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Background Undertreatment of heart valve disease creates unnecessary patient risk. Poorly integrated healthcare data systems are unequipped to solve this problem. A software program using a rules-based algorithm to search the electronic health record for heart valve disease among patients treated by healthcare systems in the United States may provide a solution. Methods A software interface allowed concurrent access to picture archiving communication systems, the electronic health record, and other sources. The software platform was created to programmatically run a rules engine to search structured and unstructured data for identification of moderate or severe heart valve disease using guideline-reported values. Incidence and progression of disease as well as compliance with a care pathway were assessed. Results In 2 health institutions in the United States 60,145 patients had 77,215 echocardiograms. Moderate or severe aortic stenosis (AS) was identified at a rate of 9.1% of patients (5474 and 6910 echocardiograms) in this population. The precision and accuracy of the algorithm for the detection of moderate or severe AS was 92.9% and 98.6%, respectively. Thirty-five percent of patients (441/1265) with moderate stenosis and a subsequent echocardiogram progressed to severe stenosis (mean interval, 358 days). In 1 sample 70.3% of moderate AS patients lacked a 6-month echocardiogram or appointment. The platform enabled 100% accountability for all patients with severe AS. Conclusions A rules-based software program enhances detection of heart valve disease and can be used to measures disease progression and care pathway compliance.

ImportanceThe frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood.ObjectiveTo evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery.Design, Setting, and ParticipantsThis post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve stenosis deemed to be at intermediate or increased risk of 30-day surgical mortality were included. Data were collected from December 2010 to June 2016, and data were analyzed from December 2021 to October 2022.InterventionsPatients were randomized to self-expanding TAVI or surgery in the RCTs or underwent self-expanding TAVI for clinical indications in the nonrandomized studies.Main Outcomes and MeasuresThe primary end point was the incidence of SVD through 5 years (from the RCTs). Factors associated with SVD and its association with clinical outcomes were evaluated for the pooled RCT and non-RCT population. SVD was defined as (1) an increase in mean gradient of 10 mm Hg or greater from discharge or at 30 days to last echocardiography with a final mean gradient of 20 mm Hg or greater or (2) new-onset moderate or severe intraprosthetic aortic regurgitation or an increase of 1 grade or more.ResultsOf 4762 included patients, 2605 (54.7%) were male, and the mean (SD) age was 82.1 (7.4) years. A total of 2099 RCT patients, including 1128 who received TAVI and 971 who received surgery, and 2663 non-RCT patients who received TAVI were included. The cumulative incidence of SVD treating death as a competing risk was lower in patients undergoing TAVI than surgery (TAVI, 2.20%; surgery, 4.38%; hazard ratio [HR], 0.46; 95% CI, 0.27-0.78; P = .004). This lower risk was most pronounced in patients with smaller annuli (23 mm diameter or smaller; TAVI, 1.32%; surgery, 5.84%; HR, 0.21; 95% CI, 0.06-0.73; P = .02). SVD was associated with increased 5-year all-cause mortality (HR, 2.03; 95% CI, 1.46-2.82; P P = .006), and valve disease or worsening heart failure hospitalizations (HR, 2.17; 95% CI, 1.23-3.84; P = .008). Predictors of SVD were developed from multivariate analysis.Conclusions and RelevanceThis study found a lower rate of SVD in patients undergoing self-expanding TAVI vs surgery at 5 years. Doppler echocardiography was a valuable tool to detect SVD, which was associated with worse clinical outcomes.Trial RegistrationClinicalTrials.gov Identifiers: NCT01240902, NCT01586910, and NCT01531374

Objectives The aim of this study was to report the 2-year results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial and confirm the interim Bayesian analysis. Background Transcatheter aortic valve replacement (TAVR) with a self-expanding valve was noninferior to surgery in patients with severe aortic stenosis and intermediate operative risk using Bayesian statistical methods. Novel Bayesian designs have been used to shorten the time to primary endpoint analysis in randomized clinical trials, although the predictive value of Bayesian analysis compared with frequentist approaches remains debated. Methods The SURTAVI trial randomized 1,660 patients. An interim analysis was performed 1 year after the 1,400th patient was treated to estimate the primary 2-year endpoint of all-cause mortality or disabling strokes for all patients. Results The Kaplan-Meier rate for the complete 2-year primary endpoint was 12.7% in the TAVR group and 12.6% in the surgery group (0.0% difference; 95% confidence interval: −3.4% to 3.5%), compared with 12.6% with TAVR and 14.0% with surgery (−1.4% difference; Bayesian credible interval: −5.2% to 2.3%) in the interim Bayesian analysis. A comparison of individual clinical, hemodynamic, and quality-of-life endpoints using Bayesian and frequentist methods found no significant differences. Conclusions The complete analysis of all patients with aortic stenosis at intermediate risk for surgery in the SURTAVI trial confirmed the noninferiority, with respect to the frequency of all-cause mortality or disabling stroke, of TAVR to surgery, as determined in the interim Bayesian analysis. Follow-up will extend out to 10 years.

To assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR).PH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown.Retrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon-expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36-49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed.Mean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III-IV. There was no significant difference in all-cause mortality at 30 days (no PH = 27.3%, mild-moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild-moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups.This study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

Background Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is know...

Clinical decision support systems are used to ensure compliance with guidelines and can assist providers in improving quality of care. This quality improvement initiative was designed to evaluate the use of a clinical decision support system to improve specialist referral rate for patients with severe aortic stenosis. A clinical decision support system for cardiology and primary care providers was implemented to improve diagnosis of severe aortic stenosis. The ordering provider received an electronic medical record in-basket alert providing feedback and recommendations for referral to specialist for evaluation. The echocardiogram data were evaluated for change in specialist referral rate. Before clinical decision support system implementation, the referral rate was 72% for a 3-month period. All providers ordering echocardiograms received clinical decision support system notification if patient results met criteria based on valve severity (aortic valve area < 1.0 cm, mean gradient ≥ 40 mm Hg, peak velocity ≥ 4.0 m/s). After implementation, clinical decision support system referral rate was 97.5%, a 24.6% increase in referral rates (P < .001). Low referral rates for patients with severe aortic stenosis are a recognized challenge. Utilizing the clinical decision support system to improve awareness of quality guidelines and recommendations was associated with increased adherence to referral guidelines by providers. This innovation is pertinent to practice and enhances the functionality of the electronic medical record by providing real-time feedback to providers to improve practice. Referral rates for patients with severe aortic stenosis can be improved with use of provider clinical decision support system.

Neurological events after aortic valve interventions are associated with increased mortality and morbidity. Transcatheter aortic valve replacement (TAVR) is increasingly offered for lower-risk patients with severe aortic stenosis, previously considered candidates for surgical aortic valve replacement (SAVR). Differences in post-procedural neurological events have important implications in treatment allocation.The authors sought to analyze the neurological events in the randomized SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial.Patients with severe, symptomatic aortic stenosis at intermediate surgical risk were randomized 1:1 to TAVR or SAVR. The rates of neurological events and quality of life were analyzed at 30 days, and 6 and 12 months post-procedure in a modified intention-to-treat population (mean age 79.8 ± 6.2 years; N = 1,660).The rates of early (30-day) stroke and post-procedural encephalopathy were higher after SAVR versus TAVR (5.4% vs. 3.3%; p = 0.031; and 7.8% vs. 1.6%; p 0.001, respectively). At 12 months, the rate of stroke was not different between SAVR and TAVR (6.9% vs. 5.2%; p = 0.136). Early stroke and early encephalopathy resulted in an elevated mortality at 12 months in both treatment groups. Quality of life after an early stroke was significantly lower in SAVR versus TAVR patients at 30 days and was similar at 6 and 12 months.The early stroke rate was lower after TAVR than SAVR. In patients with early strokes, QOL improved earlier after TAVR. At 12-month follow-up, stroke rates and QOL were not different between TAVR and SAVR patients. (Surgical Replacement and Transcatheter Aortic Valve Implantation [SURTAVI]; NCT01586910).

Background As transcatheter aortic valve replacement expands to younger and/or lower risk patients, the long‐term consequences of permanent pacemaker implantation are a concern. Pacemaker dependency and impact have not been methodically assessed in transcatheter aortic valve replacement trials. We report the incidence and predictors of pacemaker implantation and pacemaker dependency after transcatheter aortic valve replacement with the Lotus valve. Methods and Results A total of 912 patients with high/extreme surgical risk and symptomatic aortic stenosis were randomized 2:1 (Lotus:CoreValve) in REPRISE III (The Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System—Randomized Clinical Evaluation) trial. Systematic assessment of pacemaker dependency was pre‐specified in the trial design. Pacemaker implantation within 30 days was more frequent with Lotus than CoreValve. By multivariable analysis, predictors of pacemaker implantation included baseline right bundle branch block and depth of implantation; diabetes mellitus was also a predictor with Lotus. No association between new pacemaker implantation and clinical outcomes was found. Pacemaker dependency was dynamic (30 days: 43%; 1 year: 50%) and not consistent for individual patients over time. Predictors of pacemaker dependency at 30 days included baseline right bundle branch block, female sex, and depth of implantation. No differences in mortality or stroke were found between patients who were pacemaker dependent or not at 30 days. Rehospitalization was higher in patients who were not pacemaker dependent versus patients without a pacemaker or those who were dependent. Conclusions Pacemaker implantation was not associated with adverse clinical outcomes. Most patients with a new pacemaker at 30 days were not dependent at 1 year. Mortality and stroke were similar between patients with or without pacemaker dependency and patients without a pacemaker. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier NCT 02202434.

Background The risk of surgical mitral valve replacement in patients with severe mitral annular calcification (MAC) is high. Several patients worldwide with severe MAC have been treated successfully with transcatheter mitral valve replacement (TMVR) using balloon-expandable aortic transcatheter valves. The TMVR in MAC Global Registry is a multicenter registry that collects data on outcomes of these procedures. Objectives The goal of this study was to evaluate 1-year outcomes in this registry. Methods This study was a multicenter retrospective review of clinical outcomes. Results A total of 116 extreme surgical risk patients with severe MAC underwent TMVR; 106 had a procedure date >1 year before data-lock and were included in the analysis. Their mean age was 73 ± 12 years, and 68% were female. The mean Society of Thoracic Surgeons score was 15.3 ± 11.6%, and 90% were in New York Heart Association functional class III or IV. Thirty-day and 1-year all-cause mortality was 25% and 53.7%, respectively. Most patients who survived 30 days were alive at 1 year (49 of 77 [63.6%]), and the majority (71.8%) were in New York Heart Association functional class I or II. Echocardiography data at 1 year were available in 34 patients. Mean left ventricular ejection fraction was 58.6 ± 11.2%, mean mitral valve area was 1.9 ± 0.5 cm2, mean mitral gradient was 5.8 ± 2.2 mm Hg, and 75% had zero or trace mitral regurgitation. Conclusions TMVR with balloon-expandable aortic valves in extreme surgical risk patients with severe MAC is feasible but associated with high 30-day and 1-year mortality. Most patients who survive the 30-day post-procedural period are alive at 1 year and have sustained improvement of symptoms and transcatheter valve performance. The role of TMVR in patients with MAC requires further evaluation in clinical trials.

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.

Objectives This study evaluated the safety and effectiveness of self-expanding transcatheter aortic valve replacement (TAVR) in patients with surgical valve failure (SVF). Background Self-expanding TAVR is superior to medical therapy for patients with severe native aortic valve stenosis at increased surgical risk. Methods The CoreValve U.S. Expanded Use Study was a prospective, nonrandomized study that enrolled 233 patients with symptomatic SVF who were deemed unsuitable for reoperation. Patients were treated with self-expanding TAVR and evaluated for 30-day and 1-year outcomes after the procedure. An independent core laboratory was used to evaluate serial echocardiograms for valve hemodynamics and aortic regurgitation. Results SVF occurred through stenosis (56.4%), regurgitation (22.0%), or a combination (21.6%). A total of 227 patients underwent attempted TAVR and successful TAVR was achieved in 225 (99.1%) patients. Patients were elderly (76.7 ± 10.8 years), had a Society of Thoracic Surgeons Predicted Risk of Mortality score of 9.0 ± 6.7%, and were severely symptomatic (86.8% New York Heart Association functional class III or IV). The all-cause mortality rate was 2.2% at 30 days and 14.6% at 1 year; major stroke rate was 0.4% at 30 days and 1.8% at 1 year. Moderate aortic regurgitation occurred in 3.5% of patients at 30 days and 7.4% of patients at 1 year, with no severe aortic regurgitation. The rate of new permanent pacemaker implantation was 8.1% at 30 days and 11.0% at 1 year. The mean valve gradient was 17.0 ± 8.8 mm Hg at 30 days and 16.6 ± 8.9 mm Hg at 1 year. Factors significantly associated with higher discharge mean aortic gradients were surgical valve size, stenosis as modality of SVF, and presence of surgical valve prosthesis patient mismatch (all p Conclusions Self-expanding TAVR in patients with SVF at increased risk for surgery was associated with a low 1-year mortality and major stroke rate, significantly improved aortic valve hemodynamics, and low rates of moderate and no severe residual aortic regurgitation, with improved quality of life.

Background End-stage renal disease (ESRD) poses unique challenges in the treatment of patients with severe aortic stenosis. Although surgical valve replacement in ESRD patients has been associated with increased mortality, the outcomes from transcatheter aortic valve replacement (TAVR) are not clearly defined. Methods The CoreValve US Expanded Use Study is a prospective, nonrandomized study of TAVR in extreme-risk patients with comorbidities excluding them from the Pivotal Trial. We report on patients with ESRD. The primary endpoint was a composite of all-cause mortality or major stroke at 1 year. Results Ninety-six patients with ESRD underwent TAVR with the CoreValve (Medtronic, Minneapolis, MN) and have reached 1-year follow-up. Mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 16.2% ± 8.4%. The rate of all-cause mortality or major stroke at 1 year was 30.3%. The all-cause mortality rate was 5.3% at 30 days and 30.3% at 1 year. The rate at 1 year of any stroke or transient ischemic attack was 2.1%; major vascular injury was 5.2%; and new permanent pacemaker was 26.8%. Valve performance improved postprocedure and remained improved at 1 year (effective orifice area 1.71 cm 2 , mean gradient 9.33 mm Hg) Conclusions Early mortality in patients with ESRD is comparable to previously published data on extreme-risk patients without ESRD, but our data suggest a higher mortality rate at 1 year for ESRD patients, likely due to comorbid conditions. Stroke and major vascular injury are infrequent, and improved valve hemodynamics are maintained at 1 year.

Background: Valve-in-valve transcatheter aortic valve replacement (TAVR) is an option when a surgical valve demonstrates deterioration and dysfunction. This study reports 3-year results following valve-in-valve with self-expanding TAVR. Methods: The CoreValve US Expanded Use Study is a prospective, nonrandomized, single-arm study that evaluates safety and effectiveness of TAVR in extreme risk patients with symptomatic failed surgical biologic aortic valves. Study end points include all-cause mortality, need for valve reintervention, hemodynamic changes over time, and quality of life through 3 years. Patients were stratified by presence of preexisting surgical valve prosthesis-patient mismatch. Results: From March 2013 to May 2015, 226 patients deemed extreme risk (STS-PROM [Society of Thoracic Surgeons Predicted Risk of Mortality] 9.0±7%) had attempted valve-in-valve TAVR. Preexisting surgical valve prosthesis-patient mismatch was present in 47.2% of the cohort. At 3 years, all-cause mortality or major stroke was 28.6%, and 93% of patients were in New York Heart Association I or II heart failure. Valve performance was maintained over 3 years with low valve reintervention rates (4.4%), an improvement in effective orifice area over time and a 2.7% rate of severe structural valve deterioration. Preexisting severe prosthesis-patient mismatch was not associated with 3-year mortality but was associated with significantly less improvement in quality of life at 3-year follow-up ( P =0.01). Conclusions: Self-expanding TAVR in patients with failed surgical bioprostheses at extreme risk for surgery was associated with durable hemodynamics and excellent clinical outcomes. Preexisting surgical valve prosthesis-patient mismatch was not associated with mortality but did limit patient improvement in quality of life over 3-year follow-up. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01675440.

Objectives This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification (MAC) and reports the first large series from a multicenter global registry. Background The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population. Methods We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR. Results From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm 2 . SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25). Conclusions TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.

Objectives To assess the treatment effect of TAVR versus SAVR on clinical outcomes to 3 years in patients stratified by chronic kidney disease (CKD) by retrospectively studying patients randomized to TAVR or SAVR. Background The impact of CKD on mid-term outcomes of patients undergoing TAVR versus SAVR is unclear. Methods Patients randomized to TAVR or SAVR in the CoreValve US Pivotal High Risk Trial were retrospectively stratified by eGFR: none/mild or moderate/severe CKD. To evaluate the impact of baseline CKD in TAVR patients only, all patients undergoing an attempted TAVR implant in the US Pivotal Trial and CAS were stratified by baseline eGFR into none/mild, moderate, and severe CKD. The primary endpoint was major adverse cardiovascular and renal events (MACRE), a composite of all-cause mortality, myocardial infarction, stroke/TIA, and new requirement of dialysis. Results Moderate/severe CKD was present in 62.7% and 60.7% of high-risk patients randomized to TAVR or SAVR, respectively. Baseline characteristics were similar between TAVR and SAVR patients in both CKD subgroups, except for higher rates of diabetes and higher serum creatinine in SAVR patients. Among high-risk patients with moderate/severe CKD, TAVR provided a lower 3-year MACRE rate compared with SAVR: 42.1% vs. 51.0, P = .04. Of 3,733 extreme- and high-risk TAVR patients, 39.9% had none/mild, 53.8% moderate, and 6.4% severe CKD. Worsening baseline CKD was associated with increased 3-year MACRE rates [none/mild 51.5%, moderate 54.5%, severe 63.1%, P = .001]. Conclusions TAVR results in lower 3-year MACRE versus SAVR in high-risk patients with moderate/severe CKD. In patients undergoing TAVR, worsening CKD increases mid-term mortality and MACRE. Randomized trials of TAVR vs. SAVR in patients with moderate-severe CKD would help elucidate the best treatment for these complex patients. Trial registration CoreValve US Pivotal Trial: NCT01240902. CoreValve Continued Access Study: NCT01531374.

Introduction: Right and left atria have different susceptibilities toward developing atrial fibrillation (AF). The molecular bases of these differences are not well characterized. Given the complexity of AF development and progression, understanding AF-associated changes in myocardial energetics between the atria will help improve mechanistic insights and therapeutics for better clinical management of AF. The aim was to compare changes in mitochondrial oxidative phosphorylation system (OXPHOS), glycolysis and Krebs cycle metabolites in right atrial (RAA) and left atrial (LAA) appendage tissue from patients with (AF) and without (non-AF) AF. Methods: RAA and LAA from well-matched AF (n=54) and non-AF (n=58) patients undergoing elective open heart surgery was collected. Functional activity of OXPHOS complexes I-V was measured spectrophotometrically. Protein expression level of OXPHOS complexes was determined by Western blot. OXPHOS gene expression level was performed using RT-PCR. Metabolites were profiled using high performance liquid chromatography coupled to tandem mass spectrometry. Comparison between groups was done applying the 2 sample t - and Wilcoxon rank sum tests with 5% level of significance. Results: The most significant AF-associated alterations in myocardial energetics were observed in RAA. In AF patients, out of 84 OXPHOS genes, expression of 14 genes was significantly reduced in RAA (p+ (p=0.03), GDP (p=0.05), citrate (p=0.03), total pool of adenine nucleotides (p=0.02) and glutathione (p=0.03) level in RAA without changes in LAA. Conclusion: AF is associated with different energetic remodeling in right and left atria, suggesting that dissimilar mechanisms may contribute to development and progression of AF.

CoreValve is widely used in transcatheter aortic valve replacement, but the impact of its deployment location on hemodynamics is unexplored despite a potential role in subsequent aortic and coronary artery pathologies. The objectives of this investigation were to perform fluid-structure interaction (FSI) simulations for a 29 mm CoreValve deployed in annular vs supra-annular locations, and characterize resulting hemodynamics including velocity and wall shear stress (WSS). Patient-specific geometry was reconstructed from computed tomography scans and CoreValve was deployed using a finite element approach. FSI simulations were then performed using a boundary conforming method and realistic boundary conditions. Results showed that CoreValve deployment location impacts hemodynamics in the ascending aorta and flow patterns in the coronary arteries. During peak-systole, annularly deployed CoreValve produced a jet-like flow structure impinging on the outer-curvature of the ascending aorta. Supra-annularly deployed CoreValve having a lateral tilt of 10° led to a more centered jet impinging further downstream. At mid-systole, valve leaflets of the annularly deployed CoreValve closed asymmetrically leading to disorganized flow patterns in the ascending aorta vs those from the supra-annular position. Supra-annularly deployed CoreValve also led to high-velocity para-valvular flow supplying the coronary arteries. CoreValve in the supra-annular position significantly (P

Transcatheter aortic valve replacement (TAVR) using a self-expanding valve has been shown to be superior to an open operation in high-risk patients. Extensive iliofemoral peripheral vascular disease can prohibit femoral access. In these cases, direct aortic (DA) implantation may be a suitable option.The current analysis compared outcomes in patients undergoing TAVR with the self-expanding CoreValve prosthesis (Medtronic, Minneapolis, MN) by direct aortic (DA) access vs iliofemoral (IF) access. Patients treated in the CoreValve US High Risk and Extreme Risk Pivotal Trials and Continued Access Study were included. Propensity score matching was used to account for differences in baseline characteristics between groups. Clinical outcomes were compared at 30 days and 1 year.We identified 394 matched pairs of IF and DA patients. The all-cause mortality rate was significantly higher in the DA group than in the IF group at 30 days (10.9% vs 4.1%, p0.001), but this difference was reduced at 1 year (28.1% vs 23.2%, p = 0.063). All-cause mortality or major stroke was significantly higher for DA vs IF access at 30 days (13.5% vs 5.3%, p0.001) and at 1 year (30.4% vs 24.2%, p = 0.025). Major/life-threatening bleeding and acute kidney injury were significantly greater in the DA group at 30 days (66.7% vs 35.4% and 19.7% vs 10.0%, respectively, both p0.001).When femoral access is not feasible, DA access allows effective delivery of the valve but incurs an increased risk of death and adverse events, potentially the result of procedural differences.

The current guideline for optimal sizing in self-expanding (Medtronic Core, Evolut R and Pro) transcatheter aortic valve replacement (TAVR) is between 10-20% oversizing, measured by aortic valve perimetry equation applied to CT data. This recommendation is based on limited data to achieve the lowest

The 34 mm EVOLUT R (Medtronic, Minneapolis, MN) self-expanding transcatheter aortic valve replacement (TAVR) was designed to treat patients with larger annuli. We describe clinical and procedural outcomes with this prosthesis in the largest single-center experience to date. Clinical, demographic

Background— The risk for stroke after transcatheter aortic valve replacement (TAVR) is an important concern. Identification of predictors for stroke is likely to be a critical factor aiding patient selection and management as TAVR use becomes widespread. Methods and Results— Patients enrolled in the CoreValve US Extreme Risk and High Risk Pivotal Trials or Continued Access Study treated with the self-expanding CoreValve bioprosthesis were included in this analysis. The 1-year stroke rate after TAVR was 8.4%. Analysis of the stroke hazard rate identified an early phase (0–10 days; 4.1% of strokes) and a late phase (11–365 days; 4.3% of strokes). Baseline predictors of early stroke included National Institutes of Health stroke scale score >0, prior stroke, prior transient ischemic attack, peripheral vascular disease, absence of prior coronary artery bypass surgery, angina, low body mass index (2 ), and falls within the past 6 months. Significant procedural predictors were total time in the catheterization laboratory or operating room, delivery catheter in the body time, rapid pacing used during valvuloplasty, and repositioning of the prosthesis. Predictors of stroke between 11 and 365 days were small body surface area, severe aortic calcification, and falls within the past 6 months. There were no significant imaging predictors of early or late stroke. Conclusions— Predictors of early stroke after TAVR included clinical and procedural factors; predictors of later stroke were limited to patient but not anatomic characteristics. These findings indicate that further refinement of imaging to identify anatomic factors predisposing to embolization may help improve stroke prediction in patients undergoing TAVR. Clinical Trial Registrations— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT01240902, NCT01531374.

Transcatheter aortic valve replacement (TAVR) is now a well-accepted alternative to surgical AVR (SAVR) for patients with symptomatic aortic stenosis at increased operative risk. There is interest in whether TAVR would benefit patients at lower risk.The Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) has trended downward in US TAVR trials and the STS/American College of Cardiology Transcatheter Valve Therapy Registry. We hypothesized that if the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) alone is sufficient to define decreased risk, the contribution to survival based on the degree of invasiveness of the TAVR procedure will decrease, making it more difficult to show improved survival and benefit over SAVR.The CoreValve US Pivotal High Risk Trial was a multicenter, randomized, noninferiority trial. This retrospective analysis evaluated patients who underwent an attempted implant and had an STS PROM of 7% or less. The trial was performed at 45 US sites. Patients had severe aortic stenosis and were at increased surgical risk based on their STS PROM score and other risk factors.Eligible patients were randomly assigned (1:1) to self-expanding TAVR or to SAVR.We retrospectively stratified patients by the overall median STS PROM score (7%) and analyzed clinical outcomes and quality of life using the Kansas City Cardiomyopathy Questionnaire in patients with an STS PROM score of 7% or less.The mean (SD) ages were 81.5 (7.6) years for the TAVR group and 81.2 years (6.6) for the SAVR group. A little more than half were men (57.9% in the TAVR group and 55.8% in the SAVR group). Of 750 patients who underwent attempted implantation, 383 (202 TAVR and 181 SAVR) had an STS PROM of 7% or less (median [interquartile range]: TAVR, 5.3% [4.3%-6.1%]; SAVR, 5.3% [4.1%-5.9%]). Two-year all-cause mortality for TAVR vs SAVR was 15.0% (95% CI, 8.9-10.0) vs 26.3% (95% CI, 19.7-33.0) (log rank P = .01). The 2-year rate of stroke for TAVR vs SAVR was 11.3% vs 15.1% (log rank P = .50). Quality of life by the Kansas City Cardiomyopathy Questionnaire summary score showed significant and equivalent increases in both groups at 2 years (mean [SD] TAVR, 20.0 [25.0]; SAVR, 18.6 [23.6]; P = .71; both P .001 compared with baseline). Medical benefit, defined as alive with a Kansas City Cardiomyopathy Questionnaire summary score of at least 60 and a less than 10-point decrease from baseline, was similar between groups at 2 years (TAVR, 51.0%; SAVR, 44.4%; P = .28).Self-expanding TAVR compares favorably with SAVR in high-risk patients with STS PROM scores traditionally considered intermediate risk.Clinicaltrials.gov Identifier: NCT01240902.

This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification (MAC) and reports the first large series from a multicenter global registry.The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population.We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR.From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm(2). SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25).TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.

REPRISE III is the first large randomized comparison of 2 TAVR platforms: the mechanically-expanded Lotus valve (Boston Scientific, Marlborough, MA) and self-expanding CoreValve (Medtronic, Dublin, Ireland). In aortic stenosis patients with high/extreme surgical risk, Lotus was noninferior to

Valve-in-valve transcatheter aortic valve replacement (ViV TAVR) has become a reliable therapy for failing bioprostheses (AVR), and mean gradient < 20 mmHg is a desirable result post procedure. We sought to evaluate serial echocardiographic hemodynamics in patients post ViV TAVR. We reviewed

Paravalvular leak (PVL) following TAVR has been associated with worse long-term outcomes including an increased risk of mortality. REPRISE III was a large randomized trial comparing 2 contemporary TAVR devices: Lotus and CoreValve (CV). Lotus incorporates an adaptive seal designed to minimize PVL.

Surgical treatment of mitral stenosis with extreme calcification remains a challenge. Recently, the balloon-expandable valve prosthesis, anchored by radial force, offers a new option for these patients. We present 2 cases of transcatheter mitral valve replacement in patients with severe native mitral valve stenosis and annular calcification deemed too extensive for conventional surgical techniques.

A 77-year-old man with severe aortic stenosis presented for transcatheter aortic valve replacement (TAVR). His clinical history was significant for severe chronic obstructive lung disease (COPD) and prior treatment of lung cancer with surgery and chest radiation. Given his co-morbidities and frailty, he was classified as prohibitive risk for surgical aortic valve replacement. Given the anaesthesia …

ABO matched cynomolgus monkey to baboon heterotopic xenografts were performed using three different immunosuppressant regimens. Group 1 (n = 4) baboons, which did not receive immunosuppression, had a mean graft survival of 9 days. Group 2 (n = 6) received cyclosporine (CsA) and methylprednisolone acetate which prolonged graft survival to an average of 78 days. Group 3 (n = 5) received CsA, Pred, and azathioprine (Aza) as well as steroid pulses and antithymocyte globulin (ATG) for rejection episodes. Survival in this group averaged 94 days. In Group 4 (n = 3), the same regimen as group 3 was used; however, Mycophenolate Mofetil was substituted for Aza. This resulted in a mean survival of 296 days. Histologic examination of the coronary vasculature in baboons treated with Mofetil showed a reduction in vascular pathologic changes when compared to those treated with Aza. Long-term cardiac xenograft survival is possible using currently available immunosuppressive agents.

Background: HMG-CoA reductase inhibitors (statins) have been shown to reduce the incidence of atrial fibrillation (AF) and its progression but the underlying mechanisms are not fully elucidated. Since atrial fibrosis plays a major role in the development of the substrate for AF progression, we hypothesized that statins antagonize the effect of profibrotic cytokines, reducing their stimulatory effect on fibroblast proliferation, differentiation and activation. Methods: The effect of TGF-β1, a major profibrotic cytokine, on fibroblast proliferation and activation of myofibroblasts was assessed by expression of alpha smooth muscle actin (α-SMA) message (qPCR) and proteins (western and immunofluorocytochemistry) in the presence and absence of simvastatin (1-10μM). The inhibitory effect of simvastatin on SMAD 2/3 phosphorylation (western) and its nuclear translocation by TGF-β1 (5ng) was determined by immunofluorescence antibodies using fluorescent microscopy. Results: TGF-β1 treatment increased fibroblast proliferation (cell count) by 63% compared to control (p Conclusion: Simvastatin inhibits TGFβ-1-mediated cardiac fibroblast proliferation and myofibroblast differentiation by antagonizing SMAD phosphorylation and its translocation into the nucleus.

Severe aortic stenosis is associated with acquired Von Willebrand deficiency (vWD) manifesting with recurrent gastrointestinal bleed (GIB) if left untreated. Few small studies have shown decreased incidence of GIB after surgical aortic valve replacement (SAVR) but limited data are available with

Background . The saphenous vein is an important conduit for coronary artery bypass grafting. Wound complications from traditional open vein harvesting occur often. Minimally invasive endoscopic saphenous vein harvesting may decrease wound complications. Vein quality may be an issue with endoscopic harvesting. Methods . We reviewed 568 patients who had bypass grafting and saphenous vein harvesting either endoscopic (group A, n=180) versus open (group B, n=388). Both groups were demographically similar and management identical. Wound complication was defined by the need for intervention and included lymphocele, hematoma, cellulitis, edema, eschar, and infection. Multiple vein segments were obtained from 8 patients, 4 from each group, and examined histologically. Results . Wound complications were significantly less in group A (9/180, 5%) versus group B (55/388, 14.2%), p value equal to or less than 0.001. Open harvesting ( p ≤ 0.001), diabetes ( p ≤ 0.001), and obesity ( p ≤ 0.02) were risk factors for wound complication by univariate analysis. By multiple logistic analysis, open harvesting ( p ≤ 0.0007) and diabetes ( p ≤ 0.0001) were independent risk factors for wound infection. Histologic evaluation of vein samples showed that there was no difference between the groups and vascular structural integrity was maintained. Conclusions . Endoscopic saphenous vein harvesting was associated with fewer wound complications and infections. Vein quality was not adversely effected because of endoscopic harvesting.