Cerebral and Retinal Infarction in Bicuspid Aortic Valve

Background Description of cerebral and retinal infarction in patients with bicuspid aortic valve (BAV) is limited to case reports. We aimed to characterize cerebral and retinal infarction and examine outcomes in patients with BAV. Methods and Results Consecutive patients from 1975 to 2015 with BAV (n=5401) were retrospectively identified from the institutional database; those with confirmed cerebral or retinal infarction were analyzed. Infarction occurring after aortic valve replacement was not included. Patients were grouped according to infarction pathogenesis: embolism from a degenerative calcific BAV (BAVi); non‐BAV, large artery atherosclerotic or lacunar infarction (LAi); and non‐BAV, non‐large artery embolic infarction (nLAi). There were 83/5401 (1.5%) patients, mean age 54±12 years and 28% female, with confirmed cerebral or retinal infarction (LAi 23/83 [28%]; nLAi 30/83 [36%]; BAVi 26/83 [31%]; other 4/83 [5%]). Infarction was embolic in 72/83 (87%), and 35/72 (49%) were cardioembolic. CHA2DS2‐VASc score was 1.4±1.2 in BAVi (P=0.188 versus nLAi) and 2.3±1.2 in LAi (P=0.005). Recurrent infarction occurred in 41% overall (50% BAVi, P=0.164 and 0.803 versus LAi and nLAi). BAVi was more commonly retinal (39% BAVi versus 13% LAi, P=0.044 versus 0% nLAi, P=0.002). Patients with BAVi and LAi were more likely to have moderate‐to‐severe aortic stenosis and undergo aortic valve replacement compared with patients with nLAi. Conclusions Cardioembolism, often from degenerative calcification of the aortic valve, is a predominant cause of cerebral and retinal infarction in patients with BAV and is frequently recurrent. Cerebral and retinal infarction should be regarded as a complication of BAV

Underestimation of aortic stenosis severity by doppler mean gradient during atrial fibrillation : insights from aortic valve weight

Background: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity when obtained during atrial fibrillation (AF) compared with sinus rhythm (SR). Aortic valve weight (AVW) is a flow-independent measure of AS severity. The objective of this study was to determine whether AVW or AVW/MG ratio was increased in AF versus SR in patients with AS. Methods: Excised native aortic valves from 495 consecutive patients (median age, 77 years; interquartile range [IQR], 71-82 years; 40% women), with left ventricular ejection fractions ≥50% who underwent surgical aortic valve replacement for native valve severe AS (aortic valve area ≤ 1 cm2 or indexed aortic valve area ≤ 0.6 cm2/m2) were weighed. Excised AVW/MG ratios were compared in AF versus SR in patients with high-gradient AS (aortic peak velocity ≥ 4 m/sec or MG ≥ 40 mm Hg) and low-gradient AS (aortic peak velocity < 4 m/sec and MG < 40 mm Hg) in sex-specific analyses. Results: AF was present in 51 patients (10%; 11 of 51 [22%] had low-gradient AS) and SR in 444 (90%; 23 of 444 [5%] had low-gradient AS). There was no difference in sex distribution between AF and SR. Aortic valve area was not different, but forward stroke volume index and transaortic valve flow rate were lower in AF (P ≤ .002 for all); MG was lower in AF versus SR (median, 46 mm Hg [IQR, 37-50 mm Hg] vs 50 mm Hg [IQR, 44-61 mm Hg]; P < .0001). Overall AVW was not different (median, 2,290 mg [IQR, 1,830-3,063 mg] vs 2,140 mg [IQR, 1,530-2,958 mg]; P = .31), but overall AVW/MG ratio was higher in AF (median, 55 [IQR, 41-67] vs 42 [IQR, 30-55]; P = .001). In sex- and MG-specific analyses, the AVW/MG ratio was higher in AF compared with SR in men with high-gradient AS (median, 58 [IQR, 41-75] vs 51 [IQR, 39-61]; P = .03), but the differences were not statistically significant between AF and SR in other groups. Conclusions: AVW was discordant to Doppler MG in AF compared with SR in men with high-gradient AS. Additional studies of the relationship of MG to other measures of AS severity, such as leaflet fibrosis, are needed

Recellularization of a novel off-the-shelf valve following xenogenic implantation into the right ventricular outflow tract.

Current research on valvular heart repair has focused on tissue-engineered heart valves (TEHV) because of its potential to grow similarly to native heart valves. Decellularized xenografts are a promising solution; however, host recellularization remains challenging. In this study, decellularized porcine aortic valves were implanted into the right ventricular outflow tract (RVOT) of sheep to investigate recellularization potential. Porcine aortic valves, decellularized with sodium dodecyl sulfate (SDS), were sterilized by supercritical carbon dioxide (scCO2) and implanted into the RVOT of five juvenile polypay sheep for 5 months (n = 5). During implantation, functionality of the valves was assessed by serial echocardiography, blood tests, and right heart pulmonary artery catheterization measurements. The explanted valves were characterized through gross examination, mechanical characterization, and immunohistochemical analysis including cell viability, phenotype, proliferation, and extracellular matrix generation. Gross examination of the valve cusps demonstrated the absence of thrombosis. Bacterial and fungal stains were negative for pathogenic microbes. Immunohistochemical analysis showed the presence of myofibroblast-like cell infiltration with formation of new collagen fibrils and the existence of an endothelial layer at the surface of the explant. Analysis of cell phenotype and morphology showed no lymphoplasmacytic infiltration. Tensile mechanical testing of valve cusps revealed an increase in stiffness while strength was maintained during implantation. The increased tensile stiffness confirms the recellularization of the cusps by collagen synthesizing cells. The current study demonstrated the feasibility of the trans-species implantation of a non-fixed decellularized porcine aortic valve into the RVOT of sheep. The implantation resulted in recellularization of the valve with sufficient hemodynamic function for the 5-month study. Thus, the study supports a potential role for use of a TEHV for the treatment of valve disease in humans

Sex-related differences in calcific aortic stenosis : correlating clinical and echocardiographic characteristics and computed tomography aortic valve calcium score to excised aortic valve weight

Aims; Calcific aortic valve stenosis (AS) is purportedly associated with less calcium burden in women than in men. We sought to examine sex-related differences and correlates of surgically excised aortic valve weight (AVW) in pure AS. Methods and results: Clinical and echocardiographic characteristics of 888 consecutive patients who underwent aortic valve replacement for severe AS were correlated to AVW, and in 126 patients, AVW was also correlated to computed tomography aortic valve calcium (AVC) score. Women and men had similar indexed valve area (0.42 ± 0.09 vs. 0.42 ± 0.07 cm2/m2, P = 0.95) and mean systolic gradient (53 ± 15 vs. 52 ± 13 mmHg, P = 0.11), but women had higher New York Heart Association class (2.63 ± 0.70 vs. 2.50 ± 0.70, P = 0.01) and less prevalent coronary artery disease (38 vs. 52%, P < 0.0001). Aortic valve weight was lower in women (1.94 ± 0.88 vs. 3.08 ± 1.32 g, P < 0.0001) even when indexed to body surface area (1.09 ± 0.48 vs. 1.48 ± 0.62 g/m2, P < 0.0001) or left ventricular outflow tract (LVOT) area (0.54 ± 0.23 vs. 0.71 ± 0.29 g/cm2, P < 0.0001). Using multivariate analysis, male sex (P < 0.0001), bicuspid valve (P < 0.0001), and larger LVOT area (P < 0.0001) were the major determinants of increased AVW, along with current cigarette smoking (P = 0.007). Diabetes (P = 0.004) and hypertension (P = 0.03) were independently associated with lower AVW. Aortic valve calcium correlated well with AVW (r = 0.81, P < 0.0001) and was lower in women than in men (2520 ± 1199 vs. 3606 ± 1632 arbitrary units, P < 0.0001). Conclusions: Despite the same degree of AS severity, women have less AVC and lower AVW compared with men, irrespective of valve morphology. Aortic valve calcium is correlated to excised AVW. Hypertension, diabetes, and current cigarette smoking were independently associated with AVW

2-year clinical and echocardiography follow-up of transcatheter mitral valve replacement with the transapical intrepid system

Background: Thirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. Objectives: The authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. Methods: Patient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. Results: The cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, \u3e50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. Conclusions: This analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years

Thirty-day outcomes following transfemoral transseptal transcatheter mitral valve replacement: Intrepid TMVR early feasibility study results

Objectives: To evaluate outcomes of transcatheter mitral valve replacement (TMVR) with transfemoral access in patients at prohibitive or high surgical risk. Background: Prohibitive surgical risk may preclude MVR surgery in some patients. The investigational Intrepid TMVR system (Medtronic, Minneapolis, MN) has previously been evaluated using transapical access for delivery of a self-expanding bioprosthetic valve. Methods: This prospective, multi-center, non-randomized early feasibility study (EFS) evaluated safety and performance of the Intrepid valve using transfemoral/transseptal access in patients with moderate-severe/severe, symptomatic mitral regurgitation (MR) at high surgical risk. Candidacy was determined by heart teams with approval by a central screening committee. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. Results: Fifteen patients were enrolled at 6 sites from Feb 2020-May 2021. Median age was 80 years and STS-PROM was 4.7%; 87% were male and 53% had prior sternotomy. Fourteen implants were successful. One patient converted to surgery during the index procedure. Patients stayed a median 5 days post-procedure. There were 6 (40%) access site bleeds and 11 (73%) iatrogenic ASD closures. At 30 days, there were no deaths, strokes, or reinterventions. All implanted patients had trace/no valvar or paravalvar MR and mean gradient was 4.7±1.8 mmHg. Conclusions: Thirty-day results from the Intrepid transfemoral TMVR EFS demonstrate excellent valve function and no mortality or stroke. Additional patients and longer follow-up are needed to confirm these findings

Mechanical properties.

<p>(A.) Stiffness comparison of native porcine, decellularized porcine with sterilization, and recellularized porcine explant after 5 months in vivo. (B.) Ultimate tensile strength comparison of native porcine, decellularized porcine implant with sterilization, and recellularized porcine explant after 5-months in vivo.</p