The role of computational methods in cardiovascular medicine: a narrative review.

Background and Objective: Computational models of the cardiovascular system allow for a detailed and quantitative investigation of both physiological and pathological conditions, thanks to their ability to combine clinical-possibly patient-specific-data with physical knowledge of the processes underlying the heart function. These models have been increasingly employed in clinical practice to understand pathological mechanisms and their progression, design medical devices, support clinicians in improving therapies. Hinging upon a long-year experience in cardiovascular modeling, we have recently constructed a computational multi-physics and multi-scale integrated model of the heart for the investigation of its physiological function, the analysis of pathological conditions, and to support clinicians in both diagnosis and treatment planning. This narrative review aims to systematically discuss the role that such model had in addressing specific clinical questions, and how further impact of computational models on clinical practice are envisaged. Methods: We developed computational models of the physical processes encompassed by the heart function (electrophysiology, electrical activation, force generation, mechanics, blood flow dynamics, valve dynamics, myocardial perfusion) and of their inherently strong coupling. To solve the equations of such models, we devised advanced numerical methods, implemented in a flexible and highly efficient software library. We also developed computational procedures for clinical data post-processing-like the reconstruction of the heart geometry and motion from diagnostic images-and for their integration into computational models. Key Content and Findings: Our integrated computational model of the heart function provides non-invasive measures of indicators characterizing the heart function and dysfunctions, and sheds light on its underlying processes and their coupling. Moreover, thanks to the close collaboration with several clinical partners, we addressed specific clinical questions on pathological conditions, such as arrhythmias, ventricular dyssynchrony, hypertrophic cardiomyopathy, degeneration of prosthetic valves, and the way coronavirus disease 2019 (COVID-19) infection may affect the cardiac function. In multiple cases, we were also able to provide quantitative indications for treatment. Conclusions: Computational models provide a quantitative and detailed tool to support clinicians in patient care, which can enhance the assessment of cardiac diseases, the prediction of the development of pathological conditions, and the planning of treatments and follow-up tests.

Normative computed tomography angiography values of the main and branch pulmonary arteries in children.

Non-invasive cardiac imaging like echocardiogram, cardiac magnetic resonance imaging (CMR), and computed tomography angiography (CTA) play a key role in the diagnosis, aid in management and follow-up of congenital heart disease patients. Normative data for intracardiac and extracardiac vascular structures in children are currently available for echocardiogram, CMR, and non-gated CTA. We sought to establish systolic and diastolic normative data for main and branch pulmonary arteries in children using electrocardiogram (ECG)-gated CTA. Diameters and cross-sectional areas of the main and branch pulmonary arteries were measured in systole and diastole based on the aortic valve position (open versus closed) in 100 subjects who had ECG-gated cardiac CTA at our center between January 2015 through December 2020 and met our inclusion criteria. The allometric exponent (AE) for each parameter was derived, and the parameter/body surface area (BSAAE) was established using the previously described methods. A total of 100 children aged 0-18 years were analyzed; mean age was 5.3 years (SD, 6.1 years). Z-score curves were plotted in relation to the BSA for the mean, maximum, and minimum diameters and cross-sectional area of the main and branch pulmonary arteries for systole and diastole.   Conclusion: We report systolic and diastolic mean, maximum, and minimum diameters and cross-sectional areas along with Z-scores and normative curves for the main and branch pulmonary arteries in children derived using ECG-gated cardiac CTA. We believe our results can help identify abnormally sized main and branch pulmonary arteries. What is Known: • Normative data for intracardiac and extracardiac vascular structures in the pediatric population are available for echocardiography, cardiac MRI and non-ECG gated CTA. • Z-scores with standard deviations are commonly used in children, but SDs are not constant across body sizes due to heteroscedasticity. What is New: • Allometric exponent was derived for each parameter and the parameter/body surface area (BSA) was established. • This is the first ECG-gated CTA study to provide normative en face systolic, diastolic diameters and cross-sectional areas along with Z-scores and normative curves for the main and branch pulmonary arteries in children.

Computed Tomography Tissue Characterization of Pediatric Cardiac Tumor.

Little is known about tissue characterization of cardiac tumors by dedicated cardiac computed tomography (CT) protocols in pediatric patients. We report using arterial and delayed CT acquisitions to characterize a large left ventricular free wall tumor in a 12-year-old female with congenital mitral insufficiency and an automatic implantable cardioverter defibrillator. (Level of Difficulty: Intermediate.).

Role of Cardiac CTA to Evaluate Branch Pulmonary Artery Stenosis and Ductal Insertion Pattern in Right-Sided Congenital Heart Defects.

There is limited experience in evaluating abnormal ductus arteriosus (DA) insertion pattern by contrast-enhanced cardiac computed tomography (cardiac CT) in patients with right-sided obstructive cardiac defects. Retrospective review of 38 infants with right-sided obstructive cardiac defects who underwent a preoperative cardiac CT between 2016 and 2021. We reviewed the types of cardiac lesions, patterns of ductal insertion, frequency of pulmonary artery (PA) stenosis requiring intervention, total dose length product (DLP), and effective radiation dose. Of 38 infants, 45% were female, the median gestational age and weight were 37 (range 34-40) weeks and 2.95 (range 2-4) kg. The most common pathologies were pulmonary atresia with ventricular septal defect (24%) and tetralogy of Fallot (24%). The abnormal ductal insertion patterns were DA inserting into the left PA in 39%, DA bifurcating into branch PA in 32%, and DA inserting into the right PA in 13%. Of the 38 infants, 76% developed branch PA stenosis requiring intervention. Among patients with abnormal DA insertion, 44% required branch PA arterioplasty during their index surgery compared to 17% without abnormal DA insertion. Regardless of the type of abnormal DA insertion, 67% developed bilateral branch PA stenosis over time. The mean DLP was 8 mGy-cm and the mean calculated effective radiation dose was 0.312 mSv. The utilization of contrast-enhanced cardiac CT in infants with right-sided obstructive heart defects can offer crucial insights into abnormal ductus arteriosus insertion patterns. This information is valuable for effective procedure planning and for monitoring the development of branch pulmonary artery stenosis.

Essential role of cardiac computed tomography for surgical decision making in children with total anomalous pulmonary venous connection and single ventricle.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a major risk factor in infants with single ventricle (SV). Exact definition of TAPVC anatomy is crucial for surgical planning. AIM: To evaluate the role of cardiac computed tomography (CT) in this setting. METHODS: Retrospective review of 13 infants who underwent TAPVC repair associated with SV from May 2016 to October 2021. Anatomy, incidence, and mechanisms of pulmonary venous obstruction (PVO) were described. Cardiac CT diagnostic yield was compared to echocardiography (echo). RESULTS: Of 13 infants, median age and weight were 24 days (range 2-303 days) and 3.2 (range 2.6-9.1) kg, 8 (62%) were male, 4 (31%) premature, and 11 (85%) had heterotaxy syndrome. All infants had pre- and postoperative echo; 13 had preoperative and 8 (62%) had postoperative cardiac CT. Type of TAPVC: six (46%) supracardiac, two (15%) intracardiac, one (8%) infracardiac, and four (31%) mixed, with pulmonary veins draining in >1 confluence in nine (69%). PVO was present in 6/13 (46%) preoperatively and 5/13 (31%) postoperatively. Mechanisms of PVO: 9/11 (82%) stenosis, 1/9 (9%) membrane formation, and 1/9 (9%) external compression. The sensitivity to diagnose PVO was 45.5% for echo and 100% for cardiac CT, the specificity was 100% for both. No discrepancy was found between cardiac CT and intraoperative findings, but echo had a complete preoperative diagnosis in 1/13 (8%) (p < .00001, Fisher exact test). CONCLUSIONS: Cardiac CT is essential to evaluate pre- and postoperative TAPVC in SV for surgical decision making and long term follow up.

Virtual Simulated Implantation of an Adult-Sized Left Ventricular Assist Device in a Pediatric Patient.

There is very limited experience with simulated virtual implantation of left ventricular assist devices (LVADs) to assess device fitness in pediatric patients. In this clinical vignette, we report the case of a 9-year-old male patient with dilated cardiomyopathy who underwent successful placement of an LVAD after virtual simulated implantation was performed. (Level of Difficulty: Advanced.).

Pre- and post-operative cardiovascular CT in Stage I single ventricle palliation.

OBJECTIVES: The aim of this study is to describe clinical utility of low dose cardiac computed tomography (CT) in the evaluation of single ventricle physiology before and after Stage I palliation. BACKGROUND: Despite the increased utilization of CT imaging and advancement of CT technology, there are limited studies describing the routine clinical use of cardiac CT and radiation dose parameters in the single ventricle Stage I palliation. METHODS: This single center, retrospective study included 57 infants with single ventricle physiology who underwent cardiac CT scans between January 1, 2016 and November 30, 2020. Patients' demographic information, diagnosis, indication, total dose length product (DLP), computed tomographic dose index volume (CTDIvol), cardiac CT findings and intraoperative or intraprocedural findings were reviewed. Estimated effective radiation dose was calculated using a previously published conversion rate. RESULTS: The studies were performed using different generations of CT scanners over the 4 years period: Somatom AS 128, Somatom definition edge, Somatom Force (Siemens Medical Solutions). The studies performed with dual source scanner with prospective gated technique have lower radiation dose exposure with median effective radiation dose of 0.32 mSv. CONCLUSION: Pre- and post-operative cardiovascular CT in Stage I single ventricle palliation using newer generation scanners with prospective gated technique can be done with minimal radiation exposure and good image quality. Cardiac CT is a powerful imaging modality for better management planning in this group of patients.

Modern advances regarding interatrial communication in congenital heart defects.

BACKGROUND: The interatrial communication, one of the most frequent congenital heart defects, represents an important intracardiac shunt between systemic and pulmonary circulations. Direction and magnitude of the interatrial shunting depends upon several features, including defect size, shape and location, pressure difference between right and left atrium, and difference in right and left ventricular compliance. METHODS: In this review article, the presence or absence of interatrial communication, and its role, have been analyzed, as they can have a critical impact on the cardiovascular physiopathology, and the interatrial communication can prove to be either clinically harmful, useful or indispensable. Accordingly, the utility and role of the interatrial communication in modern congenital, pediatric and adult, disease has evolved, with modification of the indications to close, maintain patency, or create an interatrial communication. RESULTS: The interatrial communication and shunting can be manipulated to maximize the oxygen delivery to the tissues, accordingly with the underlying congenital heart defect. While not always relevant to patients with bi-ventricular circulations, this becomes extremely important in children and adults with complex congenital heart defects. CONCLUSIONS: With improving long-term survival for the vast majority of congenital heart patients, an advanced understanding of the role and utility of the interatrial communication, and of all the possibilities of its manipulation, is essential to improve the patient outcomes.

Surgical approach for anomalous aortic origin of a coronary artery: A comparison of two techniques.

BACKGROUND: Un-roofing is the most common technique utilized for repair of anomalous aortic origin of a coronary artery (AAOCA). There are very few publications directly comparing un-roofing to another surgical technique, like reimplantation. METHODS: The prospectively collected Children's Memorial Hermann Heart Institute Society of Thoracic Surgeon's Database was retrospectively reviewed from 2007 to 2021. Surgical patients were included if they underwent un-roofing or reimplantation of the AAOCA. The primary outcomes of this study were operative characteristics and postoperative outcomes. Secondary outcomes included angiographic outcomes, aortic regurgitation incidence, ventricular function, and symptom relief. RESULTS: From 2007 to 2021, there were 12 patients who underwent either a reimplantation (n = 9, 73%) or un-roofing (n = 3, 27%) for an AAOCA. The hospital length of stay was a median of 1.8 days longer for reimplantation compared to un-roofing. The last follow-up echocardiogram was a median of 52.2 days later in the reimplantation group. There was one patient (11%) in the reimplantation group that had more than or equal to mild aortic regurgitation and mild systolic ventricular dysfunction. Outpatient follow-up was incomplete and there was no postoperative computed tomographic angiography in the un-roofing cohort. CONCLUSIONS: Coronary artery reimplantation is a valuable alternative surgical technique to un-roofing for the repair of AAOCA. There are still some concerns with the creation of aortic regurgitation or incomplete symptom relief with any surgical technique. Longer-term follow-up and prospective studies will be needed to show an effective reduction of myocardial ischemia and risk of sudden cardiac death.

Perioperative Anomalous Pulmonary Venous Return Evaluation With Low-Dose Cardiac Computed Tomography.

BACKGROUND: Low-dose multidetector computed tomographic angiography (MDCTA) is playing an increasingly larger role in the diagnosis of anomalous pulmonary venous return (APVR). Despite advances in new computed tomographic (CT) techniques with radiation dose reduction, there are limited studies describing radiation dose parameters to allow routine use of cardiac CT in infants and children with APVR. This study compares cardiac CT findings with intraoperative findings and describes comprehensive radiation exposure parameters. METHODS: A retrospective analysis of 27 patients compared MDCTA and intraoperative or cardiac catheterization findings of the pulmonary venous anatomy. RESULTS: A total of 32 MDCTA studies were performed on these 27 patients. Of the 28 studies with subsequent intervention, MDCTA accurately diagnosed the anomalous pulmonary venous anatomy in 27 (96.4%) patients. Narrowing of the pulmonary venous confluence entrance to the coronary sinus was missed on cardiac CT in one patient due to motion artifact, but it was noted intraoperatively. Median estimated effective radiation dose was 0.98 mSv (range: 0.39-3.2 mSv), and mean estimated effective radiation dose was 1.1 ± 0.68 mSv. Median total dose length product (DLP) was 25 mGy cm (range: 10-83 mGy cm), and mean total DLP was 28 ± 18 mGy cm. Median CTDI volume was 3.8 mGy (range: 2.5-14.6 mGy), and mean CTDI volume was 5.0 ± 3.2 mGy. CONCLUSIONS: We conclude that modern cardiac MDCTA is the best imaging modality to guide management in both preintervention and postintervention APVR patients. In this study, we describe comprehensive radiation exposure parameters in infants and children with APVR.

Development of a biventricular conversion program: A new paradigm.

BACKGROUND: Borderline small ventricular size or technical issues precluding the use of both ventricles may lead to single ventricle palliation. Fontan complications have led some centers to look for alternatives to the traditional pathway. The objective of this study is to evaluate the essential philosophy and outcomes of a new biventricular (BiV) conversion program. METHODS: The prospectively collected Children's Memorial Hermann Heart Institute Society of Thoracic Surgeon's Database was retrospectively reviewed between July 2017 and July 2020. RESULTS: Thirteen patients met inclusion criteria and underwent BiV conversion during that time. The most frequent diagnosis was malposed great arteries and a ventricular septal defect (VSD) in 4 (31%) patients. Seven (54%) patients were in the first interstage, and 1 (8%) patient had already undergone a Fontan operation before their BiV conversion operation. One or more risk factors for single ventricle palliation (genetic syndrome ≥ moderate atrioventricular valve regurgitation ≥ moderate ventricular dysfunction, presence of signs of Fontan failure) were present in 3 (23%) patients. The median left ventricular end diastolic pressure increased from 5.5 mmHg (4-10 mmHg) to 10 mmHg (6-20 mmHg) postoperatively (p < .05). The right ventricular pressure (RVP) was estimated as less than half systemic in all six patients who were able to be estimated. At a median follow-up of 22.6 months (0.3-36.4 months), 12 (92%) patients are alive. CONCLUSIONS: BiV conversion is feasible with reasonable short-term clinical outcomes. Mortality risk is low, but as seen in other studies, the risk of reintervention is high.

Evaluation of complex congenital heart disease in infants using low dose cardiac computed tomography.

Despite advances in new CT techniques with radiation dose reduction, there are limited studies describing radiation dose. Describing radiation dose might help to educate physicians on how the benefit of cardiac CT outweighs the potential risk of radiation. The aim of this study was to describe the radiation exposure parameters in newborns and infants and the role of CT scan in providing useful information for optimal surgical planning and management of newborns and infants with complex congenital heart disease. In complex congenital heart disease delineating the anatomy and using the CT images as needed for three-dimensional modelling helps for optimal surgical planning. This single center, retrospective study included 74 infants with CHD (median age 2 months, range 1 day to 9 months) who underwent cardiac CT evaluation from September 2018 to April 2019, using the Siemens Somatom Definition Edge scanner. Total dose length product (DLP) and computed tomographic dose index volume (CTDIvol) were recorded, and the estimated effective radiation dose was calculated using a previously published conversion rate. Median effective radiation dose for the computed tomographic angiography (CTA) was 0.6 mSv. The median DLP was 13 mGycm and median CTDIvol was 3.5 mGy. Cardiac CT can be done with a sub-mSv dose in infants. Cardiac CT completes the standard initial evaluation of neonates and infants with complex CHD, allowing thorough understanding of complex spatial relationships between anatomical and defective structures, and is achievable with minimal radiation exposure.

Persistence of Late Gadolinium Enhancement on Follow-Up CMR Imaging in Children with Acute Myocarditis.

Cardiac magnetic resonance (CMR) imaging is the gold standard non-invasive test for the diagnosis of acute myocarditis. Late gadolinium enhancement (LGE) on CMR imaging signifies myocardial fibrosis or scar but information on long-term follow-up in pediatric patients is limited. The aim of this study is to evaluate the persistence of LGE in follow-up CMR imaging and highlight the need for serially following LGE after acute myocarditis in children. A retrospective review of the CMR images in pediatric patients less than 18 years of age at Children's Memorial Hermann Hospital was performed from October 31, 2010, to December 31, 2017. The ages of the patients included in the study ranged from 10 to 17 years. Out of 34 subjects, 12 subjects had a follow-up CMR imaging after the initial CMR imaging. Cardiac enzymes and inflammatory markers were elevated in all patients on initial presentation with normalization seen for all patients on follow-up testing. Baseline CMR imaging demonstrated depressed function in 50% of patients (6/12) with recovery of biventricular function seen in all except for one patient. LGE was detected in 10 out of 12 patients on baseline CMR and persisted in all on follow--up CMR imaging. Two patients did not have LGE at baseline CMR and had no evidence of LGE at follow-up CMR. Despite resolution of acute myocardial inflammation, LGE persisted in all of our study subjects. There is neither an agreement on time interval to perform follow-up CMR, nor on duration of follow-up. We recommend large-scale prospective CMR study for long-term follow-up evaluation of children after acute myocarditis.

Cardiac Magnetic Resonance to Evaluate Percutaneous Pulmonary Valve Implantation in Children and Young Adults.

Experience with cardiac magnetic resonance to evaluate coronary arteries in children and young adult patients is limited. Because noninvasive imaging has advantages over coronary angiography, we compared the effectiveness of these techniques in patients who were being considered for percutaneous pulmonary valve implantation. We retrospectively reviewed the cases of 26 patients (mean age, 12.53 ± 4.85 yr; range, 5-25 yr), all of whom had previous right ventricular-to-pulmonary artery homografts. We studied T2-prepared whole-heart images for coronary anatomy, velocity-encoded cine images for ventricular morphology, and function- and time-resolved magnetic resonance angiographic findings. Cardiac catheterization studies included coronary angiography, balloon compression testing, right ventricular outflow tract, and pulmonary artery anatomy. Diagnostic-quality images were obtained in 24 patients (92%), 13 of whom were considered suitable candidates for valve implantation. Two patients (8%) had abnormal coronary artery anatomy that placed them at high risk of coronary artery compression during surgery. Twelve patients underwent successful valve implantation after cardiac magnetic resonance images and catheterization showed no increased risk of compression. We attempted valve implantation in one patient with unsuitable anatomy but ultimately placed a stent in the homograft. Magnetic resonance imaging of coronary arteries is an important noninvasive study that may identify patients who are at high risk of coronary artery compression during percutaneous pulmonary valve implantation, and it may reveal high-risk anatomic variants that can be missed during cardiac catheterization.

Cardiac Magnetic Resonance Feature Tracking Biventricular Two-Dimensional and Three-Dimensional Strains to Evaluate Ventricular Function in Children After Repaired Tetralogy of Fallot as Compared with Healthy Children.

Cardiac magnetic resonance imaging is an important tool to evaluate cardiac anatomy and ventricular size and function after repaired tetralogy of Fallot. Magnetic resonance tissue tagging is the gold standard for evaluation of myocardial strain. However, myocardial tagging strain requires tagged images to be obtained prospectively, during the scan and with limited temporal resolution. Cardiac magnetic resonance feature tracking is a new tool that allows the retrospective analysis of cine images. There is limited experience with cardiac magnetic resonance feature tracking strain analysis in children. The medical records of patients with repaired tetralogy of Fallot that had a cardiac magnetic resonance (CMR) study from December 2013 to June 2015 were reviewed. The control group included patients who underwent a CMR with normal cardiac anatomy and ventricular function. Global longitudinal, circumferential and radial strain parameters (2D and 3D) were obtained by retrospectively contouring cine images from ventricular short axis, two chamber and four chamber views using post-processing software (Circle CVi42, Calgary, Canada). The correlation between conventional ventricular function parameters and ventricular strain was performed using Pearson's correlation. The mean age of tetralogy of Fallot and control subjects was 12.4 and 14.1 years, respectively. In patients after repaired tetralogy of Fallot, the mean left ventricular global 2D and 3D circumferential strains were -17.4 ± 2.9 and -10.1 ± 3, respectively. The mean indexed right ventricular end-diastolic volume was 135.4 cc m2 ± 46 compared to 75.7 cc m2 ± 17 in control subjects (P = 0.0001, CI 95%). Left ventricular global circumferential 3D strain showed a statistically significant difference in patients after TOF repair compared to normal subjects (-10.1 ± 3 vs. -14.71 ± 1.9, P = 0.00001). A strong correlation between left ventricular global circumferential 3D strain and right ventricular end-diastolic volume (P ≤ 0.0001) was noted. We found a strong correlation between left ventricular circumferential 3D strain and indexed right ventricular end-diastolic volume, as well as a strong correlation between left ventricular longitudinal 2D strain and right ventricular ejection fraction. Circumferential 3D strain may be a suitable tool to detect early abnormalities of ventricular myocardium even before the ejection fraction becomes compromised. Large-scale prospective studies are recommended.

Anomalous origin of the right coronary artery from the posterior, non-coronary sinus of Valsalva diagnosed by cardiac magnetic resonance imaging.

Anomalous origin of the right coronary artery from the posterior, non-coronary sinus is extremely rare and has never been reported in a paediatric-age competitive athlete. We report this very rare case of the right coronary artery arising from the posterior sinus. In the anomalous right coronary from the posterior sinus, the proximal right coronary artery appears widely patent and has no interarterial course.

Fetal complete common atrioventricular canal defect: spontaneous closure of the ventricular septal defect--in utero anatomic evolution and postnatal outcomes.

BACKGROUND: We describe in utero anatomic evolution and postnatal outcome of complete common atrioventricular canal defect (CCAVCD). METHODS: Retrospective data on 31 fetuses with CCAVCD were analyzed. We reviewed prenatal and postnatal echocardiograms, karyotype, and postnatal outcomes. RESULTS: A total of 20 fetuses had complete data, 18 with serial fetal echocardiograms and postnatal data and 2 terminations. At initial examination, isolated CCAVCD was seen in 12 (67%) fetuses while 6 (33%) were associated with heterotaxy syndrome. On follow-up, 4 fetuses (22%) had spontaneous closure of the inlet ventricular septal defect (VSD) component of the CCAVCD, seen both at 30 to 35 weeks of gestation and on postnatal echocardiograms. These 4 fetuses had previously demonstrated CCAVCD between 18 and 25 weeks of gestation. A total of 15 (83%) patients underwent operative correction, 10 with isolated complete atrioventricular septal defect and 5 with heterotaxy had surgical repair. Four infants in whom spontaneous intrauterine closure of the VSD component was observed had no VSD noted at surgery and underwent closure of primum atrial septal defect and repair of the left atrioventricular (AV) valve cleft. CONCLUSIONS: Our data demonstrate that CCAVCD diagnosed during fetal life is not a static anomaly. In our series, an inlet VSD less than 4 mm and Rastelli type A anatomy (AV valve attachment to septal crest) during second trimester may evolve during third trimester by formation of AV sulcus pouch and spontaneous closure of the VSD. To the best of our knowledge, this is the first study to report such anatomic evolution of CCAVCD in the fetus. This information is vital for appropriate counseling for expectant parents.