Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

BACKGROUND: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. OBJECTIVES: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. METHODS: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. RESULTS: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. CONCLUSIONS: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.

The Pandemic and Beyond: Innovation in Cardiovascular Training to Improve Quality of Education and Trainees' Well-being.

During the first 2 years of the coronavirus-19 pandemic, many changes and innovations occurred to overcome the challenges associated with the pandemic and improve cardiovascular training. This review highlights the literature on the pandemic response regarding cardiovascular fellowship education and identifies areas of need to ensure future opportunities for fellows to achieve competency and career advancement. Specifically, we describe the recent changes to the four cornerstones of cardiovascular training: core content education, procedural training, career development, and the well-being of trainees.

Functional assessment of bioprosthetic mitral valves by cardiovascular magnetic resonance: An in vitro validation and comparison to Doppler echocardiography.

BACKGROUND: A comprehensive non-invasive evaluation of bioprosthetic mitral valve (BMV) function can be challenging. We describe a novel method to assess BMV effective orifice area (EOA) based on phase contrast (PC) cardiovascular magnetic resonance (CMR) data. We compare the performance of this new method to Doppler and in vitro reference standards. METHODS: Four sizes of normal BMVs (27, 29, 31, 33 mm) and 4 stenotic BMVs (27 mm and 29 mm, with mild or severe leaflet obstruction) were evaluated using a CMR- compatible flow loop. BMVs were evaluated with PC-CMR and Doppler methods under flow conditions of; 70 mL, 90 mL and 110 mL/beat (n = 24). PC-EOA was calculated as PC-CMR flow volume divided by the PC- time velocity integral (TVI). RESULTS: PC-CMR measurements of the diastolic peak velocity and TVI correlated strongly with Doppler values (r = 0.99, P < 0.001 and r = 0.99, P < 0.001, respectively). Across all conditions tested, the Doppler and PC-CMR measurement of EOA (1.4 ± 0.5 vs 1.5 ± 0.7 cm2, respectively) correlated highly (r = 0.99, P < 0.001), with a minimum bias of 0.13 cm2, and narrow limits of agreement (- 0.2 to 0.5 cm2). CONCLUSION: We describe a novel method to assess BMV function based on PC measures of transvalvular flow volume and velocity integration. PC-CMR methods can be used to accurately measure EOA for both normal and stenotic BMV's and may provide an important new parameter of BMV function when Doppler methods are unobtainable or unreliable.

Four-dimensional flow cardiovascular magnetic resonance in aortic dissection: Assessment in an ex vivo model and preliminary clinical experience.

OBJECTIVE: Four-dimensional flow cardiovascular magnetic resonance may improve assessment of hemodynamics in patients with aortic dissection. The purpose of this study was to evaluate the feasibility and accuracy of 4-dimensional flow cardiovascular magnetic resonance assessment of true and false lumens flow. METHODS: Thirteen ex vivo porcine aortic dissection models were mounted to a flow loop. Four-dimensional flow cardiovascular magnetic resonance and 2-dimensional phase-contrast cardiovascular magnetic resonance measurements were performed, assessed for intraobserver and interobserver variability, and compared with a reference standard of sonotransducer flow volume measurements. Intraobserver and interobserver variability of 4-dimensional flow cardiovascular magnetic resonance were also assessed in 14 patients with aortic dissection and compared with 2-dimensional phase-contrast cardiovascular magnetic resonance. RESULTS: In the ex vivo model, the intraobserver and interobserver measurements had Lin's correlation coefficients of 0.98 and 0.96 and mean differences of 0.17 (±3.65) mL/beat and -0.59 (±5.33) mL/beat, respectively; 4-dimensional and sonotransducer measurements had a Lin's concordance correlation coefficient of 0.95 with a mean difference of 0.35 (±4.92) mL/beat, respectively. In patients with aortic dissection, the intraobserver and interobserver measurements had Lin's concordance correlation coefficients of 0.98 and 0.97 and mean differences of -0.95 (±8.24) mL/beat and 0.62 (±10.05) mL/beat, respectively; 4-dimensional and 2-dimensional flow had a Lin's concordance correlation coefficient of 0.91 with a mean difference of -9.27 (±17.79) mL/beat because of consistently higher flow measured with 4-dimensional flow cardiovascular magnetic resonance in the ascending aorta. CONCLUSIONS: Four-dimensional flow cardiovascular magnetic resonance is feasible in patients with aortic dissection and can reliably assess flow in the true and false lumens of the aorta. This promotes potential future work on functional assessment of aortic dissection hemodynamics.

Transcatheter aortic valve replacement in patients with severe mitral or tricuspid regurgitation at extreme risk for surgery.

OBJECTIVES: Patients with symptomatic severe aortic stenosis and severe mitral regurgitation or severe tricuspid regurgitation were excluded from the major transcatheter aortic valve replacement trials. We studied these 2 subgroups in patients at extreme risk for surgery in the prospective, nonrandomized, single-arm CoreValve US Expanded Use Study. METHODS: The primary end point was all-cause mortality or major stroke at 1 year. A favorable medical benefit was defined as a Kansas City Cardiomyopathy Questionnaire overall summary score greater than 45 at 6 months and greater than 60 at 1 year and with a less than 10-point decrease from baseline. RESULTS: There were 53 patients in each group. Baseline characteristics for the severe mitral regurgitation and severe tricuspid regurgitation cohorts were age 84.2 ± 6.4 years and 84.9 ± 6.5 years; male, 29 (54.7%) and 22 (41.5%), and mean Society of Thoracic Surgeons score 9.9% ± 5.0% and 9.2% ± 4.0%, respectively. Improvement in valve regurgitation from baseline to 1 year occurred in 72.7% of the patients with severe mitral regurgitation and in 61.8% of patients with severe tricuspid regurgitation. A favorable medical benefit occurred in 31 of 47 patients (66.0%) with severe mitral regurgitation and 33 of 47 patients (70.2%) with severe tricuspid regurgitation at 6 months, and in 25 of 44 patients (56.8%) with severe mitral regurgitation and 24 of 45 patients (53.3%) with severe tricuspid regurgitation at 1 year. All-cause mortality or major stroke for the severe mitral regurgitation and severe tricuspid regurgitation cohorts were 11.3% and 3.8% at 30 days and 21.0% and 19.2% at 1 year, respectively. There were no major strokes in either group at 1 year. CONCLUSIONS: Transcatheter aortic valve replacement in patients with severe mitral regurgitation or severe tricuspid regurgitation is reasonable and safe and leads to improvement in atrioventricular valve regurgitation.

Functional Assessment of Bioprosthetic Aortic Valves by CMR.

OBJECTIVES: The aim of this study was to evaluate cardiac magnetic resonance (CMR) phase-contrast (PC) measures of a bioprosthetic aortic valve velocity time integral (PC-VTI) to derive the effective orifice area (PC-EOA) and to compare these findings with the clinical standard of Doppler echocardiography. BACKGROUND: Bioprosthetic aortic valve function can be assessed with CMR planimetry of the anatomic orifice area and PC measurement of peak transvalvular systolic velocity. However, bioprosthetic valves can create image artifact and data dropout, which makes planimetry measures a challenge for even experienced CMR readers. METHODS: From our institutional database, we identified 38 patients who had undergone 47 paired imaging studies (CMR and Doppler) within 46 days (median 3 days). Transvalvular forward flow volume by CMR was determined by 3 methods: ascending aorta flow, transvalvular flow, and left ventricular stroke volume. PC-EOA was derived as flow divided by PC-VTI, calculated with a semiautomated MATLAB (Mathworks, Natick, Massachusetts) application for integration of the instantaneous peak transvalvular velocity. Doppler EOA was assessed by the continuity method. RESULTS: PC-EOA by all 3 flow approaches demonstrated a strong correlation with Doppler EOA (r = 0.949, 0.947, and 0.874, respectively; all p < 0.001) and revealed good agreement (bias = 0.03, 0.03, and 0.28 cm(2), respectively). With Doppler-derived EOA as the reference standard, CMR was able to correctly characterize 24 of 26 valves as normal (EOA >1.2 cm(2)), 12 of 14 possibly stenotic valves (0.8 < EOA < 1.2 cm(2)), and 5 of 7 stenotic valves (EOA <0.8 cm(2); k = 0.826). CONCLUSIONS: We describe a new CMR-based method to derive the EOA for bioprosthetic aortic valves. This method compares favorably to traditional Doppler methods and might be an important additional parameter in the evaluation of prosthetic valves by CMR, particularly when Doppler methods are suboptimal or considered discordant with the clinical presentation.

Comparative Assessment of Mitral Regurgitation Severity by Transthoracic Echocardiography and Cardiac Magnetic Resonance Using an Integrative and Quantitative Approach.

Although transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) are validated in quantitation of mitral regurgitation (MR), discrepancies may occur. This study assesses the agreement between TTE and CMR in MR and evaluates characteristics and clinical outcome of patients with discrepancy. From our institutional database, 70 subjects with MR underwent both TTE and CMR within 30 days (median 3 days). MR was evaluated semiquantitatively (n = 70) using a 4-grade scale and quantitatively (n = 60) with calculation of regurgitant volume (RVol) and regurgitant fraction (RF). Of the 70 subjects, qualitative assessment by TTE yielded 30 subjects with mild MR, 17 moderate, and 23 moderately severe or severe MR. Exact concordance in MR grade was seen in 50% and increased to 91% when considering concordance within one grade of severity (κ = 0.44). A modest correlation was observed for RVol and RF between both methods (r = 0.59 and 0.54, respectively, p <0.0001). Ten patients had a significant discrepancy in quantitative MR (difference in RF >20%); the frequency of secondary MR was higher (100% vs 46%; p = 0.003) in patients with discrepancy. Although interobserver variability in RF was higher with TTE compared with CMR (-5.5 ± 15% vs 0.1 ± 7.3%), patients with discrepancy were equally distributed by severity and clinical outcome without an overestimation by either method. In conclusion, there is a modest agreement between TTE and CMR in assessing MR severity. In patients with discrepancy, there is a higher prevalence of functional MR, without a consistent overestimation of MR severity by either method.

Assessment of prosthetic valve function and para-valvular regurgitation after trans-catheter aortic valve replacement.

PURPOSE OF REVIEW: To review the current literature on prosthetic valve function and para-valvular regurgitation (PVR) after trans-catheter aortic valve replacement (TAVR). TAVR is a new alternative for the treatment of severe aortic stenosis in patients at high risk for surgical aortic valve replacement and nonsurgical candidates. RECENT FINDINGS: The innovations in three-dimensional trans-esophageal echocardiography have made it an integral part of the TAVR procedure. PVR is more frequent with TAVR than surgical aortic valve replacement and is associated with worse cardiovascular outcomes. Recent publications focus on echocardiographic techniques to better assess the structural components of aortic valve complex, and begin to define the mechanism and risks of PVR after TAVR. SUMMARY: Imaging innovations before, during, and after TAVR may lead to improved patient selection, accelerated development of TAVR prostheses, and ultimately a fuller characterization of the performance and potential limitations of a new generation of prosthetic heart valves.

Impact of blood pressure on the Doppler echocardiographic assessment of severity of aortic stenosis.

OBJECTIVE: To investigate the impact of blood pressure (BP) on the Doppler echocardiographic (Doppler-echo) evaluation of severity of aortic stenosis (AS). METHODS: Handgrip exercise or phenylephrine infusion was used to increase BP in 22 patients with AS. Indices of AS severity (mean pressure gradient (DeltaP(mean)), aortic valve area (AVA), valve resistance, percentage left ventricular stroke work loss (% LVSW loss) and the energy loss coefficient (ELCo)) were measured at baseline, peak BP intervention and recovery. RESULTS: From baseline to peak intervention, mean (SD) BP increased (99 (8) vs 121 (10) mm Hg, p<0.001), systemic vascular resistance (SVR) increased (1294 (264) vs 1552 (372) dynexs/cm(5), p<0.001) and mean (SD) transvalvular flow rate (Q(mean)) decreased (323 (67) vs 306 (66) ml/s, p = 0.02). There was no change in DeltaP(mean) (36 (13) vs 36 (14) mm Hg, p = NS). However, there was a decrease in AVA (1.15 (0.32) vs 1.09 (0.33) cm(2), p = 0.02) and ELCo (1.32 (0.40) vs 1.24 (0.42) cm(2), p = 0.04), and an increase in valve resistance (153 (63) vs 164 (74) dynexs/cm(5), p = 0.02), suggesting a more severe valve stenosis. In contrast, % LVSW loss decreased (19.8 (6) vs 16.5 (6)%, p<0.001), suggesting a less severe valve stenosis. There was an inverse relationship between the change in mean BP and AVA (r = -0.34, p = 0.02); however, only the change in Q(mean) was an independent predictor of the change in AVA (r = 0.81, p<0.001). CONCLUSIONS: Acute BP elevation due to increased SVR can affect the Doppler-echo evaluation of AS severity. However, the impact of BP on the assessment of AS severity depends primarily on the associated change in Q(mean), rather than on an independent effect of SVR or arterial compliance, and can result in a valve appearing either more or less stenotic depending on the direction and magnitude of the change in Q(mean).

Dynamic contrast-enhanced MR urography in the evaluation of pediatric hydronephrosis: Part 1, functional assessment.

OBJECTIVE: The purpose of our study was to derive time-intensity curves for the renal cortex and medulla from 3D dynamic MR urography and to assess whether these curves are predictive of obstruction. MATERIALS AND METHODS: Fifty-nine examinations were performed in 53 pediatric patients and the degree of obstruction assessed using the renal transit time. The cortex and medulla were segmented using a semiautomatic method, and mean time-intensity curves were derived for the segmented volumes. The basic parameters of the curves (amplitude, washout) were assessed, as was the presence of certain characteristic features of the curves. RESULTS: The images allowed clear visualization of three phases of the uptake of contrast material in the cortex, the medulla, and the collecting system. Both the amplitude of the curves and the washout of the contrast material were predictive of obstruction. The distal tubular peak was reliably detected in the cortex of nonobstructed kidneys. CONCLUSION: Combining signal-intensity-versus-time-curve analysis with the other parameters that can be derived from the same MR urography data set provides a powerful tool for the diagnosis of obstruction.

Dynamic contrast-enhanced MR urography in the evaluation of pediatric hydronephrosis: Part 2, anatomic and functional assessment of ureteropelvic junction obstruction [corrected].

OBJECTIVE: The purpose of our study was to retrospectively review our experience using MR urography in the diagnosis of ureteropelvic junction (UPJ) obstruction in children. MATERIALS AND METHODS: Sixty-one studies were performed in 50 children with hydronephrosis but without hydroureter. Anatomic criteria assessed included degree of hydronephrosis, morphology of the renal pelvis, atrophy of medulla, swirling contrast material, fluid levels, and the presence of fetal folds and crossing vessels. Functional criteria included renal transit time, differential renal function, and time-intensity curves when available. RESULTS: Thirty-one kidneys were classified as obstructed, 15 as equivocal, and 15 as nonobstructed. Obstructed systems had more marked hydronephrosis, more extensive medullary atrophy, more fluid levels, and more swirling contrast material. Fetal folds were seen in only the equivocal and nonobstructed groups. Crossing vessels were seen in all groups. Obstructed systems also showed greater functional derangement, decreased split renal function, and abnormal time-intensity curves. CONCLUSION: MR urography provides both excellent anatomic and functional information in children with UPJ obstruction in a single test that does not use ionizing radiation. MR urography may lead to greater understanding of the pathophysiology of UPJ obstruction.

The impact of FDA guidance on pharmacogenomic data submissions on drug development.

After a long wait, the US Food and Drug Administration (FDA) finally released the much anticipated 'Guidance on Pharmacogenomic Data Submissions on Drug Development' in March 2005, but what impact will this have on the drug industry as a whole? It is becoming increasingly apparent that the field of pharmacogenomics can add value to both clinical trial design and the drug development process, but uptake by the pharmaceutical industry has so far been variable between companies. The opinion of the FDA is that the use of pharmacogenomics in drug development is a 'good thing' and one that it wishes to promote, hence, this new guidance is designed to assist drug companies to adopt pharmacogenomic technology in clinical development, and covers both targeted and exploratory aspects. While targeted pharmacogenomics must be included as part of any regulatory submission, exploratory approaches may be submitted voluntarily with assurances from the FDA that any such submissions will not be used to make regulatory decisions. With this regulatory framework now in place it is only a matter of time before it is known how the industry reacts and the impact it will have on drug development.

DxS Ltd.

DxS is a pharmacogenomics business operating at the interface between genetic diagnostics and the pharmaceutical industry. The company strategy is to enable pharmacogenomics by the provision of genetic analysis services to the healthcare sector. The services provide support for drug discovery, drug development and also drug marketing via the introduction of "personalized medicines". Rather than specialize in a particular field of medicine, DxS has chosen to operate on a fee for service basis and concentrate on the provision of exceptional levels of customer, technical and logistical support to facilitate the development and introduction of pharmacogenomics. A major focus is the provision of genetic analysis services to support clinical trials and consequently the service operation is carried out under stringent quality systems. The business is also developing the Genetwork--a global alliance of diagnostic service laboratories to provide the diagnostic genotyping needed to implement personalized medicine.