Cardiac computed tomography: from anatomy to function.

Ischaemic heart disease (IHD) is one of the world's leading causes of morbidity and mortality. Likewise, the diagnosis and risk stratification of patients with coronary artery disease (CAD) have always been based on the detection of the presence and extent of ischaemia by physical or pharmacological stress tests with or without the aid of imaging methods (e.g. exercise stress, test, stress echocardiography, single-photon emission computed tomography, or stress cardiac magnetic resonance). These methods show high performance to assess obstructive CAD, whilst they do not show accurate power to detect non-obstructive CAD. The introduction into clinical practice of coronary computed tomography angiography, the only non-invasive method capable of analyzing the coronary anatomy, allowed to add a crucial piece in the puzzle of the assessment of patients with suspected or chronic IHD. The current review evaluates the technical aspects and clinical experience of coronary computed tomography in the evaluation of atherosclerotic burden with a special focus about the new emerging application such as functional relevance of CAD with fractional flow reserve computed tomography (CT)-derived (FFRct), stress CT perfusion, and imaging inflammatory makers discussing the strength and weakness of each approach.

Cardiac magnetic resonance imaging of myocarditis and pericarditis following COVID-19 vaccination: a multicenter collection of 27 cases.

OBJECTIVES: To assess clinical and cardiac magnetic resonance (CMR) imaging features of patients with peri-myocarditis following Coronavirus Disease 2019 (COVID-19) vaccination. METHODS: We retrospectively collected a case series of 27 patients who underwent CMR in the clinical suspect of heart inflammation following COVID-19 vaccination, from 16 large tertiary centers. Our patient's cohort was relatively young (36.6 ± 16.8 years), predominately included males (n = 25/27) with few comorbidities and covered a catchment area of approximately 8 million vaccinated patients. RESULTS: CMR revealed typical mid-subepicardial non-ischemic late gadolinium enhancement (LGE) in 23 cases and matched positively with CMR T2 criteria of myocarditis. In 7 cases, typical hallmarks of acute pericarditis were present. Short-term follow-up (median = 20 days) from presentation was uneventful for 25/27 patients and unavailable in two cases. CONCLUSIONS: While establishing a causal relationship between peri-myocardial inflammation and vaccine administration can be challenging, our clinical experience suggests that CMR should be performed for diagnosis confirmation and to drive clinical decision-making and follow-up. KEY POINTS: • Acute onset of dyspnea, palpitations, or acute and persisting chest pain after COVID-19 vaccination should raise the suspicion of possible myocarditis or pericarditis, and patients should seek immediate medical attention and treatment to help recovery and avoid complications. • In case of elevated troponin levels and/or relevant ECG changes, cardiac magnetic resonance should be considered as the best non-invasive diagnostic option to confirm the diagnosis of myocarditis or pericarditis and to drive clinical decision-making and follow-up.

Clinical Management of Facemasks for Early Treatment of Class III Malocclusion: A Survey among SIDO Members.

To evaluate whether there are differences among orthodontists in the clinical management of facemask treatment for early treatment of Class III malocclusion, a survey consisting of 16 questions was conducted among members of the Italian Society of Orthodontics (SIDO). Sixty percent of the respondents were Specialists in Orthodontics (S) whereas 40% were General Dentists practicing Orthodontics (GD). Descriptive statistics were calculated to summarize the collected data. Differences in answers between S and GD were assessed with the Fisher's exact test for dichotomous variables, chi-square test for qualitative variables, and Mann-Whitney test for ordinal variables. A total of 151 clinicians participated in this survey. As for treatment timing, about 80% of the participants reported treating Class III patients with RPE and facemask between 5 and 8 years of age. Most of the participants requested the patients to wear the facemask in the afternoon and at night for a period of 9 or 12 months with recommended forces of 500 g per side. Comparisons between S and GD showed that S preferred the Petit facemask whereas GD favored the Delaire's type facemask (Fisher's Exact test, p = 0.0005). S and GD also differed significantly in their judgment of the most critical time of treatment, which for the majority of GD was the initial period but for the S was the final period (Chi-square test p = 0.0188). This survey showed that the facemask is not well received by the patients who, along with their parents, express concerns regarding its tolerability.

The Role of Multimodality Imaging (CT & MR) as a Guide to the Management of Chronic Coronary Syndromes.

Chronic coronary syndrome (CCS) is one of the leading cardiovascular causes of morbidity, mortality, and use of medical resources. After the introduction by international guidelines of the same level of recommendation to non-invasive imaging techniques in CCS evaluation, a large debate arose about the dilemma of choosing anatomical (with coronary computed tomography angiography (CCTA)) or functional imaging (with stress echocardiography (SE), cardiovascular magnetic resonance (CMR), or nuclear imaging techniques) as a first diagnostic evaluation. The determinant role of the atherosclerotic burden in defining cardiovascular risk and prognosis more than myocardial inducible ischemia has progressively increased the use of a first anatomical evaluation with CCTA in a wide range of pre-test probability in CCS patients. Functional testing holds importance, both because the role of revascularization in symptomatic patients with proven ischemia is well defined and because functional imaging, particularly with stress cardiac magnetic resonance (s-CMR), gives further prognostic information regarding LV function, detection of myocardial viability, and tissue characterization. Emerging techniques such as stress computed tomography perfusion (s-CTP) and fractional flow reserve derived from CT (FFRCT), combining anatomical and functional evaluation, appear capable of addressing the need for a single non-invasive examination, especially in patients with high risk or previous revascularization. Furthermore, CCTA in peri-procedural planning is promising to acquire greater importance in the non-invasive planning and guiding of complex coronary revascularization procedures, both by defining the correct strategy of interventional procedure and by improving patient selection. This review explores the different roles of non-invasive imaging techniques in managing CCS patients, also providing insights into preoperative planning for percutaneous or surgical myocardial revascularization.

PROGnostic RolE of strain measurements in stress cardiac MRI in predicting major adverse cardiac events.

OBJECTIVES: We aimed to investigate the role of feature-tracking (FT) strain in long-term risk stratification of patients with known or suspected coronary artery disease (CAD) who underwent stress cardiac MRI with dipyridamole; to determine if contrast-free stress cardiac MRI with strain measurements could provide comparable prognostic value to myocardial perfusion. MATERIALS AND METHODS: This retrospective study included consecutive patients with stable symptoms suggesting possible cardiac ischemia who underwent stress cardiac MRI with dipyridamole. The mean follow-up period was 5.8 years ±1.2 [SD]. FT cardiac MRI analysis was performed for each patient to obtain 2D global peak circumferential strain (GCS). The primary outcome measure was major adverse cardiac events (MACE), defined as nonfatal myocardial infarction and cardiac death. RESULTS: A total of 729 patients (mean age, 63 years ±10 [SD]; 616 males) were included. MACE occurred in 70 (9.6%) patients. The presence of late gadolinium enhancement (LGE) ([HR] 2.74, [95% CI: 1.53, 4.88]; P < .001) and stress GCS (HR, 1.06 [95% CI: 1.01, 1.12]; P = .016) were independently associated with MACE. A model based on contrast-free assessment of LVEF and stress GCS showed similar performance for predicting MACE than LVEF and perfusion (P = .056). CONCLUSIONS: In patients with known or suspected CAD undergoing stress cardiac MRI with dipyridamole, GCS and LGE presence were independent predictors of MACE. Contrast-free stress cardiac MRI with stress GCS measurement offered prognostic value akin to myocardial perfusion assessment. CLINICAL RELEVANCE STATEMENT: Stress global circumferential strain represented an additional method to predict major adverse cardiac events in patients undergoing stress cardiac MRI, even without the use of contrast agents. This would be of particular significance in patients with severe renal impairment.

STress computed tomogRaphy perfusion and stress cArdiac magnetic resonance for ThE manaGement of suspected or known coronarY artery disease: resources and outcomes impact.

BACKGROUND: The aim of this study is to describe resources and outcomes of coronary computed tomography angiography plus Stress CT perfusion (CCTA â€‹+ â€‹Stress-CTP) and stress cardiovascular magnetic resonance (Stress-CMR) in symptomatic patients with suspected or known CAD. METHODS: Six hundred and twenty-four consecutive symptomatic patients with intermediate to high-risk pretest likelihood for CAD or previous history of revascularization referred to our hospital for clinically indicated CCTA â€‹+ â€‹Stress-CTP or Stress-CMR were enrolled. Stress-CTP scans were performed in 223 patients while 401 patients performed Stress-CMR. Patient follow-up was performed at 1 year after index test performance. Endpoints were all cardiac events, as a combined endpoint of revascularization, non-fatal MI and death, and hard cardiac events, as combined endpoint of non-fatal MI and death. RESULTS: Twenty-nine percent of patients who underwent CCTA â€‹+ â€‹Stress-CTP received revascularization, 7% of subjects assessed with Stress-CMR were treated invasively, and a low number of non-fatal MI and death was observed with both strategies (hard events in 0.4% of patients that had CCTA â€‹+ â€‹Stress-CTP as index test, and in 3% of patients evaluated with Stress-CMR). According to the predefined endpoints, CCTA â€‹+ â€‹Stress-CTP group showed high rate of all cardiac events and low rate of hard cardiac events, respectively. The cumulative costs were 1970 â€‹± â€‹2506 Euro and 733 â€‹± â€‹1418 Euro for the CCTA â€‹+ â€‹Stress-CTP group and Stress-CMR group, respectively. CONCLUSIONS: The use of CCTA â€‹+ â€‹Stress-CTP strategy was associated with high referral to revascularization but with a favourable trend in terms of hard cardiac events and diagnostic yield in identifying individuals at lower risk of adverse events despite the presence of CAD.

DEep LearnIng-based QuaNtification of epicardial adipose tissue predicts MACE in patients undergoing stress CMR.

BACKGROUND AND AIMS: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. METHODS: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. RESULTS: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. CONCLUSIONS: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

Role of advanced CMR features in identifying a positive genotype of hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. Cardiac magnetic resonance (CMR) imaging has emerged as a powerful tool for the non-invasive assessment of HCM. CMR can accurately quantify the extent and distribution of hypertrophy, assess the presence and severity of myocardial fibrosis, and detect associated abnormalities. We will study basic and advanced features of CMR in 2 groups of HCM patients with negative and positive genotype, respectively. MATERIALS AND METHODS: The study population consisted in consecutive HCM patients referred to Centro Cardiologico Monzino who performed both CMR and genetic testing. Clinical CMR images were acquired at 1.5 T Discovery MR450 scanner (GE Healthcare, Milwaukee, Wisconsin)) using standardized protocols T1 mapping, T2 mapping and late gadolinium enhancement (LGE). Population was divided in 2 groups: group 1 with HCM patients with a negative genotype and group 2 with a positive genotype. RESULTS: The analytic population consisted of 110 patients: 75 in group 1 and 35 patients in group 2. At CMR evaluation, patients with a positive genotype had higher LV mass (136 vs. 116 g, p = 0.02), LV thickness (17.5 vs. 16.9 mm), right ventricle ejection fraction (63 % vs. 58 %, p = 0.002). Regarding the LGE patients with positive genotype have a higher absolute (33.8 vs 16.7 g, p = 0.0003) and relative LGE mass (31.6 % vs 14.6 %, p = 0.0007). On a segmental analysis all the septum (segments 2, 8, 9, and 14) had a significantly increased native T1 compared to others segments. ECV in the mid antero and infero-septum (segments 8 and 9) have lower values in positive genotype HCM. Interestingly the mean T2 was lower in positive genotype HCM as compared to negative genotype HCM (50,1 ms vs 52,4). CONCLUSIONS: Our paper identifies the mid septum (segments 8 and 9) as a key to diagnose a positive genotype HCM.

Clinically Relevant Properties of 3D Printable Materials for Intraoral Use in Orthodontics: A Critical Review of the Literature.

The review aimed at analyzing the evidence available on 3D printable materials and techniques used for the fabrication of orthodontic appliances, focusing on materials properties that are clinically relevant. MEDLINE/PubMed, Scopus, and Cochrane Library databases were searched. Starting from an initial retrieval of 669 citations, 47 articles were finally included in the qualitative review. Several articles presented proof-of-concept clinical cases describing the digital workflow to manufacture a variety of appliances. Clinical studies other than these case reports are not available. The fabrication of aligners is the most investigated application of 3D printing in orthodontics, and, among materials, Dental LT Clear Resin (Formlabs) has been tested in several studies, although Tera Harz TC-85 (Graphy) is currently the only material specifically marketed for direct printing of aligners. Tests of the mechanical properties of aligners materials lacked homogeneity in the protocols, while biocompatibility tests failed to assess the influence of intraoral conditions on eluents release. The aesthetic properties of 3D-printed appliances are largely unexplored. The evidence on 3D-printed metallic appliances is also limited. The scientific evidence on 3D printable orthodontic materials and techniques should be strengthened by defining international standards for laboratory testing and by starting the necessary clinical trials.

Circulating Small Extracellular Vesicles Reflect the Severity of Myocardial Damage in STEMI Patients.

Circulating small extracellular vesicles (sEVs) contribute to inflammation, coagulation and vascular injury, and have great potential as diagnostic markers of disease. The ability of sEVs to reflect myocardial damage assessed by Cardiac Magnetic Resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) is unknown. To fill this gap, plasma sEVs were isolated from 42 STEMI patients treated by primary percutaneous coronary intervention (pPCI) and evaluated by CMR between days 3 and 6. Nanoparticle tracking analysis showed that sEVs were greater in patients with anterior STEMI (p = 0.0001), with the culprit lesion located in LAD (p = 0.045), and in those who underwent late revascularization (p = 0.038). A smaller sEV size was observed in patients with a low myocardial salvage index (MSI, p = 0.014). Patients with microvascular obstruction (MVO) had smaller sEVs (p < 0.002) and lower expression of the platelet marker CD41-CD61 (p = 0.039). sEV size and CD41-CD61 expression were independent predictors of MVO/MSI (OR [95% CI]: 0.93 [0.87-0.98] and 0.04 [0-0.61], respectively). In conclusion, we provide evidence that the CD41-CD61 expression in sEVs reflects the CMR-assessed ischemic damage after STEMI. This finding paves the way for the development of a new strategy for the timely identification of high-risk patients and their treatment optimization.

Quantification of extracellular volume with cardiac computed tomography in patients with dilated cardiomyopathy.

BACKGROUND: Cardiac computed tomography (CCT) was recently validated to measure extracellular volume (ECV) in the setting of cardiac amyloidosis, showing good agreement with cardiovascular magnetic resonance (CMR). However, no evidence is available with a whole-heart single source, single energy CT scanner in the clinical context of newly diagnosed left ventricular dysfunction. Therefore, the aim of this study was to test the diagnostic accuracy of ECVCCT in patients with a recent diagnosis of dilated cardiomyopathy, having ECVCMR as the reference technique. METHODS: 39 consecutive patients with newly diagnosed dilated cardiomyopathy (LVEF <50%) scheduled for clinically indicated CMR were prospectively enrolled. Myocardial segment evaluability assessment with each technique, agreement between ECVCMR and ECVCCT, regression analysis, Bland-Altman analysis and interclass correlation coefficient (ICC) were performed. RESULTS: Mean age of enrolled patients was 62 â€‹± â€‹11 years, and mean LVEF at CMR was 35.4 â€‹± â€‹10.7%. Overall radiation exposure for ECV estimation was 2.1 â€‹± â€‹1.1 â€‹mSv. Out of 624 myocardial segments available for analysis, 624 (100%) segments were assessable by CCT while 608 (97.4%) were evaluable at CMR. ECVCCT demonstrated slightly lower values compared to ECVCMR (all segments, 31.8 â€‹± â€‹6.5% vs 33.9 â€‹± â€‹8.0%, p â€‹< â€‹0.001). At regression analysis, strong correlations were described (all segments, r â€‹= â€‹0.819, 95% CI: 0.791 to 0.844). On Bland-Altman analysis, bias between ECVCMR and ECVCCT for global analysis was 2.1 (95% CI: -6.8 to 11.1). ICC analysis showed both high intra-observer and inter-observer agreement for ECVCCT calculation (0.986, 95%CI: 0.983 to 0.988 and 0.966, 95%CI: 0.960 to 0.971, respectively). CONCLUSIONS: ECV estimation with a whole-heart single source, single energy CT scanner is feasible and accurate. Integration of ECV measurement in a comprehensive CCT evaluation of patients with newly diagnosed dilated cardiomyopathy can be performed with a small increase in overall radiation exposure.

Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE-ICM International Registry.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. OBJECTIVES: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. METHODS: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). CONCLUSIONS: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

Cross-Sectional Study on Lateral Skull Radiographs to Design a New Nasopharyngeal Swab for Simplified COVID-19 and Respiratory Infections Diagnostic Testing in Children.

Nasopharyngeal swab sample collection is the first-line testing method for diagnosing COVID-19 infection and other respiratory infections. Current information on how to properly perform nasopharyngeal swabbing in children is largely defective. This study aimed at collecting nostril to nasopharynx distance measurements on lateral skull radiographs of children and adolescents to design a nasopharyngeal swab meant to standardize and facilitate the sample collection procedure. A total of 323 cephalograms of 152 male and 171 female children aged 4-14 years taken for orthodontic reasons were selected. On each cephalogram, the shortest distance between the most anterosuperior point of the nostril contour and the nasopharynx outline was measured in mm parallel to the palatal plane. Descriptive statistics of the measurements were calculated for each age group. The lower limit of the 95% confidence intervals of the measurements was taken as a reference to design a swab shaft with marks that, at each age, delimitate a safety boundary for swab progression up to the posterior nasopharyngeal wall. The simplification of the procedure enabled by the newly designed nasopharyngeal swab is valuable to help healthcare providers perform specimen collection on children in a safe and effective way, perhaps under the less-than-ideal conditions possibly occurring in 'point-of-need' contexts.

Incidence and Clinical Relevance of COVID-19 in a Population of Young Competitive and Elite Football Players: A Retrospective Observational Study.

BACKGROUND: The COVID-19 pandemic dramatically changed lifestyle worldwide, including sport. A comprehensive evaluation of the prevalence of cardiac involvement in COVID-19 is essential to finalize a safe protocol for resuming elite sport. The aim of this study is to evaluate incidence of cardiac involvement and COVID-19 impact on athletic performance. MATERIALS AND METHODS: This retrospective observational study analysed the data collected from consecutive competitive athletes who performed medical-sports examinations at the J Medical Center from March 2020 to March 2021. All athletes periodically performed a molecular test using a nasopharyngeal swab to detect COVID-19 infection. Positive athletes performed laboratory (cardiac troponin T-cTnT) and instrumental (echocardiography, stress test, Holter ECG) investigations following recovery to identify any cardiac involvement. Cardiac magnetic resonance imaging (MRI) was performed in case of abnormal findings at first-level evaluation. RESULTS: Among 238 athletes (median age 20 years), 77 contracted COVID-19, mainly males (79%) with a median age of 16 years. Fifty-one athletes (66%) presented mild symptoms, and none required hospitalization. Evaluation for resuming sport was performed after a median of 30 days from the first positive test. Abnormal findings were obtained in 13 cases (5 athletes [6%] with elevated cTnT values; 13 athletes [17%] with arrhythmias on Holter ECG and/or during stress test; 2 athletes [3%] anomalies at echocardiography). Cardiac MRI discovered abnormalities in 9 cases, but none of these was clearly related to COVID-19 and none fulfilled acute myocarditis criteria. No negative impact on athletic performance was observed, and none of the athletes developed persistent COVID-related symptoms. CONCLUSIONS: Our registry confirms the predominantly self-limiting illness in young athlete population. The incidence of clear COVID-19-related structural myocardial injury was very low, but transient exertional ventricular arrhythmias or pericardial effusion was observed without significant impact on athletic performance. Implemented screening for return to activity is likely reasonable only in moderate-to-severe symptomatic athletes.

Identification of novel circulating microRNAs in advanced heart failure by next-generation sequencing.

AIMS: Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF-specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients. METHODS AND RESULTS: We performed a global miRNome analysis using next-generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real-time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty-two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR-210-3p, miR-22-5p, miR-22-3p, miR-21-3p, miR-339-3p, and miR-125a-5p) significantly correlated with HF biomarkers, among which N-terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR-125a-5p, miR-10b-5p, and miR-9-5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio-HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82). CONCLUSIONS: This discovery study has characterized, for the first time, the advanced chronic HF-specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations.

Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure-bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial.

BACKGROUND: Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance. METHODS: In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients' care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h. RESULTS: 80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function. CONCLUSION: Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion. DRAIN TRIAL: ClinicalTrials.gov number NCT03592836.

Correction to: Spot urinary sodium in acute decompensation of advanced heart failure and dilutional hyponatremia: insights from DRAIN trial.

The original version of this article unfortunately contained a mistake.

Spot urinary sodium in acute decompensation of advanced heart failure and dilutional hyponatremia: insights from DRAIN trial.

BACKGROUND: Diuretic resistance portends a poor prognosis in acute heart failure, especially in advanced stages. Early identification of a poor response to diuretics may help to improve treatment and outcomes. Spot natriuresis (UNa+) at 2 h from the start of intravenous furosemide has been proposed as an early indicator of diuretic response. Our paper aimed to determine the role of early natriuresis in patients hospitalized with advanced chronic heart failure (ACHF) and high risk of diuretic resistance. METHODS AND RESULTS: We performed a sub-analysis of the DRAIN trial, a randomized clinical trial on 80 patients with acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with low systolic blood pressure (≤ 110 mmHg) and dilutional hyponatremia (sodium ≤ 135 mMol/L) at admission. Patients were divided into two groups according to spot urinary sodium excretion (high: UNa+ > 50 or low: ≤ 50 mEq/L) at 2 h from furosemide administration. Twenty-eight patients (35%) showed a low natriuretic response. As compared to the other patients, this group showed lower daily urinary output (2275 ± 790 vs 3849 ± 2034 mL, p < 0.001), lower body weight reduction after 48 h (1.55 ± - 1.66 vs - 3.55 ± - 2.93 kg, p < 0.001), higher incidence of worsening renal function (32% vs 10%, p 0.02) and increasing rather than reducing NT-proBNP at 72 h (p 0.02). CONCLUSIONS: In patients with ACHF and dilutional hyponatremia, low natriuresis after furosemide is an early marker of poor diuretic response and correlates with higher NT-proBNP and higher incidence of worsening renal function at 72 h.

Rifaximin anti-inflammatory activity on bovine endometrium primary cell cultures: a preliminary study.

Rifaximin is an unabsorbed oral antibiotic showing anti-inflammatory properties in human pathologies like irritable bowel syndrome and inflammatory bowel disease. In veterinary medicine, rifaximin is primarily used in the treatment of dermatological diseases in all animal species, in therapy and prophylaxis of mastitis in cows and in the treatment of endometritis in cattle and horses. The aim of this preliminary study was to evaluate the anti-inflammatory properties of rifaximin on primary cell cultures from bovine endometrium in which inflammatory response was induced by Lipopolysaccaride (LPS) treatment. Epithelial and stromal cells were isolated from bovine endometrium and separately incubated for 24 h with 1 µg mL-1 LPS after rifaximin (10, 50 and 100 µmol L-1 ) or dexamethasone (10 µmol L-1 ) pre-treatment for 24 h. Supernatants were collected 24 h after LPS treatment and interleukin (IL)-6 and IL-8 accumulation was measured by ELISA. Rifaximin (10, 50 and 100 µmol L-1 ) dose dependently inhibited the LPS-induced increase in IL-6 and IL-8 in stromal cells, whereas in epithelial cells it was not possible to detect any accumulation of these interleukins. Rifaximin reduced IL-6 and IL-8 production, showing a potential anti-inflammatory effect that opens up to new possibilities for the use of this drug in uterine inflammatory diseases.