The role of cystatin C as a biomarker for prognosis in pulmonary arterial hypertension due to congenital heart disease

AbstractBackgroundAdults with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) have a poor prognosis. Identifying patients with a high risk for clinical events and death is important because their prognosis can be improved by intensifying their treatment. Cystatin C, a novel cardiac biomarker, correlates with right ventricular dimensions in patients with idiopathic PAH, giving it potential to determine prognosis in PAH-CHD patients. We investigated the predictive value of cystatin C for long-term mortality and clinical events.MethodsFifty-nine PAH-CHD patients (mean age 42 SD 13 years, 42% male) were included in this prospective observational study, with cystatin C measurements between 2005 and 2015 on the outpatient clinic. Patients were evaluated with a standardized evaluation protocol including laboratory, functional and echocardiographic variables. Clinical events comprised worsening functional classification, worsening heart failure, symptomatic hyperviscosity, haemoptysis and arrhythmia. We used Cox regression to determine predictors for mortality and clinical events.ResultsMean follow-up was 4.4years, during which 12 (20%) patients died. Cystatin C (HR 1.3, p<0.001), creatinine (HR 1.2, p<0.001), NT-pro-BNP (HR 2.0, p=0.012), hs-troponin T (HR 1.9, p=0.005), 6-MWD (HR 0.8, p=0.044) and TAPSE (HR 0.8, p<0.001) predicted mortality. Similar results were found for the prediction of clinical events. When adjusted for NT-pro-BNP or glomerular filtration rate in multivariate analysis, cystatin C remained predictive for mortality.ConclusionsCystatin C, a novel cardiac biomarker, predicts long-term mortality and clinical events in patients with PAH-CHD. Consequently, cystatin C may attribute to clinical decision making regarding treatment intensity

Accuracy of Echocardiography to Estimate Pulmonary Artery Pressures With Exercise: A Simultaneous Invasive-Noninvasive Comparison

Exercise echocardiography is often applied as a noninvasive strategy to screen for abnormal pulmonary hemodynamic response, but it is technically challenging, and limited data exist regarding its accuracy to estimate pulmonary arterial pressure during exercise. Among 65 patients with exertional intolerance undergoing upright invasive exercise testing, tricuspid regurgitation (TR) Doppler estimates and invasive measurement of pulmonary arterial pressure at rest and peak exercise were simultaneously obtained. TR Doppler envelopes were assessed for quality. Correlation, Bland-Altman, and receiver-operating characteristic curve analyses were performed to evaluate agreement and diagnostic accuracy. Mean age was 62±13 years, and 31% were male. High-quality (grade A) TR Doppler was present in 68% at rest and 34% at peak exercise. For grade A TR signals, echocardiographic measures of systolic pulmonary arterial pressure correlated reasonably well with invasive measurement at rest (r=0.72, P 3.0 mm Hg/L per minute increase), with 91% sensitivity and 82% specificity (area under the curve, 0.90; 95% confidence interval, 0.77-1.0; P=0.001). Agreement between echocardiographic and invasive measures of pulmonary pressures during upright exercise is good among the subset of patients with high-quality TR Doppler signal. While the limits of agreement are broad, our results suggest that in those patients, sensitivity is adequate to screen for abnormal pulmonary hemodynamic response during exercis

Hemodynamic and metabolic characteristics associated with development of a right ventricular outflow tract pressure gradient during upright exercise

We recently reported a novel observation that many patients with equal resting supine right ventricular(RV) and pulmonary artery(PA) systolic pressures develop an RV outflow tract(RVOT) pressure gradient during upright exercise. The current work details the characteristics of patients who develop such an RVOT gradient. We studied 294 patients (59.7±15.5 years-old, 49% male) referred for clinical invasive cardiopulmonary exercise testing, who did not have a resting RVOT pressure gradient defined by the simultaneously measured peak-to-peak difference between RV and PA systolic pressures. The magnitude of RVOT gradient did not correspond to clinical or hemodynamic findings suggestive of right heart failure; rather, higher gradients were associated with favorable exercise findings. The presence of a high peak RVOT gradient (90th percentile, ≥33mmHg) was associated with male sex (70 vs. 46%, p = 0.01), younger age (43.6±17.7 vs. 61.8±13.9 years, p <0.001), lower peak right atrial pressure (5 [3-7] vs. 8 [4-12]mmHg, p <0.001), higher peak heart rate (159±19 vs. 124±26 beats per minute, p <0.001), and higher peak cardiac index (8.3±2.3 vs. 5.7±1.9 L/min/m2, p <0.001). These associations persisted when treating peak RVOT as a continuous variable and after age and sex adjustment. At peak exercise, patients with a high exercise RVOT gradient had both higher RV systolic pressure (78±11 vs. 66±17 mmHg, p <0.001) and lower PA systolic pressure (34±8 vs. 50±19 mmHg, p <0.001). Development of a systolic RV-PA pressure gradient during upright exercise is not associated with an adverse hemodynamic exercise response and may represent a normal physiologic finding in aerobically fit young peopl

Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification

The aging congenital heart disease (CHD) population is prone to develop a variety of sequelae, including pulmonary arterial hypertension (PAH). Previous prevalence estimates are limited in applicability due to the use of tertiary centers, or database encoding only. We aimed to investigate the contemporary prevalence of PAH in adult CHD patients, using a nationwide population. A cross-sectional study was performed, using the population-based Dutch CONgenital CORvitia (CONCOR) registry. All patients born with a systemic-to-pulmonary shunt, thereby at risk of developing PAH, were identified. From this cohort, a random sample was obtained and carefully reviewed. Of 12,624 registered adults with CHD alive in 2011, 5,487 (44%) were at risk of PAH. The random sample consisted of 1,814 patients (mean age 40 ± 15 years) and 135 PAH cases were observed. PAH prevalence in patients born with a systemic-to-pulmonary shunt was 7.4%. The prevalence of PAH after corrective cardiac surgery was remarkably high (5.7%). Furthermore, PAH prevalence increased with age, from 2.5% under 30 years until 35% in the eldest. PAH prevalence in the entire CHD population was 3.2%. Based on 3000 per million adult CHD patients in the general population, we can assume that PAH-CHD is present in 100 per million. This new approach using a nationwide CHD population reports a PAH prevalence of 3.2% in CHD patients, and 100 per million in the general adult population. Especially in patients after shunt closure and the elderly, physicians should be aware of PAH-CHD, to provide optimal therapeutic and clinical car

Percutaneous mitral valve repair preserves right ventricular function

Chronic mitral regurgitation (MR) often leads to diminished right ventricular (RV) function due to long-standing pressure and volume overload. Surgical intervention often adds to the preexisting RV dysfunction. Percutaneous mitral valve (MV) repair can reduce MR, but to what extent this affects the right ventricle is unknown. Consecutive patients scheduled for percutaneous MV repair using the MitraClip system underwent transthoracic echocardiography at baseline and at 1- and 6-month follow-up. RV systolic function was evaluated using five echocardiographic parameters. RV afterload was evaluated using systolic pulmonary arterial pressure and the mean MV pressure gradient. Residual MR was defined as grade ≥ 3 and mitral stenosis (MS) as a mean MV pressure gradient ≥ 5 mm Hg. Sixty-eight patients (52% men; mean age, 75 ± 10 years) were included. Six months after MitraClip implantation, there were no significant changes in any of the RV parameters. MR decreased (P < .01) and the mean MV pressure gradient increased during follow-up (2.3 ± 1.4 mm Hg at baseline vs 4.5 ± 2.7 mm Hg at 6 months, P < .01). Patients with both residual MR and MS 6 months after MitraClip implantation showed significantly higher systolic pulmonary arterial pressure values (P < .01) and lower New York Heart Association functional classes (P < .01) compared with patients without residual MR or MS. Percutaneous MV repair, in contrast to surgical repair or replacement, does not negatively affect RV function. After repair, RV afterload and New York Heart Association functional class are improved in the case of successful repair but adversely affected in the presence of both residual MR and M

Mitral inflow patterns after MitraClip implantation at rest and during exercise

MitraClip implantation reduces mitral regurgitation effectively but decreases mitral valve area, creating iatrogenic mitral stenosis. Evaluation with transesophageal echocardiography intraprocedurally is necessary to measure mitral regurgitation and mitral valve pressure gradient (MVPG) to determine whether it is necessary and safe to place more clips. The aim of this study was to investigate whether these intraprocedural hemodynamics represent postprocedural measurements and whether exercise is affected by the stenosis. In this retrospective single-center study, 51 patients who underwent MitraClip implantation were included. Measurements were performed intraprocedurally using transesophageal echocardiography and postprocedurally using transthoracic echocardiography. In 23 of these patients, exercise echocardiography was performed at follow-up. Intraprocedural mean MVPG was 3.0 ± 1.6 mm Hg and increased to 4.3 ± 2.2 mm Hg postprocedurally (P < .001). During exercise, mean MVPG increased significantly compared with rest conditions (from 3.6 ± 1.7 to 6.3 ± 2.7 mm Hg, P < .001). Six patients had mean resting MVPGs ≥ 5 mm Hg at follow-up and had higher systolic pulmonary artery pressure (sPAPs) than patients with mean MVPGs < 5 mm Hg (47 ± 7 vs 35 ± 12 mm Hg, P = .035). Higher MVPG and sPAP did not lead to more symptoms of heart failure. Receiver operating characteristic curve analysis showed an estimated cutoff point for intraprocedural pressure half-time of 91 msec to identify patients with mitral stenosis and sPAP ≥ 50 mm Hg postprocedurally. Mean MVPG during MitraClip implantation measured by TEE underestimates the hemodynamics in daily life, of which operators should be aware when deciding on placing one or more clips. Pressure half-time seems to be the most robust parameter compared with mean and maximum MVPG and may contribute to this decision. Patients with higher mean MVPGs after MitraClip implantation have higher sPAPs at follow-up. However, more symptoms of heart failure were not detected at follow-u