Biomarkers of Neurobiologic Recovery in Adults With Sport-Related Concussion.

Importance: Sport-related concussion (SRC), a form of mild traumatic brain injury, is a prevalent occurrence in collision sports. There are no well-established approaches for tracking neurobiologic recovery after SRC. Objective: To examine the levels of serum glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in Australian football athletes who experience SRC. Design, Setting, and Participants: A cohort study recruiting from April 10, 2021, to September 17, 2022, was conducted through the Victorian Amateur Football Association, Melbourne, Australia. Participants included adult Australian football players with or without SRC. Data analysis was performed from May 26, 2023, to March 27, 2024. Exposure: Sport-related concussion, defined as at least 1 observable sign and/or 2 or more symptoms. Main Outcomes and Measures: Primary outcomes were serum GFAP and NfL levels at 24 hours, and 1, 2, 4, 6, 8, 12, and 26 weeks. Secondary outcomes were symptoms, cognitive performance, and return to training times. Results: Eighty-one individuals with SRC (median age, 22.8 [IQR, 21.3-26.0] years; 89% male) and 56 control individuals (median age, 24.6 [IQR, 22.4-27.3] years; 96% male) completed a total of 945 of 1057 eligible testing sessions. Compared with control participants, those with SRC exhibited higher GFAP levels at 24 hours (mean difference [MD] in natural log, pg/mL, 0.66 [95% CI, 0.50-0.82]) and 4 weeks (MD, 0.17 [95% CI, 0.02-0.32]), and NfL from 1 to 12 weeks (1-week MD, 0.31 [95% CI, 0.12-0.51]; 2-week MD, 0.38 [95% CI, 0.19-0.58]; 4-week MD, 0.31 [95% CI, 0.12-0.51]; 6-week MD, 0.27 [95% CI, 0.07-0.47]; 8-week MD, 0.36 [95% CI, 0.15-0.56]; and 12-week MD, 0.25 [95% CI, 0.04-0.46]). Growth mixture modeling identified 2 GFAP subgroups: extreme prolonged (16%) and moderate transient (84%). For NfL, 3 subgroups were identified: extreme prolonged (7%), moderate prolonged (15%), and minimal or no change (78%). Individuals with SRC who reported loss of consciousness (LOC) (33% of SRC cases) had higher GFAP at 24 hours (MD, 1.01 [95% CI, 0.77-1.24]), 1 week (MD, 0.27 [95% CI, 0.06-0.49]), 2 weeks (MD, 0.21 [95% CI, 0.004-0.42]) and 4 weeks (MD, 0.34 [95% CI, 0.13-0.55]), and higher NfL from 1 week to 12 weeks (1-week MD, 0.73 [95% CI, 0.42-1.03]; 2-week MD, 0.91 [95% CI, 0.61-1.21]; 4-week MD, 0.90 [95% CI, 0.59-1.20]; 6-week MD, 0.81 [95% CI, 0.50-1.13]; 8-week MD, 0.73 [95% CI, 0.42-1.04]; and 12-week MD, 0.54 [95% CI, 0.22-0.85]) compared with SRC participants without LOC. Return to training times were longer in the GFAP extreme compared with moderate subgroup (incident rate ratio [IRR], 1.99 [95% CI, 1.69-2.34]; NfL extreme (IRR, 3.24 [95% CI, 2.63-3.97]) and moderate (IRR, 1.43 [95% CI, 1.18-1.72]) subgroups compared with the minimal subgroup, and for individuals with LOC compared with those without LOC (IRR, 1.65 [95% CI, 1.41-1.93]). Conclusions and Relevance: In this cohort study, a subset of SRC cases, particularly those with LOC, showed heightened and prolonged increases in GFAP and NfL levels, that persisted for at least 4 weeks. These findings suggest that serial biomarker measurement could identify such cases, guiding return to play decisions based on neurobiologic recovery. While further investigation is warranted, the association between prolonged biomarker elevations and LOC may support the use of more conservative return to play timelines for athletes with this clinical feature.

Hypertrophic cardiomyopathy with anteriorly directed mitral regurgitation is a red flag for concomitant pathology: a case report.

Background: Hypertrophic cardiomyopathy (HCM) is often linked to systolic anterior motion (SAM) of the mitral valve, typically resulting in a posteriorly directed mitral regurgitation (MR) jet. An anteriorly directed MR jet suggests additional mitral valve pathology that may not be resolved by myectomy alone. Case summary: A 58-year-old construction worker with no significant medical history experienced a syncopal event and was admitted to the emergency department with acute pulmonary oedema. A systolic murmur was investigated with a trans-thoracic echocardiogram that revealed severe MR with an unusual anteriorly directed MR jet and a possible flail segment of the posterior leaflet. This finding was further characterized with a trans-oesophageal echocardiogram that revealed severe asymmetric septal hypertrophy with SAM of the mitral valve, severe mitral regurgitation into a dilated left atrium with pulmonary vein flow reversal not caused by HCM-associated SAM, and a markedly abnormal mitral valve with flail and prolapse. The patient underwent successful cardiac surgery, including mitral valve repair and septal myectomy. The patient's recovery was uneventful, allowing for a return to work within a month post-surgery. Discussion: The anteriorly directed MR jet served as a red flag, leading to the discovery of an independent mitral valve pathology that required surgical intervention beyond the expected treatment for SAM-associated HCM. This case highlights the complexity of assessing MR in patients with HCM and underscores the importance of characterizing MR jet direction in diagnosing additional mitral valve diseases.

Epidemiology of pediatric out-of-hospital cardiac arrest compared with adults.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with ∼90% mortality rate. In the pediatric population, this would equate to a large number of years of life lost, posing a heavy medical and economic burden to society. OBJECTIVE: The purpose of this study was to outline the characteristics and causes of pediatric OHCA (pOHCA) and associations with survival until discharge in patients enrolled in the End Unexplained Cardiac Death Registry. METHODS: A prospective statewide multisource registry identified all pOHCAs cases in patients aged 1-18 years in Victoria, Australia (population 6.5 million), from April 2019 to April 2021. Cases were adjudicated using ambulance, hospital, and forensic records; clinic assessments; and interviews of survivors and family members. RESULTS: The analysis included 106 cases after adjudication (62, 58.5% male), 45 (42.5%) of which were due to cardiac causes of OHCA, with unascertained (n = 33 [31.1%]) being the most common cardiac cause reported. Respiratory events (n = 28 [26.4%]) were the most common noncardiac cause of pOHCA. Noncardiac causes were more likely to present with asystole or pulseless electrical activity (P = .007). The overall survival to hospital discharge rate was 11.3% and associated with increasing age, witnessed cardiac arrest, and initial ventricular arrhythmias (P < .05). CONCLUSION: The incidence of pOHCA in the study population was 3.69 per 100,000 child-years. In contrast to young adults with OHCA, the most common etiology was noncardiac in pediatric patients. Prognostic factors associated with survival to discharge included increasing age, witnessed arrest, and initial ventricular arrhythmias. Rates of cardiopulmonary resuscitation and defibrillation were suboptimal.

Methamphetamine-associated cardiomyopathy: an addiction medicine perspective.

Methamphetamine-associated cardiomyopathy (MaCM) is an increasingly recognised serious complication from methamphetamine (MA) use. It is characterised as the development of otherwise unexplained heart failure in the context of MA use. MaCM predominantly affects a young and vulnerable population with high morbidity and mortality. It is the second leading cause of mortality in patients with MA use disorder (MUD). Our understanding of MaCM pathogenesis is based on observational cohorts and autopsy studies. Currently, the treatment of MaCM is predicated on abstinence. Medical therapies offer some benefit to a minority of patients; however, without abstinence, medical therapies are often ineffective. Abstinence is difficult for most patients to achieve; all clinicians require an understanding of MaCM and how to educate patients on the risks of ongoing use. Where available, referral to addiction medicine specialists to assist with treatment of MUD is recommended. This review aims to: (i) explain the proposed pathologic mechanisms of MaCM; (ii) summarise recent recommendations of the screening and treatment of MaCM; and (iii) highlight the role of addiction medicine in the management of patient with MaCM.

Pacing-induced cardiomyopathy: A systematic review and meta-analysis of definition, prevalence, risk factors, and management.

Pacing-induced cardiomyopathy is a potential complication of right ventricular pacing. Definition varies between studies and the optimal management approach is uncertain. We aimed to characterize definition, prevalence, risk factors, and treatment strategies of pacing-induced cardiomyopathy (PiCM). We performed a systematic review and meta-analysis of studies that evaluated PiCM after pacemaker implantation identified through a literature search of PubMed and EMBASE up to March 2022. We collected data on the study definition of PiCM and calculated pooled prevalence across studies. Meta-analysis with random effects modeling was used to assess the association between potential risk factors and PiCM, reported as odds ratio with 95% confidence interval. Twenty-six studies (6 prospective studies) with a total of 57,993 patients (mean/median age range was 51-78 years; female 45%) were included in the final analysis. Fifteen unique definitions of PiCM were reported. The pooled prevalence of PiCM was 12% (95% confidence interval 11%-14%). In meta-analysis, risk factors included male sex, history of myocardial infarction, chronic kidney disease, atrial fibrillation, baseline left ventricular ejection fraction, native QRS duration, right ventricular pacing percentage, and paced QRS duration. Treatment strategies identified included biventricular cardiac resynchronization therapy (6 studies) and His-bundle pacing (3 studies). Definition of PiCM varied significantly between studies. More than 1 in 10 patients with chronic right ventricular pacing developed PiCM. Key risk factors included baseline left ventricular ejection fraction, native QRS duration, RV pacing percentage, and paced QRS duration. The optimal management strategy has yet to be defined. Further research is needed to define and treat this understated complication.

Concurrent left ventricular and left anterior coronary artery thrombus: is COVID-19 an innocent bystander?

We present the angiographic findings of a case of myocardial infarction associated with COVID-19 with a heavy burden of thrombus, despite only minor obstructive coronary disease.