Congenital heart disease (CHD) is the most common congenital anomaly and a leading cause of infant morbidity and mortality. Despite extensive exploration of the monogenic causes of CHD over the last decades, ∼55% of cases still lack a molecular diagnosis. Investigating digenic interactions, the simplest form of oligogenic interactions, using high-throughput sequencing data can elucidate additional genetic factors contributing to the disease. Here, we conducted a comprehensive analysis of digenic interactions in CHD by utilizing a large CHD trio exome sequencing cohort, comprising 3,910 CHD and 3,644 control trios. We extracted pairs of presumably deleterious rare variants observed in CHD-affected and unaffected children but not in a single parent. Burden testing of gene pairs derived from these variant pairs revealed 29 nominally significant gene pairs. These gene pairs showed a significant enrichment for known CHD genes (p < 1.0 × 10-4) and exhibited a shorter average biological distance to known CHD genes than expected by chance (p = 3.0 × 10-4). Utilizing three complementary biological relatedness approaches including network analyses, biological distance calculations, and candidate gene prioritization methods, we prioritized 10 final gene pairs that are likely to underlie CHD. Analysis of bulk RNA-sequencing data showed that these genes are highly expressed in the developing embryonic heart (p < 1 × 10-4). In conclusion, our findings suggest the potential role of digenic interactions in CHD pathogenesis and provide insights into unresolved molecular diagnoses. We suggest that the application of the digenic approach to additional disease cohorts will significantly enhance genetic discovery rates.

Tetralogy of Fallot (TOF) is the most common cyanotic heart defect in neonates. While there is compelling evidence of genetic contribution to the etiology of TOF, the contribution of noncoding variants to the development of the defect remains unexplored. Potentially damaging noncoding de novo variants (NC DNVs) were detected from 141 Chinese nonsyndromic TOF trios (CHN-TOF) and compared to those detected in the Pediatric Cardiac Genomics Consortium (PCGC). Bioinformatic analyses on noncoding and previously detected coding DNVs were performed to identify developmental pathways affected in TOF. Chinese but not PCGC TOF patients showed a notably increased burden of putative damaging NC DNVs (n=249). In Chinese, NC and coding DNVs were predominantly associated with cardiomyocyte differentiation and with chamber/valve/aorta development, respectively, producing a combined enrichment in NOTCH signaling (P=1.1x10-6) and outflow tract morphogenesis (P=2.2x10-5). Genes with NC DNVs (e.g., EFNB2, HEY2 and PITX2) interacted with NOTCH1 and FLT4 in a tight STRING protein-protein interaction (PPI) network. During the in vitro cardiac differentiation process, these noncoding candidate genes, which harbored potentially damaging regulatory NC DNVs, exhibited co-expression with NOTCH signaling genes and demonstrated dysregulated gene expression at various differentiation stages following NOTCH1 downregulation. In summary, our findings highlight a significant contribution of NC DNVs to TOF and suggest the presence of population genetic heterogeneity. Integrative analyses implicate dysregulation of NOTCH signaling, with converging influences from both coding and noncoding variants, in TOF within the Chinese population.

While exome and whole genome sequencing have transformed medicine by elucidating the genetic underpinnings of both rare and common complex disorders, its utility to predict clinical outcomes remains understudied. Here, we use artificial intelligence (AI) technologies to explore the predictive value of whole exome sequencing in forecasting clinical outcomes following surgery for congenital heart defects (CHD). We report results for a prospective observational cohort study of 2,253 CHD patients from the Pediatric Cardiac Genomics Consortium with a broad range of complex heart defects, pre- and post-operative clinical variables and exome sequencing. Damaging genotypes in chromatin-modifying and cilia-related genes are associated with an elevated risk of adverse post-operative outcomes, including mortality, cardiac arrest and prolonged mechanical ventilation. The impact of damaging genotypes is further amplified in the context of specific CHD phenotypes, surgical complexity and extra-cardiac anomalies. The absence of a damaging genotype in chromatin-modifying and cilia-related genes is also informative, reducing the risk for some adverse postoperative outcomes. Thus, genome sequencing enriches the ability to forecast outcomes following congenital cardiac surgery.

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent–offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to 4 subtypes. Seven genes were only associated with isolated CHD, while 37 were associated with 1 or more extracardiac abnormalities. Genes selectively expressed in the cardiomyocyte lineage were associated with isolated CHD, while those widely expressed in the brain were also associated with neurodevelopmental delay (NDD). Missense variants introducing or removing cysteines in epidermal growth factor (EGF)-like domains of NOTCH1 were enriched in tetralogy of Fallot and conotruncal defects, unlike the broader CHD spectrum seen with loss of function variants. Transmitted damaging missense variants in MYH6 were enriched in multiple CHD phenotypes and account for ~1% of all probands. Probands with characteristic mutations causing syndromic CHD were frequently not diagnosed clinically, often due to missing cardinal phenotypes. CHD genes that were positively or negatively associated with development of NDD suggest clinical value of genetic testing. These findings expand the understanding of CHD genetics and support the use of molecular diagnostics in CHD.

Single ventricle congenital heart defects (SVCHDs) are life-threatening defects that can lead to severe circulation issues and increased stress on the heart. Without prompt treatment, these defects can prove fatal in infancy. Fontan surgery is a conventional treatment for SVCHDs, which reroutes oxygen-poor blood directly to the lungs, bypassing the non-functioning ventricle. This procedure, however, can lead to circulation inefficiencies due to the absence of a natural, functional ventricle to pump blood to the pulmonary circulation. To address this issue, our team previously developed a tissue-engineered pulsatile conduit (TEPC) by wrapping engineered heart tissues (EHTs) derived from human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) around decellularized human umbilical artery (dHUA). This conduit has demonstrated the ability to produce a luminal pressure of 0.68 mmHg from spontaneous beating, which under 2 Hz electrical stimulation, increases to 0.83 mmHg. This offers a promising modular TEPC design that has the potential to provide active pumping function to the pulmonary circulation. We have since significantly optimized our approach by providing the conduit with electrical pacing training and an additional layer of EHT. These two enhancements have achieved markedly greater contractile productivity, where the spontaneous pressure generation reached 0.96 mmHg and the stimulated luminal pressure generation attained 1.87 mmHg with 2 Hz pacing. Our studies thus underscore the effectiveness of these TEPC design modifications, marking significant progress in the ongoing effort to improve treatments for patients with SVCHDs. STATEMENT OF SIGNIFICANCE: Single ventricle congenital heart defects (SVCHDs) are a life-threatening disorder, leading to severe circulation issues and heart failure. The Fontan procedure reroutes blood to the lung but lacks active pumping required for efficient circulation, often causing long-term complications. To address this challenge, we developed a tissue-engineered pulsatile conduit (TEPC) using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and decellularized human umbilical artery (dHUA) scaffolds. Our optimized design, with electrical pacing and enhanced engineered heart tissue (EHT) approaches, significantly increased luminal pressure development (up to 1.87 mmHg at 2 Hz frequency), offering a promising solution to improve outcomes for SVCHD patients.

Single ventricle congenital heart defects (SVCHDs) are characterized by the presence of only one functional ventricular chamber. The Fontan procedure, a common palliative intervention, reroutes venous blood from the inferior vena cava directly to the pulmonary arteries using a static conduit. However, the absence of contractility results in passive flow, causing venous congestion and poor pulmonary perfusion. We hypothesize that introducing a conduit with pulsatile function could actively pump venous blood into the lungs and reduce stasis. To test this, we first generated engineered heart tissues (EHTs) by seeding human iPSC-derived cardiomyocytes (hiPSC-CMs) onto decellularized porcine heart matrix (Fig. 1A). These cells expressed cardiac troponin T (cTnT), with initially sparse Connexin 43 (Fig. 1B). Subsequently, two layers of EHTs were wrapped around decellularized human umbilical arteries to fabricate the tissue-engineered pulsatile conduit (TEPC), which were then cultured in a bioreactor under continuous electrical stimulation (Fig. 1C-E). Luminal pressure generated by the TEPCs was measured under spontaneous beating and at pacing frequencies of 1, 1.33, 1.66, and 2 Hz. Under spontaneous conditions, the TEPCs generated a luminal pressure of 0.96 mmHg. With electrical pacing, the luminal pressure increased progressively, reaching 1.07 ± 0.07 mmHg at 1 Hz, 1.45 ± 0.32 mmHg at 1.33 Hz, and 1.61 ± 0.25 mmHg at 1.66 Hz. At 2 Hz, the luminal pressure peaked at 1.87 ± 0.33 mmHg, indicating enhanced contractile performance with electrical stimulation (Fig. 1F). In addition, the molecular characteristics of the TEPCs with/without electrical pacing were evaluated. Immunofluorescence analysis demonstrated that paced TEPCs exhibited higher expression levels of cTnT, compared to non-paced controls. Moreover, the expression of Connexin 43 was notably upregulated in electrically stimulated TEPCs, with Connexin 43 predominantly localized at intercellular junctions, indicating enhanced gap junction formation and cellular connectivity. In contrast, TEPCs cultured without electrical pacing showed reduced Connexin 43 expression (Fig. 2). These results demonstrate that electrical stimulation significantly enhances the contractile performance of TEPCs. Our work presents a proof-of-concept strategy for developing a pulsatile conduit as a potential curative therapy for SVCHDs, establishing a critical foundation for future clinical translation.

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and 85 genes with zero. RGs were more prevalent among offspring of consanguineous union (4.7%, 32/675) than among nonconsanguineous probands (0.7%, 34/4749). Founder variants in GDF1 and PLD1 accounted for 74% of the contribution of RGs among 410 Ashkenazi Jewish probands. We identified genome-wide significant enrichment of RGs in C1orf127, encoding a likely secreted protein expressed in embryonic mouse notochord and associated with laterality defects. Single-cell transcriptomes from gastrulation-stage mouse embryos revealed enrichment of RGs in genes highly expressed in the cardiomyocyte lineage, including contractility-related genes MYH6, UNC45B, MYO18B, and MYBPC3 in probands with left-sided CHD, consistent with abnormal contractile function contributing to these malformations. Genes with significant RG burden account for 1.3% of probands, more than half the inferred total. These results reveal the recessive contribution to CHD, and indicate that many genes remain to be discovered, with each likely accounting for a very small fraction of the total.

Background: With the increasing adoption of robotic technology in adult cardiac surgery patients, improved surgeon experience and wider utilization have been reported. However, interpreting trends in robotic congenital surgery is more challenging. By performing a systematic review, the authors aim to evaluate the current literature on robotic congenital operations. Methods: The protocol was registered with PROSPERO. The inclusion and exclusion criteria were established based on the population, intervention, comparison, and outcome (PICO) framework. A comprehensive literature search was conducted from January 1998 to December 2021. Studies involving patients undergoing congenital cardiac surgery operations performed with robotic assistance were included. Two independent reviewers screened titles/abstracts and then full text of eligible studies. A third reviewer resolved any discrepancies. The Newcastle–Ottawa Scale was applied to quantify quality assessment for nonrandomized observational studies. Results: A total of one-hundred twenty-eight publications underwent full-text review, and 66 studies were included. Overwhelmingly, the majority are from single institutions and observational and retrospective studies. The population was mostly adults with only 10.6% (7/66) studies solely reporting pediatric patients. About 50% of the studies were case reports (28/66). Selective reporting of outcomes varied widely across studies. Cumulative mortality rates were 0.3%. The highest incidence of morbidities included pleural effusion (12.3%), reoperation for bleeding (10.7%), atrial fibrillation (10.7%), heart block (9.5%), and peripheral cannulation–related complications (8.6%). The overall quality of the studies was unsatisfactory, with the majority of studies receiving a score of 3 out of 9. Conclusions: Most publications were case reports or small case series performed in adults and restricted to a few international institutions. To address these clinical challenges, technological improvements and advanced training will be mandatory before wider application to children and complex congenital diagnoses. Unfortunately, the overall quality of studies is poor, with inconsistent outcomes reporting. Improved and standardized reporting will be necessary before an appropriate evaluation of robotics in the treatment of congenital heart disease is feasible.

Background Historically, Dr William Glenn performed the first classic superior cavopulmonary anastomosis in a seven-year-old child at Yale in 1958. By 1990, this operation was performed consecutively in over 90 patients. With over 60 years of follow-up, this is the longest survival record of early Glenn patients from the first 30 years. Methods We performed a single center, retrospective evaluation of patients undergoing a Glenn operation. A collected list of surviving patients, previously updated in 1988, included demographics, age at procedure, and underlying diagnosis. Follow-up data were obtained in May 2022 using electronic medical records to determine survival, age of survivors, and age of deceased. Results Ninety-five patients underwent the Glenn operation from 1958 to 1990: 58.9% (n = 56) were male and 41.1% (n = 39) female. Fifteen patients were lost to follow-up, but 12 were alive in 1988. Sixty patients were deceased (68.1%), with an average age of 33.5 ± 18.3(range, 2-78, excluding seven early deaths) years. The oldest patient who passed away was a 78-year-old male with tetralogy of Fallot. Twenty patients remain alive, with an average age of 47.5 (range, 32-66) years. Four patients who are still alive today (20% survivors) are older than 60 years. Conclusions Since Dr Glenn's original operation, the technique, timing, and indications have been modified (ie, bidirectional Glenn) to adapt to the current era. By following this initial group of patients, we can approach completion of the survival rates for adult congenital patients who were some of the first pediatric patients to receive this ground-breaking palliative procedure.

Objective:Post-Norwood mortality remains high and unpredictable. Current models for mortality do not incorporate interstage events. We sought to determine the association of time-related interstage events, along with (pre)operative characteristics, with death post-Norwood and subsequently predict individual mortality.Methods:From the Congenital Heart Surgeons' Society Critical Left Heart Obstruction cohort, 360 neonates underwent Norwood operations from 2005 to 2016. Risk of death post-Norwood was modeled using a novel application of parametric hazard analysis, in which baseline and operative characteristics and time-related adverse events, procedures, and repeated weight and arterial oxygen saturation measurements were considered. Individual predicted mortality trajectories that dynamically update (increase or decrease) over time were derived and plotted.Results:After the Norwood, 282 patients (78%) progressed to stage 2 palliation, 60 patients (17%) died, 5 patients (1%) underwent heart transplantation, and 13 patients (4%) were alive without transitioning to another end point. In total, 3052 postoperative events occurred and 963 measures of weight and oxygen saturation were obtained. Risk factors for death included resuscitated cardiac arrest, moderate or greater atrioventricular valve regurgitation, intracranial hemorrhage/stroke, sepsis, lower longitudinal oxygen saturation, readmission, smaller baseline aortic diameter, smaller baseline mitral valve z-score, and lower longitudinal weight. Each patient's predicted mortality trajectory varied as risk factors occurred over time. Groups with qualitatively similar mortality trajectories were noted.Conclusions:Risk of death post-Norwood is dynamic and most frequently associated with time-related postoperative events and measures, rather than baseline characteristics. Dynamic predicted mortality trajectories for individuals and their visualization represent a paradigm shift from population-derived insights to precision medicine at the patient level.

We present a case of a newborn with a rare presentation of obstructed supracardiac total anomalous pulmonary venous connection who required emergent cannulation to extracorporeal membrane oxygenation (ECMO). Computed tomographic angiography of the heart was performed and using novel virtual dissection techniques aided in surgical planning and guidance. Computed tomographic angiography can be successfully performed in neonates with complex congenital heart disease on ECMO without adjustment of flows to aid in surgical management and novel virtual dissection techniques aid in complex anatomical delineation and spatial orientation with noncardiac structures. The preoperative imaging in this case allowed for appropriate and detailed presurgical planning and contributed to the excellent outcome of this patient.

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, Nor-wood, 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 pro-portionately 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.

Objective: Tricuspid atresia with normally related great vessels (TA) is considered the optimal substrate for the Fontan pathway. The factors associated with death or transplantation after cavopulmonary shunt (CPS) are underappreciated. We aimed to determine factors associated with CPS-Fontan interstage death/transplantation versus transition to Fontan in TA. Methods: A total of 417 infants younger than 3 months of age with TA were enrolled (January 1999 to February 2020) from 40 institutions into the Congenital Heart Surgeons' Society TA cohort. Parametric competing risk methodology was used to determine factors associated with the competing end points of death/transplantation without Fontan completion, and transition to Fontan. Results: CPS was performed in 382 patients with TA; of those, 5% died or underwent transplantation without transition to Fontan and 91% transitioned to Fontan by 5 years after CPS. Prenatal diagnosis (hazard ratio [HR], 0.74; P<.001) and pulmonary artery band (PAB) at CPS (HR, 0.50; P<.001) were negatively associated with Fontan completion. Preoperative moderate or greater mitral valve regurgitation (HR, 3.0; P<.001), concomitant mitral valve repair (HR, 11.0; P<.001), PAB at CPS (HR, 3.0; P<.001), postoperative superior vena cava interventions (HR, 9.0; P<.001), and CPS takedown (HR, 40.0; P<.001) were associated with death/transplantation. Conclusions: The mortality rate after CPS in patients with TA is notable. Those with preoperative mitral valve regurgitation remain a high-risk group. PAB at the time of CPS being associated with both increased risk of death and decreased Fontan completion may represent a deleterious effect of antegrade pulmonary blood flow in the CPS circulation.

Innovation is not only the fountainhead but the life's blood of our specialty, of surgery, of medicine, of business, or of just about anything that is progressing, evolving, and improving. In the absence of innovation there is stagnation and ultimately there is decay. Cardiac surgery, particularly congenital cardiac surgery, must continue to evolve through innovation.

Tetralogy of Fallot (TOF) is the most common cyanotic heart defect, yet the underlying genetic mechanisms remain poorly understood. Here, we performed whole-genome sequencing analysis on 146 nonsyndromic TOF parent-offspring trios of Chinese ethnicity. Comparison of de novo variants and recessive genotypes of this data set with data from a European cohort identified both overlapping and potentially novel gene loci and revealed differential functional enrichment between cohorts. To assess the impact of these mutations on early cardiac development, we integrated single-cell and spatial transcriptomics of early human heart development with our genetic findings. We discovered that the candidate gene expression was enriched in the myogenic progenitors of the cardiac outflow tract. Moreover, subsets of the candidate genes were found in specific gene coexpression modules along the cardiomyocyte differentiation trajectory. These integrative functional analyses help dissect the pathogenesis of TOF, revealing cellular hotspots in early heart development resulting in cardiac malformations.

Central MessageMitral regurgitation and left ventricular outflow tract obstruction can be effectively approached and treated with complex robotic mitral valve repair in a patient with cardiac dextroversion.See Commentaries on pages 17 and 19. Mitral regurgitation and left ventricular outflow tract obstruction can be effectively approached and treated with complex robotic mitral valve repair in a patient with cardiac dextroversion. See Commentaries on pages 17 and 19. A 25-year-old woman with dextroversion was found to have moderate mitral regurgitation (MR) complicated by systolic anterior motion (SAM) of the anterior leaflet, causing obstruction of the aortic valve and left ventricular outflow tract (LVOT). The patient presented with increasing symptoms of intermittent nonexertional chest pressure and dyspnea on exertion. A preoperative transthoracic echocardiogram revealed worsening MR and LVOT obstruction with a peak resting gradient of 37 mm Hg and 70 mm Hg on provocative testing. Further imaging with computed tomography and magnetic resonance imaging was obtained for surgical planning employing the da Vinci Xi surgical robot (Intuitive Surgical, Inc, Sunnyvale, Calif). The heart was positioned in the right chest, with the apex pointing towards the right. The left ventricle was anterior to the right ventricle, with the mitral valve positioned anterior to the aortic valve and LVOT (Figure E1, A). It was noted that the posteriorly leaflet was quite long and that the acute angle from the anterior leaflet of the mitral valve to the aortic root was causing the LVOT obstruction (Figure E1, B). Intraoperative transesophageal echocardiogram showed SAM, moderate MR, anterior mitral leaflet height of 4.0 cm, posterior mitral leaflet height of 2.50 cm, LVOT of 1.1 cm, and C-sept distance of 2.39 cm (Figure E2, A). The patient was positioned supine with gel pad under the left side to rotate the chest slightly toward the right. A small access incision was made in the left fourth intercostal space and robotic ports placed in second, fourth, and sixth intercostal space (Figure 1, A). Femoral cannulation was used for cardiopulmonary bypass and IntraClude (Edwards Lifesciences) intra-aortic occlusion device for cardioplegia delivery. The robot was connected in place, the left lung was deflated, and the chest was explored. Exposure through the pericardium was carefully achieved without injury to the left phrenic nerve, which was running quite anteriorly on the pericardium. Cardiopulmonary bypass was initiated, and cardioplegia was administered after confirming a robust seal of the inflated endoballoon. The left atrium was entered just above the left superior pulmonary veins and posterior to the coronary sinus, which contained the persistent left superior vena cava. A retractor placed for exposure to the mitral valve, which was uniquely oriented in that the morphologically posterior leaflet faced anteriorly (Figure 2, A). No leaflet prolapse was observed (Figure 2, B).Figure 2Intraoperative picture showing (A) morphologic anterior mitral valve leaflet positioned inferiorly; (B) saline testing before mitral valve repair with coaptation line in center of the valve due to excessive length of morphological posterior leaflet; (C) annular advancement technique used to effectively shorten the height of the morphological posterior leaflet; and (D) saline testing after mitral valve repair with semirigid annuloplasty band restoring the normal one-third posterior to two-thirds anterior height ratio.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The valve was repaired by decreasing the height of the posterior leaflet using annular advancement technique also known as imbrication technique.1Hashim P.W. Assi R. Hashim S.W. The imbrication technique: an alternative to the sliding leaflet technique.Ann Thorac Surg. 2014; 98: 1124-1126Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar This decreases the height of the leaflet without resection of leaflet tissue and is a useful, nonresectional technique that decreases the risk of SAM after mitral valve repair. Each arm of horizontal mattress annuloplasty sutures is brought through the annulus and advanced 3 to 4 mm into the leaflet itself in the area of excessive length (Figures 1, B, and 2, C). This effectively decrease the height of the leaflet (Figure 1, C). A 32-mm Simulus Semi-Rigid Annuloplasty Band (Medtronic, Minneapolis, Minn) was selected. This particular band is semirigid and was used to further elevate the posterior leaflet away from the anterior leaflet and the LVOT. An additional suture was placed to close a small cleft between P1 and P2. Intraoperative assessment was satisfactory after repair (Figure 2, D). The heart was deaired, the endoballoon was deflated, and the patient was weaned off bypass without complication. Good function of the mitral valve with trace to mild MR, without SAM or LVOT obstruction, was confirmed under echo (Figure E2, B). Video 1 shows the conduct of the operation and imaging studies. Written consent for the patient's authorization of disclosure was obtained in compliance with the Health Insurance Portability and Accountability Act of 1996 and Yale institutional review board protocols. Dextroversion is defined by right-sided cardiac positioning with a rightward cardiac apex in the setting of situs solitus. In contrast to situs inversus, in which the visceroatrial orientation mirrors the normal organization, in dextroversion there is normal positioning of tracheobronchial tree and abdominal viscera.2Tripathi S. Ajit Kumar V.K. Comparison of morphologic findings in patients with dextrocardia with situs solitus vs situs inversus: a retrospective study.Pediatr Cardiol. 2019; 40: 302-309Crossref PubMed Scopus (6) Google Scholar It is thought that this malposition occurs because of a failure of the cardiac apex to redirect from right-facing to left-facing during the ninth week of embryologic development.3De la Cruz M.V. Anselmi G. Munos-Castellanos L. Nadal-Ginard B. Munoz-Armas S. Systematization and embryological and anatomical study of mirror-image dextrocardias, dextroversions, and laevoversions.Br Heart J. 1971; 33: 841-853Crossref PubMed Scopus (12) Google Scholar In the literature, it has been reported that approximately 40% of patients with dextrocardia belong to each of these 2 orientations, whereas just 20% of patients are classified by a third orientation situs ambiguus, which designates anatomical orientations that possess a mixture of features similar to both situs solitus and situs inversus.2Tripathi S. Ajit Kumar V.K. Comparison of morphologic findings in patients with dextrocardia with situs solitus vs situs inversus: a retrospective study.Pediatr Cardiol. 2019; 40: 302-309Crossref PubMed Scopus (6) Google Scholar Dextrocardia is rare and predisposes to congenital heart disease, and it may be more complicated in patients with situs solitus compared with situs inversus.2Tripathi S. Ajit Kumar V.K. Comparison of morphologic findings in patients with dextrocardia with situs solitus vs situs inversus: a retrospective study.Pediatr Cardiol. 2019; 40: 302-309Crossref PubMed Scopus (6) Google Scholar,4Offen S. Jackson D. Canniffe C. Choudhary P. Celermajer D.S. Dextrocardia in adults with congenital heart disease.Heart Lung Circ. 2016; 25: 352-357Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Robotic surgery has been employed for mitral valve surgery since the 1990s and has been shown to rival or exceed outcomes in open surgeries, although its popularity has been stunted by associated costs and labor-intensive training.5Sultan I. Trivedi D.P. Machiraju V.R. Surgical approaches to the mitral valve: variable paths to the same destination.Indian J Thorac Cardiovasc Surg. 2018; 34: 105-112Crossref Scopus (1) Google Scholar In dextrocardia, the pulmonary trunk may lie posterior and left of the aorta. This and other shifts in anatomical relationships require significant surgical finesse to employ traditional robotic surgery techniques for patients with this condition. Although the literature appears to contain an increasing number of cases of endoscopic surgical repairs in patients with dextrocardia and situs inversus,6Iino K. Watanabe G. Ishikawa N. Tomita S. Total endoscopic robotic atrial septal defect repair in a patient with dextrocardiac and situs inversus totalis.Interact Cardiovasc Thorac Surg. 2012; 14: 476-477Crossref PubMed Scopus (13) Google Scholar no publication to date has reported a similar robotic approach to mitral valve repair in a patient with dextroversion. This report offers a novel and safe approach to treat MR in patients with these complex anatomical relationships. Figure E2Intraoperative transthoracic echocardiography demonstrating (A) prerepair systolic anterior motion (SAM) of the anterior leaflet with moderate mitral regurgitation; and (B) postrepair with no SAM or significant mitral regurgitation.View Large Image Figure ViewerDownload Hi-res image Download (PPT) https://www.jtcvstechniques.org/cms/asset/50af5e7c-0a13-4f9f-905c-c728af9e8186/mmc1.mp4Loading ... Download .mp4 (71.1 MB) Help with .mp4 files Video 1Video demonstration of the operative technique employed for mitral valve repair in a case of dextroversion. Video available at: https://www.jtcvs.org/article/S2666-2507(21)00722-7/fulltext. Download .jpg (.27 MB) Help with files Video 1Video demonstration of the operative technique employed for mitral valve repair in a case of dextroversion. Video available at: https://www.jtcvs.org/article/S2666-2507(21)00722-7/fulltext. Commentary: Pushing the limits: Robotic mitral valve surgery in cardiac dextroversionJTCVS TechniquesVol. 11PreviewWe commend Bourdillon and colleagues1 on this case, which details the successful treatment of mitral regurgitation in a patient with cardiac dextroversion. We believe this report offers valuable insight into not only the recovery advantages of a robotic approach but also its ability to treat complex cardiac surgical pathologies that have traditionally required open intervention. Full-Text PDF Open Access

BACKGROUND Aortic valve replacement is the traditional surgical treatment for aortic valve diseases, yet standardized aortic valve neocuspidization (AVNeo) is a promising alternative that is gaining popularity. The purpose of this article is to review the available published literature of AVNeo using glutaraldehyde-treated autologous pericardium, also known as the Ozaki procedure, including indications, outcomes, potential benefits, and modes of failure for the reconstructed valve.METHODS A comprehensive literature search was performed using keywords related to aortic valve repair, AVNeo, or Ozaki procedure. All articles describing performance of AVNeo were reviewed. RESULTS Reported early mortality after AVNeo varies from 0% to 5.88%. The largest cohort of patients in the literature includes 850 patients with an inhospital mortality rate of 1.88%. Cumulative incidence of aortic valve reoperation was 4.2% in the largest series. Reoperation was uncommon and mainly due to infective endo-carditis or degeneration of the reconstructed valve (most commonly due to aortic valve regurgitation, rather than stenosis).CONCLUSIONS Aortic valve neocuspidization is a versatile and standardized alternative to aortic valve replacement with a biological prosthesis. Early to midterm outcomes from a number of centers are excellent and demonstrate the safety and durability of the procedure. Long-term outcomes and clinical trial data are necessary to determine which patients benefit the most from this procedure.(Ann Thorac Surg 2022;114:1108-17)(c) 2022 by The Society of Thoracic Surgeons