Differentiation between athlete's heart and dilated cardiomyopathy in athletic individuals.

OBJECTIVE: Distinguishing early dilated cardiomyopathy (DCM) from physiological left ventricular (LV) dilatation with LV ejection fraction 11% from baseline to peak exercise compared with 23% of patients with DCM (p63% in 92% grey-zone athletes compared with 17% patients with DCM (p11% from baseline to peak exercise or achieve a peak LV ejection fraction >63% had sensitivity of 77% and 83%, respectively, and specificity of 96% and 92%, respectively, for predicting DCM. CONCLUSION: Comprehensive assessment using a cascade of routine investigations revealed that exercise stress echocardiography has the greatest discriminatory value in differentiating between grey-zone athletes and asymptomatic patients with DCM. Our findings require validation in larger studies

Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.

Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease

Abnormal septal convexity into the left ventricle occurs in subclinical hypertrophic cardiomyopathy.

BACKGROUND: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM. METHODS: Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point. RESULTS: Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m(2) vs. 23.7 ± 5.8 ml/m(2), p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls. CONCLUSIONS: Septal convexity is an additional previously undescribed feature of subclinical HCM

Prevalence and diagnostic significance of de-novo 12-lead ECG changes after COVID-19 infection in elite soccer players.

BACKGROUND AND AIM: The efficacy of pre-COVID-19 and post-COVID-19 infection 12-lead ECGs for identifying athletes with myopericarditis has never been reported. We aimed to assess the prevalence and significance of de-novo ECG changes following COVID-19 infection. METHODS: In this multicentre observational study, between March 2020 and May 2022, we evaluated consecutive athletes with COVID-19 infection. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes. RESULTS: 511 soccer players (median age 21 years, IQR 18-26 years) were included. 17 (3%) athletes demonstrated de-novo ECG changes, which included reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7); and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed evidence of inflammatory cardiac sequelae. All 30 athletes who underwent a mandatory CMR scan had normal findings. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Among athletes without cardiac symptoms, the additional yield of de-novo ECG changes to detect cardiac inflammation was 20%. CONCLUSIONS: 3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with cardiac inflammation. Most affected athletes exhibited cardiac symptoms; however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms

Prevalence and diagnostic significance of de-novo 12-lead ECG changes after COVID-19 infection in elite soccer players.

Background and aim: The efficacy of pre-COVID-19 and post-COVID-19 infection 12-lead ECGs for identifying athletes with myopericarditis has never been reported. We aimed to assess the prevalence and significance of de-novo ECG changes following COVID-19 infection. Methods: In this multicentre observational study, between March 2020 and May 2022, we evaluated consecutive athletes with COVID-19 infection. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes. Results: 511 soccer players (median age 21 years, IQR 18-26 years) were included. 17 (3%) athletes demonstrated de-novo ECG changes, which included reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7); and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed evidence of inflammatory cardiac sequelae. All 30 athletes who underwent a mandatory CMR scan had normal findings. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Among athletes without cardiac symptoms, the additional yield of de-novo ECG changes to detect cardiac inflammation was 20%. Conclusions: 3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with cardiac inflammation. Most affected athletes exhibited cardiac symptoms; however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms

Dynamic electrocardiographic changes in patients with arrhythmogenic right ventricular cardiomyopathy

Background and objectives Electrocardiographic (ECG) abnormalities of depolarisation and repolarisation contribute to the diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC). The development of diagnostic ECG features were investigated in a genotyped cohort with ARVC to provide more sensitive markers of early disease. Methods T-wave inversion (TWI) in right precordial leads, epsilon waves, localised QRS prolongation greater than 110 ms in V1-V3 and QRS dispersion greater than 40 ms were analysed from 317 ECG from 68 genotyped patients (34 with disease-causing mutations) during follow-up of 34628 months. Results 16 patients (23%) had changes during followup, with the appearance of new ECG abnormalities in seven (10%) and dynamic changes in nine (13%). Four developed new and persistent TWI and eight had dynamic TWI in right precordial leads. Three developed new and another three had dynamic epsilon waves. No changes were observed in 10 with and 58 patients without localised QRS prolongation and in six patients with and 61 without QRS dispersion greater than 40 ms. An additional patient with QRS dispersion at baseline had normal depolarisation dispersion during follow-up. None of the nine ARVC patients with dynamic ECG changes had major structural or functional right ventricular abnormalities, suggesting an early stage of the disease. Conclusions New or dynamic ECG changes were observed in 23%. This underscores the importance of serial ECG in the diagnosis of individuals at risk of ARVC, in whom potentially lethal arrhythmia may develop before major abnormalities are detectable with conventional imaging

Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy

OBJECTIVE: To determine the range of survival rates of patients with hypertrophic cardiomyopathy (HCM) by comparing and contrasting the natural history of a cohort of patients seen between 1988 and 2002 with that of other published series. METHODS: 956 adult (⩾ 16 years old) patients with HCM (572 men, mean (SD) age 42 (15) years, range 16–88) were evaluated by ECG, Holter, exercise testing, and echocardiography. Patient characteristics and survival data were compared with those in natural history studies from referral and non‐referral centres published between 1960 and January 2003. RESULTS: The duration of follow up was 69 (45) months. 120 (12.6%) patients died or underwent cardiac transplantation. Sudden cardiac death (n  =  48) was the most common mode of death. The annual rate of sudden death or implantable cardioverter‐defibrillator discharge was 1.02 (95% confidence interval (CI) 0.76 to 1.26). Annual rates for heart failure death or transplantation and stroke related death were 0.55% (95% CI 0.37% to 0.78%) and 0.07% (95% CI 0.02% to 0.19%), respectively. When studies published within the last 10 years of the study period were compared with earlier reports, the size of individual study cohorts was larger (309 (240.6) v 136.5 (98.8), p  =  0.058) and the proportion with severe functional limitation NYHA class III/IV lower (12.4% v 24.8%, p < 0.0001), and fewer patients underwent septal myotomy‐myectomy (5.2% v 18.7%, p < 0.0001). Published sudden death rates over the last 10 years were lower than previously published figures (median 1.0% (range 0.1–1.7) v 2.0% (0–3.5)). CONCLUSION: Published survival rates in HCM cohorts have improved progressively over the past 40 years. In the modern era the prevalence of disease related complications is similar in all reporting centres

Neutrophil MMP-8 and -9 are upregulated in human TB.

<p>(<b>A</b>) Neutrophils were infected with <i>M</i>.<i>tb</i> MOI of 1. MMP-8 secretion was upregulated at 4h. (<b>B</b>) Increasing <i>M</i>.<i>tb</i> MOI caused greater neutrophil MMP-8, analyzed at 4h. Bars represent mean ± s.d. of experiments performed in triplicate and data are representative of a minimum of 2 independent experiments. (<b>C and D</b>) Human TB lung biopsy specimens stained with H&E and anti-neutrophil elastase shows neutrophil infiltration around the cavity wall. Both scale bars represent 5 mm. n = 5. (<b>E and F</b>) Magnified H&E and MMP-8 stains from <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004917#ppat.1004917.g001" target="_blank">Fig 1C</a> inset shows neutrophils immunoreactive for MMP-8 around the cavity wall. Both scale bars represent 50 μm. (<b>G</b>) MMP-9 concentrations increase in a dose-dependent manner after <i>M</i>.<i>tb</i> infection at 4 hours. Bars represent mean ± s.d. of experiments performed in triplicate and data are representative of a minimum of 2 independent experiments. *** <i>P</i><0.001 (<b>H</b>) Biopsy proven <i>M</i>.<i>tb</i> infected human lung specimens were stained for MMP-9 (inset from <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004917#ppat.1004917.g001" target="_blank">Fig 1C</a>). Neutrophils were immunoreactive for MMP-9. Scale bar represents 50 μm. Statistical analysis was performed using two-way ANOVA with Bonferroni post-test or One-way ANOVA with Tukey’s post-test. **<i>P</i><0.01, ***<i>P</i><0.001.</p