Hypoglycemic Drugs in Patients with Diabetes Mellitus and Heart Failure: A Narrative Review.

Over the last few years, given the increase in the incidence and prevalence of both type 2 diabetes mellitus (T2DM) and heart failure (HF), it became crucial to develop guidelines for the optimal preventive and treatment strategies for individuals facing these coexisting conditions. In patients aged over 65, HF hospitalization stands out as the predominant reason for hospital admissions, with their prognosis being associated with the presence or absence of T2DM. Historically, certain classes of glucose-lowering drugs, such as thiazolidinediones (rosiglitazone), raised concerns due to an observed increased risk of myocardial infarction (MI) and cardiovascular (CV)-related mortality. In response to these concerns, regulatory agencies started requiring CV outcome trials for all novel antidiabetic agents [i.e., dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is)] with the aim to assess the CV safety of these drugs beyond glycemic control. This narrative review aims to address the current knowledge about the impact of glucose-lowering agents used in T2DM on HF prevention, prognosis, and outcome.

Point-of-Care Serum Proenkephalin as an Early Predictor of Mortality in Patients Presenting to the Emergency Department with Septic Shock.

BACKGROUND: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. METHODS: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. RESULTS: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71-88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0-2.9) mg/dL, 3.6 (2.1-6.8) mmol/L, 13.1 (10.0-21.4) ng/mL, 2.06 (0.84-3.49) ng/mL, and 205 (129-425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7-84.6, p = 0.013). CONCLUSION: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock.

Differences in Health-Related Quality of Life among Patients with Heart Failure.

Heart failure (HF) is characterized by a progressive clinical course marked by frequent exacerbations and repeated hospitalizations, leading to considerably high morbidity and mortality rates. Patients with HF present with a constellation of bothersome symptoms, which range from physical to psychological and mental manifestations. With the transition to more advanced HF stages, symptoms become increasingly more debilitating, interfere with activities of daily living and disrupt multiple domains of life, including physical functioning, psychological status, emotional state, cognitive function, intimate relationships, lifestyle status, usual role activities, social contact and support. By inflicting profuse limitations in numerous aspects of life, HF exerts a profoundly negative impact on health-related quality of life (HRQOL). It is therefore not surprising that patients with HF display lower levels of HRQOL compared not only to the general healthy population but also to patients suffering from other chronic diseases. On top of this, poor HRQOL in patients with HF becomes an even greater concern considering that it has been associated with unfavorable long-term outcomes and poor prognosis. Nevertheless, HRQOL may differ significantly among patients with HF. Indeed, it has consistently been reported that women with HF display poorer HRQOL compared to men, while younger patients with HF tend to exhibit lower levels of HRQOL than their older counterparts. Moreover, patients presenting with higher New York Heart Association (NYHA) functional class (III-IV) have significantly more impaired HRQOL than those in a better NYHA class (I-II). Furthermore, most studies report worse levels of HRQOL in patients suffering from HF with preserved ejection fraction (HFpEF) compared to patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF). Last, but not least, differences in HRQOL have been noted depending on geographic location, with lower HRQOL levels having been recorded in Africa and Eastern Europe and higher in Western Europe in a recent large global study. Based on the observed disparities that have been invariably reported in the literature, this review article aims to provide insight into the underlying differences in HRQOL among patients with HF. Through an overview of currently existing evidence, fundamental differences in HRQOL among patients with HF are analyzed based on sex, age, NYHA functional class, ejection fraction and geographic location or ethnicity.

The Optimal Management of Patients with Atrial Fibrillation and Acute Heart Failure in the Emergency Department.

Atrial fibrillation (AF) and acute heart failure (AHF) are two closely interrelated conditions that frequently coexist in a manifold manner, with AF serving either as the causative factor or as the consequence or even as an innocent bystander. The interplay between these two clinical conditions is complex, given that they share common pathophysiological pathways and they can reciprocally exacerbate each other, thus triggering a vicious cycle that worsens the prognosis and increases the thromboembolic risk. The optimal management of AF in the context of AHF in the emergency department remains a challenge depending on the time onset, as well as the nature and the severity of the associated symptoms. Acute rate control, along with early rhythm control, when indicated, and anticoagulation represent the main pillars of the therapeutic intervention. The purpose of this review is to elucidate the pathophysiological link between AF and AHF and accordingly present a stepwise algorithmic approach for the management of AF in AHF patients in the emergency setting.

Optimal use of intravenous landiolol in acute cardiac care.

INTRODUCTION: B-blockers are regarded as beneficial pharmacologic agents in cardiac care, but their role in the acute setting remains ambiguous. Increasing evidence supports the important role of landiolol in critical care, a highly cardioselective intravenous b-blocker with rapid onset of action and short elimination time. Among its most valuable properties, which may aid to overcome special reservations related to b-blocker therapy in the acute setting, landiolol has a potent negative chronotropic effect while at the same time it exhibits a mild negative inotropic effect. AREAS COVERED: This expert opinion review aims to present basic pharmacologic aspects of landiolol and provide current clinical research focused on its efficacy and safety. EXPERT OPINION: Landiolol is a valuable and safe pharmacologic agent in acute cardiac care. Japanese and European guidelines have incorporated its use for the management of atrial tachyarrhythmia in patients with cardiac dysfunction. Although emerging clinical trials have experimented its use in patients with sustained ventricular tachycardia/fibrillation, acute myocardial infarction undergoing primary percutaneous intervention and in patients with septic cardiomyopathy, more studies are needed in order to establish its value in such cardiac conditions.

Systolic blood pressure ≤110 mm Hg is associated with severe coronary microvascular ischemia and higher risk for ventricular arrhythmias in hypertrophic cardiomyopathy.

Background: Coronary microvascular dysfunction (CMD) and hypertension (HTN) occur frequently in hypertrophic cardiomyopathy (HCM), but whether blood pressure (BP) influences CMD and outcomes is unknown. Objective: The purpose of this study was to test the hypothesis that HTN is associated with worse CMD and outcomes. Methods: This retrospective study included 690 HCM patients. All patients underwent cardiac magnetic resonance imaging, echocardiography, and rhythm monitoring; 127 patients also underwent rest/vasodilator stress 13NH3 positron emission tomography myocardial perfusion imaging. Patients were divided into 3 groups based on their rest systolic blood pressure (SBP) (group 1 ≤110 mm Hg; group 2 111-140; group 3 >140 mm Hg) and were followed for development of ventricular tachycardia (VT)/ventricular fibrillation (VF), heart failure (HF), death, and composite outcome. Results: Group 1 patients had the lowest age and left ventricular (LV) mass but the highest prevalence of nonobstructive hemodynamics and restrictive diastolic filling. LV scar was similar in the 3 groups. Group 1 had the lowest rest and stress myocardial blood flow (MBF) and highest SDS (summed difference score). Rest SBP was positively correlated with stress MBF and negatively correlated with SDS. Group 1 had the highest incidence of VT/VF, whereas the incidences of HF, death, and composite outcome were similar among the 3 groups. In multivariate analysis, rest SBP ≤110 mm Hg was independently associated with VT/VF (hazard ratio 2.6; 95% confidence interval 1.0-6.7; P = .04). Conclusion: SBP ≤110 mm Hg is associated with greater severity of CMD and coronary microvascular ischemia and higher incidence of ventricular arrhythmias in HCM.

The current and future status of inotropes in heart failure management.

INTRODUCTION: Heart failure (HF) is a complex syndrome with a wide range of presentations and acuity, ranging from outpatient care to inpatient management due to acute decompensated HF, cardiogenic shock or advanced HF. Frequently, the etiology of a patient's decompensation is diminished cardiac output and peripheral hypoperfusion. Consequently, there is a need for use of inotropes, agents that increase cardiac contractility, optimize hemodynamics and ensure adequate perfusion. AREAS COVERED: Inotropes are divided into 3 major classes: beta agonists, phosphodiesterase III inhibitors and calcium sensitizers. Additionally, as data from prospective studies accumulates, novel agents are emerging, including omecamtiv mecarbil and istaroxime. The aim of this review is to summarize current data on the optimal use of inotropes and to provide an expert opinion regarding their current and future use in the management of HF. EXPERT OPINION: The use of inotropes has long been linked to worsening mortality, tachyarrhythmias, increased myocardial oxygen consumption and ischemia. Therefore, individualized and evidence-based treatment plans for patients who require inotropic support are necessary. Also, better quality data on the use of existing inotropes is imperative, while the development of newer and safer agents will lead to more effective management of patients with HF in the future.

Point-of-Care Ultrasound: A Multimodal Tool for the Management of Sepsis in the Emergency Department.

Sepsis and septic shock are life-threatening emergencies associated with increased morbidity and mortality. Hence, early diagnosis and management of both conditions is of paramount importance. Point-of-care ultrasound (POCUS) is a cost-effective and safe imaging modality performed at the bedside, which has rapidly emerged as an excellent multimodal tool and has been gradually incorporated as an adjunct to physical examination in order to facilitate evaluation, diagnosis and management. In sepsis, POCUS can assist in the evaluation of undifferentiated sepsis, while, in cases of shock, it can contribute to the differential diagnosis of other types of shock, thus facilitating the decision-making process. Other potential benefits of POCUS include prompt identification and control of the source of infection, as well as close haemodynamic and treatment monitoring. The aim of this review is to determine and highlight the role of POCUS in the evaluation, diagnosis, treatment and monitoring of the septic patient. Future research should focus on developing and implementing a well-defined algorithmic approach for the POCUS-guided management of sepsis in the emergency department setting given its unequivocal utility as a multimodal tool for the overall evaluation and management of the septic patient.

Gut Failure: A Review of the Pathophysiology and Therapeutic Potentials in the Gut-Heart Axis.

Despite considerable advances in the field, heart failure (HF) still poses a significant disease burden among affected individuals since it continues to cause high morbidity and mortality rates. Inflammation is considered to play a key role in disease progression, but the exact underlying pathophysiological mechanisms involved have not yet been fully elucidated. The gut, as a potential source of inflammation, could feasibly explain the state of low-grade inflammation seen in patients with chronic HF. Several derangements in the composition of the microbiota population, coupled with an imbalance between favorable and harmful metabolites and followed by gut barrier disruption and eventually bacterial translocation, could contribute to cardiac dysfunction and aggravate HF. On the other hand, HF-associated congestion and hypoperfusion alters intestinal function, thereby creating a vicious cycle. Based on this evidence, novel pharmaceutical agents have been developed and their potential therapeutic use has been tested in both animal and human subjects. The ultimate goal in these efforts is to reverse the aforementioned intestinal derangements and block the inflammation cascade. This review summarizes the gut-related causative pathways implicated in HF pathophysiology, as well as the associated therapeutic interventions described in the literature.

Prevalence and prognostic implications of hypertensive response to exercise in patients with hypertrophic cardiomyopathy.

Objective: Hypertensive response to exercise (HRE) is observed in patients with hypertrophic cardiomyopathy (HCM) with normal resting blood pressure (BP). However, the prevalence or prognostic implications of HRE in HCM remain unclear. Methods: In this study, normotensive HCM subjects were enrolled. HRE was defined as systolic BP > 210 mmHg in men or >190 mmHg in women, or diastolic BP > 90 mmHg, or an increase in diastolic BP > 10 mmHg during treadmill exercise. All participants were followed for subsequent development of hypertension, atrial fibrillation (AF), heart failure (HF), sustained ventricular tachycardia/fibrillation (VT/VF), and all-cause death. Six hundred and eighty HCM patients were screened. Results: 347 patients had baseline hypertension, and 333 patients were baseline normotensive. 132 (40%) of the 333 patients had HRE. HRE was associated with female sex, lower body mass index and milder left ventricular outflow tract obstruction. Exercise duration and metabolic equivalents were similar between patients with or without HRE, but the HRE group had higher peak heart rate (HR), better chronotropic response and more rapid HR recovery. Conversely, non-HRE patients were more likely to exhibit chronotropic incompetence and hypotensive response to exercise. After a mean follow-up of 3.4 years, patients with and without HRE had similar risks of progression to hypertension, AF, HF, sustained VT/VF or death. Conclusion: HRE is common in normotensive HCM patients during exercise. HRE did not carry higher risks of future hypertension or cardiovascular adverse outcomes. Conversely, the absence of HRE was associated with chronotropic incompetence and hypotensive response to exercise.

Infection as an under-recognized precipitant of acute heart failure: prognostic and therapeutic implications.

As the prevalence of heart failure (HF) continues to rise, prompt diagnosis and management of various medical conditions, which may lead to HF exacerbation and result in poor patient outcomes, are of paramount importance. Infection has been identified as a common, though under-recognized, precipitating factor of acute heart failure (AHF), which can cause rapid development or deterioration of HF signs and symptoms. Available evidence indicates that infection-related hospitalizations of patients with AHF are associated with higher mortality, protracted length of stay, and increased readmission rates. Understanding the intricate interaction of both clinical entities may provide further therapeutic strategies to prevent the occurrence of cardiac complications and improve prognosis of patients with AHF triggered by infection. The purpose of this review is to investigate the incidence of infection as a causative factor in AHF, explore its prognostic implications, elucidate the underlying pathophysiological mechanisms, and highlight the basic principles of the initial diagnostic and therapeutic interventions in the emergency department.

Point of Care Ultrasonography for the Septic Patient in the Emergency Department: A Literature Review.

The point-of-care ultrasound (POCUS) has been effectively used in intensive care units for the management of septic patients. Since it is a time- and cost-effective non-invasive imaging modality, its use in the emergency department (ED) has been advocated for by medical experts. This review summarizes the existing literature regarding the breadth of POCUS as a supplementary tool to the holistic approach of septic patients in the ED setting. A literature search was conducted via PubMed (MEDLINE), Cochrane Library, and Scopus databases, analyzing studies which examined the use of POCUS in the ED for non-traumatic, septic, and/or undifferentiated hypotensive patients, resulting in 26 studies. The first cluster of studies investigates the efficiency of POCUS protocols in the differential diagnosis and its reliability for distributive/septic shock and sepsis management. In the second cluster, POCUS use results in faster sepsis cause identification and improves therapeutic management. The third cluster confirms that POCUS aids in the accurate diagnosis and management, even in rare and complicated cases. The results of the present review support the well-documented utility of POCUS and highlight the importance of POCUS incorporation in the comprehensive management of the septic patient in the ED setting.

Clinical pharmacology of SGLT-2 inhibitors in heart failure.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a class of oral antiglycemic agents that have emerged as a new therapeutic strategy for heart failure (HF) with reduced ejection fraction (HFrEF) and, potentially, for HF with preserved ejection fraction (HFpEF). AREAS COVERED: Ongoing efforts to clarify the exact mechanisms of action of SGLT2 inhibitors (SGLT2i) reveal that glycosuria and osmotic diuresis, resulting from the blockade of renal receptors, is not the sole pathophysiological mechanism. Nevertheless, the underlying mechanisms, accounting for their cardiovascular beneficial effects which have been clearly demonstrated in clinical trials, remain unclear. The aim of this review is to summarize the primary outcomes of large-scale studies regarding the use of SGLT2i in HF and provide an overview of the potential pathways involved in the SGLT2i-mediated cardioprotection. EXPERT OPINION: SGLT2i exhibit favorable pleiotropic effects, which extend beyond their primary indication as pharmaceutical agents intended for glycemic control. Given their unique pathophysiological profile, these agents have revolutionized the management of HF, while in the near future, it is possible that evolving research in the field may unfold further perspectives on their potential use in the treatment of other chronic conditions.

Emergency department risk assessment and disposition of acute heart failure patients: existing evidence and ongoing challenges.

Heart failure (HF) is a global public health burden, characterized by frequent emergency department (ED) visits and hospitalizations. Identifying successful strategies to avoid admissions is crucial for the management of acutely decompensated HF, let alone resource utilization. The primary challenge for ED management of patients with acute heart failure (AHF) lies in the identification of those who can be safely discharged home instead of being admitted. This is an elaborate decision, based on limited objective evidence. Thus far, current biomarkers and risk stratification tools have had little impact on ED disposition decision-making. A reliable definition of a low-risk patient profile is warranted in order to accurately identify patients who could be appropriate for early discharge. A brief period of observation can facilitate risk stratification and allow for close monitoring, aggressive treatment, continuous assessment of response to initial therapy and patient education. Lung ultrasound may represent a valid bedside tool to monitor cardiogenic pulmonary oedema and determine the extent of achieved cardiac unloading after treatment in the observation unit setting. Safe discharge mandates multidisciplinary collaboration and thoughtful assessment of socioeconomic and behavioural factors, along with a clear post-discharge plan put forward and a close follow-up in an outpatient setting. Ongoing research to improve ED risk stratification and disposition of AHF patients may mitigate the tremendous public health challenge imposed by the HF epidemic.

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review.

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.

Cognitive Impairment in Acute Heart Failure: Narrative Review.

Cognitive impairment (CI) represents a common but often veiled comorbidity in patients with acute heart failure (AHF) that deserves more clinical attention. In the AHF setting, it manifests as varying degrees of deficits in one or more cognitive domains across a wide spectrum ranging from mild CI to severe global neurocognitive disorder. On the basis of the significant negative implications of CI on quality of life and its overwhelming association with poor outcomes, there is a compelling need for establishment of detailed consensus guidelines on cognitive screening methods to be systematically implemented in the population of patients with heart failure (HF). Since limited attention has been drawn exclusively on the field of CI in AHF thus far, the present narrative review aims to shed further light on the topic. The underlying pathophysiological mechanisms of CI in AHF remain poorly understood and seem to be multifactorial. Different pathophysiological pathways may come into play, depending on the clinical phenotype of AHF. There is some evidence that cognitive decline closely follows the perturbations incurred across the long-term disease trajectory of HF, both along the time course of stable chronic HF as well as during episodes of HF exacerbation. CI in AHF remains a rather under recognized scientific field that poses many challenges, since there are still many unresolved issues regarding cognitive changes in patients hospitalized with AHF that need to be thoroughly addressed.

Machine Learning Methods for Identifying Atrial Fibrillation Cases and Their Predictors in Patients With Hypertrophic Cardiomyopathy: The HCM-AF-Risk Model.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients have a high incidence of atrial fibrillation (AF) and increased stroke risk, even with low CHA2DS2-VASc (congestive heart failure, hypertension, age diabetes, previous stroke/transient ischemic attack) scores. Hence, there is a need to understand the pathophysiology of AF/stroke in HCM. In this retrospective study, we develop and apply a data-driven, machine learning-based method to identify AF cases, and clinical/imaging features associated with AF, using electronic health record data. METHODS: HCM patients with documented paroxysmal/persistent/permanent AF (n = 191) were considered AF cases, and the remaining patients in sinus rhythm (n = 640) were tagged as No-AF. We evaluated 93 clinical variables; the most informative variables useful for distinguishing AF from No-AF cases were selected based on the 2-sample t test and the information gain criterion. RESULTS: We identified 18 highly informative variables that are positively (n = 11) and negatively (n = 7) correlated with AF in HCM. Next, patient records were represented via these 18 variables. Data imbalance resulting from the relatively low number of AF cases was addressed via a combination of oversampling and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. Specifically, an ensemble of logistic regression and naïve Bayes classifiers, trained based on the 18 variables and corrected for data imbalance, proved most effective for separating AF from No-AF cases (sensitivity = 0.74, specificity = 0.70, C-index = 0.80). CONCLUSIONS: Our model (HCM-AF-Risk Model) is the first machine learning-based method for identification of AF cases in HCM. This model demonstrates good performance, addresses data imbalance, and suggests that AF is associated with a more severe cardiac HCM phenotype.

INTRODUCTION: Les patients atteints d'une cardiomyopathie hypertrophique (CMH) présentent une forte incidence de fibrillation auriculaire (FA) et un risque accru d'accident vasculaire cérébral (AVC), malgré des scores CHA2DS2-VASc (congestive heart failure, hypertension, age diabetes, previous stroke/transient ischemic attack, c'est-à-dire : insuffisance cardiaque congestive, hypertension, âge, diabète, AVC ou accident ischémique transitoire antérieur) faibles. Par conséquent, il est nécessaire de comprendre la physiopathologie de la FA et de l'AVC en présence d'une CMH. Dans la présente étude rétrospective, nous avons élaboré et appliqué une méthode d'apprentissage automatique dirigée sur les données pour déterminer les cas de FA, et les caractéristiques cliniques/d'imagerie associées à la FA, à l'aide des données des dossiers de santé électroniques. MÉTHODES: Nous avons considéré les patients atteints d'une CMH qui ont une FA paroxystique/persistante/permanente documentée (n = 191) comme des cas de FA, et avons étiqueté les autres patients en rythme sinusal (n = 640) comme des cas sans FA. Nous avons évalué 93 variables cliniques; nous avons sélectionné les variables les plus informatives qui sont utiles pour distinguer les cas de FA des cas sans FA en fonction du test t pour deux échantillons et du critère de gain d'information. RÉSULTATS: Nous avons relevé 18 variables hautement informatives qui ont une corrélation positive (n = 11) et une corrélation négative (n = 7) avec la FA en présence d'une CMH. Ensuite, nous avons représenté les dossiers des patients au moyen de ces 18 variables. Nous avons remédié au déséquilibre des données, qui résulte du nombre relativement faible de cas de FA, grâce à une combinaison de stratégies de suréchantillonnage et de sous-échantillonnage. Nous avons formé et testé de nombreux classificateurs selon cette approche d'échantillonnage, qui montre une classification efficace. Particulièrement, un ensemble de régression logistique et de classificateurs bayésiens naïfs formés en fonction des 18 variables et corrigés en fonction du déséquilibre des données s'est révélé le plus efficace pour séparer les cas de FA des cas sans FA (sensibilité = 0,74, spécificité = 0,70, indice C = 0,80). CONCLUSIONS: Notre modèle (modèle de risque de CMH-FA) est la première méthode d'apprentissage automatique qui sert à déterminer les cas de FA en présence de CMH. Ce modèle permet de démontrer une bonne performance, de remédier au déséquilibre des données, et de croire que la FA est associée à un phénotype grave de CMH.

Prediction of long-term survival in patients with transfusion-dependent hemoglobinopathies: Insights from cardiac imaging and ferritin.

AIMS: The current study evaluated the association of echocardiography, cardiac magnetic resonance (CMR), and ferritin data with 10-year survival in thalassemia patients. METHODS: Demographics, ferritin, echocardiography, and CMR parameters of stable consecutive thalassemia patients were prospectively collected. RESULTS: In total, 75 patients (mean age 37 ± 11 years, 45% male) with thalassemia were included and dichotomized based on their survival status after a median follow-up period of 10.3 [9.6-10.9] years. Older age (HR: 1.071, p = 0.001), ferritin ≥2000 ng/ml (HR: 4.682, p = 0.007) and ≥1700 ng/ml (HR: 7.817, p = 0.002), elevated LV end-diastolic pressure (HR: 1.019, p = 0.044), TR Vmax >2.8 m/s (HR: 6.845, p = 0.005), and CMR T2∗ ≤20 msec (HR: 3.602, p = 0.043) and ≤34 msec (HR: 5.854, p = 0.026) were associated with increased all-cause mortality (primary endpoint). A baseline model including age was created and became more predictive of worse survival by adding TR Vmax >2.8 m/s instead of elevated LV end-diastolic pressure (C index 0.767 vs. 0.760, respectively), ferritin ≥1700 ng/ml instead of ≥2000 ng/ml (C index 0.890 vs. 0.807, respectively), or CMR T2∗≤34 msec instead of ≤20 msec (C index 0.845 vs. 0.839, respectively). Parameters associated with the combined endpoint of cardiac mortality/cardiac hospitalization (secondary endpoint) after adjusting for age were ferritin ≥1700 ng/ml (HR 3.770, p = 0.014), ratio E/A wave >2 (HR 3.565, p = 0.04), TR Vmax >2.8 m/s (HR 4.541, p = 0.049), CMR T2∗ ≤20 ms (HR 9.462, p = 0.001), and CMR T2∗ ≤34 ms (HR 11.735, p = 0.002). The model including age and T2∗ ≤34 ms instead of T2∗ ≤20 ms was more predictive of the secondary endpoint (C-index 0.844 vs 0.838, respectively). CONCLUSIONS: In thalassemia patients, TR Vmax >2.8 m/s, ferritin ≥2000 ng/ml, and CMR T2∗ ≤20 ms were associated with worse long-term survival. In the current era of advanced chelation therapy, aiming for ferritin ≤1700 ng/ml and CMR T2∗ ≥34 ms may improve their prognosis.

Bloodstream Infection by Saccharomyces cerevisiae in Two COVID-19 Patients after Receiving Supplementation of Saccharomyces in the ICU.

Co-infections have an unknown impact on the morbidity and mortality of the new clinical syndrome called coronavirus disease 2019 (COVID-19). The syndrome is caused by the new pandemic coronavirus SARS-CoV-2 and it is probably connected with severe traces in the elements of the immune system. Apart from possible Aspergillus infections, particularly in patients with acute respiratory distress syndrome (ARDS), other fungal infections could occur, probably more easily, due to the immunological dysregulation and the critical condition of these patients. Probiotic preparations of Saccharomyces are broadly used for the prevention of antibiotic-associated complications, especially in the intensive care units (ICU). On the other hand, Saccharomyces organisms are reported as agents of invasive infection in immunocompromised or critically ill patients. We report two cases of bloodstream infection by Saccharomyces in two patients hospitalised in the ICU, due to severe COVID-19, after Saccharomyces supplementation.

Sex-specific cardiac phenotype and clinical outcomes in patients with hypertrophic cardiomyopathy.

BACKGROUND: It is unknown whether sex-specific differences in mortality observed in HCM are due to older age of women at presentation, or whether women have greater degree of LV myopathy than men. METHODS: We retrospectively compared clinical/imaging characteristics and outcomes between women and men in our overall cohort composed of 728 HCM patients, and in an age-matched subgroup comprised of 400 age-matched patients. We examined sex-specific differences in LV myopathy, and dissected the influence of age and sex on outcomes. LV myopathy was assessed by measuring LV mass, LVEF, global peak longitudinal systolic strain (LV-GLS), diastolic function (E/A, E/e'), late gadolinium enhancement (LV-LGE) and myocardial blood flow (MBF) at rest/stress. The primary endpoint was a composite outcome, comprising heart failure (HF), atrial fibrillation (AFib), ventricular tachycardia/fibrillation (VT/VF) and death; individual outcomes were defined as the secondary endpoint. RESULTS: Women in the overall cohort were older by 6 years. Women were more symptomatic and more likely to have obstructive HCM. Women had smaller LV cavity size, stroke volume and LV mass, higher indexed maximum wall thickness (IMWT), more hyperdynamic LVEF and higher/similar LV-GLS. Women had similar LV-LGE and E/A, but higher E/e' and rest/stress MBF. Female sex was independently associated with the composite outcome in the overall cohort, and with HF in the overall cohort and age-matched subgroup after adjusting for obstructive HCM, LA diameter, LV-GLS. CONCLUSIONS: Our results suggest that sex-specific differences in LV geometry, hyper-contractility and diastolic function, not greater degree of LV myopathy, contribute to a higher, age-independent risk of diastolic HF in women with HCM.