Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and risk stroke.

BACKGROUND: Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase. METHODS: We performed a retrospective analysis on a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of 2 tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF). RESULTS: After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia, advanced atrioventricular block, heart failure, and cardiogenic shock. In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p<0.001), without differences in stroke incidence (10.1% vs. 9.3%). CONCLUSIONS: As a conclusion, patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-year follow-up, they exhibit a high risk of AF recurrence and mortality, with no significant differences in stroke incidence.

The management of heart failure cardiogenic shock: an international RAND appropriateness panel.

BACKGROUND: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. METHODS: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1-3 as inappropriate, 4-6 as uncertain and as 7-9 appropriate). RESULTS: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. CONCLUSION: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Assessment of a medical student mentoring programme to improve attitudes related to grief and coping with death.

Objectives: To evaluate the impact of a mentoring programme for medical students doing a palliative care rotation, aimed at improving coping with death and attitudes towards the suffering produced by illness. Methods: A quasi-experimental study without a control group was carried out on second-year medical students. Five 1-h group sessions were conducted. Attitudes towards grief and coping with death were assessed before the mentoring programme began and afterwards, using the Brief Humanizar Scale and the Bugen's Coping with Death Scale, respectively. Results: In terms of the sense of grieving as measured by the Brief Humanizar Scale, the mean score for the 'Burden' factor was 7 points and for the 'Change' factor it was 28.6, indicating that suffering makes more sense as a lever for positive change than as a burden. Regarding Bugen's Coping with Death Scale, the mean score was 127.8 points before the mentoring programme and 139.2 afterwards. Hence, the score after the mentoring programme increased by 11.4 points, improving strategies to cope with death. Conclusion: Medical professionals must cope with death and end-of-life patients. In addition to scientific knowledge, students need to acquire competencies for better coping with the death of patients, with mentoring programmes helping to enhance this process of learning.

The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.

Aims: Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management. Methods and results: Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction. Conclusion: In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.

Early renal recovery after acute kidney injury in patients on venoarterial extracorporeal membrane oxygenation: A retrospective study.

PURPOSE: The impact of VA-ECMO on early renal recovery (within 7 days after ECMO onset) in patients with pre-ECMO acute kidney injury and cardiogenic shock is unknown. MATERIAL AND METHODS: This retrospective single-center study included adult patients with cardiogenic shock rescued by VA-ECMO and severe AKI occurring before ECMO implantation (pre-ECMO AKI). Patients with early renal recovery (defined as at least a 50% decrease in peak serum creatinine or weaning from renal replacement therapy) were compared to patients without early renal recovery. RESULTS: During 7 years, 145 patients with severe pre-ECMO AKI were included. Eighty-two patients had no early renal recovery whereas 63 had early renal recovery within 7 days after VA-ECMO onset. The median time to early renal recovery was 4 (3,6) days. Nephrotoxic antibiotics (HR = 0.35 [95% CI, 0.21-0.59], p < 0.001), median fluid balance during the first 7 days of VA-ECMO (HR = 0.77 [95% CI, 0.64-0.93], p = 0.008), pre-ECMO AKI stage 3 (HR = 0.36 [95% CI, 0.20-0.64], p < 0.001) and median vasoactive-inotropic score (HR = 0.99 [95% CI, 0.98,1.00], p = 0.035) were independently associated with no early renal recovery. CONCLUSIONS: Only 43% of patients with severe pre-ECMO AKI had early renal recovery after VA-ECMO initiation.

New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II.

Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones. CDA II is caused by biallelic mutations in the SEC23B gene. In this study, we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel. The newly reported variants in SEC23B include three missenses (p.Thr445Arg, p.Tyr579Cys, and p.Arg701His), one frameshift (p.Asp693GlyfsTer2), and two splicing variants (c.1512-2A>G, and the complex intronic variant c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT in the same allele). Computational analyses of the missense variants indicated a loss of key residue interactions within the beta sheet and the helical and gelsolin domains, respectively. Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation. Reduced SEC23B mRNA expression was only detected in two probands carrying nonsense and frameshift variants; the remaining patients showed either higher gene expression levels or no expression changes at all. The skipping of exons 13 and 14 in the newly reported complex variant c.1512-3delinsTT/c.1512-16_1512-7delACTCTGGAAT results in a shorter protein isoform, as assessed by RT-PCR followed by Sanger sequencing. In this work, we summarize a comprehensive spectrum of SEC23B variants, describe nine new CDA II cases accounting for six previously unreported variants, and discuss innovative therapeutic approaches for CDA II.

Evaluation of learning outcomes of humanities curricula in medical students. A meta-review of narrative and systematic reviews.

Objectives: To assess the expected learning outcomes of medical humanities subjects in medical studies curricula. To connect those expected learning outcomes with the types of knowledge to be acquired in medical education. Methods: Meta-review of systematic and narrative reviews. Cochrane Library, MEDLINE (Pubmed), Embase, CINAHL, and ERIC were searched. In addition, references from all the included studies were revised, and the ISI Web of Science and DARE were searched. Results: A total of 364 articles were identified, of which six were finally included in the review. Learning outcomes describe the acquisition of knowledge and skills to improve the relationship with patients, as well as the incorporation of tools to reduce burnout and promote professionalism. Programs that focus on teaching humanities promote diagnostic observation skills, the ability to cope with uncertainty in clinical practice, and the development of empathetic behaviors. Conclusion: The results of this review show heterogeneity in the teaching of medical humanities, both in terms of content and at the formal level. Humanities learning outcomes are part of the necessary knowledge for good clinical practice. Consequently, the epistemological approach provides a valid argument for including the humanities in medical curricula.

Spirituality in Critical Care: An Observational Study of the Perceptions of Professionals, Patients and Families, in Spain and Latin America.

This research aims to describe the perspectives of health care professionals, patients, and family members regarding spiritual care options in intensive care units (ICUs). Participants were recruited consecutively from January to August 2019, during which time data collection was conducted. A total of 1211 Spanish-language questionnaires were collected from 41 ICUs in Spain and Latin America. Approximately 655 participants worked as ICU professionals (74.5% of these participants were women, and 47.5% were nurses). Additionally, 340 questionnaires were sent to patients' families, and patients completed 216 questionnaires; 59.7% of these participants were men, and their mean age was 59.4 years. Most (69.7%) of the critical care professionals considered this type of care to be a part of their profession, 50.1% did not feel competent to provide this type of care, and 83.4% felt that training in this area was necessary. Most families (71.7%) and patients (60.2%) felt that spiritual suffering occurred during their stay in the ICU. The results of this study suggest a perceived deficit in spiritual care in ICUs.

Performance analysis of a STEMI network: prognostic impact of the type of first medical contact facility.

INTRODUCTION AND OBJECTIVES: Prognosis in ST-elevation myocardial infarction (STEMI) is determined by delay in primary percutaneous coronary intervention (PPCI). The impact of first medical contact (FMC) facility type on reperfusion delays and mortality remains controversial. METHODS: We performed a prospective registry of primary coronary intervention (PCI)-treated STEMI patients (2010-2020) in the Codi Infart STEMI network. We analyzed 1-year all-cause mortality depending on the FMC facility type: emergency medical service (EMS), community hospital (CH), PCI hospital (PCI-H), or primary care center (PCC). RESULTS: We included 18 332 patients (EMS 34.3%; CH 33.5%; PCI-H 12.3%; PCC 20.0%). Patients with Killip-Kimball classes III-IV were: EMS 8.43%, CH 5.54%, PCI-H 7.51%, PCC 3.76% (P <.001). All comorbidities and first medical assistance complications were more frequent in the EMS and PCI-H groups (P <.05) and were less frequent in the PCC group (P <.05 for most variables). The PCI-H group had the shortest FMC-to-PCI delay (median 82 minutes); the EMS group achieved the shortest total ischemic time (median 151 minutes); CH had the longest reperfusion delays (P <.001). In an adjusted logistic regression model, the PCI-H and CH groups were associated with higher 1-year mortality, OR, 1.22 (95%CI, 1.00-1.48; P=.048), and OR, 1.17 (95%CI 1.02-1.36; P=.030), respectively, while the PCC group was associated with lower 1-year mortality than the EMS group, OR, 0.71 (95%CI 0.58-0.86; P <.001). CONCLUSIONS: FMC with PCI-H and CH was associated with higher adjusted 1-year mortality than FMC with EMS. The PCC group had a much lower intrinsic risk and was associated with better outcomes despite longer revascularization delays.

Time course, factors related to, and prognostic impact of venoarterial extracorporeal membrane flow in cardiogenic shock.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the 'optimal' flow. We aimed to describe the evolution of VA-ECMO flows in a cardiogenic shock population and determine the risk factors of 'high-ECMO flow'. METHODS AND RESULTS: A 7 year database of patients supported with VA-ECMO was used. Based on the median flow during the first 48 h of the VA-ECMO run, patients were classified as 'high-flow' or 'low-flow', respectively, when median ECMO flow was ≥3.6 or <3.6 L/min. Outcomes included rates of ventilator-associated pneumonia, ECMO-related complications, days on ECMO, days on mechanical ventilation, intensive care unit and hospitalization lengths of stay, and in-hospital and 60 day mortality. Risk factors of high-ECMO flow were assessed using univariate and multivariate cox regression. The study population included 209 patients on VA-ECMO, median age was 51 (40-59) years, and 78% were males. The most frequent aetiology leading to cardiogenic shock was end-stage dilated cardiomyopathy (57%), followed by acute myocardial infarction (23%) and fulminant myocarditis (17%). Among the 209 patients, 105 (50%) were classified as 'high-flow'. This group had a higher rate of ischaemic aetiology (16% vs. 30%, P = 0.023) and was sicker at admission, in terms of worse Simplified Acute Physiology Score II score [40 (26-58) vs. 56 (42-74), P < 0.001], higher lactate [3.6 (2.2-5.8) mmol/L vs. 5.2 (3-9.7) mmol/L, P < 0.001], and higher aspartate aminotransferase [97 (41-375) U/L vs. 309 (85-939) U/L, P < 0.001], among others. The 'low-flow' group had less ventilator-associated pneumonia (40% vs. 59%, P = 0.007) and less days on mechanical ventilation [4 (1.5-7.5) vs. 6 (3-12) days, P = 0.009]. No differences were found in lengths of stay or survival according to the ECMO flow. The multivariate analysis showed that risk factors independently associated with 'high-flow' were mechanical ventilation at cannulation [odds ratio (OR) 3.9, 95% confidence interval (CI) 2.1-7.1] and pre-ECMO lactate (OR 1.1, 95% CI 1.0-1.2). CONCLUSIONS: In patients with refractory cardiogenic shock supported with VA-ECMO, sicker patients had higher support since early phases, presenting thereafter higher rates of ventilator-associated pneumonia but similar survival compared with patients with lower flows.

Mechanical complications in STEMI: prevalence and mortality trends in the primary PCI era. The Ruti-STEMI registry.

INTRODUCTION AND OBJECTIVES: Mechanical complications confer a dreadful prognosis in ST-elevation myocardial infarction (STEMI). Their prevalence and prognosis are not well-defined in the current era of primary percutaneous coronary intervention (pPCI) reperfusion networks. We aimed to analyze prevalence and mortality trends of post-STEMI mechanical complications over 2 decades, before and after the establishment of pPCI networks. METHODS: Prospective, consecutive registry of STEMI patients within a region of 850 000 inhabitants over 2 decades: a pre-pPCI period (1990-2000) and a pPCI period (2007-2017). We analyzed the prevalence of mechanical complications, including ventricular septal rupture, papillary muscle rupture, and free wall rupture (FWR). Twenty eight-day and 1-year mortality trends were compared between the 2 studied decades. RESULTS: A total of 6033 STEMI patients were included (pre-pPCI period, n=2250; pPCI period, n=3783). Reperfusion was supported by thrombolysis in the pre-pPCI period (99.1%) and by pPCI in in the pPCI period (95.7%). Mechanical complications developed in 135 patients (2.2%): ventricular septal rupture in 38 patients, papillary muscle rupture in 24, and FWR in 73 patients. FWR showed a relative reduction of 60% in the pPCI period (0.8% vs 2.0%, P<.001), without significant interperiod changes in the other mechanical complications. After multivariate adjustment, FWR remained higher in the pre-pPCI period (OR, 1.93; 95%CI, 1.10-3.41; P=.023). At 28 days and 1 year, mortality showed no significant changes in all the mechanical complications studied. CONCLUSIONS: The establishment of regional pPCI networks has modified the landscape of mechanical complications in STEMI. FWR is less frequent in the pPCI era, likely due to reduced transmural infarcts.

Acute LDL-C reduction post ACS: strike early and strike strong: from evidence to clinical practice. A clinical consensus statement of the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Association of Preventive Cardiology (EAPC) and the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

After experiencing an acute coronary syndrome (ACS), patients are at a high risk of suffering from recurrent ischaemic cardiovascular events, especially in the very early phase. Low density lipoprotein-cholesterol (LDL-C) is causally involved in atherosclerosis and a clear, monotonic relationship between pharmacologic LDL-C lowering and a reduction in cardiovascular events post-ACS has been shown, a concept termed 'the lower, the better'. Current ESC guidelines suggest an LDL-C guided, step-wise initiation and escalation of lipid-lowering therapy (LLT). Observational studies consistently show low rates of guideline-recommended LLT adaptions and concomitant low rates of LDL-C target goal achievement, leaving patients at residual risk, especially in the vulnerable post-ACS phase. In addition to the well-established 'the lower, the better' approach, a 'strike early and strike strong' approach in the early post-ACS phase with upfront initiation of a combined lipid-lowering approach using high-intensity statins and ezetimibe seems reasonable. We discuss the rationale, clinical trial evidence and experience for such an approach and highlight existing knowledge gaps. In addition, the concept of acute initiation of PCSK9 inhibition in the early phase is reviewed. Ultimately, we focus on hurdles and solutions to provide high-quality, evidence-based follow-up care in post-ACS patients.

Non-STEMI vs. STEMI Cardiogenic Shock: Clinical Profile and Long-Term Outcomes.

Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI). In AMI-CS, the ST segment deviation on ECG may be elevated (STEMI-CS) or non-elevated (NSTEMI-CS), which may influence prognosis. Our aim was to analyze the clinical profile, acute-phase prognosis, and long-term outcomes of CS relative to the ST pattern on admission. In a prospective registry of 4647 AMI patients admitted to the intensive cardiac care unit of a university hospital between 2010 and 2019, we compared the clinical characteristics, 30-days case fatality, and long-term outcomes of AMI-CS, based on the presence of ST-segment deviation. AMI-CS developed in 239 (5.1%) patients (26.4% women): 190 (79.5%) STEMI-CS and 49 (20.5%) NSTEMI-CS. The mean age was 69.7 years. The STEMI-CS patients had larger infarcts and more mechanical complications than the NSTEMI-CS patients. The NSTEMI-CS patients had a greater prevalence of hypertension, diabetes, peripheral vascular disease, previous cardiovascular comorbidities, three-vessel disease, and left main disease than the STEMI-CS patients. The STEMI-CS patients had higher 30-day mortality than the NSTEMI-CS (59.5% vs. 36.7%; p = 0.004), even after multivariable adjustment (HR 1.91; 95% CI 1.16-3.14), but no differences in mortality were observed at 3 years. In conclusion, the 30-day case-fatality is higher in STEMI-CS, but the long-term outcome is similar in both groups.

Venoarterial extracorporeal membrane oxygenation flow or dobutamine to improve microcirculation during ECMO for refractory cardiogenic shock.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (VA ECMO) effectively supports refractory cardiogenic shock (rCS), and sustains macro- and microcirculations. We investigated the respective impact of increasing VA ECMO flow or dobutamine dose on microcirculation in stabilized VA ECMO-treated patients with rCS. METHODS: In this prospective interventional study, we included consecutive intubated patients, with ECMO-supported rCS and hemodynamic stability, able to tolerate stepwise incremental dobutamine doses (from 5 to 20 gamma/kg/min) or ECMO flows (progressive increase by 25% above baseline ECMO flow. Baseline was defined as the lowest VA ECMO flow and dobutamine 5 µg/kg/min (DOBU5) to maintain mean arterial pressure (MAP) ≥ 65 mmHg. Macro- and microcirculations were evaluated after 30 min at each level. RESULTS: Fourteen patients were included. Macro- and microcirculations were assessed 2 [2-5] days post-ECMO onset. Dobutamine-dose increments did not modify any microcirculation parameters. Only the De Backer score tended to be reduced (p = 0.08) by ECMO-flow increments whereas other microcirculation parameters were not affected. These findings did not differ between patients successfully weaned-off ECMO (n = 6) or not. CONCLUSIONS: When macrocirculation has already been restored in patients with ECMO-supported rCS, increasing dobutamine (above 5 µg/kg/min) or ECMO flow did not further improve microcirculation.

Circulating virome and inflammatory proteome in patients with ST-elevation myocardial infarction and primary ventricular fibrillation.

Primary ventricular fibrillation (PVF) is a life-threatening complication of ST-segment elevation myocardial infarction (STEMI). It is unclear what roles viral infection and/or systemic inflammation may play as underlying triggers of PVF, as a second hit in the context of acute ischaemia. Here we aimed to evaluate whether the circulating virome and inflammatory proteome were associated with PVF development in patients with STEMI. Blood samples were obtained from non-PVF and PVF STEMI patients at the time of primary PCI, and from non-STEMI healthy controls. The virome profile was analysed using VirCapSeq-VERT (Virome Capture Sequencing Platform for Vertebrate Viruses), a sequencing platform targeting viral taxa of 342,438 representative sequences, spanning all virus sequence records. The inflammatory proteome was explored with the Olink inflammation panel, using the Proximity Extension Assay technology. After analysing all viral taxa known to infect vertebrates, including humans, we found that non-PVF and PVF patients only significantly differed in the frequencies of viruses in the Gamma-herpesvirinae and Anelloviridae families. In particular, most showed a significantly higher relative frequency in non-PVF STEMI controls. Analysis of systemic inflammation revealed no significant differences between the inflammatory profiles of non-PVF and PVF STEMI patients. Inflammatory proteins associated with cell adhesion, chemotaxis, cellular response to cytokine stimulus, and cell activation proteins involved in immune response (IL6, IL8 CXCL-11, CCL-11, MCP3, MCP4, and ENRAGE) were significantly higher in STEMI patients than non-STEMI controls. CDCP1 and IL18-R1 were significantly higher in PVF patients compared to healthy subjects, but not compared to non-PVF patients. The circulating virome and systemic inflammation were not associated with increased risk of PVF development in acute STEMI. Accordingly, novel strategies are needed to elucidate putative triggers of PVF in the setting of acute ischaemia, in order to reduce STEMI-driven sudden death burden.

New Cases of Hypochromic Microcytic Anemia Due to Mutations in the SLC11A2 Gene and Functional Characterization of the G75R Mutation.

Divalent metal-iron transporter 1 (DMT1) is a mammalian iron transporter encoded by the SLC11A2 gene. DMT1 has a vital role in iron homeostasis by mediating iron uptake in the intestine and kidneys and by recovering iron from recycling endosomes after transferrin endocytosis. Mutations in SLC11A2 cause an ultra-rare hypochromic microcytic anemia with iron overload (AHMIO1), which has been described in eight patients so far. Here, we report two novel cases of this disease. The first proband is homozygous for a new SLC11A2 splicing variant (c.762 + 35A > G), becoming the first ever patient reported with a SLC11A2 splicing mutation in homozygosity. Splicing studies performed in this work confirm its pathogenicity. The second proband harbors the previously reported DMT1 G75R mutation in homozygosis. Functional studies with the G75R mutation in HuTu 80 cells demonstrate that this mutation results in improper DMT1 accumulation in lysosomes, which correlates with a significant decrease in DMT1 levels in patient-derived lymphoblast cell lines (LCLs). We also suggest that recombinant erythropoietin would be an adequate therapeutic approach for AHMIO1 patients as it improves their anemic state and may possibly contribute to mobilizing excessive hepatic iron.

Fulminant myocarditis in adults: a narrative review.

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe hemodynamic compromise secondary to acute myocardial inflammation, often presenting as profound cardiogenic shock, life-threatening ventricular arrhythmias and/or electrical storm. FM may be refractory to conventional therapies and require mechanical circulatory support (MCS). The immune system has been recognized as playing a pivotal role in the pathophysiology of myocarditis, leading to an increased focus on immunosuppressive treatment strategies. Recent data have highlighted not only the fact that FM has significantly worse outcomes than non-FM, but that prognosis and management strategies of FM are heavily dependent on histological subtype, placing greater emphasis on the role of endomyocardial biopsy in diagnosis. The impact of subtype on severity and prognosis will likewise influence how aggressively the myocarditis is managed, including whether MCS is warranted. Many patients with refractory cardiogenic shock secondary to FM end up requiring MCS, with venoarterial extracorporeal membrane oxygenation demonstrating favorable survival rates, particularly when initiated prior to the development of multiorgan failure. Among the challenges facing the field are the need to more precisely identify immunopathophysiological pathways in order to develop targeted therapies, and the need to better optimize the timing and management of MCS to minimize complications and maximize outcomes.