Enhanced Energy Dissipation in Stepped Chutes. (Discussion)

The contribution is a timely reminder that most research on stepped chute hydraulics has been narrowly limited to flat identical horizontal steps in straight prismatic rectangular channels (Chanson 2001). For completeness, the writer wishes to provide relevant information on early stepped spillways and related works. He also adds some pertinent comment

The use of attention-deficit hyperactivity disorder medications in cardiac disease

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset usually in childhood characterized by inattention, impulsivity, and hyperactivity causing a functional impairment. Untreated ADHD, or treatment delay is associated with adverse outcomes and poor quality of life. Although conservative management strategies such as behavioral and psychological interventions are important, pharmacological treatment has a strong evidence base with improved outcomes. ADHD medications are broadly divided into stimulant and non-stimulant medications. Stimulant medications are generally more effective than non-stimulants. Cardiovascular safety of ADHD medication has been a matter of debate for decades. Treatment guidelines advise the careful consideration of risks and benefits in people with cardiovascular diseases such as congenital heart disease or cardiomyopathy. Although stimulants can increase systemic blood pressure and heart rate, no significant associations were found between their use and serious cardiovascular events. Concerns regarding QT effects and attendant sudden cardiac death risks deter clinicians from initiating much-needed ADHD medications in patients with heart disease. This overly cautious approach is potentially depriving low-risk individuals from significant benefits associated with timely ADHD drug treatment. This review discusses the cardiovascular risks reportedly associated with ADHD medications, the evidence base for their safe usage in persons with established cardiovascular disease, and highlights future research directions

Meta-analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease, as penetrance (proportion of G+ who develop disease) is variable, age-dependent, and not reliably predicted. METHODS: A systematic search of the literature was performed. We employed random effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere genes in two different contexts: clinically-based studies on patients and families with HCM versus population/community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up. FINDINGS: 455 full text manuscripts were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in non-proband relatives carrying P/LP variants identified during cascade screening was 57% (95% confidence interval [CI] [52,63]) and the mean age of HCM diagnosis was 38 years (95% CI [36, 40]). Penetrance varied from ~32% for myosin light chain (MYL3) to ~55% for myosin binding protein C (MYBPC3), ~60% troponin T (TNNT2) and troponin I (TNNI3), and ~65% for myosin heavy chain (MYH7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population, but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower; approximatively 11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ~8 years of follow up, starting from a mean age of ~16 years. However, short-term gene-specific phenotypic conversion varied between ~12% for MYBPC3 to ~23% for MYH7. CONCLUSIONS: The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve understanding of true lifetime penetrance in families and in the community, and to identify drivers of the transition from subclinical to overt HCM

CMR in Heart Failure

Heart Failure (HF) is a common syndrome with multiple causes. Cardiovascular magnetic resonance (CMR) is a medical imaging technique with significant advantages, allowing the understanding of aetiology and pathophysiology of HF in the individual patient, permitting specific therapy to be administered and predicting prognosis. This paper discusses the diverse role of CMR in HF

Declining Levels and Bioavailability of IGF-I in Cardiovascular Aging Associate With QT Prolongation-Results From the 1946 British Birth Cohort

BACKGROUND: As people age, circulating levels of insulin-like growth factors (IGFs) and IGF binding protein 3 (IGFBP-3) decline. In rat cardiomyocytes, IGF-I has been shown to regulate sarcolemmal potassium channel activity and late sodium current thus impacting cardiac repolarization and the heart rate-corrected QT (QTc). However, the relationship between IGFs and IGFBP-3 with the QTc interval in humans, is unknown. OBJECTIVES: To examine the association of IGFs and IGFBP-3 with QTc interval in an older age population-based cohort. METHODS: Participants were from the 1946 Medical Research Council (MRC) National Survey of Health and Development (NSHD) British birth cohort. Biomarkers from blood samples at age 53 and 60–64 years (y, exposures) included IGF-I/II, IGFBP-3, IGF-I/IGFBP-3 ratio and the change (Δ) in marker levels between the 60–64 and 53y sampled timepoints. QTc (outcome) was recorded from electrocardiograms at the 60–64y timepoint. Generalized linear multivariable models with adjustments for relevant demographic and clinical factors, were used for complete-cases and repeated after multiple imputation. RESULTS: One thousand four hundred forty-eight participants were included (48.3% men; QTc mean 414 ms interquartile range 26 ms). Univariate analysis revealed an association between low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y with QTc prolongation [respectively: β −0.30 ms/nmol/L, (95% confidence intervals −0.44, −0.17), p < 0.001; β−28.9 ms/unit (-41.93, −15.50), p < 0.001], but not with IGF-II or IGFBP-3. No association with QTc was found for IGF biomarkers sampled at 53y, however both ΔIGF-I and ΔIGF-I/IGFBP-3 ratio were negatively associated with QTc [β −0.04 ms/nmol/L (−0.08, −0.008), p = 0.019; β −2.44 ms/unit (-4.17, −0.67), p = 0.007] while ΔIGF-II and ΔIGFBP-3 showed no association. In fully adjusted complete case and imputed models (reporting latter) low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y [β −0.21 ms/nmol/L (−0.39, −0.04), p = 0.017; β −20.14 ms/unit (−36.28, −3.99), p = 0.015], steeper decline in ΔIGF-I [β −0.05 ms/nmol/L/10 years (−0.10, −0.002), p = 0.042] and shallower rise in ΔIGF-I/IGFBP-3 ratio over a decade [β −2.16 ms/unit/10 years (−4.23, −0.09), p = 0.041], were all independently associated with QTc prolongation. Independent associations with QTc were also confirmed for other previously known covariates: female sex [β 9.65 ms (6.65, 12.65), p < 0.001], increased left ventricular mass [β 0.04 ms/g (0.02, 0.06), p < 0.001] and blood potassium levels [β −5.70 ms/mmol/L (−10.23, −1.18) p = 0.014]. CONCLUSIONS: Over a decade, in an older age population-based cohort, declining levels and bioavailability of IGF-I associate with prolongation of the QTc interval. As QTc prolongation associates with increased risk for sudden death even in apparently healthy people, further research into the antiarrhythmic effects of IGF-I on cardiomyocytes is warranted

Myocardial extracellular volume quantification by cardiovascularagn magnetic resonance and computed tomography

Purpose of review This review article discusses the evolution of extracellular volume (ECV) quantification using both cardiovascular magnetic resonance (CMR) and computed tomography (CT). Recent findings Visualizing diffuse myocardial fibrosis is challenging and until recently, was restricted to the domain of the pathologist. CMR and CT both use extravascular, extracellular contrast agents, permitting ECV measurement. The evidence base around ECV quantification by CMR is growing rapidly and just starting in CT. In conditions with high ECV (amyloid, oedema and fibrosis), this technique is already being used clinically and as a surrogate endpoint. Non-invasive diffuse fibrosis quantification is also generating new biological insights into key cardiac diseases. Summary CMR and CT can estimate ECV and in turn diffuse myocardial fibrosis, obviating the need for invasive endomyocardial biopsy. CT is an attractive alternative to CMR particularly in those individuals with contraindications to the latter. Further studies are needed, particularly in CT

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis