Cardiac Manifestations of Myotonic Dystrophy in a Pediatric Cohort.

Myotonic dystrophy type 1 (DM1) is the most prevalent inherited neuromuscular dystrophy in adults. It is a multisystem disease with cardiac manifestations. Whilst these are well-defined in adults, there are scarce published data in the pediatric population. This study aimed to investigate the yield and progression of cardiac disease in pediatric DM1 patients, focusing on congenital DM1 (cDM1). Methods: A retrospective observational study of all pediatric DM1 patients referred to our center (December 2000-November 2020) was conducted. Patients were classified into DM1 forms according to age of symptom onset and disease severity. Patients underwent clinical and cardiac evaluation with 12-lead ECG, transthoracic echocardiography and 24-h ECG Holter monitoring. Results: 67 DM1 pediatric patients were included: 56 (83.6%) cDM1 and 11 (16.4%) non-cDM1. Median follow-up time of cDM1 patients was 8.0 [3.25-11.0] years. 49 (87.5%) cDM1 patients had baseline 12-lead ECG and 44 (78.6%) had a follow-up 12-lead-ECG, with a median follow-up time from diagnosis to baseline ECG of 2.8 [1.0-8.5] years and to follow-up ECG of 10.9 [5.7-14.2] years. Overall, 43 (87.8%) presented ECG abnormalities, most commonly in the form of asymptomatic conduction disease (n = 23, 46.9%), of which 21 (42.9%) had first degree atrioventricular block (1st AVB). There was an increase of prevalence from baseline to follow-up ECG in low QRS voltage (16.7%), poor R wave progression (13.9%), abnormal repolarisation (11.9%) and 1st AVB (7.6%). one patient (1.8%) underwent pacemaker implantation for syncope in the context of progressive conduction disease. No patients developed left ventricular systolic dysfunction. 4 (7.1%) cDM1 patients died during follow up, including three who died suddenly with no clear cause of death. Conclusions: This study is the first to analyse the prevalence and progression of ECG abnormalities in cDM1 pediatric patients. The high prevalence of abnormal findings, progressive changes and number of potentially associated events (1 pacemaker implantation and 3 unexplained sudden deaths) stresses the importance of systematic and continued cardiac evaluation of these patients.

The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy.

AIMS: The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. METHODS AND RESULTS: Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484-0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7. CONCLUSION: In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

Clinical significance of inferolateral early repolarisation and late potentials in children with Brugada Syndrome.

INTRODUCTION: The clinical utility of inferolateral early repolarisation (ER) and late potentials (LP) in children with Brugada Syndrome (BrS) has not been previously evaluated. The aim of this study was to determine the prevalence of electrocardiographic (ECG) abnormalities in children with BrS, and to investigate their relationship with clinical outcomes. METHODS: 43 patients with BrS and 47 controls aged ≤18 undergoing systematic clinical and ECG evaluation, including signal-averaged ECG (SAECG) and pharmacological provocation testing, between 2003 and 2019 were included. RESULTS: Four patients with BrS (9%) presented with a spontaneous type 1 Brugada pattern; the remaining 39 (91%) were diagnosed following ajmaline provocation testing. Twelve BrS patients (28%) had late potentials (LP) on SAECG compared to 1 (2%) in controls (p = 0.001). LP were more common in 5 patients with a high-risk phenotype (60% vs 24%) but this was not statistically significant. Twelve patients with BrS (28%) had inferolateral early repolarisation (ER) and 2 (5%) had fractionated QRS (f-QRS), but there were no statistically-significant differences with controls in these parameters. A significant arrhythmia (non-sustained ventricular tachycardia or atrial fibrillation) was seen in 4 patients (9%). CONCLUSIONS: This study shows a high prevalence of SAECG abnormalities in children with BrS compared with controls, but this was not significantly associated with a high-risk phenotype.

Fatty Acid Content of Retail Cow's Milk in the Northeastern United States-What's in It for the Consumer?

The fatty acid (FA) composition and content of whole milk (3.25% fat) from organic, omega-3 (n-3) FA fortified, and conventional retail brands available in the northeastern U.S. were assessed monthly via gas chromatography. Among the retail labels, organic milk stood out as it contained a distinct and more healthful FA profile, consistently comprising a higher content of unique bioactive FAs (short-chain FAs, odd- and branched-chain FAs, vaccenic acid, and conjugated linoleic acids) per serving, particularly during the warm season. The total content of saturated FAs did not differ by retail label. While organic and n-3 fortified milk contained a similar content of total n-3 FAs, the proportion of individual n-3 FAs differed significantly (organic milk: 18:3 n-3; n-3 fortified milk: 20:6 n-3) as a result of the production system and process, respectively. Overall, per serving, the FA profile of organic milk may provide added nutritional and health benefits.

A comparison of the effects of indexation on standard echocardiographic measurements of the left heart in a healthy multi-racial population.

Accurate reference ranges for measurements from echocardiography rely on an understanding of the distribution of each measurement in the diverse, multi-racial world population. The aim of this study was to determine the influence of gender, age and ethnicity on common echocardiographic measures of the left heart, and to evaluate the effect of different methods of indexation on measurements from healthy, non-Caucasian populations. Standard echocardiographic measurements of left heart size and left ventricular mass (LVM) were assessed in 341 healthy volunteers. Indexation was performed using height, body surface area, and fat free mass (FFM). Quantile regression was used to derive age-adjusted values at the 5th, 50th and 95th‰ of each measurement, by gender, within Caucasians. The effect of indexation method across ethnic groups could then be compared. Indexation of m-mode dimensions may overcompensate for body size, resulting in people of smaller build (women and those of South or East Asian descent) developing higher indexed values than those of larger build (men and people of Maori or Pacific descent). Indexation of 2D volumes by any method improves the integration of values across ethnic groups, with FFM yielding the greatest integration. LVM increases with age, suggesting that the static reference values currently recommended for this measurement may not be appropriate. There are important differences in the distribution of measurements of left heart size by gender, ethnicity and age.

Effects of carbonation on probiotic survivability, physicochemical, and sensory properties of milk-based symbiotic beverages.

Drinkable yogurt is a popular beverage in the United States and there may be a niche for carbonated drinkable yogurt in the functional foods market. Pomegranate (P) and vanilla (V) yogurt beverages were formulated, containing inulin as a prebiotic, along with probiotic bacteria Lactobacillus acidophilus and Bifidobacterium, to produce symbiotic products. These beverages were stabilized with high-methoxyl pectin and whey protein concentrate and compared to samples with approximately 2 volumes of added carbon dioxide (CO2 ). Samples were stored in sealed glass bottles at 4 °C for 9 wk for evaluation of physicochemical and functional properties. Trials were carried out in triplicate and 3 replicates from each trial were analyzed. Physicochemical attributes were analyzed using standard AOAC methods. Survivability of the probiotics and changes in pH and viscosity were measured weekly. Chemical composition of the carbonated beverages was: protein: 1.58 ± 0.05%, 1.59 ± 0.06%, fat: 1.24 ± 0.2%, 1.18 ± 0.11%, total solids: 14.78 ± 0.11%, 14.93 ± 0.05%, ash: 0.49 ± 0.02%, 0.46 ± 0.03%, and carbohydrate (by difference): 11.47 ± 0.12%, 11.69 ± 0.14% for P and V, respectively. Both L. acidophilus and Bifidobacterium were stable and remained above 10(6) CFU/g for both flavors of beverage both with and without carbonation. The new manufacturing technology for these prototypes may have potential for commercialization of carbonated symbiotic milk-based beverages.

Rapid detection of Grapevine leafroll-associated virus type 3 using a reverse transcription loop-mediated amplification method.

Grapevine leafroll disease (GLD) is the most important disease of Grapevines in South Africa. Grapevine leafroll-associated virus type 3 (GLRaV-3) has a close association with the disease and is prevalent in South African vineyards. GLD can be controlled using a combination of virus-free planting material, systemic insecticides to control vector populations and removal of infected vines by roguing. Infected vines are identified each autumn using either symptom display (in red cultivars) or ELISA (in white cultivars). While ELISA is a simple, reliable means of testing for GLRaV-3, it is time consuming, laborious and insensitive and a quicker, more sensitive method of detecting GLRaV-3 in the field is needed. A single-tube one-step reverse transcription (RT) loop-mediated isothermal amplification (LAMP) assay combined with a simple RNA extraction protocol was developed for the rapid and easy detection of GLRaV-3. Hydroxy napthol blue was included as an indicator and under isothermal conditions at 60 °C the target viral gene could be amplified in under 2h and positive results could be easily seen by examining the colour change from violet to sky blue. Using this method, 50 samples could be also pooled together with a single positive sample still being detected. A direct comparison of ELISA, nested PCR and RT-LAMP showed that RT-LAMP is as sensitive as nested PCR and could be performed in a much shorter time with less equipment. This assay is may be a possible alternative to ELISA for the detection of GLRaV-3 in the field.

Physico-chemical properties, probiotic survivability, microstructure, and acceptability of a yogurt-like symbiotic oats-based product using pre-polymerized whey protein as a gelation agent.

Consumption of a food product containing prebiotics and probiotics has been recognized as an important factor in lowering risk of intestinal cancer and gastrointestinal diseases and risks associated with high cholesterol. An oats-based symbiotic yogurt-like food (Oagurt) was developed using oats and probiotics (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium), with pre-polymerized whey protein (PWP) as a gelation agent. The product was also fortified with inulin to increase soluble fiber, minerals, and vitamins. Physico-chemical analyses and 9 wk shelf life for viability of probiotics and changes in pH and viscosity were carried out for formulations with (F) and without (C) fortification. Results of the shelf life study showed that both L. casei and Bifidobacterium remained at therapeutic levels: 4.8 x 10(6) CFU/g (F), 4.3 x 10(6) CFU/g (C) and 3.1 x 10(6) CFU/g (F), 3.17 x 10(6) CFU/g (C) after 9 wk. However L. acidophilus did not survive after 3 wk. Viscosity and pH decreased significantly during the study with the difference between formulations also significant for pH (P < 0.0001). Scanning electron microscopy of samples revealed that the pre-polymerized whey protein played a major role in the structure of the gel with an increased protein network structure visible at higher PWP levels. A consumer acceptability study showed that the product was "fair" for all organoleptic attributes.

Changes in tissue-Doppler echocardiographic assessment of left ventricular filling during NT-proBNP guided heart failure treatment titration: a pilot study.

BACKGROUND: Although brain natriuretic peptide (BNP) and E/Ea are closely related in heart failure (HF) patients and may be helpful to guide HF therapy, the response of E/Ea to changes in BNP over several weeks of intensive HF treatment optimisation is unknown. This study was designed to investigate this relationship. METHODS AND RESULTS: In 17 patients with decompensated HF, treatment was titrated to reduce the NT-proBNP level to <200pg/mL over 10 weeks. Paired NT-proBNP measurements and echocardiograms were performed at two weekly intervals during the study. Treatment titration was associated with a reduction in E/Ea (17.6+/-6.8S.D. to 13.7+/-5.0S.D., p=0.018) in keeping with the reduction in NT-proBNP (median 603 [S.E. 561] to 311 [S.E. 235], p=0.045). This relationship remained in those who responded to titration (reduction in NT-proBNP of >or=50%), and those who did not. The overall change in E/Ea was similar to the changes observed in NT-proBNP in each group however there appeared to be temporal differences in the changes in E/Ea and NT-proBNP. CONCLUSION: This pilot study demonstrates that the E/Ea decreases after NT-proBNP guided HF therapy. E/Ea may be a complementary target for HF therapy optimisation; this hypothesis should be further evaluated in larger scale randomised trials.

Caring for bereaved people 2: nursing management.

This two-part unit examines caring for bereaved people. Part 1 discussed the manifestations of grief and explored bereavement models. Part 2 examines nurses' role in helping bereaved relatives.

Prognostic role of echocardiography and brain natriuretic peptide in symptomatic breathless patients in the community.

AIMS: Brain natriuretic peptide (BNP), left ventricular (LV) systolic function, and mitral filling pattern (MFP) are prognostic indicators in patients with heart failure (HF). This study evaluated the potential role of E/Ea for predicting cardiovascular (CV) events in patients with suspected HF. This non-invasive measure of LV filling pressure has been shown to predict outcome in more advanced HF, but not in mild HF in the community. METHODS AND RESULTS: Two hundred and twenty-eight elderly symptomatic general practice patients (dyspnoea/oedema) were recruited and underwent clinical evaluation, NT-proBNP assay, and comprehensive echocardiography. The Kaplan-Meier analysis of time to first CV hospitalization or CV death was performed for 1 year after presentation according to nominated thresholds of LV systolic function, NT-proBNP, MFP, and E/Ea ratio. Mean age was 70.3 +/- 7.3 years, mean NT-proBNP was 111.4 +/- 185.8, and 148 (65%) were female. Twenty-six patients (11%) experienced a CV event within 18 months of baseline (6 deaths and 20 admissions). Time to first CV event predicted by NT-proBNP (P < 0.0001), MFP (P = 0.009), and E:Ea (P = 0.0076), but not EF (P = 0.098). When NT-proBNP was elevated, E:Ea >15 identified a group of patients with lower survival (P < 0.0001). CONCLUSION: Both E/Ea and NT-proBNP predicted hospitalization and when used in a two-step approach (NT-proBNP first, followed by E/Ea), the combination of both (elevated NT-proBNP and elevated E/Ea) identified those patients at highest risk, thus supporting a complementary approach for echocardiography and NT-proBNP in patients with HF symptoms.

The relationship between BNP and E/Ea in patients hospitalized with acute heart failure.

BNP and echocardiographic E/Ea are variables helpful in the management of patients with heart failure (HF). The response of E/Ea to treatment for acute decompensated HF remains uncertain. This pilot study aimed to explore this relationship. 24 patients (17 male, mean age 69 years, median ejection fraction 26%) hospitalized with HF were enrolled in this study. Paired clinical examination, BNP-32 level, and echocardiogram were performed at admission and discharge. By discharge patient symptoms and BNP-32 had significantly improved, however E/Ea did not change. Our data suggests that BNP-32 and E/Ea may not be interchangeable indices and may respond differently during treatment of acute decompensated HF.

Caring for bereaved people 1: models of bereavement.

This is part 1 of a two-part unit on caring for bereaved relatives. It discusses manifestations of grief and explores three theoretical perspectives.

The effect of type 2 diabetes on diastolic function.

PURPOSE: This study aimed to determine whether sedentary overweight subjects with type 2 diabetes have impaired diastolic function compared with equally sedentary and overweight nondiabetic subjects. METHODS: Mitral valve pulsed Doppler echocardiography and tissue Doppler imaging (TDI) were used to assess left ventricular structure and diastolic function in 40- to 60-yr-old sedentary overweight subjects with type 2 diabetes (N = 13) and age- and body mass-matched sedentary nondiabetic subjects (N = 15). Pseudonormal filling was identified using preload reduction and TDI. RESULTS: Traditional Doppler mitral inflow parameters were not different between groups; however, early diastolic relaxation, as measured by peak early mitral annular velocity (E') and the ratio of E' and peak late mitral annular velocity (E'/A'), was reduced in type 2 diabetic subjects (P < 0.05). The ratio of peak early mitral inflow (E) to E' (E/E'), an estimate of left ventricular filling pressure, was also higher in the type 2 diabetes group (P < 0.05). The proportions of diastolic impairment (69 vs 40%) and pseudonormal filling (39 vs 20%) were not different between groups (P = 0.18). CONCLUSION: These findings suggest that type 2 diabetes has an effect on diastolic function that is independent of age and body composition.

Comparison of different methods for detection of diastolic filling abnormalities.

OBJECTIVE: Heart failure is associated with poor prognosis and the differentiation of patients on the basis of diastolic filling patterns helps to identify several groups of patients with incrementally higher risk. However, this is reliant on accurate definition of filling patterns. The aim of this study was to compare preload reduction with contrast-enhanced pulmonary venous Doppler recordings for the correct assessment of diastolic filling pattern. METHODS: In all, 20 patients with heart failure and 25 healthy volunteers were studied on 2 separate days. Preload reduction was achieved with the Valsalva maneuver (nonstandardized and standardized) and sublingual nitroglycerin. Responses were compared among the 3 methods and the filling patterns obtained on each day with the various methods compared. RESULTS: Although pulmonary venous Doppler improved the diastolic classification over mitral Doppler, preload reduction resulted in better classification and improved sensitivity, specificity, and positive and negative predictive values. No advantage was observed for either the standardized Valsalva or pharmacologic preload reduction. CONCLUSION: Preload reduction is an essential part of the assessment of diastolic filling grade in patients with heart failure as it can identify pseudonormal filling (mildly increased filling pressures), reversible restrictive filling (high filling pressures), and nonreversible restrictive filling pattern (very high filling pressures).

Quantitative evaluation of regional endocardial visualisation with second harmonic imaging and contrast left ventricular opacification in heart failure patients.

AIMS: Wall motion score index (WMSI) is an important prognostic indicator in heart failure (HF) patients but requires endocardial visualisation. This study evaluated the role tissue harmonic imaging (THI) and contrast opacification (LVO) for improving endocardial visualisation and the determination of WMSI in HF patients. METHODS AND RESULTS: Thirty-one HF patients and 30 controls underwent apical echocardiography with fundamental imaging (FUND), THI and THI with contrast agent (Levovist). Visualisation and motion were graded in the six segments from each of the apical two and four chamber views. Both THI and LVO reduced the percentage of non-visualised segments (FUND 13.6%, THI 5.6%, LVO 2.8%, p=0.01) in the controls, but in HF patients, only THI improved visualisation (% segments not visualised FUND 9.7%, THI 3.5%, LVO 4.8%, p=0.06). The anterior and lateral walls were the least well visualised with FUND, but improved with LVO (anterior p=0.0026, lateral p=0.0003). No improvement was seen in the inferior wall (p=0.30) or septum (p=0.2). WMSI was similar by all methods and negatively correlated with ejection fraction (FUND r=-0.69, THI r=-0.74, LVO r=-0.77, all p<0.001). CONCLUSION: THI improved endocardial visualisation in all subjects and LVO offered additional benefit in the controls, but not in HF patients. Regional endocardial visualisation was inconsistent. Thus, both patient factors and wall segment site need to be considered when using contrast agents for endocardial visualisation.

Role of echocardiography in the contemporary management of chronic heart failure.

Echocardiography is an excellent noninvasive tool for the assessment of ventricular size and both systolic and diastolic function, and it is routinely used in patients with heart failure. This review will discuss the role of echocardiography in heart failure diagnosis, prognostic assessment and in the management of heart failure patients.

Association of fat-free mass and training status with left ventricular size and mass in endurance-trained athletes.

OBJECTIVES: We sought to study the relationship between left ventricular (LV) size and body composition in male endurance athletes and age-matched control subjects. BACKGROUND: Endurance training is associated with increases in both left ventricular mass (LVM) and left ventricular end-diastolic dimension (LVEDD) in athletes. In other populations, LVM is independently predicted by fat-free mass (FFM). We hypothesized that the increase in LV size and mass observed with training may be a normal response to increased FFM. METHODS: Twelve young and 18 older male endurance athletes and 10 young and 18 older untrained men underwent exercise testing, echocardiography, and dual-photon x-ray absorptiometry body composition analysis. Univariate correlates (Spearman) and multivariate determinants of LVM and LVEDD were sought from: height, height(1.4), height(2.7), height(3.0), body surface area (BSA), FFM, weight, and body mass index. Un-indexed and indexed LVM and LVEDD were then compared. RESULTS: Athletes were of a similar age, weight, and height, but had higher FFM and maximum oxygen uptake than untrained men. Both LVM and LVEDD were correlated with body size, including FFM, BSA, weight, and height (all p < 0.05). On multivariate analysis, FFM was the only independent predictor of both LVM (R(2) = 0.36, p < 0.001) and LVEDD (R(2) = 0.35, p < 0.001). Furthermore, LVM and LVEDD (un-indexed and indexed to BSA and height) were different between athletes and non-athletes, but not when indexed to height(2.7) or FFM. CONCLUSIONS: Both LVM and LVEDD are predicted by FFM in endurance athletes, and when indexed to FFM, no training-related differences were observed. Thus, the extent of LV remodeling (athletic heart) in trained individuals may reflect a normal physiologic response to increased FFM induced by training.