Inflammatory markers in Eisenmenger syndrome and their association with clinical outcomes. A cross-sectional comparative study.

BACKGROUND: Inflammation may be an important factor contributing to the progression of Eisenmenger syndrome (ES). The purpose of the current study was to: characterize the inflammatory profile in ES patients and compare measures to reference values for congenital heart disease and pulmonary arterial hypertension (CHD-PAH); and investigate whether inflammatory markers are associated with other clinical markers in ES. METHODS: Twenty-seven ES patients were prospectively selected and screened for systemic inflammatory markers, including interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF-α) and IL-10. Clinical data and echocardiographic parameters were obtained, with concomitant analysis of ventricular function. Functional capacity was assessed using the 6-min walk test (6MWT). Renal function and blood homeostasis were evaluated by the level of blood urea nitrogen (BUN), creatinine, and plasma electrolytes. RESULTS: Patients with ES expressed higher IL-10, IL-1ß and TNF-α compared to reference values of patients with CHD-PAH. IL-10 was negatively associated with BUN (r = -0.39,p = 0.07), creatinine (r = -0.35, p = 0.002), sodium (r = -0.45, p = 0.03), and potassium (r = -0.68, p = 0.003). IL-10 was positively associated with bicarbonate (r = 0.45, p = 0.02) and trended toward a positive association with right ventricular fractional area change (RVFAC) (r = 0.35, p = 0.059). IL-1ß was negatively associated with potassium (r = -0.5, p = 0.01). TNF-α demonstrated positive association with creatinine (r = 0.4,p = 0.006), BUN (r = 0.63,p = 0.003), sodium (r = 0.44, p = 0.04), potassium (r = 0.41, p = 0.04), and was negatively associated with RVFAC (r = -0.38,p = 0.03) and 6MWT distance (r = -0.54, p = 0.004). CONCLUSION: ES patients exhibit a more severe inflammatory profile compared to reference values for CHD-PAH. Furthermore, inflammatory markers are related to renal dysfunction, right ventricular impairment and poorer functional capacity.

A Novel MGP Gene Mutation Causing Keutel Syndrome in a Brazilian Patient.

Keutel syndrome is caused by mutations in the matrix gamma-carboxyglutamic acid (MGP) gene (OMIM 154870) and is inherited in an autosomal recessive fashion. It is characterized by brachydactyly, pulmonary artery stenosis, a distinctive facial phenotype, and cartilage calcification. To date, only 36 cases have been reported worldwide. We describe clinical and molecular findings of the first Brazilian patient with Keutel syndrome. Keutel syndrome was suspected based on clinical and morphological evaluation, so we sequenced the MGP gene using the TruSight One Sequencing Panel (Illumina). The obtained MGP gene sequence was then validated by Sanger sequencing. We identified a novel pathogenic homozygous variant of the MGP gene (c.2T>C; p.Met1Thr) confirming Keutel syndrome. Proper diagnosis of this syndrome is important for clinical management and is an indication for genetic counseling. Keutel syndrome should be suspected in patients with cartilage calcifications and brachydactyly when associated with a distinctive facial phenotype and pulmonary artery stenosis.

Effects of acute oxygen supplementation on functional capacity and heart rate recovery in Eisenmenger syndrome.

BACKGROUND: Eisenmenger syndrome (ES) precipitates the extreme manifestation of pulmonary hypertension, which leads to severe functional limitation and poor quality of life. The propose of the current study was: 1) examined the acute effects of 40% oxygen supplementation during the 6-minute walk test (6MWT); and 2) evaluate the relation between exercise capacity and clinical cardiac parameters in patients with ES. METHODS: Thirty subjects were prospectively included; all were submitted to a 6MWT with compressed air and with 40% of oxygen. Heart rate recovery at the first minute (HRR1) and perceived effort Borg scale for dyspnea and lower limb fatigue were recorded in both tests scenarios. RESULTS: The 6MWT distance was modestly, negatively associated with pulmonary vascular resistance (PVR) [r=0.46, p=0.02]. Patients improved 6MWT distance (p<0.001) and exhibited a faster HRR1 (p<0.001) with 40% supplemental oxygen compared to compressed air. With 40% supplemental oxygen, subjects revealed lower dyspnea and lower limb fatigue compared to 6MWT without oxygen supplementation (p<0.001). The amount of change in the 6MWT distance from air to oxygen was moderate, positively associated with tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) [r=0.50, p=0.03; r=0.64, p<0.001, respectively]. CONCLUSION: Acute 40% oxygen supplementation in patients with Eisenmenger syndrome led to an improvement in 6MWT distance, faster HRR1 and lower dyspnea and lower limb fatigue perception. Moreover, functional capacity was positively associated with right ventricular parameters.

Influência dos critérios de indexação da massa do ventrículo esquerdo no diagnóstico de hipertrofia ao ecocardiograma em crianças com insuficiência renal crônica / Influence of left ventricular mass indexation criteria in the diagnosis of left ventricular hypertrophy by echocardiogram: study in children with chronic renal disease

Fundamento: O diagnóstico ecocardiográfico de hipertrofia ventricular esquerda (HVE) em crianças baseia-se no cálculo damassa do ventrículo esquerdo (VE) indexada. Entretanto, o critério de indexação ainda não é consenso.Objetivo: Comparar diferentes critérios usados no diagnóstico de HVE à ecocardiografia em crianças.Método: Foram incluídas crianças com doença renal crônica (DRC) em diálise (grupo DI) ou em tratamento conservador (grupoTC). Foram obtidas as medidas e calculada a massa do VE conforme recomendado. Os critérios de HVE utilizados foram: 1)massa (g) – HVE conforme gênero e área da superfície corporal (ASC); 2) massa (g) indexada à ASC (g/m2) – HVE conforme gênero e ASC; 3) massa em gramas indexada à altura (m) à potência de 2,7 (g/m2,7) – diagnóstico de HVE conforme nomograma de idade, gênero e altura; 4) escore z http://parameterz.blogspot.com/2008/09/lv-mass-z-scores – HVE se > 2 desvios-padrão).As proporções de HVE foram comparadas por teste do X2; significante se p < 0,05.Resultados: Sessenta crianças com DRC foram incluídas; 34 no grupo DI (17 meninos; mediana da idade = 109 meses) e 26no grupo TC (15 meninos; mediana da idade = 80 meses). Conforme o critério, no grupo total, as proporções de HVE foram, respectivamente, 31/60, 33/60, 41/60 e 31/60 (p = 0,049), menor pelo critério 2 em relação ao 3 (p = 0,026); no grupo DI foram23/34; 23/34; 31/34 e 29/34 (p = 0,006), maior com o critério 3 em relação aos critérios 1 (p = 0,033) e 2 (p = 0,004) e com ocritério 4 em relação ao 2 (p = 0,029); no grupo TC foram 8/26; 10/26; 10/26 e 2/26 (p = 0,038), menor pelo critério 4 em relaçãoaos critérios 2 (p = 0,038) e 3 (p = 0,009).

Background: the echocardiographic diagnosis of left ventricular hypertrophy (LVH) in children is based on the indexed left ventricle mass calculation.However, the indexation criterion is still not defined.Objective: to compare different criteria used for the diagnosis of LVH by echocardiography in children.Method: The study included children with chronic renal disease (CRD) in dialysis (DI) or in conservative treatment (CT). Measures for left ventriclemass calculation were obtained as recommended. The criteria used for LVH were: 1) mass (g) – LVH according to gender and body surface area(BSA, m2) – based on large study of normal Brazilian children; 2) mass indexed to body surface area (g/m2) – LVH according to gender and bodysurface area (BSA, m2) – based on large study of normal Brazilian children; 3) g/altura2,7 but diagnosis of LVH by a nomogram of age, gender andheight; 4) z score (http://parameterz.blogspot.com/2008/09/lv-mass-z-scores) – LVH if > 2 standard-deviation. The proportion of LVH among thegroups were compared by X2; significant if p < 0.05.Results: 60 children with CKD were included; 34 in DI (17 boys; median of age= 109 months) and 26 in CT (15 boys; median of age= 80 months).According to each criteria, in the hole group, the proportions of LVH were, respectively, 31/60, 33/60, 41/60 e 31/60 (p=0.049), lower for criterion2 compared to 3 (p=0.026); in DI group were 23/34; 23/34; 31/34 e 29/34 (p=0.006), higher with criterion 3 compared to criteria 1 (p=0.033)and 2 (p=0.004), and with 4 compared to 2 (p=0.029); in TC group were 8/26; 10/26; 10/26 e 2/26 (p=0.038), lower for criterion 4 comparedto criteria 2 (p=0.038) and 3 (p=0.009). Conclusion: in children with CKD the proportion of LVH by echocardiography was different according to the criterion used. (Arq Bras Cardiol:Imagem cardiovasc. 2016;29(2):42-46).

A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis.

Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung disease. The prevalence of pulmonary hypertension diagnosed by right heart catheterisation and its cardiopulmonary function findings in patients with chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic patients with chronic hypersensitivity pneumonitis were prospectively evaluated. All patients were submitted to right heart catheterisation, pulmonary function testing, a 6-min walk test, echocardiography, blood gas determination and N-terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also underwent incremental cardiopulmonary exercise testing. 50 patients underwent right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22 (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary pulmonary hypertension had lower forced vital capacity (mean ± sd 50 ± 17% versus 69 ± 22% predicted, p<0.01), carbon monoxide diffusing capacity (37 ± 12% versus 47 ± 14% predicted, p<0.01), arterial oxygen tension (median (interquartile range) 59.0 (47.8-69.3) versus 73.0 (62.2-78.5) mmHg, p<0.01) and saturation after the 6-min walk test (78 ± 8% versus 86 ± 7%, p<0.01). In pre-capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic threshold (41 ± 11% versus 50 ± 8% predicted, p=0.04) and at peak exercise (12.8 ± 1.6 versus 15.0 ± 2.5 mL · kg(-1) · min(-1), p=0.02). Pre-capillary pulmonary hypertension is common in symptomatic chronic hypersensitivity pneumonitis and is related to interstitial lung disease severity. Additionally, pulmonary hypertension is more prevalent in hypoxaemic patients with impaired lung function and exercise capacity.

Usefulness of pulmonary capillary wedge pressure as a correlate of left ventricular filling pressures in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by a pulmonary capillary wedge pressure (PCWP) of ≤15 mm Hg, given a normal left ventricular filling pressure (LVFP). However, recent studies have shown that, in PAH patients, diagnosis based on PCWP can erroneously classify a significant number of patients compared with diagnosis based on left ventricular end-diastolic pressure (LVEDP). Therefore, we sought to compare the diagnostic accuracy of end-expiratory PCWP and LVEDP measurements in patients suspected of having pulmonary hypertension (PH). METHODS: We reviewed the hemodynamic data from 122 patients suspected of having PH who underwent simultaneous right- and left-side heart catheterizations at a PH referral center from 2006 to 2011. RESULTS: PH was diagnosed in 105 patients, 79% of whom (n = 83) showed a pre-capillary pattern according to the LVEDP measurement. Ninety percent of patients with PCWP ≤15 mm Hg were correctly classified as having pre-capillary PH. However, 39% of patients with a PCWP >15 mm Hg had LVEDP ≤15 mm Hg and would have been erroneously diagnosed with pulmonary venous hypertension based on their PCWP measurements alone. The sensitivity and specificity was 0.89 and 0.64, respectively. A Bland-Altman analysis of the PCWP and LVEDP measurements revealed a mean bias of 0.3 mm Hg with 95% limits of agreement of -7.2 to 7.8 mm Hg. CONCLUSIONS: A PCWP ≤15 mm Hg was found to be a reliable indicator of normal LVFP in pre-capillary PH patients. When measured properly and analyzed in the clinical context, PCWP is a valuable tool for accurate diagnosis of PAH.

Infracardiac total anomalous pulmonary venous drainage: a diagnostic challenge.

Infracardiac total anomalous pulmonary venous drainage can be erroneously diagnosed as respiratory distress of several different etiologies during the neonatal period. A cross-sectional echocardiography study with Doppler color flow mapping can preoperatively determine the precise drainage site and pulmonary venous return pattern, thereby allowing cardiac surgery to be performed promptly, prior to any clinical deterioration.

Drenagem anômala total das veias pulmonares, em sua forma infracardíaca: desafio diagnóstico / Infracardiac total anomalous pulmonary venous drainage: a diagnostic challenge

No período neonatal, a drenagem anômala total das veias pulmonares, em sua forma infracardíaca, pode ser erroneamente diagnosticada como desconforto respiratório decorrente de diferentes etiologias. No pré-operatório, a ecocardiografia bidimensional com Doppler orientado pelo mapeamento de fluxo em cores pode definir o local exato da drenagem e o padrão de retorno venoso pulmonar, permitindo, dessa forma, que a cirurgia cardíaca seja realizada imediatamente antes que ocorra qualquer dano clínico.

Infracardiac total anomalous pulmonary venous drainage can be erroneously diagnosed as respiratory distress of several different etiologies during the neonatal period. A cross-sectional echocardiography study with Doppler color flow mapping can preoperatively determine the precise drainage site and pulmonary venous return pattern, thereby allowing cardiac surgery to be performed promptly, prior to any clinical deterioration.

Homocysteine concentrations and molecular analysis in patients with congenital heart defects.

BACKGROUND: Congenital heart defects are the result of incomplete heart development and, like many diseases, have been associated with high homocysteine concentration. METHODS: We evaluated homocysteine, folic acid and vitamin B(12) concentrations, and the mutations 677C>T and 1298A>C in MTHFR, 844ins68 in CBS and 2756A>G in MTR genes in 58 patients with congenital heart defects, 38 control subjects, and mothers of 49 patients and 26 controls. RESULTS: Control and patients presented normal range concentrations for homocysteine (7.66 +/- 3.16 microM and 6.95 +/- 3.12 microM, respectively), folic acid (8.31 +/- 3.00 ng/mL and 11.84 +/- 10.74 ng/mL) and vitamin B(12,) (613.56 +/- 307.57 pg/mL and 623.37 +/- 303.12 pg/mL), which did not differ among groups. For the mothers studied, homocysteine and vitamin B(12) concentrations also did not differ between groups. However, folic acid concentrations of mothers showed significant difference, the highest values being in the group of patients. No difference was found in allele frequencies among all groups studied. CONCLUSIONS: In the studied groups, high homocysteine seems not to be correlated with congenital heart defects, as well as folic acid and vitamin B(12). The mutations studied, in isolation, were not related to congenital heart defects, but high concentration of maternal homocysteine is associated with the presence of three or four mutated alleles.

The case for utilizing more strict quantitative Doppler echocardiographic criterions for diagnosis of subclinical rheumatic carditis.

AIM: Our aim was to perform a comparative, quantitative and qualitative, analysis of valvar echocardiographic findings in patients with acute rheumatic fever, with or without clinical manifestations of carditis, as compared to healthy controls. METHODS AND RESULTS: We analyzed cross-sectional Doppler echocardiographic images of 31 patients with acute rheumatic fever diagnosed according to the Jones criterions as modified in 1992. Of 31 patients, 22 presented with clinical carditis, while 9 had subclinical carditis. The patients, and a control group of 20 healthy individuals, underwent cardiac examination and echocardiographic assessment, assessing quantitative and qualitative findings of mitral and aortic valvar abnormalities. The leaflets of the mitral valve were statistically thicker in those with clinical and subclinical carditis when compared to controls (p less than 0.001). We observed a greater frequency of mitral variance, convergence of mitral flow, and aortic regurgitation for those with clinical and subclinical carditis when compared to controls (p less than 0.001, p less than 0.001 and p equal to 0.003, respectively). Patients with clinical and subclinical carditis had more quantitative and qualitative changes in the parameters than did the controls. CONCLUSION: Echocardiography is a sensitive method to detect valvar abnormalities in patients with acute rheumatic fever and carditis. Additionally, by using regular standardized criterions, abnormalities that lead to a diagnosis of subclinical carditis are found in those patients with acute rheumatic fever in the apparent absence of cardiac involvement.