Dasiglucagon Effects on QTc in Healthy Volunteers: A Randomized, Placebo-Controlled, Dose-Escalation, Double-Blind Study.

Background: Dasiglucagon is a novel glucagon analog that is stable in aqueous formulation and approved for use in severe hypoglycemia. Concentration QTc analyses are critical for assessing risk of drug-induced QTc prolongation and potential for fatal cardiac arrhythmias such as torsades de pointes. Objective: The aim of this study was to determine whether dasiglucagon treatment resulted in any clinically relevant effect on cardiac repolarization in healthy volunteers. Methods: This double-blind, placebo-controlled, dose-escalation Phase I trial was conducted at a single center in Germany between November 2018 and June 2019. Sixty healthy volunteers aged 18 to 45 years were randomized within dose cohorts to receive intravenous dasiglucagon, intravenous placebo, or subcutaneous dasiglucagon. In the intravenous administration cohorts, doses ranged from 0.03 mg to 1.5 mg. The subcutaneous administration cohort received the approved 0.6 mg dose. In the intravenous administration cohorts, serial electrocardiograms were extracted from continuous Holter monitors at prespecified time points beginning the day before dosing and through 24 hours postdose. Heart rate, PR interval, and QRS duration were evaluated. Concentration-QT analyses corrected by Fridericia's formula (QTcF) were performed using both a linear mixed-effects and a maximum estimated effect (Emax) model. Results: At the doses studied, dasiglucagon did not have any clinically relevant effect on heart rate, PR interval, or QRS duration. A minor prolongation of the QTcF interval was observed without any clear dose or concentration dependency. Both the linear and Emax models predicted mean and 90% CIs of placebo-corrected change in QTcF remained below 10 ms (the threshold of regulatory concern), although the linear model did not fit the data well at low dasiglucagon plasma concentrations. In the Emax model, the Emax of dasiglucagon was 3.6 ms (90% CI, 1.23-5.95 ms), and the amount to produce half the effect of Emax) was 426.0 pmol/L (90% CI, -48.8 to 900.71 pmol/L). The treatment effect-specific intercept was -0.44 ms (90% CI, -2.37 to 1.49 ms). The most frequently observed treatment-emergent adverse events reported in the trial were gastrointestinal disorders such as nausea and vomiting. Conclusions: Dasiglucagon does not cause clinically relevant QTc prolongation in concentrations up to ≈30,000 pmol/L, a level 5-fold higher than the highest observed plasma concentrations in clinical trials investigating use of the approved 0.6 mg SC dose. ClinicalTrials.gov Identifier: NCT03735225; EudraCT identifier: 2018-002025-32. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

BACKGROUND: Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. METHODS: We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. RESULTS: At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). Rates of death from cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal. CONCLUSIONS: In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446 .).

Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment.

AIMS: To investigate whether the pharmacokinetic characteristics of semaglutide were altered in people with hepatic impairment, assessed using Child-Pugh criteria, vs those with normal hepatic function. METHODS: In this multicentre, open-label, parallel-group trial (sponsor Novo Nordisk, ClinicalTrials.gov ID NCT02210871), four groups of participants with normal hepatic function (n = 19) or mild (n = 8), moderate (n = 10) or severe (n = 7) hepatic impairment received a single, subcutaneous dose of 0.5 mg semaglutide. Semaglutide plasma concentrations were assessed frequently for 35 days after dosing. The primary endpoint was area under the semaglutide plasma concentration-time curve from time zero to infinity (AUC0-∞ ). No effect of hepatic impairment was declared if the 90% confidence interval (CI) for the between-group ratio (hepatic impairment/normal function) was within the interval 0.70 to 1.43. RESULTS: Semaglutide exposure was similar across all groups, with AUC0-∞ treatment ratios for mild impairment/normal function of 0.95 (90% CI 0.77, 1.16), moderate impairment/normal function 1.02 (90% CI 0.93, 1.12), and severe impairment/normal function 0.97 (90% CI 0.84, 1.12). The maximum plasma semaglutide concentration (Cmax ) did not appear to be influenced by hepatic function, with mild impairment/normal function treatment ratios of 0.99 (90% CI 0.80, 1.23), moderate impairment/normal function 1.02 (90% CI 0.88, 1.18) and severe impairment/normal function 1.15 (90% CI 0.89, 1.48; sensitivity analysis excluding one extreme semaglutide concentration: 1.05 [90% CI 0.88, 1.25]). In all, 10 participants reported 12 mild or moderate non-serious adverse events. No unexpected safety or tolerability issues were observed. CONCLUSIONS: Semaglutide exposure did not appear to be affected by hepatic impairment, suggesting that dose adjustment may not be necessary in patients with hepatic impairment. Semaglutide was well tolerated and there were no unexpected safety issues.

Sterilizing photocurable materials by irradiation: preserving UV-curing properties of photopolymers following E-beam, gamma, or X-ray exposure.

We have developed novel photopolymer gels to function as separators in blood collection tubes. By incorporating antioxidants such as α-tocopherol and nitroxides (TEMPO and TEMPOL), the new formulation can be sterilized with electron beam or gamma rays at a dose level of 17 kGy, without inducing premature curing of the photopolymers. For the blood separator gels that contain α-tocopherol, our results show that α-tocopherol plays a decisive role in impeding C-centered free radical propagation reactions through an H-transfer mechanism. This mechanism involves the transfer of an H-atom from the hydroxyl group (OH) of α-tocopherol to the propagating C-centered radical leading to the termination of the polymerization. The sterilization radiation-induced premature curing of the photopolymer was also prevented in the blood separator gel containing nitroxides. For the gels containing TEMPO or TEMPOL, inhibition of the premature curing was achieved through an addition reaction or an H-transfer reaction, respectively. Our results also show that while α-tocopherol is not a contributing factor in the subsequent (time-of-use) UV curing of the gels, nitroxides enhance the UV curing process through nitroxide-mediated living free radical polymerization reactions leading to a decrease in UV curing time. The photopolymer separator gels are shown to function advantageously in clinical laboratory testing, especially for cell-free DNA measurements in blood.

Using scenario-based training to promote information literacy among on-call consultant pediatricians.

BACKGROUND: Traditionally, teaching hospital staff to search for medical information relies heavily on educator-defined search methods. In contrast, the authors describe our experiences using real-time scenarios to teach on-call consultant pediatricians information literacy skills as part of a two-year continuing professional development program. CASE PRESENTATION: Two information-searching workshops were held at Sahlgrenska University Hospital in Gothenburg, Sweden. During the workshops, pediatricians were presented with medical scenarios that were closely related to their clinical practice. Participants were initially encouraged to solve the problems using their own preferred search methods, followed by group discussions led by clinical educators and a medical librarian in which search problems were identified and overcome. The workshops were evaluated using questionnaires to assess participant satisfaction and the extent to which participants intended to implement changes in their clinical practice and reported actual change. CONCLUSIONS: A scenario-based approach to teaching clinicians how to search for medical information is an attractive alternative to traditional lectures. The relevance of such an approach was supported by a high level of participant engagement during the workshops and high scores for participant satisfaction, intended changes to clinical practice, and reported benefits in actual clinical practice.

SARS-CoV-2 viral variants can rapidly be identified for clinical decision making and population surveillance using a high-throughput digital droplet PCR assay.

Epidemiologic surveillance of circulating SARS-CoV-2 variants is essential to assess impact on clinical outcomes and vaccine efficacy. Whole genome sequencing (WGS), the gold-standard to identify variants, requires significant infrastructure and expertise. We developed a digital droplet polymerase chain reaction (ddPCR) assay that can rapidly identify circulating variants of concern/interest (VOC/VOI) using variant-specific mutation combinations in the Spike gene. To validate the assay, 800 saliva samples known to be SARS-CoV-2 positive by RT-PCR were used. During the study (July 2020-March 2022) the assay was easily adaptable to identify not only existing circulating VAC/VOI, but all new variants as they evolved. The assay can discriminate nine variants (Alpha, Beta, Gamma, Delta, Eta, Epsilon, Lambda, Mu, and Omicron) and sub-lineages (Delta 417N, Omicron BA.1, BA.2). Sequence analyses confirmed variant type for 124/124 samples tested. This ddPCR assay is an inexpensive, sensitive, high-throughput assay that can easily be adapted as new variants are identified.

High-frequency electrocardiogram as a supplement to standard 12-lead ischemia monitoring during reperfusion therapy of acute inferior myocardial infarction.

BACKGROUND: Resolution of ST-segment elevation in the electrocardiogram (ECG) is used as a reperfusion sign during thrombolytic therapy in acute myocardial infarction. Analysis of high-frequency QRS components (HF-QRS) might provide additional information. The study compares changes in HF-QRS (150-250 Hz) to ST-segment changes in the standard ECG during thrombolytic therapy. METHODS: Twelve patients receiving intravenous thrombolytic therapy were included. A continuous 12-lead ECG recording was acquired for 4 hours. RESULTS: After 1 hour of therapy, 3 patients showed ST-elevation resolution as well as an increase in HF-QRS. These changes in ST and HF-QRS occurred simultaneously. No other patient showed significant changes in ST or HF-QRS after 1 hour. After 2 and 4 hours, there was less concordance between the standard and high-frequency ECGs. CONCLUSIONS: In patients with early ST-elevation resolution, the standard and high-frequency ECGs show similar results. Later changes are more disparate and may provide different clinical information.

Comparison of high-frequency QRS components and ST-segment elevation to detect and quantify acute myocardial ischemia.

OBJECTIVE: This study tests the ability of high-frequency components of the depolarization phase (HF-QRS) vs conventional ST-elevation criteria to detect and quantify myocardial ischemia. METHODS: Twenty-one patients admitted for elective percutaneous coronary intervention were included. Quantification of the ischemia was made by myocardial scintigraphy. High-resolution electrocardiogram before and during percutaneous coronary intervention was recorded and signal averaged. The HF-QRS were determined within the frequency band 150 to 250 Hz. ST-segment deviation was measured in the standard frequency range (<100 Hz). RESULTS: HF-QRS criteria were met by 76% of the patients, whereas 38% met the ST-elevation criteria (P = .008). Both HF-QRS reduction and ST elevation correlated significantly with the amount of ischemia (HF-QRS: r = 0.59, P = .005 for extent and r = 0.69, P = .001 for severity; ST elevation: r = 0.49, P = .023 for extent and r = 0.57, P = .007 for severity). CONCLUSIONS: This study suggests that HF-QRS analysis could provide valuable information both to detect acute ischemia and to quantify myocardial area at risk.

A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin.

The antigenicity, structural location, and function of the predicted lipoprotein TP0136 of Treponema pallidum subsp. pallidum were investigated based on previous screening studies indicating that anti-TP0136 antibodies are present in the sera of syphilis patients and experimentally infected rabbits. Recombinant TP0136 (rTP0136) protein was purified and shown to be strongly antigenic during human and experimental rabbit infection. The TP0136 protein was exposed on the surface of the bacterial outer membrane and bound to the host extracellular matrix glycoproteins fibronectin and laminin. In addition, the TP0136 open reading frame was shown to be highly polymorphic among T. pallidum subspecies and strains at the nucleotide and amino acid levels. Finally, the ability of rTP0136 protein to act as a protective antigen to subsequent challenge with infectious T. pallidum in the rabbit model of infection was assessed. Immunization with rTP0136 delayed ulceration but did not prevent infection or the formation of lesions. These results demonstrate that TP0136 is expressed on the outer membrane of the treponeme during infection and may be involved in attachment to host extracellular matrix components.

Biodegradable poly-beta-hydroxybutyrate scaffold seeded with Schwann cells to promote spinal cord repair.

Cavity formation is an important obstacle impeding regeneration after spinal cord injury and bridging strategies are essential to provide physical substrate allowing axons to grow across the lesion site. In this study we evaluated effects of biodegradable tubular conduit made from poly-beta-hydroxybutyrate (PHB) scaffold with predominantly unidirectional fiber orientation and supplemented with cultured adult Schwann cells on axonal regeneration after cervical spinal cord injury in adult rats. After transplantation into the injured spinal cord, plain PHB conduit was well-integrated into posttraumatic cavity and induced modest astroglial reaction. Regenerating axons were found mainly outside the PHB with only single fibers crossing the host-graft interface. No host Schwann cells migrated into the graft. In contrast, when suspension of adult Schwann cells was added to the PHB during transplantation, neurofilament-positive axons filled the conduit and became associated with the implanted cells. Although rubrospinal fibers did not enter the PHB, numerous raphaespinal and CGRP-positive axons were found within the conduit. Modification of PHB surface with fibronectin, laminin or collagen significantly increased Schwann cell attachment and proliferation in vitro. However, transplantation of PHB conduit pre-coated with fibronectin and seeded with Schwann cells did not alter axonal growth response. The results demonstrate that a PHB scaffold promotes attachment, proliferation and survival of adult Schwann cells and supports marked axonal regeneration within the graft.

Muscular exercise can cause highly pathological liver function tests in healthy men.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. WHAT THIS STUDY ADDS: Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. AIM: To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. METHODS: Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. RESULTS: Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, gamma GT and ALP remained within the normal range. CONCLUSION: The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

Gain of TP53 Mutation in Imatinib-treated SDH-Deficient Gastrointestinal Stromal Tumor and Clinical Utilization of Targeted Next-generation Sequencing Panel for Therapeutic Decision Support.

Patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) have few therapeutic options. Despite lack of KIT or platelet-derived growth factor receptor A (PDGFRA) driver mutations, SDH-deficient GISTs display strong expression of KIT by immunohistochemistry and these patients are often treated with tyrosine kinase inhibitors, including imatinib as a first-line therapy. Using a targeted next-generation sequencing panel of mutation hotspots of 50-clinically relevant genes, we investigated (1) concurrence of somatic/actionable mutations and (2) tumor molecular evolution by comparing 2 resection specimens 1.5 years apart while the patient was on imatinib adjuvant therapy. We found the tumors did not harbor KIT, PDGFRA, or any other clinically actionable mutations. However, a TP53 mutation (c.422G>A; p.C141Y) was detected in the second recurrent lesion. This represents the first study to monitor the molecular evolution of a SDH-deficient GIST during adjuvant treatment. These findings emphasize the critical need for next-generation sequencing testing before initiating targeted therapy.

No QTc Prolongation with Semaglutide: A Thorough QT Study in Healthy Subjects.

INTRODUCTION: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the once-weekly treatment of type 2 diabetes. The objective of this 16-week, double-blind, single-center thorough QT study was to confirm that semaglutide treatment does not prolong cardiac repolarization versus placebo. Prolongation of the QT interval is a biomarker for ventricular tachyarrhythmia. METHODS: In a parallel design, 168 healthy subjects were randomized to the treatment or placebo arms, of whom 166 were treated with subcutaneous semaglutide (N = 83; escalated to a supratherapeutic dose of 1.5 mg) or placebo (N = 83). The subjects (60% males) had a mean age of 38.2 years and body mass index of 25.1 kg/m2. To assess QT assay sensitivity, subjects in the placebo group received a single 400 mg moxifloxacin dose as positive control, and placebo in a crossover fashion. The primary endpoint was the time-matched change from baseline in QT interval corrected individually for heart rate (ΔQTcI), calculated from 11 electrocardiogram recordings from 0 to 48 h after the last 1.5 mg dose. Similar assessments were made for the therapeutic 0.5 and 1.0 mg semaglutide dose levels. RESULTS: No QTcI prolongation occurred with any semaglutide dose; the upper limits of two-sided 90% confidence intervals of the placebo-subtracted ΔQTcI were < 10 ms at all doses and time points. Exposure-response analysis showed no dependence of QTcI on semaglutide concentration. QT assay sensitivity was confirmed. The semaglutide safety profile was similar to that of other GLP-1 receptor agonists. CONCLUSION: Based on investigations of QT/QTc, no concern with regard to ventricular arrhythmias was raised as semaglutide did not prolong the cardiac repolarization duration in healthy subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT 02064348. FUNDING: Novo Nordisk.

Reduced high-frequency QRS components in electrocardiogram leads facing an area of the heart with intraventricular conduction delay due to bundle branch block.

BACKGROUND: The mechanisms underlying high-frequency QRS components (HF-QRS) are incompletely understood. One theory is that HF-QRS are related to the conduction velocity of the heart. The purpose was to test this hypothesis by comparing HF-QRS in patients with left or right bundle branch block (LBBB and RBBB, respectively) to those in healthy subjects and in patients with ischemic heart disease (IHD). METHODS: Twenty-two patients with LBBB, 19 patients with RBBB, 63 normal subjects, and 64 patients with IHD were included. Twelve-lead electrocardiograms were analyzed in the frequency interval 150 to 250 Hz. RESULTS: The study showed reduced HF-QRS in patients with LBBB compared with healthy subjects and patients with IHD. The difference, however, was small in lead V(1) and V(2). In patients with RBBB, no differences in HF-QRS could be detected except in few leads; among those is lead V(1). CONCLUSION: The results support the theory that HF-QRS are related to the conduction velocity of the heart.

Assessment of QT-measurement accuracy using the 12-lead electrocardiogram derived from EASI leads.

The purpose of the present study is to assess QT-interval measurements from the EASI 12-lead electrocardiogram (ECG) as compared with the standard 12-lead ECG. The QT interval was automatically determined in simultaneously recorded standard and EASI 12-lead ECGs, using a validated wavelet-based delineator. The agreement between the 2 sets of measurements was quantified both on a lead-by-lead basis and a multilead basis with global definitions of QRS onset and T-wave end. The results show that the agreement between QT-interval measurements from the 2 lead systems is acceptable, with negligible mean differences and with correlation coefficients ranging from 0.91 to 0.98 depending on the lead studied. Although the SD shows a clear dependence on the selected lead (ranging from 9.2 to 26.4 milliseconds), differences are within the accepted tolerances for automatic delineation. In a few patients, large differences were found, mainly because of changes in morphology present in both lead systems. QT intervals measured by the multilead approach were considerably more stable than single-lead measurements and resulted in a much better agreement between the 2 lead systems (correlation coefficient, 0.98; QT difference, 1.1 +/- 9.8 milliseconds). Thus, the EASI 12-lead ECG may be used for reliable QT monitoring when the multilead delineation approach is adopted.

High-frequency electrocardiogram analysis in the ability to predict reversible perfusion defects during adenosine myocardial perfusion imaging.

BACKGROUND: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on adenosine myocardial perfusion imaging (MPI) scans. The purpose of the present study was to try to reproduce those findings. METHODS: Twelve-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine (99m)Tc-tetrofosmin MPI tests. The HF-QRS were analyzed regarding morphology and changes in root mean square voltages from before the adenosine infusion to peak infusion. RESULTS: The best area under the curve (AUC) was found in supine patients (AUC = 0.736) in a combination of morphology and root mean square changes. None of the measurements, however, were statistically better than tossing a coin (AUC = 0.5). CONCLUSION: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.

Comparison of ST-segment deviation to scintigraphically quantified myocardial ischemia during acute coronary occlusion induced by percutaneous transluminal coronary angioplasty.

This study compared ST-segment changes during acute coronary artery occlusion with measurements of ischemia by myocardial scintigraphy. Forty patients who were referred for elective prolonged percutaneous transluminal coronary angioplasty underwent 12-lead electrocardiographic recording before the procedure (baseline) and continuously during the entire balloon inflation (occlusion). For each patient, the summed ST-segment deviation was calculated as the maximal absolute difference, elevation or depression, between baseline and occlusion recordings in all 12 leads. Each patient underwent 2 myocardial scintigraphies, 1 with technetium-99m sestamibi injected during the balloon inflation and 1 on the following day as a control study. Ischemia that was induced by balloon occlusion was quantified in terms of extent and severity. Results for the entire study group showed that summed ST deviation correlated with extent (r = 0.59, p < 0.0001) and severity (r = 0.61, p < 0.0001) of ischemia. The location of maximal ST deviation differed for the 3 arteries. For occlusion of the left anterior descending artery, maximal ST deviation was elevated in lead V3. For occlusion of the left circumflex artery, maximal ST deviation was depressed in lead V2. Occlusion of the right coronary artery caused ST elevation in lead III and ST depression in lead V2. In conclusion, this study demonstrated a significant correlation between summed ST deviation and myocardial ischemia during coronary occlusion that is induced by percutaneous transluminal coronary angioplasty.

Determination of the ability of high-frequency ECG to estimate left ventricular mass in humans, determined by magnetic resonance imaging.

BACKGROUND: Previous studies have shown a significantly higher correlation between left ventricular mass index (LVMi) and high-frequency QRS components (HF-QRS) than between LVMi and QRS amplitudes in the standard frequency range in rabbits. The purpose of the present study was to compare ECG measurements from standard and high-frequency ranges with left ventricular mass (LVM) and LVMi determined by magnetic resonance imaging in humans. METHODS: Sixty-two normal subjects were studied. Signal-averaged ECGs from the 12 standard leads were analysed in the standard frequency range (0.05-150 Hz), in the middle (25-100 Hz) and high end (50-150 Hz) of the standard frequency range and in the 150-250 Hz range. Root-mean square (RMS) values from the HF-QRS and QRS amplitude measurements from the standard ECGs were compared with LVM and LVMi. RESULTS: The correlations between LVMi and HF-QRS were similar to those between LVMi and standard ECG. When regarding LVM, however, the correlations found in the standard ECG were higher than those found in HF-QRS. CONCLUSIONS: Contrary to previous results in animals, we found in humans no better correlation between HF-QRS and LVM/LVMi than between standard ECG and LVM/LVMi.

Serial changes in the high-frequency ECG during the first year following acute myocardial infarction.

BACKGROUND: Previous studies have shown reduced high-frequency QRS components (HF-QRS) after acute myocardial infarction (MI). The purpose of this study was to investigate serial changes in HF-QRS during the first year following acute MI. METHODS: A total of 75 patients were included. Standard- and high-frequency ECGs were recorded on five occasions during the year following the MI (a few days after the MI, after 6 weeks, and after 3, 6 and 12 months). RESULTS: There was a statistically significant increase in HF-QRS during the follow-up year (P = 0.002). There were no significant differences in HF-QRS when comparing either the infarct location or the presence or absence of reperfusive therapy. Large differences in HF-QRS were observed, both intra-individually and inter-individually, during the year. CONCLUSIONS: There was a statistically significant increase in HF-QRS during the year following acute MI.