Cardiac adaptation to exercise in adolescent athletes of African ethnicity: an emergent elite athletic population.

BACKGROUND/AIMS: Adult black athletes (BA) exhibit left ventricular hypertrophy (LVH) on echocardiography and marked ECG repolarisation changes resembling those observed in hypertrophic cardiomyopathy (HCM). Limited data are available for adolescent BA, the group most vulnerable to exercise-related sudden cardiac death. METHODS: Between 1996 and 2011, 245 male and 84 female adolescent BA from a wide variety of sporting disciplines underwent cardiac evaluation including ECG and echocardiography. Athletes exhibiting T-wave inversions and/or echocardiographic LVH were investigated further for quiescent cardiomyopathies. Results were compared with 903 adolescent white athletes (WA) and 134 adolescent sedentary black controls (BC). RESULTS: LVH on echocardiography was present in 7% of BA compared to only 0.6% of WA and none of the BC. In the very young (<16 years), 5.5% of BA, but none of the WA, demonstrated LVH. Within the BA group, LVH was more prevalent in men compared to women (9% vs 1.2%, p=0.012). T-wave inversions were present in 22.8% BA, 4.5% WA and 13.4% BC. T-wave inversions in BA occurred with similar frequency in men and women and were predominantly confined to leads V1-V4. T-wave inversions in the lateral leads, commonly associated with cardiomyopathies, were present in 2.4% of BA. On a further evaluation and mean follow-up of 8.3 years, none of the athletes exhibited HCM. CONCLUSIONS: Athletic training has a pronounced effect on adolescent BA. Black athletes as young as 14 years of age may exhibit left ventricular wall thicknesses of 15 mm and marked repolarisation changes resembling HCM. Male and female BA demonstrate a high prevalence of T-wave inversions.

Distinct effects of AMPAR subunit depletion on spatial memory.

Pharmacological studies established a role for AMPARs in the mammalian forebrain in spatial memory performance. Here we generated global GluA1/3 double knockout mice (Gria1/3-/-) and conditional knockouts lacking GluA1 and GluA3 AMPAR subunits specifically from principal cells across the forebrain (Gria1/3ΔFb). In both models, loss of GluA1 and GluA3 resulted in reduced hippocampal GluA2 and increased levels of the NMDAR subunit GluN2A. Electrically-evoked AMPAR-mediated EPSPs were greatly diminished, and there was an absence of tetanus-induced LTP. Gria1/3-/- mice showed premature mortality. Gria1/3ΔFb mice were viable, and their memory performance could be analyzed. In the Morris water maze (MWM), Gria1/3ΔFb mice showed profound long-term memory deficits, in marked contrast to the normal MWM learning previously seen in single Gria1-/- and Gria3-/- knockout mice. Our results suggest a redundancy of function within the pool of available ionotropic glutamate receptors for long-term spatial memory performance.

Association between troponin level and medium-term mortality in 20 000 hospital patients.

INTRODUCTION: Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test. METHOD: This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. RESULTS: A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log10 cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted. CONCLUSION: In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested.

The prevalence, distribution, and clinical outcomes of electrocardiographic repolarization patterns in male athletes of African/Afro-Caribbean origin.

AIMS: Athletic training in male black athletes (BAs) is associated with marked ECG repolarization changes that overlap with hypertrophic cardiomyopathy (HCM). Differentiating between the two entities is prudent since BAs exhibit a higher prevalence of exercise-related sudden death from HCM compared with white athletes (WAs). METHODS AND RESULTS: Between 1996 and 2010, 904 BAs underwent serial cardiac evaluations including ECG and echocardiography. Athletes exhibiting T-wave inversions were investigated further for HCM. Results were compared with 1819 WAs, 119 black controls (BCs), and 52 black HCM patients. Athletes were followed up for 69.7 ± 29.6 months. T-wave inversions were present in 82.7% HCM patients, 22.8% BAs, 10.1% BCs, and 3.7% WAs. In athletes, the major determinant of T-wave inversions was black ethnicity. T-wave inversions in BAs (12.7%) were predominantly confined to contiguous anterior leads (V1-V4). Only 4.1% of BAs exhibited T-wave inversions in the lateral leads. In contrast, both BCs and HCM patients exhibited lower prevalence of T-wave inversions in leads V1-V4 (4.2 and 3.8%, respectively) with most T-wave inversions in HCM patients (76.9%) involving the lateral leads. During follow-up one BA survived cardiac arrest and two athletes (one BA, one WA) were diagnosed with HCM. All three exhibited T-wave inversions in the lateral leads. CONCLUSIONS: T-wave inversions in leads V1-V4 appear to represent an ethnic variant of 'athlete's heart'. Conversely, T-wave inversions in the lateral leads may represent the initial expression of underlying cardiomyopathy and merit further evaluation and regular surveillance.

TAVI Between a Rock and a Hard Place in a Transplanted Heart.

We describe a 61-year-old male patient at our institution who was being reviewed by the heart team for consideration of transcatheter aortic valve intervention. Gated cardiac computed tomography revealed extensive eccentric calcification of the left ventricular outflow tract (LVOT) extending into the mitral valve leaflet and a large aortic annulus (33 mm; mean annular diameter/area, 854 mmsup2;). This is larger than all recommended manufacturer annular size limits, although observational data support the use of both Edwards Sapien 3 and Medtronic Evolut R in such annuli.

'Valve for Life': tackling the deficit in transcatheter treatment of heart valve disease in the UK.

Transcatheter aortic valve implantation (TAVI) is a proven treatment for life-threatening aortic valve disease, predominantly severe aortic stenosis. However, even among developed nations, access to TAVI is not uniform. The Valve for Life initiative was launched by the European Association of Percutaneous Cardiovascular Interventions in 2015 with the objective of improving access to transcatheter valve interventions across Europe. The UK has been identified as a country with low penetration of these procedures and has been selected as the fourth nation to be included in the initiative. Specifically, the number of TAVI procedures carried out in the UK is significantly lower than almost all other European nations. Furthermore, there is substantial geographical inequity in access to TAVI within the UK. As a consequence of this underprovision, waiting times for TAVI are long, and mortality among those waiting intervention is significant. This article reviews these issues, reports new data on access to TAVI in the UK and presents the proposals of the UK Valve for Life team to address the current problems in association with the British Cardiovascular Intervention Society.

Relation of High-Sensitivity Troponin to 1 Year Mortality in 20,000 Consecutive Hospital Patients Undergoing a Blood Test for Any Reason.

This was an observational study of the 1-year outcomes of the 20,000 patients included in the original CHARIOT study. The aim of the study was to assess the association between high sensitivity troponin I (hs-cTnI) concentration and 1 year mortality in this cohort. The original CHARIOT study included a consecutive cohort of in- and out-patients undergoing blood tests for any reason. Hs-cTnI concentrations were measured regardless of whether the clinician requested them. These results were nested and not revealed to the team unless requested for clinical reasons. One year mortality data was obtained from NHS Digital as originally planned. Overall, 1782 (8.9%) patients had died at 1 year. Multivariable Cox regression analysis showed that a hs-cTnI concentration above the upper limit of normal was independently associated with the hazard of mortality (HR 2.23; 95% confidence intervals 1.97 to 2.52). Furthermore, the log (10) hs-cTnI concentration was independently associated with the hazard of 1 year mortality (HR 1.77; 95% confidence intervals 1.64 to 1.91). In conclusion, in a large, unselected hospital population of both in- and out-patients, in 18,282 (91.4%) of whom there was no clinical indication for testing, hs-cTnI concentration was associated with 1 year mortality.

Voltage-independent GluN2A-type NMDA receptor Ca2+ signaling promotes audiogenic seizures, attentional and cognitive deficits in mice.

The NMDA receptor-mediated Ca2+ signaling during simultaneous pre- and postsynaptic activity is critically involved in synaptic plasticity and thus has a key role in the nervous system. In GRIN2-variant patients alterations of this coincidence detection provoked complex clinical phenotypes, ranging from reduced muscle strength to epileptic seizures and intellectual disability. By using our gene-targeted mouse line (Grin2aN615S), we show that voltage-independent glutamate-gated signaling of GluN2A-containing NMDA receptors is associated with NMDAR-dependent audiogenic seizures due to hyperexcitable midbrain circuits. In contrast, the NMDAR antagonist MK-801-induced c-Fos expression is reduced in the hippocampus. Likewise, the synchronization of theta- and gamma oscillatory activity is lowered during exploration, demonstrating reduced hippocampal activity. This is associated with exploratory hyperactivity and aberrantly increased and dysregulated levels of attention that can interfere with associative learning, in particular when relevant cues and reward outcomes are disconnected in space and time. Together, our findings provide (i) experimental evidence that the inherent voltage-dependent Ca2+ signaling of NMDA receptors is essential for maintaining appropriate responses to sensory stimuli and (ii) a mechanistic explanation for the neurological manifestations seen in the NMDAR-related human disorders with GRIN2 variant-meidiated intellectual disability and focal epilepsy.

Prevalence and significance of T-wave inversions in predominantly Caucasian adolescent athletes.

AIMS: Athletic activity is associated with electrocardiographic T-wave inversions in some adults, resembling those observed in cardiomyopathy. The prevalence and significance of T-wave inversions in adolescent athletes, the group most vulnerable to exercise-related sudden death from cardiomyopathy, is unknown. METHODS AND RESULTS: This study evaluated 1710 adolescent athletes and 400 healthy controls. Subjects with T-wave inversions underwent intensive cardiac investigations to identify a potential cause. There was no significant difference in the overall prevalence of T-wave inversions between athletes and controls (4 vs. 3%; P = 0.46). T-wave inversions in leads V1-V3 were largely confined to athletes and controls aged <16 years. Only 0.1% of athletes aged >or=16 years exhibited T-wave inversions beyond V2. T-wave inversions in the inferior and/or lateral leads and deep T-wave inversions occurred infrequently in athletes (1.5 and 0.8%, respectively) and were associated with a high prevalence of left ventricular hypertrophy or congenital cardiac anomalies. Despite intensive investigations, no athlete was diagnosed with a cardiomyopathy. CONCLUSIONS: T-wave inversions in V1-V3 are relatively common in athletes <16 years and probably represent the juvenile electrocardiogram pattern. In adolescent athletes, T-wave inversions beyond V2 if >or=16 years, T-wave inversions in the inferior/lateral leads and deep T-wave inversions in any lead are unusual, warranting further investigations for underlying cardiomyopathy.

NMDA receptor subunit NR2A is required for rapidly acquired spatial working memory but not incremental spatial reference memory.

NMDA receptors (NMDARs) containing NR2A (epsilon1) subunits are key contributors to hippocampal long-term potentiation (LTP) induction in adult animals and have therefore been widely implicated in hippocampus-dependent spatial learning. Here we show that mice lacking the NR2A subunit or its C-terminal intracellular domain exhibit impaired spatial working memory (SWM) but normal spatial reference memory (SRM). Both NR2A mutants acquired the SRM version of the water maze task, and the SRM component of the radial maze, as well as controls. They were, however, impaired on a non-matching-to-place T-maze task, and on the SWM component of the radial maze. In addition, NR2A knock-out mice displayed a diminished spatial novelty preference in a spontaneous exploration Y-maze task, and were impaired on a T-maze task in which distinctive inserts present on the floor of the maze determined which goal arm contained the reward, but only if there was a discontiguity between the conditional cue and the place at which the reward was delivered. This dissociation of spatial memory into distinctive components is strikingly similar to results obtained with mice lacking glutamate receptor-A (GluR-A)-containing AMPA receptors, which support long-term potentiation expression. These results identify a specific role for a NMDAR-dependent signaling pathway that leads to the activation of a GluR-A-dependent expression mechanism in a rapidly acquired, flexible form of spatial memory. This mechanism depends on the C-terminal intracellular domain of the NR2A subunit. In contrast, the ability to associate a particular spatial location with the water maze escape platform or food reward is NR2A independent, as well as GluR-A independent.

Left ventricular hypertrophy in athletes.

Participation in regular intensive exercise is associated with a modest increase in left ventricular wall thickness (LVWT) and cavity size. The magnitude of these physiological changes is predominantly determined by a variety of demographic factors which include age, gender, size, ethnicity, and sporting discipline. A small minority of male athletes participating in sporting disciplines involving intensive isotonic and isometric exercise may exhibit substantial increases in cardiac size that overlap with the phenotypic manifestation of the cardiomyopathies. The most challenging clinical dilemma incorporates the differentiation between physiological left ventricular hypertrophy (LVH) (athlete's heart) and hypertrophic cardiomyopathy (HCM), which is recognized as the commonest cause of non-traumatic exercise related sudden cardiac death in young (<35 years old) athletes. This review aims to highlight the distribution and physiological upper limits of LVWT in athletes, determinants of LVH in athletes, and echocardiographic methods of differentiating athlete's heart from HCM.

Frequency and impact of incidental findings on computed tomography during work-up for transcatheter aortic valve implantation: single centre experience and review of the literature.

OBJECTIVE: To assess the frequency and impact of incidental findings (IF) on CT during work-up for transcatheter aortic valve intervention (TAVI). METHODS: A consecutive cohort of patients referred for consideration of TAVI who underwent a CT scan between 2009 and 2018 were studied retrospectively. CT reports were reviewed for the presence of IFs and categorised based upon their clinical significance: (a) insignificant-findings that did not require specific treatment or follow-up; (b) intermediate-findings that did not impact on the decision-making process but required follow-up; (c) significant-findings that either required urgent investigation or meant that TAVI was clinically inappropriate. RESULTS: A total of 652 patients were included, whose median age was 82 years. One or more insignificant IF was found in 95.6% of patients. Intermediate IFs were documented in 5.4%. 91 (14%) patients had at least one significant IF. These included possible malignancy in 67 (74%). The ultimate decision to offer aortic valve intervention was only changed by the presence of an IF in 3.5% of cases. CONCLUSION: Clinically significant IFs are detected in more than 1 in 10 of patients undergoing CT as part of a TAVI work-up, although just over half of these patients still receive aortic valve intervention. ADVANCES IN KNOWLEDGE: This study is the largest UK cohort, which, when combined with a review of existing literature, provides a clear picture of the frequency and clinical impact of IFs found at CT for TAVI assessment.

True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study.

OBJECTIVE: To determine the distribution, and specifically the true 99th centile, of high sensitivity cardiac troponin I (hs-cTnI) for a whole hospital population by applying the hs-cTnI assay currently used routinely at a large teaching hospital. DESIGN: Prospective, observational cohort study. SETTING: University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, between 29 June 2017 and 24 August 2017. PARTICIPANTS: 20 000 consecutive inpatients and outpatients undergoing blood tests for any clinical reason. Hs-cTnI concentrations were measured in all study participants and nested for analysis except when the supervising doctor had requested hs-cTnI for clinical reasons. MAIN OUTCOME MEASURES: Distribution of hs-cTnI concentrations of all study participants and specifically the 99th centile. RESULTS: The 99th centile of hs-cTnI for the whole population was 296 ng/L compared with the manufacturer's quoted level of 40 ng/L (currently used clinically as the upper limit of normal; ULN). Hs-cTnI concentrations were greater than 40 ng/L in one in 20 (5.4%, n=1080) of the total population. After excluding participants diagnosed as having acute myocardial infarction (n=122) and those in whom hs-cTnI was requested for clinical reasons (n=1707), the 99th centile was 189 ng/L for the remainder (n=18 171). The 99th centile was 563 ng/L for inpatients (n=4759) and 65 ng/L for outpatients (n=9280). Patients from the emergency department (n=3706) had a 99th centile of 215 ng/L, with 6.07% (n=225) greater than the recommended ULN. 39.02% (n=48) of all patients from the critical care units (n=123) and 14.16% (n=67) of all medical inpatients had an hs-cTnI concentration greater than the recommended ULN. CONCLUSIONS: Of 20 000 consecutive patients undergoing a blood test for any clinical reason at our hospital, one in 20 had an hs-cTnI greater than the recommended ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the recommended ULN to diagnose acute myocardial infarction, in order to avoid misdiagnosis in the absence of an appropriate clinical presentation. TRIAL REGISTRATION: Clinicaltrials.gov NCT03047785.

Transcatheter aortic valve implantation: where are we now?

Transcatheter aortic valve implantation (TAVI) was first used in clinical practice in 2002. Since 2002, there has been a rapid increase in TAVI activity in patients with symptomatic severe aortic stenosis. This has been supported by systematic randomized data comparing TAVI against the gold standard treatment for the last 50 years' surgical aortic valve replacement. TAVI is now currently a recommended therapeutic intervention in the treatment of severe aortic stenosis patients who are deemed either high risk or inoperable. The indications for TAVI continue to expand. Within this review we will focus on the current guidelines for TAVI, the evidence for it, the complications of TAVI, postprocedure care, the technology available to clinicians now and finally the future perspectives for TAVI.

Jamaica's Critically Endangered Butterfly: A Review of the Biology and Conservation Status of the Homerus Swallowtail (Papilio (Pterourus) homerus Fabricius).

The Homerus swallowtail, Papilio (Pterourus) homerus Fabricius, is listed as an endangered species and is endemic to the Caribbean island of Jamaica. The largest butterfly in the Western Hemisphere, P. homerus once inhabited seven of Jamaica's 14 parishes and consisted of at least three populations; however, now only two stronghold populations remain, a western population in the rugged Cockpit Country and an eastern population in the Blue and John Crow Mountains. Despite numerous studies of its life history, much about the population biology, including estimates of total numbers of individuals in each population, remains unknown. In addition, a breeding program is needed to establish an experimental population, which could be used to augment wild populations and ensure the continued survival of the species. Here, we present a review of the biology of P. homerus and recommendations for a conservation plan.

Variation in emergency percutaneous coronary intervention in ventilated patients in the UK: Insights from a national database.

AIMS: Pre-procedural ventilation is a marker of high risk in PCI patients. Causes include out-of-hospital cardiac arrest (OHCA) and cardiogenic shock. OHCA occurs in approximately 60,000 patients in the UK per annum. No consensus exists regarding the need/timing of coronary angiography ± revascularization without ST elevation. The aim was to describe the national variation in the rate of emergency PCI in ventilated patients. METHODS AND RESULTS: Using the UK national database for PCI in 2013, we identified all procedures performed as 'emergency' or 'salvage' for whom ventilation had been initiated before the PCI. Of the 92,589 patients who underwent PCI, 1342 (5.5%) fulfilled those criteria. There was wide variation in practice. There was no demonstrable relationship between the number of emergency PCI patients with pre-procedure ventilation per annum and (i) total number of PPCIs in a unit (r=-0.186), and (ii) availability of 24h PCI, (iii) on-site surgical cover. CONCLUSION: We demonstrated a wide variation in practice across the UK in rates of pre-procedural ventilation in emergency PCI. The majority of individuals will have suffered an OHCA. In the absence of a plausible explanation for this discrepant practice, it is possible that (a) some patients presenting with OHCA that may benefit from revascularization are being denied treatment and (b) procedures may be being undertaken that are futile. Further prospective data are needed to aid in production of guidelines aiming at standardized care in OHCA.