3D Characterization of the Aortic Valve and Aortic Arch in Bicuspid Aortic Valve Patients.

Patients with bicuspid aortic valve (BAV) commonly have associated aortic stenosis and aortopathy. The geometry of the aortic arch and BAV is not well defined quantitatively, which makes clinical classifications subjective or reliant on limited 2D measurements. The goal of this study was to characterize the 3D geometry of the aortic arch and BAV using objective and quantitative techniques. Pre-TAVR computed tomography angiogram (CTA) in patients with BAV and aortic stenosis (AS) were analyzed (n = 59) by assessing valve commissural angle, presence of a fused region, percent of fusion, and calcium volume. The ascending aorta and aortic arch were reconstructed from patient-specific imaging segmentation to generate a centerline and calculate maximum curvature and maximum area change for the ascending aorta and the descending aorta. Aortic valve commissural angle signified a bimodal distribution suggesting tricuspid-like (≤ 150°, 52.5% of patients) and bicuspid-like (> 150°, 47.5%) morphologies. Tricuspid like was further classified by partial (10.2%) or full (42.4%) fusion, and bicuspid like was further classified into valves with fused region (27.1%) or no fused region (20.3%). Qualitatively, the aortic arch was found to have complex patient-specific variations in its 3D shape with some showing extreme diameter changes and kinks. Quantitatively, subgroups were established using maximum curvature threshold of 0.04 and maximum area change of 30% independently for the ascending and descending aorta. These findings provide insight into the geometric structure of the aortic valve and aortic arch in patients presenting with BAV and AS where 3D characterization allows for quantitative classification of these complex anatomic structures.

Early Intervention in Asymptomatic Aortic Stenosis: What Are We Waiting For?

Aortic stenosis (AS) contributes to significant cardiovascular morbidity and mortality worldwide, and the natural history from symptoms to ventricular decompensation, heart failure, and death has been well documented. For more than 2 decades, technologies including imaging and biomarkers have shown a promising ability to detect myocardial damage associated with AS before symptoms arise. Current treatment guidelines rely heavily on symptoms or ventricular decompensation as triggers for aortic valve intervention. There is increasing appreciation of the relationship between myocardial damage due to AS before the emergence of symptoms, and a number of published randomised trials suggest a benefit to early intervention in asymptomatic AS, with additional trials actively enrolling. Future treatment paradigms may incorporate early detection of ventricular damage by noninvasive new technologies as triggers for asymptomatic intervention. Enthusiasm for early aortic valve replacement should be tempered by consideration of the competing risks of early valve intervention, but an increasing preponderance of evidence continues to suggest that earlier intervention in AS is warranted.

Risk factors and early outcomes of repeat sternotomy in 1960 adults with congenital heart disease: A 30-year, single-center study.

OBJECTIVE: Patients with congenital heart disease (CHD) increasingly live into adulthood, often requiring cardiac reoperation. We aimed to assess the outcomes of adults with CHD (ACHD) undergoing repeat sternotomy at our institution. METHODS: Review of our institution's cardiac surgery database identified 1960 ACHD patients undergoing repeat median sternotomy from 1993 to 2023. The primary outcome was early mortality, and the secondary outcome was a composite end point of mortality and significant morbidity. Univariable and multivariable logistic regression models were used to determine factors independently associated with outcomes. RESULTS: Of the 1960 ACHDs patient undergoing repeat sternotomy, 1183 (60.3%) underwent a second, third (n = 506, 25.8%), fourth (n = 168, 8.5%), fifth (n = 70, 3.5%), and sixth sternotomy or greater (n = 33, 1.6%). CHD diagnoses were minor complexity (n = 145, 7.4%), moderate complexity (n = 1380, 70.4%), and major complexity (n = 435, 22.1%). Distribution of procedures included valve (n = 549, 28%), congenital (n = 625, 32%), aortic (n = 104, 5.3%), and major procedural combinations (n = 682, 34.7%). Overall early mortality was 3.1%. Factors independently associated with early mortality were older age at surgery, CHD of major complexity, preoperative renal failure, preoperative ejection fraction, urgent operation, and postoperative blood transfusion. In addition, sternotomy number and bypass time were independently associated with the composite outcome. CONCLUSIONS: Despite the increase in early mortality with sternotomy number, sternotomy number was not independently associated with early mortality but with increased morbidity. Improvement strategies should target factors leading to urgent operations, early referral, along with operative efficiency including bypass time and blood conservation.

Autologous Umbilical Cord Blood-Derived Mononuclear Cell Therapy Promotes Cardiac Proliferation and Adaptation in a Porcine Model of Right Ventricle Pressure Overload.

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

Impact of Hospital Volume on Outcomes of Septal Myectomy for Hypertrophic Cardiomyopathy.

BACKGROUND: Left ventricular outflow tract obstruction is common among symptomatic patients with hypertrophic cardiomyopathy, yet septal reduction by surgical myectomy (septal myectomy [SM]) is performed infrequently in many centers. This study examined the possible relationship between institutional case volume and early outcomes of SM. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was queried for patients with hypertrophic cardiomyopathy who underwent SM from January 2012 to December 2019. The study defined center case volume categories as <1, 1 to 4.99, 5 to 9.99, and ≥10 cases performed on average per year. RESULTS: The study population included 5935 patients at 481 centers with 933 surgeons. The range of average center volume was <1 to 138 cases per year. Overall early mortality was 2.6%, ventricular septal defect (VSD) occurred in 1.9%, and complete heart block occurred in 9.0%. Concomitant mitral valve (MV) repair was performed in 28.7%, and MV replacement was performed in 17.1%. In multivariable analysis, the lowest annual case volume (average <1 case/y) was consistently associated with greater early mortality (odds ratio [OR], 5.4; CI, 3.0-9.9; P < .001), greater risk of VSD (OR, 9.3; CI ,4.2-20.4; P < .001), increased incidence of complete heart block (OR, 2.0; CI, 1.5-2.7; P < .001), and a higher likelihood of MV replacement (OR, 9.4; CI, 7.5-11.8; P < .001). CONCLUSIONS: Volume of SM cases varies widely among institutions reporting to the Society of Thoracic Surgeons Adult Cardiac Surgery Database. There appears to be an important association between surgical experience, as reflected by institutional case volume, and early outcomes, including mortality, as well as the occurrence of VSD, heart block, and MV replacement.

From Safety to Benefit in Cell Delivery During Surgical Repair of Ebstein Anomaly: Initial Results.

BACKGROUND: The objective of this study is to assess the safety and early impact of intramyocardial delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) at time of surgical Ebstein repair. METHODS: Patients with Ebstein anomaly (ages 6 months to 30 years) scheduled to undergo repair of the tricuspid valve were eligible to participate in this open-label, non-randomized phase I clinical trial. BM-MNC target dose was 1-3 million cells/kg. Ten patients have undergone surgical intervention and cell delivery to the right ventricle (RV) and completed 6-month follow-up. RESULTS: All patients underwent surgical tricuspid valve repair and uneventful BM-MNC delivery; there were no ventricular arrhythmias and no adverse events related to study product or delivery. Echocardiographic RV myocardial performance index improved and RV fractional area change showed an initial decline and then through study follow-up. There was no evidence of delayed myocardial enhancement or regional wall motion abnormalities at injection sites on 6-month follow-up magnetic resonance imaging. CONCLUSIONS: Intramyocardial delivery of BM-MNC after surgical repair in Ebstein anomaly can be performed safely. Echocardiography variables suggest a positive impact of cell delivery on the RV myocardium with improvements in both RV size and wall motion over time. Additional follow-up and comparison to control groups are required to better characterize the impact of cell therapy on the myopathic RV in Ebstein anomaly.

Cone Reconstruction for Ebstein Anomaly: Ventricular Remodeling and Preliminary Impact of Stem Cell Therapy.

OBJECTIVE: To define the impact of tricuspid valve cone reconstruction (CR) on ventricular performance in Ebstein anomaly, both independently and after stem cell therapy. PATIENTS AND METHODS: The control group included 257 patients who had CR between June 2007 and December 2019. Ten subjects of a phase I stem cell therapy trial (May 2017 - March 2019) were compared with the controls to assess the echocardiographic impact on ventricular remodeling. RESULTS: After CR, right ventricular (RV) size decreased and left ventricular (LV) volume increased in all patients. Apical and biplane RV fractional area change (FAC) initially decreased, but rebounded by 6 months postoperation. Short-axis FAC increased early and was maintained at 6 months post-CR in the control group. At 6 months post-CR, cell therapy patients showed a significantly larger increase in short-axis FAC (24.4% vs 29.9%, P=.003). In addition, whereas LV ejection fraction (EF) was unchanged at 6 months post-CR in controls, cell therapy patients showed a significant increase in EF relative to baseline and to controls (55.6% vs 65.0%, P=.007). CONCLUSION: Cone reconstruction reduces tricuspid regurgitation and RV size, but is also associated with increased RV FAC and LV volume. Furthermore, injection of bone marrow-derived stem cells augmented the increase in RV FAC and was associated with improved LV EF at 6 months post-CR. This is evidence of a favorable interventricular interaction. These findings provide motivation for continued investigation into the potential benefits of stem cell therapy in Ebstein anomaly and other congenital cardiac malformations. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02914171.