Hydrodynamic Assessment of Explanted Degenerated Transcatheter Aortic Valves: Novel Insights Into Noncalcific and Calcific Mechanisms.

BACKGROUND: The etiology of transcatheter aortic valve (TAV) degeneration is poorly understood, particularly noncalcific mechanisms. OBJECTIVES: The authors sought to investigate noncalcific and calcific mechanisms of TAV degeneration and evaluate their impact on leaflet function by bench testing, imaging, and histology. METHODS: TAV explants were obtained from the EXPLANT THV registry and clinical institutions. Hydrodynamic assessment was performed using a heart valve pulse duplicator system under physiological conditions. Micro-computed tomography, high-resolution photography, high speed video, and hematoxylin and eosin staining were used to evaluate the morphological appearance, leaflet kinematics, and calcium burden of TAVs. RESULTS: A total of 14 explants were evaluated: 10 self-expanding CoreValve/Evolut TAVs (Medtronic), 3 balloon-expandable SAPIEN 3 TAVs (Edwards Lifesciences), and 1 mechanically expandable Lotus TAV (Boston Scientific). The median patient age at explantation was 73.0 years (Q1-Q3: 64.5-80.0 years), with a time to explantation of 4 years 1 month (1 year 5 months to 4 years 11 months). Six TAV explants were found to have leaflet calcification (162.4 mm3; 58.8-603.0 mm3), and 8 had no calcification detectable by micro-computed tomography and histology. All samples had impaired leaflet kinematics. There was no significant difference in the hydrodynamic mean gradient between calcified (47.2 mm Hg; 26.6-74.1 mm Hg) and noncalcified (27.6 mm Hg; 15.2-36.7 mm Hg; P = 0.28) TAVs. Leaflet calcification had a weak but nonsignificant association with the hydrodynamic mean gradient (r = 0.42; P = 0.14). CONCLUSIONS: TAV function can be severely impacted by noncalcific and calcific mechanisms of tissue degeneration. Importantly, functional stenosis can occur in TAVs in the absence of obvious and significant calcification.

Aortic Valve Calcification Density Measured by MDCT in the Assessment of Aortic Stenosis Severity.

BACKGROUND: Aortic valve calcification (AVC) indexation to the aortic annulus (AA) area measured by Doppler echocardiography (AVCdEcho) provides powerful prognostic information in patients with aortic stenosis (AS). However, the indexation by AA measured by multidetector computed tomography (AVCdCT) has never been evaluated. The aim of this study was to compare AVC, AVCdCT, and AVCdEcho with regard to hemodynamic correlations and clinical outcomes in patients with AS. METHODS: Data from 889 patients, mainly White, with calcific AS who underwent Doppler echocardiography and multidetector computed tomography within the same episode of care were retrospectively analyzed. AA was measured both by Doppler echocardiography and multidetector computed tomography. AVCdCT severity thresholds were established using receiver operating characteristic curve analyses in men and women separately. The primary end point was the occurrence of all-cause mortality. RESULTS: Correlations between gradient/velocity and AVCd were stronger (both P≤0.005) using AVCdCT (r=0.68, P<0.001 and r=0.66, P<0.001) than AVC (r=0.61, P<0.001 and r=0.60, P<0.001) or AVCdEcho (r=0.61, P<0.001 and r=0.59, P<0.001). AVCdCT thresholds for the identification of severe AS were 334 Agatston units (AU)/cm2 for women and 467 AU/cm2 for men. On a median follow-up of 6.62 (6.19-9.69) years, AVCdCT ratio was superior to AVC ratio and AVCdEcho ratio to predict all-cause mortality in multivariate analyses (hazard ratio [HR], 1.59 [95% CI, 1.26-2.00]; P<0.001 versus HR, 1.53 [95% CI, 1.11-1.65]; P=0.003 versus HR, 1.27 [95% CI, 1.11-1.46]; P<0.001; all likelihood test P≤0.004). AVCdCT ratio was superior to AVC ratio and AVCdEcho ratio to predict survival under medical treatment in multivariate analyses (HR, 1.80 [95% CI, 1.27-1.58]; P<0.001 compared with HR, 1.55 [95% CI, 1.13-2.10]; P=0.007; HR, 1.28 [95% CI, 1.03-1.57]; P=0.01; all likelihood test P<0.03). AVCdCT ratio predicts mortality in all subgroups of patients with AS. CONCLUSIONS: AVCdCT appears to be equivalent or superior to AVC and AVCdEcho to assess AS severity and predict all-cause mortality. Thus, it should be used to evaluate AS severity in patients with nonconclusive echocardiographic evaluations with or without low-flow status. AVCdCT thresholds of 300 AU/cm2 for women and 500 AU/cm2 for men seem to be appropriate to identify severe AS. Further studies are needed to validate these thresholds, especially in diverse populations.

Aortic stenosis assessment from the 3-chamber cine: Ratio of balanced steady-state-free-precession (bSSFP) blood signal between the aorta and left ventricle predicts severity.

BACKGROUND: Cardiovascular magnetic resonance (CMR) imaging is an important tool for evaluating the severity of aortic stenosis (AS), co-existing aortic disease, and concurrent myocardial abnormalities. Acquiring this additional information requires protocol adaptations and additional scanner time, but is not necessary for the majority of patients who do not have AS. We observed that the relative signal intensity of blood in the ascending aorta on a balanced steady state free precession (bSSFP) 3-chamber cine was often reduced in those with significant aortic stenosis. We investigated whether this effect could be quantified and used to predict AS severity in comparison to existing gold-standard measurements. METHODS: Multi-centre, multi-vendor retrospective analysis of patients with AS undergoing CMR and transthoracic echocardiography (TTE). Blood signal intensity was measured in a ∼1 cm2 region of interest (ROI) in the aorta and left ventricle (LV) in the 3-chamber bSSFP cine. Because signal intensity varied across patients and scanner vendors, a ratio of the mean signal intensity in the aorta ROI to the LV ROI (Ao:LV) was used. This ratio was compared using Pearson correlations against TTE parameters of AS severity: aortic valve peak velocity, mean pressure gradient and the dimensionless index. The study also assessed whether field strength (1.5 T vs. 3 T) and patient characteristics (presence of bicuspid aortic valves (BAV), dilated aortic root and low flow states) altered this signal relationship. RESULTS: 314 patients (median age 69 [IQR 57-77], 64% male) who had undergone both CMR and TTE were studied; 84 had severe AS, 78 had moderate AS, 66 had mild AS and 86 without AS were studied as a comparator group. The median time between CMR and TTE was 12 weeks (IQR 4-26). The Ao:LV ratio at 1.5 T strongly correlated with peak velocity (r = -0.796, p = 0.001), peak gradient (r = -0.772, p = 0.001) and dimensionless index (r = 0.743, p = 0.001). An Ao:LV ratio of < 0.86 was 84% sensitive and 82% specific for detecting AS of any severity and a ratio of 0.58 was 83% sensitive and 92% specific for severe AS. The ability of Ao:LV ratio to predict AS severity remained for patients with bicuspid aortic valves, dilated aortic root or low indexed stroke volume. The relationship between Ao:LV ratio and AS severity was weaker at 3 T. CONCLUSIONS: The Ao:LV ratio, derived from bSSFP 3-chamber cine images, shows a good correlation with existing measures of AS severity. It demonstrates utility at 1.5 T and offers an easily calculable metric that can be used at the time of scanning or automated to identify on an adaptive basis which patients benefit from dedicated imaging to assess which patients should have additional sequences to assess AS.

Slice positioning in phase-contrast MRI impacts aortic stenosis assessment.

AIMS: To determine the phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) slice-position above aortic leaflet-attachment-plane (LAP) that provides flow-velocity, -volume and aortic valve area (AVA) measurements with best agreement to invasive and echocardiographic measurements in aortic stenosis (AS). METHODS AND RESULTS: Fifty-five patients with moderate/severe AS underwent cardiac catheterization, transthoracic echocardiography (TTE) and CMR. Overall, 171 image-planes parallel to LAP were measured via PC-CMR between 22 mm below and 24 mm above LAP. AVA via PC-CMR was calculated as flow-volume divided by peak-velocity during systole. Stroke volume (SV) and AVA were compared to volumetric SV and invasive AVA via the Gorlin-formula, respectively. Above LAP, SV by PC-CMR showed no significant dependence on image-plane-position and correlated strongly with volumetry (rho: 0.633, p < 0.001, marginal-mean-difference (MMD): 1 ml, 95 % confidence-interval (CI): -4 to 6). AVA assessed in image-planes 0-10 mm above LAP differed significantly from invasive measurement (MMD: -0.14 cm2, 95 %CI: 0.08-0.21). In contrast, AVA-values by PC-CMR measured 10-20 mm above LAP showed good agreement with invasive determination without significant MMD (0.003 cm2, 95 %CI: -0.09 to 0.09). Within these measurements, a plane 15 mm above LAP resulted in the lowest bias (MMD: 0.02 cm2, 95 %CI:-0.29 to 0.33). SV and AVA via TTE correlated moderately with volumetry (rho: 0.461, p < 0.001; bias: 15 ml, p < 0.001) and cardiac catheterization (rho: 0.486, p < 0.001, bias: -0.13 cm2, p < 0.001), respectively. CONCLUSION: PC-CMR measurements at 0-10 mm above LAP should be avoided due to significant AVA-overestimation compared to invasive determination. AVA-assessment by PC-CMR between 10 and 20 mm above LAP did not differ from invasive measurements, with the lowest intermethodical bias measured 15 mm above LAP.

The role of 4-dimensional flow in the assessment of bicuspid aortic valve and its valvulo-aortopathies.

Bicuspid aortic valve is the most common congenital cardiac malformation and the leading cause of aortopathy and aortic stenosis in younger patients. Aortic wall remodelling secondary to altered haemodynamic flow patterns, changes in peak velocity, and wall shear stress may be implicated in the development of aortopathy in the presence of bicuspid aortic valve and dysfunction. Assessment of these parameters as potential predictors of disease severity and progression is thus desirable. The anatomic and functional information acquired from 4D flow MRI can allow simultaneous visualisation and quantification of the pathological geometric and haemodynamic changes of the aorta. We review the current clinical utility of haemodynamic quantities including velocity, wall sheer stress and energy losses, as well as visual descriptors such as vorticity and helicity, and flow direction in assessing the aortic valve and associated aortopathies.

Changing epidemiology of calcific aortic valve disease: 30-year trends of incidence, prevalence, and deaths across 204 countries and territories.

Calcific aortic valve disease (CAVD) is associated with increased morbidity and mortality. We aimed to elucidate the 30-year epidemiology of CAVD globally. Global CAVD incidence, prevalence, and deaths increased 3.51-, 4.43-, and 1.38-fold from 1990 to 2019, respectively, without any decreasing trends, even after age standardization. In 2019, Slovenia had the highest age-standardized rate (ASR) of CAVD incidence (62.21/100,000 persons) and prevalence (1,080.06/100,000) whereas Cyprus had the highest ASR of deaths (8.20/100,000). Population aging was an important contributor to incidence. Compared with women, more men had CAVD and men had earlier peaks in disease prevalence. High systolic blood pressure, diet high in sodium, and lead exposure were the main risk factors for deaths owing to CAVD. The estimated annual percentage change, a measure to estimate the variation of ASR, was significantly associated with the ASR and sociodemographic index (SDI) in 2019 for incidence and prevalence across all 204 countries and territories (all p<0.0001). With increased lifespan and risk factors, the overall burden of CAVD is high and remains on the rise, with differences by sex, age, and SDI level. Our findings serve to sound the alarm for organizations, institutions, and resources whose primary purpose is to improve human health.

Drugs for Prevention and Treatment of Aortic Stenosis: How Close Are We?

Aortic stenosis is one of the most common cardiovascular diseases in the world. Extensive work on the underlying pathophysiology responsible for calcific aortic valve disease and its progression to aortic stenosis has described a complex process involving inflammation, lipid deposition, mineralisation, and genetic factors such as elevated lipoprotein(a). With the advancement of gene silencing technology and development of novel therapeutic agents, we may now be closer than ever to having medical therapies that prevent, or at least slow the progression of aortic stenosis. In this review, we highlight the pathophysiology and risk factors of calcific aortic valve disease, along with current, potential, and emerging novel medical therapies. We also provide potential explanations for the failure of statin trials and suggest new avenues for research and new randomised trials in this area.

Mitral annular calcification in the elderly - Quantitative assessment.

PURPOSE: To determine the reliability of subjective and objective quantification of mitral annular calcification (MAC) in elderly patients with severe aortic stenosis, to define quantitative sex- and age-related reference values of MAC, and to correlate quantitative MAC with mitral valve disease. METHODS: In this retrospective, IRB-approved study, we included 559 patients (268 females, median age 81 years, inter-quartile range 77-85 years) with severe aortic stenosis undergoing CT. Four independent readers performed subjective MAC categorization as follows: no, mild, moderate, and severe MAC. Two independent readers performed quantitative evaluation of MAC using the Agatston score method (AgatstonMAC). Mitral valve disease was determined by echocardiography. RESULTS: Subjective MAC categorization showed high inter-reader agreement for no (k â€‹= â€‹0.88) and severe MAC (k â€‹= â€‹0.75), whereas agreement for moderate (k â€‹= â€‹0.59) and mild (k â€‹= â€‹0.45) MAC was moderate. Intra-reader agreement for subjective MAC categorization was substantial (k â€‹= â€‹0.69 and 0.62). Inter- and intra-reader agreement for AgatstonMAC were excellent (ICC â€‹= â€‹0.998 and 0.999, respectively), with minor inconsistencies in MAC involving the left ventricular outflow tract/aortic valve. There were significantly more women than men with MAC (n â€‹= â€‹227, 85% versus n â€‹= â€‹209, 72%; p â€‹< â€‹0.001), with a significantly higher AgatstonMAC (median 597, range 81-2055 versus median 244; range 0-1565; p â€‹< â€‹0.001), particularly in patients ≥85 years of age. AgatstonMAC showed an area-under-the-curve of 0.84 to diagnose mitral stenosis, whereas there was no association of AgatstonMAC with mitral regurgitation (p â€‹> â€‹0.05). CONCLUSIONS: Our study in elderly patients with severe aortic stenosis shows that quantitative MAC scoring is more reliable than subjective MAC assessment. Women show higher AgatstonMAC scores than men, particularly in the elderly population. AgatstonMAC shows high accuracy to diagnose mitral stenosis.

Validity of visual assessment of aortic valve morphology in patients with aortic stenosis using two-dimensional echocardiography.

The diagnostic value of a visual assessment of aortic valve (AV) morphology for grading aortic stenosis (AS) remains unclear. A visual score (VS) for assessing the AV was developed and its reliability with respect to Doppler measurements and the calcium score (ctCS) derived by multislice computed tomography was evaluated. 99 Patients with AS of various severity and 38 patients without AS were included in the analysis. Echocardiographic studies were evaluated using the new VS which includes echogenicity, thickening, localization of lesions and leaflet mobility, with a total score ranging from 0 to 11. The association of VS with ctCS and the severity of AS was analyzed. There was a significant correlation of VS with AV hemodynamic parameters and with ctCS. The cut-off value for the detection of AS of any grade was a VS of 6 (sensitivity 95%, specificity 85% for women; sensitivity 85%, specificity 88% for men). A VS of 9 for women and of 10 for men was able to predict severe AS with a high specificity (96% in women and 94% in men, AUC 0.8 and 0.86, respectively). The same cut-off values were identified for the detection of ctCS of ≥ 1600 AU and ≥ 3000 AU with a specificity of 77% and 82% (AUC 0.69 and 0.81, respectively). Assessment of aortic valve morphology can serve as an additional diagnostic tool for the detection of AS and an estimation of its severity.

Age, Sex, and Valve Phenotype Differences in Fibro-Calcific Remodeling of Calcified Aortic Valve.

Background In calcific aortic valve disease on tricuspid aortic valves (TAVs), men have higher aortic valve calcification and less fibrosis than women. However, little is known in bicuspid aortic valves (BAV). We thus aimed to investigate the impact of age, sex, and valve phenotype (TAVs versus BAVs) on fibro-calcific remodeling in calcific aortic valve disease. Methods and Results We included 2 cohorts: 411 patients who underwent multidetector computed tomography (37% women) for aortic valve calcification density assessment and 138 explanted aortic valves (histological cohort; 50% women). The cohorts were divided in younger (<60 years old) or older patients with BAV (≥60 years old), and TAV patients. In each group, women and men were matched. Women presented less aortic valve calcification density than men in each group of the multidetector computed tomography cohort (all P≤0.01). Moreover, in women, younger patients with BAV had the lowest aortic valve calcification density (both P=0.02). In multivariate analysis, aortic valve calcification density correlated with age (ß estimate±standard error: 6.5±1.8; P=0.0004) and male sex (109.2±18.4; P<0.0001), and there was a trend with TAVs (41.5±23.0; P=0.07). Women presented a higher collagen content than men (77.8±10.8 versus 69.9±12.9%; P<0.001) in the entire cohort. In women, younger patients with BAV had denser connective tissue than TAV and older patients with BAV (both P≤0.05), while no difference was observed between men. Conclusions In calcific aortic valve disease, women had less calcification and more fibrotic remodeling than men, regardless of the phenotype of the valve or age of the patient. Moreover, younger women with BAVs had less valve calcification. Thus, mineralization/fibrosis of the aortic valve is likely to have sex/age-specific mechanisms and be influenced by the valve morphology.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Third generation dual source CT with ultra-high pitch protocol for TAVI planning and coronary tree assessment: feasibility, image quality and diagnostic performance.

PURPOSE: To evaluate the feasibility, image quality (IQ) and diagnostic performance of third generation 192 × 2 dual source computer tomography (DSCT) with ultra-high pitch acquisition for trans-catheter aortic valve implantation (TAVI) planning and coronary tree assessment. METHOD: In this prospective study, 223 patients underwent to DSCT for TAVI. Coronary calcium scoring (CCS) was calculated. Attenuation values were measured at aortic levels, femoral and coronary arteries. IQ was evaluate with a 4-point scale. The CT performance, in the assessment of coronary stenosis ≥50 % and ≥70 %, was compared with invasive coronary angiography (ICA), served as reference standard. Aortic annulus (AoA) CT derived area and implanted prosthesis size were correlate with Spearman's test. RESULTS: Attenuation values >400HU were obtain in all segments. IQ median value was ≥ 3. In the assessment of stenosis ≥50 %, on a segment-based analysis, CT sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were 97.6 %, 87.6 %, 64.2 %, 99.0 % and 89.6 %, on patient-based analysis were 97.8 %, 88.8 %, 68.8 %, 99.4 % and 90.6 %, respectively. In the assessment of stenosis ≥70 %, on segment-based analysis, were 88.5 %, 83.8 %, 54.7 %, 96.8 % and 84.8 %, and on patient-based analysis were 92.5 %, 85.8 %, 58.7 %, 98.1 % and 87.0 %, respectively. The CT performed better in the group with lower CCS. A direct correlation was found between AoA CT derived area and prosthesis size. CONCLUSION: DSCT, using a single prospective ECG-triggered ultra-high pitch acquisition, is feasible for TAVI planning and in the assessment of coronary stenosis. CT performed worse in patients with severe coronary calcifications.

Calcium Pattern Assessment in Patients with Severe Aortic Stenosis Via the Chou's 5-Steps Rule.

BACKGROUND: Progression of aortic valve calcifications (AVC) leads to aortic valve stenosis (AS). Importantly, the AVC degree has a great impact on AS progression, treatment selection and outcomes. Methods of AVC assessment do not provide accurate quantitative evaluation and analysis of calcium distribution and deposition in a repetitive manner. OBJECTIVE: We aim to prepare a reliable tool for detailed AVC pattern analysis with quantitative parameters. METHODS: We analyzed computed tomography (CT) scans of fifty patients with severe AS using a dedicated software based on MATLAB version R2017a (MathWorks, Natick, MA, USA) and ImageJ version 1.51 (NIH, USA) with the BoneJ plugin version 1.4.2 with a self-developed algorithm. RESULTS: We listed unique parameters describing AVC and prepared 3D AVC models with color pointed calcium layer thickness in the stenotic aortic valve. These parameters were derived from CT-images in a semi-automated and repeatable manner. They were divided into morphometric, topological and textural parameters and may yield crucial information about the anatomy of the stenotic aortic valve. CONCLUSION: In our study, we were able to obtain and define quantitative parameters for calcium assessment of the degenerated aortic valves. Whether the defined parameters are able to predict potential long-term outcomes after treatment, requires further investigation.

Aggressive tissue aortic valve replacement in younger patients and the risk of re-replacement: Implications from microsimulation analysis.

OBJECTIVE: Advances in transcatheter aortic valve replacement have led to the consideration of tissue aortic valve replacement in younger patients. Part of this enthusiasm is the presumption that younger patients would have more flexibility in future treatment options, such as a primary surgical aortic valve replacement followed later by transcatheter aortic valve replacement(s) (valve-in-valve), vice versa, or other permutations. We created a microsimulation model using published longevity of tissue valves to predict the outcomes of patients after primary tissue surgical aortic valve replacement. METHODS: The model calculated survival by incorporating annual mortality (Social Security Administration) and mortality from re-replacements (Society of Thoracic Surgeons) in patients with surgical aortic valve replacement. Freedom from reoperation for structural valve degeneration incorporated best published data to determine the annual risk of re-replacement for structural valve degeneration based on implant duration and stratified by patient age. A constant rate of re-replacement for nonstructural valve degeneration indications was also incorporated. Each simulation was performed for 50,000 individuals. Kaplan-Meier curves were generated to represent survival. All simulations were run within the MATLAB environment (The MathWorks, Inc, Natick, Mass). RESULTS: Earlier decades of life at primary surgical aortic valve replacement were associated with higher incidences of re-replacements and especially multiple re-replacements. For those patients receiving a primary tissue surgical aortic valve replacement at age 50 years, 57.2% will require a second valve, 18.0% will require a third valve, and 1.6% will require a fourth valve with average operative mortalities of 2.9%, 4.8%, and 7.3%, respectively. A 50-year-old patient at primary surgical aortic valve replacement has a 13.1% chance of re-replacement before turning 60 years of age. CONCLUSIONS: Microsimulation incorporates changing hazards to estimate the risk of aortic valve re-replacement in patients undergoing tissue surgical aortic valve replacement and may be a starting point for patient education and health care economic planning.

Risk factors for atrioventricular block after transcatheter aortic valve implantation: a single-centre analysis including assessment of aortic calcifications and follow-up.

AIMS: To assess the contribution of aortic valve calcification to the occurrence of transient or permanent atrioventricular block (AVB) and the need for permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) in a large single-centre cohort. METHODS AND RESULTS: We retrospectively analysed pre-operative contrast-enhanced multidetector computed tomography scans of patients who underwent TAVI in our centre between 2012 and 2016. Calcium volume was calculated for each aortic cusp above (aortic valve), and below [left ventricular outflow tract (LVOT)] the basal plane. Clinical and procedural data as well as pre-operative electrocardiograms were evaluated. Multivariate analysis was performed to evaluate risk factors for transient and permanent AVB. A total of 342 patients receiving a balloon-expandable prosthesis were included in the study. Overall incidence of transient and permanent AVB was 4% (n = 14) and 7.6% (n = 26), respectively. On logistic regression analysis, baseline right bundle branch block [odds ratio (OR) 7.36, 95% confidence interval (CI) 2.6-20.6; P < 0.01], degree of oversizing (OR 1.04, 95% CI 1.01-1.07 P = 0.02), prior percutaneous coronary intervention (OR 2.8, 95% CI 1.1-7.3), and LVOT calcification beneath the non-coronary cusp (OR for an increase of 10 mm3 = 1.06, 95% CI 1-1.1; P = 0.03) were found to be independently associated with permanent AVB and PPI, whereas calcification of LVOT beneath the right coronary cusp (OR for an increase of 10 mm3 = 1.16, 95% CI 1.02-1.3; P = 0.02) and balloon post-dilation (OR 3.8, 95% CI 1.2-11.8; P = 0.02) were associated with reversible AVB. CONCLUSION: Left ventricular outflow tract calcifications are associated with transient and non-reversible AVB after TAVI, and its evaluation could help in predicting onset and reversibility of AVB.

Impact of a Claims-Based Frailty Indicator on the Prediction of Long-Term Mortality After Transcatheter Aortic Valve Replacement in Medicare Beneficiaries.

Background Prospectively collected frailty markers are associated with an incremental 1-year mortality risk after transcatheter aortic valve replacement (TAVR) compared with comorbidities alone. Whether information on frailty markers captured retrospectively in administrative billing data is similarly predictive of long-term mortality after TAVR is unknown. We sought to characterize the prognostic importance of frailty factors as identified in healthcare billing records in comparison to validated measures of frailty for the prediction of long-term mortality after TAVR. Methods and Results Adult patients undergoing TAVR between August 25, 2011, and September 29, 2015, were identified among Medicare fee-for-service beneficiaries. The Johns Hopkins Claims-based Frailty Indicator was used to identify frail patients. We used nested Cox regression models to identify claims-based predictors of mortality up to 4 years post-procedure. Four groups of variables, including cardiac risk factors, noncardiac risk factors, patient procedural risk factors, and nontraditional markers of frailty, were introduced sequentially, and their integrated discrimination improvement was assessed. A total of 52 338 TAVR patients from 558 clinical sites were identified, with a mean follow-up time period of 16 months. In total, 14 174 (27.1%) patients died within the study period. The mortality rate was 53.9% at 4 years post-TAVR. A total of 34 863 (66.6%) patients were defined as frail. The discrimination of each of the 4 models was 0.60 (95% CI, 0.59-60), 0.65 (95% CI, 0.64-0.65), 0.68 (95% CI, 0.67-0.68), and 0.70 (95% CI, 0.69-0.70), respectively. The addition of nontraditional frailty markers as identified in claims improved mortality prediction above and beyond traditional risk factors (integrated discrimination improvement: 0.019; P<0.001). Conclusions Risk prediction models that include frailty as identified in claims data can be used to predict long-term mortality risk after TAVR. Linkage to claims data may allow enhanced mortality risk prediction for studies that do not collect information on frailty.

Computed Tomography Assessment for Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement has become a mainstream therapeutic option for patients with severe aortic stenosis who are at intermediate risk or high risk for surgical valve replacement. Computed tomography (CT) is now the standard imaging modality for preoperative vascular access planning an aortic annular sizing. This article reviews the established and potential future roles of CT in transcatheter aortic valve replacement.

Superiority of novel automated assessment of aortic annulus by intraoperative three-dimensional transesophageal echocardiography in patients with severe aortic stenosis: Comparison with conventional cross-sectional assessment.

BACKGROUND: Previous studies have demonstrated that three-dimensional (3D) transesophageal echocardiography (TEE) is an alternative to multi-detector computed tomography (MDCT) for aortic valve sizing in transcatheter aortic valve replacement (TAVR). However, conventional cross-sectional analysis of aortic annulus by 3D TEE has some limitations such as lengthy analytical time. A novel software for automated valve measurement has been developed for 3D TEE. We evaluated the accuracy and analytical time of aortic annular measurements using this novel automated software in the clinical setting. METHODS: We retrospectively studied 43 patients with symptomatic severe aortic stenosis (AS) who underwent TAVR. All patients underwent intraoperative TEE and MDCT. We measured aortic annular area by automated, semi-automated, and cross-sectional methods using 3D TEE datasets. These measurements were compared to the corresponding MDCT reference values. We also compared the analytical time of the three methods. RESULTS: Automated and semi-automated analyses required significantly shorter analytical time compared to cross-sectional analysis (automated: 30.1±5.79s, semi-automated: 74.1±15.0s, manual: 81.8±18.5s, p<0.05). Compared to MDCT measurement (393.7±81.0mm2), annular areas measured by automated and cross-sectional methods were significantly smaller (automated: 380.6±77.1mm2, cross-sectional: 374.7±76.8mm2, p<0.05), while that obtained by semi-automated method was not significantly different (387.7±75.8mm2). Annular areas determined by semi-automated and cross-sectional analyses had narrower limits of agreement (LOA) with MDCT measurements, compared to automated analysis (automated: -68.6 to 94.7mm2, semi-automated: -48.3 to 60.2mm2, cross-sectional: -40.0 to 77.9mm2). Measurements by all three methods using 3D TEE showed high correlation with MDCT measurement (automated: r=0.86, semi-automated: r=0.94, cross-sectional: r=0.93). CONCLUSIONS: For aortic annular measurements using 3D TEE in AS patients, semi-automated analysis using the novel automated software reduced analytical time while maintaining similar accuracy compared to the conventional cross-sectional analysis. This automated software may have acceptable feasibility in the clinical setting.