Double-Hit Mutations in Bicuspid Aortic Valve and Blunt Traumatic Acute Aortic Dissection.

We report on a young patient with a bicuspid aortic valve operated on for type A acute aortic dissection because of a blunt thoracic trauma. Aortic root replacement and ascending aortic and total arch repair together with the postoperative course were uneventful. Multigenerational genetic analyses revealed mutations in the NOTCH1 and ACTA2 genes in the patient and his father. The screening of his parents and children revealed no bicuspid aortic valve or aortic root dilation. This exceptionally rare case of double-hit mutations and the presence of blunt trauma reveals the complex etiology of aortic dissection in patients with a bicuspid aortic valve.

Novel Association of a Familial TGFBR1 Mutation in Loeys-Dietz Syndrome with Concomitant Hematologic Malignancy.

Concomitant Loeys-Dietz syndrome (LDS) and hematologic malignancies are exceptionally rare. This is the first report of a patient operated on for aortic root dilation who had been previously diagnosed with LDS and B-cell-lymphoma. After completion of chemotherapy and complete remission, an elective valve-sparing aortic root replacement (using the David-V method) was performed. Due to the positive family history, pre-operative genetic counseling was conducted, and revealed LDS with a TGFBR1 (transforming growth factor beta receptor type I) mutation in 6 probands of the family, albeit in 1 of them posthumously. This missense mutation has been previously described in relation to aortic dissection, but a causative relationship to malignancy has so far neither been proposed nor proven.

Transforming Growth Factor Beta-2 Mutations in Barlow's Disease and Aortic Dilatation.

We report on a patient operated on for degenerative myxomatous mitral and tricuspid valve disease (Barlow's disease) and aortic root dilatation. A valve repair operation and the postoperative course were uneventful. Multigenerational genetic analyses revealed two different mutations in the transforming growth factor beta-2 gene in the same patient. The two mutations in different exons were inherited from both parents each. None of the parents presented with either valve dysfunction or aortic root dilatation. This rare case illustrates potentially common genetic and signaling pathways of concomitant myxomatous valve disease and aortic root dilatation.

Genetic abnormalities in bicuspid aortic valve root phenotype: preliminary results.

OBJECTIVES: Genetic defects associated with bicuspid aortopathy have been infrequently analysed. Our goal was to examine the prevalence of rare genetic variants in patients with a bicuspid aortic valve (BAV) with a root phenotype using next-generation sequencing technology. METHODS: We investigated a total of 124 patients with BAV with a root dilatation phenotype who underwent aortic valve ± proximal aortic surgery at a single institution (BAV database, n = 812) during a 20-year period (1995-2015). Cross-sectional follow-up revealed 63 (51%) patients who were still alive and willing to participate. Systematic follow-up visits were scheduled from March to December 2015 and included aortic imaging as well as peripheral blood sampling for genetic testing. Next-generation sequencing libraries were prepared using a custom-made HaloPlex HS gene panel and included 20 candidate genes known to be associated with aortopathy and BAV. The primary end-point was the prevalence of genetic defects in our study cohort. RESULTS: A total of 63 patients (mean age 46 ± 10 years, 92% men) with BAV root phenotype and mean post-aortic valve replacement follow-up of 10.3 ± 4.9 years were included. Our genetic analysis yielded a wide spectrum of rare, potentially or likely pathogenic variants in 19 (30%) patients, with NOTCH1 variants being the most common ( n = 6). Moreover, deleterious variants were revealed in AXIN1 ( n = 3), NOS3 ( n = 3), ELN ( n = 2), FBN1 ( n = 2) , FN1 ( n = 2) and rarely in other candidate genes. CONCLUSIONS: Our preliminary study demonstrates a high prevalence and a wide spectrum of rare genetic variants in patients with the BAV root phenotype, indicative of the potentially congenital origin of associated aortopathy in this specific BAV cohort.

Late post-AVR progression of bicuspid aortopathy: link to hemodynamics.

BACKGROUND AND AIM OF THE STUDY: The ascending aortic dilatation may progress after aortic valve replacement (AVR) in bicuspid aortic valve (BAV) patients. Our aim was to evaluate rheological flow patterns and histological characteristics of the aneurysmal aorta in BAV patients at the time of reoperative aortic surgery. MATERIALS AND METHODS: 13 patients (mean age: 42 ± 9 years, 10 (77%) male) with significant progression of proximal aortopathy after isolated AVR surgery for BAV disease (i.e., 16.7 ± 8.1 years post-AVR) were identified by cardiac phase-contrast cine magnetic resonance imaging (MRI) in our hospital. A total of nine patients (69%) underwent redo aortic surgery. Based on the MRI data, the aortic area of the maximal flow-induced stress (jet sample) and the opposite site (control sample) were identified and corresponding samples were collected intraoperatively. Histological sum-score values [i.e. aortic wall changes were graded based on a summation of seven histological criteria (each scored from 0 to 3)] were compared between these samples. RESULTS: Mean proximal aortic diameter at MRI follow-up was 55 ± 6 mm (range 47-66mm). Preoperative cardiac MRI demonstrated eccentric systolic flow pattern directed towards right-lateral/right posterior wall of the proximal aorta in 9/13 (69%) patients. Histological sum-score values were significantly higher in the jet sample vs control sample (i.e., 8.3 ± 3.8 vs 5.6 ± 2.4, respectively, p = 0.04). CONCLUSIONS: Hemodynamic factors may still be involved in the late progression of bicuspid aortopathy even after isolated AVR surgery for BAV disease.

Evidence of subannular and left ventricular morphological differences in patients with bicuspid versus tricuspid aortic valve stenosis: magnetic resonance imaging-based analysis.

Objectives: Prospective analysis of left ventricular (LV) morphological/functional parameters in patients with bicuspid versus tricuspid aortic valve (TAV) stenosis undergoing aortic valve replacement (AVR) surgery. Methods: A total of 190 consecutive patients with BAV ( n = 154) and TAV stenosis ( n = 36) (mean age 61 ± 8 years, 65% male) underwent AVR ± concomitant aortic surgery from January 2012 through May 2015. All patients underwent preoperative cardiac magnetic resonance imaging in order to evaluate: (i) left ventricular outflow tract (LVOT) dimensions, (ii) length of anterior mitral leaflet (AML), (iii) end-systolic and end-diastolic LV wall thickness, (iv) LV area, (v) LV end-systolic and end-diastolic diameters (LVESD, LVEDD), (vi) LV end-diastolic and end-systolic volumes (LVEDV, LVESV) and (vii) maximal diameter of aortic root. These parameters were compared between the two study groups. Results: The LVOT diameter was significantly larger in BAV patients (21.7 ± 3 mm in BAV vs 18.9 ± 3 mm in TAV, P < 0.001). Moreover, BAV patients had significantly longer AML (24 ± 3 mm in BAV vs 22 ± 4 mm in TAV, P = 0.009). LVEDV and LVESV were significantly larger in BAV patients (LVEDV: 164.9 ± 68.4 ml in BAV groups vs 126.5 ± 53.1 ml in TAV group, P = 0.037; LVESV: 82.1 ± 57.9 ml in BAV group vs 52.9 ± 25.7 ml in TAV group, P = 0.008). A strong linear correlation was found between LVOT diameter and aortic annulus diameter in BAV patients ( r = 0.7, P < 0.001), whereas significantly weaker correlation was observed in TAV patients ( r = 0.5, P = 0.006, z = 1.65, P = 0.04). Presence of BAV morphology was independently associated with larger LVOT diameters (OR 9.0, 95% CI 1.0-81.3, P = 0.04). Conclusions: We found relevant differences in LV morphological/functional parameters between BAV and TAV stenosis patients. Further investigations are warranted in order to determine the cause of these observed differences.

Mitral regurgitation after previous aortic valve surgery for bicuspid aortic valve insufficiency.

BACKGROUND: Regurgitant bicuspid aortic valves (BAV) are reported to be associated with myxomatous degeneration of the anterior mitral leaflet. We examined the risk of late new-onset mitral regurgitation (MR) in patients who underwent aortic valve/aortic root surgery for BAV regurgitation and concomitant root dilatation. METHODS: A total of 97 consecutive patients (47±11 years, 94% men) were identified from our institutional BAV database (N.=640) based on the following criteria: 1) BAV regurgitation; 2) aortic root diameter >40 mm; 3) no relevant mitral valve disease (i.e., MR<2+) and no simultaneous mitral intervention at the time of BAV surgery. All patients underwent isolated aortic valve replacement (AVR subgroup, N.=59) or aortic root replacement with a composite graft (i.e., for root aneurysm >50 mm) (ARR subgroup, N.=38) from 1995 through 2008. Echocardiographic follow-up (1009 patient-years) was obtained for all 96 (100%) hospital survivors. The primary endpoint was freedom from new-onset MR>2+ and redo mitral valve surgery. RESULTS: Nine patients (9.4%) showed new-onset MR>2+ after mean echocardiographic follow-up of 10.4±4.0 years postoperatively. Myxomatous degeneration and prolapse of the anterior mitral leaflet was found in all 9 patients, and the posterior leaflet was involved in 3 of them. Two patients (2%) in AVR subgroup underwent re-do mitral surgery. No MR>2+ occurred in ARR subgroup. Freedom from MR>2+ or mitral surgery at 15 years was significantly lower in AVR subgroup vs. ARR subgroup (i.e., 38% vs. 100%, P=0.01). CONCLUSIONS: The risk of new-onset MR is significantly increased in patients with BAV regurgitation and aortic root dilatation who undergo isolated AVR rather than root replacement. The mechanism by which aortic root replacement may prevent the occurrence of late MR in BAV root phenotype patients is to be determined.

Pathophysiological Factors Associated with Left Ventricular Perforation in Transcatheter Aortic Valve Implantation by Transfemoral Approach.

BACKGROUND AND AIM OF THE STUDY: Left ventricular (LV) perforation is one of the rare and most serious complications of transcatheter aortic valve implantation (TAVI). The study aim was to determine the pathophysiological factors associated with this serious complication. METHODS: A retrospective study was conducted of pathophysiological factors shown in echocardiograms and computed tomography angiograms performed preoperatively in patients who developed LV perforation during transfemoral TAVI (study group) with regards to anatomic and functional variables. Results were then compared with data acquired from a randomly selected sample of patients without perforation (control group). Among 963 TAVI cases, LV perforation occurred in 11 patients (three males, eight females; mean age 79 years). These patients showed complications of LV perforation that required emergency sternotomy and repair of injury to the left ventricle. Ten patients were rescued by the procedure, but one patient died during surgery. RESULTS: Focus on preoperative factors and intraoperative steps was established in favor to identify possible predictors of LV perforation. A LV cavity size <4.2 cm and a hypercontractile ventricle were identified in 10 patients (90%). Only one patient had a dilated cardiomyopathic left ventricle, with a cavity size of 6.1 cm and an ejection fraction of 10%. The present study results revealed other specific patient-related factors, namely a narrow aorto-mitral angle and a thin ventricular muscular wall despite long-standing aortic stenosis. All 11 patients had an average mid-LV muscular wall thickness of 5 mm. An inverse proportional relationship between the aorto-mitral angle and the incidence of perforation was noted, where in all 11 patients the wire had directed itself towards the anterior free wall of the left ventricle, where it induced injury. CONCLUSIONS: A small LV cavity, a hypercontractile state, a thin muscular wall, and a narrow aorto-mitral angle may be considered potential predictors of the occurrence of LV perforation during TAVI.

Morphologic and Functional Markers of Aortopathy in Patients With Bicuspid Aortic Valve Insufficiency Versus Stenosis.

BACKGROUND: Bicuspid aortic valve (BAV)-associated aortopathy is heterogeneous and still insufficiently defined. We prospectively analyzed the morphologic and functional variables of aortopathy in patients undergoing operations for BAV insufficiency (BAV-AI) vs stenosis (BAV-AS). METHODS: A total of 172 consecutive patients (71% male, 59 ± 10 years) underwent aortic valve replacement with or without proximal aortic operation for BAV-AS (n = 137), and BAV-AI (n = 35) from January 2012 through December 2014. All patients underwent preoperative cardiac magnetic resonance imaging to evaluate morphologic and functional variables of the aortic root. Magnetic resonance imaging data were used to guide sampling of aortic tissue intraoperatively (ie, from the area where flow jet impacts on the aortic wall [jet sample] and the opposite aortic wall [control sample]). Aortic wall lesions were graded based on the histologic sum score (range, 0 to 21). Expression and severity of aortopathy were quantified by means of proximal aortic phenotype, indexed aortic diameters, and a sum score. RESULTS: Cross-sectional aortic diameters were significantly larger in the BAV-AI group vs the BAV-AS group (47 ± 8 mm vs 41 ± 8 mm, p = 0.001). Moreover, root dilatation phenotype was more frequent in the BAV-AI group (27% vs 6%, p = 0.01) and was associated with a significantly larger aortic annulus diameter (32 ± 3 mm vs 27 ± 3 mm, p < 0.001). The histologic sum score was significantly different between the study groups (3.7 ± 2.6 BAV-AI vs 2.5 ± 1.4 BAV-AS, p = 0.03). Logistic regression revealed a significant association between BAV-AI and indexed aortic diameter exceeding 22 mm/m2 (odds ratio, 4.7; p = 0.007). CONCLUSIONS: Our study demonstrates that BAV functional phenotype correlates significantly with the expression and severity of bicuspid aortopathy.

Aortopathy in Bicuspid Aortic Valve Stenosis with Fusion of Right-Left versus Right-Non-Coronary Cusps: Are These Different Diseases?

BACKGROUND: The study aim was to prospectively analyze the impact of cusp fusion pattern on aortopathy severity in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. METHODS: A total of 137 consecutive patients with BAV stenosis (93 males, 44 females; mean age 61 ± 9 years) underwent aortic valve replacement with or without concomitant aortic surgery between January 2012 and March 2015. All patients underwent preoperative cardiac magnetic resonance imaging (cMRI) in order to evaluate morphological/functional parameters of the aortic root. Fusion of the right-left coronary cusps was identified in 99 patients (72%) (R/L group), while the remaining 38 patients (28%) had right-noncoronary cusp fusion (R/N group). cMRI data were used to guide sampling of the proximal aorta during surgery. The expression/severity of aortopathy was quantified by means of proximal aortic phenotype, indexed aortic diameter, and a histological sum-score. RESULTS: There were no significant differences in proximal aortic diameter between the R/L and R/N groups. Moreover, there was no significant difference in the prevalence of distinct aortic phenotypes between the study subgroups. The histological sumscore was comparable between the R/L and R/N groups (2.9 ± 1.5 versus 2.5 ± 1.1, p = 0.2). The angle LV/aorta was significantly larger in the R/L group than in the R/N group (52.1 ± 10.6° versus 45.1 ± 8.5°, p = 0.001). Logistic regression analysis demonstrated the angle LV/aorta and the angle jet/aorta to be predictive of a mid-ascending phenotype. The cusp fusion pattern had no significant impact on the occurrence of aortic phenotype. CONCLUSIONS: The study results demonstrated that cusp fusion morphotype has no significant impact on the expression and severity of bicuspid aortopathy in patients undergoing surgery for BAV stenosis.

Unusual Case of Overt Aortic Dissection Mimicking Aortic Intramural Hematoma.

We report an interesting case in which overt aortic dissection mimicked two episodes of aortic intramural hematoma (IMH) (Stanford A, DeBakey I). This took place over the course of four days and had a major influence on the surgical treatment strategy. The first episode of IMH regressed completely within 15 hours after it was clinically diagnosed and verified using imaging techniques. The recurrence of IMH was detected three days thereafter, resulting in an urgent surgical intervention. Overt aortic dissection with evidence of an intimal tear was diagnosed intraoperatively.

Functional Aortic Root Parameters and Expression of Aortopathy in Bicuspid Versus Tricuspid Aortic Valve Stenosis.

BACKGROUND: The correlation between bicuspid aortic valve (BAV) disease and aortopathy is not fully defined. OBJECTIVES: This study aimed to prospectively analyze the correlation between functional parameters of the aortic root and expression of aortopathy in patients undergoing surgery for BAV versus tricuspid aortic valve (TAV) stenosis. METHODS: From January 1, 2012 through December 31, 2014, 190 consecutive patients (63 ± 8 years, 67% male) underwent aortic valve replacement ± proximal aortic surgery for BAV stenosis (n = 137, BAV group) and TAV stenosis (n = 53, TAV group). All patients underwent pre-operative cardiac magnetic resonance imaging to evaluate morphological/functional parameters of the aortic root. Aortic tissue was sampled during surgery on the basis of the location of eccentric blood flow contact with the aortic wall, as determined by cardiac magnetic resonance (i.e., jet sample and control sample). Aortic wall lesions were graded using a histological sum score (0 to 21). RESULTS: The largest cross-sectional aortic diameters were at the mid-ascending level in both groups and were larger in BAV patients (40.2 ± 7.2 mm vs. 36.6 ± 3.3 mm, respectively, p < 0.001). The histological sum score was 2.9 ± 1.4 in the BAV group versus 3.4 ± 2.6 in the TAV group (p = 0.4). The correlation was linear and comparable between the maximum indexed aortic diameter and the angle between the left ventricular outflow axis and aortic root (left ventricle/aorta angle) in both groups (BAV group: r = 0.6, p < 0.001 vs. TAV group r = 0.45, p = 0.03, z = 1.26, p = 0.2). Logistic regression identified the left ventricle/aorta angle as an indicator of indexed aortic diameter >22 mm/m(2) (odds ratio: 1.2; p < 0.001). CONCLUSIONS: Comparable correlation patterns between functional aortic root parameters and expression of aortopathy are found in patients with BAV versus TAV stenosis.

Are normal-sized ascending aortas at risk of late aortic events after aortic valve replacement for bicuspid aortic valve disease?

OBJECTIVES: Bicuspid aortic valve (BAV)-associated aortopathy has been proposed to progress after isolated aortic valve replacement (AVR) surgery, which has been traditionally used as an argument against a TAVR procedure in this clinical subset. Still, more than half of BAV patients have a normal-sized proximal aorta at the time of AVR surgery. We aimed to analyse the long-term risk of adverse aortic events after isolated conventional AVR surgery for BAV and normal-sized proximal aorta. METHODS: A total of 200 consecutive patients (mean age 56 ± 13 years, 73% men) with BAV disease and ascending aortic diameter of <40 mm underwent isolated conventional AVR from 1995 through 2008 and were identified from our institutional BAV database. Long-term follow-up data (a total of 1532 patient-years) were obtained for all hospital survivors. Composite adverse aortic/cardiovascular events were defined as the need for redo aortic surgery, the occurrence of aortic dissection/rupture, or sudden cardiac death during follow-up. RESULTS: A total of 25 (13%) patients died after a mean follow-up of 8.5 ± 5 years post-AVR surgery, which resulted in an overall survival rate of 75 ± 6 and 87 ± 7% at 15 years postoperatively, for BAV-aortic stenosis and BAV-aortic regurgitation, respectively (P = 0.6). An adverse aortic event occurred in 1 (0.5%) study patient, while 5 (2.5%) further patients suffered sudden cardiac death. Only 1 patient required redo aortic surgery. No documented aortic dissection/rupture occurred. Redo AVR surgery due to endocarditis or structural valve degeneration was performed in 6 (3%) patients. The rate of freedom from composite adverse events was 92 ± 5 and 95 ± 4% at 15 years, for the AS and AR subgroups, respectively (P = 0.7). CONCLUSIONS: BAV patients with aortic valve dysfunction and normal-sized ascending aorta are at considerably low risk of late adverse aortic events after isolated AVR.

The fate of mild-to-moderate proximal aortic dilatation after isolated aortic valve replacement for bicuspid aortic valve stenosis: a magnetic resonance imaging follow-up study†.

OBJECTIVES: The treatment of mild-to-moderate aortic dilatation at the time of aortic valve replacement (AVR) in patients with bicuspid aortic valve (BAV) disease is still controversial. We aimed to estimate late progression of aortopathy in patients who underwent isolated AVR for BAV stenosis with concomitant proximal aortic dilatation of ≥40 mm. METHODS: The review of our institutional BAV database (n = 510) revealed a subgroup of 96 consecutive BAV patients (57 ± 10 years, 78% male) with BAV stenosis and concomitant ascending aortic dilatation of ≥40 mm [i.e. as defined by magnetic resonance imaging (MRI)/computed tomography (CT)], who underwent isolated AVR from 1995 to 2006. Aortic diameters were quantified by preoperative MRI/CT in all patients (i.e. all cases without MRI/CT were excluded). Moreover, we excluded all cases of simultaneous aortic surgery. MRI/CT follow-up (855 patient-years) was obtained in 83 (87%) patients. Study end-points were progression of proximal aortic diameters (mm/patient-year) and prevalence of aortic events (sudden death, aortic dissection and aortic surgery). RESULTS: MRI/CT follow-up (mean 10.3 ± 3.8 years post-AVR) revealed no significant progress of maximal cross-sectional aortic diameters (i.e. 46.4 ± 4.4 mm pre-AVR vs 46.9 ± 4.6 mm post-AVR, P = 0.1). Aortic diameters were identical in 54 (65%) patients. The mean progression rate of maximal cross-sectional aortic diameter was 0.09 mm/patient-year for the whole study cohort, whereas diameter increase of ≥5 mm was revealed in 1 (1%) patient. No aortic dissection occurred. Five (5%) patients underwent redo aortic surgery for aneurysm, whereas 3 of them had aortic diameters identical to pre-AVR. CONCLUSIONS: Mild-to-moderate ascending aortic dilatation remains stable in most BAV patients who underwent isolated AVR surgery for aortic valve stenosis at least 10-year post-AVR.

Aortopathy in patients with bicuspid aortic valve stenosis: role of aortic root functional parameters.

OBJECTIVES: We prospectively examined functional characteristics of the aortic root and transvalvular haemodynamic flow in order to define factors associated with the severity of aortopathy in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. METHODS: A total of 103 consecutive patients with BAV stenosis (mean age 61 ± 9 years, 66% male) underwent aortic valve replacement ± concomitant aortic surgery from January 2012 through March 2014. All patients underwent preoperative cardiac magnetic resonance imaging (MRI) in order to evaluate the systolic transvalvular flow and the following functional parameters: (i) angulation between the left ventricular outflow axis and the aortic root, (ii) geometrical orientation of residual aortic valve orifice and (iii) BAV cusp fusion pattern. MRI data were used to guide sampling of the ascending aorta during surgery [i.e. jet-sample from the area where the flow-jet impacts on the aortic wall and control sample from the opposite aortic wall (obtained from the aortotomy site)]. Aortopathy was quantified by means of a histological sum-score (0 to 21+) in each sample. RESULTS: A significant correlation was found between histological sum-score in the jet-sample and the angle between the LV outflow axis and the aortic root (r = 0.6, P = 0.007). Moreover, there was a linear correlation between proximal aortic diameter and the angle between systolic flow-jet and ascending aortic wall (r = 0.5, P = 0.006). Logistic regression identified the angle between the LV outflow axis and the aortic root (OR 1.1, P = 0.04) and the angle between the flow-jet and the aortic wall (OR 1.2, P = 0.001) as independent predictors of an indexed proximal aortic diameter ≥22 mm/m(2). CONCLUSIONS: Functional parameters of the aortic root may be used to predict the severity of aortopathy in patients with BAV stenosis, and may be useful in predicting future risk of aortic disease in such patients.

Long-Term Recovery of Reduced Left Ventricular Ejection Fraction after Aortic Valve Replacement in Patients with Bicuspid Aortic Valve Disease.

Background Long-term prognosis of patients with bicuspid aortic valve (BAV) disease and poor left ventricular ejection fraction (LVEF) who underwent aortic valve replacement (AVR) is unknown. We aimed to analyze the recovery of LVEF and incidence of adverse events after AVR in patients with BAV and poor LVEF. Materials and Methods A total of 90 consecutive BAV patients (mean age 57 ± 10 years, 89% male) with baseline LVEF ≤40% underwent an isolated AVR between January 1, 1995, and June 30, 2008, and served as our study population. Follow-up data (800 patient-years) were obtained for all 90 hospital survivors. A subgroup of patients who underwent AVR for BAV stenosis (Group aortic stenosis [AS], n = 70) was compared with those who underwent AVR for BAV regurgitation (Group aortic regurgitation [AR], n = 20). Primary end point was the recovery of LVEF in AS Group versus AR Group. Secondary end points were survival and freedom from adverse cardiac events (i.e., cardiac-related death and need for reinterventions due to persisting heart failure). Results There was a significant increase in LVEF (mean follow-up 9.0 ± 5 years) in AS versus AR Group (i.e., 32 ± 7% [baseline] and 53 ± 9% [follow-up], p < 0.001 in AS Group vs. 33 ± 7% [baseline] and 38 ± 13% [follow-up], p = 0.07 in AR Group). Recovery rate of LVEF was significantly higher in AS Group versus AR Group (i.e., 2.8 percentage points (pp)/year vs. 0.7 pp/year, respectively). In Group AS, 86% of patients were responders, whereas in Group AR, only 30% (p < 0.001). The subjects in Group AR did not show a difference between baseline and follow-up left ventricular end-diastolic diameter (LVEDD) (baseline 61 ± 12 vs. follow-up 58 ± 8, p = 0.813), whereas in Group AS, there was a significant difference of LVEDD (baseline 56 ± 7 vs. follow-up 54 ± 6 mm, p = 0.019). Ten-year survival was 76 ± 6.5% in AS Group versus 78 ± 11% in AR Group (p = 0.3). Prevalence of late adverse cardiac events was 7% in AS Group versus 40% in AR Group (p = 0.03). Conclusion The recovery of reduced LVEF after AVR surgery is significantly impaired in patients with BAV regurgitation as compared with BAV stenosis.

Aortic events after isolated aortic valve replacement for bicuspid aortic valve root phenotype: echocardiographic follow-up study.

OBJECTIVES: Various forms of bicuspid aortic valve (BAV) aortopathy exist, and the optimal treatment for the different subgroups is insufficiently defined. We aimed to analyse the risk of adverse aortic events after aortic valve replacement (AVR) for BAV insufficiency and concomitant mild-to-moderate dilatation of the aortic root (i.e. BAV root phenotype). METHODS: A total of 56 consecutive patients (mean age 47 ± 11 years, 95% men) with BAV insufficiency and a root diameter of 40-50 mm underwent AVR surgery from 1995 to 2008. All patients, as identified from our institutional BAV database, had a dilated aortic annulus (i.e. defined as valve prosthesis size ≥27 mm) without aortic stenosis (i.e. mean gradient ≤20 mmHg). Patients who underwent concomitant aortic surgery were excluded. Follow-up (622 patient-years) including echocardiography data was available for all patients. Aortic events were defined as the need for proximal aortic surgery, the occurrence of aortic dissection/rupture, echocardiographic evidence of increasing aortic root diameter/occurrence of late paravalvular leakage or sudden death during follow-up. RESULTS: Actuarial survival was 90% at 10 years and 78% at 15 years. Adverse aortic events occurred in 19 (34%) study patients. Redo aortic surgery was performed in 6 patients (11%), 2 of which were for aortic dissection. Four patients (7%) suffered sudden cardiac death. Moreover, follow-up echocardiography revealed a significant, progressive enlargement of the aortic root diameter in 7 (13%) patients and occurrence of late de novo paravalvular leakage in 2 (3%) patients. The resultant freedom from aortic events was 81% at 10 years and 51% at 15 years. CONCLUSIONS: Patients with a BAV root phenotype are at significant risk of aortic events after isolated AVR. Simultaneous root/ascending aortic surgery should be strongly considered in such patients.

Correlation between systolic transvalvular flow and proximal aortic wall changes in bicuspid aortic valve stenosis.

OBJECTIVES: The purpose of this study was to analyse the correlation between preoperative systolic transvalvular flow patterns and proximal aortic wall lesions in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. METHODS: A total of 48 consecutive patients with BAV stenosis (mean age 58 ± 9 years, 65% male) underwent aortic valve replacement (AVR) ± proximal aortic surgery from January 2012 through February 2013. Preoperative cardiac phase-contrast cine magnetic resonance imaging (MRI) assessment was performed in all patients in order to detect the area of maximal flow-induced stress in the proximal aorta. Based on these MRI data, two aortic wall samples (i.e. area of the maximal stress (jet sample) and the opposite aortic wall (control sample)) were collected during AVR surgery. Aortic wall changes were graded based on a summation of seven histological criteria (each scored from 0 to 3). Histological sum score (0-21) was separately calculated and compared between the two aortic samples (i.e. jet sample vs control sample). RESULTS: An eccentric transvalvular flow jet hitting the proximal aortic wall could be identified in all 48 (100%) patients. The mean histological sum score was significantly higher in the jet sample vs control sample areas of the aorta (i.e. 4.1 ± 1.8 vs 2.2 ± 1.5, respectively) (P = 0.02). None of the patients had a higher sum score value in the control sample. CONCLUSIONS: Our study demonstrates a strong correlation between the systolic pattern of the transvalvular flow jet and asymmetric proximal aortic wall changes in patients undergoing AVR for BAV stenosis.

Risk of proximal aortic dissection in patients with bicuspid aortic valve: how to address this controversy?

The risk of acute aortic events in patients with bicuspid aortic valve (BAV) disease is a controversial issue. The real risk of aortic dissection in patients with BAV disease is unknown. An indirect assessment of this risk, however, could be gained with a more detailed understanding of the pathogenesis of BAV aortopathy. There are two major issues that should be clarified before one addresses the question of aortic dissection risk in BAV patients. The first issue, when analysing the data from previous BAV cohorts, is to determine what stage of BAV disease was present in the described patient population. In particular, was the risk of aortic dissection in BAV patients determined before or after aortic valve replacement (AVR) surgery? The second issue to consider is the functional state of the pathological valve within the observed population. In particular, did patients predominantly suffer from BAV stenosis or BAV insufficiency? Unfortunately, the vast majority of published reports do not separate between the different BAV phenotypes, thereby complicating interpretation of the results. Considering these two important clinical variables (i.e. the stage of BAV disease and the functional phenotype), we herein aim to explain the inconsistency of the published data with regard to the risk of aortic dissection in patients with BAV disease.