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Left ventricular assist devices (LVADs) have revolutionized the management of patients with advanced heart failure refractory to medical therapy. Current indications of LVADs include Bridge to Transplantation (BTT), Destination Therapy (DT) for long-term use, Bridge to the Decision (BTD) used as a temporary measure, and lastly Bridge to Recovery (BTR). Here, we briefly review the clinical evidence and the molecular mechanisms behind myocardial recovery following LVAD placement. We also share institutional protocols used at 2 major medical centers in the USA., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: There is growing evidence of coexistence of aortic stenosis (AS) and transthyretin cardiac amyloidosis (CA). Not screening AS patients at the time of hospital/clinic visit for CA represents a lost opportunity., Methods: We surveyed studies that reported the prevalence of CA among AS patients. Studies that compared patients with aortic stenosis with cardiac amyloidosis (AS-CA) and AS alone were further analyzed, and meta-regression was performed., Results: We identified nine studies with 1,321 patients of AS, of which 131 patients had concomitant CA, with a prevalence of 11%. When compared to AS-alone, the patients with AS-CA were older, more likely to be males, had higher prevalence of carpal tunnel syndrome, right bundle branch block. On echocardiogram, patients with AS-CA had thicker interventricular septum, higher left ventricular mass index (LVMI), lower myocardial contraction fraction, and lower stroke volume index. Classical low-flow low-gradient (LFLG) physiology was more common among patients with AS-CA. Patients with AS-CA had higher all-cause mortality than patients with AS alone (33% vs. 22%, P = 0.02) in a follow-up period of at least 1 year., Conclusions: CA has a high prevalence in patients with AS and is associated with worse clinical, imaging, and biochemical parameters than patients with AS alone., Competing Interests: None of the authors have any conflict of interest to declare., (Copyright 2022, Arshad et al.)

Background and Objective: As one of the most prevalent valvular pathologies affecting millions globally, moderate-to-severe tricuspid regurgitation (TR) predisposes to increased mortality. Despite the well-established risk of adverse outcomes, an overwhelming majority of TR patients are managed conservatively due to challenges associated with timely diagnosis, clinical course of the disease, competing comorbities that carry prohibitive surgical risk, and poor surgical outcomes. These challenges highlight the importance of transcatheter tricuspid valve replacement (TTVR) which has restructured TR management in promising and innovative ways., Methods: We start with an overview of the pathophysiology of TR considering its implications in management. We then elaborate on the current state of TR management, including its limitations, thereby highlighting the unique role of TTVR. This is followed by a review of perioperative considerations such as careful patient selection, role of multimodality imaging, the various imaging techniques that are available and their contribution towards successful TTVR. We then review the valves that are currently available and under investigation, including the latest data available on device efficacy and safety, and highlight the ongoing clinical trials., Results and Conclusions: TTVR is evolving at an exponential pace and has made its mark in the treatment of severe symptomatic tricuspid regurgitation. The promising results sustained by currently available devices and ongoing investigation of valves under development continue to pave the path for further innovation in transcatheter interventions. However, it is important to acknowledge and appreciate the novelty of this approach, the lack of long-term data on safety, efficacy, morbidity, and mortality, and use the lessons learned from real-world experiences to provide a definitive and reproducible solution for patients with symptomatic TR., Competing Interests: The authors declare no conflict of interest. Azeem Latib, MD has served on Advisory Boards or as a consultant for Medtronic, Boston Scientific, Edwards Lifesciences, Abbott, and V-dyne. Azeem Latib is serving as Guest Editor of this journal. We declare that Azeem Latib had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Eustachio Agricola., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Background: Increasing reports suggest the safe use of direct oral anticoagulants (DOACs) in electrical cardioversion. The aim of this study was to assess the trends and 30-day outcomes associated with anticoagulation for cardioversion., Methods: Patients who underwent electrical cardioversion from January 2015 to October 2020 with a 30-day follow-up were included; and outcomes including stroke, transient ischemic attack, intracranial hemorrhage (ICH), and major gastrointestinal bleeding were recorded., Results: Of the 515 patients, 351 (68%) were men and 164 (32%) were women, with a mean CHA 2 DS 2 VASc score of 2.6 ± 1.6. Outpatient apixaban use increased from 10% in 2015 to 46% in 2020 (P < 0.001) with a decline in the use of warfarin from 24% in 2015 to 10% in 2020 (P = 0.023). Apixaban use peri-procedurally for cardioversion increased from 32% in 2015 to 35% in 2020 (P = 0.317), while warfarin use decreased from 23% in 2015 to 14% in 2020 (P = 0.164). At discharge, apixaban prescriptions increased from 21% in 2015 to 61% in 2020 (P < 0.001), while warfarin prescriptions declined from 30% in 2015 to 13% in 2020 (P = 0.009). No ICH was recorded in the 30 days after cardioversion. Ischemic stroke occurred in four (0.7%) patients with one (0.29%) of the 338 patients on a DOAC, one (0.8%) of the 124 patients on warfarin and two (5.5%) of the 36 patients not receiving anticoagulation post cardioversion. There were seven (1%) major gastrointestinal bleeding events in patients on oral anticoagulation, of which four (3%) were on warfarin and three (0.8%) were on DOACs., Conclusions: Our study shows the increasing and safe use of DOACs for the purpose of cardioversion. The rates of 30-day ischemic stroke post cardioversion were low and only occurred in patients admitted in the intensive care unit., Competing Interests: None of the authors has any conflict of interest to declare., (Copyright 2022, Arshad et al.)

Background: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy., Methods: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis., Results: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922])., Conclusions: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.)., (Copyright © 2021 Massachusetts Medical Society.)

Severe tricuspid regurgitation is relatively common, especially in the elderly, and portends poor survival. Neither medical therapy nor conventional surgery is efficacious for most patients. In contrast, transcatheter tricuspid valve interventions are showing promise to improve quality of life and mortality. Although there is more clinical experience with transcatheter tricuspid valve repair, there are many patients for which repair is either not possible or cannot optimally reduce the severity of tricuspid regurgitation. Transcatheter tricuspid valve replacement is rapidly emerging and may ultimately become the preferred treatment option. In this review, we discuss transcatheter tricuspid valve replacement, analyze the devices in development and in clinical trials, and highlight the advantages and drawbacks of transcatheter tricuspid valve replacement vs. repair., Competing Interests: AL is a consultant and advisory board member for Edwards Lifesciences, Abbott, Medtronic, and V-Dyne. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Goldberg, Ho, Chau and Latib.)

Background: The American Society for Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) 2016 guidelines for assessment of diastolic dysfunction (DD) are based primarily on the effects of diastolic dysfunction on left ventricular filling hemodynamics. However, these measures do not provide quantifiable mechanistic information about diastolic function. The Parameterized Diastolic Filling (PDF) formalism is a validated theoretical framework that describes DD in terms of the physical properties of left ventricular filling., Aims: We hypothesized that PDF analysis can provide mechanistic insight into the mechanical properties governing higher grade DD., Methods: Patients referred for echocardiography showing reduced left ventricular ejection fraction (< 45%) were prospectively classified into DD grade according to 2016 ASE/EACVI guidelines. Serial E-waves acquired during free breathing using pulsed wave Doppler of transmitral blood flow were analyzed using the PDF formalism., Results: Higher DD grade (grade 2 or 3, n = 20 vs grade 1, n = 30) was associated with increased chamber stiffness (261 ± 71 vs 169 ± 61 g/s 2 , p < 0.001), increased filling energy (2.0 ± 0.9 vs 1.0 ± 0.5 mJ, p < 0.001) and greater peak forces resisting filling (median [interquartile range], 18 [15-24] vs 11 [8-14] mN, p < 0.001). DD grade was unrelated to chamber viscoelasticity (21 ± 4 vs 20 ± 6 g/s, p = 0.32). Stiffness was inversely correlated with ejection fraction (r = - 0.39, p = 0.005)., Conclusions: Higher grade DD was associated with changes in the mechanical properties that determine the physics of poorer left ventricular filling. These findings provide mechanistic insight into, and independent validation of the appropriateness of the 2016 guidelines for assessment of DD.

Importance: Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question., Objective: To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method., Design, Setting, and Participants: This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States. Patients with established ASCVD treated in routine clinical practice within the network are eligible. Patient recruitment began in April 2016. Enrollment was completed in June 2019. Final follow-up is expected to be completed by June 2020., Interventions: Participants are randomized on a web platform in a 1:1 fashion to either 81 mg or 325 mg of aspirin daily., Main Outcomes and Measures: The primary efficacy end point is the composite of all-cause mortality, hospitalization for nonfatal myocardial infarction, or hospitalization for a nonfatal stroke. The primary safety end point is hospitalization for major bleeding associated with a blood-product transfusion. End points are captured through regular queries of the health systems' common data model within the structure of PCORnet's distributed data environment., Conclusions and Relevance: As a pragmatic study and the first interventional trial conducted within the PCORnet electronic data infrastructure, this trial is testing several unique and innovative operational approaches that have the potential to disrupt and transform the conduct of future patient-centered randomized clinical trials by evaluating treatments integrated in clinical practice while at the same time determining the optimal dosage of aspirin for secondary prevention of ASCVD., Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Background: Despite the 2008 revision of a previously issued black box warning of the US Food and Drug Administration against the use of perflutren ultrasound contrast agents, the warning still reports fatalities having occurred following their administration. We sought to assess 1-day mortality associated with contrast use across a wide range of clinical settings and co-morbidities., Methods: We conducted a retrospective study involving 96,705 transthoracic echocardiograms (TTE) in 63,189 adults at our institution between July 2003 and June 2008. A contrast agent was used in 2,518 TTE during this time. The primary outcome was total mortality within 1 day of TTE., Results: Death occurred in 10 patients (0.44%) in the contrast group and in 421 patients (0.69%) in the non-contrast group (p = 0.14). In a multivariate model, use of contrast enhancement was not associated with increased mortality (p = 0.67) after adjustment for age, gender, race, patient location, ejection fraction, and the presence of various co-morbidities. Cause of death analysis did not identify any cases where contrast played a likely role., Conclusion: Definity contrast use during TTE was not associated with increased acute mortality risk. Contrast administration during TTE should not be withheld when the additional information obtained could potentially improve patient management., (Copyright © 2012 S. Karger AG, Basel.)

Aims: Pulsed Doppler measurement of left atrial appendage (LAA) emptying velocity, a marker of left atrium contractile function, has been shown to predict success of cardioversion, thrombo-embolic risk, and maintenance of sinus rhythm after cardioversion and pulmonary vein isolation. However, in the published literature, emptying velocity measurement location is not uniform, and no standard currently exists. We assessed the hypothesis that emptying velocity when acquired near the LAA orifice differs from that at the LAA apex., Methods and Results: The study group comprised 44 patients (32 in sinus rhythm and 12 in atrial fibrillation) who were able to complete a non-emergent transoesophageal echocardiography. Pulsed Doppler recordings were obtained with the sample volume first positioned 1 cm from the LAA orifice, and then positioned within 1 cm of the LAA apex. At each location, we calculated the average of the peak end-diastolic LAA emptying velocity from five consecutive cardiac cycles. LAA orifice emptying velocity was higher than the apex emptying velocity in all patients. The median velocity at the orifice was 72 cm/s, which was 45% higher than the median velocity at the apex (43 cm/s, P < 0.001). Lower LAA emptying velocity at the orifice was associated with a larger discrepancy between orifice and apex velocities. The ratio of orifice to apex velocity did not vary with orifice velocity. Multivariate analysis demonstrated that clinical patient characteristics were not significant predictors of the discrepancy between orifice and apex velocities., Conclusion: LAA emptying velocity is greater at the LAA orifice compared with the LAA apex. Higher, more easily measured velocity and greater variability observed with orifice measurements make it the location of choice for research and clinical applications.