Barbara J.M. Mulder

Evaluating the systemic right ventricle by CMR: the importance of consistent and reproducible delineation of the cavity

BackgroundThe method used to delineate the boundary of the right ventricle (RV), relative to the trabeculations and papillary muscles in cardiovascular magnetic resonance (CMR) ventricular volume analysis, may matter more when these structures are hypertrophied than in individuals with normal cardiovascular anatomy. This study aimed to compare two methods of cavity delineation in patients with systemic RV.MethodsTwenty-nine patients (mean age 34.7 ± 12.4 years) with a systemic RV (12 with congenitally corrected transposition of the great arteries (ccTGA) and 17 with atrially switched (TGA) underwent CMR. We compared measurements of systemic RV volumes and function using two analysis protocols. The RV trabeculations and papillary muscles were either included in the calculated blood volume, the boundary drawn immediately within the apparently compacted myocardial layer, or they were manually outlined and excluded. RV stroke volume (SV) calculated using each method was compared with corresponding left ventricular (LV) SV. Additionally, we compared the differences in analysis time, and in intra- and inter-observer variability between the two methods. Paired samples t-test was used to test for differences in volumes, function and analysis time between the two methods. Differences in intra- and inter-observer reproducibility were tested using an extension of the Bland-Altman method.ResultsThe inclusion of trabeculations and papillary muscles in the ventricular volume resulted in higher values for systemic RV end diastolic volume (mean difference 28.7 ± 10.6 ml, p < 0.001) and for end systolic volume (mean difference 31.0 ± 11.5 ml, p < 0.001). Values for ejection fraction were significantly lower (mean difference -7.4 ± 3.9%, p < 0.001) if structures were included. LV SV did not differ significantly from RV SV for both analysis methods (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and showed better inter-observer reproducibility for ejection fraction (p < 0.01).ConclusionThe choice of method for systemic RV cavity delineation significantly affected volume measurements, given the CMR acquisition and analysis systems used. We recommend delineation outside the trabeculations for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible measurements.

Gender and Outcome in Adult Congenital Heart Disease

Background— Gender differences in prognosis have frequently been reported in cardiovascular disease but less so in congenital heart disease. We investigated whether gender is associated with outcome in adult patients with congenital heart disease. Methods and Results— From the CONgenital CORvitia (CONCOR) national registry for adults with congenital heart disease, 7414 patients were identified. All outcomes before entry into the registry and during subsequent follow-up were recorded, and differences between men and women were analyzed with the underlying congenital heart defect taken into account. Median age at the end of follow-up was 35 years (range, 17 to 91 years); 49.8% were female. No gender difference in mortality was found. Women had a 33% higher risk of pulmonary hypertension (odds ratio [OR]=1.33; 95% CI, 1.07 to 1.65; P=0.01), a 33% lower risk of aortic outcomes (OR=0.67; 95% CI, 0.50 to 0.90; P=0.007), a 47% lower risk of endocarditis (OR=0.53; 95% CI, 0.40 to 0.70; P<0.001), and a 55% lower risk of an implantable cardioverter-defibrillator (OR=0.45; 95% CI, 0.26 to 0.80; P=0.006). Furthermore, the risk of arrhythmias appeared to be lower in women (OR=0.88; 95% CI, 0.77 to 1.02; P=0.08). Conclusions— The risk of several major cardiac outcomes in adult patients with congenital heart disease appears to vary by gender.

Social Burden and Lifestyle in Adults With Congenital Heart Disease

We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group.

Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome

Pulmonary arterial hypertension associated with congenital heart disease caused by systemic-to-pulmonary shunting was associated with a high risk of morbidity and mortality. In this retrospective study, the longer term treatment effect of bosentan on exercise capacity and quality of life (QoL) were evaluated in 58 adult patients (>18 years) with pulmonary arterial hypertension associated with congenital heart disease, including patients with Downs syndrome. All patients were evaluated at baseline and during follow-up using laboratory tests, 6-minute walk test, QoL questionnaires, and Doppler echocardiography. Treatment efficacy was analyzed separately for patients without (n = 30) and with Downs syndrome (n = 28). Median follow-up of all patients treated with bosentan was 22 months (range 3 to 36). In patients without Downs syndrome, mean 6-minute walk distance increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment, followed by a gradual return to baseline and disease stabilization. QoL improved significantly during treatment and was maintained during 18 months of follow-up (p <0.05). In patients with Downs syndrome, 6-minute walk distance and QoL were stable during treatment. In conclusion, findings suggested that in patients without Downs syndrome, longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity.

Linee guida ESC 2015 per il trattamento dell'endocardite infettiva: Task Force per il Trattamento dell'Endocardite Infettiva della Società Europea di Cardiologia (ESC): Con il patrocinio dell'Associazione Europea di Chirurgia Cardiotoracica (EACTS) e dell'Associazione Europea di Medicina Nucleare (EANM)

Authors/Task Force Members: Gilbert Habib* (Chairperson) (France), Patrizio Lancellotti* (co-Chairperson) (Belgium), Manuel J. Antunes (Portugal), Maria Grazia Bongiorni (Italy), Jean-Paul Casalta (France), Francesco Del Zotti (Italy), Raluca Dulgheru (Belgium), Gebrine El Khoury (Belgium), Paola Anna Erba (Italy), Bernard Iung (France), Jose M. Miro (Spain), Barbara J. Mulder (The Netherlands), Edyta Plonska-Gosciniak (Poland), Susanna Price (UK), Jolien Roos-Hesselink (The Netherlands), Ulrika Snygg-Martin (Sweden), Franck Thuny (France), Pilar Tornos Mas (Spain), Isidre Vilacosta (Spain), and Jose Luis Zamorano (Spain)Autori/Membri della Task Force Gilbert Habib (Chairperson) (Francia), Patrizio Lancellotti (co-Chairperson) (Belgio), Manuel J. Antunes (Portogallo), Maria Grazia Bongiorni (Italia), Jean-Paul Casalta (Francia), Francesco Del Zotti (Italia), Raluca Dulgheru (Belgio), Gebrine El Khoury (Belgio), Paola Anna Erbaa (Italia), Bernard Iung (Francia), Jose M. Mirob (Spagna), Barbara J. Mulder (Olanda), Edyta Plonska-Gosciniak (Polonia), Susanna Price (UK), Jolien Roos-Hesselink (Olanda), Ulrika Snygg-Martin (Svezia), Franck Thuny (Francia), Pilar Tornos Mas (Spagna), Isidre Vilacosta (Spagna), Jose Luis Zamorano (Spagna)

Comparable Systemic Ventricular Function in Healthy Adults and Patients With Unoperated Congenitally Corrected Transposition Using MRI Dobutamine Stress Testing

BACKGROUNDnFailure of the systemic right ventricle (RV) often complicates adult survival in unoperated or physiologically repaired congenitally corrected transposition of the great arteries (CCTGA). Healthy controls schematically represent an optimal outcome of anatomic repair, which is increasingly performed to treat CCTGA. Magnetic resonance imaging dobutamine stress testing measures cardiac reserve, and sets to compare the left ventricle of controls with the systemic RV of unoperated and physiologically repaired patients with CCTGA.nnnMETHODSnBaseline and stress magnetic resonance imaging (maximum dobutamine dose, 15 microg/kg/min) assessed systemic RV function in 13 minimally or asymptomatic adult patients with CCTGA (unoperated, n = 7; physiologically repaired, n = 6). The left ventricles of 11 healthy age-matched adults served as controls.nnnRESULTSnBaseline and stress end-diastolic volumes similar between the systemic RV of unoperated patients and the left ventricle of controls, as well as base end-systolic volumes. Stress ejection fraction was lower in unoperated and physiologically repaired patients (70 +/- 6% and 60 +/- 5%, respectively, vs healthy controls (84 +/- 8%). However, comparable with healthy controls, both subsets of CCTGA patients responded appropriately to dobutamine stress, as illustrated by similar RV stroke volume, heart rate, mean blood pressure, and cardiac index.nnnCONCLUSIONSnCompared with the left ventricles of healthy controls, both patient groups had larger systemic RV volumes, diminished ejection fraction, but an appropriate response to dobutamine stress. Values of unoperated patients are closer to normal than physiologically repaired patients. Magnetic resonance imaging dobutamine may help to define the subgroups of CCTGA patients with favorable anatomy, whereby asymptomatic adult survival could be anticipated without the need for an operation.

Tricuspid Valve Surgery in Adults With a Dysfunctional Systemic Right Ventricle Repair or Replace

Background— In patients with a right ventricle (RV) in the systemic position, tricuspid valve surgery for regurgitation beyond adolescence is a subject of debate. The aim of the present study was to evaluate the complications, survival, and benefit of tricuspid surgery in adult patients with an atrium-level correction for transposition of the great arteries or congenitally corrected transposition of the great arteries. Methods and Results— All adult patients (n=16; 7 men, 9 women; age 35±11 years) who underwent tricuspid valvuloplasty (n=8) or replacement (n=8) in the period 1999 to 2008 were included. Complications and survival were analyzed, and postoperative changes in RV function and functional class were evaluated. Tricuspid regurgitation was graded 1 to 4 according to its severity, RV dysfunction was graded as 1 to 4 (1=no dysfunction to 4=severe dysfunction), and functional status was determined according to New York Heart Association class. Although complications occurred in 11 patients, all could be managed adequately. Three patients died 109, 180, and 659 days after surgery, respectively, the first patient after tricuspid valve replacement and the latter 2 after tricuspid valvuloplasty. Overall, tricuspid valve function improved (from grade 3.1±0.8 to 0.9±1.0; P=0.001) and functional class improved (from 2.7±0.6 to 2.1±0.8; P=0.007), whereas RV function remained unchanged. After tricuspid valvuloplasty, however, recurrent moderate tricuspid valve regurgitation was observed frequently (n=3; 37%). Conclusions— Mortality is rather low after tricuspid surgery in adult patients with mild to moderate RV dysfunction. In general, tricuspid valve function and functional class improve significantly after surgery, and systemic RV function is preserved. Tricuspid valvuloplasty, however, is associated with a high rate of recurrence of regurgitation.

Relation of Physical Activity, Cardiac Function, Exercise Capacity, and Quality of Life in Patients With a Systemic Right Ventricle

Exercise is recommended in patients with left ventricular failure. Although right ventricular failure is common in patients with a systemic right ventricle (RV), no data are available on the effect of physical activity in these patients. The aim of this study was to evaluate the relation of physical activity and cardiac function, exercise capacity, and quality of life in patients with a systemic RV. Forty-seven patients (64% men, mean age 35 years, range 21 to 69) with a systemic RV (31 with an atrially switched transposition of the great arteries and 16 with a congenitally corrected transposition of the great arteries) were included. Cardiac function was assessed by cardiovascular magnetic resonance or computed tomography, exercise tests, and serum N-terminal prohormone brain natriuretic peptide (NT-pro-BNP) levels. Habitual physical activity was assessed using the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH) and quality of life using the Medical Outcomes Study Short Form 36-Item Health Survey. Mean systemic right ventricular ejection fraction was impaired (36.8 +/- 7.8%), as was maximal exercise capacity (78.5 +/- 23.9% of predicted). NT-pro-BNP level was increased (median 269 ng/L, range 34 to 4,476). Mean SQUASH score was 6,808 +/- 3,241, indicating a decreased level of habitual physical activity. Although patients scores on mental quality-of-life domains were comparable to the general population, scores on most physical quality-of-life domains were significantly lower. SQUASH scores were found to be a significant predictor for exercise capacity (p <0.01) and physical quality of life (p <0.001). However, we found no relation between SQUASH scores and right ventricular ejection fraction or NT-pro-BNP. In conclusion, physical activity in patients with a systemic RV is positively associated with exercise capacity and quality of life, irrespective of cardiac performance.

Down patients with Eisenmenger syndrome: Is bosentan treatment an option?

BACKGROUNDnFavorable results of treatment with bosentan in patients with Eisenmenger syndrome are available. However, data in Down patients are lacking. In this study, we evaluate the therapeutic role of bosentan treatment in Down patients with Eisenmenger syndrome.nnnMETHODSnIn this open-label study, 24 Down patients (>18 years) with Eisenmenger syndrome (17 males) were treated with bosentan. Their mean age was 38 years (range 19-55 years). All Down patients were evaluated at baseline and during follow-up with laboratory tests, six-minute walk test (6-MWT), Doppler echocardiography, and quality of life questionnaires.nnnRESULTSnThe median follow-up of Down patients treated with bosentan was 11.5 months (range 3-23 months). Induction of oral bosentan therapy was well tolerated among all 24 Down patients. Bosentan treatment was generally well tolerated. No serious adverse drug reactions were noted. Median 6-MWT increased from 296 m (range 40-424 m) to 325 m (range 84-459 m, p<0.05) after 12 weeks. After 26 and 52 weeks of treatment with bosentan, median 6-MWT distance was 276 m (range 140-462 m, n=15, p=0.6) and 287 m (range 131-409 m, n=7, p=0.3), respectively. Quality of life questionnaire scores remained stable during treatment.nnnCONCLUSIONnAlso patients with Down syndrome may benefit from bosentan treatment when they have Eisenmenger syndrome. Medical treatment appears to be safe and the treatment effects do not deviate from those observed in Eisenmenger patients without Down syndrome.

Latest insights in therapeutic options for systemic right ventricular failure: a comparison with left ventricular failure.

The number of adult patients with a systemic right ventricle (RV) is steadily increasing. Survival is relatively good in these patients, but deterioration of the systemic RV seems inevitable. Although therapeutic options for patients with LV failure are well established, their role in patients with systemic RV failure is often undefined. To appreciate the potency of LV failure therapy in patients with a systemic RV, insight into pathophysiology of systemic RV failure and into recent developments in therapeutic research are indispensible. This review provides these insights, and will facilitate and ameliorate therapeutic decision making in patients with a systemic RV.