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Aims: Uncertainty exists about defining true iron deficiency (ID) in heart failure (HF) patients. We assessed the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in HF outpatients., Methods and Results: Iron deficiency was defined according to guidelines (G-ID: ferritin <100 ng/ml or ferritin 100-299 ng/ml with transferrin saturation [TSAT] <20%). Alternative ID definitions based on TSAT (<20%), iron (≤13 μmol/L), and ferritin (<100 or < 300 ng/ml) were explored. Relationships with rest/exercise measures of cardiac function and congestion using ultrasound, effort intolerance and adverse outcome (HF hospitalizations or all-cause mortality) were assessed. Of 1502 patients (72% with left ventricular ejection fraction [LVEF] ≥50%), 471 (31%) had TSAT <20%, while 728 (48%) had G-ID. Patients with TSAT <20% or G-ID had greater left atrial volume but similar LVEF. Lower TSAT, iron and haemoglobin, but not ferritin, were associated with more signs of congestion by ultrasound. After correcting for multiple clinical variables, including haemoglobin, TSAT was directly associated with peak oxygen uptake (standardized coefficient 0.069, p = 0.041), while ferritin was not. There was no interaction with HF phenotype (HF with preserved vs. reduced LVEF). During a median follow-up of 18 months, TSAT <20% and iron ≤13 μmol/L were associated with worse outcomes in models adjusted for clinical variables, including LVEF and N-terminal pro-B-type natriuretic peptide (hazard ratio 2.48, 95% confidence interval 1.88-3.17 and 1.93, 1.48-2.52, respectively), while G-ID or ferritin <100 or <300 ng/ml were not., Conclusion: In HF outpatients, TSAT <20% is more consistently associated with congestion by ultrasound and poorer functional capacity than other ID definitions, irrespective of LVEF. TSAT <20% and iron ≤13 μmol/L, but not G-ID or ferritin-based ID, predict a worse prognosis in HF outpatients with preserved and reduced LVEF., (© 2024 European Society of Cardiology.)

The Irpinia Fault, also known as the Monte Marzano Fault System, located in the Southern Apennines (Italy), is one of the most seismically active structures in the Mediterranean. It is the source of the 1980, Ms 6.9, multi-segment rupture earthquake that caused significant damage and nearly 3,000 casualties. Paleoseismological surveys indicate that this structure has generated at least four Mw ~ 7 surface-rupturing earthquakes in the past 2 ka. This paper presents a comprehensive, high-resolution geophysical investigation focused on the southernmost fault segment of the Monte Marzano Fault System, i.e., the Pantano-Ripa Rossa Fault, outcropping within the Pantano di San Gregorio Magno intramontane basin. The project, named TEst Site IRpinia fAult (TESIRA), was supported by the University of Napoli Federico II to study the near-surface structure of this intra-basin fault splay that repeatedly ruptured co-seismically in the past thousands of years. Our imaging approach included 2D and 3D electrical and seismic surveys, gravimetry, 3D FullWaver electrical tomography, drone-borne GPR and magnetic surveys, and CO 2 soil flux assessment across the surface rupture. This multidisciplinary investigation improved our understanding of the basin shallow structure, providing an image of a rather complex subsurface fault and basin geometry. Seismic data suggest that fault activity at the Pantano segment of MMFS is characterized by a near-surface cumulative displacement greater than previous estimations, calling into question earlier assumptions about the timing of its activation. Despite some challenges with our drone-mounted survey equipment, the integrated dataset provides a comprehensive and reliable image of the subsurface structure. This work demonstrates the utility of developing an integrated approach at high-resolution geophysical imaging and interpretation of fault zones with weak morphological expressions., (© 2024. The Author(s).)

The seismic water gun is widely used and plays an important role in seabed imaging acquisition; however, acoustic impacts on marine organisms are currently poorly understood. The aim of this study was to analyse the biochemical responses on the peristomial membrane (PM) of the sea urchin, Arbacia lixula, when exposed to water gun shots in open water. The PM (located around the mouth) is involved in vital functions, such as nutrition and protection. Individuals of sea urchins (n = 7 for each time slot) were sampled before, at the end, and at intervals of 3 h and 24 h after acoustic emission (duration of 20 min). Significant increases in superoxide dismutase, peroxidase, esterase and alkaline were observed immediately after water gun shots, highlighting an increase in the oxidative and inflammatory state of the tissue. Our results showed that acoustic impacts could interfere with PM vital functions, compromising the health, survival and ultimately the conservation of the species. Understanding these effects is crucial to predicting consequences on sea urchin populations and marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In heart failure (HF), congestion is a key pathophysiologic hallmark and a major contributor to morbidity and mortality. However, the presence of congestion is often overlooked in both acute and chronic settings, particularly when it is not clinically evident, which can have important clinical consequences. Ultrasound (US) is a widely available, non-invasive, sensitive tool that might enable clinicians to detect and quantify the presence of (subclinical) congestion in different organs and tissues and guide therapeutic strategies. In particular, left ventricular filling pressures and pulmonary pressures can be estimated using transthoracic echocardiography; extravascular lung water accumulation can be evaluated by lung US; finally, systemic venous congestion can be assessed at the level of the inferior vena cava or internal jugular vein. The Doppler evaluation of renal, hepatic and portal venous flow can provide additional valuable information. This review aims to describe US techniques allowing multi-organ evaluation of congestion, underlining their role in detecting, monitoring, and treating volume overload more objectively., (© 2024. The Author(s).)

Cardiometabolic diseases (CMDs) are interrelated and multifactorial conditions, including arterial hypertension, type 2 diabetes, heart failure, coronary artery disease, and stroke. Due to the burden of cardiovascular morbidity and mortality associated with CMDs' increasing prevalence, there is a critical need for novel diagnostic and therapeutic strategies in their management. In clinical practice, innovative methods such as epicardial adipose tissue evaluation, ventricular-arterial coupling, and exercise tolerance studies could help to elucidate the multifaceted mechanisms associated with CMDs. Similarly, epigenetic changes involving noncoding RNAs, chromatin modulation, and cellular senescence could represent both novel biomarkers and targets for CMDs. Despite the promising data available, significant challenges remain in translating basic research findings into clinical practice, highlighting the need for further investigation into the complex pathophysiology underlying CMDs.

Background: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L -1 ·min -1 . A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown., Methods: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm 2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141)., Results: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P =0.036), indexed left atrial volume (OR per SD, 2.15; P =0.001), E/e' at rest (OR per SD, 1.61; P =0.012), mPAP/CO slope (OR per SD, 2.01; P =0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P =0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P =0.219). Peak Vo 2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area ( P <0.001). These results were confirmed in the validation cohort., Conclusions: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo 2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo 2 and mPAP/CO slope cumulatively improved risk stratification., Competing Interests: Disclosures None.

Aims: Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise., Methods and Results: We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO 2 ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO 2 in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden., Conclusion: Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF., (© 2023 European Society of Cardiology.)

Background : We evaluated the bio-humoral and non-invasive haemodynamic correlates of renal congestion evaluated by Doppler renal venous flow (RVF) across the heart failure (HF) spectrum, from asymptomatic subjects with cardiovascular risk factors (Stage A) and structural heart disease (Stage B) to patients with clinically overt HF (Stage C). Methods : Ultrasound evaluation, including echocardiography, lung ultrasound and RVF, along with blood and urine sampling, was performed in 304 patients. Results : Continuous RVF was observed in 230 patients (76%), while discontinuous RVF (dRVF) was observed in 74 (24%): 39 patients had pulsatile RVF, 18 had biphasic RVF and 17 had monophasic RVF. Stage C HF was significantly more common among patients with dRVF. Monophasic RVF was associated with worse renal function and a higher urinary albumin-to-creatinine ratio (uACR). After adjusting for hypertension, diabetes mellitus, the presence of Stage C HF and serum creatinine levels, worsening RVF patterns were associated with higher NT-proBNP levels, worse right ventricular-arterial coupling, larger inferior vena cava and higher echo-derived pulmonary artery wedge pressure. This trend was confirmed when only patients with HF Stage C were analysed after adjusting for the left ventricle ejection fraction (LVEF). Conclusion : Abnormal RVF is common across the HF spectrum. Worsening RVF patterns are independently associated with increased congestion, worse non-invasive haemodynamics and impaired RV-arterial coupling. RVF evaluation could refine prognostic stratification across the HF spectrum, irrespective of LVEF.

Exercise intolerance is a prominent feature of several cardiovascular conditions. However, the physical effort requires the intertwined adaptation of several factors, namely the cardiovascular system, the lungs, and peripheral muscles. Several abnormalities in each domain may be present in a given patient. Cardiopulmonary exercise testing (CPET) has been used to investigate metabolic and ventilatory alterations responsible for exercise intolerance but does not allow for direct evaluation of cardiovascular function. However, this can readily be obtained by concomitant exercise-stress echocardiography (ESE). The combined CPET-ESE approach allows for precise and thorough phenotyping of the pathophysiologic mechanisms underpinning exercise intolerance. Thus, it can be used to refine the diagnostic workup of patients with dyspnoea of unknown origin, as well as improve risk stratification and potentially guide the therapeutic approach in specific conditions, including left and right heart failure or valvular heart disease. However, given its hitherto sporadic use, both the conceptual and technical aspects of CPET-ESE are often poorly known by the clinician. Improving knowledge in this field could significantly aid in anticipating individual disease trajectories and tailoring treatment strategies accordingly. Therefore, we designed this review to revise the pathophysiologic correlates of exercise intolerance, the practical principles of the combined CPET-ESE examination, and its main applications according to current literature., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: We investigated the prevalence and clinical value of assessing multi-organ congestion by ultrasound in heart failure (HF) outpatients., Methods and Results: Ultrasound congestion was defined as inferior vena cava of ≥21 mm, highest tertile of lung B-lines, or discontinuous renal venous flow. Associations with clinical characteristics and prognosis were explored. We enrolled 310 HF patients [median age: 77 years, median NT-proBNP: 1037 ng/L, 51% with a left ventricular ejection fraction (LVEF) <50%], and 101 patients without HF. There were no clinical signs of congestion in 224 (72%) patients with HF, of whom 95 (42%) had at least one sign of congestion by ultrasound (P < 0.0001). HF patients with ≥2 ultrasound signs were older, and had greater neurohormonal activation, lower urinary sodium concentration, and larger left atria despite similar LVEF. During a median follow-up of 13 (interquartile range: 6-15) months, 77 patients (19%) died or were hospitalized for HF. HF patients without ultrasound evidence of congestion had a similar outcome to patients without HF [reference; hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.86-1.35], while those with ≥2 ultrasound signs had the worst outcome (HR 26.7, 95% CI 12.4-63.6), even after adjusting for multiple clinical variables and NT-proBNP. Adding multi-organ assessment of congestion by ultrasound to a clinical model, including NT-proBNP, provided a net reclassification improvement of 28% (P = 0.03)., Conclusion: Simultaneous assessment of pulmonary, venous, and kidney congestion by ultrasound is feasible, fast, and identifies a high prevalence of sub-clinical congestion associated with poor outcomes., Competing Interests: Conflict of interest: P.P. has received consultancy honoraria and/or sponsorship support from Boehringer Ingelheim, Pharmacosmos, Novartis, Vifor, AstraZeneca, and Caption Health and research support from Bristol Myers Squibb. L.G. has received consultancy honoraria from GE Healthcare, Philips Healthcare, Caption Health. Other authors have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Type 2 diabetes mellitus (T2DM) represents a major health issue worldwide, as patients with T2DM show an excess risk of death for cardiovascular causes, twice as high as the general population. Among the many complications of T2DM, heart failure (HF) deserves special consideration as one of the leading causes of morbidity and reduced life expectancy. T2DM has been associated with different phenotypes of HF, including HF with reduced and preserved ejection fraction. Cardiopulmonary exercise testing (CPET) can evaluate the metabolic and ventilatory alterations related to myocardial dysfunction and/or peripheral impairment, representing a unique tool for the clinician to study the whole HF spectrum. While CPET allows for a thorough evaluation of functional capacity, it cannot directly differentiate central and peripheral determinants of effort intolerance. Combining CPET with imaging techniques could provide even higher accuracy and further insights into the progression of the disease since signs of left ventricular systolic and diastolic dysfunction can be detected during exercise, even in asymptomatic diabetic individuals. This review aims to dissect the alterations in cardiopulmonary function characterising patients with T2DM and HF to improve patient risk stratification., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: We explored multiple cardiometabolic patterns, including inflammatory and congestive pathways, in patients with heart failure (HF)., Methods and Results: We enrolled 270 HF patients with reduced (<50%, HFrEF; n = 96) and preserved (≥50%, HFpEF; n = 174) ejection fraction. In HFpEF, glycated hemoglobin (Hb1Ac) seemed to be relevant in its relationship with inflammation as Hb1Ac positively correlated with high-sensitivity C-reactive protein (hs-CRP; Spearman's rank correlation coefficient ρ = 0.180, p < 0.05). In HFrEF, we found a correlation between Hb1Ac and norepinephrine (ρ = 0.207, p < 0.05). In HFpEF, we found a positive correlation between Hb1Ac and congestion expressed as pulmonary B lines (ρ = 0.187, p < 0.05); the inverse correlation, although not significant, was found in HFrEF between Hb1Ac and N-terminal pro-B-type natriuretic peptide (ρ = 0.079) and between Hb1Ac and B lines (ρ = -0.051). In HFrEF, we found a positive correlation between E/e' ratio and Hb1Ac (ρ = 0.203, p < 0.05) and a negative correlation between tricuspid annular systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (sPAP) (TAPSE/sPAP ratio) (ρ = -0.205, p < 0.05) and Hb1Ac. In HFpEF, we found a negative correlation between TAPSE/sPAP ratio and uric acid (ρ = -0.216, p < 0.05)., Conclusion: In HF patients, HFpEF and HFrEF phenotypes are characterized by different cardiometabolic indices related to distinct inflammatory and congestive pathways. Patients with HFpEF showed an important relationship between inflammatory and cardiometabolic parameters. Conversely, in HFrEF, there is a significant relationship between congestion and inflammation, while cardiometabolism appears not to influence inflammation, instead affecting sympathetic hyperactivation.

Arterial hypertension (AH) is a global burden and the leading risk factor for mortality worldwide. Haemodynamic abnormalities, longstanding neurohormonal and inflammatory activation, which are commonly observed in patients with AH, promote cardiac structural remodeling ultimately leading to heart failure (HF) if blood pressure values remain uncontrolled. While several epidemiological studies have confirmed the strong link between AH and HF, the pathophysiological processes underlying this transition remain largely unclear. The combined cardiopulmonary-echocardiography stress test (CPET-ESE) represents a precious non-invasive aid to detect alterations in patients at the earliest stages of HF. The opportunity to study the response of the cardiovascular system to exercise, and to differentiate central from peripheral cardiovascular maladaptations, makes the CPET-ESE an ideal technique to gain insights into the mechanisms involved in the transition from AH to HF, by recognizing alterations that might be silent at rest but influence the response to exercise. Identifications of these subclinical alterations might allow for a better risk stratification in hypertensive patients, facilitating the recognition of those at higher risk of evolution towards established HF. This may also lead to the development of novel preventive strategies and help tailor medical treatment. The purpose of this review is to summarise the potential advantages of using CPET-ESE in the characterisation of hypertensive patients in the cardiovascular continuum., (© 2022. The Author(s).)

This paper describes an approach to detect and investigate the main characteristics of a solid waste landfill through the integration of geological, geographical and geophysical methods. In particular, a multi-temporal analysis of the landfill morphological evolution was carried out using aerial and satellite photos, since there were no geological and geophysical data referring to the study area. Subsequently, a surface geophysical prospection was performed through geoelectric and geomagnetic methods. In particular, the combination of electrical resistivity, induced polarization and magnetic measurements removed some of the uncertainties, generally associated with a separate utilization of these techniques. This approach was successfully tested to support the Prosecutor Office of Salerno (S Italy) during a specific investigation about an illegal landfill. All the collected field data supported the reconstruction of the site-specific history, while the real quarry geometry and site geology were defined. Key elements of novelty of this method are the combination and the integration of different methodological approaches, as the parallel and combined use of satellite, aerial and in-situ collected data, that were validated in a real investigation and that revealed the effectiveness of this strategy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

New high resolution seismic data (Subbottom Chirp) coupled to high resolution Multibeam bathymetry collected in the frame of the Stromboli geophysical experiment aimed at recording active seismic data and tomography of the Stromboli Island are here presented. The Stromboli geophysical experiment has been already carried out based on onshore and offshore data acquisition in order to investigate the deep structure and the location of the magma chambers of the Stromboli volcano. A new detailed swath bathymetry of Stromboli Island is here shown and discussed to reconstruct an up-to-date morpho-bathymetry and marine geology of the area compared to the volcanologic setting of the Aeolian Arc volcanic complex. Due to its high resolution the new Digital Terrain Model of the Stromboli Island gives interesting information about the submerged structure of the volcano, particularly about the volcano-tectonic and gravitational processes involving the submarine flanks of the edifice. Several seismic units have been identified based on the geologic interpretation of Subbottom Chirp profiles recorded around the volcanic edifice and interpreted as volcanic acoustic basement pertaining to the volcano and overlying slide chaotic bodies emplaced during its complex volcano-tectonic evolution. They are related to the eruptive activity of Stromboli, mainly poliphasic and to regional geological processes involving the intriguing geology of the Aeolian Arc, a volcanic area still in activity and needing improved research interest.