Pre- and postoperative left atrial and ventricular volumetric and deformation analyses in severe aortic regurgitation.

BACKGROUND: The impact of volume overload due to aortic regurgitation (AR) on systolic and diastolic left ventricular (LV) indices and left atrial remodeling is unclear. We assessed the structural and functional effects of severe AR on LV and left atrium before and after aortic valve replacement. METHODS: Patients with severe AR scheduled for aortic valve replacement (n = 65) underwent two- and three-dimensional echocardiography, including left atrial strain imaging, before and 1 year after surgery. A control group was selected, and comprised patients undergoing surgery for thoracic aortic aneurysm without aortic valve replacement (n = 20). Logistic regression analysis was used to assess predictors of impaired left ventricular functional and structural recovery, defined as a composite variable of diastolic dysfunction grade ≥ 2, EF < 50%, or left ventricular end-diastolic volume index above the gender-specific normal range. RESULTS: Diastolic dysfunction was present in 32% of patients with AR at baseline. Diastolic LV function indices and left atrial strain improved, and both left atrial and LV volumes decreased in the AR group following aortic valve replacement. Preoperative left atrial strain during the conduit phase added to left ventricular end-systolic volume index for the prediction of impaired LV functional and structural recovery after aortic valve replacement (model p < 0.001, accuracy 70%; addition of left atrial strain during the conduit phase to end-systolic volume index p = 0.006). CONCLUSIONS: One-third of patients with severe AR had signs of diastolic dysfunction. Aortic valve surgery reduced LV and left atrial volumes and improved diastolic indices. Left atrial strain during the conduit phase added to the well-established left ventricular end-diastolic dimension for the prediction of impaired left ventricular functional and structural recovery at follow-up. However, long-term follow-up studies with hard endpoints are needed to assess the value of left atrial strain as predictor of myocardial recovery in aortic regurgitation.

Aortic dimensions in relation to bicuspid and tricuspid aortic valve pathology.

BACKGROUND AND AIM OF THE STUDY: The relationship between aortic valve pathology and the aortic root and ascending aortic dimensions in cardiac surgery patients is unclear, and its clarification was the objective of this study. METHODS: The severity of valve pathology, whether aortic valve stenosis (AS) or aortic valve regurgitation (AR), and the aortic dimensions (aortic root and ascending aorta) were prospectively evaluated with echocardiography in 500 consecutive patients with tricuspid aortic valve (TAV) or bicuspid aortic valve (BAV) who had undergone surgery due to aortic valve and/or ascending aortic disease. RESULTS: The distribution of valve pathology was similar in TAV and BAV patients when the aorta was non-dilated. However, when the aorta was dilated, AS was seen predominantly in BAV patients (n = 76) compared to TAV patients (n = 2). In TAV and BAV patients with non-dilated aortas, an increased severity of valve pathology was associated with smaller dimensions of the aortic root and the ascending aorta. In TAV and BAV patients with dilated aortas, an increase in the severity of AR was associated with a decreasing dimension of the ascending aorta but an increasing dimension of the aortic root. In BAV patients with aneurysm, the severity of AS was associated with a decreased dimension of the aortic root and the ascending aorta. CONCLUSION: Patients with AS and ascending aortic dilatation almost exclusively have a BAV. An increasing severity of valve pathology was related to decreasing dimensions of the aortic root and the ascending aorta, and the pattern was strikingly similar in TAV and BAV patients. The high frequency of ascending aortic dilatations in BAV patients cannot be explained by the valve pathology.

Impaired splicing of fibronectin is associated with thoracic aortic aneurysm formation in patients with bicuspid aortic valve.

OBJECTIVE: Thoracic aortic aneurysm is a common complication in patients with bicuspid aortic valve (BAV). Alternatively spliced extra domain A (EDA) of fibronectin (FN) has an essential role in tissue repair. Here we analyze the expression of FN spliceforms in dilated and nondilated ascending aorta of tricuspid aortic valve (TAV) and BAV patients. METHODS AND RESULTS: The mRNA expression was analyzed in the ascending aorta by Affymetrix Exon arrays in patients with TAV (n=40) and BAV (n=69). EDA and extra domain B (EDB) expression was increased in dilated aorta from TAV patients compared with nondilated aorta (P<0.001 and P<0.05, respectively). In contrast, EDA expression was not increased in dilated aorta from BAV patients (P=0.25), whereas EDB expression was upregulated (P<0.01). The expression of EDA correlated with maximum aortic diameter in TAV (ρ=0.58) but not in BAV (ρ=0.15) patients. Protein analyses of EDA-FN showed concordant results. Transforming growth factor-ß treatment influenced the splicing of FN and enhanced the formation of EDA-containing FN in cultured medial cells from TAV patients but not in cells derived from BAV patients. Gene set enrichment analysis together with multivariate and univariate data analyses of mRNA expression suggested that differences in the transforming growth factor-ß signaling pathway may explain the impaired EDA inclusion in BAV patients. CONCLUSIONS: Decreased EDA expression may contribute to increased aneurysm susceptibility of BAV patients.

Laser Doppler Measurements of Systolic Blood Pressure on the First and Second Toe in Patients with Peripheral Arterial Disease.

Laser Doppler was used to measure toe blood pressure (TBP) in 40 consecutive patients with various degree of peripheral arterial disease. The aim of this methodological study was to increase the usefulness of TBP by exploring the interchangeability between TBP from the first and second toe and by investigating daily routine reproducibility and measurement variability. According to our study design pressure values were based on three measurements that were averaged. At simultaneous measurements, TBP of the first toe was 71 mm Hg (standard deviation [SD] 25) compared with 70 mm Hg (SD 25) on the second toe. The correlation ( r ) between first and second toe pressure measurements was 0.84 and intraclass correlation coefficient (ICC) was 0.84. The difference between TBP on the first and second toe was not related to gender, diabetes, or magnitude of the pressures. Repeated TBP measurements of the right first toe after disconnection of cuffs, 5 to 10 minutes rest, and reconnection of cuffs had a coefficient of variation (CV) of 9% and an ICC of 0.93. CV for toe-brachial index (TBI) was 8%. Our results show that measurements of TBP from the second toe to a large extent are interchangeable with those assessed from the first toe and can be used in clinical situations where measurements from the first toe are not feasible. Flow detection with three averaged laser Doppler measurements generates TBP and TBI with low variability.

Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study.

Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (<4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.

Circumferential strain by velocity vector imaging and speckle-tracking echocardiography: validation against sonomicrometry in an aortic phantom.

BACKGROUND: Evaluation of arterial deformation and mechanics using strain analysis on ultrasound greyscale images has gained increasing scientific interest. The aim of this study was to validate in vitro measurements of circumferential strain by velocity vector imaging (VVI) and speckle-tracking echocardiography (STE) against sonomicrometry as a reference method. METHOD: Two polyvinyl alcohol phantoms sized to mimic the descending aorta were constructed and connected to a pulsatile flow pump to obtain high-resistance flow profiles. The ultrasound images of the phantom used for strain analyses were acquired with a transesophageal probe. Global and regional circumferential strains were estimated using VVI and STE and were compared with the strain acquired by sonomicrometry. RESULTS: Global circumferential peak strain estimated by VVI and STE correlated well to sonomicrometry (r = 0·90, P≤0·001; and r = 0·97, P≤0·01) with a systematic bias of -0·78% and +0·63%, respectively. The reference strain levels were 1·07-2·54%. Circumferential strain values obtained by VVI were significantly lower than those obtained by STE (bias -1·41%, P≤0·001). CONCLUSION: Global circumferential strain measured by VVI and STE correlates well with sonomicrometry. However, strain values obtained by VVI and STE differ significantly, which should be taken into consideration when comparing results from studies using different software for aortic strain measurements.

Aortic versus carotid intima-media thickness and impact of aortic valve disease.

BACKGROUND AND AIMS: Intima-media thickness is a marker for atherosclerosis but is also influenced by shear stress and flow. We evaluated the relation between intima-media thickness of the descending aorta (AoIMT) and the common carotid artery (CIMT) in patients with and without severe aortic valve disease (sAVD). METHODS: A total of 310 patients (233 with sAVD, 77 without) were examined with regard to AoIMT and CIMT using transesophageal echocardiography and carotid ultrasound, respectively, before valvular and/or aortic surgery. Digitally stored B-mode images were used for semiautomatic AoIMT and CIMT measurements. RESULTS: There were no significant differences in patients with or without sAVD with regard to AoIMT (1·35 ± 0·31 vs. 1·35 ± 0·33 mm) or CIMT (0·80 ± 0·15 vs. 0·78 ± 0·16 mm). The correlations between AoIMT and CIMT were r = 0·29 in patients with and r = 0·51 in patients without sAVD, and the difference between these correlations was significant (P<0·05). In multivariate regression, age was the main determinant for AoIMT and CIMT in both groups, further in sAVD, the aortic mean pressure gradient (Pmean ) was a determinant of AoIMT, but not of CIMT. CONCLUSIONS: The correlation between CIMT and AoIMT is weaker in patients with sAVD compared to those without sAVD. Pmean is also a significant predictor of AoIMT, but not of CIMT. This implies that, in addition to the atherosclerotic process, turbulent aortic flow or altered blood flow helicity created by large stroke volumes and diastolic flow reversal or high-velocity jets, affect the intima-media of the descending aorta and common carotid artery differently.

Intima-media thickness of the descending aorta in patients with bicuspid aortic valve.

OBJECTIVE: A bicuspid aortic valve (BAV) is associated with accelerated aortic valve disease (AVD) and abnormalities in aortic elasticity. We investigated the intima-media thickness of the descending aorta (AoIMT) in patients with AVD with or without an ascending aortic aneurysm (AscAA), in relation to BAV versus tricuspid aortic valve (TAV) phenotype, type of valve disease, cardiovascular risk factors, and single-nucleotide polymorphisms (SNPs) with a known association with carotid IMT. METHODS AND RESULTS: 368 patients (210 with BAV, 158 with TAV,); mean age 64 ± 13 years) were examined using transesophageal echocardiography (TEE) before valvular and/or aortic surgery. No patient had a coronary disease (CAD). The AoIMT was measured on short-axis TEE images of the descending aorta using a semi-automated edge-detection technique. AoIMT was univariately (P < 0.05) related to age, blood pressure, smoking, creatinine, highly sensitive C-reactive protein, HDL, valve hemodynamics and BAV. In the TAV subgroup it was also associated with the rs200991 SNP. Using multivariate regression analysis, age was the main determinant for AoIMT (P < 0.001), followed by male gender (P = 0.02), BAV was no longer a significant predictor of AoIMT. AoIMT was still related to the rs200991 SNP in TAV (P = 0.034), and to creatinine in BAV (P = 0.019), when other variables were accounted for. CONCLUSIONS: Intima-media thickness of the descending aorta is not affected by aortic valve morphology (BAV/TAV); age is the main determinant of AoIMT. Genetic markers (SNPs) known to influence IMT in the carotid artery seem to correlate to IMT in the descending aorta only in patients with TAV.

Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves.

Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.

Aortic valve type and calcification as assessed by transthoracic and transoesophageal echocardiography.

INTRODUCTION: Aortic valve calcification (AVC) may predict poor outcome. Bicuspid aortic valve (BAV) leads to several haemodynamic changes accelerating the progress of aortic valve (AV) disease. AIMS: To compare the diagnostic accuracy of transoesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) in the assessment of aortic valve phenotype and degree of AVC, with intra-operative evaluation as a reference. METHODS: We examined 169 patients (median age 65 years, 51 women) without significant coronary artery disease undergoing AV and/or aortic root surgery. TTE was performed within a week prior to surgery and TEE at the time of surgery. RESULTS: Compared with surgical AVC assessment, visual evaluation using a 5-grade scoring system and real-time images showed a higher correlation (TTE r = 0·83 and TEE r = 0·82) than visual (TTE r = 0·64 and TEE 0·63) or grey scale mean (GSMn) (TTE r = 0·63 and TEE r = 0·52) assessment of end-diastolic still frames. AVC assessment using real-time images showed high intraclass correlation coefficients (TTE 0·94 and TEE 0·93). With regard to BAV, TEE was superior to TTE with a higher interobserver agreement, sensitivity and specificity (0·86, 92% and 94% versus 0·57, 77% and 82%, respectively). CONCLUSION: Semi-quantitative AVC assessment of real-time cine loops from both TEE and TTE correlated well with intra-operative evaluation of AVC. Applying a predefined scoring system for AVC evaluation assures a high interobserver correlation. TEE was superior to TTE for evaluation of valve phenotype and should be considered when a diagnosis of BAV is clinically important.

Elastic properties of the descending aorta in patients with a bicuspid or tricuspid aortic valve and aortic valvular disease.

BACKGROUND: The aim of this study was to explore possible differences in aortic strain, distensibility, and stiffness in the descending thoracic aorta between patients with bicuspid aortic valves (BAVs) and those with tricuspid aortic valves (TAVs) in relation to type of aortic valve disease and known cardiovascular risk factors. METHODS: Transesophageal echocardiography was used to examine 288 patients (mean age, 64 ± 13 years) in the operating room before surgery. The transesophageal echocardiographic images were analyzed offline using Velocity Vector Imaging software. One hundred forty patients had isolated severe aortic stenosis (AS) (89 of those with BAVs, 51 of those with TAVs), and 52 patients had isolated severe aortic regurgitation (AR) (24 of those with BAVs, 28 of those with TAVs). RESULTS: In patients with AS, stiffness in the descending aorta was 10 (range, 7.3-16) in those with BAVs and 13 (range, 11-18) in those with TAVs (P < .001). Distensibility was 19 kPa(-1) 10(-3) (range, 13-27 kPa(-1) 10(-3)) in patients with BAVs and 15 kPa(-1) 10(-3) (range, 11-19 kPa(-1) 10(-3)) in those with TAVs (P < .01). In patients with AR, stiffness was 6.9 (range, 5.5-7.8) in those with BAVs and 8.0 (range, 6.6-11) in those with TAVs (P < .05). After correction for age, dimension of the ascending aorta, cholesterol, and stroke volume in a multivariate regression model, BAV was associated with lower strain and distensibility of the descending aorta in the AR group and higher distensibility in the AS group, whereas stiffness was no longer related to aortic valve morphology in either of the two groups. CONCLUSIONS: The presence of BAVs in patients with severe AR is associated with lower strain and distensibility, suggesting that impairment of the elastic aortic properties may extend to the descending aorta. In patients with AS, BAVs correlate weakly with higher distensibility.

Real-time imaging required for optimal echocardiographic assessment of aortic valve calcification.

INTRODUCTION: Aortic valve calcification (AVC), even without haemodynamic significance, may be prognostically import as an expression of generalized atherosclerosis, but techniques for echocardiographic assessment are essentially unexplored. METHODS: Two-dimensional (2D) echocardiographic recordings (Philips IE33) of the aortic valve in short-axis and long-axis views were performed in 185 consecutive patients within 1 week before surgery for aortic stenosis (n = 109, AS), aortic regurgitation (n = 61, AR), their combination (n = 8) or dilation of the ascending aorta (n = 7). The grey scale mean (GSMn) of the aortic valve in an end-diastolic short-axis still frame was measured. The same frame was scored visually 1-5 as indicating that the aortic valve was normal, thick, or had mild, moderate or severe calcification. The visual echodensity of each leaflet was determined real time applying the same 5-grade scoring system for each leaflet, and the average for the whole valve was calculated. Finally, a similar calcification score for the whole valve based on inspection and palpation by the surgeon was noted. RESULTS: Visual assessment of real-time images using the proposed scoring system showed better correlation with the surgical evaluation of the degree of valve calcification (r = 0·83, P<0·001) compared to evaluation of stop frames by visual assessment (r = 0·66, P< 0·001) or the GSMn score (r = 0·64, P< 0·001). High inter- and intra-observer correlations were observed for real-time visual score (both intraclass correlation coefficient = 0·93). CONCLUSION: Real-time evaluation of the level of AVC is superior to using stop frames assessed either visually or by dedicated computer grey scale measurement software.

Bicuspid aortic valve leaflet morphology in relation to aortic root morphology: a study of 300 patients undergoing open-heart surgery.

OBJECTIVE: There is an ongoing discussion regarding the mechanism of aortic dilatation in bicuspid aortic valve (BAV) disease, that is, is this a hemodynamic effect or related to an inborn weakness of the aortic wall? This study evaluated the possibility of BAV morphology being related to ascending aorta morphology as such a correlation would strengthen the idea that hemodynamic alterations cause the dilatation of the aorta. METHODS: The morphology of the ascending aorta of 300 patients admitted for aortic valve and/or ascending aorta disease was evaluated by echocardiography and related to the surgeon's inspection of the aortic valve. RESULTS: A tricuspid aortic valve (TAV), BAV, or unicuspid aortic valve (UAV) was present in 130, 160, and 10 patients, respectively. Ascending aortic aneurysm was more common in patients with BAV compared with TAV (36% and 12%, respectively; p < 0.001), while ectasia of the aorta was similarly common (8% in both groups). Aortic stenosis or regurgitation was equally distributed in TAV and BAV patients with normal aortas (p=0.82). When the aorta was dilated, aortic stenosis was predominantly associated with BAV (BAV 56%, TAV 4%; p < 0.001), while aortic regurgitation was more common in TAV (TAV 81%, BAV 29%; p<0.001). In BAV patients, fusion of the right- and left coronary cusp was predominant (74%) followed by right- and non-coronary cusp fusion (14%) and true BAV (fusion of the right- and left coronary cusp without remnant raphe; 11%) (p < 0.001). The relative distribution of ascending aortic aneurysm or ectasia was similar in all morphologically different BAV (p = 0.95). CONCLUSIONS: In our study population, >50% of the patients admitted for surgery had a bicuspid valve. Aortic aneurysm was more common in BAV than in TAV patients. Aortic stenosis and aortic regurgitation were equally common in TAV and BAV with normal aortic dimensions, while aortic regurgitation was predominant in TAV with dilated aortas and aortic stenosis in BAV with dilated aortas. Dilatation of the aorta was similarly distributed regardless of BAV leaflet morphology. These findings support the idea of an intrinsic mechanisms underlying dilatation of the aorta in BAV patients.

The feasibility of velocity vector imaging by transesophageal echocardiography for assessment of elastic properties of the descending aorta in aortic valve disease.

BACKGROUND: Velocity vector imaging (VVI) is a novel two-dimensional speckle-based imaging technique for evaluation of tissue deformation. The aim of this study was to determine the feasibility and variability of VVI for the assessment of aortic strain, distensibility, and stiffness in patients with aortic valve disease. METHOD: Eighty-five patients (mean age 66 +/- 11 years) with aortic stenosis (AS) or aortic regurgitation (AR) were examined in the operating room before the operation using transesophageal echocardiography (TEE). The two-dimensional short-axis images and M-mode recordings of the descending aorta were acquired simultaneously with the invasive blood pressure measurement in the radial artery. The TEE images were analyzed off-line using VVI software. RESULTS: In comparison with patients with AS, patients with AR displayed significantly higher circumferential strain (7.6% +/- 4.5% vs. 3.7% +/- 1.9%, P < .001) and distensibility (27.1 +/- 12.8 kPa(-1)10(-3) vs. 17.2 +/- 7.2 kPa(-1)10(-3), P < .001) by VVI and distensibility (32.8 +/- 16.7 kPa(-1)10(-3) vs. 21.7 +/- 10.6 kPa(-1)10(-3), P < .004) by M-mode. Stiffness was higher in AS than AR, as measured by VVI (13.3 +/- 6.0 vs. 10.5 +/- 6.0, P < .01) and M-mode (11.2 +/- 6.1 vs. 10.4 +/- 9.1, P < .048). The correlations between VVI and M-mode distensibility (r = 0.84) and stiffness (r = 0.84) were both highly significant (P < .0001). The VVI strain measurements showed low inter- and intraobserver variability with intraclass correlations greater than 0.95 and coefficients of variation less than 10%. CONCLUSION: VVI-derived strain, distensibility, and stiffness differ significantly between AR and AS and correlate strongly with the corresponding M-mode-derived parameters. VVI is a feasible method for the assessment of the elastic properties of the descending aorta with low variability and has the advantage of incorporating the entire aortic wall circumference in the analysis, consequently accounting for local variations in the elastic properties of the aorta.