A Novel Echocardiographic Parameter to Confirm Low-Gradient Aortic Stenosis Severity.

Background: In patients with low-gradient (LG) aortic stenosis (AS), confirming disease severity and indication of intervention often requires dobutamine stress echocardiography (DSE) or aortic valve calcium scoring by computed tomography. We hypothesized that the mean transvalvular pressure gradient to effective orifice area ratio (MG/EOA, in mm Hg/cm2) measured during rest echocardiography identifies true-severe AS (TSAS) and is associated with clinical outcomes in patients with low-flow, LG-AS. Objectives: The purpose of this study was to evaluate the diagnostic and prognostic value of MG/EOA ratio. Methods: The diagnostic accuracy of MG/EOA ratio to identify TSAS was retrospectively assessed in: 1) an in vitro data set obtained in a circulatory model including 93 experimental conditions; and 2) an in vivo data set of 188 patients from the TOPAS (True or Pseudo-Severe Aortic Stenosis) study (NCT01835028). Receiver operating characteristic curves were used to assess the diagnostic accuracy of MG/EOA ratio for identifying TSAS, and Cox proportional hazards regression analyses were performed to assess its association with clinical outcomes. Results: The optimal cutoff of MG/EOA ratio to identify TSAS in patients with low-flow, LG-AS was ≥25 mm Hg/cm2 (correct classification 85%), as well as in vitro (100%). During a median follow-up of 1.41 ± 0.75 years, 146 (78%) patients met the composite endpoint of aortic valve replacement or all-cause mortality. A MG/EOA ratio ≥25 mm Hg/cm2 was independently associated with an increased risk of the composite endpoint (adjusted HR: 2.36 [95% CI: 1.63-3.42], P < 0.001). The Harell's C-index of MG/EOA was 0.68, equaling projected EOA (0.67) measured by DSE. Conclusions: MG/EOA ratio can be useful in low-flow, LG-AS to confirm AS severity and may complement DSE or aortic valve calcium scoring.

Degenerative Mitral Regurgitation Outcomes in Asian Compared With European-American Institutions.

Background: Clinical outcome and interventional thresholds for degenerative mitral regurgitation (DMR) were developed in studies of patients at European and American institutions (EAIs), but little is known about patients at Asian institutions (AsIs). Objectives: This study sought to contrast DMR presentation/management/outcomes of AsI patients vs EAI patients. Methods: Patients with DMR due to flail leaflet from Hong Kong and Singapore (AsI cohort, n = 737) were compared with EAI patients (n = 682) enrolled in the MIDA (Mitral regurgitation International Database) registry with similar eligibility criteria. Results: AsI patients presented similar DMR lesion/consequences vs EAI patients, but they were younger, with fewer symptoms (74% vs 44% Class I), more sinus rhythm (83% vs 69%), and lower EuroSCORE II (European System for Cardiac Operative Risk Evaluation II) (0.9 ± 0.5 vs 1.4 ± 1.5; all P < 0.0001). Imaging showed smaller absolute left atrial/ventricular dimensions in AsI patients, belying cardiac dilatation with larger body surface area-indexed diameters (all P < 0.01). Surgical/interventional mitral repair was similarly predominant (90% vs 91%; P = 0.47), and early repair was similarly beneficial (for AsI patients, adjusted HR: 0.28; 95% CI: 0.16-0.49; for EAI patients, HR: 0.32; 95% CI: 0.20-0.49; both P < 0.0001). However, AsI patients underwent fewer interventions (55% ± 2% vs 77% ± 2% at 1 year; P < 0.0001) and incurred excess mortality (adjusted HR: 1.60 [95% CI: 1.13-2.27] vs EAI patients; P = 0.008) at long-term postdiagnosis. Propensity score matching (434 patient pairs), which balanced all clinical characteristics, confirmed that there was undertreatment and excess mortality in the long term in AsI patients with DMR (P < 0.0001). Conclusions: Imaging may underestimate volume overload in AsI patients due to smaller cardiac cavities related to smaller body size compared with EAI patients with similar mitral lesions and DMR severity. AsI patients enjoy similar mitral repair predominance and early intervention benefits but undergo fewer mitral interventions than EAI patients and incur subsequent excess mortality, suggesting the need to account for imaging and cultural specificity to improve DMR outcomes worldwide.

Sex-related differences among patients undergoing surgical aortic valve replacement-a propensity score matched study.

OBJECTIVES: We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). METHODS: Data from 2 prospective registries, the INSPIRIS RESILIA Durability Registry (INDURE) and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. The PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. RESULTS: Females had a lower body mass index (median 27.1 vs 28.0 kg/m2; P = 0.008), fewer bicuspid valves (52% vs 59%; P = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; P < 0.001) and Society of Thoracic Surgeons score (mean 1.6 vs 0.9%; P < 0.001), were more often in New York Heart Association functional class III/IV (47% vs 30%; P < 0.001) and angina Canadian Cardiovascular Society III/IV (8.2% vs 4.4%; P < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; P = 0.028) compared to males. These differences vanished after PSM, except for the EuroSCORE II and Society of Thoracic Surgeons scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, P < 0.001). There were no differences in the length of hospital stay (median 8 days) or intensive care unit stay (median 24 vs 25 hours) between the 2 sexes. At 2 years, post-SAVR outcomes were comparable between males and females, even after PSM. CONCLUSIONS: Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females.

Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes.

BACKGROUND AND AIMS: Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. METHODS: In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. RESULTS: At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. CONCLUSIONS: Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

egr3 is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis.

Biomechanical forces, and their molecular transducers, including key mechanosensitive transcription factor genes, such as KLF2, are required for cardiac valve morphogenesis. However, klf2 mutants fail to completely recapitulate the valveless phenotype observed under no-flow conditions. Here, we identify the transcription factor EGR3 as a conserved biomechanical force transducer critical for cardiac valve formation. We first show that egr3 null zebrafish display a complete and highly penetrant loss of valve leaflets, leading to severe blood regurgitation. Using tissue-specific loss- and gain-of-function tools, we find that during cardiac valve formation, Egr3 functions cell-autonomously in endothelial cells, and identify one of its effectors, the nuclear receptor Nr4a2b. We further find that mechanical forces up-regulate egr3/EGR3 expression in the developing zebrafish heart and in porcine valvular endothelial cells, as well as during human aortic valve remodeling. Altogether, these findings reveal that EGR3 is necessary to transduce the biomechanical cues required for zebrafish cardiac valve morphogenesis, and potentially for pathological aortic valve remodeling in humans.

One-year clinical outcomes following Edwards INSPIRIS RESILIA aortic valve implantation in 487 young patients with severe aortic stenosis: a single-center experience.

Introduction: The use of an aortic bioprosthesis is on the rise in younger patients with severe aortic stenosis despite the risk of accelerated structural valve degeneration (SVD). In the search for an optimal valve substitute that would not be prone to SVD, the INSPIRIS bioprosthesis represents a promising solution to lowering the risk of SVD. Here, we report the 1-year outcomes of the INSPIRIS RESILIA aortic bioprosthesis in a population of young patients who underwent aortic valve replacement. Methods: In this prospective single-center study, we included all consecutive patients receiving INSPIRIS RESILIA bioprosthesis between June 2017 and July 2021. Patients with isolated severe aortic regurgitation were excluded. Clinical assessment and transthoracic echocardiography were performed preoperatively and at 1 year post-operatively. The primary outcome was overall mortality at one year. Results: A total of 487 patients were included. The mean age was 58.2 ± 11.5 years, 75.2% were men. Most of the interventions were elective, with a mean EuroSCORE II of 4.8 ± 7.9. The valve annulus size in most cases was either 23 mm or 25 mm. Overall mortality at 1-year was 4.1%. At 1-year, 7 patients (1.4%) had a stroke, 4 patients (0.8%) had a myocardial infarction, and 20 patients (4.1%) were hospitalized for congestive heart failure. The Kaplan-Meier estimated survival rates and survival without major adverse cardiac events at 1-year were 96.4% and 96.7%, respectively. At 1-year follow-up, 10 patients (2.1%) had endocarditis and 1 patient (0.2%) had partial prosthetic thrombosis. Pacemaker implantation at 1-year post-operative was necessary in 27 patients (5.5%). Severe patient prosthesis mismatch and severe intra valvular regurgitation were 1.2% and 0.6%, respectively. The Kaplan-Meier estimated survival rates at 1-year of no infective endocarditis preoperative and infective endocarditis preoperative were 97.9 ± 0.7% and 89.5 ± 3.3%, respectively (P < 0.001). Excluding endocarditis-related complication, no structural valve deterioration and no valve failure requiring redo surgery were reported. Conclusion: This is the largest single-center descriptive study of the 1-year outcomes after INSPIRIS RESILIA bioprosthesis implantation. The EDWARDS INSPIRIS RESILIA bioprosthesis provides encouraging clinical outcomes with an excellent 1- year survival rates and good hemodynamic performance. Long-term studies are mandatory to assess valve durability.

Durability of bioprosthetic aortic valve replacement in patients under the age of 60 years - 1-year follow-up from the prospective INDURE registry.

OBJECTIVES: We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. METHODS: The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. RESULTS: A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. CONCLUSIONS: The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03666741.

Partial Atrioventricular Septal Defect with Left Atrioventricular Valve Aneurysm Mimicking Valve Perforation.

Left atrioventricular valve aneurysm is a rare condition. Here we present a rare case of partial atrioventricular septal defect with an extremely thin left atrioventricular valve aneurysm mimicking valve perforation. Preoperative echocardiography demonstrated severe left sided atrioventricular valve regurgitation on the "cleft" and leaflet perforation. But we discovered a left sided atrioventricular valve aneurysm instead of a valve perforation. The "cleft" edge and the aneurysm were closed.

Prognostic value of forward flow indices in primary mitral regurgitation due to mitral valve prolapse.

Background: Degenerative mitral regurgitation (DMR) due to mitral valve prolapse (MVP) is a common valve disease associated with significant morbidity and mortality. Timing for surgery is debated for asymptomatic patients without Class I indication, prompting the search for novel parameters of early left ventricular (LV) systolic dysfunction. Aims: To evaluate the prognostic impact of preoperative forward flow indices on the occurrence of post-operative LV systolic dysfunction. Methods: We retrospectively included all consecutive patients with severe DMR due to MVP who underwent mitral valve repair between 2014 and 2019. LVOTTVI, forward stroke volume index, and forward LVEF were assessed as potential risk factors for LVEF <50% at 6 months post-operatively. Results: A total of 198 patients were included: 154 patients (78%) were asymptomatic, and 46 patients (23%) had hypertension. The mean preoperative LVEF was 69 ± 9%. 35 patients (18%) had LVEF ≤ 60%, and 61 patients (31%) had LVESD ≥40 mm. The mean post-operative LVEF was 59 ± 9%, and 21 patients (11%) had post-operative LVEF<50%. Based on multivariable analysis, LVOTTVI was the strongest independent predictor of post-operative LV dysfunction after adjustment for age, sex, symptoms, LVEF, LV end systolic diameter, atrial fibrillation and left atrial volume index (0.75 [0.62-0.91], p < 0.01). The best sensitivity (81%) and specificity (63%) was obtained with LVOTTVI ≤15 cm based on ROC curve analysis. Conclusion: LVOTTVI represents an independent marker of myocardial performance impairment in the presence of severe DMR. LVOTTVI could be an earlier marker than traditional echo parameters and aids in the optimization of the timing of surgery.

Expanding the phenome and variome of the ROBO-SLIT pathway in congenital heart defects: toward improving the genetic testing yield of CHD.

BACKGROUND: Recent studies have shown the implication of the ROBO-SLIT pathway in heart development. Within this study, we aimed to further assess the implication of the ROBO and SLIT genes mainly in bicuspid aortic valve (BAV) and other human congenital heart defects (CHD). METHODS: We have analyzed a cohort of singleton exome sequencing data comprising 40 adult BAV patients, 20 pediatric BAV patients generated by the Pediatric Cardiac Genomics Consortium, 10 pediatric cases with tetralogy of Fallot (ToF), and one case with coarctation of the aorta. A gene-centered analysis of data was performed. To further advance the interpretation of the variants, we intended to combine more than 5 prediction tools comprising the assessment of protein structure and stability. RESULTS: A total of 24 variants were identified. Only 4 adult BAV patients (10%) had missense variants in the ROBO and SLIT genes. In contrast, 19 pediatric cases carried variants in ROBO or SLIT genes (61%). Three BAV patients with a severe phenotype were digenic. Segregation analysis was possible for two BAV patients. For the homozygous ROBO4: p.(Arg776Cys) variant, family segregation was consistent with an autosomal recessive pattern of inheritance. The ROBO4: c.3001 + 3G > A variant segregates with the affected family members. Interestingly, these variants were also found in two unrelated patients with ToF highlighting that the same variant in the ROBO4 gene may underlie different cardiac phenotypes affecting the outflow tract development. CONCLUSION: Our results further reinforce the implication of the ROBO4 gene not only in BAV but also in ToF hence the importance of its inclusion in clinical genetic testing. The remaining ROBO and SLIT genes may be screened in patients with negative or inconclusive genetic tests.

Variations in the poly-histidine repeat motif of HOXA1 contribute to bicuspid aortic valve in mouse and zebrafish.

Bicuspid aortic valve (BAV), the most common cardiovascular malformation occurs in 0.5-1.2% of the population. Although highly heritable, few causal mutations have been identified in BAV patients. Here, we report the targeted sequencing of HOXA1 in a cohort of BAV patients and the identification of rare indel variants in the homopolymeric histidine tract of HOXA1. In vitro analysis shows that disruption of this motif leads to a significant reduction in protein half-life and defective transcriptional activity of HOXA1. In zebrafish, targeting hoxa1a ortholog results in aortic valve defects. In vivo assays indicates that these variants behave as dominant negatives leading abnormal valve development. In mice, deletion of Hoxa1 leads to BAV with a very small, rudimentary non-coronary leaflet. We also show that 17% of homozygous Hoxa1-1His knock-in mice present similar phenotype. Genetic lineage tracing in Hoxa1-/- mutant mice reveals an abnormal reduction of neural crest-derived cells in the valve leaflet, which is caused by a failure of early migration of these cells.

Genetic and phenotypic continuum of HOXA genes: A case with double HOXA9/HOXA13 mutations.

The HOXA genes cluster plays a key role in embryologic development. Mutations in HOXA genes have been linked to different human phenotypes, including developmental delay, limb anomalies, and urogenital malformations. The present study reported a clinical and genetic investigation of a female patient with polymalformative syndrome including left arm agenesis, bicornuate uterus and bicuspid aortic valve. Using whole exome sequencing, two heterozygous missense variants were identified. Of these, one was a novel variant in the HOXA13 gene [p.(Tyr290Ser)] and the second a heterozygous variant in the HOXA9 gene [p.(Ala102Pro)]. To the best of our knowledge, this is the first association of HOXA9/HOXA13 point mutations linked to a syndromic case. In conclusion, the present study suggested that the phenotypic spectrum of vertebral anomalies, anal atresia, cardiac defects, tracheo­esophageal fistula, renal anomalies and limb abnormalities/hand­foot­genital syndrome may be attributable to the combination of different HOXA variants, particularly in patients with a severe clinical presentation. The current report contributed as well to the molecular understanding of HOXA genes­related phenotypes via the identification of novel variant and genes associations.

Incidence of Persistent Left Bundle Branch Block After Rapid-Deployment Aortic Valve Replacement.

BACKGROUND: We evaluated the incidence, prognosis, and predictive factors of new onset of persistent left bundle branch block (NOP-LBBB) after rapid-deployment aortic valve replacement (RD-AVR). METHODS: This was an observational, retrospective, single-center study of 274 consecutive patients with no baseline ventricular conduction disorder and no previous permanent pacemaker implantation (PPI) who underwent RD-AVR with an INTUITY valve (n = 55) or INTUITY Elite Valve (n = 219) (Edwards Lifesciences). Transthoracic echocardiography and 12-lead electrocardiography was performed preoperatively, at discharge, and at 1-month and 1-year intervals. The incidence, prognosis, and predictive factors of NOP-LBBB were evaluated. RESULTS: NOP-LBBB occurred in 58 patients (21.2%) after discharge. In multivariate analysis, age (P < .01), INTUITY valve diameter ≥23 mm (P = .02), and INTUITY Elite implantation (P = .01) were independent predictors of NOP-LBBB. By 1:1 propensity matching analysis between the NOP-LBBB group and the control group, there were no significant differences in 1-year overall mortality (P = .23), hospitalization for congestive heart failure (P = .99), or PPI (P = .99). NOP-LBBB exposed patients to a high rate of dysrhythmic events (12.1% vs 1.4%, P < .01) and was associated with a significant decrease in left ventricular ejection fraction (0.62 ± 0.095 vs 0.652 ± 0.0783, P = .02) without an impact on New York Heart Association functional status (1.25 ± 0.32 and 1.52 ± 0.70, P = .32). PPI was performed in 17 patients (6.2%) before discharge, including 14 NOP-LBBB patients. CONCLUSIONS: NOP-LBBB after RD-AVR is prevalent in patients with no prior conduction disorders. INTUITY Elite is associated with a significantly higher rate of NOP-LBBB. The persistence of NOP-LBBB predisposed patients to the occurrence of high-grade conduction disorders and might have led to PPI but did not increase death or hospitalization for congestive heart failure.

Partial Atrioventricular Septal Defect with Left Atrioventricular Valve Aneurysm Mimicking Valve Perforation

ABSTRACT Left atrioventricular valve aneurysm is a rare condition. Here we present a rare case of partial atrioventricular septal defect with an extremely thin left atrioventricular valve aneurysm mimicking valve perforation. Preoperative echocardiography demonstrated severe left sided atrioventricular valve regurgitation on the "cleft" and leaflet perforation. But we discovered a left sided atrioventricular valve aneurysm instead of a valve perforation. The "cleft" edge and the aneurysm were closed.

SCN5A Variants as Genetic Arrhythmias Triggers for Familial Bileaflet Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is a common valvular heart defect with variable outcomes. Several studies reported MVP as an underestimated cause of life-threatening arrhythmias and sudden cardiac death (SCD), mostly in young adult women. Herein, we report a clinical and genetic investigation of a family with bileaflet MVP and a history of syncopes and resuscitated sudden cardiac death. Using family based whole exome sequencing, we identified two missense variants in the SCN5A gene. A rare variant SCN5A:p.Ala572Asp and the well-known functional SCN5A:p.His558Arg polymorphism. Both variants are shared between the mother and her daughter with a history of resuscitated SCD and syncopes, respectively. The second daughter with prodromal MVP as well as her healthy father and sister carried only the SCN5A:p.His558Arg polymorphism. Our study is highly suggestive of the contribution of SCN5A mutations as the potential genetic cause of the electric instability leading to ventricular arrhythmias in familial MVP cases with syncope and/or SCD history.

Long-Term Prognosis Value of Paravalvular Leak and Patient-Prosthesis Mismatch following Transcatheter Aortic Valve Implantation: Insight from the France-TAVI Registry.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is the preferred treatment for symptomatic severe aortic stenosis (AS) in a majority of patients across all surgical risks. PATIENTS AND METHODS: Paravalvular leak (PVL) and patient-prosthesis mismatch (PPM) are two frequent complications of TAVI. Therefore, based on the large France-TAVI registry, we planned to report the incidence of both complications following TAVI, evaluate their respective risk factors, and study their respective impacts on long-term clinical outcomes, including mortality. RESULTS: We identified 47,494 patients in the database who underwent a TAVI in France between 1 January 2010 and 31 December 2019. Within this population, 17,742 patients had information regarding PPM status (5138 with moderate-to-severe PPM, 29.0%) and 20,878 had information regarding PVL (4056 with PVL ≥ 2, 19.4%). After adjustment, the risk factors for PVL ≥ 2 were a lower body mass index (BMI), a high baseline mean aortic gradient, a higher body surface area, a lower ejection fraction, a smaller diameter of TAVI, and a self-expandable TAVI device, while for moderate-to-severe PPM we identified a younger age, a lower BMI, a larger body surface area, a low aortic annulus area, a low ejection fraction, and a smaller diameter TAVI device (OR 0.85; 95% CI, 0.83-0.86) as predictors. At 6.5 years, PVL ≥ 2 was an independent predictor of mortality and was associated with higher mortality risk. PPM was not associated with increased risk of mortality. CONCLUSIONS: Our analysis from the France-TAVI registry showed that both moderate-to-severe PPM and PVL ≥ 2 continue to be frequently observed after the TAVI procedure. Different risk factors, mostly related to the patient's anatomy and TAVI device selection, for both complications have been identified. Only PVL ≥ 2 was associated with higher mortality during follow-up.

Identification of non-synonymous variations in ROBO1 and GATA5 genes in a family with bicuspid aortic valve disease.

Bicuspid aortic valve (BAV) is the most common congenital heart defect with a high index of heritability. Patients with BAV have different clinical courses and disease progression. Herein, we report three siblings with BAV and clinical differences. Their clinical presentations include moderate to severe aortic regurgitation, aortic stenosis, and ascending aortic aneurysm. Genetic investigation was carried out using Whole-Exome Sequencing for the three patients. We identified two non-synonymous variants in ROBO1 and GATA5 genes. The ROBO1: p.(Ser327Pro) variant is shared by the three BAV-affected siblings. The GATA5: p.(Gln3Arg) variant is shared only by the two brothers who presented BAV and ascending aortic aneurysm. Their sister, affected by BAV without aneurysm, does not harbor the GATA5: p.(Gln3Arg) variant. Both variants were absent in the patients' fourth brother who is clinically healthy with tricuspid aortic valve. To our knowledge, this is the first association of ROBO1 and GATA5 variants in familial BAV with a potential genotype-phenotype correlation. Our findings are suggestive of the implication of ROBO1 gene in BAV and the GATA5: p.(Gln3Arg) variant in ascending aortic aneurysm. Our family-based study further confirms the intrafamilial incomplete penetrance of BAV and the complex pattern of inheritance of the disease.

Prosthesis-Patient Mismatch in Small Aortic Annuli: Self-Expandable vs. Balloon-Expandable Transcatheter Aortic Valve Replacement.

Prosthesis−patient mismatch (PPM) is associated with worse outcomes following surgical aortic valve replacement (SAVR). PPM has been identified in a significant proportion of TAVR, particularly in patients with small aortic annuli. Our objective was to evaluate the hemodynamic performances of balloon-expandable (BE) (Sapiens 3TM) versus two different self-expandable (SE) (Evolut ProTM, Accurate NeoTM) TAVR devices in patients with small aortic annulus defined by a computed tomography aortic annulus area (AAA) between 330 and 440 mm2. We enrolled 131 consecutive patients corresponding to 76 Sapiens 3 23 mm (58.0%), 26 Evolut Pro (19.9%) and 29 Accurate Neo (22.1%). Mean age was 82.5 ± 7.06 years, 22.9% of patients were male and mean Euroscore was 4.0%. Mean AAA was 374 ± 27 mm2 for Sapiens 3, 383 ± 29 mm2 for Corevalve Evolut Pro and 389 ± 25 mm2 for Accurate Neo. BE devices were associated with significantly higher rates of PPM (39.5%) as compared to SE devices (15.4% for Corevalve Evolut Pro and 6.9% for Accurate Neo) (p < 0.0001). Paravalvular leaks ≥ 2/4 were more often observed in SE devices (15.4% for Corevalve Evolut Pro and 17.2% for Accurate Neo) than in BE devices (2.6%) (p = 0.007). In conclusion, SE TAVR devices did achieve better hemodynamic results despite higher rates of paravalvular leaks. Therefore, SE TAVI devices could be considered as first choice in small aortic anatomy.

Myocardial Revascularization Strategies in ST Elevation Myocardial Infarction Without Urgent Revascularization: Insight From a Nationwide Study.

OBJECTIVE: To analyze the outcomes of patients presenting with ST-segment elevation myocardial infarction (STEMI) without early (<48 hours) revascularization, according to percutaneous versus surgical revascularization. PATIENTS AND METHODS: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients seen for a STEMI in France between January 1, 2010, to June 31, 2019, who underwent either a first percutaneous coronary intervention (PCI) or a first coronary artery bypass graft between 48 hours and 90 days after the index hospitalization. Propensity score matching was used for the analysis of outcomes. RESULTS: Of 71,365 patients with STEMI in the analysis, 59,340 patients underwent PCI and 12,025 patients underwent coronary artery bypass graft. In a matched analysis of 12,012 patients by arm, surgical revascularization was associated with lower rates of all cause (5.1% vs 7.1%; hazard ratio [HR], 0.70; 95% CI, 0.66 to 0.75) and cardiovascular (2.6% vs 3.1%; HR, 0.83; 95% CI, 0.76 to 0.91) death. Rehospitalization for heart failure was less often reported after surgery (5.5% vs 7.5%; HR, 0.76; 95% CI, 0.71 to 0.81) whereas stroke incidence was not statistically different between the two arms (2.1% vs 2.3%; HR, 0.90; 95% CI, 0.80 to 1.00). Major bleeding was less often reported in the PCI arm (4.6% vs 6.1%; HR, 1.31; 95% CI, 1.22 to 1.41). CONCLUSION: In patients with STEMI who did not undergo urgent revascularization (ie, within 48 hours after presentation), surgical revascularization was associated with better outcomes and should be individually considered as an alternative to PCI.