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Aims: Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary oedema (ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE. Methods and results: A randomized, multicentre, open-label, blinded endpoint clinical trial was performed in seven Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnoea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in-hospital all-cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and the composite endpoint included 30-day mortality and SAE. Analyses were made on an intention-to-treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no significant differences in the primary endpoint (in-hospital mortality for midazolam vs. morphine 12.7% vs. 17.9%; risk ratio[RR] 0.71, 95% confidence interval [CI] 0.29–1.74; p = 0.60). SAE were less common with midazolam versus morphine (18.2% vs. 42.9%; RR 0.42, 95% CI 0.22–0.80; p = 0.007), as were the composite endpoint (23.6% vs. 44.6%; RR 0.53, 95% CI 0.30–0.92; p = 0.03). Conclusion: Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group. Instituto de Salud Carlos III supported with funds from the Spanish Ministry of Health and FEDER (PI17/01590) No data IDR 2020 18.174 JCR (2021) Q1, 7/143 Cardiac & Cardiovascular Systems 5.231 SJR (2021) Q1, 7/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEC

Objective: To study the outcomes of patients with acute heart failure (AHF) presenting renal dysfunction (RD) or hyperkalaemia (Hk) alone or in combination. Method: We analysed the data of the EAHFE registry, a multicentre, non interventionist cohort with prospective follow-up of patients with AHF. Four groups were defined based on the presence or not of RD or Hk alone or in combination. The primary endpoint was 30-day all-cause mortality. Results: A total of 11,935 of the 13,791 patients included in the EAHFE registry were analysed. Of these, 5088 (42.6%) did not have RD or Hk (NoRD-NoHk), 150 (1.3%) had no RD but had Hk (NoRD-Hk), 6012 (50.4%) had RD but not Hk (RD-NoHk) and 685 (5.7%) had both RD and Hk (RD-Hk). Thirty-day all-cause mortality was greatest in the RD-Hk group with an adjusted Hazard Ratio (HR) of 2.44 (confidence interval 95% [CI95%] 1.67-3.55; p < 0.001) and in the RD-NoHk group with an adjusted HR of 1.34 (CI95% 1.04-1.71; p = 0.022). There were no significant differences in in-hospital mortality and reconsultation at 30 days for HF. For the combined endpoint of 30-day all-cause mortality the adjusted HR was 1.33 (CI95% 1.04-1.70); (p = 0.021) for the RD-Hk group. Conclusions: The association of 30-day all-cause mortality with the presence of RD and Hk in patients presenting AHF at admission is greater than in those without this combination.

Even with improvements in lifestyle interventions, better control of cardiovascular (CV) risk factors, and improvements in CV outcomes, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in Portugal and Europe. Atherogenic dyslipidemias, particularly hypercholesterolemia, have a crucial causal role in the development of atherosclerotic CVD. The clinical approach to a patient with dyslipidemia requires an accurate diagnosis, based on harmonized and standardized lipid and lipoprotein laboratory assessments. Results and reports of these tests, together with assessment of total CV risk and the respective therapeutic targets, will help ensure that clinical guidelines and good clinical practices are followed, increasing the reliability of screening for lipid disorders, producing more accurate diagnoses and CV risk stratification, and improving CV prevention. To this end, this consensus aims to provide clinicians with practical guidance for the harmonization and standardization of laboratory lipid tests, focusing on the most recent dyslipidemia management guidelines.

To determine the characteristics and prognostic factors of early death in the very elderly with acute heart failure (AHF).We performed a prospective, observational study of AHF patients attended in Emergency Departments (ED), analyzing 45 variables collected in ED and studying troponin, natriuretic peptides and echocardiographies, not always available in the ED. The patients were divided into 2 groups: nonagenarian (age ≥ 90 years) and controls (age90 years). The study variables were mortality and death or reconsultation to the ED for AHF within 30 days after inclusion.We included 4700 patients (nonagenarians: 520, 11.1%). The 30-day mortality was 21.5% and 8.7% (p0.01), respectively with a combined event of 33.3% and 26.7% (p=0.001). Age ≥ 90 years was maintained in all the models associated with death (OR: 1.94, CI 95%: 1.40-2.70). In nonagenarians, chronic kidney insufficiency (OR: 2.07, CI95%: 1.16-3.69), severe functional dependence (OR: 2.18, CI95%; 1.30-3.64) and basal oxygen saturation90% (OR: 1.97, CI95%: 1.17-3.32) and hyponatremia135 mEq/L (OR: 1.89, CI95%: 1.05-3.42) were predictive variables of mortality. We observed an association between elevated troponin levels and natriuretic peptide values5,180 pg/mL and mortality (OR: 4.26, CI95%: 1.83-9.89; and OR: 3.51, CI95%: 1.45-8.48; respectively).The profile of nonagenarians with AHF differs from that of younger patients. Although very advanced age is an independent prognostic factor of mortality, these patients have fewer predictive factors of mortality, being only functional deterioration, basal kidney disease, hyponatremia and respiratory insufficiency on arrival at the ED and probably troponin values and elevated natriuretic peptides.

This study aims to evaluate the relationship between IMR (Index of Microcirculatory Resistance) and the echocardiographic evolution of left ventricular (LV) systolic and diastolic performance after ST-elevation acute myocardial infarction (STEMI), undergoing primary angioplasty (P-PCI).IMR was evaluated immediately after P-PCI. Echocardiograms were performed within the first 24 hours (Echo1) and at 3 months (Echo2): LV volumes, ejection fraction (LVEF), wall motion score index (WMSI), E/é ratio, global longitudinal strain (GLS), and left atrial volume were measured.Forty STEMI patients were divided in 2 groups according to median IMR: Group 1 (IMR 26), with less microvascular dysfunction, and Group 2 (IMR = 26), with more microvascular dysfunction. In Echo1 GLS was significantly better in Group 1 (-14.9 vs. -12.9 in Group 2, P = 0.005). However, there were no significant differences between the two groups in LV systolic volume, LVEF and WMS. Between Echo1 and Echo2, there were significant improvements in LVEF (0.48 ± 0.06 vs. 0.55 ± 0.06, P 0.0001), GLS (-14.9 ± 1.3 vs. -17.3 ± 7.6, P = 0.001), and E/é ratio (9.3 ± 3.4 vs. 8.2 ± 2.0, P = 0.037) in Group 1, but not in Group 2: LVEF (0.49 ± 0.06 vs. 0.50 ± 0.05, P = 0.47), GLS (-12.9 ± 2.4 vs. -14.4 ± 3.2, P = 0.052), and E/é ratio (8.8 ± 2.4 vs. 10.0 ± 4.7, P = 0.18). WMSI improved significantly more in Group 1 (reduction of -17.1% vs. -6.8% in Group 2, P = 0.015).Lower IMR was associated with better myocardial GLS acutely after STEMI, and with a significantly higher recovery of the LVEF, WMSI, E/E' ratio and GLS, suggesting that IMR is an early marker of cardiac recovery, after acute myocardial infarction.

The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder due to an abnormal cholesterol synthesis. It was first described by Smith, Lemli and Opitz in 1964. Many cases of SLOS have been described since then, leading to the recognition as a relatively common malformation syndrome. Affected individuals have dysmorphism, microcephaly, multiple congenital malformations, mental retardation, aggressiveness and hyperactivity. The severity of physical defects correlates with the severity of the cholesterol deficiency, which is caused by an abnormally low activity of 7-dehydrocholesterol reductase, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. The occurrence of hypothyroidism in association with SLOS is very unusual. We describe the first Venezuelan case in which both anomalies are associated.

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al., CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg), expressing a circulating soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5 function. These shCD5EmTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE), as well as an increased antitumoral response in non-orthotopic cancer models (B16 melanoma). This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+), and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens., This study was supported by grants from the Spanish Ministerio de Economía y Competitividad [Plan Nacional de I+D+i, SAF2010-19717], Generalitat de Catalunya [2009SGR1101], and Instituto de Salud Carlos III [Spanish Network for Research in Infectious Diseases, REIPI RD12/0015/0018] to FL, from Spanish Ministerio de Economía y Competitividad [SAF2011-22463], co-funded by the European Regional Development Fund, to RM, from Ministerio de Economía y Competitividad [SAF2012-34059], co-funded by the European Regional Development Fund, and the Spanish Ministerio de Economía y Competitividad (IPT2011-1527-010000) associated to Fibrostatin SL, to JM, and from NIH AI1076562 and National Multiple Sclerosis Society RG3891 to CR. MM-F and VGM are recipients of fellowships from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) of the Generalitat de Catalunya [2010TEM37] and from Spanish Ministerio de Economía y Competitividad [JCI-2010-06378], respectively.

Premature atherosclerosis is well-documented both in Systemic Lupus Erythematosus (SLE) and in Rheumatoid Arthritis (RA) patients, but cardiovascular (CV) risk is particularly high in lupus women. Although conventional CV risk factors do not fully explain the excessive risk in inflammatory diseases, they remain major contributors to atherosclerosis. The aim of the present study was to investigate whether CV risk factors are differentially associated with SLE and RA.One hundred women with SLE, 98 with RA and 102 controls matched on age and without overt CV or renal disease were assessed for the presence of Framingham (hypertension, hypercholesterolemia, low HDL, diabetes, smoking) and other CV risks (atherogenic index of plasma (AIP), insulin resistance, obesity, central obesity, metabolic syndrome, uric acid, sedentarism, hypothyroidism and family history of premature CV disease).Modifiable CV risk factors are highly prevalent and occur more frequently in SLE and RA than in age-matched controls. Some differences in Framingham risk factors were found between SLE and RA, with hypertension being more common in young lupus women, hypercholesterolemia more frequent in RA and low HDL-C more frequent in SLE. However, the estimated 10-year Framingham CHD risk or the Reynolds Risk Score was comparable in both diseases. Although hypercholesterolemia was more frequent in RA, lupus women display a more atherogenic lipid profile, with significantly lower HDL-C levels (56.5±16 mg/dl versus 63.7±18; p=0.005), and more cases above the high risk cutpoints for cholesterol/HDL-C (14% versus 4.1%; p=0.01) and for AIP (15% versus 6.1%; p=0.03). Also, uric acid levels are higher in SLE women (4.8±1.5 mg/dl) than in RA (4.1±1.1 mg/dl), p=0.001. On the other hand, insulin resistance is significantly higher in women with RA as compared with SLE (median HOMA-IR 3.5 [6.4]) versus 0.72 [2.5]; p0.0001) and the difference remained significant after adjustment for BMI and corticosteroids.Cardiovascular risk profile is distinct in SLE and RA women and the contribution of traditional CV risk factors to atherogenesis may be different in these two diseases. Prospective studies are necessary to understand how the control of modifiable risks can improve CV outcome in different inflammatory settings.

An implantable cardioverter defibrillator (ICD) is designed to sense life-threatening ventricular arrhythmias and terminate them, either by rapid pacing or by delivering an electrical shock. Nowadays it is a proven therapy for both primary and secondary prevention of sudden cardiac death. The typical configuration of an ICD consists of a right ventricular sensing/defibrillator lead with two coils (one distal, located in the right ventricle, and one proximal, located at the superior vena cava-right atrium junction) and an active can, the so-called "ventricular triad". Although effective in the vast majority of patients, it could be argued that this is not the most rational arrangement in electrical terms, since the main shock vector is anteriorly displaced in relation to the greater portion of the left ventricular mass. We describe a case of an ICD defibrillation failure that was solved by placing an additional defibrillator lead in a tributary of the coronary sinus.

To analyze the clinical characteristics of patients from a Department of Autoimmune Diseases presenting chronic hepatitis C virus (HCV) infection, systemic autoimmune disease, and B cell lymphoma.We analyzed the records of 100 consecutive patients with systemic autoimmune diseases and associated HCV infection seen in our department between 1994 and 2000. We retrospectively investigated the development of B cell malignancies after the diagnosis of HCV related autoimmune disease.Six patients with HCV related systemic autoimmune disease presented B cell non-Hodgkin's lymphoma (NHL). These patients fulfilled the diagnostic criteria for Sjögren's syndrome (n = 4) and polyarteritis nodosa (PAN; n = 2). Four patients were female and 2 male, with a mean age at lymphoma diagnosis of 62 years (range 45-78). The main immunologic markers were hypocomplementemia in all patients and cryoglobulinemia in 5 (83%). Primary extranodal localization of lymphoma was observed in 3 (50%) patients: prostate (n = 1), liver and ovary (n = 1), and ocular annexa (n = 1). Clinically, NHL was classified as indolent lymphoma in 3 patients and aggressive lymphoma in 3. NHL histologic types were diffuse large cell lymphoma (n = 4), extranodal marginal zone B cell lymphoma (n = 1), MALT lymphoma (n = 1), and lymphoplasmacytic lymphoma (n = 1).We describe 6 patients with a triple association of HCV infection, systemic autoimmune disease, and NHL. Characteristics of these patients included a high prevalence of cryoglobulinemia (that clearly contributes to fulfillment of diagnostic criteria for PAN) and an elevated frequency of primary extranodal involvement. We recommend careful evaluation of patients with B cell NHL to detect silent autoimmune or chronic viral diseases. This triple association reinforces the suspected links between autoimmunity, infection, and cancer.

Primary malignant cardiac tumors, particularly lymphoma, are rare entities. Cardiac involvement or metastization of the heart from neoplasia located elsewhere are more frequently found. We present the case of a 79-year-old patient admitted with heart failure symptoms with a 3-week evolution. Evaluation led to the identification of a cardiac tumor with unusual clinical presentation and with a rapid and fatal evolution. Pathologic analysis identified a B-cell non-Hodgkin lymphoma.

Myocardial perfusion SPECT is often used to exclude late restenosis or disease progression after coronary angioplasty (PTCA), but few studies have been published regarding the prognostic value of a negative study.To examine the long-term prognostic value of a non-ischemic SPECT result after successful PTCA.We retrospectively reviewed 783 patients (pts) who underwent scintigraphy 3 months to 3 years after successful PTCA. In 118 no significant myocardial ischemia (moderate or severe) was observed. There was a history of myocardial infarction (MI) in 38.1%, multivessel disease in 36.8% and LVEF50% in 15.3%. Referral for SPECT was chronic angina in 50.5% and acute coronary syndrome in 32.2%. SPECT was performed using a treadmill exercise test in 72%, adenosine in 21%, dipyridamole in 3% and dobutamine in 4%. Fifty-three percent of pts were under anti-ischemic medication. Patients were divided into two groups according to the SPECT result: group A pts (n = 70) had mild or no ischemia and group B pts (n = 48) had non-reversible defects of small or moderate size. The endpoint was the combined occurrence of death, MI, unstable angina (UA) and repeated revascularization.There were one MI, 2 UA episodes and 4 repeated PTCAs (1 for UA). Event-free survival rate at two-year follow-up was slightly lower in patients from group B compared with group A, respectively 91.7% versus 97.1% (p = 0.16, log rank test).This study suggests an excellent prognosis for patients with no or mild ischemia as assessed by SPECT performed more than 3 months after coronary angioplasty. Those patients with mild persistent defects did not present a significantly worse outcome.

To determine the prevalence of Raynaud's phenomenon (RP) in a large series of patients with primary Sjögren's syndrome (SS) and to identify the clinical and immunological features related to its presence.In a cross sectional study, we investigated 320 consecutive patients with primary SS (294 women, 26 men; mean age at onset 60 yrs, range 16-87 yrs). All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Diagnosis of RP in patients with SS was defined as intermittent attacks of digital pallor and/or cyanosis in the absence of any other associated disease or anatomical abnormalities.RP was present in 40 (13%) patients. All were women, with a mean age of 57 yrs (range 18-78). RP preceded onset of sicca symptomatology in 18 (45%) patients. The main triggering factor was exposure to cold, which induced RP in all patients, while emotional stress was a factor in 12 patients, as was job related predisposition in 2. Fifteen (38%) patients required pharmacological treatment with calcium channel blockers (12 patients) or angiotensin converting enzyme inhibitors (2 patients) during colder months, and one patient required treatment with intravenous prostacyclin for ischemic complications. Compared with SS patients without RP, those with RP showed a higher prevalence of articular involvement (50 vs 31%; p = 0.031), cutaneous vasculitis (30 vs 11%; p = 0.003), antinuclear antibodies (95 vs 65%; p0.001), anti-Ro/SSA (59 vs 31%; p0.001) and anti-La/SSB antibodies (44 vs 20%, p = 0.003).We found RP in 13% of patients with primary SS, in almost half of whom RP was the first autoimmune symptomatology. These patients constituted a subset of SS with a higher frequency of some extraglandular features and positive immunological markers. The clinical course of RP seems to be milder in patients with primary SS than in those with other systemic autoimmune diseases such as systemic sclerosis, with no vascular complications and pharmacological treatment needed in only 40% of patients.