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Objective Management of the pandemic caused by the novel coronavirus SARS-CoV-2 challenges both scientists and physicians to rapidly develop, and urgently assess, effective diagnostic tests and therapeutic interventions. The initial presentation of the disease in symptomatic patients is invariably respiratory, with dry cough being the main symptom, but an increasing number of reports reveal multiple-organ involvement. The aim of this review is to summarize the potential role of the renin-angiotensin system activated phagocytes in the pathogenesis of COVID-19 disease. Methods Data for this review were identified by searches of PubMed and references from relevant articles using the search terms “SARS,” “COVID-19,” “renin-angiotensin-system,” “phagocyte,” “reactive free radical,” “antioxidant,” “ARDS,” “thrombosis,” “myocardial,” “ischaemia,” “reperfusion,” “microvascular,” and “ACE2.” Abstracts and reports from meetings were not included in this work. Only articles published in English between 1976 and 2020 were reviewed. Results The cellular target of SARS viruses is the angiotensin-converting enzyme 2, a critical regulating protein in the renin-angiotensin system. The elimination of this enzyme by the viral spike protein results in excessive activation of phagocytes, migration into the tissues via the high endothelial venules, and an oxidative burst. In the case of an overstimulated host immune response, not only devastating respiratory symptoms but even systemic or multiorgan involvement may be observed. Conclusions Early-stage medical interventions may assist in returning the exaggerated immune response to a normal range; however, some therapeutic delay might result in excessive tissue damages, occasionally mimicking a systemic disease with a detrimental outcome.

Aim:Radiation therapy has historically used margins for target volume to ensure dosimetric planning criteria. The size of margin for a given treatment site is still uncertain particularly for moving targets along with set-up variations leading to a fuzziness of target volume. In this study, we have estimated the dosimetric benefit of normal structures using biological-based optimal margins. The treatment margins are derived by knowledge-based fuzzy logic technique which is considering the radiotherapy uncertainties in treatment planning.Materials and methods:All treatment plans were performed using stepped increments of asymmetric margins to estimate prostate radiobiological indices such as tumour control probability (TCP) and normal tissue complication probability (NTCP). An absolute NTCP of 5% was considered to be the maximum acceptable value while TCP of 85% was considered to be the minimal acceptable limit for each volumetric modulated arc therapy (VMAT) plan of localised prostate cancer radiotherapy. Results were used to formulate rules and membership functions for Mamdani-type fuzzy inference system (FIS). In implementing the rules for the fuzzy system for ΔNTCP values above 10%, the PTV margin was not permitted to exceed 5 mm to avoid rectal complications due to margin selection. The new margins were applied in VMAT planning of prostate cancer for standard displacement errors. The dosimetric results of normal tissue predictors were estimated such as organ mean doses, rectum V60 (volume receiving 60 Gy), bladder V65 (volume receiving 65 Gy) and other clinically significant dose–volume indicators and compared with VMAT plans using current margin formulations.Results:Dosimetric results compared well to the results obtained by current techniques. Good agreement was obtained between proposed fuzzy model margins and currently used margins in lower error magnitude, but significant results were observed at higher error magnitude when organ toxicity concerned without compromising the target volumes.Findings:The new margins may be helpful to estimate possible outcomes of normal tissue complications and thus may improve complication free survival particularly when organ motion errors are inevitable, case by case.

Background: The short and long-term effects of volume overload elimination on left ventricular (LV) volumetric reverse-remodeling and systemic hemodynamic after surgery for chronic primary mitral r...

As the options for how we treat severe aortic stenosis (AS) evolve, so does the way we organize and deliver health care with these patients. The Center for Medicare and Medicaid Services (CMS) is a...

PURPOSE: Patients with atrial fibrillation (AF) undergoing cardiac surgery are at substantially increased risk for stroke. Increasing evidence has suggested that surgical left atrial appendage occlusion (S-LAAO) may have the potential to substantially mitigate this stroke risk; however, S-LAAO is performed in a minority of patients with AF undergoing cardiac surgery. We sought to identify factors associated with usage of S-LAAO. METHODS: In a nationally-representative, contemporary cohort (07/2011–06/2012) of older patients undergoing cardiac surgery with preoperative AF (n=11,404) from the Medicare-linked Society of Thoracic Surgeons Adult Cardiac Surgery Database, we evaluated patient and hospital characteristics associated with S-LAAO use by employing logistic and linear regression models. RESULTS: In this cohort (average age, 76 years; 39% female), 4,177 (37%) underwent S-LAAO. Neither S-LAAO nor discharge anticoagulation was used in 25% (“unprotected” patients). The overall propensity for S-LAAO decreased significantly with increasing CHA(2)DS(2)-VASc (Congestive heart failure; Hypertension; Age 75 years or older; Diabetes mellitus; Stroke, transient ischemic attack, or thromboembolism; Vascular disease; Age 65 to 74 years; Sex Category [female]) score (p(trend)

Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identify candidates for human profiling. We then tested associations between circulating SASP proteins and clinical data from individuals throughout the life span and older adults undergoing surgery for prevalent but distinct age-related diseases. A community-based sample of people aged 20–90 years (retrospective cross-sectional) was studied to test associations between circulating SASP factors and chronological age. A subset of this cohort aged 60–90 years and separate cohorts of older adults undergoing surgery for severe aortic stenosis (prospective longitudinal) or ovarian cancer (prospective case-control) were studied to assess relationships between circulating concentrations of SASP proteins and biological age (determined by the accumulation of age-related health deficits) and/or postsurgical outcomes. We showed that SASP proteins were positively associated with age, frailty, and adverse postsurgery outcomes. A panel of 7 SASP factors composed of growth differentiation factor 15 (GDF15), TNF receptor superfamily member 6 (FAS), osteopontin (OPN), TNF receptor 1 (TNFR1), ACTIVIN A, chemokine (C-C motif) ligand 3 (CCL3), and IL-15 predicted adverse events markedly better than a single SASP protein or age. Our findings suggest that the circulating SASP may serve as a clinically useful candidate biomarker of age-related health and a powerful tool for interventional human studies.

AIMS Bicuspid aortic valve (BAV) and mitral valve prolapse (MVP) are common but the prevalence and significance of coexistent conditions are unknown. This study investigated the prevalence, phenotypic expression, and clinical significance of coexistent MVP-BAV. METHODS AND RESULTS Retrospective comparison of MVP-BAV and MVP-tricuspid aortic valve (TAV) prevalence including de novo echocardiographic analysis of all MVP-BAV patients between 2005 and 2015 was performed. The community prevalence of MVP-BAV was 2.7% vs. 3.4% for MVP-TAV (P = 0.45). Posterior mitral leaflet (PML)-MVP was the most common phenotype in both BAV and TAV (P = 0.38), but anterior mitral leaflet (AML)-MVP was twice more prevalent in BAV (31% vs. 15%, P

Objectives The aim of this study was to further evaluate clinical outcomes in patients with and without PCS. Background Prior cardiac surgery (PCS) is associated with increased surgical risk and post-operative complications following surgical aortic valve replacement (SAVR), but whether this risk is similar in transcatheter aortic valve replacement (TAVR) is unclear. Methods In the PARTNER 2A (Placement of Aortic Transcatheter Valve) trial, 2,032 patients with severe aortic stenosis at intermediate surgical risk were randomized to TAVR with the SAPIEN XT valve or SAVR. Adverse clinical outcomes at 30 days and 2 years were compared using Kaplan-Meier event rates and multivariate Cox proportional hazards regression models. The primary endpoint of the PARTNER 2 trial was all-cause death and disabling stroke. Results Five hundred nine patients (25.1%) had PCS, mostly (98.2%) coronary artery bypass grafting. There were no significant differences between TAVR and SAVR in patients with or without PCS in the rates of the primary endpoint at 30 days or 2 years. Nevertheless, an interaction was observed between PCS and treatment arm; whereas no-PCS patients treated with TAVR had higher rates of 30-day major vascular complications than patients treated with SAVR (adjusted hazard ratio: 2.66; 95% confidence interval: 1.68 to 4.22), the opposite was true for patients with PCS (adjusted hazard ratio: 0.27; 95% confidence interval: 0.11 to 0.66) (pinteraction Conclusions In the PARTNER 2A trial of intermediate-risk patients with severe aortic stenosis undergoing SAVR versus TAVR, the relative risk for 2-year adverse clinical outcomes was similar between TAVR and SAVR in patients with or without PCS.

AIM To evaluate the safety and efficacy of surgical left atrial appendage occlusion (s-LAAO) during concomitant cardiac surgery. METHODS We performed a comprehensive literature search through May 31st 2018 for all eligible studies comparing s-LAAO vs no occlusion in patients undergoing cardiac surgery. Clinical outcomes during follow-up included: embolic events, stroke, all-cause mortality, atrial fibrillation (AF), reoperation for bleeding and postoperative complications. We further stratified the analysis based on propensity matched studies and AF predominance. RESULTS Twelve studies (n = 40107) met the inclusion criteria. s-LAAO was associated with lower risk of embolic events (OR: 0.63, 95%CI: 0.53-0.76; P < 0.001) and stroke (OR: 0.68, 95%CI: 0.57-0.82; P < 0.0001). Stratified analysis demonstrated this association was more prominent in the AF predominant strata. There was no significant difference in the incidence risk of all-cause mortality, AF, and reoperation for bleeding and postoperative complications. CONCLUSION Concomitant s-LAAO during cardiac surgery was associated with lower risk of follow-up thromboembolic events and stroke, especially in those with AF without significant increase in adverse events. Further randomized trials to evaluate long-term benefits of s-LAAO are warranted.

Background Patients with heart failure (HF) and symptomatic secondary mitral regurgitation (SMR) have a poor prognosis, with morbidity and mortality directly correlated with MR severity. Correction of isolated SMR with surgery is not well established in this population, and medical management remains the preferred approach in most patients. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial was designed to determine whether transcatheter mitral valve (MV) repair with the MitraClip device is safe and effective in patients with symptomatic HF and clinically significant SMR. Study design The COAPT trial is a prospective, randomized, parallel-controlled, open-label multicenter study of the MitraClip device for the treatment of moderate-to-severe (3+) or severe (4+) SMR (as verified by an independent echocardiographic core laboratory) in patients with New York Heart Association class II-IVa HF despite treatment with maximally tolerated guideline-directed medical therapy (GDMT) who have been determined by the site’s local heart team as not appropriate for MV surgery. A total of 614 eligible subjects were randomized in a 1:1 ratio to MV repair with the MitraClip plus GDMT versus GDMT alone. The primary effectiveness end point is recurrent HF hospitalizations through 24 months, analyzed when the last subject completes 12-month follow-up, powered to demonstrate superiority of MitraClip therapy. The primary safety end point is a composite of device-related complications at 12 months compared to a performance goal. Follow-up is ongoing, and the principal results are expected in late 2018. Conclusions HF patients with clinically significant SMR who continue to be symptomatic despite optimal GDMT have limited treatment options and a poor prognosis. The randomized COAPT trial was designed to determine the safety and effectiveness of transcatheter MV repair with the MitraClip in symptomatic HF patients with moderate-to-severe or severe SMR.

Left ventricular outflow obstruction after transcatheter mitral valve replacement is a life-threatening complication. We report a case of a 68-year old female with early degeneration of a transcatheter aortic valve and severely calcified mitral valve stenosis who was considered inoperable by a multidisciplinary heart team and referred for transcatheter aortic and mitral valve replacement. Our aim is to report the planning, procedural aspects, and management of device-related left-ventricular outflow tract obstruction after transcatheter double valve replacement.

Data from The Society of Thoracic Surgeons Adult Cardiac Surgery Database were analyzed to identify trends in patient characteristics and outcomes of mitral valve operations in North America.All patients with isolated primary mitral valve operations with or without tricuspid valve repair, surgical atrial fibrillation ablation, or atrial septal defect closure performed July 2011 to September 2016 were identified. A subgroup analysis assessed patients with degenerative leaflet prolapse (DLP).Isolated primary mitral valve operations were performed on 87,214 patients at 1,125 centers, increasing by 24% between 2011 (n = 14,442) and 2016 (n = 17,907). The most common etiology was DLP (60.7%); 4.3% had functional mitral regurgitation. Preoperatively, 47.3% of patients had an ejection fraction less than 60% and 34.2% had atrial fibrillation. Overall mitral valve repair rate was 65.6%, declining from 67.1% (2011) to 63.2% (2016; p 0.0001). Repair rates were related to etiology (DLP, 82.5%; rheumatic, 17.5%). Of the 29,970 mitral valve replacements, 16.2% were preceded by an attempted repair. Repair techniques included prosthetic annuloplasty (94.3%), leaflet resection (46.5%), and artificial cord implantation (22.7%). Bioprosthetic valves were implanted with increasing frequency (2011, 65.4%; 2016, 75.8%; p 0.0001). Less-invasive operations were performed in 23.0% and concomitant tricuspid valve repair in 15.7%. Unadjusted operative mortality was 3.7% (replacements) and 1.1% (repairs).Patients undergoing primary isolated mitral valve operations commonly have ventricular dysfunction, atrial fibrillation, and heart failure. Although contemporary outcomes are excellent, earlier guideline-directed referral and increased frequency and quality of repair may further improve results of mitral valve operations.

Background: It is unclear whether moderate or less functional tricuspid regurgitation (TR) should be repaired during surgery for degenerative mitral valve (MV) disease. We studied the natural course of unaddressed moderate or less TR and identified risk factors for TR progression after surgery for degenerative MV disease. Methods: From 2001 to 2011, 2,982 patients with isolated degenerative MV disease and no evidence of coronary artery disease underwent MV surgery. To generate an enriched sample of patients with TR, by random selection 200 patients without TR, 197 with mild TR, and 177 with moderate TR were studied. A total of 1,150 echocardiograms were available for longitudinal analysis of TR progression after surgery in 550 of these 574 patients. Results: Overall prevalence of severe TR was 1.1%, 2.2%, 3.6%, and 4.4% by 1, 3, 5, and 7 years, respectively. Patients with moderate preoperative TR were more likely to progress to severe TR by 7 years (8.6%) than those with mild TR (3.2%) or no TR (1.3%) preoperatively (p p = 0.03), shorter right ventricular base-to-apex length (p = 0.0004), smaller tethering area (p = 0.01), older age, and preoperative heart failure. During follow-up, no patient underwent TV intervention. Conclusion: Routine repair of moderate or less functional TR during surgery for degenerative MV disease does not appear to be warranted, because progression to severe TR is uncommon. Instead, we suggest a tailored approach, reserving TR repair during surgery for degenerative MV disease for patients with known risk factors.

Background The Placement of Aortic Transcatheter Valves 2A (PARTNER-2A) randomized trial compared outcomes of transfemoral transcatheter and surgical aortic valve replacement (SAVR) in intermediate-risk patients with severe aortic stenosis. The purpose of the present study was to perform an in-depth analysis of outcomes after SAVR in the PARTNER-2A trial. Methods From January 2012 to January 2014, 937 patients underwent SAVR at 57 centers. Mean age was 82 ± 6.7 years and 55% were men. Less-invasive operations were performed in 140 patients (15%) and concomitant procedures in 198 patients (21%). Major outcomes and echocardiograms were adjudicated by an independent events committee. Follow-up was 94% complete to 2 years. Results Operative mortality was 4.1% (n = 38, Society of Thoracic Surgeons predicted risk of mortality: 5.2% ± 2.3%), observed to expected ratio (O/E) was 0.8, and in-hospital stroke was 5.4% (n = 51), twice expected. Aortic clamp and bypass times were 75 ± 30 minutes and 104 ± 46 minutes, respectively. Patients having severe prosthesis–patient mismatch (n = 260, 33%) had similar survival to patients without ( p > 0.9), as did patients undergoing less-invasive SAVR ( p = 0.3). Risk factors for death included cachexia ( p = 0.004), tricuspid regurgitation ( p = 0.01), coronary artery disease ( p = 0.02), preoperative atrial fibrillation ( p = 0.001), higher white blood cell count ( p p = 0.0002). Conclusions In this adjudicated prospective study, SAVR in intermediate-risk patients had excellent results at 2 years. However, there were more in-hospital strokes than expected, most likely attributable to mandatory neurologic assessment after the procedure. No pronounced structural valve deterioration was found during 2-year follow-up. Continued long-term surveillance remains important.

Historically, mitral valve repair has been preferred over replacement in the treatment of degenerative mitral valve disease, and the conventional sternotomy approach has demonstrated excellent safety and long-term durability. However, surgeons continue to seek less invasive surgical approaches that maintain the high standards set for mitral valve repair. Robotic mitral valve surgery was introduced in 1998 to reproduce excellent conventional sternotomy results with less invasive techniques. This technology is now routinely performed for delivering complete anatomic correction of all categories of mitral valve prolapse, regardless of disease complexity, with or without concomitant tricuspid valve repair and atrial fibrillation ablation procedures. Herein, we review current status of robotic mitral valve surgery techniques.

Transcatheter aortic valve replacement is a transformative technology for the treatment of severe aortic stenosis. It has allowed for the treatment of high-risk and inoperable aortic stenosis patients that would previously have not been able to undergo surgical aortic valve replacement. The safety and efficacy of transcatheter aortic valve replacement has been evaluated rigorously in multiple pivotal randomized clinical trials. Advancements in the technology with significant improvement in clinical outcomes and safety of the procedure have allowed for the extension to lower-risk groups. Future development will focus on continued refinement in the device and technique with expansion to low-risk patients and other clinical indications.

BACKGROUND: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. OBJECTIVES: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. METHODS: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. RESULTS: Among 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values

Robotic and minimally invasive mitral valve (MV) procedures have been performed with increasing frequency over time. These alternatives offer similar efficacy to that achieved via standard median sternotomy, particularly in large volume centers, along with low perioperative morbidity and mortality rates. Moreover, patient acceptance is oftentimes increased due to less postoperative pain and shorter recovery times, as well as superior cosmetic results. However, these techniques are technically complex and associated with a significant learning curve. The following review offers an overview of the most relevant aspects related to minimally invasive and robotic MV repair. Although these techniques are well established in referral centers, future innovations should concentrate on decreasing complexity and improving reproducibility of these procedures.

Many patients with asthma use inhalers incorrectly. Better inhaler technique is associated with better asthma control. We tested the effectiveness of a computer-based video training solution versus traditional written instructions, both which may be used in a resource-limited setting, for teaching inhaler technique. We hypothesized that computer based training will provide a higher quality of instruction which will improve technique more effectively than written training.50 asthma patients were recruited from pulmonary clinic at the Junta De Beneficencia Hospital, Ecuador (average age 48.2 years, 58% female). Inhaler technique was taught using written instructions in 20 and video in 30 patients. Inhaler technique was analyzed by video recording pre and post training inhaler use. Inhaler technique score was calculated for each video recording.Baseline performance was equivalent in each group, achieving an average of around 5 of 11 of the inhaler steps. Video training was significantly more effective than written instructions (change of 3.6 points vs. change of 0.4 points, p 0.001), and improved inhaler technique by 70% (8.6 vs 5.03, p 0.001); written training did not result in a significant increase in inhaler competency (5.9 vs. 5.5, p = 0.11).We conclude that written instruction appears to be inadequate to achieve safe and effective administration of inhaled medicine. In contrast, video-based education can effectively create adequate inhaler technique without additional provider time. REGISTRATION NUMBER (CLINICALTRIALS.GOV IDENTIFIER): NCT02660879.

Background Frailty confers risk for surgical morbidity and mortality. Whether patient-reported measures of health, well-being, or quality of life respond differently to surgery in non-frail and frail individuals is unknown. Methods Older adults with severe aortic stenosis presenting for surgery were assessed for frailty using Cardiovascular Health Study Criteria. Patient-reported measures of functional capacity (Duke Activity Status Index [DASI]), physical and mental health (Medical Outcomes Study Short Form-Physical and Mental Component Scales [SF-12 PCS and SF-12 MCS, respectively]), well-being (linear analogue self-assessment [LASA]), and quality of life (LASA) were administered before and 3 months after surgery. Results Of 103 participants (mean age of 80.6 years), 54 were frail. Frail participants had lower baseline DASI, SF-12 PCS, SF-12 MCS, physical well-being, and quality of life scores than non-frail participants. At follow-up, frail participants showed significant improvement in physical function, with DASI and SF-12 PCS scores improving by 50% and 14%, respectively. Non-frail subjects did not significantly improve in these measures. SF-12 MCS scores also improved to a greater extent in frail compared to non-frail participants (3.6 vs < 1 point). Furthermore, the frail participants improved to a greater extent than non-frail participants in physical well-being (21.6 vs 7.1 points) and quality of life measures (25.1 vs 8.7 points). Conclusions Frailty is prevalent in older adults with severe aortic stenosis and is associated with poor physical and mental function, physical well-being, and quality of life. In response to surgery, frail participants exhibited greater improvement in these patient-centered outcomes than non-frail peers.

Myxomatous degeneration of mitral valve apparatus affects 2–3% of the general population and it is the most common cause of severe mitral regurgitation in western countries. More than 90% of degenerative mitral valves are suitable for valve repair rather than replacement, with short and long term clinical outcomes being superior after repair. In addition to the clinical benefits, mitral valve repair is associated with an economic benefit in the form of reduced short and long term medical expenses. Patients who have undergone mitral valve repair have mitral function restored, have avoided the added expense of a prosthetic valve and are free from lifelong anti-coagulation requirement. A variety of surgical approaches (sternotomy, anterolateral thoracotomy, and robotic assisted procedures) and repair techniques have been developed over the last four decades to treat mitral valve regurgitation. In this chapter, we delineate different aspects of mitral valve repair techniques.

In the fight against cancer, half of the battle is won based on its early detection. Early detection of cancer significantly increases the chances for its successful treatment. Early detection of breast cancer, especially before cancer cells metastasize, is critical for its diagnosis and for its treatment.

Objectives To perform a meta-analysis including all available randomized controlled trials (RCTs) to date comparing transcatheter aortic valve replacement (TAVR) to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) and low surgical risk. Background Current guidelines recommend SAVR for patients with severe symptomatic AS and low surgical risk. A few RCTs have evaluated TAVR in low surgical risk patients but equipoise exists related to TAVR valve durability, paravalvular leak (PVL) and role of TAVR in younger, low surgical risk patients. Methods Five databases were analyzed from January-2000 to March-2019 for RCTs comparing SAVR to TAVR in low-risk severe AS patients. Results Four RCTs on low-risk TAVR patients with 2887 patients were included. Mean follow-up was ~24.1 ± 24 months. Early mortality was lower with TAVR compared to SAVR (RR: 0.44, 95% CI: 0.20–0.95, P = 0.038) whereas long-term mortality was similar (RR: 0.67, 95% CI: 0.39–1.14, P = 0.141). Both early and long-term stroke rates were similar. TAVR was associated with lower risk of atrial fibrillation, major bleeding, acute kidney injury (AKI) and rehospitalization, but higher rates of permanent pacemaker implantation (PPM) and moderate or severe PVL. There was no difference in major vascular complications, myocardial infarction, endocarditis, aortic valve gradients and valve area at follow-up. Conclusions In low-risk patients with severe AS, TAVR has a lower early mortality compared to SAVR with no difference in long-term mortality. Although complication rates varied between TAVR and SAVR, our study findings suggest that transfemoral-TAVR is an appropriate treatment option for severe symptomatic AS in patients with low surgical risk.

Executive Summary Surgical ablation for atrial fibrillation (AF) can be performed without additional risk of operative mortality or major morbidity, and is recommended at the time of concomitant mitral operations to restore sinus rhythm. (Class I, Level A) Surgical ablation for AF can be performed without additional operative risk of mortality or major morbidity, and is recommended at the time of concomitant isolated aortic valve replacement, isolated coronary artery bypass graft surgery, and aortic valve replacement plus coronary artery bypass graft operations to restore sinus rhythm. (Class I, Level B nonrandomized) Surgical ablation for symptomatic AF in the absence of structural heart disease that is refractory to class I/III antiarrhythmic drugs or catheter-based therapy or both is reasonable as a primary stand-alone procedure, to restore sinus rhythm. (Class IIA, Level B randomized) Surgical ablation for symptomatic persistent or longstanding persistent AF in the absence of structural heart disease is reasonable, as a stand-alone procedure using the Cox-Maze III/IV lesion set compared with pulmonary vein isolation alone. (Class IIA, Level B nonrandomized) Surgical ablation for symptomatic AF in the setting of left atrial enlargement (≥4.5 cm) or more than moderate mitral regurgitation by pulmonary vein isolation alone is not recommended. (Class III no benefit, Level C expert opinion) It is reasonable to perform left atrial appendage excision or exclusion in conjunction with surgical ablation for AF for longitudinal thromboembolic morbidity prevention. (Class IIA, Level C limited data) At the time of concomitant cardiac operations in patients with AF, it is reasonable to surgically manage the left atrial appendage for longitudinal thromboembolic morbidity prevention. (Class IIA, Level C expert opinion) In the treatment of AF, multidisciplinary heart team assessment, treatment planning, and long-term follow-up can be useful and beneficial to optimize patient outcomes. (Class I, Level C expert opinion)

Background The potential additive utility of baseline resting left ventricular global longitudinal strain (LV-GLS) and exercise stress testing in risk stratification of patients with significant mitral regurgitation (MR) has not been studied. Objectives The goal of this study was to determine whether resting LV-GLS and exercise testing provide incremental prognostic utility in asymptomatic patients with ≥3+ primary MR and preserved left ventricular ejection fraction. Methods Between 2000 and 2011, resting and exercise echocardiography data, Society of Thoracic Surgeons (STS) scores, and death were recorded in 737 patients (mean age 58 ± 13 years; 68% men). Results Coronary artery disease and flail leaflet were seen in 10% and 28% of patients, respectively. STS score, resting left ventricular ejection fraction, mitral effective regurgitant orifice, resting right ventricular systolic pressure (RVSP), exercise metabolic equivalents (METs), and percentage of age-/sex-predicted METs were 1.5 ± 1%, 62 ± 2%, 0.45 ± 0.2 cm2, 31 ± 12 mm Hg, 9.8 ± 3, and 115 ± 27, respectively. Median LV-GLS was –21.7%. Within 3 months (interquartile range: 1 to 15 months), 65% underwent mitral valve surgery. At 8.3 ± 3 years, 64 (9%) patients died (0% 30-day post-operative deaths). On multivariable Cox survival analysis, higher STS score (hazard ratio [HR]: 1.14), more abnormal resting LV-GLS (HR: 1.60), higher baseline RVSP (HR: 1.35), and lower percentage of age-/sex-predicted METs (HR: 1.13) were associated with higher mortality, whereas mitral valve surgery (HR: 0.82) was associated with improved survival (all p Conclusions Reduced exercise capacity and worsening resting LV-GLS were associated with mortality, providing additive prognostic utility.

In patients with frequent premature ventricular contractions (PVCs), little is known about the profile of PVCs and the outcome of treatment in patients with mitral valve prolapse (MVP) compared to those without MVP.Patients with documented PVCs between January 2001 and October 2012 were divided into 2 groups: MVP and non-MVP. The PVC characteristics, efficacy of therapy, and outcome were compared between the 2 groups. A total of 112 patients with MVP and 952 without MVP were identified. The frequency of PVCs was similar between the 2 groups (P.05). In patients who underwent cardiac mapping, PVCs originating in papillary muscles (26.7% vs 2.3%; P.001) and fascicle (13.3% vs 3.4%; P.001) were more frequently seen in the MVP group than in the non-MVP group, which raises the difficulty of catheter ablation. The 2 groups had similar response to catheter ablation or medical therapy (P.05). The survival rate was similar between the 2 groups (P=.95).In patients with significant PVC burden, MVP patients had similar PVC frequency, treatment outcome, and survival rate to those without MVP.

Background Anticoagulation with warfarin following bioprosthetic mitral valve replacement (BMVR) is recommended by multiple practice guidelines. We assessed practice variability and patient characteristics associated with warfarin prescription following BMVR. Methods We analyzed 7,637 patients in the Society of Thoracic Surgeons Database (January 1, 2008 to June 30, 2011) who were discharged following isolated primary nonemergent BMVR. Patients requiring preoperative warfarin, those with preoperative atrial fibrillation, or those with a contraindication to warfarin were excluded. The association between patient, hospital, and surgeon characteristics and warfarin prescription were evaluated. Results Fifty-eight percent of this cohort (median age, 66 years; female sex, 58.7%) was prescribed warfarin. Patients receiving warfarin were older (67 vs 65 years; P P P P P P P P P P P = .20) and those with postoperative stroke (53.6 % vs 46.4 %; P = .30). After adjusting for patient characteristics, significant surgeon and hospital variation in warfarin prescription at hospitals was observed. Conclusions Although patient characteristics and postoperative events may be associated with the prescription of warfarin following BMVR, substantial surgeon and hospital variability remains. This variability largely ignores the established practice guidelines and warrants further study to define the optimal anticoagulation strategy in patients undergoing BMVR.

The most recent American College of Cardiology/American Heart Association heart valve guidelines recommend that prompt surgical correction of severe degenerative mitral valve regurgitation, ideally mitral valve repair, should be performed to decrease the risks of long-term mortality and heart failure risks associated with this condition. Mitral valve repair performed using a minimally invasive robotic approach can now be successfully carried out in nearly all cases of degenerative disease with very low risks of stroke or death. Experienced groups have further shown specific advantages of robotic mitral valve repair compared with conventional approaches, including reduced blood loss, lower risks of infection and atrial fibrillation, shorter hospital length of stay, quicker return to normal activities, and a superior cosmetic result. Herein, we discuss the current status of robotic mitral valve repair including indications, technical advances, safety, effectiveness, and durability.

Primary mitral regurgitation (MR) is a growing health problem due to the aging population.The purpose of this study was to assess the impact of baseline pulmonary hypertension on long-term outcomes in patients with significant primary MR and preserved left ventricular ejection fraction (LVEF).We studied 1,318 patients with ≥3+ primary MR and LVEF ≥60% using echocardiography at rest; they were evaluated at our center from 2005 to 2008. Baseline clinical and echocardiography data were recorded, and the Society of Thoracic Surgeons (STS) score was calculated. The primary outcome was death.Mean STS score was 3.98 ± 1%; 54% of patients were in New York Heart Association (NYHA) functional class I and 31% were in NYHA functional class II; and 18% had atrial fibrillation (AF). Mean LVEF, mitral effective regurgitant orifice, indexed LV end-systolic diameter (LVESD), and right ventricular systolic pressure (RVSP) were 62 ± 2%, 0.56 ± 0.30 cm(2), 1.6 ± 0.3 cm/m(2), and 37 ± 14 mm Hg, respectively. At 7.1 ± 2.0 years, 86% had mitral valve (MV) surgery. Death occurred in 130 (10%) patients. On Cox multivariable analysis, baseline RVSP, together with age, baseline NYHA functional class, pre-operative AF, coronary artery disease, and indexed LVESD were associated with a higher rate of longer term mortality (all p 0.01), whereas MV surgery (as a time-dependent covariate) was associated with improved survival (p 0.001). Addition of RVSP to the STS score significantly reclassified the risk for longer term mortality (integrated discrimination index: 0.07; p 0.001); 77% patients who died had RVSP ≥35 mm Hg.In patients with significant primary MR and preserved LVEF, baseline RVSP is independently associated with long-term survival. Impact of RVSP is progressive and not confined to those with the highest baseline values.

Objective To define the benefit of sutureless and rapid deployment valves in current minimally invasive approaches in isolated aortic valve replacement. Methods A panel of 28 international experts with expertise in both minimally invasive aortic valve replacement and rapid deployment valves was constituted. After thorough literature review, the experts rated evidence-based recommendations in a modified Delphi approach. Results No guideline could be retrieved. Thirty-three clinical trials and 9 systematic reviews could be identified for detailed text analysis to obtain a total of 24 recommendations. After rating by the experts 12, final recommendations were identified: preoperative computed to-mographic scan as well as intraoperative transesophageal echocardiography are highly recommended. Suitable annular sizes are 19 to 27 mm. There is a contraindication for bicuspid valves only for type 0 and for annular abscess or destruction due to infective endocarditis. The use of sutureless and rapid deployment valves reduces extracorporeal circulation and aortic cross-clamp time and leads to less early complications as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions, paravalvular leakages and aortic regurgitation, and renal replacement therapy, respectively. These clinical outcomes result in reduced intensive care unit and hospital stay and reduced costs. The use of sutureless and rapid deployment valves will lead to a higher adoption rate of minimally invasive approaches in aortic valve replacement. Respect should be taken to a necessary short learning curve for both sutureless and minimally invasive programs. Conclusions Sutureless and rapid deployment aortic valve replacement together with minimally invasive approaches offers an attractive option in aortic valve placement for patients requiring biological valve replacement.

Summary Background Transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve demonstrates good 30 day clinical outcomes in patients with severe aortic stenosis who are at intermediate risk of surgical mortality. Here we report longer-term data in intermediate-risk patients given SAPIEN 3 TAVR and compare outcomes to those of intermediate-risk patients given surgical aortic valve replacement. Methods In the SAPIEN 3 observational study, 1077 intermediate-risk patients at 51 sites in the USA and Canada were assigned to receive TAVR with the SAPIEN 3 valve [952 [88%] via transfemoral access) between Feb 17, 2014, and Sept 3, 2014. In this population we assessed all-cause mortality and incidence of strokes, re-intervention, and aortic valve regurgitation at 1 year after implantation. Then we compared 1 year outcomes in this population with those for intermediate-risk patients treated with surgical valve replacement in the PARTNER 2A trial between Dec 23, 2011, and Nov 6, 2013, using a prespecified propensity score analysis to account for between-trial differences in baseline characteristics. The clinical events committee and echocardiographic core laboratory methods were the same for both studies. The primary endpoint was the composite of death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. We did non-inferiority (margin 7·5%) and superiority analyses in propensity score quintiles to calculate pooled weighted proportion differences for outcomes. Findings At 1 year follow-up of the SAPIEN 3 observational study, 79 of 1077 patients who initiated the TAVR procedure had died (all-cause mortality 7·4%; 6·5% in the transfemoral access subgroup), and disabling strokes had occurred in 24 (2%), aortic valve re-intervention in six (1%), and moderate or severe paravalvular regurgitation in 13 (2%). In the propensity-score analysis we included 963 patients treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. For the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, TAVR was both non-inferior (pooled weighted proportion difference of −9·2%; 90% CI −12·4 to −6; p Interpretation TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year. The propensity score analysis indicates a significant superiority for our composite outcome with TAVR compared with surgery, suggesting that TAVR might be the preferred treatment alternative in intermediate-risk patients. Funding None.

Objectives The purpose of this study was to compare women and men with organic mitral regurgitation (MR) using pre- and post-operative comprehensive imaging and to analyze the effect on outcome. Background Management of organic MR has no sex-specific guideline recommendation, and sex differences on the basis of comprehensive imaging and links to outcome remain largely unknown. Methods Comprehensive imaging (MR cause, quantitation, ventricular and atrial measures, and post-operative reverse cardiac remodeling) was analyzed in 217 women and 447 men who underwent operations for organic MR from 1990 to 2000 with long-term follow-up analysis. Results Pre-operatively, women and men had similar age and ejection fraction. In women, a smaller left ventricle (LV) more often labeled as normal size (23% vs. 13%), left atrium size, and regurgitant volume (all p 0.06). During follow-up (10.4 ± 3.7 years) women had similar survival as men (p = 0.5) but experienced more heart failure (at 15 years: 36 ± 7% vs. 19 ± 3%; p = 0.03; adjusted hazard ratio 1.63 [95% confidence interval: 1.08 to 2.43]; p = 0.02) linked to more frequent pre-operative heart failure symptoms (p Conclusions Women who undergo mitral surgery for organic MR receive similar repair for similar degenerative lesions defined by echocardiography and enjoy similar survival and reverse cardiac remodeling, but they incur excess post-operative heart failure linked to worse pre-operative presentation. Imaging that does not account for body size shows smaller absolute cardiac dimensions and regurgitant volumes, which tends to underestimate MR severity in women.

Objective To determine the incidence and predictors of infective endocarditis (IE) in a population-based cohort of patients with mitral valve prolapse (MVP). Patients and Methods We identified all adult Olmsted County residents with MVP diagnosed by echocardiography from January 1989 to December 1998 and cross-matched them with the Rochester Epidemiology Project–identified Olmsted County cases of IE from January 1, 1986, through December 31, 2006. We retrospectively analyzed and de novo confirmed each IE case using the modified Duke criteria. Results There were 896 Olmsted County residents with echocardiographically diagnosed MVP (mean age, 53±21 years; 565 women [63%]). The mean follow-up period was 11±5 years. The 15-year cohort risk of IE after MVP diagnosis was 1.1%±0.4% (incidence, 86.6 cases per 100,000 person-years; 95% CI, 43.3-173.2 cases per 100,000 person-years); thus, the age- and sex-adjusted relative risk of IE in patients with MVP was 8.1 (95% CI, 3.6-18.0) in comparison to the general population of Olmsted County ( P P =.02 compared with trivial, mild, or mild-moderate MR) and in patients with a flail mitral leaflet (715.5 cases per 100,000 person-years; 95% CI, 178.9-2861.0 cases per 100,000 person-years; P =.02 compared with no flail mitral leaflet). Conclusion The population-based incidence of IE in adults with MVP is higher than those previously reported in case-control, tertiary care center studies. Patients with MVP and moderate, moderate-severe, or severe MR or a flail mitral leaflet are at a notable risk of developing IE in comparison with those without MR.

Background Extreme-risk patients (ie, Society of Thoracic Surgeons [STS] risk 15% or higher) with severe aortic valve stenosis may not obtain mortality benefit from aortic valve replacement (AVR). We reviewed our experience with this group of patients to better understand our triage process and outcomes. Methods We performed a retrospective review of 97 patients with severe aortic valve stenosis and STS risk of 15% or higher treated from 2008 through 2013. The median patient age was 85 years (minimum, 44; maximum, 97 years), and 47 patients (48.5%) were male. The STS risk of mortality was 19.8% (minimum, 15.1%; maximum, 60.9%). Patients were assigned to treatment groups based on the first aortic valve intervention of balloon aortic valvuloplasty (BAV group, 66 [68%]) or de novo AVR (d-AVR group, 31 [32%]). Results Patients in the BAV group were sicker, with a reduced ejection fraction (0.35 vs 0.57; p = 0.002) and greater prevalence of urgent/emergency operative status (32% vs 10%; p = 0.004) compared with those in the d-AVR group. After BAV, 33 patients (50%) demonstrated clinical improvement and went on to receive subsequent staged AVR after a median of 64 days (minimum, 3; maximum, 390 days). The mortality rate at 2 years was worse in the BAV group (57.3% ± 6.3%) than in the d-AVR group (29.5% ± 8.3%; p = 0.015), but was similar in patients who received BAV followed by staged AVR and de novo AVR ( p = 0.426). Conclusions BAV may triage select patients with STS risk 15% or higher who are questionable candidates for AVR. Patients with clinical improvement after BAV experience benefit from staged AVR.

Background The risk for and consequences of recurrent mitral regurgitation (MR) following degenerative mitral valve repair are poorly understood. Objectives This study sought to examine recurrent MR risk along with reoperation and survival rates. Methods We evaluated patients undergoing primary mitral repair for isolated degenerative MR over 1 decade. Median follow-up was 11.5 years (interquartile range: 9.2 to 13.6 years) and was 99% complete. Multivariate analysis of post-repair MR recurrence employed Cox proportional hazards and multistate modeling. Results A total of 1,218 patients met the study criteria; the mean age was 64 ± 13 years, mean ejection fraction was 63 ± 9%, and 864 (71%) patients were men. Prolapse was posterior in 62%, bileaflet in 26%, and anterior in 12%. The 15-year incidence of recurrent MR (i.e., MR ≥2) was 13.3%, incidence of mitral reoperation was 6.9%, and overall mortality was 44.0%. Repair before 1996 independently predicted MR recurrence (hazard ratio: 1.52). Additional determinants were: age, mild intraoperative residual MR, anterior leaflet prolapse, bileaflet prolapse, perfusion time >90 min, and lack of annuloplasty. Recurrence of moderate or greater MR was associated with adverse left ventricular remodeling and increased likelihood of death (hazard ratio: 1.72). Among those undergoing repair after 1996, MR recurrence rate was 1.5 per 100 patient-years during the first year post-repair, decreasing markedly to 0.9 thereafter. Conclusions Our study demonstrated that recurrent MR following degenerative mitral valve repair is associated with adverse left ventricular remodeling and late death. The incidence of MR recurrence decreases markedly following the first year after intervention. A transparent discussion of recurrent MR risk has pressing relevance when referring patients with complex mitral valve prolapse.

Objectives The aim of this study was to examine trends in the rates of complications and outcomes of patients undergoing transfemoral transcatheter aortic valve replacement (TF-TAVR). Background It is unknown whether an evolution of case selection or accrual of case experience over time has resulted in a change in the rates of complications and outcomes of patients undergoing TF-TAVR. Methods TF-TAVR patients enrolled in the PARTNER (Placement of AoRTic TraNscathetER Valve Trial) nonrandomized continued access registry (N = 1,063, enrolled March 2011 to January 2012 after completion of the randomized trial) were divided into tertiles (T1 through T3) based on enrollment date. Patient characteristics and rates of adverse events were compared over time. Results There were no significant differences in sex, New York Heart Association functional classes III/IV, diabetes, coronary artery disease, previous revascularization, pulmonary hypertension, renal disease, or liver disease. There was an increase in mean age, but a decrease in porcelain aorta, chronic obstructive pulmonary disease (including oxygen-dependent chronic obstructive pulmonary disease), previous chest wall radiation, and a slight decrease in the median Society of Thoracic Surgeons Predicted Risk of Mortality score. There was a significant decline in the frequency of patients deemed “inoperable” (cohort B) and in need for post-dilation. Percutaneous access increased significantly. There were no differences in post-procedural stroke, major bleeding, major vascular complications, or the need for aortic valve reintervention over time. The incidence of moderate/severe paravalvular regurgitation declined significantly as did all-cause mortality at 1 and 2 years. Conclusions A significant reduction in the incidence of moderate/severe paravalvular regurgitation as well as longer term all-cause mortality was observed over time. The cause of these reductions was likely multifactorial, including improved case selection and procedural techniques and increased site experience. (THE PARTNER TRIAL [Placement of AoRTic TraNscathetER Valve Trial]; NCT00530894 )

Conjunctival melanoma is a rare malignant neoplasm that can present in childhood in any part of the conjunctiva. The infrequency with which conjunctival melanoma is encountered in childhood caruncular lesions makes it a formidable but important aspect of the differential diagnosis. We report the case of a 10-year-old boy who presented with a left caruncular lesion. On histopathologic analysis, the lesion was determined to be BRAF-negative invasive melanoma arising in association with melanocytic nevus. The melanoma was excised using no-touch technique and double freeze thaw cryotherapy. A full systemic work-up revealed no metastasis or abnormality.

Lower blepharoplasty has evolved significantly over the last several decades from a volume-depleting procedure to a volume-preserving procedure. In the days past, the surgeon would remove significant amounts of fat with aggressive skin-muscle resection utilizing the skin-muscle flap approach. This led to a hollowed, surgical look that soon began to fall out of favor not to mention an unacceptably high incidence of lower eyelid retraction [1]. In the last two decades, lower eyelid blepharoplasty has progressed to a volume conservation procedure with more conservative resection of fat or repositioning of fat using a transconjunctival approach with skin maintenance using a separate method such as laser resurfacing, skin pinch, lateral orbicularis muscle or lateral canthal tightening, or excising skin laterally [2–4]. This maximally preserves orbital septum and infraciliary orbicularis muscle minimizing the risk of lower eyelid retraction and ectropion.

Robotic mitral valve surgery was introduced in 1998 to reproduce excellent conventional sternotomy results with less invasive techniques. This technology is now routinely performed for delivering complete anatomic correction of all categories of mitral valve prolapse, regardless of disease complexity, with or without concomitant tricuspid valve repair and atrial fibrillation ablation procedures. Recent studies have demonstrated broad advantages of robotic mitral valve surgery, including reduced bleeding, extubation on the operating room table, shorter hospital length of stay, quicker return to normal activities, and a superior cosmetic result. Here we discuss the current status of robotic mitral valve surgery techniques.

It is well-known that ejection fraction and strain are both load dependent, and it is very important to establish a load independent echocardiographic index for patients with mitral regurgitation. The aim of the current study is to associate this new index to the endpoint of reverse left atrial

Start your abstract here…External beam radiation therapy (EBRT) is a process in which therapeutic radiation dose is delivered to targettissues whilst seeking the risk of healthynormal and critical organs is minimal. In case of Complex radiation therapy technique such as volumetric modulated arc radiotherapy (VMAT), there is requirement of precise and optimal treatment margin selection so that not only the resulting dose distributions gives high tumor control probability(TCP) but also dose close to critical organs will get minimal. A fuzzy logic application was used here to derive the optimal radiotherapy treatment margins to be used in radiation therapy treatment planning. Here major all possible radiotherapy uncertainties accounted such as translational set-up, organdelineation and organ motion-induced errors for calculating the quantitative variations in target volume radiobiological parameters for treatment plans using fixed step sized increments of treatment margins up to maximum possible variations of tumor volumes. Therules and membership functions were adopted from dosimetricresults of treatment planning for the fuzzy inference system. The imprecision and smoothness of the original fuzzy output was corrected with application of a convolution technique. The results demonstrate that performance of the applied fuzzy model margins against current used radiotherapy margins was consistent inlower range of error magnitude but beyond that a significant non-linearly margin performance was found when considering the normal tissue complication probability (NTCP) and constraint factors into account in the margin recipe formulation. With the new margins obtained then applied for the study of prostate cancer treatment planning and results were compared well with current volumetric modulated arc radiotherapy (VMAT)technique.

Background Ventricular-annular decoupling is thought to exist in all degenerative myxomatous mitral valve (MV) diseases. However, the annular physiology of degenerative MV disease may differ when severe mitral regurgitation (MR) presents at different stages. The aim of this study was to assess differences in mitral annular physiology and surgical effects between early- and late-stage severe MR. Methods Three-dimensional (3D) transesophageal echocardiography was performed before and after MV surgery in 74 patients with degenerative MV disease, including 57 with early-stage severe MR (without left ventricular remodeling) and 17 with late-stage MR (with left ventricular remodeling). A control group comprised 46 patients without MV disease. Novel 3D MV software was used to evaluate mitral annular dynamics. The degree of annular saddle shape was calculated as the ratio of annular height (AH) to lateromedial diameter (LM). Ventricular-annular decoupling was defined as insufficient systolic AH/LM compared with the control group. Results Prebypass 3D measurements demonstrated that systolic AH/LM in the early-stage group (0.19 ± 0.04) was similar to that in the control group (0.21 ± 0.05; P = .101), while systolic AH/LM in the late-stage group (0.17 ± 0.04) was lower than that in the control group (P = .011). Postbypass comparison showed saddle shape accentuation in the early-stage group (0.20 ± 0.04), similar to that in the control group (P = .3127); the mitral annulus remained flat in the late-stage group (0.17 ± 0.03; P = .004). Conclusions Ventricular-annular decoupling, present in the late-stage group, was absent in the early-stage group. MV repair surgery did not disrupt mitral annular saddle shape in the early-stage group; however, it failed to correct annular dysfunction in the late-stage group. Sequential 3D transesophageal echocardiographic analysis provides comprehensive mitral annular evaluation beyond conventional two-dimensional parameters for determining stages of severe MR.

Patients with low-flow aortic stenosis (LFAS) have worse outcomes compared with patients with normal flow. The mechanism by which LFAS occurs is incompletely understood. Patients are typically stratified based on normal or reduced ejection fraction (EF), but whether clinical risk factors or