Physiological and clinical consequences of relief of right ventricular outflow tract obstruction late after repair of congenital heart defects.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a common problem after repair of congenital heart disease. Percutaneous pulmonary valve implantation (PPVI) can treat this condition without consequent pulmonary regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical and physiological response to relieving RVOTO. METHODS AND RESULTS: We studied 18 patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a total of 93 who had this procedure for various indications. All had a right ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without important pulmonary regurgitation (less than mild or regurgitant fraction <10% on magnetic resonance imaging [MRI]). Cardiopulmonary exercise testing, tissue Doppler echocardiography, and MRI were performed before and within 50 days of PPVI. PPVI reduced RVOT gradient (51.4 to 21.7 mm Hg, P<0.001) and right ventricular systolic pressure (72.8 to 47.3 mm Hg, P<0.001) at catheterization. Symptoms and aerobic (25.7 to 28.9 mL.kg(-1).min(-1), P=0.002) and anaerobic (14.4 to 16.2 mL.kg(-1).min(-1), P=0.002) exercise capacity improved. Myocardial systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P=0.05; mitral 4.7 to 5.5 cm/s, P=0.01), whereas isovolumic acceleration was unchanged. The tricuspid annular velocity was not maintained on intermediate follow-up. Right ventricular end-diastolic volume (99.9 to 89.7 mL/m2, P<0.001) fell, whereas effective stroke volume (43.7 to 48.3 mL/m2, P=0.06) and ejection fraction (48.0% to 56.8%, P=0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4 mL/m2, P=0.145), stroke volume (45.3 to 50.6 mL/m2, P=0.02), and ejection fraction (62.6% to 65.8%, P=0.03) increased. CONCLUSIONS: PPVI relieves RVOTO, which leads to an early improvement in biventricular performance. Furthermore, it reduces symptoms and improves exercise tolerance. These findings have important implications for the management of this increasingly common condition

Percutaneous pulmonary valve implantation in humans - Results in 59 consecutive patients

Background - Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life.Methods and Results - Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n = 36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n = 8). The right ventricular (RV) pressure (64.4 +/- 17.2 to 50.4 +/- 14 mm Hg, P < 0.001), RVOT gradient (33 +/- 24.6 to 19.5 +/- 15.3, P < 0.001), and pulmonary regurgitation ( PR) (grade 2 of greater before, none greater than grade 2 after, P < 0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21 +/- 13% versus 3 +/- 4%, P < 0.001) and in RV end-diastolic volume (EDV) (94 +/- 28 versus 82 +/- 24 mL (.) beat(-1) (.) m(-2), P < 0.001) and a significant increase in left ventricular EDV ( 64 +/- 12 versus 71 +/- 13 mL (.) beat(-1.) m(-2), P = 0.005) and effective RV stroke volume ( 37 +/- 7 versus 42 +/- 9 mL (.) beat(-1) (.) m(-2), P = 0.006) in 28 patients (age 19 +/- 8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in V(O2)max (26 +/- 7 versus 29 +/- 6 mL (.) kg(-1) (.) min(-1), P < 0.001). There was no mortality.Conclusions - PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity

Piloting the Use of Patient-Specific Cardiac Models as a Novel Tool to Facilitate Communication During Cinical Consultations

This pilot study aimed to assess the impact of using patient-specific three-dimensional (3D) models of congenital heart disease (CHD) during consultations with adolescent patients. Adolescent CHD patients (n = 20, age 15-18 years, 15 male) were asked to complete two questionnaires during a cardiology transition clinic at a specialist centre. The first questionnaire was completed just before routine consultation with the cardiologist, the second just after the consultation. During the consultation, each patient was presented with a 3D full heart model realised from their medical imaging data. The model was used by the cardiologist to point to main features of the CHD. Outcome measures included rating of health status, confidence in explaining their condition to others, name and features of their CHD (as a surrogate for CHD knowledge), impact of CHD on their lifestyle, satisfaction with previous/current visits, positive/negative features of the 3D model, and open-ended feedback. Significant improvements were registered in confidence in explaining their condition to others (p = 0.008), knowledge of CHD (p < 0.001) and patients' satisfaction (p = 0.005). Descriptions of CHD and impact on lifestyle were more eloquent after seeing a 3D model. The majority of participants reported that models helped their understanding and improved their visit, with a non-negligible 30% of participants indicating that the model made them feel more anxious about their condition. Content analysis of open-ended feedback revealed an overall positive attitude of the participants toward 3D models. Clinical translation of 3D models of CHD for communication purposes warrants further exploration in larger studies

Can finite element models of ballooning procedures yield mechanical response of the cardiovascular site to overexpansion?

Patient-specific numerical models could aid the decision-making process for percutaneous valve selection; in order to be fully informative, they should include patient-specific data of both anatomy and mechanics of the implantation site. This information can be derived from routine clinical imaging during the cardiac cycle, but data on the implantation site mechanical response to device expansion are not routinely available. We aim to derive the implantation site response to overexpansion by monitoring pressure/dimensional changes during balloon sizing procedures and by applying a reverse engineering approach using a validated computational balloon model. This study presents the proof of concept for such computational framework tested in-vitro. A finite element (FE) model of a PTS-X405 sizing balloon (NuMed, Inc., USA) was created and validated against bench tests carried out on an ad hoc experimental apparatus: first on the balloon alone to replicate free expansion; second on the inflation of the balloon in a rapid prototyped cylinder with material deemed suitable for replicating pulmonary arteries in order to validate balloon/implantation site interaction algorithm. Finally, the balloon was inflated inside a compliant rapid prototyped patient-specific right ventricular outflow tract to test the validity of the approach. The corresponding FE simulation was set up to iteratively infer the mechanical response of the anatomical model. The test in this simplified condition confirmed the feasibility of the proposed approach and the potential for this methodology to provide patient-specific information on mechanical response of the implantation site when overexpanded, ultimately for more realistic computational simulations in patient-specific settings

An interactive simulation tool for patient-specific clinical decision support in single-ventricle physiology

OBJECTIVE: Modeling of single-ventricle circulations has yielded important insights into their unique flow dynamics and physiology. Here we translated a state-of-the-art mathematical model into a patient-specific clinical decision support interactive Web-based simulation tool and show validation for all 3 stages of single-ventricular palliation. METHODS: Via the adoption a validated lumped parameter method, complete cardiovascular-pulmonary circulatory models of all 3 stages of single-ventricle physiology were created within a simulation tool. The closed-loop univentricular heart model includes scaling for growth and respiratory effects, and typical patient-specific parameters are entered through an intuitive user interface. The effects of medical or surgical interventions can be simulated and compared. To validate the simulator, patient parameters were collected from catheterization reports. Four simulator outputs were compared against catheterization findings: pulmonary to systemic flow ratio (Qp:Qs), systemic arterial saturation (SaO2), mean pulmonary arterial pressure (mPAp), and systemic–venous oxygen difference (SaO2–SvO2). RESULTS: Data from 60 reports were used. Compared with the clinical values, the simulator results were not significantly different in mean Qp:Qs, SaO2, or mPAp (P > .09). There was a statistical but clinically insignificant difference in average SaO–SvO2 (average difference 1%, P < .01). Linear regression analyses revealed a good prediction for each variable (Qp:Qs, R2 = 0.79; SaO2, R2 = 0.64; mPAp, R2 = 0.69; SaO2–SvO2, R2 = 0.93). CONCLUSIONS: This simulator responds quickly and predicts patient-specific hemodynamics with good clinical accuracy. By predicting postoperative and postintervention hemodynamics in all 3 stages of single-ventricle physiology, the simulator could assist in clinical decision-making, training, and consultation. Continuing model refinement and validation will further its application to the bedside

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

BACKGROUND: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. METHODS: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. FINDINGS: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. INTERPRETATION: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications