Jolien W. Roos-Hesselink

Clinical value of real-time three-dimensional echocardiography for right ventricular quantification in congenital heart disease: validation with cardiac magnetic resonance imaging.

BACKGROUNDnThe objective of this study was to test the feasibility, accuracy, and reproducibility of the assessment of right ventricular (RV) volumes and ejection fraction (EF) using real-time three-dimensional echocardiographic (RT3DE) imaging in patients with congenital heart disease (CHD), using cardiac magnetic resonance (CMR) as a reference.nnnMETHODSnRT3DE data sets and short-axis cine CMR images were obtained in 62 consecutive patients (mean age, 26.9 +/- 10.4 years; 65% men) with various CHDs. RV volumetric quantification was done using semiautomated 3-dimensional border detection for RT3DE images and manual tracing of contours in multiple slices for CMR images.nnnRESULTSnAdequate RV RT3DE data sets could be analyzed in 50 of 62 patients (81%). The time needed for RV acquisition and analysis was less for RT3DE imaging than for CMR (P < .001). Compared with CMR, RT3DE imaging underestimated RV end-diastolic and end-systolic volumes and EF by 34 +/- 65 mL, 11 +/- 55 mL, and 4 +/- 13% (P < .05) with 95% limits of agreement of +/-131 mL, +/-109 mL, and +/-27%, as shown by Bland-Altman analyses, with highly significant correlations (r = 0.93, r = 0.91, and r = 0.74, respectively, P < .001). Interobserver variability was 1 +/- 15%, 6 +/- 17%, and 8 +/- 13% for end-diastolic and end-systolic volumes and EF, respectively.nnnCONCLUSIONnIn the majority of unselected patients with complex CHD, RT3DE imaging provides a fast and reproducible assessment of RV volumes and EF with fair to good accuracy compared with CMR reference data when using current commercially available hardware and software. Further studies are warranted to confirm our data in similar and other patient populations to establish its use in clinical practice.

Right ventricular quantification in clinical practice: two-dimensional vs. three-dimensional echocardiography compared with cardiac magnetic resonance imaging.

AIMSnTo establish the additional value of three-dimensional echocardiography (3D echo) for assessment of right ventricular (RV) size and function in patients with congenital heart disease (CHD) in everyday clinical practice, the accuracy and reproducibility of 3D echo were compared with conventional two-dimensional echocardiography (2D echo) and cardiac magnetic resonance (CMR) imaging as reference.nnnMETHODS AND RESULTSnPatients with CHD and primarily affected right ventricles (n = 62), patients with CHD and primarily affected left ventricles (LV group, n = 27), and healthy controls (n = 31) were studied. 2D echo-, 3D echo- and CMR data sets were obtained. Moderate correlations were found between RV dimensions by 2D echo and CMR-derived RV end-diastolic volumes (r = 0.32-0.77). The correlations between RV volumes obtained by 3D echo and CMR imaging were better (r = 0.71-0.97) than the 2D echo-derived correlations (P < 0.001). Only the 2D echo-derived RV inlet diameter correlated better in healthy controls than in the RV group. Receiver operating characteristic curve analysis revealed that 3D echo-derived end-diastolic volume best identified RV dysfunction (sensitivity 95% and specificity 100%). The 3D echo-derived measurements were as reproducible as the 2D echo-derived measurements (n = 37, coefficients of variation ranging from 5 to 19%), with tricuspid annular plane systolic excursion being the most reproducible measurement (coefficient of variation of 6%).nnnCONCLUSIONn3D echo improved quantitative RV size and function assessment compared with 2D echo in patients as well as in healthy controls. Everyday clinical use of 3D echo for RV assessment can be reality with the currently available software and provides incremental benefit in assessment of the right ventricle.

Mutations in a TGF-β Ligand, TGFB3, Cause Syndromic Aortic Aneurysms and Dissections

Background Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-β signaling. Objectives This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. Methods We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. Results Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-β signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-β signaling in association with up-regulation of the expression of TGF-β ligands. Conclusions Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk.

Pregnancy in Women With a Mechanical Heart Valve Data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC)

Background— Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. Methods and Results— Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve (P=1.000), and in 0.2% of patients without a prosthetic valve (P=0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve (P<0.001), and in 4.9% of patients without a prosthetic valve (P<0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve (P<0.001) and 78% of patients without a prosthetic valve (P<0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P<0.001) and late fetal death (7.1% versus 0.7%; P=0.016). Conclusions— Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.Background— Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity.nnMethods and Results— Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve ( P =1.000), and in 0.2% of patients without a prosthetic valve ( P =0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve ( P <0.001), and in 4.9% of patients without a prosthetic valve ( P <0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve ( P <0.001) and 78% of patients without a prosthetic valve ( P <0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P <0.001) and late fetal death (7.1% versus 0.7%; P =0.016).nnConclusions— Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.nn# CLINICAL PERSPECTIVE {#article-title-24}

Quantitative cardiovascular magnetic resonance in pregnant women: cross-sectional analysis of physiological parameters throughout pregnancy and the impact of the supine position.

BackgroundThere are physiological reasons for the effects of positioning on hemodynamic variables and cardiac dimensions related to altered intra-abdominal and intra-thoracic pressures. This problem is especially evident in pregnant women due to the additional aorto-caval compression by the enlarged uterus. The purpose of this study was to investigate the effect of postural changes on cardiac dimensions and function during mid and late pregnancy using cardiovascular magnetic resonance (CMR).MethodsHealthy non-pregnant women, pregnant women at 20th week of gestation and at 32nd week of gestation without history of cardiac disease were recruited to the study and underwent CMR in supine and left lateral positions. Cardiac hemodynamic parameters and dimensions were measured and compared between both positions.ResultsFive non-pregnant women, 6 healthy pregnant women at mid pregnancy and 8 healthy pregnant women at late pregnancy were enrolled in the study. In the group of non-pregnant women left ventricular (LV) cardiac output (CO) significantly decreased by 9% (p = 0.043) and right ventricular (RV) end-diastolic volume (EDV) significantly increased by 5% (p = 0.043) from the supine to the left lateral position. During mid pregnancy LV ejection fraction (EF), stroke volume (SV), left atrium lateral diameter and left atrial supero-inferior diameter increased significantly from the supine position to the left lateral position: 8%, 27%, 5% and 11%, respectively (p < 0.05). RV EDV, SV and right atrium supero-inferior diameter significantly increased from the supine to the left lateral position: 25%, 31% and 13% (p < 0.05), respectively. During late pregnancy a significant increment of LV EF, EDV, SV and CO was observed in the left lateral position: 11%, 21%, 35% and 24% (p < 0.05), respectively. Left atrial diameters were significantly larger in the left lateral position compared to the supine position (p < 0.05). RV CO was significantly increased in the left lateral position compared to the supine position (p < 0.05).ConclusionsDuring pregnancy positional changes affect significantly cardiac hemodynamic parameters and dimensions. Pregnant women who need serial studies by CMR should be imaged in a consistent position. From as early as 20 weeks the left lateral position should be preferred on the supine position because it positively affects venous return, SV and CO.

Autograft and pulmonary allograft performance in the second post-operative decade after the Ross procedure: insights from the Rotterdam Prospective Cohort Study

AIMSnThe objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up.nnnMETHODS AND RESULTSnAll consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037).nnnCONCLUSIONnWe observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR.

Usefulness of real-time three-dimensional echocardiography to identify right ventricular dysfunction in patients with congenital heart disease.

Because right ventricular (RV) dysfunction predicts a poor outcome in patients with congenital heart disease (CHD), regular monitoring of RV function is indicated. To date, cardiac magnetic resonance (CMR) imaging has been the reference method. A more practical, more accessible, and accurate tool would be preferred. We defined normality regarding RV systolic function using healthy controls and tested the ability of real-time 3-dimensional echocardiographic (RT3DE) findings to identify patients with CHD with RV dysfunction. The cutoff values for the RV volumes and ejection fraction (EF) were derived from the CMR imaging findings from 41 healthy controls (mean age 27 +/- 8 years, 56% men). In 100 patients with varying CHDs (mean age 27 +/- 11 years, 65% men), both RT3DE data sets (iE33) and short-axis CMR imaging (1.5 T) were obtained within 2 hours. The RT3DE and CMR RV volumes and EF were calculated using commercially available software. Receiver operating characteristic curves were created to obtain the sensitivity and specificity of the RT3DE data to identify RV dysfunction. Applying the cutoff values derived from the healthy controls using the CMR data of patients with CHD, we identified 23 patients with an enlarged indexed end-diastolic volume, 29 patients with an enlarged indexed end-systolic volume, and 21 patients with an impaired RVEF. The best cutoff values predicting RV dysfunction using the RT3DE findings were identified (indexed end-diastolic volume >105 ml/m(2), indexed end-systolic volume >54 ml/m(2), and EF <43%). The RT3DE findings revealed 23 patients with impaired RVEF, with 95% sensitivity, 89% specificity, and a negative predictive value of 99%. In conclusion, real-time 3-dimensional echocardiography is a very sensitive tool to identify RV dysfunction in patients with CHD and could be applied clinically to rule out RV dysfunction or to indicate additional quantitative analysis of RV function.

Seventeen years of adult congenital heart surgery: a single centre experience §

OBJECTIVEnWith a growing number of children with congenital heart disease (CHD) reaching adulthood, an extensive experience with cardiac surgery in adults with CHD is accumulating. To increase insight in this patient category we report our 17-year single centre experience including predictors for adverse outcome and EuroSCORE performance.nnnMETHODSnPatients and operative characteristics of all consecutive adult CHD patients operated upon between January 1990 and January 2007 were collected. Categorisation was done according to the EACTS/STS congenital database. Early and late morbidity and mortality were assessed with follow-up extending up to 17 years. EuroSCORE performance was assessed.nnnRESULTSnNine hundred and sixty-three procedures were performed in 830 patients (mean age 39.3 years, 50.3% male). A total of 49% were re-do procedures, frequent procedures were for left heart lesions (37%), right heart lesions (31%) and septal defects (8%). The 51% primary procedures largely consisted of less complex procedures but also included 1.4% of tetralogy of Fallot repairs, 4.1% of aortic coarctation repairs and 2.7% of Ebsteins disease repairs. Thirty-day mortality was 1.5% (n=14); predicted mortality by logistic EuroSCORE was 4.6%. c-index was 0.61 (95% CI 0.46-0.75). Major complications such as tamponade requiring intervention occurred in 3.2%, postoperative bleeding requiring re-exploration in 7.1% and renal insufficiency requiring dialysis in 4 (0.4%). Pulmonary hypertension was a strong predictor for short-term mortality; impaired ventricular function and cyanosis for long-term mortality. Overall 17-year survival was 71% (95% CI 61%-82%). Eighty percent of patients were in NYHA class I at last follow-up, 17% in II, 3% in III, 0% in IV.nnnCONCLUSIONSnSurgery in adult CHD patients can be performed with low operative mortality and good clinical outcome. EuroSCORE is not a good model for risk assessment in this group of patients.

Test-Retest Variability of Volumetric Right Ventricular Measurements Using Real-Time Three-Dimensional Echocardiography

BACKGROUNDnSubstantial variability in sequential echocardiographic right ventricular (RV) quantification may exist. Interobserver and intraobserver values are well known, but acquisition (test-retest) variability has been rarely assessed. The objective of this study was to determine the test-retest variability of sequential RV volume and ejection fraction (EF) measurements by real-time three-dimensional echocardiography in patients with congenital heart disease and healthy controls.nnnMETHODSnTwenty-eight participants (21 patients with congenital heart disease, seven healthy controls; mean age, 30 ± 14 years; 43% men) underwent a series of three echocardiographic studies. To obtain interobserver and intraobserver test-retest variability, two sonographers acquired sequential RV data sets in each participant during one outpatient visit. RV volumetric quantification was done using semiautomated three-dimensional border detection. The variability data were analyzed using correlation coefficients, Bland-Altman analysis, and coefficients of variation.nnnRESULTSnAbsolute mean differences for sequential intraobserver acquisitions were 12 ± 12 mL for end-diastolic volume, 7 ± 6 mL for end-systolic volume, and 4 ± 3% for EF. Interobserver and intraobserver test-retest variability, respectively, were 7% and 7% for RV end-diastolic volume, 14% and 7% for end-systolic volume, and 8% and 6% for EF.nnnCONCLUSIONSnGood test-retest variability, besides the practical nature of real-time three-dimensional echocardiography for RV volume and EF assessment, makes it a valuable technique for serial follow-up. Although it may be challenging to diminish all factors that can influence echocardiographic examination for serial follow-up, standardization of RV size and functional measurements should be a goal to produce more interchangeable data.

Pregnancy Outcomes in Women With Aortic Valve Substitutes

Young women who require aortic valve replacement need information on the potential cardiac and obstetric complications of pregnancy for the different valve substitutes available. We, therefore, assessed the pregnancy outcomes in women who had received an autograft, homograft, or mechanical valve in the aortic position. Women who were pregnant after surviving aortic valve replacement at our institution from 1987 to 2011 were included. Information on cardiac status and pregnancy outcome was obtained through the hospital medical records and by an extensive patient questionnaire. A total of 40 women experienced 67 pregnancies, of which 55 (82%) were completed pregnancies, 6 (9%) were miscarriages, and 6 (9%) were terminated. Of the 40 women, 18 (45%) had a pulmonary autograft, 13 (32%) a homograft, and 9 (23%) a mechanical valve. The mean age at the first pregnancy was 30.0 ± 5.7 years. No maternal mortality but 1 fetal death (1.8%) and 1 neonatal death (1.8%) occurred. Maternal cardiac complications developed in 13% and obstetric complications in 38% of the completed pregnancies. Heart failure (9%), arrhythmias (7%), hypertension-related disorders (7%), preterm delivery (24%), and small-for-gestational-age infants (15%) were most often encountered. Mechanical valve recipients had the greatest incidence of both cardiac and obstetric complications. In conclusion, pregnancy-associated complications after aortic valve replacement were common, and human tissue valves should be considered in the discussion for the optimal aortic valve substitute in a young woman. However, careful obstetric monitoring is mandatory.