The COVID-19 in athletes (COVA) study: a national study on cardio-pulmonary involvement of SARS-CoV-2 infection among elite athletes.

Background: COVID-19 can cause cardiopulmonary involvement. Physical activity and cardiac complications can worsen prognosis, while pulmonary complications can reduce performance. Aims: To determine the prevalence and clinical implications of SARS-CoV-2 cardiopulmonary involvement in elite athletes. Methods: An observational study between 1 July 2020 and 30 June 2021 with the assessment of coronary biomarkers, electrocardiogram, echocardiography, Holter-monitoring, spirometry, and chest X-ray in Danish elite athletes showed that PCR-tested positive for SARS-CoV-2. The cohort consisted of male football players screened weekly (cohort I) and elite athletes on an international level only tested if they had symptoms, were near-contact, or participated in international competitions (cohort II). All athletes were categorized into two groups based on symptoms and duration of COVID-19: Group 1 had no cardiopulmonary symptoms and duration ≤7 days, and; Group 2 had cardiopulmonary symptoms or disease duration >7 days. Results: In total 121 athletes who tested positive for SARS-CoV-2 were investigated. Cardiac involvement was identified in 2/121 (2%) and pulmonary involvement in 15/121 (12%) participants. In group 1, 87 (72%), no athletes presented with signs of cardiac involvement, and 8 (7%) were diagnosed with radiological COVID-19-related findings or obstructive lung function. In group 2, 34 (28%), two had myocarditis (6%), and 8 (24%) were diagnosed with radiological COVID-19-related findings or obstructive lung function. Conclusions: These clinically-driven data show no signs of cardiac involvement among athletes who tested positive for SARS-CoV-2 infection without cardiopulmonary symptoms and duration <7 days. Athletes with cardiopulmonary symptoms or prolonged duration of COVID-19 display, exercise-limiting cardiopulmonary involvement.

Left Atrial Volumes and Function, and Long-Term Incidence of Ischemic Stroke in the General Population.

Background Left atrial (LA) volumes and emptying fraction in the general population may address structural and functional aspects of atrial cardiomyopathy associated with long-term risk of ischemic stroke in the absence of atrial fibrillation or prior stroke. We investigated the association between LA volumes and function and ischemic stroke. Methods and Results In a community-based cohort, we measured LA minimal volume, LA maximal volume, and LA emptying fraction by transthoracic echocardiography. The primary end point was ischemic stroke. Participants with known atrial fibrillation or prior ischemic stroke were excluded, which resulted in 1866 participants. The mean age was 58±16 years, and 57% were women. During a median follow-up of 16.5 years (interquartile range: 11.4-16.8 years), 176 (9.4%) ischemic strokes occurred. In multivariable cause-specific regression models and competing risk models with death as a competing risk, LA emptying fraction was associated with ischemic stroke (hazard ratio [HR], 1.14 per 10% decrease [95% CI, 1.02-1.28]) and (subdistribution HR, 1.14 [95% CI, 1.01-1.29]). This association remained when adjusting for participants who developed atrial fibrillation during follow-up (HR, 1.12 per 10% decrease [95% CI, 1.00-1.26]). Indexed LA volumes were not associated with ischemic stroke in the same models. LA emptying fraction and indexed LA volumes were not associated with all-cause mortality. Conclusions Lower LA emptying fraction measured by transthoracic echocardiography was associated with future ischemic stroke independently of incident atrial fibrillation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993172.

Reaching Frail Elderly Patients to Optimize Diagnosis and Management of Atrial Fibrillation (REAFEL): A Feasibility Study of a Cross-Sectoral Shared-Care Model.

Introduction: Atrial fibrillation (AF) management in primary care often requires a referral to cardiology clinics, which can be strenuous for frail patients. We developed "cardio-share" (CS), a new cross-sector collaboration model, to ease this process. General practitioners (GPs) can use a compact Holter monitor (C3 from Cortrium) to receive remote advice from the cardiologist. Objective: To test the feasibility and acceptability of the CS model to manage suspected AF in frail elderly patients. Methods: We used a mixed methods design, including the preparation of qualitative semistructured interviews of GPs and nurses. Results: Between MAR-2019 and FEB-2020, 54 patients were consulted through the CS model, of whom 35 underwent C3 Holter monitoring. The time from referral to a final Holter report was shortened from a mean (SD) of 117 (45) days in usual care to 30 days (13) with the CS model. Furthermore, 90% of the patients did not need to attend visits at the cardiology clinic. The GPs and nurses highlighted the ease of using the C3 monitor. Their perception was that patients were confident in the GPs' collaboration with cardiologists. Conclusions: The CS model using a C3 monitor for AF is both feasible and seems acceptable to GPs. The elapsed time from referral to the Holter report performed for the diagnosis was significantly reduced.

Hearing loss in fabry disease: A 16 year follow-up study of the Danish nationwide cohort.

Background: Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide (Gb3) causing multi-organ dysfunction. The audiologic involvement in FD has been neglected in previous studies; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life. Objective: To investigate hearing loss from baseline through 16 years follow-up of the Danish FD cohort and to compare audiometric data to other clinical variables. Methods: Data was collected prospectively and assessed retrospectively during a period of 16 years from 83 patients (age: 9-72 years; sex: 29 males and 54 females). 55 patients underwent treatment. Air conduction thresholds was assessed at six frequencies between 0.25 and 8 kHz bilaterally. Data was analyzed using multilinear models. Results: Mean follow-up period for patients undergoing a FD specific treatment was 7.8 years (0-12.8 years, SD 3.8 years, n = 55). Hearing thresholds for FD patients deviated from healthy individuals at all frequencies for both sexes (p < 0.001). Males had more profound hearing loss than females at high frequencies (4,8 kHz) (p = 0.025). There was no improvement in hearing with treatment (p = 0.343♂, p = 0.256♀). No associations between hearing loss and measured glomerular filtration rate, left ventricular wall thickness or cerebral white matter lesions were found. Lower plasma Gb3 concentration correlated with better hearing (p = 0.046) in males. Conclusion: Our findings demonstrated significant hearing loss in FD patients compared to audiologically healthy individuals at all frequencies, and no change in hearing during treatment. Lower plasma Gb3 concentrations correlated with better hearing in males.

Significant hearing loss in Fabry disease: Study of the Danish nationwide cohort prior to treatment.

BACKGROUND: Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide resulting in multi-organ dysfunction e.g. cerebral, cardiac, renal and audiologic complications. The audiologic involvement in FD has often been neglected; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life. OBJECTIVES: To investigate baseline hearing status of the Danish Fabry cohort prior to treatment, compared to sex- and age-expected hearing levels and correlating hearing to renal and cerebral findings. MATERIAL AND METHODS: Retrospective study of baseline hearing status of the Danish Fabry cohort (n = 83, 9-72 years). Air conduction and speech discrimination scores were assessed at 6 frequencies between 0.25-8 kHz bilaterally. Data were collected between 2001-2014 and compiled in STATA using multilinear mixed modelling for statistical evaluation. RESULTS: Hearing thresholds at all frequencies deviated from the expected thresholds of an otologically normal cohort (p<0.001) and ranged 0.5 to 1.5 standard deviations below expected values. In total 29 males and 54 females were included. Hearing loss was more pronounced in the higher frequencies. There was a trend of association between hearing loss and measured glomerular filtration rate (mGFR) (p = 0.084). No association was present between hearing loss and albuminuria (p = 0.90), Fabry related cerebral abnormalities (p = 0.84) and cardiac left ventricular mass index, (LVMi) (p = 0.67) independent of sex. Hearing thresholds were poorer for men compared to women (p = 0.001). Sex differences were present at 0.25, 4 and 8 kHz. CONCLUSION: Our findings demonstrated significant hearing loss in Danish FD patients before treatment initiation, being more profound than in otologically healthy individuals at all frequencies. Additionally, we observed no association between hearing loss and LVMi, albuminuria or FD cerebral abnormalities, with a trend of association to mGFR. SYNOPSIS: Patients with Fabrys disease have hearing loss of all frequencies and most prominently at high frequencies (4-8 kHz), with no association between the hearing loss and cerebral abnormalities, and cardiac mass but with a trend of association to measured glomerular filtration rate.

Does Left Atrial Appendage Amputation During Routine Cardiac Surgery Reduce Future Atrial Fibrillation and Stroke?

PURPOSE OF REVIEW: Stroke is the most feared complication of atrial fibrillation. To prevent stroke, left atrial appendage exclusion has been targeted, as it is the prevalent site for formation of heart thrombi during atrial fibrillation. We review the historic development of methods for exclusion of the left atrial appendage and the evidence to support its amputation during routine cardiac surgery. RECENT FINDINGS: Evidence is not yet sufficient to routinely recommend left atrial exclusion during heart surgery, despite a high prevalence of postoperative atrial fibrillation. Observational studies indicate that electrical isolation of scarring from clip or suture techniques reduces the arrhythmogenic substrate. Randomized studies comparing different methods of closure of the left atrial appendage before amputation do not exist. Such studies are therefore warranted, as well as studies that can elucidate whether amputation is superior to leaving the left atrial appendage stump. Potentially, thrombogenic remaining pouch after closure should be addressed.

Cognitive Impairments and Subjective Cognitive Complaints in Fabry Disease: A Nationwide Study and Review of the Literature.

Fabry disease is a rare progressive X-linked lysosomal storage disorder which leads to neuropathic pain, organ dysfunction and cerebral pathology. Few studies have investigated cognitive impairment in Fabry disease and these previous studies are difficult to compare due to heterogeneous methodological designs and small cohorts. The objective was to investigate the frequency of cognitive impairment in the Danish nationwide cohort of Fabry patients. Further, we examined if subjective cognitive complaints were associated with objective cognitive performances in this patient group. Neuropsychological tests (17 measures) and evaluation of subjective complaints with the Perceived Deficits Questionnaire (PDQ) were applied in 41 of 63 patients. According to an a priori definition, 12 patients (29.3%) were cognitively impaired. Tests tapping psychomotor speed, attention and executive functions had the highest frequency of impairment. In general, disease related variables as Mainz Severity Score Index, enzyme activity and years since onset and depression did not have a significant impact on the categorisation of patients as being cognitively impaired or non-impaired. Thus, cognitive impairment in Fabry disease does not seem to occur solely by having symptoms for many years or by having high disease burden. However, impaired neuropsychological test results were significantly more common in patients with cerebrovascular disease. Only three patients had scores in the abnormal range of the PDQ scale and subjective perceptions of cognition were not associated with cognitive performances. The levels of subjective cognitive complaints were generally very low in the studied patients demonstrating that the absence of subjective cognitive complaints does not exclude the presence of objective cognitive problems.

Echocardiographic and clinical findings in patients with Fabry disease during long-term enzyme replacement therapy: a nationwide Danish cohort study.

OBJECTIVES: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT. METHODS: We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort. We followed clinical signs, symptoms and findings by echocardiography, electrocardiography and Holter-monitoring. RESULTS: We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0-12] years and 6 [0-13] years, respectively. Comparison between ERT and non-ERT receiving patients by left ventricular mass (echocardiographic assessment) and Sokolow-Lyon voltage- and Cornell product criteria (electrocardiographic assessment) revealed no significant differences. In the ERT group, we observed no change in left ventricular mass but a decrease in Sokolow-Lyon voltage- and Cornell product criteria from baseline to follow-up; 30 mm [15-53] vs. 25 mm [3-44], p < 0.005 and 1710 mm·ms [480-3740] vs. 1520 mm·ms [550-5740], p < .05, respectively. There were no changes within the non-ERT group. During follow-up, cardiac symptoms and use of cardiovascular procedures and -medication increased significantly in the ERT group, whereas no differences were observed within the non-ERT group. DISCUSSION: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research.