Exploring the Prognostic Value of Novel Markers in Adults With a Systemic Right Ventricle.

Background Adults with a systemic right ventricle (sRV) have a high risk of cardiac complications. This study aimed to identify prognostic markers in adults with sRV based on clinical evaluation, echocardiography, and blood biomarkers. Methods and Results In this prospective cohort study, consecutive clinically stable adults with sRV caused by Mustard- or congenitally corrected transposition of the great arteries were included (2011-2013). Eighty-six patients were included (age 37±9 years, 65% male, 83% New York Heart Association functional class I, 76% Mustard transposition of the great arteries, 24% congenitally corrected transposition of the great arteries). Venous blood sampling was performed including N-terminal pro B-type natriuretic peptide, high-sensitive-troponin-T, high-sensitivity C-reactive protein, growth differentiation factor-15, galectin-3, red cell distribution width, estimated glomerular filtration rate, and hemoglobin. Besides conventional echocardiographic measurements, longitudinal, circumferential, and radial strain were assessed using strain analysis. During a median follow-up of 5.9 (interquartile range 5.3-6.3) years, 19 (22%) patients died or had heart failure (primary end point) and 29 (34%) patients died or had arrhythmia (secondary end point). Univariable Cox regression analysis was performed using dichotomous or standardized continuous variables. New York Heart Association functional class >I, systolic blood pressure, and most blood biomarkers were associated with the primary and secondary end point (galectin-3 not for primary, N-terminal pro B-type natriuretic peptide and high-sensitivity C-reactive protein not for secondary end point). Growth differentiation factor-15 showed the strongest association with both end points (hazard ratios; 2.44 [95% CI 1.67-3.57, P<0.001], 2.00 [95% CI 1.46-2.73, P<0.001], respectively). End-diastolic basal dimension of the subpulmonary ventricle was associated with both end points (hazard ratio: 1.95 [95% CI 1.34-2.85], P<0.001, 1.70 [95% CI 1.21-2.38, P=0.002], respectively). Concerning strain analysis, only sRV septal strain was associated with the secondary end point (hazard ratio 0.58 [95% CI 0.39-0.86], P=0.006). Conclusions Clinical, conventional echocardiographic, and blood measurements are important markers for risk stratification in adults with a sRV. The value of novel echocardiographic strain analysis seems limited.

The Prognostic Value of Myocardial Deformation in Adult Patients With Corrected Tetralogy of Fallot.

BACKGROUND: Adult patients with repaired tetralogy of Fallot (ToF) are at risk for complications such as heart failure and sudden cardiac death, and identifying high-risk patients is important. Reduced left ventricular (LV) and right ventricular (RV) function has been identified as a predictor of outcomes. However, LV ejection fraction is often preserved, and RV function is difficult to assess. With the introduction of strain analysis, an easy and more sensitive parameter became available. The aim of this study was to investigate the association between strain variables and cardiovascular events in patients with ToF. METHODS: Stable adult patients with repaired ToF were consecutively included in a prospective observational study between 2011 and 2013 (N = 151; median age, 33.2 years [interquartile range, 25.5-42.0 years]; 61.6% men). For the left ventricle, global longitudinal strain and apical and basal rotation were measured, and longitudinal strain was measured for the right ventricle. The primary endpoint was a composite of death or heart failure. The secondary endpoint was a composite of death, heart failure, arrhythmia, reintervention, or hospitalization for cardiac reasons. RESULTS: During a median follow-up period of 71.5 months (interquartile range, 64.0-75.3 months), the primary and secondary endpoints occurred in 14 (9%) and 62 (41%) patients, respectively. After adjusting for LV ejection fraction and LV global longitudinal strain, RV longitudinal strain remained independently associated with the primary endpoint in a ridge regression analysis. LV apical rotation remained independently associated with the secondary end point (adjusted hazard ratio, 0.72; 95% CI, 0.52-0.98; P = .035) after adjusting for age, New York Heart Association functional class, QRS duration, LV ejection fraction, RV longitudinal strain, and LV global longitudinal strain. CONCLUSIONS: Myocardial deformation variables of both the left and right ventricles were associated with cardiovascular events in patients with ToF. LV and RV longitudinal strain and LV rotation should become part of the routine assessment of patients with ToF.

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.

In-depth echocardiographic analysis of left atrial function in healthy adults using speckle tracking echocardiography and volumetric analysis.

PURPOSE: Left atrial (LA) dilatation is predictive for complications in a multitude of cardiac diseases; therefore, adequate assessment is essential. Technological advances have made it possible to quantify LA function with Speckle Tracking Echocardiography (STE); however, there are currently no recommendations for normal values with regard to LA function. We aimed to assess LA myocardial and volumetric function in a healthy cohort and investigate correlations with baseline characteristics. METHODS: This prospective cohort study included 147 (aged 20-72) healthy individuals and assessed LA volumetric function using maximum, minimum and pre-a-wave volumes and myocardial function using reservoir function using peak strain in LA relaxation (LA-strain), conduit function using peak strain rate in early LA contraction (LA-SRe) and pump function using peak strain rate in late LA contraction (LA-SRa). RESULTS: Mean LA-strain was 39.7 ± 6.2%, LA-SRe -2.78 ± 0.62 s-1 and LA-SRa -2.56 ± 0.62 s-1 . Subjects were divided into 5 age decades (each 50% female). LA-strain and LA-SRe were lower in the oldest groups, whereas LA-SRa was higher. LA-SRa was higher in males(-2.69 ± 0.68 s-1 vs -2.42 ± 0.52 s-1 ). Age-specific values are provided. Age proved to be an independent predictor for LA-SRa after correction for blood pressure and heart rate. LA expansion index and passive emptying fraction decreased with age, while active emptying fraction increased with age. LA maximum volume did not increase with age. CONCLUSION: This study provides normal values for the three phasic functions of the LA, assessed with STE and volumetric function. Our results suggest the need for age-specific reference ranges, and normal values for this cohort have been calculated.

Prognostic significance of anterior mitral valve leaflet length in individuals with a hypertrophic cardiomyopathy gene mutation without hypertrophic changes.

PURPOSE: Previous studies suggest that anterior mitral valve leaflet (AMVL) elongation is a primary phenotypic feature in hypertrophic cardiomyopathy (HCM). Our aim was to assess AMVL length in individuals with HCM gene mutations and in healthy controls and to identify predictors of the development of HCM during follow-up. METHODS: A total of 133 HCM mutation carriers and 135 controls underwent cardiac examination including electro- and echocardiography. AMVL length was measured in the parasternal long axis and apical three chamber view during diastole. Univariate and multivariable cox proportional hazard regression analyses were performed to identify predictors of HCM. RESULTS: There were no significant differences between HCM mutation carriers and controls regarding age and sex. In the parasternal long axis view, AMVL length was similar in mutation carriers and controls (24 ± 4 vs 24 ± 4 mm, p = 0.8). In the apical three chamber view, AMVL were shorter in mutation carriers (29 ± 4 vs 30 ± 4 mm, p = 0.02). When averaged for both views, AMVL length was similar in mutation carriers and controls (27 ± 3 vs 27 ± 3 mm, p = 0.2). During 5.8 ± 3.0 years follow-up, 13 (14%) HCM mutation carriers developed HCM. Pathological Q wave (hazard ratio 9.89, p = 0.004), E/e' ratio (hazard ratio 2.52, p = 0.001), and maximal wall thickness (hazard ratio 2.15, p = 0.001) were independent predictors of HCM. AMVL length was not predictive of the development of HCM. CONCLUSIONS: AMVL length is similar in HCM mutation carriers and controls. AMVL length is not predictive of the development of HCM, in contrast to pathological Q wave, E/e' ratio, and maximal wall thickness.

Three-dimensional echocardiography for the assessment of left ventricular geometry and papillary muscle morphology in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HC) is characterized by left ventricular (LV) hypertrophy and associated with papillary muscle (PM) abnormalities. The aim of this study was to evaluate the utility of three-dimensional echocardiography (3DE) for the geometric assessment of LV hypertrophy and PM morphology. METHODS: The study included 24 patients with an established diagnosis of HC and 31 healthy controls. 3DE was performed using an iE33 or EPIQ 7C ultrasound system with an X5-1 transducer. QLAB software was used for the 3D analysis of LV wall thickness (LVWT) and PM morphology and hypertrophy; the number and cross-sectional area (CSA) of anterolateral and posteromedial PMs; and the presence of bifid or accessory PMs. RESULTS: Patients with HC had a larger LVWT compared to controls in all segments (p < 0.001), and LVWT was largest in the midventricular septal segment (2.12 ± 0.68 cm). The maximum LVWT followed a spiral pattern from the LV base to the apex. The CSA of both anterolateral and posteromedial PMs was larger in patients with HC than in controls (1.92 vs. 1.15 cm2; p = 0.001 and 1.46 vs. 1.08 cm2; p = 0.033, respectively). The CSA of the posteromedial PM was larger in patients with LVOT obstruction than in those without (2.64 vs 1.16 cm2, p = 0.021). CONCLUSIONS: 3DE allows the assessment of LV geometry and PM abnormalities in patients with HC. 3DE demonstrated that the maximum hypertrophy was variable and generally located in a spiral from the LV base to the apex.

Prognostic value of galectin-3 in adults with congenital heart disease.

OBJECTIVE: Galectin-3 is an emerging biomarker for risk stratification in patients with heart failure. This study aims to investigate the release of galectin-3 and its association with cardiovascular events in patients with adult congenital heart disease (ACHD). METHODS: In this prospective cohort study, 602 consecutive patients with ACHD who routinely visited the outpatient clinic were enrolled between 2011 and 2013. Galectin-3 was measured in thaw serum by batch analysis. The association between galectin-3 and a primary endpoint of all-cause mortality, heart failure, hospitalisation, arrhythmia, thromboembolic events and cardiac interventions was investigated using multivariable Cox models. Reference values and reproducibility were established by duplicate galectin-3 measurements in 143 healthy controls. RESULTS: Galectin-3 was measured in 591 (98%) patients (median age 33 (25-41) years, 58% male, 90% New York Heart Association (NYHA) class I). Median galectin-3 was 12.7 (range 4.2-45.7) ng/mL and was elevated in 7% of patients. Galectin-3 positively correlated with age, cardiac medication use, NYHA class, loss of sinus rhythm, cardiac dysfunction and N-terminal pro-B-type natriuretic peptide (NT-proBNP). During a median follow-up of 4.4 (IQR 3.9-4.8) years, the primary endpoint occurred in 195 patients (33%). Galectin-3 was significantly associated with the primary endpoint in the univariable analysis (HR per twofold higher value 2.05; 95% CI 1.44 to 2.93, p<0.001). This association was negated after adjustment for NT-proBNP (HR 1.04; 95% CI 0.72 to 1.49, p=0.848). CONCLUSIONS: Galectin-3 is significantly associated with functional capacity, cardiac function and adverse cardiovascular events in patients with ACHD. Nevertheless, the additive value of galectin-3 to a more conventional risk marker such as NT-proBNP seems to be limited.

The unnatural history of pulmonary stenosis up to 40†years after surgical repair.

OBJECTIVE: To provide prospective information on long-term outcome after surgical correction of valvular pulmonary stenosis (PS). METHODS: Fifty-three consecutive patients operated for PS during childhood between 1968 and 1980 in one centre are followed longitudinally for 37±3.4 years, including extensive in-hospital examination every 10 years. RESULTS: Survival information was available in 100% of the original 53 patients. Cumulative survival was 94% at 20 years and 91% at 40 years. Excluding perioperative mortality (<30 days), survival was 94% at 40 years. Of 46 eligible survivors, 29 participated in the in-hospital examination and 15 gave permission to use their hospital records (96% participation). Cumulative event-free survival was 68% after 40 years: 25% needed a reintervention, 12% underwent pacemaker implantation and 9% had supraventricular arrhythmias. Early reinterventions were mainly for residual PS, late reinterventions for pulmonary regurgitation. Subjective health status was good. Exercise capacity was normal in 74% (median 96 (82-107)% of expected workload). Right ventricular and left ventricular (LV) dysfunction was found in 13% and 41%, respectively. The use of a transannular patch and younger age at surgery were predictive for late events (HR 3.02 (95% CI 1.09 to 8.37) and HR 0.81/year (95% CI 0.66 to 0.98), respectively). Use of inflow occlusion compared with cardiopulmonary bypass showed a trend towards more reinterventions (HR 3.19 (95% CI 0.97 to 10.47)). CONCLUSIONS: Survival up to 40 years after successful PS repair is nearly normal. Subjective health status is good and there is a low incidence of arrhythmias. Reinterventions, however, are necessary in one-quarter and 40 years postoperatively several patients show LV dysfunction.

Quantitative assessment of the entire right ventricle from one acoustic window: an attractive approach.

AIMS: The aim of this prospective study was to evaluate the feasibility and establish normal values of functional right ventricle (RV) parameters as assessed in our four, long-axis view RV model using iRotate echocardiography. Furthermore, we evaluated the potential use of this model in patients with abnormally loaded RVs. METHOD AND RESULTS: One hundred and fifty-five healthy subjects aged 20-72 years (≥28 subjects per decile) were prospectively recruited. We used non-dedicated RV speckle-tracking software to test the feasibility and to establish normal range values of peak systolic global longitudinal RV strain (RV-GLS) from the RV free-walls (septum was excluded). Also normal range values for: dimensions, tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TDI-S') were established. The feasibility of RV-GLS was 88, 84, and 62%, respectively, in the lateral, inferior, and anterior free wall. Mean RV-GLS normal values were -24.5 ± 4.9% for lateral wall and -25.4 ± 5.0% for anterior wall. Mean RV-GLS in the inferior wall was -23.2 ± 4.4% in the aortic (Ao) view and -20.7 ± 5.0% in the coronal (CV) view. The feasibility of mean RV-GLS was 100% in the anterior, lateral, and inferior walls in abnormally dilated RVs. CONCLUSION: The feasibility of all RV parameters assessed in the four-view iRotate model is good to excellent. Normal values for RV dimension and function of the anterior, inferior, and lateral RV walls have been established. Further studies and dedicated RV speckle-tracking software are warranted to discover the full potential of this new technique.

Normal myocardial strain values using 2D speckle tracking echocardiography in healthy adults aged 20 to 72 years.

AIMS: Evaluation of left ventricular (LV) myocardial deformation by speckle tracking echocardiography (STE) is useful for clinical and research purposes. However, strain measurements depend on the used software. Normative data for QLAB 10 (Philips) are scarce. Additionally, little is known about the influence of anthropometric factors. We aimed to establish normal adult STE-derived strain and strain rate values and to evaluate associations with anthropometrics. METHODS: One hundred fifty-five healthy subjects aged 20 to 72 years (≥28 subjects per decile) were prospectively gathered and examined with electrocardiography and two-dimensional echocardiography. With STE, we assessed peak systolic LV global longitudinal strain (GLS), segmental longitudinal strain, and strain rate from the three standard apical views. RESULTS: We included 147 healthy subjects (age 44.6±13.7 years, 50% female, GLS -20.8±2.0%). Men had significantly lower GLS than women (-20.1±1.8% vs -21.5±2.0%, P<.001). GLS was significantly lower in subjects with age above 55 years (P=.029), higher blood pressure (P<.001), higher body surface area (BSA, P<.001), larger LV end-systolic and end-diastolic volumes (both P<.001), lower LV ejection fraction (P<.001), and some indices of diastolic function. After multivariable regression analysis, the correlation with systolic blood pressure, E-wave, and LV end-systolic volume remained significant. The systolic strain rates of most segments correlated with BSA. CONCLUSIONS: Our study resulted in normative LV GLS values assessed with QLAB 10. Male sex, higher BSA, and higher blood pressure negatively influence GLS. Therefore, these factors should be taken into account for strain interpretation in clinical practice.

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.

A Novel 13-Segment Standardized Model for Assessment of Right Ventricular Function Using Two-Dimensional iRotate Echocardiography.

AIMS: The aim of this study was to evaluate the feasibility of transthoracic two-dimensional (2D) iRotate, a new echo modality, to assess the whole right ventricle (RV) from a single transducer position based on anatomic landmarks. METHODS AND RESULTS: The anatomic landmarks were first defined based on three-dimensional echocardiographic datasets using multiplane reconstruction analyses. Thereafter, we included 120 healthy subjects (51% male, age range 21-67 years). Using 2D iRotate, four views of the RV could be acquired based on these landmarks. The anterior, lateral, inferior wall (divided into three segments: basal-mid-apical), and right ventricular outflow tract (RVOT) anterior wall of the RV were determined. The feasibility of visualization of RV segments and tricuspid annular plane systolic excursion (TAPSE) and tissue Doppler imaging (TDI) measurements were assessed. To evaluate this model for diseased RVs, a small pilot study of 20 patients was performed. In 98% of healthy subjects and 100% of patients, iRotate mode was feasible to assess the RV from one single transducer position. In total, 86% and 95%, respectively, of the RV segments could be visualized. The visualization of the RVOT anterior wall was worse 23% and 75%, respectively. TAPSE and TDI measurements on all four views were feasible 93% and 92%, respectively, of the healthy subjects and in 100% of the patients. CONCLUSION: With 2D iRotate, a comprehensive evaluation of the entire normal and diseased RV is feasible from a fixed transducer position based on anatomic landmarks. This is less time-consuming than the multiview approach and enhances accuracy of RV evaluation. Imaging of the RVOT segment remains challenging.

Assessment of ventricular function in adults with repaired Tetralogy of Fallot using myocardial deformation imaging.

AIMS: Many patients with repaired Tetralogy of Fallot (ToF) have right ventricular (RV) volume overload due to pulmonary regurgitation (PR). We studied the effect of volume overload on global and regional RV and left ventricular (LV) deformation, and their relationships with conventional diagnostic parameters. METHODS AND RESULTS: In this cross-sectional study, 94 prospectively recruited ToF patients (61% male, age 32.8 ± 9.5 years, age at repair 1.9 [0.8-5.7] years, 39% pulmonary homograft) and 85 healthy controls of similar age and sex underwent echocardiography and electrocardiography. In a subset of patients, cardiac magnetic resonance imaging, bicycle ergometry, and NT-proBNP measurement were performed within the same day. With speckle-tracking echocardiography, we analysed peak systolic global longitudinal strain (GLS), segmental longitudinal strain and strain rate of the RV free wall, LV lateral wall, and septum. Patients had a lower RV free wall strain than controls (-18.1 ± 4.5 vs. -26.5 ± 4.5%, P < 0.001), especially at the apical segment (-15.9 ± 7.4 vs. -28.2 ± 7.7%, P < 0.001), and lower RV strain rate. LV GLS was also lower (-17.4 ± 2.5 vs. -19.6 ± 1.9%, P < 0.001), mainly due to the interventricular septum. Patients with PR >25% had higher LV GLS and RV free wall strain than patients with PR ≤25% (P = 0.004, P = 0.039, respectively). No relationships were found with NT-proBNP or exercise capacity. CONCLUSION: RV free wall strain and strain rate are decreased in adults late after ToF repair, especially at the apical segment suggesting that apical function is most affected in these RVs. Regarding the LV, septal strain is decreased indicating that RV dysfunction adversely affects LV function, probably by mechanical coupling of the ventricles.

The unnatural history of the ventricular septal defect: outcome up to 40 years after surgical closure.

BACKGROUND: Few prospective data are available regarding long-term outcomes after surgical closure of a ventricular septal defect (VSD). OBJECTIVES: The objective of this study was to investigate clinical outcomes>30 years after surgical VSD closure. METHODS: Patients who underwent surgical VSD closure during childhood between 1968 and 1980 were reexamined every 10 years. In 2012, we invited eligible patients to undergo another examination, which included electrocardiography, Holter monitoring, echocardiography, bicycle ergometry, measurement of N-terminal pro-B-type natriuretic peptide, and subjective health assessment. RESULTS: Cumulative survival was 86% at 40 years. Causes of mortality were arrhythmia, heart failure, endocarditis, during valvular surgery, pulmonary hypertension, noncardiac causes, and unknown causes. Cumulative event-free survival after surgery was 72% at 40 years. Symptomatic arrhythmias occurred in 13% of patients and surgical or catheter-based reinterventions in 12%. Prevalence of impaired right ventricular systolic function increased from 1% in 2001 to 17% in 2012 (p=0.001). Left ventricular systolic function was impaired but stable in 21% of patients. Aortic regurgitation occurred more often in the last 20 years (p=0.039), and mean exercise capacity decreased (p=0.003). N-terminal pro-B-type natriuretic peptide (median: 11.6 pmol/l [interquartile range: 7.0 to 19.8 pmol/l]) was elevated (>14 pmol/l) in 38% of patients. A concomitant cardiac lesion, for example, patent ductus arteriosus, and aortic cross-clamp time were determinants of late events (hazard ratio: 2.84 [95% confidence interval: 1.23 to 6.53] and hazard ratio: 1.47 per 10 min [95% confidence interval: 1.22 to 1.99], respectively). Patients rated their subjective health status significantly better than a reference population. CONCLUSIONS: Survival up to 40 years after successful surgical VSD closure is slightly lower than in the general Dutch population. Morbidity is not negligible, especially in patients with a concomitant cardiac lesion.

Quantitative assessment of systolic right ventricular function using myocardial deformation in patients with a systemic right ventricle.

AIMS: Late systolic dysfunction of the systemic right ventricle (RV) in patients with transposition of the great arteries (TGA) is of major concern. Right ventricular global longitudinal strain (GLS) might be able to identify early dysfunction. METHODS AND RESULTS: Adults with TGA after Mustard operation (TGA-Mustard) or congenitally corrected-TGA (ccTGA) underwent echocardiography, electrocardiography, and NT-proBNP measurement. Using speckle-tracking echocardiography, we analysed longitudinal strain and strain rate, and compared findings in both patients groups, to healthy controls and with clinical parameters. We included 42 patients (mean age 37 ± 7 years, 69% male) with a systemic RV [32 TGA-Mustard (34 ± 4 years after corrective surgery) and 10 ccTGA], and 32 healthy controls (mean age 36 ± 11 years). Global longitudinal strain of the systemic RV was lower in patients than GLS of the systemic LV in controls (-14.2 ± 3.5 vs. -20.0 ± 3.0%, P < 0.001). Average LS of the RV lateral wall was lower in patients with TGA-Mustard (-15.5 ± 3.4%) than ccTGA (-18.3 ± 3.6%, P = 0.047). Right ventricular GLS tended to be lower in patients in NYHA class II than I, and correlated with NT-proBNP (r = 0.49, P = 0.001), RV fractional area change (r = -0.39, P = 0.019), RV apex-base-diameter (r = 0.37, P = 0.021), and QRS duration (r = 0.41, P = 0.014). CONCLUSION: Global longitudinal strain of the systemic RV in patients is lower than GLS of the systemic LV in healthy controls, especially in the apical segment, and tended to be lower in TGA-Mustard than ccTGA patients. Since RV GLS correlates with RV function, myocardial deformation is useful as a more quantitative tool to measure systemic RV function. Decreased GLS was associated with elevated NT-proBNP and tended to correlate with worsening NYHA class, which strengthens the potential prognostic value of GLS in patients with a systemic RV.

Ventricular myocardial deformation in adults after early surgical repair of atrial septal defect.

AIMS: It is unknown whether right-ventricular (RV) volume overload caused by an atrial septal defect (ASD) still has its effect on RV deformation long after repair. We evaluated RV and left-ventricular (LV) deformation beyond 30 years after surgical ASD repair in childhood, and studied relationships with conventional diagnostic parameters. METHODS AND RESULTS: In this prospective study, we included 102 subjects: 51 patients with repaired ASD (39% male, age 43.3 ± 4.9 years, age at repair 7.9 ± 3.6 years) and 51 healthy controls of similar age and sex. All subjects underwent echocardiography and electrocardiography. Additionally, ASD patients underwent cardiac magnetic resonance imaging (CMR), bicycle ergometry, and NT-proBNP measurement. With speckle-tracking echocardiography, we analysed peak systolic longitudinal strain of the RV lateral wall, LV lateral wall, and septum. RV lateral wall global longitudinal strain (GLS) was lower in patients (-20.4 ± 2.7%) than controls (-26.8 ± 4.2%, P < 0.001), due mainly to decreased apical strain (-19.3 ± 6.2 vs. -28.8 ± 8.3%, P < 0.001). RV lateral wall GLS correlated with CMR-derived RV and LV end-diastolic volumes (ρ = 0.49, P = 0.014; ρ = 0.53, P = 0.005), and with RV and LV end-systolic volumes (ρ = 0.43, P = 0.034; ρ = 0.46, P = 0.019). LV GLS was similar between patients and controls (P = 0.144). No significant correlations were found with NT-proBNP or exercise capacity. CONCLUSION: Although ASD repair was already performed in childhood, RV longitudinal strain, especially of the apical segment, is decreased in patients 35 years after surgery. This suggests that RV function has still been affected in the long run, probably due to the early RV volume overload, but possibly also as sequel of surgery.

Unnatural history of tetralogy of Fallot: prospective follow-up of 40 years after surgical correction.

BACKGROUND: Prospective data on long-term survival and clinical outcome beyond 30 years after surgical correction of tetralogy of Fallot are nonexistent. METHODS AND RESULTS: This longitudinal cohort study consists of the 144 patients with tetralogy of Fallot who underwent surgical repair at <15 years of age between 1968 and 1980 in our center. They are investigated every 10 years. Cumulative survival (data available for 136 patients) was 72% after 40 years. Late mortality was due to heart failure and ventricular fibrillation. Seventy-two of 80 eligible survivors (90%) participated in the third in-hospital investigation, consisting of ECG, Holter, echocardiography, cardiopulmonary exercise testing, N-terminal pro-brain natriuretic peptide measurement, cardiac magnetic resonance (including dobutamine stress testing), and the Short Form-36 questionnaire. Median follow-up was 36 years (range, 31-43 years). Cumulative event-free survival was 25% after 40 years. Subjective health status was comparable to that in the normal Dutch population. Although systolic right and left ventricular function declined, peak exercise capacity remained stable. There was no progression of aortic root dilation. A previous shunt operation, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality (hazard ratio, 2.9, 1.1, and 2.5, respectively). An increase in QRS duration and a deterioration of exercise tolerance and ventricular dysfunction did not predict mortality. Insertion of a transannular patch was a predictor for late arrhythmias (hazard ratio, 4.0; 95% confidence interval, 1.2-13.4). CONCLUSIONS: Although many patients needed a reoperation or developed arrhythmias, late mortality was low, and the clinical condition and subjective health status of most patients remained good. Previous shunt, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality.

Associations between N-terminal pro-B-type natriuretic peptide and cardiac function in adults with corrected tetralogy of Fallot.

BACKGROUND: Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with echocardiography and exercise capacity. METHODS AND RESULTS: NT-proBNP measurement, electrocardiography and detailed 2D-echocardiography were performed on the same day in 177 consecutive adults with ToF (mean age 34.6 ± 11.8 years, 58% male, 89% NYHA I, 29.3 ± 8.5 years after surgical correction). Thirty-eight percent of the patients also underwent a cardiopulmonary-exercise test. Median NT-proBNP was 16 [IQR 6.7-33.6] pmol/L, and was elevated in 55%. NT-proBNP correlated with right ventricular (RV) dilatation (r = 0.271, p < 0.001) and RV systolic dysfunction (r = -0.195, p = 0.022), but more strongly with LV systolic dysfunction (r=-0.367, p<0.001), which was present in 69 patients (39%). Moderate or severe pulmonary regurgitation was not associated with higher NT-proBNP. Tricuspid and pulmonary regurgitation peak velocities correlated with NT-proBNP (r = 0.305, p < 0.001 and r = 0.186, p = 0.045, respectively). LV twist was measured with speckle-tracking echocardiography in 71 patients. An abnormal LV twist (20 patients, 28%) was associated with elevated NT-proBNP (p = 0.030). No relationship between NT-proBNP and exercise capacity was found. CONCLUSIONS: NT-proBNP levels are elevated in more than 50% of adults with corrected ToF, while they are in stable clinical condition. Higher NT-proBNP is most strongly associated with elevated pulmonary pressures, and with LV dysfunction rather than RV dysfunction. NT-proBNP has the potential to become routine examination in patients with ToF to monitor ventricular function and may be used for timely detection of clinical deterioration.

Abnormal left ventricular rotation and twist in adult patients with corrected tetralogy of Fallot.

AIMS: Left ventricular (LV) dysfunction is a major determinant of late adverse clinical outcome in adult patients with tetralogy of Fallot (ToF). Therefore, early detection is important. Speckle-tracking echocardiography (STE) has emerged as a quantitative technique to assess LV function. The aim of this study was to evaluate LV rotation and twist with STE in adult ToF patients and their association with right ventricular (RV) and LV dimensions and function, exercise capacity, and NT-proBNP level. METHODS: Eighty-two ToF patients and 56 healthy controls matched for age and gender underwent echocardiography, electrocardiography, cardiac magnetic resonance imaging (CMR), bicycle ergometry, and NT-proBNP measurement. For STE, short-axis parasternal views were obtained at the LV base and apex. We analysed LV apical and basal rotation curves and calculated LV twist. RESULTS: Of the 82 ToF patients (55% male, age 33 ± 10 years, 98% NYHA I), 58 (71%) had normal twist, but lower than the controls [12.5 (IQR: 6.6) vs. 16.9 (IQR: 8.2) degrees, P = 0.002] mainly due to decreased apical rotation. Twenty-one (26%) patients had abnormal apical rotation which was associated with larger LV dimensions and decreased systolic biventricular function. Multivariable regression analyses showed positive relations of LV twist with biventricular systolic function measured with echocardiography as well as CMR. CONCLUSION: The majority of adults with corrected ToF show a reduced LV twist. Strikingly, one-quarter of these patients have an abnormal apical rotation which is associated with decreased systolic LV and RV function. These findings suggest that abnormal apical rotation is a new objective diagnostic criterion for detection of ventricular dysfunction.