natriuretic-peptide--brain and Eisenmenger-Complex

Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.. Patients with Eisenmenger syndrome aged ≥12 years and in World Health Organization functional class II-III were randomized 1:1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline.. Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5; P=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of ≥2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group).. Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01743001.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Biomarkers; Child; Double-Blind Method; Down Syndrome; Eisenmenger Complex; Endothelin Receptor Antagonists; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Pyrimidines; Recovery of Function; Sulfonamides; Time Factors; Treatment Outcome; Walk Test; Young Adult

Citrulline is an amino acid which is produced by the urea cycle and also a precursor for NO, that is, a vasodilator for normal function of pulmonary vasculature. Thereby, enhancing l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and those with congenital heart disease identified as Eisenmenger Syndrome results in reduction of pulmonary hypertension.. In this clinical trial before and after study, we assigned 25 patients with arterial pulmonary hypertension (idiopathic or Eisenmenger Syndrome) to receive l-citrulline malate 1g three times daily for two weeks. The primary measurement was the change in exercise capacity, as considered as a result of the total distance walked in six minutes, from baseline to week 2. We also assessed mean pulmonary artery pressure, the change in the quality of life, and the change in pro-brain natriuretic peptide (BNP) level. The study was not powered to evaluate mortality.. The mean walking distance in six minutes was significantly increased by about 44m (p=0.005) after receiving l-citrulline malate. Mean pulmonary artery pressure significantly reduced from 83.34mmHg before receiving l-citrulline malate to 79.1mmHg after that (p=0.01). All dimensions of the quality of life had statistical differences after receiving l-citrulline malate except limit due to physical health, limit due to emotional health and social functioning (p>0.05). Finally, pro-BNP difference was not statistically significant (p=0.9).. l-Citrulline malate improves the distance walk in six minutes and also the quality of life of patients with idiopathic arterial pulmonary hypertension and Eisenmenger Syndrome and also reduced mean arterial pulmonary hypertension.

Topics: Administration, Oral; Adult; Arterial Pressure; Citrulline; Eisenmenger Complex; Familial Primary Pulmonary Hypertension; Female; Humans; Malates; Male; Natriuretic Peptide, Brain; Pulmonary Artery; Quality of Life; Treatment Outcome; Walking; Young Adult

Differences in clinical effects between selective and dual endothelin (ET) receptor antagonists (ERA) in patients with pulmonary arterial hypertension (PAH) are currently unknown. We aimed to assess prospectively how transition from selective (sitaxsentan) to dual (bosentan) ERA affected exercise capacity and cardiocirculatory performance in patients with Eisenmenger's syndrome.. A series of seven stable patients with Eisenmenger's syndrome aged 40.0 (30.0-56.0) years old treated with sitaxsentan were assessed before and three months after transition to bosentan. Six minute walk test and magnetic resonance to assess LV and RV mass, volume and ejection fraction, and pulmonary flow, and laboratory tests were performed.. We observed an increase in LV mass [96.5 (66.0-116.0) vs. 123.0 (93.0-146.0)g; p=0.03], LV ejection fraction [55.0 (44.0-63.0) vs. 65.0 (58.0-70.0)%; p=0.02)], and pulmonary flow [64 (53.0-71.0) vs. 69.0 (55.0-84.0)ml/beat; p=0.046]. This was accompanied by an increase of oxygen saturation, elongation of 6MWD [435.0 (378.0-482.3) vs. 474 (405.0-534.7); p=0.02], decrease of NTproBNP level and increase of ET-1 level.. Three month follow-up of stable patients with Eisenmenger's syndrome transitioned from sitaxsentan to bosentan revealed improvement of exercise capacity despite significant elevation of ET-1 level. Concurrent increase of LV ejection fraction and pulmonary flow might have contributed to these favourable effects.

Topics: Adult; Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin Receptor Antagonists; Endothelin-1; Exercise; Female; Follow-Up Studies; Humans; Isoxazoles; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Sulfonamides; Thiophenes

Current guidelines emphasize that accurate risk stratification is important for patients with pulmonary arterial hypertension (PAH), however, few suggestions have been specified for PAH associated with congenital heart disease (PAH-CHD).. The aim of this study was to propose an accurate and simple system based on current guidelines for risk stratification in PAH-CHD patients during 12-month follow-up.. We reviewed 288 Chinese PAH-CHD patients between January 2014 and December 2016 in this retrospective cohort study. The low-risk criteria according to 2015 European Society of Cardiology guidelines and the adverse events (AEs) during follow-up were collected. The association between low-risk criteria and AEs was assessed with Cox regression, and a simplified risk stratification system was proposed.. There were 105 PAH-CHD patients included in the final analysis. Twenty-nine patients had AEs defined as death, initiation of new or combined medication treatment, or re-hospitalisation because of the PAH worsening. Among the low-risk criteria, WHO/NYHA functional class, 6-minute walking distance (6MWD), NT-proBNP and SvO. Among the low-risk criteria proposed by current guidelines, 6MWD and NT-proBNP predicted AEs independently for PAH-CHD patients. Simplified risk stratification system by taking these two parameters numerically provides accurate prognostic information in PAH-CHD patients.

Topics: Adult; China; Eisenmenger Complex; Female; Health Plan Implementation; Heart Defects, Congenital; Humans; Incidence; Infant; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Pulmonary Arterial Hypertension; Retrospective Studies; Risk Assessment; Walk Test

To determine the values of microvolt T-wave alternans (MTWA) in children and adolescents with Eisenmenger syndrome (ES) and controls.. Thirteen were included in the study. After analyzing the 24-h ECG recordings, MTWA was considered using three leads (V5, V1, and aVF). Right heart catheterization and 6-minute walk test (6-MWD) were applied to the patients and pro-brain natriuretic peptide levels were assessed; echocardiographic parameters were obtained from both the groups and the results were compared.. The MTWA value in lead V5 was 81.08±10.73 µV in the patient group (63.50±18.78 µV in the control group), in lead V1 was 75.00±16.86 µV (73.94±16.77 µV in the control group), and in lead aVF was 73.77±17.81 µV (72.61±16.21 µV in the control group). Comparison of MTWA values between patients and controls revealed that only lead V5 values were statistically different in the ES group. The 6-MWD scores significantly correlated with lead V5. Right atrial volume and right ventricular fractional area change were significantly correlated with lead V1. The Tei index was significantly correlated with lead aVF.. The MTWA lead V5 value was significantly higher in children with ES than in controls and was also correlated with decreased exercise tolerance.

Topics: Adolescent; Cardiac Catheterization; Case-Control Studies; Child; Child, Preschool; Echocardiography; Eisenmenger Complex; Electrocardiography; Exercise Test; Female; Heart Conduction System; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Young Adult

Topics: Adult; Arrhythmias, Cardiac; Biomarkers; Case-Control Studies; Echocardiography; Eisenmenger Complex; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Male; Natriuretic Peptide, Brain; Troponin I

Eisenmenger syndrome (ES) is commonly associated with depressive symptoms and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). We investigated the predictive value of depressive symptoms and NTproBNP levels for long-term outcomes in patients with ES.. Blood was drawn to measure NT-proBNP, and depressive symptoms were measured using the Korean version of the Beck Depression Inventory (BDI) in an outpatient clinic sample of 64 patients with ES (67% female; median age = 41.5 years [range, 21.0-74.8 years]). Cardiac events (hospitalization, emergency department visits, and cardiac death) were monitored during 3 years of follow-up.. During the follow-up period, 15 (23.4%) patients experienced a cardiac event. The combination of depressive symptoms and NT-proBNP levels better predicted future cardiac events than either variable alone. Patients with NT-proBNP > 510 pg/ml and a total BDI score > 10 had a 9.6 times higher risk for cardiac events than did patients with NT-proBNP ≤ 510 pg/ml or total BDI score ≤ 10 (p < .001).. Depressive symptoms and NT-proBNP levels are both associated with adverse clinical outcomes in ES.

Topics: Adult; Aged; Depression; Eisenmenger Complex; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Severity of Illness Index; Young Adult

The effect of bosentan on the ventricular and atrial performance in patients with Eisenmenger syndrome is unclear. In adult patients with Eisenmenger syndrome, we aimed to evaluate the midterm effect of bosentan on physical exercise, ventricular and atrial function, and pulmonary hemodynamics.. Forty adult patients before and after 24 weeks bosentan therapy underwent 6 min walk test, two-dimensional speckle tracking echocardiography, plasma NT-proBNP measurement and cardiac catheterization.. After 24 weeks, bosentan therapy an improvement was observed regarding the 6 min walk distance from a median (quartile 1-quartile 3) of 382.5 (312-430) to 450 (390-510) m (p = 0.0001), NT-proBNP from 527.5 (201-1,691.25) to 369 (179-1,246) pg/ml (p = 0.021), right ventricular mean longitudinal systolic strain from 18 (13-22) to 19 (14.5-25) % (p = 0.004), left ventricular mean longitudinal systolic strain from 16 (12-21) to 17 (16-22) % (p = 0.001), right atrial mean peak longitudinal strain from 26 (18-34) to 28 (22-34) % (p = 0.01) and right atrial mean peak contraction strain from 11 (8-16) to 13 (11-16) % (p = 0.005). The invasively obtained Qp:Qs and Rp:Rs did not significantly change under bosentan therapy.. In adult patients with Eisenmenger syndrome, bosentan therapy improves ventricular and atrial functions resulting in enhancement of physical exercise and reduction in the NT-proBNP level, while the pulmonary vascular resistance does not change substantially.

Topics: Adult; Antihypertensive Agents; Atrial Function; Bosentan; Cardiac Catheterization; Echocardiography; Eisenmenger Complex; Exercise Test; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sulfonamides; Vascular Resistance; Ventricular Function; Young Adult

To assess the relationship between elevated levels of B-type natriuretic peptide (BNP) and outcome in patients with Eisenmenger syndrome.. Retrospective study.. Tertiary centre for adult congenital heart disease.. All patients with Eisenmenger syndrome (n=181, age 36.9±12.1 years, 31% with Down syndrome) in whom BNP concentrations were measured as part of routine clinical care were included.. The study end point was all cause mortality.. During a median follow-up period of 3.3 years, 20 patients (7 with Down syndrome) died. Higher BNP concentrations were predictive of all cause mortality on univariate analysis in patients with or without Down syndrome. On multivariable Cox proportional hazard analysis, BNP predicted survival independently of renal function, Down syndrome, or 6 min walk test distance (p=0.004). Temporal increases in BNP concentration were also found to predict mortality. Treatment with disease targeting therapies was associated with a significant reduction in BNP concentrations.. BNP concentrations predict outcome in contemporary Eisenmenger patients. Increases in BNP concentrations over time are also of prognostic significance. In addition, disease targeting therapies may help to reduce BNP concentrations in this population, while treatment-naïve patients have static or rising BNP concentrations.

Topics: Adult; Biomarkers; Cardiac Surgical Procedures; Cause of Death; Eisenmenger Complex; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Severity of Illness Index; Survival Rate; Time Factors; United Kingdom

Topics: Cardiac Surgical Procedures; Eisenmenger Complex; Female; Humans; Male; Natriuretic Peptide, Brain

The aim of this study was to evaluate the prognostic value of brain natriuretic peptide (BNP) in outpatients with the Eisenmenger syndrome (ES). BNP is often elevated in patients with cyanotic congenital heart disease. The clinical utility of BNP in patients with cyanotic congenital heart disease and the ES has not been clearly delineated. Records of adults with ES who had undergone serum BNP measurement were reviewed. The primary end point was death or heart failure admission. Fifty-three patients were included, with 15 patients (28%) meeting the primary end point (death in 7, heart failure hospitalization in 8). Mean and median baseline BNP in patients meeting the primary end point were 322 ± 346 and 179 pg/ml, compared to 100 ± 157 and 41 pg/ml in those not meeting the primary end point (p = 0.0029). A Cox proportional-hazards model using baseline BNP between the 2 groups yielded a hazard ratio of 1.84 (95% confidence interval [CI] 1.19 to 2.85, p = 0.006). The relative risk for baseline BNP level >140 pg/ml was 4.62 (95% CI 1.80 to 11.3, p = 0.008). Patients who met the primary end point increased their BNP levels by 42.5 pg/ml per year (95% CI 12.09 to 72.95, p = 0.006) compared to 7.2 pg/ml per year (95% CI 2.01 to 12.47, p = 0.007) in patients who did not meet the primary end point. In conclusion, elevated BNP levels are predictive of death or heart failure admission in patients with the ES. A serum BNP level >140 pg/ml is a useful tool in identifying high-risk patients.

Topics: Adult; Biomarkers; California; Disease Progression; Eisenmenger Complex; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Survival Rate

Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression.. We recruited 41 patients with Eisenmenger syndrome (13 with Down syndrome), 55 with idiopathic PAH, and 47 healthy control subjects. Flow cytometry and in vitro assays were used to quantify EPCs and to assess cell function. The number of circulating CD34+, CD34+/AC133+, CD34+/KDR+, and CD34+/AC133+/KDR+ progenitor cells was low in Eisenmenger patients compared with healthy control subjects, and those with Down syndrome displayed even fewer EPCs. Reductions in EPC numbers correlated with New York Heart Association functional class, 6-minute walk distance, and plasma brain-type natriuretic peptide levels. The capacity of cultured peripheral blood mononuclear cells to form colonies and incorporate into tube-like structures was impaired in Eisenmenger patients. Idiopathic PAH patients had reduced numbers of EPCs, and the number of circulating EPCs correlated with invasive hemodynamic parameters in this cohort. Levels of immune inflammatory markers, cGMP, stable nitric oxide oxidation products, and asymmetric dimethylarginine were abnormal in patients with PAH and related to numbers of EPCs. Within the idiopathic PAH population, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers, resulting in levels consistently above those found with other therapies.. Circulating EPC numbers are reduced in 2 well-characterized forms of PAH, which also exhibit raised levels of inflammatory mediators. Sildenafil treatment may represent a pharmacological means of increasing circulating EPC numbers long-term.

Topics: AC133 Antigen; Aged; Antigens, CD; Antigens, CD34; Arginine; Cells, Cultured; Cyclic GMP; Down Syndrome; Eisenmenger Complex; Endothelium, Vascular; Exercise; Female; Flow Cytometry; Glycoproteins; Hematopoietic Stem Cells; Humans; Hypertension, Pulmonary; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Stem Cells; Sulfones; Vascular Endothelial Growth Factor Receptor-2; Vasodilator Agents

B-type natriuretic peptide (BNP) reflects volume overload on left ventricle and pulmonary hypertension (PH) in patients with ventricular septal defect (VSD). Pulmonary vascular resistance (PVR) has been reported to correlate positively with BNP in VSD patients with various degrees of PH. We aimed to investigate the relationship between PVR and BNP in VSD patients with severe PH. We examined 24 subjects with VSD concomitant severe PH aged from 2 months to 17 years (median: 4 months). The ratio of pulmonary to systemic pressure (Pp/Ps), the ratio of pulmonary to systemic flow (Qp/Qs), the ratio of pulmonary to systemic resistance (Rp/Rs), and PVR were determined by cardiac catheterization. PVR and Rp/Rs ranged from 1.6 to 15.5 (mean: 5.7 +/- 3.9) Wood unit . m(2) and 0.1 to 0.8 (mean: 0.4 +/- 0.2), respectively. BNP ranged from 5.5 to 69 (mean: 31 +/- 19) pg/ml. Negative correlations were observed between BNP and PVR (r = -0.56, p = 0.004) and BNP and Rp/Rs (r = -0.51, p = 0.01). BNP was significantly lower (<10 pg/ml) in VSD patients with Eisenmenger physiology as compared with the others (p = 0.003). We should draw attention to evaluate BNP values in VSD patients with severe PH.

Topics: Adolescent; Cardiac Catheterization; Child; Child, Preschool; Comorbidity; Echocardiography, Doppler; Eisenmenger Complex; Female; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Vascular Resistance