Lifetime Management of Adolescents and Young Adults with Congenital Aortic Valve Disease.

In this invited expert review, we focus on evolving lifetime management strategies for adolescents and young adults with congenital aortic valve disease, acknowledging that these patients often require multiple interventions during their lifetime. Our goal is to preserve the native aortic valve when feasible. Leveraging advanced multimodality imaging, a detailed assessment of the aortic valve and root complex can be obtained, and a surgically approach tailored to an individual patient's anatomy and pathology can be used. In turn, aortic valve repair and reconstruction can be offered to a greater number of patients, either as a definitive strategy or as a component of a staged strategy to delay the need for aortic valve replacement until later in life when more options are available.

Transcatheter management of obstructed baffle repairs of partial anomalous pulmonary veins: a case series.

Background: Partial anomalous pulmonary venous return (PAPVR) can be surgically corrected using a pericardial baffle. This baffle can become obstructed post-surgery, leading to pulmonary hypertension and right heart dysfunction if not detected and corrected. Case summary: We describe three patients with occluded PAPVR baffles who underwent drug-coated balloon angioplasty and stenting of the obstructed baffle. In each case, baffle obstruction was detected post-operatively on surveillance cross-sectional imaging, and an invasively measured pulmonary capillary wedge-to-left atrium gradient was noted to be elevated. Post-intervention, each patient had an improvement in baffle flow by angiography as well as lung perfusion as assessed by nuclear medicine scintigraphy. Discussion: Given the subtle symptomatology of obstructed PAPVR pericardial baffle repairs, surveillance imaging is necessary to detect occluded baffles and intervene before downstream right heart disease and pulmonary hypertension develops. Given the high rates of re-stenosis in pulmonary vein stenting, pre-treatment of occluded PAPVR baffles with drug-coated balloons may help reduce re-intervention rates.

Anomalous Aortic Origin of a Coronary Artery.

BACKGROUND: Although anomalous aortic origin of a coronary artery (AAOCA) is associated with risk of sudden cardiac arrest (SCA), there is a spectrum of disease, with the appropriate management for many remaining unclear. Increasing data warrant review for an updated perspective on management. METHODS: A panel of congenital cardiac surgeons, cardiologists, and imaging practitioners reviewed the current literature related to AAOCA and its management. Survey of relevant publications from 2010 to the present in PubMed was performed. RESULTS: The prevalence of AAOCA is 0.4% to 0.8%. Anomalous left coronary artery is 3 to 8 times less common than anomalous right coronary, but carries a much higher risk of SCA. Nevertheless, anomalous right coronary is not completely benign; 10% demonstrate ischemia, and it remains an important cause of SCA. Decision-making regarding which patients should be recommended for surgical intervention includes determining anatomic features associated with ischemia, evidence of ischemia on provocative testing, and concerning cardiovascular symptoms. Ischemia testing continues to prove challenging with low sensitivity and specificity, but the utility of new modalities is an active area of research. Surgical interventions focus on creating an unobstructed path for blood flow and choosing the appropriate surgical technique given the anatomy to accomplish this. Nontrivial morbidity has been reported with surgery, including new-onset ischemia. CONCLUSIONS: A proportion of patients with AAOCA demonstrate features and ischemia that warrant surgical intervention. Continued work remains to improve the ability to detect inducible ischemia, to risk stratify these patients, and to provide guidance in terms of which patients warrant surgical intervention.

Transcatheter Aortic Valve Replacement in Congenital Heart Disease.

Transcatheter aortic valve replacement is not widely used in patients with congenital heart disease. We describe our single-center experience of transcatheter aortic valve replacement in congenital heart disease, demonstrating short-term feasibility and safety, role in lifetime management of congenital aortic valve disease, and use as a bridge to recovery, future surgery, or transplantation.

Multifocal disease progression and subsequent intervention in patients with actin alpha-2 variants: A single-center experience.

OBJECTIVES: To describe patient characteristics and indications for surgical intervention, reoperation, and outcomes in patients with actin alpha-2 (ACTA2) variants. METHODS: A single-center retrospective cohort study with prospective follow-up was performed for 38 patients with an ACTA2 variant. RESULTS: From 1999 to 2020, 26 (70%) patients underwent surgery; 11 remain under surveillance (mean follow-up, 7.5 ± 5 years). Median age at index operation was 42 (range, 10-69) years, with 4 pediatric cases. Thoracic aortic aneurysm was present in 19 (73%) patients (mean adult max diameter, 5.2 ± 0.8 cm; pediatric z score, 10.7 ± 5.4). Aortic dissection was present in 13 (50%) patients, with 4 (15%) having type A dissection. Operations included replacement of the aortic root in 16 (17%), ascending aorta in 20 (77%), and aortic arch in 14 (54%) patients. Four (15%) patients had coronary artery disease, and 2 (7.7%) underwent concomitant coronary artery bypass grafting. There was no operative mortality, stroke, reoperation for bleeding, or dialysis-dependent renal failure; One (3.8%) patient developed acute on chronic kidney injury. Three patients (12%) required prolonged ventilation. Eleven (42%) patients underwent 26 reoperations, median time 45 (range, 4-147) months, including 5 open thoracoabdominal aneurysm repairs. CONCLUSIONS: Patients with ACTA2 variants frequently develop aortic aneurysm and are at risk of aortic dissection and coronary artery disease. However, age at diagnosis and symptoms at presentation are highly variable. Multiple operations are often required for disease management, particularly after dissection. Close monitoring and timely intervention are important in mitigating disease progression and improving outcomes.

Characteristics and immediate outcomes of patients who underwent percutaneous balloon mitral valvuloplasty at the Jakaya Kikwete Cardiac Institute, Tanzania.

BACKGROUND: For rheumatic mitral stenosis (MS), a multidisciplinary evaluation is mandatory to determine the optimal treatment: medical, percutaneous balloon mitral valvuloplasty (PBMV) or valve surgery. Clinical and imaging evaluations are essential for procedural risk assessment and outcomes. PBMV interventions are increasingly available in Africa and are feasible options for selected candidates. Enhancing PBMV training/skills transfer across most of African countries is possible. OBJECTIVES: The aim of this study was to provide insight into the clinical practice of patients with rheumatic MS evaluated for PBMV in a Tanzanian teaching hospital and to define the role of imaging, and evaluate the heart team and training/skills transfer in PBMV interventions. METHODS: From August 2019 to May 2022, 290 patients with rheumatic MS were recruited consecutively in the Tanzania Mitral Stenosis study. In total, 43 (14.8%) patients were initially evaluated for eligibility for PBMV by a heart team. We carried out the clinical assessment, laboratory investigations, transthoracic/oesophageal echocardiography (TTE/TEE) and electrocardiography. RESULTS: The median age was 31 years (range 11-68), and two-thirds of the patients were female (four diagnosed during pregnancy). Two patients had symptomatic MS at six and eight years. Nine patients had atrial fibrillation with left atrial thrombus in three, and two were detected by TEE. Nine patients in normal sinus rhythm had spontaneous echo contrast. The mean Wilkins score was 8.6 (range 8-12). With re-evaluation by the local and visiting team, 17 patients were found to have unfavourable characteristics: Bi-commissural calcification (four), ≥ grade 2/4 mitral regurgitation (six), high scores and left atrial thrombus (three), left atrial thrombus (two), and severe pulmonary hypertension (two). Three patients died before the planned PBMV. Eleven patients were on a waiting list. We performed PBMV in 12 patients, with success in 10 of these, and good short-term outcomes [mean pre-PBMV (16.03 ± 5.52 mmHg) and post-PBMV gradients (3.08 ± 0.44 mmHg, p < 0.001)]. There were no complications. CONCLUSIONS: PBMV had good outcomes for selected candidates. TEE is mandatory in pre-PBMV screening and for procedural guidance. In our cohort, patients with Wilkins score of up to 11 underwent successful PBMV. We encourage PBMV skills expansion in low- and middle-income countries, concentrating on expertise centres.

Concomitant Mitral Valve Re-Repair for Mixed Congenital and Degenerative Mitral Disease, Tricuspid Repair, and Cox-Maze Procedure in a College Athlete.

A significant proportion of patients undergoing repair of congenital mitral valve disease will require a subsequent reoperation. During somatic growth, mitral valve repair is preferable to replacement as it allows for annular growth, preservation of ventricular function, and avoidance of lifelong anticoagulation. Techniques to facilitate successful re-repairs for congenital and non-rheumatic mixed degenerative mitral valve disease are not well-described in the literature. Description of the encountered pathology and surgical maneuvers utilized in this case provides real-world tools to help surgeons deal with limited orifice availability, fibrosis, and multilevel lesions. We describe a mitral valve re-repair in a young athlete for a rare cleft posterior mitral leaflet, with a simultaneous tricuspid valve repair and Cox-Maze procedure. We focus on technical pearls that address specific anatomic challenges within our surgical approach.

Coronary artery disease in adults with anomalous aortic origin of a coronary artery.

Objectives: This study sought to characterize coronary artery disease (CAD) among adults diagnosed with an anomalous aortic origin of a coronary artery (AAOCA). We hypothesized that coronaries with anomalous origins have more severe CAD stenosis than coronaries with normal origins. Methods: This single-center study of 763 adults with AAOCA consisted of 620 patients from our cardiac catheterization database (1958-2009) and 273 patients from electronic medical records query (2010-2021). Within left main, anterior descending, circumflex, and right coronary arteries, the CAD stenosis severity, assessed by invasive or computer tomography angiography, was modeled with coronary-level variables (presence of an anomalous origin) and patient-level variables (age, sex, comorbidities, and which of the four coronaries was anomalous). Results: Of the 763 patients, 472 (60%) had obstructive CAD, of whom, 142/472 (30%) had obstructive CAD only in the anomalous coronary. Multivariable modeling showed similar CAD stenosis severity between coronaries with anomalous versus normal origins (P = .8). Compared with AAOCA of other coronaries, the anomalous circumflex was diagnosed at older ages (59.7 ± 11.1 vs 54.3 ± 15.8 years, P < .0001) and was associated with increased stenosis in all coronaries (odds ratio, 2.7; 95% confidence interval, 2.2-3.4, P < .0001). Conclusions: Among adults diagnosed with AAOCA, the anomalous origin did not appear to increase the severity of CAD within the anomalous coronary. In contrast to the circumflex, AAOCA of the other vessels may contribute a greater ischemic burden when they present symptomatically at younger ages with less CAD. Future research should investigate the interaction between AAOCA, CAD, and ischemic risk to guide interventions.

Patient-specific fluid-structure simulations of anomalous aortic origin of right coronary arteries.

Objectives: Anomalous aortic origin of the right coronary artery (AAORCA) may cause ischemia and sudden death. However, the specific anatomic indications for surgery are unclear, so dobutamine-stress instantaneous wave-free ratio (iFR) is increasingly used. Meanwhile, advances in fluid-structure interaction (FSI) modeling can simulate the pulsatile hemodynamics and tissue deformation. We sought to evaluate the feasibility of simulating the resting and dobutamine-stress iFR in AAORCA using patient-specific FSI models and to visualize the mechanism of ischemia within the intramural geometry and associated lumen narrowing. Methods: We developed 6 patient-specific FSI models of AAORCA using SimVascular software. Three-dimensional geometries were segmented from coronary computed tomography angiography. Vascular outlets were coupled to lumped-parameter networks that included dynamic compression of the coronary microvasculature and were tuned to each patient's vitals and cardiac output. Results: All cases were interarterial, and 5 of 6 had an intramural course. Measured iFRs ranged from 0.95 to 0.98 at rest and 0.80 to 0.95 under dobutamine stress. After we tuned the distal coronary resistances to achieve a stress flow rate triple that at rest, the simulations adequately matched the measured iFRs (r = 0.85, root-mean-square error = 0.04). The intramural lumen remained narrowed with simulated stress and resulted in lower iFRs without needing external compression from the pulmonary root. Conclusions: Patient-specific FSI modeling of AAORCA is a promising, noninvasive method to assess the iFR reduction caused by intramural geometries and inform surgical intervention. However, the models' sensitivity to distal coronary resistance suggests that quantitative stress-perfusion imaging may augment virtual and invasive iFR studies.

Case report: successful emergent transcatheter pulmonary valve replacement within failing pulmonary artery conduit in the setting of cardiogenic shock with extracorporeal membrane oxygenation support.

BACKGROUND: To the best of our knowledge, this is the first reported case of transcatheter pulmonary valve replacement (TPVR) with extracorporeal membrane oxygenation (ECMO) support with successful decannulation as a bridge to recovery in a young adult with complex congenital heart disease. CASE SUMMARY: We describe a 24-year-old male patient with a history of D-transposition of the great arteries with ventricular septal defect status post-Rastelli repair at age three lost to follow-up and presenting with severe biventricular failure, left ventricular thrombus, and critical pulmonary conduit stenosis, deemed non-surgical and non-transplant candidate, who underwent conduit stenting and TPVR in the setting of cardiogenic shock. Upon intubation for general anaesthesia, the patient suffered from ventricular tachycardia arrest requiring cardiopulmonary resuscitation and veno-arterial ECMO. Once stabilized, conduit stenting and TPVR was performed with significant haemodynamic improvement and immediate ECMO decannulation with subsequent biventricular function improvement. DISCUSSION: In critically ill patients with complex congenital heart disease that are neither surgical nor transplant candidates, ECMO support can be used as a means of support during a transcatheter intervention to improve haemodynamics and a bridge to recovery, allowing time for future potential candidacy for surgery or transplantation as indicated. Patients with congenital heart disease need regular follow-up in specialty clinics to prevent the development of such critical illness.

Early Outcomes of Transconal Repair of Transseptal Anomalous Left Coronary Artery From Right Sinus.

BACKGROUND: Anomalous aortic origin of the left coronary artery (AAOCLA) with an extended transseptal course behind the right ventricular outflow tract (RVOT) is a rare variant that poses challenges not addressed by current surgical techniques. We utilized a novel transconal approach in 7 consecutive patients. METHODS: A retrospective review was made of a prospectively collected database for consecutive patients undergoing transconal unroofing of transseptal AAOLCA. Surgical repair entails transection of the RVOT, unroofing the septal course of the AAOLCA, followed by RVOT extension with a rectangular strip of autologous pericardium. Preoperative characteristics, operative details, and postoperative course were abstracted. RESULTS: All 7 patients identified were symptomatic. Median age was 48 years (range, 12 to 62). The AAOLCA with transseptal course was confirmed by computed tomography angiography. Three patients had provocative testing demonstrating anterolateral ischemia. Four patients underwent cardiac catheterization with intravascular ultrasound and indexed fractional flow reserve, confirming flow-limiting lesion. Importantly, 3 patients had negative provocative noninvasive testing for ischemia. Median postoperative hospital length of stay was 6 days (range, 4 to 12). No mortality or major complications occurred during a median follow-up of 0.75 years. Postoperative evaluation demonstrated anatomically patent unroofed AAOLCA with improved indexed fractional flow reserve compared with preoperative (0.59 ± 0.16 vs 0.90 ± 0.03, P = .05). CONCLUSIONS: Complete unroofing of AAOLCA with transseptal course repaired with posterior extension of RVOT is an effective technique with excellent early outcome. Multimodality provocative testing is critical to evaluate these lesions as individual studies may be misleading. Intravascular ultrasound with indexed fractional flow reserve is clinically useful to confirm the hemodynamic significance of specific lesions.

Anomalous Aortic Origin of a Coronary Artery in Adults.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden death in youth. However, its significance and optimal management in adults is poorly understood. Our objective is to characterize AAOCA in a large single-center adult cohort based on coronary anatomic variants and surgical management strategies. METHODS: We reviewed imaging, clinic, and operative reports for 645 adults with an encounter diagnosis code of congenital coronary anomaly from July 2015 to July 2017. After excluding other congenital heart defects, we characterized 167 patients with AAOCAs by anatomic variant, symptoms at diagnosis, indication for advanced imaging, and if performed, surgical repair. To describe the anatomic variant, we classified the origin and course by following the atomization scheme developed by the Congenital Heart Surgeon's Society's AAOCA registry. RESULTS: Among adults with AAOCA, the anomalous origin involved the right coronary artery in 57% (96 of 167), left main coronary artery in 23% (39 of 167), left anterior descending in 2% (4 of 167), circumflex in 16% (26 of 167), and multiple coronaries in 1% (2 of 167). Anomalous right coronary arteries were diagnosed at an older median age than anomalous left main coronary arteries (55 vs 51 years, respectively; P = .026). Surgical repair of AAOCA occurred in 22% (36 of 167) of patients. Concomitant cardiac surgical procedures accompanied 36% (13 of 36) of them. No deaths occurred over a median follow-up of 2.5 years. CONCLUSIONS: Most patients in our single-center AAOCA registry were diagnosed in the presence of cardiac symptoms. Concomitant aortic valve disease and coronary atherosclerotic burden complicate both the evaluation and surgical approach to adult AAOCA repair.

Malignant Phyllodes Tumor in an Adolescent Female: A Rare Case Report and Review of the Literature.

Primary breast neoplasms are rare in adolescent females, most of which are benign. Phyllodes tumors constitute a remarkably small subset of breast neoplasms (0.3-0.9%) with malignant phyllodes tumors being even more uncommon. Malignant phyllodes tumors tend to progress rapidly though only 1.5% metastasize. They are also associated with a higher rate of recurrence than their benign counterparts, underlying the importance of adequate surgical margins. It is therefore imperative to be able to identify these tumors early allowing for prompt resection and close follow-up. Here, we present the rare case of a 17-year-old female presenting with a rapidly enlarging breast mass, which was ultimately found to be a malignant phyllodes tumor. We further performed a review of the literature to highlight only 22 other cases reported in adolescent females.

Anomalous Aortic Origin of the Coronary Arteries: A Novel Unroofing Technique in an Adult Cohort.

BACKGROUND: Anomalous aortic origin of the coronary arteries (AAOCA) is associated with sudden cardiac death and frequently treated with unroofing of an intramural segment. Most reports on AAOCA are of patients less than 30 years of age. We have reviewed our "older" patients who have undergone surgical repair and report a novel unroofing technique. METHODS: A retrospective review was conducted of 40 adult patients who underwent surgery for AAOCA from June 2005 to June 2016. Our surgical approach changed from traditional sharp excision to electrical fulguration of the shared intramural wall segment. We assessed our population for symptom relief, resolution of ischemia, and reintervention. More than 6 months of follow-up was available for 34 patients. RESULTS: Mean age was 47.1 ± 11.6 years (range, 19 to 67); 17 patients were female. The coronary anomaly was right from left in 35 patients, left from right 4, and left coronary from noncoronary sinus in 1 patient. Thirty-nine of 40 patients were symptomatic, with two prior sudden cardiac arrests. Preoperatively, 22 of 31 patients tested positive for ischemia, including the asymptomatic. The operation was unroofing in 37 of 40 patients, 17 by sharp excision and 20 by electrical fulguration. There were no 30-day deaths or complications and no reinterventions. Isolated unroofing by fulguration required shorter cardiopulmonary bypass and cross-clamp times than excision: 39 versus 62 minutes (p = 0.02) and 28 versus 42 minutes (p = 0.02), respectively. At an average follow-up of 5.0 years, 28 of 34 patients reported symptomatic improvement. There were two unrelated late deaths. CONCLUSIONS: Unroofing by sharp excision and by electrical fulguration were equally safe in the short term. Fulguration is technically easier and faster while still equally effective.

Proteomic analysis of waldenstrom macroglobulinemia.

To better understand the molecular changes that occur in Waldenstrom macroglobulinemia (WM), we employed antibody-based protein microarrays to compare patterns of protein expression between untreated WM and normal bone marrow controls. Protein expression was defined as a >2-fold or 1.3-fold change in at least 67% of the tumor samples. Proteins up-regulated by >2-fold included Ras family proteins, such as Rab-4 and p62DOK, and Rho family proteins, such as CDC42GAP and ROKalpha. Other proteins up-regulated by >1.3-fold included cyclin-dependent kinases, apoptosis regulators, and histone deacetylases (HDAC). We then compared the samples of patients with symptomatic and asymptomatic WM and showed similar protein expression signatures, indicating that the dysregulation of signaling pathways occurs early in the disease course. Three proteins were different by >2-fold in symptomatic versus asymptomatic, including the heat shock protein HSP90. Elevated protein expression was confirmed by immunohistochemistry and immunoblotting. Functional significance was validated by the induction of apoptosis and inhibition of proliferation using specific HDAC and HSP90 inhibitors. This study, therefore, identifies, for the first time, multiple novel proteins that are dysregulated in WM, which both enhance our understanding of disease pathogenesis and represent targets of novel therapeutics.

Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma.

The mechanisms by which multiple myeloma (MM) cells migrate and home to the bone marrow are not well understood. In this study, we sought to determine the effect of the chemokine SDF-1 (CXCL12) and its receptor CXCR4 on the migration and homing of MM cells. We demonstrated that CXCR4 is differentially expressed at high levels in the peripheral blood and is down-regulated in the bone marrow in response to high levels of SDF-1. SDF-1 induced motility, internalization, and cytoskeletal rearrangement in MM cells evidenced by confocal microscopy. The specific CXCR4 inhibitor AMD3100 and the anti-CXCR4 antibody MAB171 inhibited the migration of MM cells in vitro. CXCR4 knockdown experiments demonstrated that SDF-1-dependent migration was regulated by the P13K and ERK/ MAPK pathways but not by p38 MAPK. In addition, we demonstrated that AMD3100 inhibited the homing of MM cells to the bone marrow niches using in vivo flow cytometry, in vivo confocal microscopy, and whole body bioluminescence imaging. This study, therefore, demonstrates that SDF-1/CXCR4 is a critical regulator of MM homing and that it provides the framework for inhibitors of this pathway to be used in future clinical trials to abrogate MM trafficking.