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Background: Reduced cardiac energy is a hallmark feature of heart failure and is common in cardiac amyloidosis (CA) and can be aggravated by the presence of iron deficiency. Methods: Retrospective analysis of a single tertiary care center CA registry. Prevalence of iron deficiency was determined based on two definitions: (1) Classic definition, ferritin < 100 µg/L irrespective of transferin saturation (TSAT) or ferritin between 100 and 300 µg/L with a TSAT < 20%, and (2) TSAT-based definition, TSAT < 20%. Results: Out of a total of 393 CA patients who had a full set of iron indices (44% light chain [AL]-CA, 50% transthyretin [ATTR]-CA, remainder other or unspecified CA subtype), 56% had iron deficiency according to the classic definition and 58% according to the TSAT definition, with similar prevalence in AL-CA vs ATTR-CA (p = .135). Per both definitions 58% had anemia. Only the TSAT-based definition was associated with worse functional status (p = .039) and worse cardiac function. CA patients with a TSAT < 20% illustrated features of more pronounced right ventricular (RV) failure including lower TAPSE on echocardiography, lower RV ejection fraction and RV stroke volume index on CMR, increased right-sided filling pressures, lower pulmonary artery pulsatility index, and higher RAP/PCWP ratio by right heart catheterization. Neither the classic nor the TSAT-based definition was associated with a higher risk of all-cause mortality after covariate adjustment. Conclusion: Iron deficiency is common in cardiac amyloidosis and, when identified with a TSAT < 20%, is associated with worse functional status and more pronounced RV disease, but not with a higher risk of all-cause mortality.

Background Sarcopenia and hypoalbuminemia have been identified as independent predictors of increased adverse outcomes, including mortality and readmissions, in hospitalized older adults with acute decompensated heart failure (ADHF). However, the impact of coexisting sarcopenia and hypoalbuminemia on morbidity and death in adults with ADHF has not yet been investigated. We aimed to investigate the combined effects of lower muscle mass (LMM) as a surrogate for sarcopenia and hypoalbuminemia on in‐hospital and postdischarge outcomes of patients hospitalized for ADHF. Methods and Results A total of 385 patients admitted for ADHF between 2017 and 2020 at a single institution were retrospectively identified. Demographic and clinical data were collected, including serum albumin levels at admission and discharge. Skeletal muscle indices were derived from semi‐automated segmentation software analysis on axial chest computed tomography at the twelfth vertebral level. Our analysis revealed that patients who had LMM with admission hypoalbuminemia experienced increased diagnoses of infection and delirium with longer hospital length of stay and more frequent discharge to a facility. Upon discharge, 27.9% of patients had higher muscle mass without discharge hypoalbuminemia (reference group), 9.7% had LMM without discharge hypoalbuminemia, 38.4% had higher muscle mass with discharge hypoalbuminemia, and 24.0% had LMM with discharge hypoalbuminemia; mortality rates were 37.6%, 51.4%, 48.9%, and 63.2%, respectively. 1‐ and 3‐year mortality risks were highest in those with LMM and discharge hypoalbuminemia; this relationship remained significant over a median 23.6 (3.1–33.8) months follow‐up time despite multivariable adjustments (hazard ratio, 2.03 [95% CI, 1.31–3.16]; P=0.002). Conclusions Hospitalization with ADHF, LMM, and hypoalbuminemia portend heightened mortality risk.

Myocarditis is most recognized in patients with moderate to severe, recent‐onset heart failure. However, less typical presentations including myocardial infarction with normal coronary arteries and arrhythmias are important manifestations but less commonly recognized to be caused by myocarditis. Most cases of myocarditis can be self‐limiting without specific treatment; however, appropriate identification of risk during the diagnostic process of myocarditis and once a diagnosis is established is of primordial importance to identify patients in need for more specific follow‐up and management. We propose a flexible, multitiered approach to the diagnostic process, allowing for capturing of the spectrum of myocarditis at an early time‐point, individualized use of diagnostic resources through disease severity phenotyping, and providing structured follow‐up care once myocarditis is confirmed. Such diagnostic processes allow for identification of specific etiologies with potential therapeutic consequences or allows for the comprehension of disease chronicity by understanding genetic contributions or elements of persistent immune dysregulation and degree of cardiac damage. The article highlights the evolving field of immunophenotyping in myocarditis, generating a potential for the development of targeted therapeutic approaches. Currently long‐term follow‐up should be titrated to the refined risk assessments of patients with a diagnosis of myocarditis and includes arrhythmia monitoring and imaging when the results will likely impact management. Genetic testing should be considered in selected cases, and histologic diagnosis may be considered in nonresponders even at later stages.

Abstract Aims Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step‐wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively. Methods and results The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT‐HF) study is an international, multicentre, non‐randomized, open‐label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N‐terminal pro‐B‐type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in‐hospital mortality, and length of hospitalization. Conclusions The ENACT‐HF study will investigate whether a step‐wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.

Over the past decade, the detrimental impact of iron deficiency in heart failure with reduced ejection fraction has become abundantly clear, showing a negative impact on functional status, quality of life, cardiac function and structure, exercise capacity and an increased risk of hospitalisation due to heart failure. Mechanistic studies have shown the impact of iron deficiency in altering mitochondrial function and negatively affecting the already altered cardiac energetics in heart failure with reduced ejection fraction. Such failing energetics form the basis of the alterations to cellular myocyte shortening, culminating in reduced systolic function and cardiac performance. The IRON-CRT trials show that ferric carboxymaltose is capable of improving cardiac structure and cardiac performance. This article discusses the effect of iron deficiency on cardiac function and structure and how it can be alleviated.

Abstract Aims Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF). In patients with cardiac resynchronization therapy (CRT), it is associated with a diminished reverse remodelling response and poor functional improvement. The latter is partially related to a loss in contractile force at higher heart rates (negative force–frequency relationship). Methods and results The effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy (IRON‐CRT) trial is a multicentre, prospective, randomized, double‐blind controlled trial in HFrEF patients who experienced incomplete reverse remodelling (defined as a left ventricular ejection fraction below

Background: Sacubitril/valsartan (SV) is a novel and effective therapy for heart failure with reduced ejection fraction (HFrEF). Despite several sex-specific particularities that may influence drug effects, there has been no prior study evaluating the safety of SV in women with HFrEF in the “real-world.” Methods: We performed a literature search to identify observational studies evaluating SV. We contacted all authors to obtain sex-specific data on major adverse outcomes. We compared all-cause and cardiovascular (CV) deaths, heart failure hospitalizations, hyperkalemia, and hypotension in men and women. Results: We identified five cohort studies enrolling 8,981 patients; 6,092 men (67.8%) and 2,889 women (32.2%). The mean age was 67 years in both sexes. The rates for all-cause mortality, CV mortality, heart failure hospitalizations, hypotension, and hyperkalemia were similar between women and men. Although the unadjusted aggregate rates of all-cause and CV mortalities were numerically higher in men than in women, these differences did not reach statistical differences. Conclusion: Our meta-analysis showed similar rates of major adverse events in men and women with HFrEF treated with SV. Larger observational studies with longer duration and a higher number of women are needed to confirm the long-term safety of SV in women in the clinical practice. Résumé: Contexte: Le sacubitril/valsartan (SV) est un médicament novateur et efficace contre l’insuffisance cardiaque à fraction d’éjection réduite (ICFER). Malgré le fait que plusieurs particularités sexospécifiques peuvent influencer les effets du médicament, aucune étude préalable n’a été menée pour évaluer l’innocuité du SV chez les femmes atteintes d’ICFER dans la ''vraie vie''. Méthodologie: Nous avons effectué une recherche de la littérature pour recenser les études observationnelles évaluant le SV Nous avons communiqué avec tous les auteurs pour obtenir des données sexospécifiques sur les principaux issus défavorables. Nous avons comparé les données sur les décès toutes causes confondues et les décès d’origine cardiovasculaire (CV), les hospitalisations pour cause d’insuffisance cardiaque, l’hyperkaliémie et l’hypotension tant chez les hommes que chez les femmes. Résultats: Nous avons recensé cinq études de cohortes auxquelles ont participé 8 981 patients, soit 6 092 hommes (67,8 %) et 2 889 femmes (32,2 %). L’âge moyen était de 67 ans chez les patients des deux sexes. Les taux de décès toutes causes confondues, de décès d’origine CV, d’hospitalisation pour cause d’insuffisance cardiaque, d’hypotension et d’hyperkaliémie chez les femmes étaient similaires à ceux notés chez les hommes. Les taux globaux non ajustés de décès toutes causes confondues et de décès d’origine CV étaient numériquement plus élevés chez les hommes que chez les femmes, mais il n’y avait pas de différence sur le plan statistique. Conclusion: Notre méta-analyse a mis en évidence des taux similaires d’événements indésirables majeurs chez les hommes et chez les femmes atteints d’ICFER traités par le SV. Des études observationnelles à plus grande échelle avec de plus longue durée et un nombre plus élevé de femmes devront être menées pour confirmer l’innocuité à long terme du SV en pratique clinique chez les femmes.

Aims To explore the effects of dapagliflozin on congestion through CardioMEMS (Abbott Inc., Atlanta, USA) and Cordella™ pulmonary artery Sensor (Endotronix Inc., Lisle, Il, USA) devices, which are implantable systems that provide real‐time remote monitoring of pulmonary artery pressure (PAP). Methods and results Single‐centre open label observational pilot trial, to investigate the short‐term effects of dapagliflozin in consecutive heart failure and reduced ejection fraction patients with elevated PAP between October and December 2019, previously implanted with CardioMEMS or Cordella™ Sensor. Changes in PAP were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mmHg/day) for 7 days before and after starting dapagliflozin relative to the first day of each period. Nine patients (72 ± 10 years, N‐terminal pro b‐type natriuretic peptide 1027 ± 510 pg/mL, estimated glomerular filtration rate 45 ± 15 mL/kg/m2, left ventricular ejection fraction 35 ± 10%), all on optimal guideline‐directed therapy was included. The mean PAP was reduced from 42 ± 9.16 to 38 ± 9.95 mmHg with dapagliflozin therapy (P

The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion.

Background Ultrafiltration is not commonly used because of higher incidence of worsening renal function without improved decongestion. We examined differential outcomes of high versus low fluid removal and preserved versus reduced ejection fraction (EF) in CARRESS‐HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Methods and Results Baseline characteristics in the ultrafiltration arm were compared according to 24‐hour ultrafiltration‐based fluid removal above versus below the median. Patients were stratified by EF (≤40% or >40%). We compared clinical parameters of clinical decongestion during the hospitalization based on initial (≤24 hours) response to ultrafiltration. Cox‐proportional hazards models were used to identify associations between fluid removal 40% group demonstrated larger increases of change in creatinine (P=0.023) and aldosterone (P=0.038) from baseline to 96 hours. Among patients with EF >40%, those with above median fluid removal (n=17) when compared with below median (n=17) had an increased rate of the combined end point (87.5% versus 47.1%, P=0.014). Conclusions In patients with acute heart failure, higher initial fluid removal with ultrafiltration had no association with worsening renal function. In patients with EF >40%, ultrafiltration was associated with worsening renal function irrespective of fluid removal rate and higher initial fluid removal was associated with higher rates of adverse clinical outcomes, highlighting variable responses to decongestive therapy.

The church of Scherpenheuvel was built from 1609 during the reign and with the support of Archdukes Albrecht and Isabella, who were personally closely involved in the adoration of the miraculous statue of the Virgin Mary. The church building forms the centre of the seven-cornered concentrically laid-out town square already designed for it, which at that time embodied the most modern views on ideal town planning. The dome-shaped church is built in an utterly modern Italian architectural language and its concept implies a complete break with the local tradition (Illustr. l, 2, 3). Until now the court architect of the Archduke and Archduchess, Wenceslas Cobergher, who had spent a long period in Rome, was considered to have provided the inspiration for the church building. Within the direct family context of the Archduke, however, we come across a building project of which the form language and meanings show strong similarity with Scherpenheuvel. On March 11, 1585 Carlo Emanuele I, duke of Savoie and Prince of Piemont, married his cousin, Catalina Michaela and younger sister of the Archduchess Infanta Isabella, in Zaragoza. When Catalina unexpectedly dies in 1597, the duke decides to bury her in the church of Mondovi, a Marian pilgrims' church designed on the basis of an oval-shaped central ground plan, which had been started a few years previously. It is likely that Albrecht was told about this project just before and during his honeymoon, when he stayed in the duchy of Savoie for some months. The occurrence of this architecture project within the family context of Archduke Albrecht makes it very likely that he had claimed a more prominent role for himself in the active design process of the church of Scherpenheuvel than was assumed until recently. Contemporary examples show that other monarchs also regarded this as an appropriate regal occupation and used these architectural designs to visualize their political aspirations.

A 16-year-old boy was admitted for anuria, ascites, and abdominal pain. The patient had undergone a laparoscopic appendectomy two days prior to admission. Initial laboratory analysis revealed a plasma creatinine level of 5,07 mg/dL and blood urea nitrogen level of 75 mg/dL. Computed tomography imaging revealed diffuse abdominal ascites with normal kidneys without signs of hydronephrosis. Laprascopic revision found a 3 mm bladder tear and yielded an aspirate of 1,8 litre abdominal fluid. The abdominal fluid exhibited a fluid : serum creatinine ratio exceeding 1, indicating uroperitoneum. This case underscores the importance of bladder ruptures causing uroperitoneum presenting with azotemia.