Mid-regional pro-adrenomedullin: an indicator of the failing Fontan circuit in patients with univentricular hearts?

AIMS: In patients after the Fontan procedure, assessment of a failing Fontan circuit is difficult. Natriuretic peptides failed to be reliable markers of functional status or systemic ventricular function in this patient cohort. The aim of the study was to assess the clinical utility of mid-regional pro-adrenomedullin (MR-proADM) in patients after the Fontan procedure. METHODS AND RESULTS: Plasma MR-proADM levels were measured in 53 patients after the Fontan procedure and compared with clinical status, echocardiographic, and laboratory parameters including NT-proBNP. Median MR-proADM levels were 0.668 nmol/L in patients with a failing Fontan circuit as compared with 0.357 nmol/L in those without Fontan failure (P = 0.001). Levels of MR-proADM were significantly related to the presence of Fontan failure (r = 0.444, P = 0.001), NYHA class (r = 0.434, P < 0.001), and γ-glutamyltransferase levels (r = 0.554, P < 0.001). According to receiver operating characteristic (ROC) curve analysis, Fontan failure was best predicted by MR-proADM [area under the curve (AUC) 0.985, P = 0.001], NT-proBNP (AUC 0.947, P = 0.003), NYHA class (AUC 0.962, P = 0.002), and the inspiratory/expiratory ratio of the inferior vena cava diameter (AUC 0.973, P = 0.007). The optimal cut-off of MR-proADM for the prediction of Fontan failure was 0.520 nmol/L with a sensitivity of 100%, specificity of 93.9%, positive predictive value of 57.1%, negative predictive value of 100%, and overall accuracy of 94.3%. However, the data should also be validated in a larger cohort of patients. CONCLUSION: Serial measurements of MR-proADM levels may help identify patients at risk for a failing Fontan circulation especially when exceeding 0.520 nmol/L. In these patients, intensified medical care should be considered to prevent further clinical deterioration.

Ventricular performance assessed by 2-dimensional strain analysis after Ross operation versus aortic valve reconstruction.

BACKGROUND: The Ross procedure is an established option for aortic valve replacement in young patients. It does, however, involve implantation of a valved conduit in the pulmonary position and dissection in the right ventricular (RV) myocardium with the possibility of RV impairment. Aortic valve reconstruction (AVr) may avoid the drawbacks of this method. METHODS: To assess ventricular performance, 2-dimensional (2D) echocardiography and longitudinal strain analysis were performed in 19 patients after a Ross procedure and 19 patients after AVr and compared with 19 age-matched healthy controls. RESULTS: Left ventricular (LV) volumes were significantly increased in both patient groups compared with controls (p < 0.05). Right ventricular (RV) volumes were significantly elevated in the Ross group compared with the AVr group (p < 0.05) and controls (p < 0.01). Peak longitudinal LV strain was significantly reduced in the Ross group (-14.8% ± 4.7%) compared with the AVr group (-18.8% ± 2.5%; p = 0.003) and healthy controls (-20.2% ± 3.9%; p = 0.001). Peak longitudinal RV strain was also significantly reduced in the Ross group (-21.8% ± 4.8%) compared with the AVr group (-25.1% ± 2.5%; p = 0.02) and healthy controls (-26.5% ± 3.2%; p = 0.003). Reduced RV strain was associated with increased pressure gradients of the pulmonary substitute (r = 0.48; p = 0.04) but not with follow-up time, RV volumes, or RV ejection fraction (EF). CONCLUSIONS: Elevation of LV volumes can still be noticed in patients years after the Ross operation or AVr. Increased RV volumes and a reduced RV longitudinal strain are found after the Ross operation, indicating persistent systolic RV dysfunction even in patients with mild RV pressure overload.

Growth differentiation factor 15--an early marker of abnormal function of the Fontan circuit in patients with univentricular hearts.

BACKGROUND: In patients after the Fontan procedure, assessment of ventricular function is difficult and amino-terminal pro-B-type natriuretic peptide levels failed to be directly related to echocardiographic measures of systolic ventricular function. The aim of the study was to evaluate growth differentiation factor 15 (GDF-15), a marker of various stress pathways in the heart and extracardiac tissues. METHODS: Plasma GDF-15 levels were measured in 38 consecutive patients after the Fontan procedure and compared to clinical, echocardiographic, and laboratory data; liver tissue stiffness; and venous hepatic flow velocities. RESULTS: Mean GDF-15 levels were 987.2±440.5 pg/mL in patients with an ejection fraction (EF)<50% as compared to 520.2±143.1 pg/mL in those with an EF≥50% (P<.001). Growth differentiation factor 15 levels were significantly related to the EF of the single ventricle (r=-0.66, P<.001), New York Heart Association functional class (r=0.43, P=.008), and γGT levels (r=0.50, P=.002) but weakly to liver tissue stiffness. According to receiver operating characteristic curve analysis, an EF<50% was best predicted by GDF-15 levels (area under the curve [AUC] 0.90, P<.001), peak venous hepatic flow at deep inspiration (AUC 0.89, P=.002), and age at Fontan operation (AUC 0.86, P=.001). Growth differentiation factor 15 and age at Fontan operation proved to be independent predictors in the multivariate analysis. The optimal cutoff of GDF-15 for the prediction of an EF<50% was calculated to be 613 pg/mL with a sensitivity of 90.0% and specificity of 85.7%. CONCLUSIONS: Growth differentiation factor 15 might be helpful in detecting early abnormal function of the Fontan circuit in patients with univentricular hearts. In patients with GDF-15 levels exceeding 613 pg/mL, further cardiac evaluation should be considered because impaired systolic function of the single ventricle may be present.

Serial measurement of the N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts poor outcome in a patient with congenitally corrected transposition of the great arteries (ccTGA).

The usefulness of natriuretic peptides to assess myocardial function in patients with a systemic morphological right ventricle is still unclear. In this report we describe the clinical course of a young woman with congenitally corrected transposition of the great arteries (ccTGA) who suffered from a progressive deterioration of myocardial function after child birth despite intensive medical treatment and additional cardiac resynchronization therapy. In this woman, serial measurement of NT-proBNP levels was related to the velocity time integral over the aortic valve and indicated worsening of the patient's haemodynamic status and finally death.

Assessment of left ventricular dyssynchrony and function using real-time 3-dimensional echocardiography in patients with congenital right heart disease.

BACKGROUND: Patients after repair of congenital right heart disease (CRHD) may exhibit left ventricular (LV) dyssynchrony (LVD). However, the diagnosis of LVD is difficult and its reliability limited because current methods do not assess LVD of the whole LV simultaneously. The aim of the study was to assess LVD according to a novel global systolic dyssynchrony index (SDI) derived from real-time 3-dimensional echocardiography in patients after repaired CRHD. METHODS: Two-dimensional echocardiography and real-time 3-dimensional echocardiography were performed in 30 patients after CRHD repair and in 30 matched healthy controls. Real-time 3-dimensional echocardiography data sets provided time-volume curves, and 2 global SDIs were derived from the dispersion of time to reach minimal systolic volume according to a 16- or 17-LV segment model. RESULTS: Both SDIs were significantly elevated in the patient as compared with the control group (P < .001). A cutoff value for both SDIs was calculated and LVD defined as one of the SDIs exceeding cutoff. Left ventricular dyssynchrony was present in 5 (100%) of 5 patients with a LV ejection fraction (EF) <50% and 13 (52%) of 25 patients with preserved LVEF, thus being diagnosed in a total of 18 (60%) of 30 patients. Moreover, patients with LVD showed a significantly higher degree of pulmonary regurgitation (P = .01) with elevated right ventricular volumes and altered septal motion. Stepwise multivariate analysis identified LVEF (P = .005) and the degree of pulmonary regurgitation (P = .02) as independent predictors of LVD. CONCLUSIONS: Left ventricular dyssynchrony can be detected in about 60% of patients after CRHD repair and is mainly due to significant pulmonary regurgitation resulting in an altered septal motion and systolic LV function.

Validity of N-terminal propeptide of the brain natriuretic peptide in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver disease.

BACKGROUND AND AIMS: Left ventricular diastolic dysfunction has been reported in patients with liver cirrhosis. Although conventional Doppler echocardiography has been used to assess diastolic filling dynamics, this technique is limited in diagnosing left ventricular diastolic dysfunction. The aim of the study was to validate the N-terminal propeptide of the brain natriuretic peptide (NT-proBNP) in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver disease. METHODS: In 64 patients, left ventricular diastolic dysfunction was classified using tissue Doppler imaging and serum levels of NT-proBNP were measured. RESULTS: Left ventricular diastolic dysfunction was found in 25 of 31 (80.6%) patients with severe liver fibrosis/cirrhosis versus 2 of 8 (25.0%) patients with moderate and 6 of 25 (24.0%) patients with mild liver fibrosis (P<0.001). Mean NT-proBNP levels were 407.1+/-553.4 pg/ml in patients with severe fibrosis/cirrhosis as compared with 60.8+/-54.9 pg/ml and 55.4+/-41.4 pg/ml in patients with mild and moderate fibrosis (P=0.001). NT-proBNP was most accurate in predicting advanced left ventricular diastolic dysfunction with an area under the receiver-operating characteristic curve of 0.90 (95% confidence interval, 0.77-1.0; P<0.001). A cutoff value of greater than 290 pg/ml was highly predictive of advanced left ventricular diastolic dysfunction. CONCLUSION: NT-proBNP is a useful marker in detecting advanced left ventricular diastolic dysfunction in patients with chronic liver disease. Patients with severe liver fibrosis/cirrhosis and NT-proBNP levels exceeding 290 pg/ml should undergo further cardiac evaluation.