Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Crystalluria in adolescent and adult patients with congenital heart disease.

INTRODUCTION: Crystalluria is a frequent finding in normal individuals and in patients suffering from urolithiasis. As nephrolithiasis has been associated with cardiovascular risk factors and most congenital heart disease (CHD) patients reach adulthood, the objective of this study is to determine the presence of crystalluria and if it influences their cardiovascular outcome. METHODS: Case-control and observational prospective study design of patients with CHD older than 14 years with a stable CHD verified with imaging tests and a control population. RESULTS: 214 patients with CHD [median age 21 (17-35) years and 41 (19%) males] and 345 controls were studied and followed up. None of them had symptoms of renal calculi. Nine (4%) patients with CHD and 24 (7%) patients in the control group showed crystalluria (p = 0.180), all of them composed of calcium oxalate. No significant differences were seen in age, sex, body mass index, CHD complexity, cardiovascular risk factors, NYHA functional class, cyanosis, and medical treatment between CHD patients with and without crystalluria. In relation to survival, 18 patients with CHD had a major acute cardiovascular event (MACE) (3 strokes, 2 myocardial infarction, 9 cardiovascular death and 4 non cardiovascular mortality) during the follow up time [7.3 (4.4-8.5) years] without significant differences in the Kaplan-Meier analysis (p = 0.358) between patients with and without crystalluria. CONCLUSION: No significant differences were found between CHD and control patients in relation to crystalluria and it had no impact on the occurrence of cardiovascular events in the medium term follow up of patients with CHD.

Gamma-glutamyl transferase and cardiovascular events in patients with congenital heart disease.

INTRODUCTION: Serum gamma-glutamyl transferase activity (GGT) seems to predict cardiovascular events in different populations. However, no data exist on patients with congenital heart disease (CHD). METHODS: Observational, analytic, prospective cohort study design involving CHD patients and a control population to determine the effect of GGT levels on survival. RESULTS: A total of 589 CHD patients (58% males, 29 ± 14 years old) and 2745 matched control patients were followed up. A total of 69 (12%) CHD patients had a major acute cardiovascular event (MACE) during the follow-up time (6.1 [0.7-10.4] years). Patients with CHD and a GGT >60 U/L were significantly older, more hypertensive and dyslipidemic, had a worse NYHA functional class and a greater anatomical complexity than CHD patients with a GGT ≤60 U/L. The binary logistic regression analysis showed that age, a great CHD anatomical complexity, and having atrial fibrillation/flutter were the predictive factors of higher GGT levels (>60 U/L). The Kaplan-Meier analysis showed that patients with CHD and a GGT concentration above 60 UL showed the lowest probability of survival compared to that of CHD with GGT ≤60 U/L and controls irrespective of their GGT concentrations (p < .001). Similarly, the multivariable Cox regression analysis found an independent association between higher GGT levels (>60 U/L) and a worse prognosis (HR 2.44 [1.34-4.44], p = .003) among patients with CHD. CONCLUSION: Patients with CHD showed significant higher GGT levels than patients in the control group having those with higher GGT concentrations (>60 U/L) the worst survival.

C3 glomerulopathy associated with monoclonal gammopathy: impact of chronic histologic lesions and beneficial effects of clone-targeted therapies.

BACKGROUND: C3 glomerulopathy associated with monoclonal gammopathy (C3G-MIg) is a rare entity. Herein we analysed the clinical and histologic features of a cohort of C3G-MIg patients. METHODS: We conducted a retrospective, multicentre, observational study. Patients diagnosed with C3G-MIg between 1995 and 2021 were enrolled. All had genetic studies of the alternative complement pathway. The degree of disease activity and chronicity were analysed using the C3G histologic index. Descriptive statistics and propensity score matching (PSM) analysis were used to evaluate the main outcome of the study [kidney failure (KF)]. RESULTS: The study group included 23 patients with a median age 63 of years [interquartile range (IQR) 48-70], and 57% were males. Immunoglobulin G kappa was the most frequent MIg (65%). The diagnosis of C3G-MIg was made in transplanted kidneys in seven patients (30%). Five (22%) patients had C3 nephritic factor and five (22%) had anti-factor H antibodies. One patient carried a pathogenic variant in the CFH gene. During a follow-up of 40 months (IQR 14-69), nine patients (39%) reached KF and these patients had a significantly higher total chronicity score on kidney biopsy. Patients who received clone-targeted therapy had a significantly higher survival compared with other management. Those who achieved haematological response had a significantly higher kidney survival. Outcome was remarkably poor in kidney transplant recipients, with five of them (71%) reaching KF. By PSM (adjusting for age, kidney function, proteinuria and chronicity score), no significant differences were observed in kidney survival between C3G patients with/without MIg. CONCLUSIONS: The C3G histologic index can be used in patients with C3G-MIg to predict kidney prognosis, with higher chronicity scores being associated with worse outcomes. Clone-targeted therapies and the development of a haematological response are associated with better kidney prognosis.

Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy.

INTRODUCTION: The association between a change in proteinuria over time and its impact on kidney prognosis has not been analysed in complement component 3 (C3) glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure. METHODS: This was a retrospective, multicentre observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modelling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure. RESULTS: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (hazard ratio 0.79; 95% confidence interval 0.56-0.97; P < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up. CONCLUSIONS: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.

Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

Malnutrition is independently associated with an increased risk of major cardiovascular events in adult patients with congenital heart disease.

BACKGROUND AND AIMS: Malnutrition is found frequently during chronic diseases, and its prevalence and relation to disease outcome in adult patients with congenital heart disease (CHD) remains unknown. METHODS AND RESULTS: A cohort of 393 consecutive stable congenital heart disease (CHD) patients was followed up in a single dedicated clinical unit. Demographic, clinical and laboratory parameters, along with a nutritional risk index (NRI), were studied, as well as major acute cardiovascular events (MACE), defined as arterial thrombotic events, heart failure requiring hospitalization or cardiovascular and non-cardiovascular mortality. The median age of the patients was 23 years (17-35) and 225 (57%) were males. Median plasma albumin concentration was 4.5 (4.2-4.7) g/dL, the body mass index was 23 (21-27) kg/m2, the NRI was 112 (106-118), and 33 (8%) patients showed malnutrition (NIR<100). A worse NYHA functional class (II and III), total cholesterol and serum glucose levels were significant risk factors associated with malnutrition (NRI<100) in CHD patients. During a median follow-up of 8 (5-10) years, 39 (10%) CHD patients suffered a MACE. Multivariable Cox regression analysis showed that older patients (years) [HR 1.06 (1.04-1.09), p < 0.001], CHD patients with great anatomical complexity [HR 4.24 (2.17-8.27), p < 0.001] and those with a lower NRI [HR 0.95 (0.93-0.98), p = 0.001] had a significant worse MACE-free survival, being the NRI a better predictor of MACE than albumin concentration. CONCLUSIONS: A low NRI is independently associated with a significant increased risk of MACE in CHD patients.

Prevalence and predictors of psychological distress in congenital heart disease patients.

OBJECTIVE: To determine psychological distress in congenital heart disease (CHD) patients. METHODS: Cross-sectional study among consecutive CHD patients recruited from a single hospital outpatient clinic to determine anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS) questionnaire. RESULTS: One hundred and sixty-nine CHD patients [29 (19-39) years old, 100 (59%) males] were studied. A total of 25% and 9% of CHD patients showed anxiety and depression symptoms, respectively. Patients with an HADS score ≥ 8 had a significantly worse New York Heart Association (NYHA) functional class, needed more psychological support, had more mental health history, and took more anxiolytic/antidepressant medication than the CHD patients with an HADS score below 8. A worse NYHA functional class [OR, 1.88 (1.01-3.52)] proved to be a predictor of a borderline/abnormal HADS score. CONCLUSION: Psychological distress has a high prevalence among CHD patients and having an NYHA Class II and III is a significant predictor of an HADS score ≥ 8.

Cardiovascular risk factors and arterial thrombotic events in congenital heart disease patients.

INTRODUCTION: As congenital patients get older, it can be hypothesised that cardiovascular risk factors increase. METHODS: Retrospective study of congenital heart disease (CHD) patients attended between January 2008 and September 2018. Cardiovascular risk factors, myocardial infarction, stroke, peripheral vascular disease, and analytical data such as serum glucose and lipid profile were determined. RESULTS: Eight hundred and eighteen CHD patients and 1955 control patients matched for age and sex were studied. CHD patients were distributed in simple (462 patients), moderate (228 patients) and great (128 patients) complexity. Median age in CHD patients was 33 (25-41) years old and 56% were male. CHD patients were significantly more hypertensive and diabetic but less dyslipidemic and smokers than patients in the control group. Twenty-seven (3.3%) CHD patients had an arterial thrombotic event: 3 coronary, 22 neurological and 2 peripheral vascular disease. No significant differences were seen in the incidence of myocardial infarction between the control and the CHD groups. However CHD patients had a significant higher incidence of arterial thrombotic events (coronary, neurological and peripheral vascular events) at the expense of strokes and transient ischaemic attacks (22 vs 2 events in CHD and control patients, respectively). Also, no significant differences were seen in age, sex, BMI, arterial hypertension, diabetes mellitus, dyslipidemia, smoking habit, serum glucose, total and LDL cholesterol, statin treatment, myocardial infarction and arterial thrombotic events according to CHD complexity. Being older and having arterial hypertension, diabetes mellitus, dyslipidemia and smoking habit were more frequent among CHD patients with arterial thrombosis. CONCLUSIONS: Congenital heart diseases are more hypertensive and diabetic but less dyslipemic and smokers than patients in the control group. CHD patients have a higher incidence of neurological events but not of myocardial infarction in relation to the control population.

Anemia in Adolescents and Young Adult Patients With Congenital Heart Disease.

INTRODUCTION: Despite anemia in acquired heart disease being a common problem, little is known in patients with congenital heart disease (CHD). METHODS: In total, 544 consecutive stable noncyanotic CHD patients were studied to determine demographic, clinical, and analytic parameters. Anemia was defined as a condition in which hemoglobin concentration was <13 g/dL in male individuals and <12 g/dL in female individuals. RESULTS: In total, 49 (9%) CHD patients had anemia. Patients with complex anatomy had the highest prevalence of anemia (33%). The median hemoglobin concentration was 14.4 (13.5 to 15.6) mg/dL. Of the total anemic CHD patients, 21 of 49 (43%) were microcytic (mean corpuscular volume <84 fL) and 46 of 49 (94%) had a mean corpuscular volume under 95 fL. Oral anticoagulation, oral antiaggregation, diuretic treatment, and having valve prostheses or cardiovascular risk factors, such as arterial hypertension or diabetes mellitus, did not reach statistical significance between anemic and nonanemic CHD patients. Multivariate analyses determined as risk factors for anemia a worse New York Heart Association functional class (patients in class >II/IV) (odds ratio [OR], 8.37; 95% confidence interval [CI], 1.69-41.35), N-terminal proB-type natriuretic peptide levels >125 pg/mL (OR, 7.90; 95% CI, 2.88-21.69), and apoferritn levels below 15 ng/mL (OR, 0.21; 95% CI, 0.09-0.50). The Kaplan-Meier survival analysis showed no significant differences in mortality between anemic and nonanemic CHD patients (P=0.143). CONCLUSIONS: The incidence of anemia in CHD patients is similar to that of the normal population and iron deficiency anemia accounts for most of the cases. There were no significant differences in mortality between CHD patients with and without anemia.

Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

INTRODUCTION: Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. METHODS: Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. RESULTS: Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. CONCLUSION: NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients.

Hepatocellular carcinoma in a non-failing Fontan circulation.

Patients after a Fontan operation exhibit some degree of fibrosis which are primarily located in a sinusoidal or centrilobular pattern. Cirrhosis may develop years later and the incidence of cancer is up to 5%. That is why some authors recommend that patients who are >10 years out from their Fontan operation should undergo cardiac assessment as well as the determination of alpha-fetoprotein level, the realization of liver imaging tests or even liver biopsy to stay ahead of neoplastic transformation.

Medium-term follow-up of renal function in hypoxaemic congenital heart disease patients.

UNLABELLED: Introduction Hypoxaemic congenital heart disease (CHD) patients are at higher risk of complications. The aim of this study was to compare and follow-up blood and 24-hour urine analytical data in hypoxaemic and non-hypoxaemic CHD patients. METHODS: The inclusion criteria for this study were as follows: patients older than 14 years of age with a structural CHD with or without associated hypoxaemia. RESULTS: In total, 27 hypoxaemic and 48 non-hypoxaemic CHD patients were included in order to compare blood and 24-hour urine analytical data. Among hypoxaemic patients, 13 (48.1%) were male, two (7.4%) had diabetes mellitus, one of whom was a smoker, one (3.7%) had systemic arterial hypertension, and 11 (40.7%) showed pulmonary arterial hypertension. The mean follow-up time was 3.1±1.9 years. Hypoxaemic CHD patients showed higher proteinuria concentrations (g/24 hours) (0.09 (0.07; 0.46) versus 0.08 (0.07; 0.1), p=0.054) and 24-hour albumin excretion rate (µg/min) (16.5 (11.2; 143.5) versus 4.4 (0.0; 7.6), p<0.001) compared with non-hypoxaemic CHD patients; however, no significant differences were found in the proteinuria levels and in the 24-hour albumin excretion rate in CHD patients with associated hypoxaemia, both at baseline and at follow-up. When divided into groups, hypoxaemic patients with palliative shunts showed significantly higher proteinuria concentrations compared with hypoxaemic patients not operated on or with Fontan procedures (p=0.01). No significant differences were seen in 24-hour proteinuria and 24-hour albumin excretion rate during the follow-up of patients with palliative shunts. CONCLUSIONS: Hypoxaemic CHD patients have significant higher 24-hour proteinuria concentration and 24-hour albumin excretion rate compared with non-hypoxaemic CHD patients. Among hypoxaemic CHD patients, those with palliative shunts showed the highest 24-hour proteinuria concentrations.

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

Thrombocytopenia in congenital heart disease patients.

Thrombocytopenia has been identified as a mechanism of the increased incidence of thromboembolism and death in hypoxemic congenital heart disease (CHD) patients. About 387 CHD patients (344 non-hypoxemic and 43 hypoxemic) were followed-up during a median of 34.3 (24.5; 49.9) months. Demographic, clinical, analytical parameters, and survival curves between CHD with platelet levels above and below 150,000/µl were determined. On one hand, in the subgroup of non-hypoxemic CHD patients, 8 out of 344 (2.3%) patients showed some type of bleeding and 8 (2.3%) patients showed some type of thrombosis. On the other hand, in the hypoxemic subgroup, 6 out of 43 (13.9%) patients had some type of bleeding and 5 (11.6%) patients showed some type of thrombosis. The binary logistic regression multivariate analysis being under oral anticoagulation/antiplatelet therapy (OR, 4.192 (1.207-14.550), p = 0.024) and having hypoxemia (OR, 4.041 (1.087-15.029); p = 0.037) favored the occurrence of bleeding. Meanwhile, the only factor which favored thrombosis was being hypoxemic (OR, 5.703 (1.334-24.387); p = 0.019). Also, being hypoxemic (OR, 0.217 (0.070-0.670), p = 0.008) and having a high MPV (OR, 0.534 (0.383-0.744); p = 0.001) favored a low platelet count (< 150 × 10(3)/µl). Kaplan-Meier survival analysis showed significant differences between CHD patients with a platelet count lower and higher than 150 × 10(3)/µl (p = 0.009). Bleeding and thrombotic complications are more frequent in hypoxemic CHD patients irrespective of platelet counts. Larger platelets, as reflected by an increased mean platelet volume, and the higher CRP concentration seen in hypoxemic CHD patients may explain to some extent the higher incidence of thrombotic events in hypoxemic patients.

Proteinuria and clinical outcome in CHD patients.

INTRODUCTION: CHD patients, especially those with associated hypoxaemia, usually have some level of renal function impairment, even though they are relatively young. The aim of the study was to evaluate those clinical and analytical factors that may contribute to microalbuminuria and determine the association of 24-hour proteinuria with thrombotic events and mortality. METHODS: A total of 251 CHD patients were studied and demographic characteristics, blood test, and 24-hour urinalysis were analysed. RESULTS: Of the patients, 221 were non-hypoxaemic, and 30 were hypoxaemic (oxygen saturation of 84.3±5.9%). Of the non-hypoxaemic patients, 30 (13.6%), and of the hypoxaemic patients 9 (30%), showed proteinuria (>0.15 g/24 hours) (p=0.028). Hypoxaemic CHD patients also showed higher haematocrit (%) (50.7 (34.6; 72.1) versus 42.8 (34.6; 48.9), p<0.001), serum creatinine (mg/dl) (1.07±0.2 versus 0.96±1.9, p=0.004), microalbuminuria (mg/dl/24 hours) (1.2 (0.0; 261.5) versus 0.5 (0.0; 4.37), p<0.001), proteinuria (gr/24 hours) (1.0 (0.4; 3.1) versus 0.08 (0.04; 0.52), p=0.043), and N-terminal pro-B-type natriuretic peptide (pg/ml) (417.8 (35.7; 8534.0) versus 44.9 (0.0; 670.5), p<0.001) concentrations than non-hypoxaemic CHD patients. During a median follow-up of 26.0 (16.9; 57.7) months, five patients died - one patient had 24-hour proteinuria and four patients did not (p=0.581) - and three patients had some type of thrombosis - two patients had 24-hour proteinuria and one patient did not (p=0.014). Kaplan-Meier survival analysis showed no significant difference between CHD patients with and without 24-hour proteinuria (p=0.631). CONCLUSION: CHD patients with proteinuria have significantly more thrombosis and more hypoxaemia than those patients without proteinuria.

Follow-up of congenital heart disease patients with subclinical hypothyroidism.

INTRODUCTION: Subclinical hypothyroidism or mild thyroid failure is a common problem in patients without known thyroid disease. METHODS: Demographic and analytical data were collected in 309, of which 181 were male and 128 were female, congenital heart disease (CHD) patients. CHD patients with thyroid-stimulating hormone above 5.5 mIU/L were also followed up from an analytical point of view to determine changes in serum glucose, cholesterol, N-terminal pro b-type natriuretic peptide, and C-reactive protein concentrations. RESULTS: Of the CHD patients, 35 (11.3%) showed thyroid-stimulating hormone concentration above 5.5 mIU/L. Of them, 27 were followed up during 2.4±1.2 years - 10 were under thyroid hormone replacement treatment, and 17 were not. Of the 27 patients (25.9%), 7 with subclinical hypothyroidism had positive anti-thyroid peroxidase, and 3 of them (42.8%) with positive anti-thyroid peroxidase had Down syndrome. Down syndrome and hypoxaemic CHD patients showed higher thyroid-stimulating hormone concentrations than the rest of the congenital patients (p<0.001). No significant differences were observed in serum thyroxine, creatinine, uric acid, lipids, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations before and after the follow-up in those CHD patients with thyroid-stimulating hormone above 5.5 mIU/L whether or not they received levothyroxine therapy. CONCLUSIONS: CHD patients with subclinical hypothyroidism showed no significant changes in serum thyroxine, cholesterol, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations whether or not they were treated with thyroid hormone replacement therapy.

Hyperuricaemia in congenital heart disease patients.

INTRODUCTION: Hyperuricaemia is associated with traditional cardiovascular risk factors such as type 2 diabetes or dyslipidaemia and a higher mortality. METHODS: Out of 528 congenital heart disease patients, 329 patients, including 190 male and 139 female patients, in whom uric acid determination was performed, were studied and followed up to determine survival. RESULTS: Male congenital heart disease patients with high serum uric acid concentrations (>7 mg/dl) showed significantly (p < 0.05) higher body mass index, serum creatinine, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and C-reactive protein concentrations than those male congenital heart disease patients with lower serum uric acid levels (≤7 mg/dl). Meanwhile, female congenital heart disease patients with higher serum uric acid concentrations (>5.7 mg/dl) were significantly (p < 0.05) younger, more hypoxaemic, more obese, and with higher C-reactive protein and N-terminal-pro-B-type natriuretic peptide levels than those female congenital heart disease patients with lower serum uric acid concentrations (≤5.7 mg/dl). During a median follow-up of 90 months, 16 out of 528 congenital heart disease patients died - 14 patients of cardiac origin and two patients of non-cardiac origin - of whom 10 were hypoxaemic. Kaplan-Meier analysis showed no significant differences in mortality between male and female congenital heart disease patients with high and low serum uric acid level concentrations. CONCLUSIONS: Hypoxaemia, body mass index, and C-reactive protein concentrations are higher in hyperuricaemic congenital heart disease patients, although no significant differences were seen in mortality between congenital heart disease patients with high and low serum uric acid concentrations.

Klippel-Feil syndrome and levo-looped transposition of the great arteries.

Klippel-Feil syndrome is a skeletal disorder characterised by low hairline and a short neck due to abnormal fusion of two or more cervical vertebrae. Although congenital heart and lung defects are infrequent, some abnormalities such as cor triatriatum, coarctation of the aorta, total anomalous pulmonary venous connection, or lung agenesis have been reported. The challenge of recognising Klippel-Feil syndrome lies in the fact that there is an association of this syndrome with other significant conditions such as skeletal, genitourinary, neurological, ear, and some cardiac defects. We report a Klippel-Feil syndrome type III 14-year-old patient with a levo-looped transposition of the great arteries. In addition, the patient had agenesis of the left upper-lung lobe.

Congenital rubella syndrome: a matter of concern.

Congenital rubella syndrome (CRS), an important cause of severe birth defects, remains a public health problem in a significant number of countries. Therefore, global health experts encourage use of rubella vaccination, with the primary aim of preventing CRS. While large-scale rubella vaccination during the last decade has drastically reduced or eliminated both the virus and CRS in Europe and the Americas, many countries in Africa, South-East Asia, the Eastern Mediterranean, and the Western Pacific have not yet incorporated any type of rubella-containing vaccine into their immunization schedule. As a result, through travel and migration, rubella has been imported into countries that had successfully eliminated the virus, leading to outbreaks and the reestablishment of endemic transmission. The objective of this study was to identify the key factors required for CRS elimination (prevalence reduction, vaccination strategies, and surveillance methods) by reviewing publications in PubMed on rubella and CRS (systematic reviews, country experiences, and position papers from the World Health Organization (WHO) and other intergovernmental organizations). Based on the results of the review, to eliminate rubella and CRS in endemic areas and reduce re-emergence in previously disease-free areas, all countries should carry out two types of mass rubella vaccination campaigns: 1) one single mass national immunization campaign targeting all men and women 5-39+ years old (with the upper age limit depending on the year in which the rubella-containing vaccine was introduced and the epidemiology of rubella in the country) and 2) incorporation of an rubella-containing vaccine in routine childhood immunization programs, including regular vaccination campaigns for 12-month-olds and measles follow-up campaigns. In addition to mass rubella immunization campaigns and routine childhood vaccination programs, the following measures should be taken to help fight rubella and CRS: 1) surveillance of the number of susceptible women of childbearing age, and the emergence of imported cases; 2) coverage of susceptible populations with "second-chance" ("catch-up") campaigns (vaccination of older children and adults who may have missed earlier immunization programs); 3) rapid response to outbreaks; 4) strengthening of CRS surveillance; 5) involvement of the private sector in awareness and vaccination campaigns; and 6) reduction of the number of false-positive laboratory test results.