Novel Cardiokine GDF3 Predicts Adverse Fibrotic Remodeling After Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery by promoting the development of noncontractile fibrotic areas. The mechanisms that lead to cardiac fibrosis are diverse and incompletely characterized. We explored whether the expansion of cardiac fibroblasts after MI can be regulated through a paracrine action of cardiac stromal cells. METHODS: We performed a bioinformatic secretome analysis of cardiac stromal PW1+ cells isolated from normal and post-MI mouse hearts to identify novel secreted proteins. Functional assays were used to screen secreted proteins that promote fibroblast proliferation. The expressions of candidates were subsequently analyzed in mouse and human hearts and plasmas. The relationship between levels of circulating protein candidates and adverse post-MI cardiac remodeling was examined in a cohort of 80 patients with a first ST-segment-elevation MI and serial cardiac magnetic resonance imaging evaluations. RESULTS: Cardiac stromal PW1+ cells undergo a change in paracrine behavior after MI, and the conditioned media from these cells induced a significant increase in the proliferation of fibroblasts. We identified a total of 12 candidates as secreted proteins overexpressed by cardiac PW1+ cells after MI. Among these factors, GDF3 (growth differentiation factor 3), a member of the TGF-ß (transforming growth factor-ß) family, was markedly upregulated in the ischemic hearts. Conditioned media specifically enriched with GDF3 induced fibroblast proliferation at a high level by stimulation of activin-receptor-like kinases. In line with the secretory nature of this protein, we next found that GDF3 can be detected in mice and human plasma samples, with a significant increase in the days after MI. In humans, higher GDF3 circulating levels (measured in the plasma at day 4 after MI) were significantly associated with an increased risk of adverse remodeling 6 months after MI (adjusted odds ratio, 1.76 [1.03-3.00]; P=0.037), including lower left ventricular ejection fraction and a higher proportion of akinetic segments. CONCLUSIONS: Our findings define a mechanism for the profibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling after MI. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01113268.

Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort.

OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.

Predictive factors of glomerular filtration rate loss associated with living kidney donation: a single-center retrospective study.

PURPOSE: Living kidney donors (LKD) partially compensate the initial loss of glomerular filtration rate (GFR), a phenomenon known as renal functional reserve (RFR). RFR is reduced in the elderly, a population with increased prevalence of chronic kidney disease. We hypothesized that the selected, healthy population of LKD, would specifically inform about the physiological determinants of the RFR and studied it using measured GFR (mGFR). METHODS: We retrospectively analyzed pre-donation and post-donation mGFR in 76 LKD from Tenon Hospital (Paris, France) between 2002 and 2018. In addition to GFR measurements, we collected pre-donation morphologic parameters, demographic data, and kidney volumes. RESULTS: Mean pre-donation mGFR was 90.11 ± 12.64 mL/min/1.73 m2 and decreased to 61.26 ± 9.57 mL/min/1.73 m2 1 year after donation. Pre-donation mGFR correlated with age (p = 0.0003), total kidney volume (p = 0.0004) and pre-donation serum creatinine (p = 0.0453). Pre-donation mGFR strongly predicted 1-year post-donation mGFR. Mean RFR (increase in GFR of the remnant kidney between pre-donation and post-donation) was 36.67 ± 16.67% 1 year after donation. In the multivariate linear model, RFR was negatively correlated to total kidney volume (p = 0.02) but not with age or pre-donation serum creatinine. CONCLUSIONS: We found that pre-donation mGFR decreases with age and identified low total kidney volume as a predictor of RFR in healthy individuals. This suggests an adaptative and reversible decrease in kidney function rather than age-related damage. Older subjects may have reduced metabolic requirements with subsequent reduction in glomerular filtration and kidney volume and preserved RFR. Therefore, low GFR in older subjects should not preclude kidney donation.

Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various causes that may influence prognosis. METHODS AND RESULTS: We extracted the electronic medical records for 2180 consecutive patients hospitalized between 2016 and 2019 for decompensated heart failure. Using a text mining algorithm looking for a left ventricular ejection fraction ≥50% and plasma brain natriuretic peptide level >100 pg/mL, we identified 928 HFpEF patients. We screened for a prevailing cause of HFpEF according to European guidelines and found that 418 (45.0%) patients had secondary HFpEF due to either myocardial (n = 125, 13.5%) or loading condition abnormalities (n = 293, 31.5%), while the remaining 510 (55.0%) patients had idiopathic HFpEF. We assessed the association between the causes of HFpEF and survival collected up to 31 December 2020 using Cox proportional hazards analysis. Even though patients with idiopathic HFpEF were older, frequently female, and had frequent co-morbidities and a higher crude mortality rate compared with secondary HFpEF patients, their prognosis was similar after adjustment for age and sex. Unsupervised clustering analysis revealed three main phenogroups with different distribution of idiopathic vs. secondary HFpEF. The phenogroup with the highest proportion of idiopathic HFpEF (69%) had (i) an excess rate of non-cardiac co-morbidities including chronic obstructive pulmonary disease (31%) or obesity (41%) and (ii) a better prognosis compared with the two other phenogroups enriched with secondary HFpEF. CONCLUSIONS: Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF.

Drug-Related Hypercalcemia.

This review focuses on the commonly prescribed medicaments that can be responsible for hypercalcemia, considering the prevalence, the predominant pathophysiological mechanisms, and the optimal medical management of each drug-induced hypercalcemia. Vitamin D supplements and 1α-hydroxylated vitamin D analogues increase intestinal calcium absorption, renal calcium reabsorption as well as bone resorption. In patients with hypoparathyroidism receiving recombinant human PTH, transient hypercalcemia can occur because of overtreatment, usually during acute illness. Thiazide-induced hypercalcemia is mainly explained by enhanced renal proximal calcium reabsorption, changing preexistent asymptomatic normocalcemic or intermittently hypercalcemic hyperparathyroidism into the classic hypercalcemic hyperparathyroidism. Lithium causes hypercalcemia mainly by drug-induced hyperparathyroidism.

Cardiometabolic Disorders and the Risk of Critical COVID-19 as Compared to Influenza Pneumonia.

We aimed to compare the influence of cardiometabolic disorders on the incidence of severe COVID-19 vs. non-COVID pneumonia. We included all consecutive patients admitted with SARS-CoV-2-positive pneumonia between 12 March 2020 and 1 April 2020 and compared them to patients with influenza pneumonia hospitalized between December 2017 and December 2019 at the same tertiary hospital in Paris. Patients with COVID-19 were significantly younger and more frequently male. In the analysis adjusted for age and sex, patients with COVID-19 were more likely to be obese (adjOR: 2.25; 95% CI 1.24-4.09; p = 0.0076) and receive diuretics (adjOR: 2.13; 95% CI 1.12-4.03; p = 0.021) but were less likely to be smokers (adjOR: 0.40; 95% CI 0.24-0.64; p = 0.0002), have COPD (adjOR: 0.25; 95% CI 0.11-0.56; p = 0.0008), or have a previous or active cancer diagnosis (adjOR: 0.54, 95% CI 0.32-0.91; p = 0.020). The rate of ICU admission was significantly higher in patients with COVID-19 (32.4% vs. 5.2% p < 0.0001). Obesity was significantly associated with the risk of direct ICU admission in patients with COVID-19 but not in patients with influenza pneumonia. Likewise, pre-existing hypertension was significantly associated with mortality in patients with COVID-19 but not in patients with influenza pneumonia. Cardiometabolic disorders differentially influenced the risk of presenting with severe COVID-19 or influenza pneumonia.

Immune Signature Linked to COVID-19 Severity: A SARS-Score for Personalized Medicine.

SARS-CoV-2 infection leads to a highly variable clinical evolution, ranging from asymptomatic to severe disease with acute respiratory distress syndrome, requiring intensive care units (ICU) admission. The optimal management of hospitalized patients has become a worldwide concern and identification of immune biomarkers predictive of the clinical outcome for hospitalized patients remains a major challenge. Immunophenotyping and transcriptomic analysis of hospitalized COVID-19 patients at admission allow identifying the two categories of patients. Inflammation, high neutrophil activation, dysfunctional monocytic response and a strongly impaired adaptive immune response was observed in patients who will experience the more severe form of the disease. This observation was validated in an independent cohort of patients. Using in silico analysis on drug signature database, we identify differential therapeutics that specifically correspond to each group of patients. From this signature, we propose a score-the SARS-Score-composed of easily quantifiable biomarkers, to classify hospitalized patients upon arrival to adapt treatment according to their immune profile.

Association between coronary artery calcifications and 6-month mortality in hospitalized patients with COVID-19.

PURPOSE: The purpose of this study was to evaluate the association between coronary artery calcium (CAC) visual score and 6-month mortality in patients with coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: A single-center prospective observational cohort was conducted in 169 COVID-19 consecutive hospitalized patients between March 13 and April 1, 2020, and follow-up for 6-months. A four-level visual CAC scoring was assessed by analyzing images obtained after the first routine non-ECG-gated CT performed to detect COVID-19 pneumonia. RESULTS: Among 169 confirmed COVID-19 patients (118 men, 51 women; mean age, 65.6 ± 18.8 [SD] years; age range: 30-95 years) 63 (37%) presented with either moderate (n = 26, 15.3%) or heavy (n = 37, 21.8%) CAC detected by CT and 20 (11.8%) had history of cardiovascular disease requiring specific preventive treatment. At six months, mortality rate (45/169; 26.6%) increased with magnitude of CAC and was 7/64 (10.9%), 11/42 (26.2%), 10/26 (38.5%), 17/37 (45.9%) for no-CAC, mild-CAC, moderate-CAC and heavy-CAC groups, respectively (P = 0.001). Compared to the no CAC group, risk of death increased after adjustment with magnitude of CAC (HR: 2.23, 95% CI: 0.73-6.87, P = 0.16; HR: 2.78, 95% CI: 0.85-9.07, P0.09; HR: 5.38, 95% CI: 1.57-18.40, P = 0.007; in mild CAC, moderate and heavy CAC groups, respectively). In patients without previous coronary artery disease (154/169; 91%), mortality increased from 10.9% to 45.8% (P = 0.001) according to the magnitude of CAC categories. After adjustment, presence of moderate or heavy CAC was associated with higher mortality (HR: 2.26, 95% CI: 1.09-4.69, P = 0.03). CONCLUSION: By using non-ECG-gated CT during the initial pulmonary assessment of COVID-19, heavy CAC is independently associated with 6-month mortality in patients hospitalized for severe COVID-19 pneumonia.

Hemodynamic and biological correlates of glomerular hyperfiltration in sickle cell patients before and under renin-angiotensin system blocker.

Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (< 700 dynes/s/cm-5) in 38% of cases. mGFR association with CI and SVR were significant at baseline (respectively ρ: 0.44, p = 0.008 and ρ: - 0.37, p = 0.02) and under ACEI (p = 0.007 and 0.01 respectively), in accordance with previous data showing that hyperfiltration was linked to an increased glomerular perfusion and a glomerulomegaly rather than increased capillary hydrostatic pressure. Of notice, after adjustment on CI, mGFR remained associated with reticulocyte count and albuminuria under ACEI (p = 0.006 and 0.02 respectively). Our results suggest that hyperfiltration is tightly linked to an increased cardiac output which may account for an increased renal blood flow. Chronic hemolysis could be a relevant factor accounting for hyperfiltration potentially acting on glomerular enlargement which appears as a key factor. Our data suggest that cardiac output assessment is a relevant tool in the routine management and monitoring of SCA nephropathy.

Risk factors for CKD stage II onset in a prospective cohort of homozygous sickle cell adults.

Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients, and is responsible for a high morbidity and mortality. However, sickle cell nephropathy's natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using the Cox model. Five-hundred and thirty-five SCA patients were included with a median follow-up of 5.33 (IQR:2.10-8.13) years. Median age was 22 (IQR:19-30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 [95% CI: 1.61;9.43], diastolic blood pressure (DBP) above 70 mm Hg HR: 2.02 [1.02-3.971], LDH (for 100 IU/L increase) HR: 1.28 [1.12;1.48] and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 [1.20-6.99]. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 [1.09;1.16] and a 13.3-fold increase above 30 years (p < 0.001). Our results show a high incidence of CKD stage II with aging, with a strong significant risk increase after 30-years-old, and pinpoint baseline DBP, macroalbuminuria and increased LDH as independent risk factors raising the issue of optimal blood pressure targets for SCA patients.

Sera Neutralizing Activities Against Severe Acute Respiratory Syndrome Coronavirus 2 and Multiple Variants 6 Months After Hospitalization for Coronavirus Disease 2019.

BACKGROUND: Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. METHODS: In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). RESULTS: Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. CONCLUSIONS: Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant.

Visual lung damage CT score at hospital admission of COVID-19 patients and 30-day mortality.

OBJECTIVES: Chest CT has been widely used to screen and to evaluate the severity of COVID-19 disease in the early stages of infection without severe acute respiratory syndrome, but no prospective data are available to study the relationship between extent of lung damage and short-term mortality. The objective was to evaluate association between standardized simple visual lung damage CT score (vldCTs) at admission, which does not require any software, and 30-day mortality. METHODS: In a single-center prospective cohort of COVID-19 patients included during 4 weeks, the presence and extent of ground glass opacities(GGO), consolidation opacities, or both of them were visually assessed in each of the 5 lung lobes (score from 0 to 4 per lobe depending on the percentage and out of 20 per patient = vldCTs) after the first chest CT performed to detect COVID-19 pneumonia. RESULTS: Among 210 confirmed COVID-19 patients, the number of survivors and non-survivors was 162 (77%) and 48 (23%), respectively at 30 days. vldCTs was significantly higher in non-survivors, and the AUC of vldCTs to distinguish survivors and non-survivors was 0.72 (95%CI 0.628-0.807, p < 0.001); the best cut-off vldCTs value was 7. During follow-up, significant differences in discharges and 30-day mortality were observed between patients with vldCTs ≥ 7 versus vldCTs < 7: (98 [85.2%] vs 49 [51.6%]; p < 0.001 and 36 [37.9%] vs 12 [12.4%]; p < 0.001, respectively. The 30-day mortality increased if vldCTs ≥ 7 (HR, 3.16 (1.50-6.43); p = 0.001), independent of age, respiratory rate and oxygen saturation levels, and comorbidities at admission. CONCLUSIONS: By using chest CT in COVID-19 patients, extensive lung damage can be visually assessed with a score related to 30-day mortality independent of conventional risk factors of the disease. KEY POINTS: • In non-selected COVID-19 patients included prospectively during 4 weeks, the extent of ground glass opacities(GGO) and consolidation opacities evaluated by a simple visual score was related to 30-day mortality independent of age, respiratory rate, oxygen saturation levels, comorbidities, and hs-troponin I level at admission. • This severity score should be incorporated into risk stratification algorithms and in structured chest CT reports requiring a standardized reading by radiologists in case of COVID-19.

Comparison of 51Cr-EDTA and 99mTc-DTPA for glomerular filtration rate measurement.

PURPOSE: The production of 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for glomerular filtration rate (GFR) measurement in Europe, was recently halted by the manufacturer. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance has so far mostly been restricted to assessment of separate renal function by scintigraphy, but scarcely used and validated for GFR measurement. We compared the performances of 51Cr-EDTA and 99mTc-DTPA for GFR and extracellular fluid measurement. METHODS: In a multi-centre prospective study, 51Cr-EDTA and 99mTc-DTPA were simultaneously injected into 88 patients, and their urinary and plasma clearances, as well as their volumes of distribution, were measured during seven 30-min periods after a 90-min equilibrium time. RESULTS: Mean age was 52.2 ± 14.5 years, 59% were men. Urinary clearances of 51Cr-EDTA and 99mTc-DTPA were 64.1 ± 27.6 and 66.1 ± 28.0 mL/min, respectively, with a mean bias of 2.00 ± 2.25 mL/min, an accuracy within 10% of 95% [95% CI 91-99], and a coefficient of determination (R2) of 0.994. Plasma clearances of 51Cr-EDTA and 99mTc-DTPA were 66.1 ± 25.8 and 68.1 ± 26.6 mL/min, respectively, with a mean bias of 1.96 ± 3.32 mL/min, an accuracy within 10% of 91% [95% CI 85-97] and a R2 of 0.985. Distribution volumes were 17.3 ± 4.6 L for 51Cr-EDTA and 16.6 ± 4.6 L for 99mTc-DTPA (R2 0.930). CONCLUSION: The accuracy and precision of 99mTc-DTPA clearance, compared to 51Cr-EDTA clearance, was excellent for both urinary and plasma clearance methods, despite an approximate 2 mL/min overestimation, showing that the tracer is a reliable alternative to 51Cr-EDTA for GFR measurement.

Proteinuria and Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Single-Center Study.

BACKGROUND AND OBJECTIVES: Kidney involvement is frequent among patients with coronavirus disease 2019 (COVID-19), and occurrence of AKI is associated with higher mortality in this population. The objective of this study was to describe occurrence and significance of proteinuria in this setting. DESIGN , SETTING, PARTICIPANTS MEASUREMENTS: We conducted a single-center retrospective study to describe the characteristic features of proteinuria measured within 48 hours following admission among patients with COVID-19 admitted in a tertiary care hospital in France, and to evaluate its association with initiation of dialysis, intensive care unit admission, and death. RESULTS: Among 200 patients with available data, urine protein-creatinine ratio at admission was ≥1 g/g for 84 (42%), although kidney function was normal in most patients, with a median serum creatinine of 0.94 mg/dl (interquartile range, 0.75-1.21). Median urine albumin-creatinine ratio was 110 mg/g (interquartile range, 50-410), with a urine albumin-protein ratio <50% in 92% of patients. Urine retinol binding protein concentrations, available for 85 patients, were ≥0.03 mg/mmol in 62% of patients. Urine protein-creatinine ratio ≥1 g/g was associated with initiation of dialysis (odds ratio, 4.87; 95% confidence interval, 2.03 to 13.0; P <0.001), admission to the intensive care unit (odds ratio, 3.55; 95% confidence interval, 1.93 to 6.71; P <0.001), and death (odds ratio, 3.56; 95% confidence interval, 1.90 to 6.54; P <0.001). CONCLUSIONS: Proteinuria is very frequent among patients admitted for COVID-19 and may precede AKI. Low levels of albuminuria suggest a predominant tubular origin, confirmed by the elevated levels of urine retinol binding protein. Urine protein-creatinine ratio ≥1 g/g at admission is strongly associated with poor kidney and patient outcome.

Cardiac performance in patients hospitalized with COVID-19: a 6 month follow-up study.

AIMS: Myocardial injury is frequently observed in patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. Different cardiac abnormalities have been reported during the acute COVID-19 phase, ranging from infra-clinic elevations of myocardial necrosis biomarkers to acute cardiac dysfunction and myocarditis. There is limited information on late cardiac sequelae in patients who have recovered from acute COVID-19 illness. We aimed to document the presence and quantify the extent of myocardial functional alterations in patients hospitalized 6 months earlier for COVID-19 infection. METHODS AND RESULTS: We conducted a prospective echocardiographic evaluation of 48 patients (mean age 58 ± 13 years, 69% male) hospitalized 6 ± 1 month earlier for a laboratory-confirmed and symptomatic COVID-19. Thirty-two (66.6%) had pre-existing cardiovascular risks factors (systemic hypertension, diabetes, or dyslipidaemia), and three patients (6.2%) had a known prior myocardial infarction. Sixteen patients (33.3%) experienced myocardial injury during the index COVID-19 hospitalization as identified by a rise in cardiac troponin levels. Six months later, 60.4% of patients still reported clinical symptoms including exercise dyspnoea for 56%. Echocardiographic measurements under resting conditions were not different between patients with versus without myocardial injury during the acute COVID-19 phase. In contrast, low-level exercise (25W for 3 min) induced a significant increase in the average E/e' ratio (10.1 ± 4.3 vs. 7.3 ± 11.5, P = 0.01) and the systolic pulmonary artery pressure (33.4 ± 7.8 vs. 25.6 ± 5.3 mmHg, P = 0.02) in patients with myocardial injury during the acute COVID-19 phase. Sensitivity analyses showed that these alterations of left ventricular diastolic markers were observed regardless of whether of cardiovascular risk factors or established cardiac diseases indicating SARS-CoV-2 infection as a primary cause. CONCLUSIONS: Six months after the acute COVID-19 phase, significant cardiac diastolic abnormalities are observed in patients who experienced myocardial injury but not in patients without cardiac involvement.

24-h Urine Collection: A Relevant Tool in CKD Nutrition Evaluation.

Dietary management is a cornerstone of Chronic Kidney Disease (CKD) monitoring, and dietary surveys often difficult to perform. We studied in a CKD patient cohort with two years follow-up, whether validated 24-h urine ionogram would be a relevant tool for diet evaluation and compliance. We included 404 non-dialysis CKD patients, with three evaluations, including repeated measurements of fractional renal creatinine clearance and 24-h urine collection. Completeness of the 24-h urine collection, assessed by daily urine creatinine excretion extrapolated from fractional creatinine clearance, was 64.6%, 75.5%, and 78.2% at the first, second, and third visits, respectively. One hundred sixty-eight patients (41.6%) had three complete collections, with a measured glomerular filtration of 42.3 mL/min/1.73 m2 at baseline and prevalence of anemia and secondary hyperparathyroidism of 13.9% and 26.2%, respectively, increasing during follow-up to 15% and 31.5% (p < 0.001 and p < 0.001). The urine analysis showed at baseline a urine volume of above 2 L/day, and estimated sodium and protein intake within targets in 51.6% and 40.3% of cases, which improved during follow-up only for protein (to 45.9%, p < 0.0001). Our data suggest that a 24-h urine ionogram is an interesting, reliable tool in CKD patients for dietary monitoring to achieve target recommendation noteworthy salt and protein intake.

[Bartter-Gitelman syndromes]. / Syndromes de Bartter­Gitelman.

Bartter-Gitelman syndromes are rare inherited autosomal recessive salt-losing tubulopathies characterized by severe and chronic hypokalemia associated with metabolic alkalosis and secondary hyperaldosteronism. Bartter syndrome results from a furosemide-like defect in sodium reabsorption in the Henle's loop leading to hypercalciuria and defect in urinary concentration capacity. The antenatal Bartter syndrome is defined by polyhydramnios and an infantile polyuria with severe dehydration whereas classic Bartter syndrome appears during childhood or adulthood. Gitelman syndrome is a thiazide-like salt-losing tubulopathy. It is associated with hypomagnesemia, hypocalciuria without defect in urinary concentration capacity. The diagnosis is most often made in adolescents or adults. Clinical symptoms include tetany, delay in the height-weight growth curves, chronic tiredness, muscle weakness, myalgia and vertigo. Nephrocalcinosis in Bartter syndrome could lead to chronic kidney disease. Antenatal Bartter syndrome requires hospitalization in intensive care unit to manage the severe newborn dehydration. Chondrocalcinosis is the major complication in the Gitelman syndrome. The corner stones of treatment is the fluid and electrolyte management Bartter and Gitelman syndromes need lifelong oral supplementations of potassium, salt (Bartter) and magnesium (Gitelman). Indomethacin is efficient to reduce water and electrolyte loss in Bartter. In Gitelman, potassium-sparing diuretics may be helping for severe hypokaliemia but they will reinforce hypovolemia.