Ferric Carboxymaltose in Patients with Acute Decompensated Heart Failure and Iron Deficiency: A Real-Life Study.

Background: The correction of iron deficiency (ID) with ferric carboxymaltose (FCM) is a recommended intervention in heart failure (HF) with reduced ejection fraction. Our aim is to evaluate, in a real-life setting, the clinical significance of ID screening and FCM treatment in acute decompensated HF (ADHF). Methods: In a cohort of ADHF patients, the prevalence of ID and FCM administration were investigated. Among the 104 patients admitted for ADHF, in n = 90 (median age 84, 53.5% with preserved left ventricular ejection fraction-LVEF), a complete iron status evaluation was obtained. ID was detected in n = 73 (81.1%), 55 of whom were treated with in-hospital FCM. The target dose was reached in n = 13. Results: No significant differences were detected in terms of age, sex, comorbidities, or LVEF between the FCM-supplemented and -unsupplemented patients. During a median follow-up of 427 days (IQR 405-466) among the FCM-supplemented patients, only 14.5% received FCM after discharge; the mortality and rehospitalizations among FCM-supplemented and -unsupplemented patients were similar (p = ns). In a follow-up evaluation, ID was still present in 75.0% of the FCM-supplemented patients and in 69.2% of the unsupplemented patients (p = ns). Conclusions: In this real-life ADHF cohort, FCM was administered at lower-than-prescribed doses, thus having no impact on ID correction. The significance of our findings is that only achieving the target dose of FCM and pursuing outpatient treatment can correct ID and produce long-term clinical benefits.

Osteolytic vs. Osteoblastic Metastatic Lesion: Computational Modeling of the Mechanical Behavior in the Human Vertebra after Screws Fixation Procedure.

Metastatic lesions compromise the mechanical integrity of vertebrae, increasing the fracture risk. Screw fixation is usually performed to guarantee spinal stability and prevent dramatic fracture events. Accordingly, predicting the overall mechanical response in such conditions is critical to planning and optimizing surgical treatment. This work proposes an image-based finite element computational approach describing the mechanical behavior of a patient-specific instrumented metastatic vertebra by assessing the effect of lesion size, location, type, and shape on the fracture load and fracture patterns under physiological loading conditions. A specific constitutive model for metastasis is integrated to account for the effect of the diseased tissue on the bone material properties. Computational results demonstrate that size, location, and type of metastasis significantly affect the overall vertebral mechanical response and suggest a better way to account for these parameters in estimating the fracture risk. Combining multiple osteolytic lesions to account for the irregular shape of the overall metastatic tissue does not significantly affect the vertebra fracture load. In addition, the combination of loading mode and metastasis type is shown for the first time as a critical modeling parameter in determining fracture risk. The proposed computational approach moves toward defining a clinically integrated tool to improve the management of metastatic vertebrae and quantitatively evaluate fracture risk.

Multiscale and Multiphysics Modeling of Anisotropic Cardiac RFCA: Experimental-Based Model Calibration via Multi-Point Temperature Measurements.

Radiofrequency catheter ablation (RFCA) is the mainstream treatment for drug-refractory cardiac fibrillation. Multiple studies demonstrated that incorrect dosage of radiofrequency energy to the myocardium could lead to uncontrolled tissue damage or treatment failure, with the consequent need for unplanned reoperations. Monitoring tissue temperature during thermal therapy and predicting the extent of lesions may improve treatment efficacy. Cardiac computational modeling represents a viable tool for identifying optimal RFCA settings, though predictability issues still limit a widespread usage of such a technology in clinical scenarios. We aim to fill this gap by assessing the influence of the intrinsic myocardial microstructure on the thermo-electric behavior at the tissue level. By performing multi-point temperature measurements on ex-vivo swine cardiac tissue samples, the experimental characterization of myocardial thermal anisotropy allowed us to assemble a fine-tuned thermo-electric material model of the cardiac tissue. We implemented a multiphysics and multiscale computational framework, encompassing thermo-electric anisotropic conduction, phase-lagging for heat transfer, and a three-state dynamical system for cellular death and lesion estimation. Our analysis resulted in a remarkable agreement between ex-vivo measurements and numerical results. Accordingly, we identified myocardium anisotropy as the driving effect on the outcomes of hyperthermic treatments. Furthermore, we characterized the complex nonlinear couplings regulating tissue behavior during RFCA, discussing model calibration, limitations, and perspectives.

Cardiac injury and COVID-19 associated coagulopathy in patients with acute SARS-CoV-2 pneumonia: A rotational thromboelastometry study.

PURPOSE: Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition associated with coagulopathy which may result in severe thromboembolic complications. Cardiac injury is not uncommon in hospitalized COVID-19 patients and therefore we aimed to investigate whether it stems from an abnormal coagulative state. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study on consecutive patients hospitalized due to COVID-19. Traditional coagulation and whole blood rotational thromboelastometry tests were compared between patients with and without cardiac injury. Cardiac injury was defined by increased levels of high-sensitivity cardiac troponin I (hs-cTnI). RESULTS: The study population consisted of 104 patients (67% males, median age 65 years), of whom 40 (38%) developed cardiac injury. No clinical differences in the traditional coagulation parameters were observed between patients with and without cardiac injury. Thromboelastometry analysis revealed abnormal maximum clot firmness (MCF) levels in FIBTEM assay in 80 (77%) patients. No significant differences in MCF values (p â€‹= â€‹0.450) and percentage of abnormal MCF (p â€‹= â€‹0.290) were detected between patients with and without cardiac injury. Cardiac injury - not hypercoagulability - was associated with mortality (p â€‹= â€‹0.016). CONCLUSIONS: No differences in traditional coagulation and rotational thromboelastometry parameters were found among hospitalized COVID-19 patients with and without cardiac injury. Other mechanisms besides hypercoagulability may be a main culprit for cardiac injury in COVID-19 patients.

A Simulation Study of the Effects of His Bundle Pacing in Left Bundle Branch Block.

His bundle pacing (HBP) has emerged as a feasible alternative to right (RVP) and biventricular pacing (BVP) for Cardiac Resynchronization Therapy (CRT). This study sought to assess, in ex-vivo experimental models, the optimal setup for HBP in terms of electrode placement and pacing protocol to achieve superior electrical synchrony in the case of complete His-Purkinje block and left bundle branch block (LBBB). We developed a 3D model of His bundle and bundle branches, embedded in a patient-specific biventricular heart model reconstructed from CT images. A monodomain reaction-diffusion model was adopted to describe the propagation of cardiac action potential, and a custom procedure was developed to compute pseudo-ECGs. Experimental measurements of tip electrode potential waveforms have been performed on ex-vivo swine myocardium to determine the appropriate boundary condition for delivering the electrical stimulus in the numerical model. An extended parametric analysis, investigating the effect of the electrode orientation and helix length, pacing protocol, and atrioventricular delay, allowed us to determine the optimal setup for HBP therapy. Both selective (S-HBP) and non-selective (NS-HBP) His bundle pacing were tested, as the variable anatomical location of the His bundle can result in the activation of the surrounding myocardium. Our study indicates a perpendicular placement of the electrode as the most advantageous for restoring the physiological function of the His-Purkinje system. We found that higher-energy protocols can compensate for the effects of an angled placement though concurring to potential tip fibrosis. Promisingly, we also revealed that an increased electrode helix length can provide optimal resynchronization even with low-energy pacing protocols. Our results provide informative guidance for implant procedure and therapy optimization, which will hopefully have clinical implications further improving the procedural success rates and patients' quality of life, due to reduced incidence of lead revision and onset of complications.

Effect of pedicle screw angles on the fracture risk of the human vertebra: A patient-specific computational model.

The assessment of a human vertebra's stability after a screws fixation procedure and its fracture risk is still an open clinical problem. The accurate evaluation of fracture risk requires that all fracture mechanical determinants such as geometry, constitutive behavior, loading modes, and screws angulation are accounted for, which requires biomechanics-based analyses. As such, in the present work we investigate the effect of pedicle screws angulation on a patient-specific model of non osteoporotic lumbar vertebra, derived from clinical CT images. We propose a novel computational approach of fracture analysis and compare the effects of fixation stability in the lumbar spine. We considered a CT-based three-dimensional FE model of bilaterally instrumented L4 vertebra virtually implanting pedicle screws according to clinical guidelines. Nine screws trajectories were selected combining three craniocaudal and mediolateral angles, thus investigated through a parametric computational analysis. Bone was modeled as an elastic material with element-wise inhomogeneous properties fine-tuned on CT data. We implemented a custom algorithm to identify the thin cortical layer correctly from CT images ensuring reliable material properties in the computational model. Physiological motion (i.e., flexion, extension, axial rotation, lateral bending) was further accomplished by simultaneously loading the vertebra and the implant. We simulated local progressive damage of the bone by using a quasi-static force-driven incremental approach and considering a stress-based fracture criterion. Ductile-like and brittle-like fractures were found. Statistical analyses show significant differences comparing screws trajectories and averaging the results among six loading modes. In particular, we identified the caudomedial trajectory as the least critical case, thus safer from a clinical perspective. Instead, medial and craniolaterally oriented screws entailed higher peak and average stresses, though no statistical evidence classified such loads as the most critical scenarios. A quantitative validation procedure will be required in the future to translate our findings into clinical practice. Besides, to apply the results to the target osteoporotic population, new studies will be needed, including a specimen from an osteoporotic patient and the effect of osteoporosis on the constitutive model of bone.

Admission criteria for a cardiovascular short stay unit: a retrospective analysis on a pilot unit.

Rapid intensive observation (RIO) units have been created to guarantee high standards of care in a sustainable health-care system. Within short stay units (SSUs), which are a subgroup of RIOs, only rapidly manageable patients should be admitted. Physicians are unable to predict the length of stay (LOS) as objective criteria to make such a prediction are missing. A retrospective observational study was carried out to identify the objective criteria for admission within a cardiovascular care-oriented SSU. Over a period of 317 days, 340 patients (age 69.4 ± 14.7 years) were admitted to a pilot SSU within our internal medicine department. The most frequent diagnoses were chest pain (45.9%), syncope (12.9%), and supraventricular arrhythmias (11.2%). The median LOS was 4 days (quartile 1:3; quartile 3:7). Predictors of LOS ≤ 96 h were age < 80, hemoglobin > 115 g/L, estimated glomerular filtration rate > 45 mL/min/1.73 m2, Charlson Comorbidity Index < 3, Barthel Index > 40, diagnosis of chest pain, syncope, supraventricular arrhythmias, or acute heart failure. The HEART (history, ECG, age, risk factors, troponin) score was found to be excellent in risk stratification of patients admitted for chest pain. Blood tests and anamnestic variables can be used to predict the LOS and thus SSU admission. The HEART score may help in the classification of patients with chest pain admitted to an SSU.

Cardiac injury and mortality in patients with Coronavirus disease 2019 (COVID-19): insights from a mediation analysis.

BACKGROUNDS: Patients at greatest risk of severe clinical conditions from coronavirus disease 2019 (COVID-19) and death are elderly and comorbid patients. Increased levels of cardiac troponins identify patients with poor outcome. The present study aimed to describe the clinical characteristics and outcomes of a cohort of Italian inpatients, admitted to a medical COVID-19 Unit, and to investigate the relative role of cardiac injury on in-hospital mortality. METHODS AND RESULTS: We analyzed all consecutive patients with laboratory-confirmed COVID-19 referred to our dedicated medical Unit between February 26th and March 31st 2020. Patients' clinical data including comorbidities, laboratory values, and outcomes were collected. Predictors of in-hospital mortality were investigated. A mediation analysis was performed to identify the potential mediators in the relationship between cardiac injury and mortality. A total of 109 COVID-19 inpatients (female 36%, median age 71 years) were included. During in-hospital stay, 20 patients (18%) died and, compared with survivors, these patients were older, had more comorbidities defined by Charlson comorbidity index ≥ 3(65% vs 24%, p = 0.001), and higher levels of high-sensitivity cardiac troponin I (Hs-cTnI), both at first evaluation and peak levels. A dose-response curve between Hs-cTnI and in-hospital mortality risk up to 200 ng/L was detected. Hs-cTnI, chronic kidney disease, and chronic coronary artery disease mediated most of the risk of in-hospital death, with Hs-cTnI mediating 25% of such effect. Smaller effects were observed for age, lactic dehydrogenase, and D-dimer. CONCLUSIONS: In this cohort of elderly and comorbid COVID-19 patients, elevated Hs-cTnI levels were the most important and independent mediators of in-hospital mortality.

Lung Ultrasound Patterns and Clinical-Laboratory Correlates during COVID-19 Pneumonia: A Retrospective Study from North East Italy.

BACKGROUND AND AIM: Lung ultrasound (LUS) is a convenient imaging modality in the setting of coronavirus disease-19 (COVID-19) because it is easily available, can be performed bedside and repeated over time. We herein examined LUS patterns in relation to disease severity and disease stage among patients with COVID-19 pneumonia. METHODS: We performed a retrospective case series analysis of patients with confirmed SARS-CoV-2 infection who were admitted to the hospital because of pneumonia. We recorded history, clinical parameters and medications. LUS was performed and scored in a standardized fashion by experienced operators, with evaluation of up to 12 lung fields, reporting especially on B-lines and consolidations. RESULTS: We included 96 patients, 58.3% men, with a mean age of 65.9 years. Patients with a high-risk quick COVID-19 severity index (qCSI) were older and had worse outcomes, especially for the need for high-flow oxygen. B-lines and consolidations were located mainly in the lower posterior lung fields. LUS patterns for B-lines and consolidations were significantly worse in all lung fields among patients with high versus low qCSI. B-lines and consolidations were worse in the intermediate disease stage, from day 7 to 13 after onset of symptoms. While consolidations correlated more with inflammatory biomarkers, B-lines correlated more with end-organ damage, including extrapulmonary involvement. CONCLUSIONS: LUS patterns provide a comprehensive evaluation of patients with COVID-19 pneumonia that correlated with severity and dynamically reflect disease stage. LUS patterns may reflect different pathophysiological processes related to inflammation or tissue damage; consolidations may represent a more specific sign of localized disease, whereas B-lines seem to be also dependent upon generalized illness due to SARS-CoV-2 infection.