Virus-induced genetics revealed by multidimensional precision medicine transcriptional workflow applicable to COVID-19.

Precision medicine requires the translation of basic biological understanding to medical insights, mainly applied to characterization of each unique patient. In many clinical settings, this requires tools that can be broadly used to identify pathology and risks. Patients often present to the intensive care unit with broad phenotypes, including multiple organ dysfunction syndrome (MODS) resulting from infection, trauma, or other disease processes. Etiology and outcomes are unique to individuals, making it difficult to cohort patients with MODS, but presenting a prime target for testing/developing tools for precision medicine. Using multitime point whole blood (cellular/acellular) total transcriptomics in 27 patients, we highlight the promise of simultaneously mapping viral/bacterial load, cell composition, tissue damage biomarkers, balance between syndromic biology versus environmental response, and unique biological insights in each patient using a single platform measurement. Integration of a transcriptome workflow yielded unexpected insights into the complex interplay between host genetics and viral/bacterial specific mechanisms, highlighted by a unique case of virally induced genetics (VIG) within one of these 27 patients. The power of RNA-Seq to study unique patient biology while investigating environmental contributions can be a critical tool moving forward for translational sciences applied to precision medicine.

Three-dimensional printing for surgical planning in complex congenital heart disease.

Surgical management of complex congenital heart disease (CHD) is challenging. Three-dimensional (3D) printing can improve multidisciplinary team decision-making, patient and family understanding, and education of medical professionals. We describe 3D printing for surgical management of five patients with complex CHD. The anatomical details of the 3D printed models were instrumental in planning surgical techniques especially in determining between single ventricle, 1.5 ventricle, and biventricular repair.

Left Ventricular Pseudoaneurysm Following Surgical Repair of Ventricular Septal Defect in an Infant.

Left ventricular pseudoaneurysm (LV-PSA) is a rare complication following cardiac surgery, let alone in the pediatric population. Other known causes of LV-PSA are trauma, percutaneous cardiac intervention, and infections. This report describes the development of LV-PSA following surgical repair of ventricular septal defect (VSD) and coarctation of aorta (CoA) in an infant.

The angulation of the septal structures impacts ventricular imbalance in atrioventricular septal defects with a common atrioventricular junction.

OBJECTIVE: Multiplanar re-formatting of full-volume three-dimensional echocardiography data sets offers new insights into the morphology of atrioventricular septal defects. We hypothesised that distortion of the alignment between the atrial and ventricular septums results in imbalanced venous return to the ventricles, with consequent proportional ventricular hypoplasia. METHODS: A single observer evaluated 31 patients, with a mean age of 52.09 months, standard deviation of 55, and with a range from 2 to 264 months, with atrioventricular septal defects, of whom 17 were boys. Ventricular imbalance, observed in nine patients, was determined by two-dimensional assessment, and confirmed at surgical inspection in selected cases when a univentricular strategy was undertaken. Offline analysis using multiplanar re-formatting was performed. A line was drawn though the length of the ventricular septum and a second line along the plane of the atrial septum, taking the angle between these two lines as the atrioventricular septal angle. We compared the angle between 22 patients with adequately sized ventricles, and those with ventricular imbalance undergoing univentricular repair. RESULTS: In the 22 patients undergoing biventricular repair, the septal angle was 0 in 14 patients; the other eight patients having angles ranging from 1 to 36, with a mean angle of 7.4°, and standard deviation of 11.1°.The mean angle in the nine patients with ventricle imbalance was 28.6°, with a standard deviation of 3.04°, and with a range from 26 to 35°. Of those undergoing univentricular repair, two patients died, with angles of 26 and 30°, respectively. CONCLUSIONS: The atrioventricular septal angle derived via multiplanar formatting gives important information regarding the degree of ventricular hypoplasia and imbalance. When this angle is above 25°, patients are likely to have ventricular imbalance requiring univentricular repair.

Integration of Computed Tomography and Three-Dimensional Echocardiography for Hybrid Three-Dimensional Printing in Congenital Heart Disease.

Three-dimensional (3D) printing is an emerging technology aiding diagnostics, education, and interventional, and surgical planning in congenital heart disease (CHD). Three-dimensional printing has been derived from computed tomography, cardiac magnetic resonance, and 3D echocardiography. However, individually the imaging modalities may not provide adequate visualization of complex CHD. The integration of the strengths of two or more imaging modalities has the potential to enhance visualization of cardiac pathomorphology. We describe the feasibility of hybrid 3D printing from two imaging modalities in a patient with congenitally corrected transposition of the great arteries (L-TGA). Hybrid 3D printing may be useful as an additional tool for cardiologists and cardiothoracic surgeons in planning interventions in children and adults with CHD.

Use of Interactive Visualization and 3D Printing in the Repair of Complex Congenital Heart Disease Presenting in Adult Life.

We report a case of a 25-year-old male with a heterotaxy-like constellation of congenital heart defects consisting of complete atrioventricular septal defect, transposition of the great arteries, subpulmonary stenosis, L-looped ventricles, hypoplastic right ventricle, and a distant aorta arising from the right ventricle. This case demonstrates how 3D printing and interactive 3D visualization may facilitate a unique surgical repair.

Implantable cardioverter defibrillator therapy in paediatric practice: a single-centre UK experience with focus on subcutaneous defibrillation.

AIMS: Sudden cardiac death (SCD) risk can be managed by implantable cardioverter defibrillators (ICD). Defibrillation shocks can be delivered via ICD generator and/or intracardiac or subcutaneous coil configurations. We present our single-centre use of childhood ICDs. METHODS AND RESULTS: Twenty-three patients had ICD implantation, with median age and weight of 12.96 years and 41.35 kg. Indications included eight long QT; four hypertrophic cardiomyopathy; three Brugada syndrome; two idiopathic ventricular fibrillation; two post-congenital heart repair; two family history of SCD with abnormal repolarization; one catecholaminergic polymorphic ventricular tachycardia; and one left ventricle non-compaction. Twelve had out of hospital cardiac arrests prior to implantation. Techniques included 13 conventional ICD implants (pre-pectoral device with endocardial leads), 7 with subcutaneous defibrillation coils (sensing via epicardial or endocardial leads tunnelled to the ICD), and 3 with exclusive subcutaneous ICD (sensing and defibrillation via the same subcutaneous lead). Satisfactory defibrillation efficacy and ventricular arrhythmia sensing was confirmed at implantation. Follow-up ranged from 0.17 to 11.08 years. One child died with the ICD in situ. Ten children received appropriate shocks; five on more than one occasion. Five received inappropriate shocks (for inappropriate recognition of sinus tachycardia or supraventricular tachycardia). Five children underwent six further interventions; all had intracardiac leads. CONCLUSION: Innovative shock delivery systems can be used in children requiring an ICD. The insertion technique and device used need to accommodate the age and weight of the child, and concomitant need for pacing therapy. We have demonstrated effective defibrillation with shocks delivered via configurations employing subcutaneous coils in children.

S-Net: a multiple cross aggregation convolutional architecture for automatic segmentation of small/thin structures for cardiovascular applications.

With the success of U-Net or its variants in automatic medical image segmentation, building a fully convolutional network (FCN) based on an encoder-decoder structure has become an effective end-to-end learning approach. However, the intrinsic property of FCNs is that as the encoder deepens, higher-level features are learned, and the receptive field size of the network increases, which results in unsatisfactory performance for detecting low-level small/thin structures such as atrial walls and small arteries. To address this issue, we propose to keep the different encoding layer features at their original sizes to constrain the receptive field from increasing as the network goes deeper. Accordingly, we develop a novel S-shaped multiple cross-aggregation segmentation architecture named S-Net, which has two branches in the encoding stage, i.e., a resampling branch to capture low-level fine-grained details and thin/small structures and a downsampling branch to learn high-level discriminative knowledge. In particular, these two branches learn complementary features by residual cross-aggregation; the fusion of the complementary features from different decoding layers can be effectively accomplished through lateral connections. Meanwhile, we perform supervised prediction at all decoding layers to incorporate coarse-level features with high semantic meaning and fine-level features with high localization capability to detect multi-scale structures, especially for small/thin volumes fully. To validate the effectiveness of our S-Net, we conducted extensive experiments on the segmentation of cardiac wall and intracranial aneurysm (IA) vasculature, and quantitative and qualitative evaluations demonstrated the superior performance of our method for predicting small/thin structures in medical images.

Advances in TEE-Centric Intraprocedural Multimodal Image Guidance for Congenital and Structural Heart Disease.

Percutaneous interventions are gaining rapid acceptance in cardiology and revolutionizing the treatment of structural heart disease (SHD). As new percutaneous procedures of SHD are being developed, their associated complexity and anatomical variability demand a high-resolution special understanding for intraprocedural image guidance. During the last decade, three-dimensional (3D) transesophageal echocardiography (TEE) has become one of the most accessed imaging methods for structural interventions. Although 3D-TEE can assess cardiac structures and functions in real-time, its limitations (e.g., limited field of view, image quality at a large depth, etc.) must be addressed for its universal adaptation, as well as to improve the quality of its imaging and interventions. This review aims to present the role of TEE in the intraprocedural guidance of percutaneous structural interventions. We also focus on the current and future developments required in a multimodal image integration process when using TEE to enhance the management of congenital and SHD treatments.

Hybrid palliation versus nonhybrid management for a multi-institutional cohort of infants with critical left heart obstruction.

OBJECTIVE: To compare patient characteristics and overall survival for infants with critical left heart obstruction after hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) versus nonhybrid management (eg, Norwood, primary transplantation, biventricular repair, or transcatheter/surgical aortic valvotomy). METHODS: From 2005 to 2019, 1045 infants in the Congenital Heart Surgeons' Society critical left heart obstruction cohort underwent interventions across 28 institutions. Using a balancing score propensity analysis, 214 infants who underwent hybrid palliation and 831 infants who underwent nonhybrid management were proportionately matched regarding variables significantly associated with mortality and variables noted to significantly differ between groups. Overall survival between the 2 groups was adjusted by applying balancing scores to nonparametric estimates. RESULTS: Compared with the nonhybrid management group, infants who underwent hybrid palliation had lower birth weight, smaller gestational age, and higher prevalence of in-utero interventions, noncardiac comorbidities, preoperative mechanical ventilation, absent interatrial communication, and moderate or severe mitral valve stenosis (all P values < .03). Unadjusted 12-year survival after hybrid palliation and nonhybrid management, was 55% versus 69%, respectively. After matching, 12-year survival after hybrid palliation versus nonhybrid management was 58% versus 63%, respectively (P = .37). Among matched infants born weighing <2.5 kg, 2-year survival after hybrid palliation versus nonhybrid management was 37% versus 51%, respectively (P = .22). CONCLUSIONS: Infants born with critical left heart obstruction who undergo hybrid palliation have more high-risk characteristics and anatomy versus infants who undergo nonhybrid management. Nonetheless, after adjustment, there was no significant difference in 12-year survival after hybrid palliation versus nonhybrid management. Mortality remains high, and hybrid palliation confers no survival advantage, even for lower-birth-weight infants.

Midterm evaluation of biological prosthetic valves in the pulmonary position of grown-up patients.

OBJECTIVES: To examine the midterm clinical outcome of pulmonary valve replacement (PVR) with prosthetic valves. METHODS: We reviewed 37 consecutive patients who underwent PVR with biological prosthetic valves between September 1999 and June 2010. The median age was 22.6 years (range: 6 to 70 years; three children). The primary diagnosis was Tetralogy of Fallot in 20 patients (54%). Valve pathology was regurgitation in 27 patients (72.9%). Cardiac surgery had been previously performed in 35 patients (94.5%). The median size of the prosthesis was 25 mm (range: 21 to 31 mm). The median follow-up was 42 months (range: 1.2 to 129 months). RESULTS: There were no early valve-related deaths. Hospital mortality was 2.7% (n = 1) and no patient required early rereplacement of prosthesis. Two patients required permanent pacemaker insertion. During follow-up, there was no late death, reoperation for structural valve degeneration, or valve thrombosis. Only one patient required repeated operation for endocarditis at 37 months follow-up. The actuarial survival at 5 years was 95.1 ± 3.8%. Overall freedom from reoperation after PVR at 5 years was 93.0 ± 8.6%. At last follow-up, 34 patients (91.8%) were NYHA class I versus 20 patients (54%) preoperatively (p < 0.05). In the 35 surviving patients who did not undergo redo-PVR, there was no-mild regurgitation and the peak PV gradient was 20.4 ± 10.2 mm Hg (16.2 ± 9.3 mm Hg preoperatively). Thirty-two patients (91.4%) had good right ventricular function compared with 26 patients (74.2%) preoperatively. CONCLUSIONS: PVR with biological prosthetic valves can be performed with good midterm survival, functional status, and haemodynamics.

Valve-Sparing Aortic Root Replacement in a Patient With an FLNA Variant.

We report a case of a 38-year-old female with an FLNA variant who underwent valve-sparing aortic root replacement. FLNA encodes Filamin A, an actin-binding protein. Our patient had aortic root dilation due to this variant. Aortic root repair was conducted using the David procedure, with modifications to account for tissue fragility associated with this genetic condition. This case demonstrates the value of patient-specific genetic information for the timing of surgery and operative course planning.

Long-term outcomes in octogenarians following aortic valve replacement.

BACKGROUND: The aging of the population has resulted in an increasing number of elderly patients undergoing cardiac operations. We reviewed our experience in patients over the age of 80 undergoing primary aortic valve replacement (AVR) with or without CABG. METHODS: Between 2000 and 2008, 345 patients (226 male) ≥80 years underwent primary AVR in our unit. The notes of these patients were retrospectively reviewed and follow-up information was obtained from their general practitioners. They had a mean age of 82.9 ± 2.3 years and a median logistic EuroSCORE of 13.4 (IQR 9.4, 19.1). Isolated AVR was performed in 161 patients (45.5%), and 184 (51.6%) patients underwent combined AVR and CABG. A quality of life questionnaire was sent to all survivors. RESULTS: Hospital mortality occurred in 17 patients (4.9%), which was significantly lower than the mortality predicted by logistic EuroSCORE (16.2%, p < 0.01). Hospital mortality was comparable between patients undergoing isolated AVR and those undergoing additional CABG (4.3% vs. 5.4%, respectively). Actuarial survival at one and five years was 90.1 ± 1.6% and 77.2 ± 2.9%, respectively. There was a 62% response on the questionnaire showing 70% of the patients were NYHA I and 83.7% were satisfied with the operation outcome. CONCLUSIONS: AVR can be undertaken with excellent results in octogenarians and the current risk is significantly lower than what is predicted with conventional risk-scoring systems. Patients with advanced age should not necessarily be excluded from being candidates for AVR.

Catastrophic haemoptysis in the Fontan circulation--a novel surgical approach to denude the culprit bleeding vessels.

We describe the case of a young man aged 19 years with a double inlet left ventricle associated with transposition of the great arteries, and a mechanical aortic valve requiring anticoagulation, who presented with massive haemoptysis. At cardiac catheterisation, there were multiple feeder vessels to a bleeding leash surrounding and communicating with his left main bronchus. Despite occlusion of the larger feeder vessels, he continued to have massive haemoptysis. We describe a novel surgical strategy of denuding the peribronchial vessels through a left lateral thoracotomy. This successfully stopped his bleeding.

Congenital mitral regurgitation due to papillary muscle infarction: a case report and approach to evaluation.

Congenital mitral regurgitation is relatively rare. It can be due to congenital malformation of the valve apparatus, associated structural heart defects, or results from myocardial dysfunction leading to deformation of the valve annulus. Hence, careful delineation of the pathologic processes involved in the mechanism is critical when evaluating patients presenting with congenital mitral valve regurgitation. Congenital anomalies of the coronary system are one of the serious associations, which needs prompt recognition and treatment to prevent fatal complications. We report a case of congenital atresia of left main coronary artery in an asymptomatic 8-month-old presenting with an incidental finding of mitral valvar regurgitation. Appropriate investigations and management lead to restoration of normal coronary blood flow and valve function. This particular case illustrates that congenital coronary anomalies may present in an otherwise asymptomatic child. It should be considered as one of the possible differential diagnosis in unexplained mitral regurgitation. Early recognition and prompt surgical treatment can radically modify the prognosis.

Aortic root replacement using a biovalsalva prosthesis in comparison to a "handsewn" composite bioprosthesis.

BACKGROUND: The Biovalsalva aortic root prosthesis incorporates an Elan porcine stentless biological aortic valve suspended within a triple-layered vascular conduit with preformed aortic sinuses of Valsalva. This study compared implantation of the Biovalsalva prosthesis with a "handsewn" composite bioprosthetic graft (CE Perimount bovine bioprosthesis anastomosed to a gelatin-impregnated gelweave Dacron graft). METHODS: Between December 2004 and January 2009, 39 patients underwent elective or urgent aortic root replacement (modified Bentall procedure with coronary button reimplantation) using a Biovalsalva (n = 21) or a handsewn bioprosthesis (n = 18) for aortic root dilatation. RESULTS: There was no significant difference in the preoperative variables between the two study groups including age (70.7 +/- 1.7 vs. 67.6 +/- 2.9 years, p > 0.05). There was no in-hospital mortality. Three patients in each group underwent concomitant aortic hemi-arch replacement. Patients who underwent Biovalsalva implantation had a reduced need for transfusion of blood (1.25 +/- 0.32 vs. 3.17 +/- 0.71 units, p < 0.05) and fresh frozen plasma (2.78 +/- 0.39 vs. 1.85 +/- 0.31, p < 0.05), and reduced mediastinal blood loss (416 +/- 52 vs. 583 +/- 74 mL, p < 0.05) compared to those with a handsewn bioprosthesis. Cardiopulmonary bypass time (141 +/- 6 vs. 170 +/- 17 minutes, p = NS) and aortic cross-clamp time (113 +/- 6 vs. 115 +/- 7 minutes, p = NS) were similar. Postoperative echocardiography demonstrated excellent hemodynamic function of the Biovalsalva prosthesis (mean size 25.1 +/- 0.4 mm valved conduit) with a peak pressure gradient of 26.2 +/- 1.9 mmHg and no or trivial valvular regurgitation. CONCLUSIONS: The Biovalsalva prosthesis should be considered for patients requiring a biological aortic root replacement. It offers an "off-the-shelf" preassembled composite biological valve conduit with excellent hemostatic and hemodynamic properties.

Giant aneurysms associated with aortic coarctation: management challenges and options.

The management of giant aneurysms associated with aortic coarctation is challenging. The location, the size of the aneurysm, whether it has ruptured, previous coarctation repair, the presence of stenosis, and the ascending and distal aortic pathology will all influence the treatment approach. With more patients surviving to adulthood after early coarctation repair, a better understanding of the anatomy, pathophysiology, and radiological findings of coarctation-related aneurysms is imperative to providing sound care. We present here our experience with a series of giant aneurysms of the aorta, all with a background of underlying aortic coarctation. We highlight the decision-making process and review current management trends.

Management of 760-g Extremely Premature Infant With Dextro-Transposition of the Great Arteries.

Extremely low birth weight neonates with complex congenital heart disease have increased mortality risk. Multi-organ dysfunction, pulmonary disease, fluctuating pulmonary vascular resistance, and complex cardiovascular anatomy create a challenge for effective management. We present the case of a 760-g neonate with dextro-transposition of the great arteries, ventricular septal defect, patent ductus arteriosus, and single coronary artery with proximal intramural segment of the right coronary artery branch. We describe features of preoperative care, surgical intervention, and postoperative course that enabled this infant to survive.

Postinfarction inferior ventricular septal rupture: surgical repair through the right atrium.

Operative mortality of inferior postinfarct ventricular septal rupture (VSR) remains high. Previous reports have described a transatrial approach to access the VSR avoiding a ventriculotomy, thereby reducing the potential risks of myocardial damage, hemorrhage, and ventricular arrhythmias. The transatrial right ventricular patch or direct suture repair, however, is exposed to the left-to-right pressure gradient and is at risk of residual shunting. In this report, a transatrial approach is used, with direct suture of the VSR, patch exclusion of the right ventricle, and biological glue instillation to protect the patch from left ventricular pressures.

Renal function of patients with a failing Fontan circuit undergoing total cavopulmonary revision surgery.

This report characterizes renal dysfunction after total cavopulmonary (TCPC) revision surgery for atriopulmonary Fontan (APF) circulations, a known risk factor for a poor outcome. The perioperative data for 23 consecutively identified patients were reviewed. The preoperative mean glomerular filtration rate (GFR) was 101 +/- 30 ml/min/1.73 m(2), decreasing to 65 +/- 41 ml/min/1.73 m(2) early in the postoperative period. The preoperative GFR was highly correlated with age at APF (r = -0.5; p = 0.024), age at TCPC (r = -0.5; p = 0.01), and mixed venous saturation (r = 0.6; p = 0.01). Three of four patients requiring renal replacement therapy (RRT) died at a median age of 3 months (range, 18 days to 9 months). Determinants of early GFR and RRT were preoperative GFR (p = 0.016) and creatinine (p = 0.035). Younger age at primary Fontan (p = 0.008), higher preoperative mixed venous saturation (p = 0.019), and higher preoperative blood pressure (p = 0.006) independently predicted better GFRs at the latest follow-up evaluation. Renal function declines acutely after TCPC revision, often necessitating RRT. A requirement for RRT marks greater mortality. Higher preoperative creatinine levels identify those at greatest risk.