Multi-Modal in Vitro Experiments Mimicking the Flow Through a Mitral Heart Valve Phantom.

PURPOSE: Fluid-structure interaction (FSI) models are more commonly applied in medical research as computational power is increasing. However, understanding the accuracy of FSI models is crucial, especially in the context of heart valve disease in patient-specific models. Therefore, this study aimed to create a multi-modal benchmarking data set for cardiac-inspired FSI models, based on clinically important parameters, such as the pressure, velocity, and valve opening, with an in vitro phantom setup. METHOD: An in vitro setup was developed with a 3D-printed phantom mimicking the left heart, including a deforming mitral valve. A range of pulsatile flows were created with a computer-controlled motor-and-pump setup. Catheter pressure measurements, magnetic resonance imaging (MRI), and echocardiography (Echo) imaging were used to measure pressure and velocity in the domain. Furthermore, the valve opening was quantified based on cine MRI and Echo images. RESULT: The experimental setup, with 0.5% cycle-to-cycle variation, was successfully built and six different flow cases were investigated. Higher velocity through the mitral valve was observed for increased cardiac output. The pressure difference across the valve also followed this trend. The flow in the phantom was qualitatively assessed by the velocity profile in the ventricle and by streamlines obtained from 4D phase-contrast MRI. CONCLUSION: A multi-modal set of data for validation of FSI models has been created, based on parameters relevant for diagnosis of heart valve disease. All data is publicly available for future development of computational heart valve models.

Validation of fluid-structure interaction simulations of the opening phase of phantom mitral heart valves under physiologically inspired conditions.

BACKGROUND AND OBJECTIVE: Atrioventricular valve disease is a common cause of heart failure, and successful surgical or interventional outcomes are crucial. Patient-specific fluid-structure interaction (FSI) modeling may provide valuable insights into valve dynamics and guidance of valve repair strategies. However, lack of validation has kept FSI modeling from clinical implementation. Therefore, this study aims to validate FSI simulations against in vitro benchmarking data, based on clinically relevant parameters for evaluating heart valve disease. METHODS: An FSI model that mimics the left heart was developed. The domain included a deformable mitral valve of different stiffnesses run with different inlet velocities. Five different cases were simulated and compared to in vitro data based on the pressure difference across the valve, the valve opening, and the velocity in the flow domain. RESULTS: The simulations underestimate the pressure difference across the valve by 6.8-14 % compared to catheter measurements. Evaluation of the valve opening showed an underprediction of 5.4-7.3 % when compared to cine MRI, 2D Echo, and 3D Echo data. Additionally, the simulated velocity through the valve showed a 7.9-8.4 % underprediction in relation to Doppler Echo measurements. Qualitative assessment of the velocity profile in the ventricle and the streamlines of the flow in the domain showed good agreement of the flow behavior. CONCLUSIONS: Parameters relevant to the diagnosis of heart valve disease estimated by FSI simulations showed good agreement when compared to in vitro benchmarking data, with differences small enough not to affect the grading of heart valve disease. The FSI model is thus deemed good enough for further development toward patient-specific cases.

Mitral valve repair using leaflet expansion and subpartial annuloplasty in children.

Objective: Mitral valve reconstruction in the pediatric population is a challenge due to the frequent combination of annular dilatation and leaflet restriction and the need for growth. We present a novel strategy using leaflet expansion and subpartial annuloplasty with polytetrafluoroethylene reinforcement. Methods: From January 2014 through May 2021, 11 children aged 5 months to 14 years (median, 24 months) underwent elective mitral valve repair due to severe mitral valve regurgitation. The mitral valve abnormalities included congenital malformations (n = 7), postoperative leakage following commissurotomy (n = 1), and functional mitral valve regurgitation due to dilated cardiomyopathy (n = 3). Surgery consisted of leaflet expansions with autologous, untreated pericardium and subpartial annuloplasty with polytetrafluoroethylene reinforcement. Results: All children survived their surgeries with uneventful postoperative courses, except for 1 patient who needed an early reoperation to resolve a functional stenosis due to a spinnaker phenomenon. At discharge, mean gradient was 3.5 ± 3.9 mm Hg, with trivial mitral regurgitation in 9 patients (82%). All patients were alive and asymptomatic during the median follow-up of 3 years (range, 1-7 years). Their echocardiographic data showed a mean transmitral gradient of 4.4 ± 1.7 mm Hg and remained unchanged. Residual mitral valve regurgitation was trivial or mild in 9 patients (82%) and moderate in 2 patients (18%). Conclusions: Leaflet expansion with autologous pericardium and subpartial annuloplasty with polytetrafluoroethylene reinforcement for mitral regurgitation in the pediatric population gives stable and satisfactory results both early and at intermediate follow-up, permitting growth of the mitral valve.

Reoperations After Repair for Atrioventricular Septal Defects: >25 Years Experience at a Single Center.

Our aim was to evaluate the total burden of reoperations after previous repair for atrioventricular septal defects, including long-term survival and identify risk factors for reoperation. All patients with surgical correction for atrioventricular septal defect (AVSD) 1993- 2020 underwent a follow-up in October 2020. Clinical data were obtained by retrospective review and evaluated with Kaplan-Meier and competing risk analysis. Of 477 patients who underwent initial repair, 53 patients (11.1%) underwent a total of 82 reoperations. The perioperative mortality at reoperation was 3.8% (2/53). There were no late deaths (0/51) during follow-up. In patients requiring reoperation for left atrioventricular valve regurgitation, a re-repair was performed in 90% (26/29) at first attempt. Estimated overall survival was 96.2 ± 2.6% (95% CI 91.2-100) in the Any reoperation group and 96.7 ± 0.9% (95% CI 94.9-98.5) in the No reoperation group at 20 years (P = 0.80). The cumulative incidence function of Any reoperation (with death as competing risk) was 13.0% (95% CI 9.4-16.5) at 20 years. Independent risk factors for Any reoperation included severe mitral regurgitation after primary repair (HR 40.7; 95% CI 14.9-111; P < 0.001). The risk of perioperative mortality in AVSD patients undergoing reoperation was low in the present study. Long-term survival was very good and not significantly different when compared to patients who did not need reoperation. Re-repair for left atrioventricular valve regurgitation was possible in most cases and showed long-term durability. Our data suggest that reoperations after primary repair of AVSD have very good long-term outcomes when performed at a high-volume pediatric cardiac surgery center.

Impact of concomitant complex cardiac anatomy in nonsyndromic patients with complete atrioventricular septal defect.

OBJECTIVE: We studied a cohort of patients with nonsyndromic complete atrioventricular septal defect with and without concomitant complex cardiac anatomy and compared the outcomes after surgical repair. METHODS: Between 1993 and 2018, 62 nonsyndromic patients underwent complete atrioventricular septal defect repair. Sixteen patients (26%) had complex complete atrioventricular septal defect with variables representing concomitant cardiac anatomic complexity: tetralogy of Fallot, double outlet right ventricle, total anomalous pulmonary venous return, concomitant aortic arch reconstruction, multiple ventricular septal defects, staged repair of coarctation of the aorta, and a persisting left superior vena cava. The mean follow-up was 12.7 ± 7.9 years. Baseline variables were retrospectively evaluated and analyzed using univariable logistic regression. Survival was studied using Kaplan-Meier estimates, and group comparisons were performed using the log-rank test. A competing-risk analysis estimated the risk of reoperation with death as the competing event. A Gray's test was used to test equality of the cumulative incidence curves between groups. RESULTS: The perioperative mortality was 3.2% (2/62). Actuarial survival was 100% versus 66.7% ± 14.9% at 10 years in the noncomplex and complex groups, respectively (P < .01). There was no significant difference in the overall reoperation rate between the noncomplex group (7/46; 15%) and the complex group (4/16; 25%) (odds ratio, 1.86; 95% confidence interval, 0.46-7.45; P = .30). The competing-risk analysis demonstrated no significant difference in reoperation between the groups (P = .28). CONCLUSIONS: Our data show that nonsyndromic patients without complex cardiac anatomy have a good long-term survival and an acceptable risk of reoperation similar to contemporary outcomes for patients with complete atrioventricular septal defect with trisomy 21. However, the corresponding group of nonsyndromic patients with concomitant complex cardiac lesions are still a high-risk population, especially regarding mortality.

Long-term outcome after early repair of complete atrioventricular septal defect in young infants.

OBJECTIVE: The long-term outcome after repair of complete atrioventricular septal defect in young infants is still not fully understood. The objective of this study was to evaluate data after repair for complete atrioventricular septal defect over a 25-year period to assess survival and identify risk factors for left atrioventricular valve-related reoperations. METHODS: A total of 304 consecutive patients underwent surgical correction for complete atrioventricular septal defect between April 1993 and October 2018. The results for young infants (aged <3 months; n = 55; mean age 1.6 ± 0.6 months) were compared with older infants (aged >3 months; n = 249; mean age, 5.1 ± 5.2 months). Mean follow-up was 13.2 ± 7.8 years (median, 14.0 years; interquartile range, 7.0-20.0). The Kaplan-Meier method was used to assess overall survival and freedom from left atrioventricular valve-related reoperation. RESULTS: Overall, 30-day mortality was 1.0% (3/304) with no difference between young and older infants (P = 1.0). Overall survival in the total population at 20-year follow-up was 95.1% (±1.3%). Independent risk factors for poor survival were the presence of an additional ventricular septal defect (P = .042), previous coarctation of the aorta (P < .001), persistent left superior vena cava (P = .026), and genetic syndromes other than Trisomy 21 (P = .017). Freedom from left atrioventricular valve-related reoperation was 92.6% (±1.7%) at 20 years. There was no significant difference in left atrioventricular valve-related reoperation in young infants compared with older infants (P = .084). CONCLUSIONS: Our data demonstrated that excellent long-term survival could be achieved with early repair for complete atrioventricular septal defect, and the need for reoperations due to left atrioventricular valve regurgitation was low. Primary correction in patients aged less than 3 months is, when clinically necessary, well tolerated. Palliative procedures can be avoided in the majority of patients.

Comprehensive echocardiographic imaging of atrioventricular valves in children with atrioventricular septal defect: Accuracy of 2D and 3D imaging and reasons for disagreement.

OBJECTIVE: To compare the accuracy and reasons for disagreement of two-dimensional (2D) and three-dimensional (3D) echocardiography findings in the assessment of the atrioventricular valve complex in patients with atrioventricular septal defect. METHODS: A total of 20 children (mean age 8 months) with atrioventricular septal defect were enrolled prospectively into this study. The accuracy of and the reasons for disagreement in the assessment of the atrioventricular valve features were analyzed between 2D and 3D echocardiography and surgical findings. RESULTS: We found that in assessing the Rastelli type and the extension of the inferior leaflet into the right ventricle, 3D echocardiography was more accurate compared to 2D echocardiography. In all other features, 2D and 3D echocardiography showed similar accuracy. A significant reason for inaccuracy by both echo modalities was that the technique itself could not visualize the feature, although the image quality was considered to be adequate. In most cases, where it was not possible to visualize the atrioventricular feature by 2D, it was possible by 3D, and vice versa. CONCLUSION: The accuracy of 2D and 3D echocardiography and understanding the potential reasons for disagreements in assessing the atrioventricular valve complex with 2D and 3D can guide the use of those two techniques when combining them in the clinical practice.

The comparative relationships between locations of the papillary muscles and electrophysiologic QRS axis in patients with atrioventricular septal defect and common as opposed to separate orifices in the valve guarding the common atrioventricular junction.

BACKGROUND: Knowledge regarding factors that influence deviation of the QRS axis is important when seeking to differentiate between physiological and pathological changes. We hypothesised that, in contrast to those patients with an atrioventricular septal defect and common atrioventricular junction permitting only atrial shunting, those associated with ventricular shunting would show no relationship between the positions of the papillary muscles and the degree of the leftward deviation of the QRS axis. METHODS: We compared the positions of endocardial origin of the papillary muscles, and the frontal plane QRS axis, in patients with atrioventricular septal defects and common atrioventricular junction permitting exclusively atrial as opposed to atrial and ventricular shunting. RESULTS: We analysed 18 patients with atrial and ventricular shunting and 23 patients with exclusively atrial shunting. The correlation coefficient between the ratio of distances of the papillary muscles from the mid-septum and the amount of leftward deviation in the frontal plane QRS axis was 0.1 (p=0.4) in those with ventricular shunting and 0.26 (p=0.01) in those with exclusively atrial shunting. CONCLUSIONS: In contrast to patients with the so-called primum form of atrioventricular septal defect, in whom the locations of the papillary muscles correlate with the degree of QRS axis, such relationships are lacking in patients with defects permitting both atrial and ventricular shunting. It may be, therefore, that the presence of ventricular shunting and/or their younger age causes pressure overload, which negates the leftward QRS forces caused by the abnormally positioned papillary muscles.

The ability of mitral papillary muscle positions to explain QRS complex characteristics in humans.

Anatomical location of the conduction system may influence the characteristics of the depolarization and thus characteristics of the QRS complex. It is known that in the heart, there are electro-anatomical relationships, such as relationships among the molecular, genetic and anatomic components of the conduction system and papillary muscles. This review aims to discuss how knowledge of the electro-anatomical developmental relationships helps in understanding the known variability to be observed in the human electrocardiograms.

Relationships between cardiac magnetic resonance imaging abnormalities in the inter-ventricular septum and Selvester QRS scoring criteria for anterior-septal myocardial infarction in patients with right ventricular volume overload.

BACKGROUND: Patients with ostium secundum atrial septal defects (ASDs) were studied to determine the prevalence of Selvester anteroseptal myocardial infarction QRS points, and to test the hypothesis that there is a relationship between these criteria and thinning and/or scarring of the inter-ventricular septum (IVS). METHODS: Demographic, electrocardiographic (ECG), and cardiac magnetic resonance imaging (CMR) data were acquired on 46 patients with a secundum ASD closed percutaneously. Selvester QRS scoring on patient ECGs was performed for areas representing the anteroseptal region of the left ventricle (LV). The IVS to LV free wall thickness ratio was used to assess thinning of the IVS while late gadolinium enhancement (LGE) of the IVS was used for scarring; both using CMR. RESULTS: Twenty-four (52%) patients scored Selvester QRS points in the anteroseptal region with a mean score of 2.6±1.8. The mean IVS/LV free wall thickness ratio at the basal level and mid-ventricular level was 1.1±0.3 and 1.3±0.3, respectively. There was no association of Selvester QRS points with IVS/LV free wall ratio at the basal (p=0.59) or mid-ventricular (p=0.13) levels. The one patient with LGE in the IVS had 4 Selvester anteroseptal QRS points. CONCLUSION: The results of our study demonstrate that in our patient population there is a 52% prevalence of Selvester anteroseptal QRS points which are due to thinning and/or scarring of the IVS in only one patient.

First therapeutic use of Artesunate in treatment of human herpesvirus 6B myocarditis in a child.

BACKGROUND: Human herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis. However, insufficiency of standard antiviral treatment against HHV-6 is an emerging problem. OBJECTIVES: To describe the case of child with HHV-6 myocarditis who was treated by unloading with a left ventricular assist device and Artesunate. STUDY DESIGN: Case report supported by histological and viral diagnoses via a combination of histology/immunohistochemistry and polymerase chain reaction techniques performed on cardiac tissues before and after treatment. RESULTS: Following therapeutic intervention, the clinical status and heart function improved. Endomyocardial biopsies revealed decreased levels of HHV-6B DNA in the myocardium and the disappearance of histological findings in support of lymphocytic myocarditis. Left ventricular assist device could be explanted. No adverse effects of Artesunate were noted. CONCLUSIONS: In addition to existing heart failure treatments, Artesunate can be considered as an effective candidate for clinical use in cases of HHV-6B associated myocarditis.

Computer-based rhythm diagnosis and its possible influence on nonexpert electrocardiogram readers.

BACKGROUND: Systems providing computer-based analysis of the resting electrocardiogram (ECG) seek to improve the quality of health care by providing accurate and timely automatic diagnosis of, for example, cardiac rhythm to clinicians. The accuracy of these diagnoses, however, remains questionable. OBJECTIVES: We tested the hypothesis that (a) 2 independent automated ECG systems have better accuracy in rhythm diagnosis than nonexpert clinicians and (b) both systems provide correct diagnostic suggestions in a large percentage of cases where the diagnosis of nonexpert clinicians is incorrect. METHODS: Five hundred ECGs were manually analyzed by 2 senior experts, 3 nonexpert clinicians, and automatically by 2 automated systems. The accuracy of the nonexpert rhythm statements was compared with the accuracy of each system statement. The proportion of rhythm statements when the clinician's diagnoses were incorrect and the systems instead provided correct diagnosis was assessed. RESULTS: A total of 420 sinus rhythms and 156 rhythm disturbances were recognized by expert reading. Significance of the difference in accuracy between nonexperts and systems was P = .45 for system A and P = .11 for system B. The percentage of correct automated diagnoses in cases when the clinician was incorrect was 28% ± 10% for system A and 25% ± 11% for system B (P = .09). CONCLUSION: The rhythm diagnoses of automated systems did not reach better average accuracy than those of nonexpert readings. The computer diagnosis of rhythm can be incorrect in cases where the clinicians fail in reaching the correct ECG diagnosis.

Importance of standardized assessment of late gadolinium enhancement for quantification of infarct size by cardiac magnetic resonance: implications for comparison with electrocardiogram.

BACKGROUND: Cardiac magnetic resonance (CMR) is currently considered the reference standard for in vivo assessment of myocardial infarction (MI). There is, however, no international consensus on how MI quantification from CMR should be performed. The aim of this study was to test how previously published manual quantification of MI using CMR images compares with MI quantification using a semiautomated, validated method and how this impacts the relationship with MI size estimated by 12-lead electrocardiogram (ECG). METHODS: Twenty-five patients, from a previously published cohort, were included in the study. All patients had presented with clinical signs of acute coronary syndrome 6 to 12 months before undergoing a CMR examination. The patients had a standard 12-lead ECG recorded at the time of the CMR examination. The previously reported manually quantified MI size was compared with MI size determined using a semiautomated method validated by computer phantom data, experimental in vivo and ex vivo data, and patient data. The MI sizes from the 2 CMR approaches were then compared with the ECG-estimated MI size. RESULTS: There was a strong correlation between MI size determined with the 2 CMR methods (r(2) = 0.94, P < .001). There was, however, a systematic overestimation of MI size of approximately 50% by the previously published manually quantified MI size compared with the semiautomated method. This affected the comparison with estimated MI size by ECG, which showed a significant underestimation of MI size compared with manual CMR measurements, but no bias compared with the semiautomated CMR method. CONCLUSIONS: Manual quantification of MI size by CMR can differ significantly from semiautomated, validated methods taking partial volume effects into account and can lead to erroneous conclusions when compared with ECG.