Management and outcome trends in type 2 myocardial infarction: an investigation from the SWEDEHEART registry.

Despite poor prognosis, patients with type 2 myocardial infarction (MI) tend to be underdiagnosed and undertreated compared to those with type 1 MI. Whether this discrepancy has improved over time is uncertain. We conducted a registry-based cohort study investigating type 2 MI patients managed at Swedish coronary care units (n = 14,833) during 2010-2022. Multivariable-adjusted changes (first three vs last three calendar years of the observation period) were assessed regarding diagnostic examinations (echocardiography, coronary assessment), provision of cardioprotective medications (betablockers, renin-angiotensin-aldosterone-system inhibitors, statins) and 1-year all-cause mortality. Compared to type 1 MI patients (n = 184,329), those with type 2 MI less often had diagnostic examinations and cardioprotective medications. Increases in the use of echocardiography (OR 1.08 [95% confidence interval 1.06-1.09]) and coronary assessment (OR 1.06 [95% confidence interval 1.04-1.08]) were smaller compared to type 1 MI (pinteraction < 0.001). The provision of medications did not increase in type 2 MI. All-cause mortality rate in type 2 MI was 25.4% without temporal change (OR 1.03 [95% confidence interval 0.98-1.07]). Taken together, the provision of medications and all-cause mortality did ot improve in type 2 MI despite modest increases in diagnostic procedures. This emphasizes the need of defining optimal care pathways in these patients.

Clinical and prognostic implications of high-sensitivity cardiac troponin T concentrations in type 2 non-ST elevation myocardial infarction.

BACKGROUND: While the clinical importance of cardiac troponin is well-known in type 1 myocardial infarction (MI), evidence on this topic in type 2 MI is limited. We assessed the clinical and prognostic implications of high-sensitivity cardiac troponin (hs-cTnT) concentrations in a large sample of patients with type 2 MI. METHODS: Retrospective registry-based cohort study (SWEDEHEART) including 4607 patients with type 2 MI and 43,405 patients with type 1 MI, used for comparisons. Patients with ST-elevation MI were excluded. Multivariable-adjusted regressions were applied to investigate the associations of hs-cTnT concentrations (highest measured value during each hospitalization) with clinical variables and prognosis during a median follow-up of up to 1.9 years. RESULTS: Hs-cTnT concentrations (median 264 [25th, 75th percentiles 112-654] ng/L) were significantly associated with various cardiovascular risk factors and comorbidities in type 2 non-ST elevation MI (NSTEMI) but only weakly with the underlying triggering condition. Most of these findings including the magnitude of hs-cTn release were similar to type 1 NSTEMI. Hs-cTnT (ln) independently predicted all-cause mortality (hazard ratio 1.13 [95% confidence interval 1.09-1.17]) and major adverse events (hazard ratio 1.13 [95% confidence interval 1.10-1.17]) in type 2 NSTEMI, similar as for type 1 NSTEMI according to interaction analysis. The associations of hs-cTnT (ln) with poor prognosis tended to be stronger in type 2 NSTEMI patients without known cardiovascular disease. CONCLUSIONS: Hs-cTnT concentrations independently predict adverse outcome in type 2 NSTEMI. The similarities to type 1 NSTEMI however, are striking and emphasize the difficulty to distinguish both MI types.

Speech disfluencies in typically developing Finnish-speaking children - preliminary results.

We investigated the speech disfluencies of 54 typically fluent Finnish-speaking children: 14 children randomly selected from a longitudinal study (age levels 2, 3, and 4 years), and 40 children from a cross-sectional study (age levels 6, 7, 8, and 9 years). Speech samples, collected during a semi-structured conversation, were analysed for disfluencies per 100 words and 100 syllables. No significant within-age effect was found for the total frequency of disfluencies or disfluency types among the 2- to 4-year-olds. Across the 6- to 9-year-olds, between-group differences were found for the total frequency and type of disfluencies. Clinically relevant was that the criterion to distinguish normally fluent children from those who stutter, i.e., <3 stuttering-like disfluencies (SLD) per 100 syllables, was applicable in all age groups whereas the criterion <3SLD per 100 words was not. Consequently, these preliminary results suggest that different guidelines are needed for defining normal disfluency from stuttering in different languages.

Morbidity and cause-specific mortality in first-time myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is receiving increasing interest as a prognostically adverse entity distinct from myocardial infarction with significant coronary artery disease (MI-CAD). However, data are still limited regarding long-term cardiovascular morbidity and cause-specific mortality in MINOCA. METHODS: This is a registry-based cohort study using data from patients admitted to Swedish coronary care units. We investigated various nonfatal outcomes (recurrent MI, hospitalization for heart failure or stroke) and fatal outcomes (cardiovascular, respiratory or cancer-related mortality) in 4069 patients without apparent acute cardiovascular disease, used as non-MI controls, 7266 patients with first-time MINOCA and 69 267 patients with first-time MI-CAD. RESULTS: Almost all event rates (median follow-up 3.8 years) increased in a stepwise fashion across the three cohorts [rates of major adverse events (MAE; composite of all-cause mortality, recurrent MI, hospitalization for heart failure or stroke): n = 268 (6.6%), n = 1563 (21.5%), n = 17 777 (25.7%), respectively]. Compared to non-MI controls, MINOCA patients had an adjusted hazard ratio (HR) of 2.12 (95% confidence interval 1.84-2.43) regarding MAE. MINOCA patients had a substantial risk of cardiovascular mortality and the highest numerical risks of respiratory and cancer-related mortality. Male sex, previous heart failure and chronic obstructive pulmonary disease had a stronger prognostic impact in MINOCA than in MI-CAD. Female MINOCA patients with atrial fibrillation were at particular risk. CONCLUSIONS: Patients with first-time MINOCA have a considerable risk of adverse events. This stresses the need for a comprehensive search of the cause of MINOCA, thorough treatment of underlying disease triggers and close follow-up.

Predictors of adverse outcome in patients with myocardial infarction with non-obstructive coronary artery (MINOCA) disease.

BACKGROUND: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCAs) is an increasingly recognized entity. No previous study has evaluated predictors for new major adverse cardiacvascular events (MACEs) and death in patients with MINOCA. METHODS: We conducted an observational study of MINOCA patients recorded between July 2003 and June 2013 and followed until December 2013 for outcome events. Out of 199,163 MI admissions, 9092 consecutive unique patients with MINOCA were identified. The mean age was 65.5 years and 62% were women. MACE was defined as all-cause mortality, rehospitalization for acute MI, ischemic stroke and heart failure. Hazard ratio and 95% confidence interval (HR; 95% CI) was calculated using Cox-regression. RESULTS: A total of 2147 patients (24%) experienced a new MACE and 1254 patients (14%) died during the mean follow-up of 4.5 years. Independent predictors for MACE after adjustment, were older age (1.05; 1.04-1.06), diabetes (1.44; 1.21-1.70), hypertension (1.25; 1.09-1.43), current smoking (1.38; 1.15-1.66), previous myocardial infarction (1.38; 1.04-2.82), previous stroke (1.69; 1.35-2.11), peripheral vascular disease (1.55; 1.97-2.23), chronic obstructive pulmonary disease (1.63; 1.32-2.00), reduced left ventricular ejection fraction (2.00; 1.54-2.60), lower level of total cholesterol (0.88; 0.83-0.94) and higher level of creatinine (1.01; 1.00-1.03). Independent predictors for all cause death were age, current smoking, diabetes, cancer, chronic obstructive pulmonary disease, previous stroke, reduced left ventricular fraction, lower level of total cholesterol and higher levels of creatinine and CRP. CONCLUSIONS: The clinical factors predicting new MACE and death of MINOCA patients seem to be strikingly similar to factors previously shown to predict new cardiovascular events in patients with MI and obstructive coronary artery disease.

High-sensitivity cardiac troponin T, left ventricular function, and outcome in non-ST elevation acute coronary syndrome.

BACKGROUND: Cardiac troponin (cTn) levels reflect infarct size and depressed left ventricular ejection fraction (LVEF) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). However, there is very limited information on whether cTn measured with a high-sensitivity (hs) assay would provide incremental prognostic information to the LVEF in NSTE-ACS patients. METHODS: This was a registry-based study (SWEDEHEART registry) investigating 20,652 NSTE-ACS patients with available information on hs-cTnT (highest level recorded during the hospitalization) and the LVEF estimated using echocardiography. All patients had been followed for 1 year. RESULTS: Hs-cTnT levels independently predicted major cardiovascular events (MACE) in cohorts with normal, slightly depressed, moderately depressed, and severely depressed LVEF. The adjusted hazard ratios in these cohorts were 1.18 (95% CI 1.13-1.23), 1.12 (95% CI 1.06-1.18), 1.12 (95% CI 1.06-1.19), and 1.21 (95% CI 1.13-1.30), respectively. Hs-cTnT levels were particularly predictive for cardiovascular mortality and readmission for heart failure. Excluding patients with previous cardiac disease did not affect the overall interrelations of hs-cTnT and LVEF with MACE. CONCLUSIONS: Hs-cTnT levels provide incremental prognostic value independent of the LVEF in patients with NSTE-ACS. Hs-cTnT is particularly predictive for MACE in patients with severely depressed LVEF but also in those with a normal LVEF. Accordingly, a normal LVEF should not be used as an argument not to target patients to thorough workup.

Prognostic Biomarkers in Acute Coronary Syndromes: Risk Stratification Beyond Cardiac Troponins.

PURPOSE OF REVIEW: Cardiac troponin (cTn) plays an essential role for assessment of outcome in acute coronary syndrome (ACS). However, the prognostic value of cTn is not absolute. In this mini-review, we summarize the evidence on the utility of established biomarkers of left-ventricular dysfunction, hemodynamic stress, inflammation, and renal dysfunction for risk prediction beyond cTn in ACS. RECENT FINDINGS: Only few biomarkers consistently demonstrate additive prognostic value to cTn levels. The B-type natriuretic peptides (NPs) and growth-differentiation factor-15 (GDF-15) are most promising in this regard. However, there are uncertainties regarding the role of these biomarkers for guidance of treatment decisions, and their prognostic increment to cTn levels measured with high-sensitivity assays is largely unknown. The NPs and GDF-15 provide the strongest prognostic increment to cTn levels in ACS. However, the role of these biomarkers for clinical decision-making in contemporary settings has still to be defined.

Plasma pharmacokinetics of daptomycin in critically ill patients with renal failure and undergoing CVVHD.

BACKGROUND: Daptomycin is a novel antibiotic with primarily renal elimination. METHODS: In an open-label, prospective trial, the pharmacokinetics of daptomycin after single (8 mg/kg BW) and multiple intravenous doses (4 mg/kg BW) at steady state were determined in critically ill, dialysis-dependent patients treated with continuous veno-venous hemodialysis (CVVHD). Daptomycin levels were determined by HPLC. Subjects with normal renal function received one dose of 4 mg/kg BW of daptomycin. RESULTS: In the normal controls, daptomycin administration resulted in a mean maximum concentration (Cmax) of 60.7 ± 10.7 mg/l and an area under the time-versus-concentration curve from 0 to 24 h (AUC0-24) of 402 ± 56 mg × h/l. In the CVVHD-treated patients, a loading dose of 8 mg/kg lead to Cmax of 87.5 ± 15.0 mg/l, AUC0-24 of 537 ± 97 mg × h/l and AUC24-48 of 193 ± 69 mg × h/l, respectively. After multiple doses of 4 mg/kg every 48 h, Cmax was 41.8 ± 5.0 mg/l, AUC0-24 302 ± 43 mg × h/l and AUC 24-48 h 102 ± 24 mg × h/l, respectively. Approximately 40% of the daptomycin dose administered was removed by CVVHD. Mean plasma half-lives of daptomycin in patients were 2 - 3 times longer than in healthy controls. CONCLUSIONS: The dosing regimen of 4 mg/kg TBW of daptomycin administered to CVVHD patients every 48 h is inappropriate to achieve effective antimicrobial plasma concentrations of daptomycin in the second half of the dosing interval (24 - 48 h). Doses of ≥ 4 mg/kg TBW administered intravenously every 24 h are necessary in CVVHD patients to assure that plasma daptomycin levels are comparably high to subjects with normal renal function and to avoid underdosing.

RAGE-dependent regulation of calcium-binding proteins S100A8 and S100A9 in human THP-1.

Proinflammatory cell activation via the receptor for advanced glycation end products (RAGE) pathway may play a central pathogenetic role in atherosclerosis. Since S100A8/A9 was recently identified as ligand of RAGE, we determined the effects of proinflammatory cytokines on RAGE-mediated induction of gene expression of S100A8 and S100A9. mRNA levels of S100A8 and S100A9 were upregulated following cytokine stimulation with IL-6 (1, 10, 100 ng/ml) or TNFα (10 ng/ml) in human THP-1 cells. Preincubation of cells with 2000 ng/ml AGE (advanced glycation end products) before cytokine stimulation resulted in upregulation of RAGE. Pretreatment of THP-1 with AGE followed by stimulation with IL-6 (10 ng/ml) or TNFα (10 ng/ml) further increased S100A8 and S100A9 mRNA expression and S100A8/A9 release into cell culture supernatant, as compared to pretreatment with non-glycated albumin as control. Binding of AGE to RAGE was blocked with a neutralizing anti-RAGE antibody. Normal mouse IgG served as control. Cytokine-stimulated induction of S100A8 and S100A9 mRNA levels as well as of S100A8/A9 release after preincubation of cells with AGE were significantly suppressed by RAGE blockade, indicating a RAGE-dependent pathway of AGE-mediated S100A8/A9 expression.The cytokine-induced potentiated S100A8 and S100A9 expression under conditions with a high AGE burden is able to aggravate proinflammatory conditions via activation of the RAGE pathway.

Subarachnoid haemorrhage following spinal anaesthesia in an obstetric patient.

We describe an obstetric patient who presented for removal of a retained placenta. After insertion of the spinal anaesthetic, she developed a severe headache, and a subarachnoid haemorrhage was diagnosed. We discuss the differential diagnosis of the headache, the occurrence of intracranial haemorrhages after dural puncture and the future management of this patient.

Synthesis and characterization of photoswitchable lipids containing hemithioindigo chromophores.

The synthesis of four lipids containing the hemithioindigo chromophore as part of the fatty acid is described. Heck reaction of bromophenyl thioacetate esters with acrylonitrile, followed by reduction, ester hydrolysis, and Friedel--Craft acylation--cyclization gave a substituted thioindoxyl that condensed with an alkoxy benzaldehyde to produce the hemithioindigo. "Solventless" nitrile hydrolysis followed by mixed anhydride coupling of the acid with glycerophosphocholine produced lipids bearing two hemithioindigo chromophores. The photochemistry of various hemithioindigo derivatives was studied to confirm the expected photoisomerization in both homogeneous organic solution, and in vesicle bilayer membranes. Characteristic changes in the UV--visible spectra are consistent with fully reversible Z--E photoisomerization. Chromatographic separation of the Z and E isomers of a compound containing a single hemithioindigo chromophore confirmed the spectroscopic analysis and provided a quantitative analysis of the compositions of Z--E isomer mixtures.

Effect of oral and i.v. tenoxicam in postoperative pain after total knee replacement.

We have evaluated the effect of oral and i.v. tenoxicam on postoperative pain after unilateral total knee replacement in a double-blind, randomized, controlled study. Tenoxicam was administered to two groups of patients, either before (40 mg orally) or after (40 mg i.v.) surgery, then at 24 h after surgery (40 mg i.v.) and at the end of each day for 8 days (20 mg orally). A third group were given placebo at all times. All patients had access to PCA morphine for the first 48 h and then co-dydramol tablets for the duration of the study. We studied 101 patients, mean age 67 yr. There was no significant reduction in the requirement for PCA morphine for the duration of the study in either of the treatment groups, or for co-dydramol in the first 2 days, but tenoxicam significantly reduced the need for co-dydramol over the remaining 7 days. There were no significant differences in mobility between groups. There was a high incidence of adverse events reported, with a similar number in each of the three groups.

Low-dose rocuronium improves conditions for tracheal intubation after induction of anaesthesia with propofol and alfentanil.

We studied 60 adult patients to assess if low doses of rocuronium improved conditions for tracheal intubation during induction of anaesthesia with propofol 2.5 mg kg-1 and alfentanil 10 micrograms kg-1. In a double-blind, randomized design, patients were allocated to one of three groups: group P = saline; group R1 = rocuronium 0.1 mg kg-1; and group R3 = rocuronium 0.3 mg kg-1. Intubation conditions were judged as optimal, suboptimal or failure, based on the scoring of ease of jaw opening and laryngoscopy, position of the vocal cords and degree of straining after tracheal intubation. Intubation conditions were judged as optimal in one patient in group P, in six patients in group R1 and in 18 patients in group R3. Conditions were judged as a failure in seven patients in group P, in one patient in group R1 and in none in group R3. No laryngospasm or other complications were observed in any patient. The addition of low doses of rocuronium significantly improved intubation conditions (P < < 0.001). Ventilation was controlled during surgery, and in no patient was any problem encountered with antagonism of neuromuscular block with neostigmine. Injection of rocuronium 0.3 mg kg-1 (ED95) with propofol and alfentanil provided a high proportion of optimal intubation conditions.

Topical ibuprofen for skin analgesia prior to venepuncture.

The analgesic effect of topical ibuprofen was investigated in ten volunteers. There were no significant differences in visual analogue scale pain scores for pinprick after 15 and 60 min of application of ibuprofen, placebo and EMLA cream. Comparison of visual analogue scale scores for venous cannulation after similar durations of ibuprofen and EMLA creams found significantly (p < 0.014) lower scores for EMLA at 60 min. We do not consider ibuprofen cream to be clinically useful for venous cannulation.

Postoperative brachial plexus neuropathy after total knee replacement under spinal anaesthesia.

We describe a case of idiopathic postoperative brachial plexus neuropathy. A 68-yr-old man underwent elective total knee replacement under spinal anaesthesia. Two days after surgery, there was sensory loss and weakness in the right forearm and hand, which suggested an ulnar nerve neuropathy. Two weeks later the patient complained of a dull ache between the scapulae, followed by a burning sensation in the forearm and severe pain in the elbow. A diagnosis of brachial plexus neuropathy was made based on clinical examination and nerve conduction studies. The pain disappeared after a few months, although weakness of the right arm persisted 9 months later. The differential diagnosis between brachial plexus neuropathy and ulnar nerve neuropathy is important, as the prognosis of brachial plexus neuropathy is generally good.

Epidural infusions of bupivacaine and diamorphine in labour.

Three different concentrations of bupivacaine, 0.125%, 0.062% and 0.031%, all with diamorphine 0.0025%, were given as an epidural infusion at 10 ml.h-1 to 63 mothers in labour. When the three infusions were compared, significant differences were found in maternal requirements for top-ups and the degree of motor block, but there were no differences in the pain scores. The reduced motor block was not associated with a reduction in the instrumental delivery rate.