 39% in severe reduction (p = 0.1). When the invasive strategy was chosen, time from admission to cath lab consistently raised with worsening of EF (53 ± 35 hours in normal EF, 68 ± 46 in mildly-moderate and 104 ± 81 in severe reduction; p = 0.001), therefore the proportion of patients reaching the cath lab in However, at 1-year follow-up, the overall survival did not differ across the EF groups (p = 0.26). Figure. Conclusion in the elderly admitted with NSTE-ACS in a spoke hospital with no cath lab facility EF may be part of the "treatment-risk paradox": the worse is the EF, the less patients are sent for invasive strategy and when invasive strategy is chosen the more time they have to wait for cath lab. However, in this setting, the impact of classical classification of EF in normal, mildly-moderate and severe reduction on 1-year mortality may not be significant and should not impede the access to invasive strategy in a timely fashion. Abstract Table Abstract Figure

The prescription appropriateness of direct oral anticoagulants (DOACs [dabigatran, rivaroxaban, apixaban, and edoxaban]) is carefully regulated, taking into account the criteria established in phase III trials and listed in the summary of the product characteristics of the four DOACs. In clinical practice, prescriptions are not always in compliance with established indications. In particular, the use of doses lower than those recommended in drug data sheets is relatively frequent. Literature data show that the inappropriate prescription of DOAC doses causes drug underexposure and an up to three-fold increase in the risk of stroke/transient ischemic attack, systemic thromboembolism, and hospitalizations. Possible causes of the deviation between the dose that should be prescribed and that actually employed may include erroneous prescriptions, an overstated bleeding risk perception, and the presence of frail patients, who were not included in pivotal trials. For these reasons, we summarize DOAC indications and contraindications and suggest the appropriate use of DOACs in common clinical scenarios, in accordance with what international guidelines and national and international health regulatory agencies recommend.

Increasing evidence indicates that water activated by plasma discharge, termed as plasma-activated water (PAW), can promote plant growth and enhance plant defence responses. Nevertheless, the signalling pathways activated in plants in response to PAW are still largely unknown. In this work, we analysed the potential involvement of calcium as an intracellular messenger in the transduction of PAW by plants. To this aim, Arabidopsis thaliana (Arabidopsis) seedlings stably expressing the bioluminescent Ca2+ reporter aequorin in the cytosol were challenged with PAW generated by a plasma torch. Ca2+ measurement assays demonstrated the induction by PAW of rapid and sustained cytosolic Ca2+ elevations in Arabidopsis seedlings. The dynamics of the recorded Ca2+ signals were found to depend upon different parameters, such as the operational conditions of the torch, PAW storage, and dilution. The separate administration of nitrate, nitrite, and hydrogen peroxide at the same doses as those measured in the PAW did not trigger any detectable Ca2+ changes, suggesting that the unique mixture of different reactive chemical species contained in the PAW is responsible for the specific Ca2+ signatures. Unveiling the signalling mechanisms underlying plant perception of PAW may allow to finely tune its generation for applications in agriculture, with potential advantages in the perspective of a more sustainable agriculture.

Precise measurements of dynamic changes in free Ca

Background Current guidelines recommend an early invasive strategy in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, the role of an invasive strategy in elderly patients remains controversial and may be difficult to achieve in spoke hospitals with no cath-lab facility. Purpose We aimed to analyze characteristics and outcomes of patients ≥80 years with NSTE-ACS admitted to spoke hospitals. Methods Observational retrospective study of all consecutive NSTE-ACS patients admitted to two spoke hospitals, where a service strategy (same-day transfer between spoke hospital and hub center with a cath-lab facility to perform coronary angiography) was available. Results From 2013 to 2017, 639 patients were admitted for NSTE-ACS in a spoke hospital of our provincial cardiology network; of these, 181 (28%) were ≥80 years (median 84, IQR 82–89). In the elderly conservative strategy was chosen in 76 patients (42%). When the invasive strategy was chosen, 104 patients (93%) were managed with a Service strategy with no major adverse event observed during the back transfer from the invasive center to the referring spoke center, whereas the rest of the patients (8, 7%) were transferred from the spoke hospital to the hub center and completed their hospital stay without returning to the spoke center. Of patients initially managed with the service strategy, a shift of strategy after the invasive procedure was necessary for 11 (10%) and the patients remained in the hub center. The median time to access to cath-lab was 50 hours (IQR 25–87), with 73 patients (70%) reaching the invasive procedure Conservative strategy was associated with older age, known previous CAD, clinical presentation with symptoms of LV dysfunction, lower EF, renal failure, higher GRACE score, presence of PAD, and atrial fibrillation (all p At 1-year follow-up, the overall survival was significantly higher in patients treated with invasive strategy compared to patients managed conservatively (94%±2 vs. 54%±6, p Conclusion An invasive strategy may confer a survival benefits in the elderly with NSTE-ACS. When the invasive strategy is chosen, the same-day transfer between spoke hospital and hub center with the cath-lab facility (service strategy) is safe and granted the access to cath-lab in a timely fashion even in the elderly. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

AIMS Ageing and comorbidities are increasing frailty/complexity of heart failure (HF) patients globally. We assessed evolving trends over two decades according to patients' age and time of recruitment in a nationwide cardiology setting in Italy. METHODS AND RESULTS Chronic HF outpatients recruited between 1999 and 2018 (N = 14,823) were divided into 3 cohorts: 1999-2005 (N = 5404); 2006-2011 (N = 3971); 2012-2018 (N = 5448). We analyzed temporal changes in clinical characteristics, therapies, and outcome (1-year all-cause mortality/cardiovascular hospitalization), overall and by age group

The Ralstonia spp. genus is a group of non-fermentative, Gram-negative bacteria often resistant to many antibiotics, which are emerging as opportunistic pathogens frequently associated with infections in hospital settings. We present herein a case of combined R. pickettii and R. mannitolilytica persisting and relapsing bacteraemia, possibly caused by a septic arterial thrombosis secondary to the rupture of an internal carotid artery aneurysm. Microbiology studies showed that both Ralstonia isolates produced biofilm and carried class D oxacillinase genes. When confronted with infections caused by members of the Ralstonia genus, identification to the species level is crucial for correct clinical management, as the two species show different antibiotic susceptibility patterns.

Primary amines are activated by copper(I)-based Lewis acid promoters in an A3-coupling one-pot solventless reaction with aldehydes and phenylacetylene for the synthesis of secondary propargylamines. The reaction is promoted by a CuSO4/NaI system, a practical precursor of the in situ generated effective CuI/I2 system, that worked well, but only in a restricted number of examples. Substitution of I2 with CeCl3·7H2O in a one-pot two-step reaction provided good yields and a wider applicability, with the added value given by a safer procedure.

Non-thermal plasma technology is increasingly being applied in the plant biology field. Despite the variety of beneficial effects of plasma-activated water (PAW) on plants, information about the mechanisms of PAW sensing by plants is still limited. In this study, in order to link PAW perception to the positive downstream responses of plants, transgenic Arabidopsis thaliana seedlings expressing the Ca2+-sensitive photoprotein aequorin in the cytosol were challenged with water activated by low-power non-thermal plasma generated by a dielectric barrier discharge (DBD) source. PAW sensing by plants resulted in the occurrence of cytosolic Ca2+ signals, whose kinetic parameters were found to strictly depend on the operational conditions of the plasma device and thus on the corresponding mixture of chemical species contained in the PAW. In particular, we highlighted the effect on the intracellular Ca2+ signals of low doses of DBD-PAW chemicals and also presented the effects of consecutive plant treatments. The results were discussed in terms of the possibility of using PAW-triggered Ca2+ signatures as benchmarks to accurately modulate the chemical composition of PAW in order to induce environmental stress resilience in plants, thus paving the way for further applications in agriculture.

• Chitosan, a component of the cell wall of many fungi, has been widely used to mimic pathogen attack and has been shown to induce several defence responses. • Here we show that low concentrations (50 µg ml