Comparison of advanced echocardiographic right ventricular functional parameters with cardiovascular magnetic resonance in adult congenital heart disease

AimsAdvanced transthoracic echocardiography (TTE) using volumetric and deformational indices provides detailed quantification of right ventricular (RV) function in adults with congenital heart disease (ACHD). Two-dimensional multi-plane echocardiography (2D-MPE) has demonstrated regional wall differences in RV longitudinal strain (LS). This study aims to evaluate the association of these parameters with cardiovascular magnetic resonance (CMR).Methods and resultsOne hundred stable ACHD patients with primarily affected RVs were included (age 50±5 years; 53% male). Conventional and advanced echocardiographic RV functional parameters were compared to CMR-derived RV function.Advanced echocardiographic RV functional parameters were measurable in approximately one-half of the study co-hort, whilst multi-wall LS assessment feasibility was lower. CMR RV ejection fraction (CMR-RVEF) was moderately correlated with deformational, area and volumetric parameters (RV global LS [lateral wall and septum], n=55: r=-0.62, p<0.001; RV wall average LS, n=34: r=-0.49, p=0.002; RV lateral wall LS, n=56: r=-0.45, p<0.001; fractional area change [FAC], n=67: r=0.48, p<0.001; 3D-RVEF, n=48: r=0.40, p=0.005). Conventional measurements such as TAPSE and RV S’ correlated poorly. RV global LS best identified CMR-RVEF <45% (AUC: 0.84, p<0.001: cut-off value -19%: sensitivity 100%, specificity 57%). RVEF and LS values were significantly higher when measured by CMR compared to TTE (mean difference RVEF: 5[-9 to 18]%; lateral (free) wall LS: -7[7 to -21]%; RV global LS: -6 [5 to -16]%) whilst there was no association between respective LS values.ConclusionIn ACHD patients, advanced echocardiographic RV functional parameters are moderately correlated with CMR-RVEF, although significant differences exist between indices measurable by both modalities

Blood Biomarkers Predict 10-Year Clinical Outcomes in Adult Patients With Congenital Heart Disease

Background: The adult congenital heart disease (ACHD) population is growing and risk prediction is important to predict adverse outcome and consult patients during their lifecourse. Objectives: This study aims to describe the long-term prognostic value of blood biomarkers in ACHD. Methods: In this prospective observational cohort study, 602 patients with moderate or complex ACHD were included (median age 32.5 years [IQR: 24.7-41.2], 42% female, 90% New York Heart Association I). N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive-troponin T, growth differentiation factor 15, high-sensitive-C-reactive protein, suppression of tumorigenicity-2 and galectin-3, as well as full blood count, renal function, LDL, and HDL were measured. Cox models were applied to relate the selected biomarkers with the primary end point of all-cause mortality and secondary end point of mortality or heart failure. Standardized HRs adjusted for relevant prognostic factors, including age, sex, and complexity of diagnosis, were reported. Results: Abnormal biomarker levels were present in 424 (70.4%) patients. During a median follow-up of 10.1 years, 41 (6.8%) patients died and 81 (13.5%) developed heart failure. Associations were observed between the primary and secondary end point and red cell distribution width, NT-proBNP, and growth differentiation factor 15. In a multibiomarker model, only NT-proBNP remained associated with mortality (HR: 2.74; 95% CI: 2.01-3.74). NT-proBNP significantly improved the C-statistic of the clinical prediction model (0.85-0.92). Based on NT-proBNP alone, low-risk patients could be identified. Patients with NT-proBNP &lt;76 ng/L showed a 10-year heart failure-free survival of 98.5%. Conclusions: Blood biomarkers have prognostic value in ACHD. NT-proBNP improves risk prediction and is able to identify low-risk patients. Its routine use should be implemented in ACHD.</p

Long term outcome after surgical ASD-closure at young age:Longitudinal follow-up up to 50 years after surgery

OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia).METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years.RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified.CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.</p

Long term outcome after surgical ASD-closure at young age:Longitudinal follow-up up to 50 years after surgery

OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia).METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years.RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified.CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.</p

Prognostic value of the electrocardiogram in patients with bicuspid aortic valve disease

Background: Identifying bicuspid aortic valve (BAV) patients at risk for cardiac events remains challenging and the role of the electrocardiogram (ECG) has not yet been described. Therefore, this study aims to describe ECG parameters in BAV patients, and investigate their prognostic value. Methods: In this single-center prospective study patients with BAV without a prior aortic valve replacement (AVR) were included. Transthoracic echocardiogram and 12‑lead resting-ECG were obtained. Associations between ECG parameters and the composite endpoint of all-cause mortality and AVR were assessed using Cox-proportional hazard analysis. Results: 120 patients with BAV were included (median age 30 years, 61% male). Median aortic jet velocity was 2.4 m/s [IQR: 1.7–3.4] and 5 patients (4%) had severe aortic regurgitation. All patients were in sinus rhythm. Any ECG abnormality was present in 57 patients (48%). Median PR-interval was 156 [IQR: 138–170] msec. A deviating QRS axis was found in 17 patients (14%) and Cornell criteria for LVH were fulfilled in 20 patients (17%). Repolarization abnormalities were present in 12 patients (10%). Median follow-up duration was 7.0 [6.3–9.8] years, during which 23 patients underwent AVR and 2 patients died. After adjusting for age, a longer PR-interval was associated with worse intervention-free survival (HR 1.02, 95% CI: 1.01–1.04). Conclusion: Almost half of the patients with BAV had abnormalities on their ECG. Moreover, the PR-interval may be an interesting prognostic marker for intervention-free survival in BAV patients.</p

Blood and Imaging Biomarkers in the Long-term Follow-up of Bicuspid Aortic Valve Patients

Background: Bicuspid aortic valve (BAV) is a common congenital heart defect. Patients with BAV are at risk for long-term complications such as valve stenosis and regurgitation. This study aimed to investigate sex differences in blood and imaging biomarkers and to describe the long-term prognostic value of blood and echocardiographic biomarkers. Methods:Patients were included from 2 prospective observational cohort studies; they underwent venous blood sampling and transthoracic echocardiography including speckle tracking. Analyzed blood biomarkers were red-cell distribution width (RDW), creatinine, C-reactive protein (CRP), troponin T, N-terminal pro B-type natriuretic peptide (NT-proBNP), and transforming growth factor-beta (TGF-β). Sex differences were analyzed at baseline. Associations between biomarkers and arrhythmia-free and intervention-free survival were determined by Cox regression, adjusted for age and sex. Results:A total of 182 patients with BAV were included: median age 34; interquartile range [IQR]: 23-46 years; 55.5% male. CRP, NT-proBNP, and RDW were higher in women, whereas creatinine, troponin T and TGF-β were higher among men. After a median follow-up time of 6.9 (IQR: 6.5-9.9) years, arrhythmia-free and intervention-free survival was, 81.0% and 73.1%, respectively. NT-proBNP was associated with both arrhythmia-free and intervention-free survival (hazard ratio [HR], 1.94, P = 0.005 and HR, 2.06, P = 0.002, respectively). On echocardiography higher left atrial (LA) size, left ventricular end-diastolic diameter (LVEDD), left ventricular (LV) mass index and E/e’ ratio were associated with lower arrhythmia-free survival, whereas higher LA size, LV mass index, aortic valve peak velocity, and aortic regurgitation were associated with lower intervention-free survival. Conclusions: Differences were observed in blood biomarkers between men and women with BAV. Besides LV systolic parameters, diastolic LV function and NT-proBNP should have a more prominent role as prognostic markers in clinical care.</p

Echocardiographic parameters of severe pulmonary regurgitation after surgical repair of tetralogy of Fallot

Aims: Reliable evaluation of the severity and consequences of pulmonary regurgitation (PR) in patients with repaired tetralogy of Fallot (TOF) is crucial to timely identify the need for pulmonary valve intervention. We aimed to identify the accuracy of echocardiographic parameters to differentiate between moderate and severe PR, using phase contrast cardiac magnetic resonance imaging (CMR) as gold standard. Methods and results: In this cross-sectional study, 45 TOF patients with both echocardiographic and CMR measurements of PR were enrolled. All quantitative and semiquantitative echocardiographic measurements such as pressure half time (PHT), Color flow jet width (CFJW), ratio CFJW/right ventricle outflow tract (RVOT) diameter, PR index and the presence of early termination of the PR jet, end-diastolic antegrade flow and diastolic backflow in main pulmonary artery (MPA), and PA branches correlated significantly with PR fraction on CMR. Qualitative assessment with color flow on echocardiography overestimated PR Multivariate linear regression analysis identified the ratio of CFJW/RVOT diameter and PHT as independent predictors of PR fraction. Accuracy of echo parameters was tested to differentiate between mild-to-moderate and severe PR Combining different echocardiographic parameters increased sensitivity and specificity. The addition of diastolic flow reversal in the PA branches to PHT below 167 milliseconds increased the NPV from 87% to 89% and PPV from 62% to 76%. Conclusions: Comparison with CMR confirms that echocardiographic parameters are reliable in predicting PR severity. Combined measurement of diastolic flow reversal in the pulmonary artery branches and PHT is reliable in the detection of severe PR in the follow-up of TOF patients

Quantitative assessment of systolic left ventricular function with speckle-tracking echocardiography in adult patients with repaired aortic coarctation

Despite successful aortic coarctation (CoA) repair, systemic hypertension often recurs which may influence left ventricular (LV) function. We aimed to detect early LV dysfunction using LV global longitudinal strain (GLS) in adults with repaired CoA, and to identify associations with patient and echocardiographic characteristics. In this cross-sectional study, patients with repaired CoA and healthy controls were recruited prospectively. All subjects underwent echocardiography, ECG and blood sampling within 1 day. With speckle-tracking echocardiography, we assessed LV GLS on the apical four-, three- and two-chamber views. We included 150 subjects: 75 patients (57 % male, age 33.4 ± 12.8 years, age at repair 2.5 [IQR: 0.1–11.1] years) and 75 healthy controls of similar sex and age. LV GLS was lower in patients than in controls (−17.1 ± 2.3 vs. −20.2 ± 1.6 %, P < 0.001). Eighty percent of the patients had a normal LV ejection fraction, but GLS was still lower than in controls (P < 0.001). In patients, GLS correlated with systolic and diastolic blood pressure (r = 0.32, P = 0.009; r = 0.31, P = 0.009), QRS duration (r = 0.34, P = 0.005), left atrial dimension (r = 0.27, P = 0.029), LV mass (r = 0.30, P = 0.014) and LV ejection fraction (r = −0.48, P < 0.001). Patients with either associated cardiac lesions, multiple cardiac interventions or aortic valve replacement had lower GLS than patients without. Although the majority of adults with repaired CoA seem to have a normal systolic LV function, LV GLS was decreased. Higher blood pressure, associated cardiac lesions, and larger left atrial dimension are related with lower GLS. Therefore, LV GLS may be used as objective criterion for early detection of ventricular dysfunction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10554-016-0838-8) contains supplementary material, which is available to authorized users

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

SCUBA Diving in Adult Congenital Heart Disease

Conventionally, scuba diving has been discouraged for adult patients with congenital heart disease (ACHD). This restrictive sports advice is based on expert opinion in the absence of high-quality diving-specific studies. However, as survival and quality of life in congenital heart disease (CHD) patients have dramatically improved in the last decades, a critical appraisal whether such restrictive sports advice is still applicable is warranted. In this review, the cardiovascular effects of diving are described and a framework for the work-up for ACHD patients wishing to engage in scuba diving is provided. In addition, diving recommendations for specific CHD diagnostic groups are proposed