The genetic basis of Turner syndrome aortopathy

Our goal is to identify the genetic underpinnings of bicuspid aortic valve and aortopathy in Turner syndrome. We performed whole exome sequencing on 188 Turner syndrome study subjects from the GenTAC registry. A gene‐based burden test, SKAT‐O, was used to evaluate the data using bicuspid aortic valve (BAV) and aortic dimension z‐scores as covariates. This revealed that TIMP3 was associated with BAV and increased aortic dimensions at exome‐wide significance. It had been previously shown that genes on chromosome Xp contribute to aortopathy when hemizygous. Our analysis of Xp genes revealed that hemizygosity for TIMP1, a functionally redundant paralogue of TIMP3, increased the odds of having BAV aortopathy compared to individuals with more than one TIMP1 copy. The combinatorial effect of a single copy of TIMP1 and TIMP3 risk alleles synergistically increased the risk for BAV aortopathy to nearly 13‐fold. TIMP1 and TIMP3 are tissue inhibitors of matrix metalloproteinases (TIMPs) which are involved in development of the aortic valve and protection from thoracic aneurysms. We propose that the combination of TIMP1 haploinsufficiency and deleterious variants in TIMP3 significantly increases the risk of BAV aortopathy in Turner syndrome, and suggest that TIMP1 hemizygosity may play a role in euploid male aortic disease.     

Short- and Long-Term Outcome after Emergent Cardiac Surgery during Transcatheter Aortic Valve Implantation

Objective: Our study aimed to evaluate short- and long-term outcomes of patients who required emergent conversion from transcatheter aortic valve implantation (TAVI) to open surgery. Besides, the reasons and procedural settings of emergent cardiac surgery (ECS) were also reported.Methods: We retrospectively reviewed the patients who underwent TAVI in our institution between 2012 and 2019 and collected the clinical data of cases who converted from TAVI to bail-out surgery. Telephone and outpatient follow-ups were performed.Results: Of 516 TAVI patients, 20 required ECS, and the bail-out surgery occurred less frequently with the increase in TAVI volume. The most common reason for conversion was left ventricular perforation (7/20, 35.0%). Thirty-day mortality was 35.0% in ECS patients. Kaplan–Meier survival curves showed that the cumulative survival rate was 65.0% at 1 year, 50.1% at 5 years in all ECS patients, and 77.1% at 5 years in patients who survived over 30 days after conversion.Conclusion: Although the bail-out operation was performed immediately after TAVI abortion, ECS still associated with high 30-day mortality. The long-term survival benefit was seen in patients surviving from bail-out surgery. An experienced TAVI team is of crucial importance in avoiding ECS-related life-threatening complications and providing effective salvage surgery.     

Matrix Metalloproteinase‐2 and ‐9 Levels in Patients with Dilated Ascending Aorta and Bicuspid Aortic Valve

Background: Predictors of aortic dilatation are not well‐described in patients with bicuspid aortic valve (BAV). Changes in extracellular matrix composition in the aortic wall may play an important role. Our study aimed to examine the relationship between ascending aortic dilatation and biochemical markers for collagen metabolism, such as matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) levels in patients with BAV. Methods: All patients underwent cardiac echocardiography using a standard protocol, and aortic measurements were made in end‐diastole. One hundred twelve BAV patients with no or mild valvular impairment were recruited and grouped according to the aortic dimensions corrected for body surface area (BSA) and age. There were 54 patients with dilated ascending aorta (Group 1) and 58 patients with nondilated ascending aorta (group 2). The plasma levels of MMP‐2 and MMP‐9 were determined by ELISA. Results: The mean ascending aorta diameter was 4.49 ± 0.49 mm in group 1 and 3.51 ± 0.46 mm in group 2 (P < 0.001). There were no significant difference in gender, BSA, presence of hypertension, diabetes mellitus, hyperlipidemia, and smoking between the 2 groups. Nevertheless, no significant difference was observed in the levels of MMP‐2 and MMP‐9 between the 2 groups. The ascending aorta diameter correlated significantly with age (r = 0.438 P < 0.001). No significant correlation was observed between plasma MMP‐2 and MMP‐9 concentration and ascending aorta diameter, respectively (r = ?0.005 P = 0.58, r = ?0.106 P = 0.07). Multivariate analysis showed that age was independent predictor of aortic dilatation (P ≤ 0.001). Conclusion: Age was an independent predictor of aortic dilatation in patients with BAV, whereas MMP‐2 and 9 levels were not relevant by aortic dilatation.     

Factors impacting long-term pulmonary autograft durability after the Ross procedure

Objective

Although the Ross procedure provides excellent long-term survival and a high quality of life, its use has been limited to relatively few centers. In this study, we evaluated long-term Ross procedure results in adults to assess the predictors of pulmonary autograft durability.

Open hemiarch versus clamped ascending aorta replacement for aortopathy during initial bicuspid aortic valve replacement

BackgroundThere is controversy regarding the extent of aortic resection necessary in patients with aortopathy related to bicuspid aortic valve disease. To address this issue, we reviewed our experience in patients undergoing ascending aorta replacement during bicuspid aortic valve replacement.MethodsWe reviewed 702 patients who underwent ascending aorta replacement at the time of initial nonemergent native bicuspid aortic valve replacement at our institution between January 2000 and June 2017. Treatment cohorts included an open hemiarch replacement group (n = 225; 32%) and a clamped ascending aorta replacement group (n = 477; 68%).ResultsMedian patient age was 60 years (interquartile range [IQR], 51-67 years), female sex was present in 113 patients (16%), ejection fraction was 62% (IQR, 56%-66%), and aortic arch diameter was 33 mm (IQR, 29-36 mm). Cardiopulmonary bypass time was longer in the hemiarch replacement group (188 minutes vs 97 minutes; P < .001). Procedure-related complications (36%) and mortality (<1%) were similar in the 2 groups; however, the hemiarch group had an increased odds of blood transfusion (odds ratio, 1.62; 95% confidence interval [CI], 1.15-2.28; P = .006). The median duration of follow-up was 6.0 years (95% CI, 5.3-6.8 years). Overall survival was 94 ± 1% at 5 years and 80 ± 2% at 10 years. Multivariable analysis demonstrated similar survival in the 2 groups (hazard ratio, 0.83; 95% CI, 0.51-1.33; P = .439). No repeat aortic arch operations were done for aortopathy over the duration of clinical follow-up.ConclusionsCompared with patients in the clamped ascending aorta replacement group, patients in the hemi-arch replacement group had longer cardiopulmonary bypass and aortic cross-clamp times, along with an increased risk of blood transfusion, but similar freedom from repeat aortic arch operation and survival. We identified no advantage of performing hemiarch replacement in the absence of aortic arch dilation.     

Coexisting Bicuspid Aortic and Pulmonary Valves with Normally Related Great Vessels Diagnosed by Live/Real Time Three‐Dimensional Transesophageal Echocardiography

Coexistence of bicuspid aortic and pulmonary valves in the same patient is a very rare entity identified mainly during surgery and postmortem. To the best of our knowledge, only one case has been diagnosed by two‐dimensional echocardiography in a newborn with malposition of the great arteries but no images were presented. Here, we are reporting the first case of bicuspid pulmonary and aortic valves diagnosed by live/real time three‐dimensional transesophageal echocardiography in an adult with normally related great arteries.     

Cusp Symmetry and Coronary Ostial Eccentricity and its Impact on Coronary Access Following TAVR

ObjectivesThe aim of this study was to assess cusp symmetry and coronary ostial eccentricity and its impact on coronary access following transcatheter aortic valve replacement (TAVR) using a patient-specific commissural alignment implantation technique.BackgroundTAVR implantation techniques to obtain neocommissural alignment have been introduced. The impact of cusp symmetry and coronary ostial eccentricity on coronary access after TAVR remains unknown.MethodsCardiac computed tomographic scans from 200 tricuspid aortic valves (TAVs) and 200 type 1 bicuspid aortic valves (BAVs) were studied. Cusp symmetry and coronary ostial eccentricity were assessed. In addition, the right coronary cusp/left coronary cusp and right coronary artery (RCA)/left coronary artery (LCA) ostia overlap views were calculated and compared.ResultsSevere cusp asymmetry (>135°) was more frequent in BAVs (52.5%) than in TAVs (2.5%) (P < 0.001), with the noncoronary cusp being the most common dominant cusp. The RCA ostium was found to be more often eccentric (>20°) than the LCA ostium (28% vs 6%, respectively; P < 0.001). Considering the right/left cusp overlap view, there was <20° deviation between the right coronary cusp–left coronary cusp centered line and the RCA-LCA centered line in 95% of all patients (TAV, 97%; BAV, 93%). The right/left cusp and coronary ostia overlap view differed by <10° and <20° fluoroscopic angulation in 75% and 98% of all cases, respectively.ConclusionsUsing the right/left cusp overlap view to obtain commissural alignment in TAVR is also an effective approach to implant one of the transcatheter heart valve commissures in the near center between both coronary ostia in most TAVs and type 1 BAVs. Preprocedural CT assessment remains crucial to assess cusp symmetry and coronary ostial eccentricity.     

Catheter balloon valvuloplasty of stenotic aortic valves. Part I: Anatomic basis and mechanisms of balloon dilation

Catheter balloon valvuloplasty of stenotic aortic valves has met with generally poor short- and long-term clinical results. Part of this problem resides with the lack of recognition of various etiologies of aortic stenosis. Part I of this review discusses the various etiologies of aortic stenosis and provides an anatomic basis for successful valve dilation. Results of an in vitro study indicate stenotic aortic valves are dilated by various mechanisms (cracking, stretching) based in part upon the etiology of the aortic valve stenosis.