Assessment of mitral bioprostheses using cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>The orifice area of mitral bioprostheses provides important information regarding their hemodynamic performance. It is usually calculated by transthoracic echocardiography (TTE), however, accurate and reproducible determination may be challenging. Cardiovascular magnetic resonance (CMR) has been proven as an accurate alternative for assessing aortic bioprostheses. However, whether CMR can be similarly applied for bioprostheses in the mitral position, particularly in the presence of frequently coincident arrhythmias, is unclear. The aim of the study is to test the feasibility of CMR to evaluate the orifice area of mitral bioprostheses.</p> <p>Methods</p> <p>CMR planimetry was performed in 18 consecutive patients with mitral bioprostheses (n = 13 Hancock^®, n = 4 Labcore^®, n = 1 Perimount^®; mean time since implantation 4.5 ± 3.9 years) in an imaging plane perpendicular to the transprosthetic flow using steady-state free-precession cine imaging under breath-hold conditions on a 1.5T MR system. CMR results were compared with pressure half-time derived orifice areas obtained by TTE.</p> <p>Results</p> <p>Six subjects were in sinus rhythm, 11 in atrial fibrillation, and 1 exhibited frequent ventricular extrasystoles. CMR image quality was rated as good in 10, moderate in 6, and significantly impaired in 2 subjects. In one prosthetic type (Perimount^®), strong stent artifacts occurred. Orifice areas by CMR (mean 2.1 ± 0.3 cm²) and TTE (mean 2.1 ± 0.3 cm²) correlated significantly (r = 0.94; p < 0.001). Bland-Altman analysis showed a 95% confidence interval from -0.16 to 0.28 cm²(mean difference 0.06 ± 0.11 cm²; range -0.1 to 0.3 cm²). Intra- and inter-observer variabilities of CMR planimetry were 4.5 ± 2.9% and 7.9 ± 5.2%.</p> <p>Conclusions</p> <p>The assessment of mitral bioprostheses using CMR is feasible even in those with arrhythmias, providing orifice areas with close agreement to echocardiography and low observer dependency. Larger samples with a greater variety of prosthetic types and more cases of prosthetic dysfunction are required to confirm these preliminary results.</p

Management of patients with severe aortic stenosis in the TAVI-era: How recent recommendations are translated into clinical practice

Objective Approximately 3.4% of adults aged &gt;75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR. Methods Participants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR. Results Of 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; p&lt;0.001) below the study median; or with a left ventricular end systolic diameter above the study median (p=0.007) were more likely to be assigned to AVR. Conclusions There may be considerable discrepancies between guideline-based recommendations and clinical practice decision-making in the treatment of AS. It appears that guidelines may not fully capture the complete clinical spectrum of patients with AS. Thus, there is a need to find ways to increase their acceptance and the rate of adoption

IMPULSE: The impact of gender on the presentation and management of aortic stenosis across Europe

Aims There is an increasing awareness of gender-related differences in patients with severe aortic stenosis and their outcomes after surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). Methods Data from the IMPULSE registry were analysed. Patients with severe aortic stenosis (AS) were enrolled between March 2015 and April 2017 and stratified by gender. A subgroup analysis was performed to assess the impact of age. Results Overall, 2171 patients were enrolled, and 48.0% were female. Women were characterised by a higher rate of renal impairment (31.7 vs 23.3%; p&lt;0.001), were at higher surgical risk (EuroSCORE II: 4.5 vs 3.6%; p=0.001) and more often in a critical preoperative state (7.0vs 4.2%; p=0.003). Men had an increased rate of previous cardiac surgery (9.4 vs 4.7%; p&lt;0.001) and a reduced left ventricular ejection fraction (4.9 vs 1.3%; p&lt;0.001). Concomitant mitral and tricuspid valve disease was substantially more common among women. Symptoms were highly prevalent in both women and men (83.6 vs 77.3%; p&lt;0.001). AVR was planned in 1379 cases. Women were more frequently scheduled to undergo TAVI (49.3 vs 41.0%; p&lt;0.001) and less frequently for SAVR (20.3 vs 27.5%; p&lt;0.001). Conclusions The present data show that female patients with severe AS have a distinct patient profile and are managed in a different way to males. Gender-based differences in the management of patients with severe AS need to be taken into account more systematically to improve outcomes, especially for women

Impact of selected comorbidities on the presentation and management of aortic stenosis

Background Contemporary data regarding the impact of comorbidities on the clinical presentation and management of patients with severe aortic stenosis (AS) are scarce. Methods Prospective registry of severe patients with AS across 23 centres in nine European countries. Results Of the 2171 patients, chronic kidney disease (CKD 27.3%), left ventricular ejection fraction (LVEF) &lt;50% (22.0%), atrial fibrillation (15.9%) and chronic obstructive pulmonary disease (11.4%) were the most prevalent comorbidities (49.3% none, 33.9% one and 16.8% ≥2 of these). The decision to perform aortic valve replacement (AVR) was taken in a comparable proportion (67%, 72% and 69%, in patients with 0, 1 and ≥2 comorbidities; p=0.186). However, the decision for TAVI was more common with more comorbidities (35.4%, 54.0% and 57.0% for no, 1 and ≥2; p&lt;0.001), while the decision for surgical AVR (SAVR) was decreased with increasing comorbidity burden (31.9%, 17.4% and 12.3%; p&lt;0.001). The proportion of patients with planned AVRs that were performed within 3 months was significantly higher in patients with 1 or ≥2 comorbidities than in those without (8.7%, 10.0% and 15.7%; p&lt;0.001). Furthermore, the mean time to AVR was significantly shorter in patients with one (30.5 days) or ≥2 comorbidities (30.8 days) than in those without (35.7 days; p=0.012). Patients with reduced LVEF tended to be offered an AVR more frequently and with a shorter delay while patients with CKD were less frequently treated. Conclusions Comorbidities in severe patients with AS affect the presentation and management of patients with severe AS. TAVI was offered more often than SAVR and performed within a shorter time period

Facilitated Data Relay and Effects on Treatment of Severe Aortic Stenosis in Europe

Background: Many patients with severe aortic stenosis are referred late with advanced symptoms or inappropriately denied intervention. The objective was to investigate whether a structured communication to referring physicians (facilitated data relay) might improve the rate and timeliness of intervention. Methods and Results: A prospective registry of consecutive patients with severe aortic stenosis at 23 centers in 9 European countries with transcatheter as well as surgical aortic valve replacement being available was performed. The study included a 3-month documentation of the status quo (phase A), a 6-month intervention phase (implementing facilitated data relay), and a 3-month documentation of a legacy effect (phase-B). Two thousand one hundred seventy-one patients with severe aortic stenoses were enrolled (phase A: 759; intervention: 905; phase-B: 507). Mean age was 77.9±10.0&nbsp;years, and 80% were symptomatic, including 52% with severe symptoms. During phase A, intervention was planned in 464/696 (67%), 138 (20%) were assigned to watchful waiting, 8 (1%) to balloon aortic valvuloplasty, 60 (9%) were listed as not for active treatment, and in 26 (4%), no decision was made. Three hundred sixty-three of 464 (78%) patients received the planned intervention within 3&nbsp;months. Timeliness of the intervention improved as shown by the higher number of aortic valve replacements performed within 3&nbsp;months (59% versus 51%, P=0.002) and a significant decrease in the time to intervention (36±38 versus 30±33&nbsp;days, P=0.002). Conclusions: A simple, low-cost, facilitated data relay improves timeliness of treatment for patients diagnosed with severe aortic stenosis, resulting in a shorter time to transcatheter aortic valve replacement. This effect was mainly driven by a significant improvement in timeliness of intervention in transcatheter aortic valve replacement but not surgical aortic valve replacement. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02241447

IMPULSE: the impact of gender on the presentation and management of aortic stenosis across Europe.

AIMS: There is an increasing awareness of gender-related differences in patients with severe aortic stenosis and their outcomes after surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: Data from the IMPULSE registry were analysed. Patients with severe aortic stenosis (AS) were enrolled between March 2015 and April 2017 and stratified by gender. A subgroup analysis was performed to assess the impact of age. RESULTS: Overall, 2171 patients were enrolled, and 48.0% were female. Women were characterised by a higher rate of renal impairment (31.7 vs 23.3%; p<0.001), were at higher surgical risk (EuroSCORE II: 4.5 vs 3.6%; p=0.001) and more often in a critical preoperative state (7.0vs 4.2%; p=0.003). Men had an increased rate of previous cardiac surgery (9.4 vs 4.7%; p<0.001) and a reduced left ventricular ejection fraction (4.9 vs 1.3%; p<0.001). Concomitant mitral and tricuspid valve disease was substantially more common among women. Symptoms were highly prevalent in both women and men (83.6 vs 77.3%; p<0.001). AVR was planned in 1379 cases. Women were more frequently scheduled to undergo TAVI (49.3 vs 41.0%; p<0.001) and less frequently for SAVR (20.3 vs 27.5%; p<0.001). CONCLUSIONS: The present data show that female patients with severe AS have a distinct patient profile and are managed in a different way to males. Gender-based differences in the management of patients with severe AS need to be taken into account more systematically to improve outcomes, especially for women

Lipoprotein-associated phospholipase A2 activity, genetics and calcific aortic valve stenosis in humans.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans. METHODS AND RESULTS: Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 patients undergoing aortic valve replacement for CAVS and 414 control patients undergoing coronary artery bypass grafting. After multivariable adjustment, Lp-PLA2 activity was positively associated with the presence of CAVS (OR=1.21 (95% CI 1.04 to 1.41) per SD increment). We selected four single nucleotide polymorphisms (SNPs) at the PLA2G7 locus associated with either Lp-PLA2 mass or activity (rs7756935, rs1421368, rs1805017 and rs4498351). Genetic association studies were performed in eight cohorts: Quebec-CAVS (1009 cases/1017 controls), UK Biobank (1350 cases/349 043 controls), European Prospective Investigation into Cancer and Nutrition-Norfolk (504 cases/20 307 controls), Genetic Epidemiology Research on Aging (3469 cases/51 723 controls), Malmö Diet and Cancer Study (682 cases/5963 controls) and three French cohorts (3123 cases/6532 controls), totalling 10 137 CAVS cases and 434 585 controls. A fixed-effect meta-analysis using the inverse-variance weighted method revealed that none of the four SNPs was associated with CAVS (OR=0.99 (95% CI 0.96 to 1.02, p=0.55) for rs7756935, 0.97 (95% CI 0.93 to 1.01, p=0.11) for rs1421368, 1.00 (95% CI 1.00 to 1.01, p=0.29) for rs1805017, and 1.00 (95% CI 0.97 to 1.04, p=0.87) for rs4498351). CONCLUSIONS: Higher Lp-PLA2 activity is significantly associated with the presence of CAVS and might represent a biomarker of CAVS in patients with heart disease. Results of our genetic association study suggest that Lp-PLA2 is however unlikely to represent a causal risk factor or therapeutic target for CAVS

Symptoms, disease severity and treatment of adults with a new diagnosis of severe aortic stenosis

Objective Contemporary data on patients with previously undiagnosed severe aortic stenosis (AS) are scarce. We aimed to address this gap by gathering data from consecutive patients diagnosed with severe AS on echocardiography. Methods This was a prospective, multicentre, multinational, registry in 23 tertiary care hospitals across 9 European countries. Patients with a diagnosis of severe AS were included using echocardiography (aortic valve area (AVA) &lt;1 cm 2, indexed AVA &lt;0.6 cm 2 /m 2, maximum jet-velocity (V max) &gt;4 m/s and/or mean transvalvular gradient &gt;40 mm Hg). Results The 2171 participants had a mean age of 77.9 years and 48.0% were female. The mean AVA was 0.73 cm 2, V max 4.3 m/s and mean gradient 47.1 mm Hg; 62.1% had left ventricular hypertrophy and 27.3% an ejection fraction (EF) &lt;50%. 1743 patients (80.3%) were symptomatic (shortness-of-breath 91.0%; dizziness 30.2%, chest pain 28.9%). Patients had a EuroSCORE II of 4.0; 25.3% had a creatinine clearance &lt;50 mL/min, and 3.2% had an EF &lt;30%. Symptomatic patients were older and had more comorbidities than asymptomatic patients. Despite European Society of Cardiology 2017 valvular heart disease guideline class I recommendation, in only 76.2% a decision was made for an intervention (transcatheter 50.4%, surgical aortic valve replacement 25.8%). In asymptomatic patients, 57.7% with a class I/IIa indication were scheduled for a procedure, while 36.3% patients without an indication had their valve replaced. Conclusions The majority of patients with severe AS presented at an advanced disease stage. Management of severe AS remained suboptimal in a significant proportion of contemporary patients with severe AS. Trial registration number NCT02241447;Results

Suppression of Signal Transducer and Activator of Transcription 3–Dependent B Lymphocyte Terminal Differentiation by Bcl-6

Lymphocytes usually differentiate into effector cells within days after antigen exposure, except in germinal centers where terminal differentiation is delayed while somatic hypermutation creates high-affinity antibody mutants. Here we investigate whether arrest of terminal differentiation can be mediated by BCL-6, a transcriptional repressor that is expressed by germinal center B cells and is required for this phase of B cell development. We find that BCL-6 suppresses the differentiation of transformed and primary B cells to plasma cells by inhibiting the signal transducer and activator of transcription 3–dependent expression of the major regulator of plasma cell development, the B lymphocyte–induced maturation protein (Blimp-1). This function of BCL-6 as a repressor of B lymphocyte differentiation may also underlie the association between chromosomal translocations of its gene and B cell lymphomas