Sex and the Risk of Atheromatous and Non-Atheromatous Cardiovascular Disease in CKD: Findings From the CKD-REIN Cohort Study.

RATIONALE & OBJECTIVE: Sex differences in cardiovascular disease (CVD) are well-established, but whether chronic kidney disease (CKD) modifies these risk differences, and whether they differ between atheromatous (ACVD) and non-atheromatous (N-ACVD) CVD is unknown. Assessing this interaction was the principal goal of this study. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Adults enrolled in the CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort from from 2013 to 2020, a nationally representative sample of 40 nephrology clinics in France. EXPOSURE: Sex. OUTCOMES: Fatal and non-fatal composite ACVD events (ischaemic coronary, cerebral, and peripheral artery disease) and composite N-ACVD events (heart failure, haemorrhagic stroke, and arrhythmias). ANALYTICAL APPROACH: Multivariable cause-specific Cox proportional hazards models. RESULTS: 1,044 women and 1,976 men with moderate to severe CKD (median age, 67 vs. 69; mean estimated glomerular filtration rate [eGFR], 32±12 vs. 33±12 mL/min/1.73m2) were studied. Over a median follow-up of 5.0 (interquartile range, 4.8;5.2) years, the ACVD rate (per 100 patient-years) was significantly lower in women than men: 2.1 (95% confidence interval: 1.6-2.5) vs 3.6 (3.2-4.0) (P<0.01), while the N-ACVD rate was not: 5.7 (5.0-6.5) vs 6.4 (5.8-7.0) (P=0.55). N-ACVD had a steeper relationship with eGFR than did ACVD. There was an interaction (P<0.01) between sex and baseline eGFR and the ACVD hazard: the adjusted hazard ratio for women compared to men was 0.42 (0.25;0.71) at 45 mL/min/1.73m2 and gradually attenuated at lower levels of eGFR, reaching 1.00 (0.62;1.63) at 16 mL/min/1.73m2. In contrast, the N-ACVD hazard did not differ between the sexes across the eGFR range studied. LIMITATIONS: Cardiovascular biomarkers and sex hormones were not assessed. CONCLUSION: This study shows how the lower risk of ACVD among women compared to men attenuates fully with kidney disease progression. The equal risk of N-ACVD between sexes across CKD stages and its steeper association with eGFR suggest an important contribution of CKD to the development of this CVD type.

Prevalence of prediabetes and undiagnosed diabetes in a large urban middle-aged population: the CARVAR 92 cohort.

BACKGROUND: The aim of this study was to assess the prevalence of prediabetes and unknown diabetes and its long-term change in a large middle-aged urban population. METHODS: We conducted a screening campaign between 2007 and 2018 for cardiovascular risk factors in the western suburbs of Paris including subjects aged 40-70 (CARVAR 92). Among subjects who reported no previous diabetes, prediabetes and undiagnosed diabetes were defined as follows: fasting plasma glucose (FPG) ≥ 6.1 mmol/l (110 mg/dl) and < 7 mmol/l (126 mg/dl) for prediabetes according to WHO criteria (FPG between 5.6 and 6.9 mmol/l according to ADA criteria) and FPG ≥ 7.0 mmol/l for undiagnosed diabetes. RESULTS: Of the 32,721 subjects in the CARVAR 92 cohort, 32,675 were included in this analysis. The median age of the patients was 56 years [30, 94], 45.4% were male, 5.9% had known diabetes, 36.4% were overweight and 18.7% obese. Among patients without previously known diabetes (n = 30,759), 8.1% had prediabetes according to WHO criteria (27.2% according to ADA criteria) and 2.3% had diabetes. Subjects with prediabetes and unknown diabetes were more likely to be male, older, and overweight or obese than non-diabetic subjects. From 2007 to 2018, the prevalence of prediabetes, unknown diabetes, and known diabetes decreased, except for prediabetes which remained stable for people aged 55-64. CONCLUSION: The prevalence of prediabetes and unknown diabetes remains high but decreased during a 12-year period. About one-quarter of diabetes cases remain undiagnosed. Our results highlight that there is still a room for screening and cardiovascular prevention campaigns. TRIAL REGISTRATION: IRB00012437.

Determinants of diaphragm inspiratory motion, diaphragm thickening, and its performance for predicting respiratory restrictive pattern in Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Respiratory status is a key determinant of prognosis in patients with Duchenne muscular dystrophy (DMD). We aimed to evaluate the determinants of diaphragm ultrasound and its performance in predicting restrictive respiratory patterns in DMD. METHODS: This was a retrospective study of DMD patients followed in our center and admitted for an annual checkup from 2015 to 2018. We included DMD patients who underwent diaphragm ultrasound and pulmonary functional tests. RESULTS: This study included 74 patients with DMD. The right diaphragm thickening fraction (TF) was significantly associated with age (P = .001), Walton score (P = .012), inspiratory capacity (IC) (P = .004), upright forced vital capacity (FVC) (P < .0001), supine FVC (P = .038), and maximal inspiratory pressure (MIP) (P = .002). Right diaphragm excursion was significantly associated with age (P < .0001), steroid use (P = .008), history of spinal fusion (P < .0001), body mass index (BMI) (P = .002), Walton score (P < .0001), IC (P < .0001), upright FVC (P < .0001), supine FVC (P < .0001), and MIP (P < .0001). A right diaphragm TF >28% and a right diaphragm excursion>25.4 mm were associated with an FVC >50% with, respectively, an area under the curve (AUC) of 0.95 (P = .001) and 0.93 (P < .001). A left diaphragm TF >26.8% and a left diaphragm excursion >21.5 mm were associated with an FVC >50% with, respectively, an AUC of 0.95 (P = .011) and 0.97 (P < .001). DISCUSSION: Diaphragm excursion and diaphragm TF can predict restrictive pulmonary insufficiency in DMD.

Urea levels and cardiovascular disease in patients with chronic kidney disease.

BACKGROUND: Elevated serum urea levels are common in moderate-to-advanced CKD. Several studies have shown that urea is a direct and indirect uremic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. METHODS: CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 < 10.5, T2:10.5 to 15.1, and T3 ≥ 15.1 mmol/L). Cox proportional hazard models were used to estimate hazard ratios (HRs) for first atheromatous or nonatheromatous cardiovascular (CV) events, and all-cause mortality before RRT. The models were adjusted for baseline comorbidities, laboratory data, and medications. FINDINGS: Of the 2507 included patients (median [interquartile range (IQR)] age: 69[61-77]; mean (standard deviation) eGFR 33.5(11.6) mL/min/1.73 m²), 54% had a history of cardiovascular disease. After multiple adjustments for cardiovascular risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and nonatheromatous cardiovascular events than patient in T1 (n events = 451, HR[95%CI]: 1.93[1.39-2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31[0.97; 1.76] and 1.73[1.22; 2.45] for patients T2 and those in T3, respectively. INTERPRETATION: Our data suggested that urea is a predictor of cardiovascular outcomes beyond CV risk factors including eGFR.

Relevance of Cardiovascular Risk Factors Screening in People Aged over 65 Years: Results from a Large French Urban Population (The CARVAR92 Study).

BACKGROUND: Cardiovascular disease is the leading cause of death and disability in older people. Traditional cardiovascular risk factors (CVRFs) still have an impact on cardiovascular risk among older people. Nevertheless, screening campaigns rarely target subjects aged over 65 years. This study aimed to assess the distribution and relevance of conventional CVRF screening in people aged over 65 years. METHODS: Between 2007 and 2018, among a screening CVRF campaign in the western suburbs of Paris (32,692 subjects), we individualized 6,577 subjects aged 65 years and over. All conventional CVRFs have been systematically assessed. RESULTS: The screening allowed to suspect hypertension in a larger proportion of subjects over 65 years compared to subjects under 65 years (27% vs. 18%, p < 0.0001). Hypertension control was higher in women compared to men but not significantly different in the age-groups (p = 0.91). Screening for diabetes mellitus was positive in 3% of older subjects and 2.4% in younger (p = 0.005). Risk assessment with dedicated score (SCORE O.P.) allowed to move toward a low-risk estimation, resulting in the diminution of intermediate risk group in women over 65 years (from 68 to 61%, p < 0.001). CONCLUSIONS: Screening CVRFs especially hypertension remains relevant in people aged over 65 years as it enables to detect unknown CVRFs in numerous subjects. Increasing awareness of CVRFs may be the first step to CVRF control, which is known to be efficient on cardiovascular mortality and functional autonomy in later life.

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia.

BACKGROUND: Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS: The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS: Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS: Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

Phenotype/Genotype Relationship in Left Ventricular Noncompaction: Ion Channel Gene Mutations Are Associated With Preserved Left Ventricular Systolic Function and Biventricular Noncompaction: Phenotype/Genotype of Noncompaction.

BACKGROUND: Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC). METHODS AND RESULTS: From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate. CONCLUSIONS: Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC.

Occurrence of pulmonary embolism related to COVID-19.

Recent reports have suggested an increased risk of pulmonary embolism (PE) related to COVID-19. The aim of this cohort study is to compare the incidence of PE during a 3-year period and to assess the characteristics of PE in COVID-19. We studied consecutive patients presenting with PE (January 2017-April 2020). Clinical presentation, computed tomography (CT) and biological markers were systematically assessed. We recorded the global number of hospitalizations during the COVID-19 pandemic and during the same period in 2018-2019. We included 347 patients: 326 without COVID-19 and 21 with COVID-19. Patients with COVID-19 experienced more likely dyspnea (p=0.04), had lower arterial oxygen saturation (p<0.001), higher C-reactive protein and white blood cell (WBC) count (p<0.0001 and p=0.001, respectively), and a significantly higher in-hospital mortality (14% versus 3.4%, p=0.04). Among COVID-19 patients, diagnosis of PE was performed at admission in 38% (n=8). COVID-19 patients with diagnosis of PE during hospitalization (n=13) had significantly more dyspnea (p=0.04), lower arterial oxygen saturation (p=0.01), less proximal PE (p=0.02), and higher heart rate (p=0.009), CT severity score (p=0.001), C-reactive protein (p=0.006) and WBC count (p=0.04). During the COVID-19 outbreak, a 97.4% increase of PE incidence was observed as compared to 2017-2019 and the proportion of hospitalizations related to PE was 3.7% versus 1.3% in 2018-2019 (p<0.0001). In conclusion, the COVID-19 pandemic leads to a dramatic increased incidence of PE. Physicians should be aware that PE may be diagnosed at admission, but also after several days of hospitalization, with a different clinical, CT and biological features of thrombotic disease.

Impact of Coronavirus Disease 2019 outbreak on acute coronary syndrome admissions: four weeks to reverse the trend.

Data whether the COVID-19 outbreak impacts the acute coronary syndromes (ACS) admissions and the time required to reverse the downward curve are scarce. We included all consecutive patients referred for an ACS who underwent PCI from February 17, 2020 to April 26, 2020 in a high-volume PCI coronary care unit. We compared the number of ACS patients in 2020 to the same period in 2018 and 2019. Predictors of adverse outcome in ST-elevation myocardial infarction (STEMI) patients were recorded: symptom-onset-to-first medical contact (FMC), and FMC-to-sheath insertion times. During the studied period (calendar weeks 8-17, 2018-2020), 144 ACS patients were included. In 2020, we observed two distinct phases in the ACS admissions: a first significant fall, with a relative reduction of 73%, from the week of lockdown (week 12) to 3 weeks later and then an increase of ACS. Median symptom-onset-to-FMC time was significantly higher in 2020 than in the two previous years (600 min [298-632] versus 121 min [55-291], p < 0.001). Median FMC-to-sheath insertion did not differ significantly (93 min [81-131] in 2020 versus 90 min [67-137] in 2018-2019, p = 0.57). The main findings are (1) a pattern of a U-curve in ACS admissions, with a first decrease in ACS admissions and a return to "normality" 4 weeks after; (2) a significant increase in the total ischemic time exclusively due to an increase in the symptom-onset-to-first-medical-contact time.

Assessment of atrial function by myocardial deformation techniques in hypertrophic cardiomyopathy.

BACKGROUND: Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is common, but its assessment is difficult using conventional echocardiography. AIMS: To assess left atrial (LA) function in HCM by longitudinal strain and determine its role in understanding of symptoms. METHODS: We studied 144 patients divided into 3 age- and sex-matched groups: 48 consecutive patients with HCM, 48 control subjects, and 48 athlete subjects. We assessed LA function by conventional echocardiographic parameters and by longitudinal atrial strain (early-diastolic left atrial strain during reservoir phase [LASr]; end-diastolic left atrial strain during conduit phase; end-systolic peak of the left atrial strain during contraction phase). RESULTS: NYHA classification was as follows in HCM group: I in 46%, II in 31%, III in 19%, and IV in 4%. Conventional echocardiographic parameters of diastolic function were depressed in the HCM group as compared to the control and athlete groups, but not related to symptoms. All longitudinal atrial strain parameters were significantly reduced in HCM group as compared to two groups (P < .0001). LASr was significantly correlated to peak VO2 (r = 0.44, P = .01) and was the best parameter for detecting symptomatic patients presenting with HCM, with a cutoff value of 15%: Sensitivity was 71%, specificity was 79%, PPV was 77%, and NPV was 73%. CONCLUSION: Assessment of LA function in HCM is feasible using longitudinal strain, and this technique is more reliable than conventional echocardiographic parameters for the understanding of determinants of symptoms.

Prevalence of atheromatous and non-atheromatous cardiovascular disease by age in chronic kidney disease.

BACKGROUND: Although chronic kidney disease (CKD) and age are major risk factors for cardiovascular disease (CVD), little is known about the relative proportions of atheromatous and non-atheromatous CVD by age in CKD patients. METHODS: We used baseline data from the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort of 3033 patients (65% men) with CKD Stages 3-4 to study crude and adjusted associations between age, the estimated glomerular filtration rate (eGFR), atheromatous CVD (coronary artery disease, peripheral artery disease and stroke) and non-atheromatous CVD (heart failure, cardiac arrhythmia and valvular heart disease). RESULTS: Mean age was 66.8 and mean Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR was 32.9 mL/min/1.73 m2. In the <65, (65-74), (75-84) and ≥85 year age groups, the prevalence was, respectively, 18.7, 35.5, 42.9 and 37.8% for atheromatous CVD, and 14.9, 28.4, 38.1 and 56.4% for non-atheromatous CVD. After adjusting for albuminuria, sex and CVD risk factors, the odds ratio (OR) [95% confidence interval (CI)] for (65-74), (75-84) and ≥85 age groups (compared with the <65 group) was, respectively, 1.99 (1.61-2.46), 2.89 (2.30-3.62), 2.72 (1.77-4.18) for atheromatous CVD and 2.07 (1.66-2.58), 3.15 (2.50-3.97), 7.04 (4.67-10.61) for non-atheromatous CVD. Compared with patients with an eGFR ≥30 mL/min/1.73 m2, those with an eGFR <30 mL/min/1.73 m2 had a higher OR for atheromatous CVD [1.21 (1.01-1.44)] and non-atheromatous CVD [1.16 (0.97-1.38)]. CONCLUSIONS: In this large cohort of CKD patients, both atheromatous and non-atheromatous CVD were highly prevalent and more frequent in older patients. In a given age group, the prevalence of atheromatous and non-atheromatous CVD was similar (except for a greater prevalence of non-atheromatous CVD after 85).

Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity.

Left ventricular non-compaction (LVNC) is a cardiomyopathy that may be of genetic origin; however, few data are available about the yield of mutation, the spectrum of genes and allelic variations. The aim of this study was to better characterize the genetic spectrum of isolated LVNC in a prospective cohort of 95 unrelated adult patients through the molecular investigation of 107 genes involved in cardiomyopathies and arrhythmias. Fifty-two pathogenic or probably pathogenic variants were identified in 40 patients (42%) including 31 patients (32.5%) with single variant and 9 patients with complex genotypes (9.5%). Mutated patients tended to have younger age at diagnosis than patients with no identified mutation. The most prevalent genes were TTN, then HCN4, MYH7, and RYR2. The distribution includes 13 genes previously reported in LVNC and 10 additional candidate genes. Our results show that LVNC is basically a genetic disease and support genetic counseling and cardiac screening in relatives. There is a large genetic heterogeneity, with predominant TTN null mutations and frequent complex genotypes. The gene spectrum is close to the one observed in dilated cardiomyopathy but with specific genes such as HCN4. We also identified new candidate genes that could be involved in this sub-phenotype of cardiomyopathy.

Reliability of contrast echocardiography to rule out pulmonary arteriovenous malformations and avoid CT irradiation in pediatric patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: The overall risk of cancer is higher in people exposed to computed tomography (CT) scans in childhood or adolescence compared to adults. Transthoracic contrast echocardiography (TTCE) has recently been used to screen for pulmonary arteriovenous malformations (PAVMs) in children with hereditary hemorrhagic telangiectasia (HHT), but the value of TTCE to rule out PAVMs and avoid chest CT radiation has yet to be discussed. METHODS: Between 2003 and 2013, 92 pediatric patients with ≥3 Curaçao criteria and/or genetic mutation underwent TTCE and chest CT on the same day. We used the classification proposed by Barzilai for TTCE quantification of shunting. We considered CT findings as negative when no PAVMs or only one microscopic PAVM was detected. RESULTS: Mean age was 11.2 ± 4.1 years. The shunt was grade 0 on TTCE in 27.3%, grade 1 in 17%, grade 2 in 29.6%, grade 3 in 23.9%, and grade 4 in 2.2%. We found PAVMs on chest CT in 52.2%. All the patients with a grade 0 or 1 had a negative CT. The sensitivity and specificity of TTCE for the detection of PAVMs were 100% and 95.1%, respectively. The negative predictive value (NPV) was 100% and the positive predictive value (PPV) was 96%. CONCLUSIONS: A low-grade classification (Barzilai 0 or 1) could presumably exclude the presence of PAVMs and allow CT irradiation to be avoided in children and adolescents. The screening algorithm using TTCE first would allow more than 40% of the pediatric patients screened for PAVMs to be spared the radiation dose of CT.

Ionized and total magnesium levels in patients with chronic kidney disease: associated factors and outcomes.

Background: The association between hypo- and/or hypermagnesaemia and cardiovascular (CV) outcomes or mortality has shown conflicting results in chronic kidney disease (CKD) and has been conducted on total magnesium (tMg) levels. Thus, the objectives of the present study were to (i) describe the serum ionized Mg (iMg) concentration in patients at various CKD stages, (ii) measure the correlation between iMg and tMg concentrations, (iii) identify their associated factors and (iv) determine whether serum tMg and/or iMg concentrations are associated with major adverse cardiovascular events (MACE) and mortality before kidney replacement therapy in CKD patients. Methods: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort of CKD patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Baseline iMg and tMg serum concentrations were centrally measured. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) for first MACE and for mortality. Results: Of the 2419 included patients, median age was 68 years, and the mean eGFR was 34.8 mL/min/1.73 m2. Concentrations of serum iMg and tMg were strongly correlated (r = 0.89, P < .001) and were independently associated with eGFR. The adjusted HR [95% confidence interval (CI)] for MACE associated with the baseline serum tMg level was 1.27 (0.95; 1.69) for patients in Tertile 1 and 1.56 (1.18; 2.06) for patients in Tertile 3, relative to patients in Tertile 2. The HR (95% CI) of death according to serum tMg concentration was increased in Tertile 3 [1.48 (1.11; 1.97)]. The adjusted risk for MACE and mortality (all-cause or CV) associated with the baseline serum iMg level was not significantly different between tertiles. Conclusions: Our analysis of a large cohort of patients with moderate-to-advanced CKD demonstrated that individuals with higher serum tMg concentrations, although still within the normal range, had a greater likelihood of MACE and mortality. However, serum iMg levels were not associated with these outcomes.

In-hospital Prognostic Value of TAPSE/sPAP in Patients Hospitalized for Acute Heart Failure.

AIMS: TAPSE/sPAP (tricuspid annular plane systolic excursion over systolic pulmonary artery pressure) assessed by echocardiography appears to be a good noninvasive approach for right ventricular to pulmonary artery coupling assessment. We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for acute heart failure (AHF). METHODS AND RESULTS: 333 consecutive patients (mean age 68 ± 14 years, 70% of male, mean LVEF 44 ± 16%) hospitalized for AHF across 39 French cardiology department, with TAPSE/sPAP measured by echocardiography within the 24 first hours of hospitalization were included in this prospective study. The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 50 (15%) patients. Using receiver operating characteristics curves analysis, the best TAPSE/sPAP threshold for in-hospital MACEs was 0.40 mm/mmHg. TAPSE/sPAP <0.40 mm/mmHg was independently associated with in-hospital MACEs, even after adjustment with comorbidities (OR:3.75, 95%CI[1.87-7.93], p < 0.001), clinical severity (OR:2.80, 95%CI[1.36-5.95], p = 0.006). Using a 1:1 propensity-matched population, TAPSE/sPAP ratio <0.40 was associated with a higher rate of in-hospital MACEs (OR:2.98, 95%CI[1.53-6.12], p = 0.002). After adjustment, TAPSE/sPAP <0.40 showed the best improvement in model discrimination and reclassification above traditional prognostic factors (C-statistic improvement: 0.05; Chi-2 improvement: 14.4; LR-test p < 0.001). These results were consistent in an external validation cohort of 133 patients. CONCLUSION: TAPSE/sPAP < 0.40 mm/mmHg assessed by an early echocardiography during an AHF episode is independently associated with in-hospital MACEs suggesting enhanced close monitoring and strengthened HF-specific care in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

Prognosis of Right Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy.

Background Chronic respiratory failure and heart involvement may occur in Duchenne muscular dystrophy. We aimed to assess the prognostic value of the right ventricular (RV) systolic dysfunction in patients with Duchenne muscular dystrophy. Methods and Results We studied 90 genetically proven patients with Duchenne muscular dystrophy from 2010 to 2019, to obtain respiratory function and Doppler echocardiographic RV systolic function. Prognostic value was assessed in terms of death and cardiac events. The median age was 27.5 years, and median forced vital capacity was at 10% of the predicted value: 83 patients (92%) were on home mechanical ventilation. An RV systolic dysfunction was found in 46 patients (51%). In patients without RV dysfunction at inclusion, a left ventricular systolic dysfunction at inclusion was associated with a higher risk of developing RV dysfunction during follow-up with an odds ratio of 4.5 (P=0.03). RV systolic dysfunction was significantly associated with cardiac events, mainly acute heart failure (62%) and cardiogenic shock (23%). In a multivariable Cox model, the adjusted hazard ratio was 4.96 (95% CI [1.09-22.6]; P=0.04). In terms of death, we found a significant difference between patients with RV dysfunction versus patients without RV dysfunction in the Kaplan-Meier curves (log-rank P=0.045). Conclusions RV systolic dysfunction is frequently present in patients with Duchenne muscular dystrophy and is associated with increased risk of cardiac events, irrespective of left ventricular dysfunction and mechanical ventilation. Registration URL: https://www.clinicaltrials.org; unique identifier: NCT02501083.

Effectiveness of Simulation-Based Training on Transesophageal Echocardiography Learning: The SIMULATOR Randomized Clinical Trial.

Importance: Evidence is scarce on the effectiveness of simulation-based training in transesophageal echocardiography (TEE). Objective: To assess the effectiveness of simulation-based teaching vs traditional teaching of TEE knowledge and skills of cardiology fellows. Design, Setting, and Participants: Between November 2020 and November 2021, all consecutive cardiology fellows inexperienced in TEE from 42 French university centers were randomized (1:1; n = 324) into 2 groups with or without simulation support. Main Outcomes and Measures: The co-primary outcomes were the scores in the final theoretical and practical tests 3 months after the training. TEE duration and the fellows' self-assessment of their proficiency were also assessed. Results: While the theoretical and practical test scores were similar between the 2 groups (324 participants; 62.6% male; mean age, 26.4 years) before the training (33.0 [SD, 16.3] points vs 32.5 [SD, 18.5] points; P = .80 and 44.2 [SD, 25.5] points vs 46.1 [SD, 26.1] points; P = .51, respectively), the fellows in the simulation group (n = 162; 50%) displayed higher theoretical test and practical test scores after the training than those in the traditional group (n = 162; 50%) (47.2% [SD, 15.6%] vs 38.3% [SD, 19.8%]; P < .001 and 74.5% [SD, 17.7%] vs 59.0% [SD, 25.1%]; P < .001, respectively). Subgroup analyses showed that the effectiveness of the simulation training was even greater when performed at the beginning of the fellowship (ie, 2 years or less of training) (theoretical test: an increase of 11.9 points; 95% CI, 7.2-16.7 vs an increase of 4.25 points; 95% CI, -1.05 to 9.5; P = .03; practical test: an increase of 24.9 points; 95% CI, 18.5-31.0 vs an increase of 10.1 points; 95% CI, 3.9-16.0; P < .001). After the training, the duration to perform a complete TEE was significantly lower in the simulation group than in the traditional group ( 8.3 [SD, 1.4] minutes vs 9.4 [SD, 1.2] minutes; P < .001, respectively). Additionally, fellows in the simulation group felt more ready and more confident about performing a TEE alone after the training (mean score, 3.0; 95% CI, 2.9-3.2 vs mean score, 1.7; 95% CI, 1.4-1.9; P < .001 and mean score, 3.3; 95% CI, 3.1-3.5 vs mean score, 2.4; 95% CI, 2.1-2.6; P < .001, respectively). Conclusions and Relevance: Simulation-based teaching of TEE showed a significant improvement in the knowledge, skills, and self-assessment of proficiency of cardiology fellows, as well as a reduction in the amount of time needed to complete the examination. These results should encourage further investigation of clinical performance and patient benefits of TEE simulation training.

Relationship between Exercise Intensity and IL-6 Increase during an 80 km Long-Distance Running Race.

Background: IL-6 plasma concentration (IL-6PC) reflects the systemic inflammation related to exercise intensity level. This study aims to describe the IL-6PC kinetics during a long-distance running race. IL-6PC was measured in 20 male runners before (0 km), at each refreshment point (at 21 and 53 km, i.e., k21 and k53, respectively) and at the end of an 80 km long-distance run (k80). Methods: IL-6PC variations (absolute and relative values in each of the three sections (S)) were calculated over S1 (0_k21), S2 (k21_k53) and S3 (k53_k80) and compared with the exercise intensity (duration*race speed) within each section. Results: The mean IL-6PC increased during the run: 2.1 ± 0.6 ng.L-1 at 0 km, 21.0 ± 11.3 ng.L-1 at k21, 38.9 ± 13.0 ng.L-1 at k53 and 49.8 ± 11.9 ng.L-1 at k80. Exercise intensity increased between S1 (24.2 ± 0.5) and S2 (51.9 ± 3.2) (p = 0.04) but not between S2 and S3 (67.4 ± 4.5) (p = 0.69). IL-6PC variation was associated with exercise intensity within S1 (p = 0.03) and S2 (p = 2 × 10-3) and showed at least a trend within S3 (p = 0.06). Conclusions: IL-6PC increases that occur during the early stages of a long-distance run are associated with the running intensity, and then IL-6PC remain stable after the reduction in intensity related to the decrease in running speed.

High parasternal intercostal muscle thickening prior to intubation in COVID-19 infection.

Acute hypoxemic respiratory failure (AHRF) is a major complication of COVID-19 pneumonia and parasternal intercostal muscle thickening may be used as a biomarker to assess inspiratory effort. We report the case of a high utilization of parasternal intercostal muscle prior to the introduction of invasive ventilation in a 66-year old male none vaccinated COVID -19 patient admitted in hospital because of AHRF.