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Non-valvular atrial fibrillation (NVAF) is the most common cause of cardioembolic stroke. The left atrial appendage (LAA) is the major source of cardiac emboli in patients with NVAF. Anticoagulation (AC) is the standard of care for stroke prevention in atrial fibrillation (AF), but many patients are intolerant of AC. Surgical exclusion of the LAA may result in incomplete closure and is associated with an increased risk of embolism. We report a case of a woman in her 50s with a history of persistent AF, mitral valve prolapse s/p repair with surgical LAA exclusion, and multifocal haemorrhagic stroke presented for elective LAA closure who underwent a Watchman placement successfully. This case demonstrates that a percutaneous approach for occlusion of the LAA when surgical exclusion was incomplete may be feasible with appropriate planning. Clinical outcome data for this patient group are needed.

BACKGROUND: SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are known to reduce blood pressure variability and may thus offer benefit against dementia. Beyond this effect, the impact of calcium-channel blockers on hypertension-induced neuroinflammation, and especially, microglial phenotype remains unknown. We aimed to study the ability of amlopidine to alleviate microglia inflammation, and slow down cognitive dysfunction in aged hypertensive mice.METHODS: Hypertensive BPH/2J and normotensive BPN/3J mice were studied until 12 months of age. Hypertensive mice were untreated or received amlodipine (10 mg/kg per day). Blood pressure parameters were measured by telemetry and tail cuff plethysmography. Mice underwent repeated series of cognitive tasks. Brain immunohistochemistry was performed to study blood-brain barrier dysfunction and microglial pro-inflammatory phenotype (CD68 + Iba1 + cells; morphological analysis).RESULTS: Amlodipine normalized SBP over the entire life span and decreased blood pressure variability. BPH/2J mice exhibited impaired short-term memory that was prevented by amlodipine at 12 months (discrimination index 0.41 ± 0.25 in amlodipine-treated vs. 0.14 ± 0.15 in untreated BPH/2J mice, P = 0.02). Amlopidine treatment of BPH/2J did not prevent blood-brain barrier leakage, a measure of cerebral small vessel disease, but limited its size. Microglia's inflammatory phenotype in BPH/2J, characterized by an increased number of Iba1 + CD68 + cells, increased soma size and shortened processes, was partly reduced by amlodipine.CONCLUSION: Amlodipine attenuated the short-term memory impairment in aged hypertensive mice. Beyond its blood pressure lowering capacity, amlodipine may be cerebroprotective by modulating neuroinflammation.

In the wake of rapid advancement in cardiovascular procedural technologies, physician-led preprocedural planning utilizing multi-modality imaging training is increasingly recognized as invaluable for procedural accuracy. Left atrial appendage occlusion (LAAO) is one such procedure in which complications such as device leak, cardiac injury, and device embolization can be decreased substantially with incorporation of physician driven imaging and digital tools. We discuss the benefits of cardiac CT and 3D printing in preprocedural planning for the Heart Team, as well as novel applications by physicians of intraprocedural 3D angiography and dynamic fusion imaging. Furthermore, incorporation of computational modeling and artificial intelligence (AI) may yield promise. For optimal patient-centric procedural success, we advocate for standardized preprocedural imaging planning by physicians within the Heart Team as an essential part of LAAO.

A comprehensive evaluation is necessary to identify the etiologic factors in order to select optimal stroke-prevention measures. Atrial fibrillation is one of the most important stroke causes. Although anticoagulant therapy is the treatment of choice for patients with nonvalvular atrial fibrillation, it should not be considered uniformly to treat all patients given the high mortality associated with anticoagulant-related hemorrhages. The authors propose a risk-stratified individualized approach for stroke prevention in patients with nonvalvular atrial fibrillation by considering nonpharmacologic approaches for patients at high hemorrhage risk or otherwise unsuitable for lifelong anticoagulation.

Cardiac rehabilitation (CR) has evolved over time not only to improve cardiorespiratory fitness through exercise but also to promote lifestyle-related behaviors to manage cardiovascular disease risk factors. Given the prevalence of obesity, diabetes mellitus, metabolic syndrome, and heart failure, CR serves as an ideal setting to monitor and, when indicated, intervene to ensure that individuals are optimally treated.The objective of this report was to review current antihyperglycemic agents and discuss the role for these medications in the care and treatment of individuals participating in CR.There is strong evidence that the benefits provided by some antihyperglycemic medications go beyond glycemic control to include general cardiovascular disease risk reduction. Health care professionals in CR should be aware of the cardiovascular benefits of newer antihyperglycemic agents, as well as the treatment approach to patients with type 2 diabetes, obesity, and heart failure.

Background: As patients with heart failure experience worsening of their condition, including acute decompensated heart failure, quality of life deteriorates. However, the trajectory of quality of life changes and their determinants in the context of the Rehabilitation Therapy in Older Acute Heart Failure Patients trial physical rehabilitation intervention are unknown. Methods: Patients ≥60 years old admitted for acute decompensated heart failure (n=349) were randomized to either attention control or intervention. Quality of life outcomes (Kansas City Cardiomyopathy Questionnaire; 12-Item Short-Form Health Survey) were measured at baseline (inpatient), 1 month, and 3 months. Intervention effects were assessed using linear mixed effects regression, including covariates to model the main effects of the intervention and timing of outcome assessments. Mediation analysis determined if changes in Kansas City Cardiomyopathy Questionnaire were due to improvement in physical function (short physical performance battery, 6-minute walk distance). Results: Baseline Kansas City Cardiomyopathy Questionnaire summary score was similarly poor in the intervention and control arms (40.2±20.6 versus 41.5±20.6). Although the intervention experienced nominally greater Kansas City Cardiomyopathy Questionnaire improvement than control at 1 month (64.7±1.9 versus 61.1±1.9, P =0.13), the difference was not statistically significant until 3 months (67.7±1.9 versus 60.8±1.9, P =0.004). Twelve-Item Short-Form Health Survey Physical and Mental Composite Scores increased in both arms at 1 month and continued improvement only in the intervention. The 3-month improvement in short physical performance battery score explained 64.1% of the improvement in Kansas City Cardiomyopathy Questionnaire ( P Conclusions: In older patients hospitalized for acute decompensated heart failure, quality of life improves in the first month after discharge. The quality of life benefit of a post-discharge physical rehabilitation intervention is detected early with large significant improvements at 3 months achieved primarily through improvement in short physical performance battery. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT02196038.

Cardiovascular reactivity (CVR) during physical stress is prognostic for incident cardiovascular disease. CVR is influenced by perceived pain. However, there is limited data on the effect of sex differences and repeated exposures to painful stimuli on CVR. We measured blood pressure (BP) and carotid-femoral pulse wave velocity (cf-PWV; an index of arterial stiffness) at rest, during isometric handgrip (HG) exercise at 30% of maximum voluntary contraction, and during postexercise circulatory occlusion (PECO) during two identical trials in 39 adults (20M/19F; 18-39 yr). We assessed participants' perceived pain using a visual analog scale after the first minute of each stimulus. We collected BP during

Background Stiff left atrial syndrome (SLAS) and pulmonary vein (PV) occlusion are rare yet potentially major life-long complications after radiofrequency ablation for atrial fibrillation. While mostly controlled by medical management, SLAS can progress to refractory congestive heart failure. Treatment of PV stenosis and occlusion remains a challenging problem with ongoing risk for recurrence regardless of techniques employed. Herein we present the case of a now 51-year-old male with acquired PV occlusion and SLAS who, over the course of eleven years, despite multiple interventions, ultimately required heart transplantation. Case presentation After undergoing three radiofrequency catheter procedures for paroxysmal atrial fibrillation (AF), a hybrid ablation was planned due to reappearance of symptomatic AF. Preoperative echocardiography and chest computed tomography (CT) revealed an occlusion of both left PVs. Furthermore, left atrial dysfunction, high pulmonary artery and pulmonary wedge pressures were diagnosed as well as an important reduction of the left atrial volume. The diagnosis of stiff left atrial syndrome was made. Primary surgical repair of the left-sided PVs was performed using a pericardial patch as a tubular neo-vein, combined with cryoablation in the left and right atrium to treat the patient’s arrhythmia. Initial results were favorable, however, after two years the patient experienced progressive restenosis with hemoptysis. Therefore, stenting of the common left PV was performed. Over the years, progressive right heart failure with severe tricuspid regurgitation developed, despite maximal medical therapy, which led to the need for heart transplantation. Conclusion The impact of PV occlusion and SLAS after percutaneous radiofrequency ablation can be lifelong and devastating for the clinical course of the patient. Since the presence of a small left atrium could be an important predictor for SLAS in case of redo ablation, preprocedural imaging should guide the operator to an algorithm of a decision-making containing lesion set, energy source, and safety of re-ablation.

OBJECTIVES: The present study aimed to compare safety and long-term prognosis of patients with chronic total coronary occlusions (CTO) stratified for remaining CTOs after percutaneous coronary intervention (PCI).DESIGN: The study cohort consisted of patients with coronary artery disease who underwent CTO PCI in a high volume tertiary center from 2009 to 2019 and were registered in Danish high-quality registers. Patients with successful PCI of all CTOs were compared to patients with ≥1 remaining CTO post-procedural. Primary endpoints were analysed using Cox-regression and Kaplan-Meier estimates, and included all-cause mortality, major adverse cardio- and cerebrovascular events (MACCE) and a 30-day safety endpoint.RESULTS: Procedural success rate was 87.7%, and 76.5% of patients had all CTO(s) opened post-PCI. Safety endpoint occurred in 4.6% of patients, and more frequently in patients with remaining CTO(s) (RD 4.9, 95%CI 0.1, 9.8). All-cause mortality was higher in patients with remaining CTO(s) (Unadjusted HR 1.65, 95% CI 1.03, 2.47, p = .015. Adjusted HR 1.32, 95%CI 0.88-1.99, p = .18) after eight years of follow-up. Risk of MACCE was significantly higher in patients with remaining CTO(s) (Unadjusted HR 1.79, 95% CI 1.34-2.41, p CONCLUSIONS: In our centre, CTO PCI was associated with high success rate and low risk of 30-days complications. Presence of remaining CTO(s) after final revascularization attempt was associated with higher but statistically insignificant long-term mortality but was an independent predictor of MACCE.

ObjectiveThe primary objective of this study was to evaluate whether the COVID-19 pandemic altered the racial and ethnic composition of patients receiving cardiac procedural care.DesignThis was a retrospective observational study.SettingThis study was conducted at a single tertiary-care university hospital.ParticipantsA total of 1,704 adult patients undergoing transcatheter aortic valve replacement (TAVR) (n=413), coronary artery bypass grafting (CABG) (n=506), or atrial fibrillation (AF) ablation (n=785) from March 2019 through March 2022 were included in this study.InterventionsNo interventions were performed as this was a retrospective observational study.Measurements and main resultsPatients were grouped based on the date of their procedure: pre-COVID (March 2019 to February 2020), COVID Year 1 (March 2020 to February 2021), and COVID Year 2 (March 2021 to March 2022). Population-adjusted procedural incidence rates during each period were examined and stratified based on race and ethnicity. The procedural incidence rate was higher for White patients versus Black, and non-Hispanic patients versus Hispanic patients for every procedure and every period. For TAVR, the difference in procedural rates between White patients versus Black patients decreased between the pre-COVID and COVID Year 1 (12.05-6.34 per 1,000,000 persons). For CABG, the difference in procedural rates between White patients versus Black, and non-Hispanic patients versus Hispanic patients did not change significantly. For AF ablations, the difference in procedural rates between White patients versus Black patients increased over time (13.06 to 21.55 to 29.64 per 1,000,000 persons in the pre-COVID, COVID Year 1, and COVID Year 2, respectively).ConclusionRacial and ethnic disparities in access to cardiac procedural care were present throughout all study time periods at the authors' institution. Their findings reinforce the continuing need for initiatives to reduce racial and ethnic disparities in healthcare. Further studies are needed to fully elucidate the effects of the COVID-19 pandemic on healthcare access and delivery.

BACKGROUND: Heart transplantation (HTx) after donation after circulatory death (DCD) is an expanding practice but is associated with increased warm ischemic time. The impact of DCD HTx on cardiac mechanics and myocardial fibrosis has not been reported. We aimed to compare cardiac mechanics and myocardial fibrosis using cardiovascular magnetic resonance (CMR) imaging in donation after brain death (DBD) and DCD HTx recipients and healthy controls. METHODS AND RESULTS: Consecutive HTx recipients between March 2015 and March 2021 who underwent routine surveillance CMR imaging were included. Cardiac mechanics were assessed using CMR feature tracking to compute global longitudinal strain, global circumferential strain, and right ventricular free-wall longitudinal myocardial strain. Fibrosis was assessed using late gadolinium enhancement imaging and estimation of extracellular volume. There were 82 (DBD n = 42, DCD n = 40) HTx recipients (aged 53 years, interquartile range 41-59 years, 24% female) who underwent CMR imaging at median of 9 months (interquartile range 6-14 months) after transplantation. HTx recipients had increased extracellular volume (29.7 ± 3.6%) compared with normal ranges (25.9%, interquartile range 25.4-26.5). Myocardial strain was impaired after transplantation compared with controls (global longitudinal strain -12.6 ± 3.1% vs -17.2 ± 1.8%, P < .0001; global circumferential strain -16.9 ± 3.1% vs -19.2 ± 2.0%, P = .002; right ventricular free-wall longitudinal strain -15.7 ± 4.5% vs -21.6 ± 4.7%, P < .0001). There were no differences in fibrosis burden (extracellular volume 30.6 ± 4.4% vs 29.2 ± 3.2%; P = .39) or cardiac mechanics (global longitudinal strain -13.1 ± 3.0% vs -12.1 ± 3.1%, P = .14; global circumferential strain -17.3 ± 2.9% vs -16.6 ± 3.1%, P = .27; right ventricular free-wall longitudinal strain -15.9 ± 4.9% vs -15.5 ± 4.1%, P = .71) between DCD and DBD HTx. CONCLUSIONS: HTx recipients have impaired cardiac mechanics compared with controls, with increased myocardial fibrosis. There were no differences in early CMR imaging characteristics between DBD and DCD heart transplants, providing further evidence that DCD and DBD HTx outcomes are comparable.

Purpose of Review Formation of the heart requires the coordinated addition of multiple progenitor sources which have undergone different pathways of specification and differentiation. In this review, I aim to put into context how recent studies defining cardiac progenitor heterogeneity build on our understanding of early heart development and also discuss the questions raised by this new insight. Recent Findings With the development of sequencing technologies and imaging approaches, it has been possible to define, at high temporal resolution, the molecular profile and anatomical location of cardiac progenitors at the single-cell level, during the formation of the mammalian heart. Summary Given the recent progress in our understanding of early heart development and technical advances in high-resolution time-lapse imaging and lineage analysis, we are now in a position of great potential, allowing us to resolve heart formation at previously impossible levels of detail. Understanding how this essential organ forms not only addresses questions of fundamental biological significance but also provides a blueprint for strategies to both treat and model heart disease.

Background: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. Methods: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute –funded Multi-Ethnic Study of Atherosclerosis. Results: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04–1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06–1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87–1.18]). Similarly, a very high LDL-C level ( > 193 mg/dL) versus LDL-C 0 (aHR, 2.42 [95% CI, 1.59–3.67]) but not in those without CAC (aHR, 0.92 [0.48–1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. Conclusions: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

We herein summarize currently available and clinically relevant information regarding the human immune responses to SARS-CoV-2 infection and vaccination, in relation to COVID-19 outcomes with a focus on acute respiratory distress syndrome (ARDS) and myocarditis.

Introduction: Frailty is a multidimensional syndrome characterized by the loss of functional reserve, associated with higher mortality and less functional survival in cardiac surgery patients. The Edmonton Frail Scale (EFS) is a comprehensive tool devised for brief frailty detection. To the best of our knowledge, there are no culturally adapted and validated frailty screening tools that enable the identification of vulnerability domains suited for use in the preoperative setting in Portugal. This was the motivation for this study. Objectives: To assess the validity and reproducibility of the Portuguese version of the EFS. Methods: Prospective observational study, in a sample of elective cardiac surgery patients. The Edmonton Frail Scale (EFS) translation and backtranslation were performed. Demographic and clinical data were collected, and the translated EFS translated, Geriatric Depression Scale, and Mini Mental State Examination Portuguese versions, Katz and Clinical Frailty Scales were administered. To assess validity Mann-Whitney test, Spearman's correlation coefficient, marginal homogeneity test and Kappa coefficient were employed. Reproducibility was assessed estimating kappa coefficient for the frailty diagnosis and the 11 EFS items. Intra-class correlation coefficients and the corresponding 95% confidence interval were estimated using linear mixed effects model. Results: The EFS Portuguese version revealed construct validity for frailty identification, as well as criterion validity for cognition and mood domains. Reproducibility was demonstrated, with k=0.62 (95% confidence interval (CI) 0.42-0.82) and intraclass correlation (ICC)=0.94 (95% CI 0.89-0.97) in inter-observer test and k=0.48 (95% CI 0.26-0.70) and ICC=0.85 (95% CI 0.72-0.92) in intra-observer test. Conclusions: The EFS Portuguese version is valid and reproducible for use, suiting pre-operative frailty screening in a cardiac surgery setting. Introdução: A fragilidade é uma síndrome multidimensional caracterizada pela perda de reserva funcional, associada a maior mortalidade e menor sobrevivência funcional após cirurgia cardíaca. A Escala de Fragilidade de Edmonton (EFS) é uma ferramenta abrangente de deteção de fragilidade. Não existe ainda em Portugal uma ferramenta de rastreio culturalmente adaptada e validada que permita a identificação de domínios específicos de vulnerabilidade para utilização no pré-operatório. Objetivos: Avaliar a validade e reprodutibilidade da versão portuguesa da EFS. Métodos: Estudo prospetivo observacional, realizado numa amostra de doentes propostos para cirurgia cardíaca. A EFS foi traduzida e retrotraduzida. Colheram-se dados demográficos e clínicos, aplicaram-se as versões traduzidas da EFS, Escala de Depressão Geriátrica e MMSE, as escalas de Katz e Clinical Frailty Scale. Validade avaliada utilizando o teste de Mann-Whitney, o coeficiente de correlação de Spearman, o teste de homogeneidade marginal e o coeficiente Kappa. Reprodutibilidade avaliada pelo cálculo do coeficiente kappa para o diagnóstico de fragilidade e para os 11 itens da escala. Coeficientes de correlação intraclasse e correspondentes intervalos de confiança a 95% estimados usando um modelo linear de efeitos mistos. Resultados: A versão portuguesa da EFS demonstrou validade de constructo, assim como validade de critério nos domínios de cognição e humor. É reprodutível, com k=0,62 (95% IC 0,42-0,82) e CCI=0,94 (95% IC 0,89-0,97) no teste interobservador e k=0,48 (95% IC 0,26-0,70) e CCI=0,85 (95% IC 0,72-0,92) no teste intraobservador. Conclusões: A versão portuguesa da EFS é adequada para rastreio pré-operatório de fragilidade em cirurgia cardíaca. info:eu-repo/semantics/publishedVersion

The Coronavirus 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus, has resulted in unprecedented morbidity and mortality worldwide. While COVID-19 typically presents as viral pneumonia, cardiovascular manifestations such as acute coronary syndromes, arterial and venous thrombosis, acutely decompensated heart failure (HF), and arrhythmia are frequently observed. Many of these complications are associated with poorer outcomes, including death. Herein we review the relationship between cardiovascular risk factors and outcomes among patients with COVID-19, cardiovascular manifestations of COVID-19, and cardiovascular complications associated with COVID-19 vaccination.

The global health crisis caused by the COVID-19 pandemic has evolved rapidly to overburden health care organizations around the world and has resulted in significant morbidity and mortality. Many countries have reported a substantial and rapid reduction in hospital admissions for acute coronary syndromes and percutaneous coronary intervention. The reasons for such abrupt changes in health care delivery are multifactorial and include lockdowns, reduction in outpatient services, reluctance to seek medical attention for fear of contracting the virus, and restrictive visitation policies adopted during the pandemic. This review discusses the impact of COVID-19 on important aspects of acute MI care.

Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on invasive coronary angiographic images. Calculating QFR is less invasive than measuring FFR and may be associated with lower costs. Current evidence supports the call for an adequately powered randomised comparison of QFR and FFR for the evaluation of intermediate coronary stenosis. The aim of the FAVOR III Europe Japan trial is to investigate if a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with a standard FFR-guided strategy in the evaluation of patients with intermediary coronary stenosis. FAVOR III Europe Japan is an investigator-initiated, randomised, clinical outcome, non-inferiority trial scheduled to randomise 2,000 patients with either 1) stable angina pectoris and intermediate coronary stenosis, or 2) indications for functional assessment of at least 1 non-culprit lesion after acute myocardial infarction. Up to 40 international centres will randomise patients to either a QFR-based or a standard FFR-based diagnostic strategy. The primary endpoint of major adverse cardiovascular events is a composite of all-cause mortality, any myocardial infarction, and any unplanned coronary revascularisation at 12 months. QFR could emerge as an adenosine- and wire-free alternative to FFR, making the functional evaluation of intermediary coronary stenosis less invasive and more cost-effective.

Introduction: Patients with advanced heart failure (HF) have high morbidity and mortality, with only a small proportion being eligible for advanced therapies. Intermittent outpatient levosimendan infusion has been shown to provide symptomatic relief and reduce the rate of HF events. Our aim was to assess the safety and efficacy of outpatient levosimendan administration in an advanced HF population. Methods: This is a report of a single-center experience of consecutive advanced HF patients referred for intermittent intravenous outpatient administration of levosimendan, between January 2018 and March 2021. Baseline and follow-up evaluation included clinical assessment, laboratory tests, transthoracic echocardiography and cardiopulmonary exercise testing. Baseline and clinical follow-up data were compared using the Wilcoxon signed-rank test. Results: A total of 24 patients (60.8 years, 83% male, mean left ventricular ejection fraction [LVEF] 24%), with a median of 1.5 HF hospitalizations in the previous six months, were referred for outpatient levosimendan pulses, the majority as a bridge to transplantation or due to clinical deterioration. At six-month follow-up there was a significant reduction in HF hospitalizations to 0.4±0.7 (p

Purpose Genicular artery embolization (GAE) is a new treatment option for symptomatic knee osteoarthritis. Genicular arterial anatomy is complex with limited published reports. This study describes the genicular artery anatomy utilizing intraprocedural cone-beam computed tomography (CBCT) during GAE. Materials and Methods This retrospective single-center study was approved by the institutional review board. All patients who underwent GAE between May 2018 and April 2022 were reviewed. Patients with a technically adequate CBCT were included in the analysis. CBCTs were analyzed to determine the presence, course, and branching patterns of the genicular arteries. Results A total of 222 patients underwent GAE and 205 (92%) were included for analysis. The descending genicular artery was present in 197 (96%) CBCTs with two branches in 152 (77%). The superior medial genicular artery (SMGA) was present in 186 (91%), superior lateral genicular artery (SLGA) in 203 (99%), inferior medial genicular artery (IMGA) in 195 (95%), inferior lateral genicular artery (ILGA) in 196 (95%), and median genicular artery (MGA) in 200 (97%). Four unique branching patterns were identified: common origin of SLGA and MGA (115, 56%), unique origins (45, 22%), trifurcation of SLGA, SMGA, and MGA (32, 15.5%), and common origin of SMGA and MGA (12, 6%). The recurrent ascending tibial was identified in 156 (76%) CBCTs and superior patellar artery in 175 (85%) CBCTs. Conclusion Genicular artery anatomy is complex with numerous common variants. CBCT is a powerful adjunct in GAE to rapidly identify target vessels for embolization and potentially decrease the risk of nontarget embolization.

Fluid restriction and diuretic management are mainstays in the postoperative management of cardiac patients, at risk of volume overload and its deleterious effects on primary cardiac function and multi-organ systems. The importance of fluid homeostasis is further emphasized among orthotopic heart transplant recipients (OHT). We sought to investigate the relationship between postoperative volume overload, mortality, and allograft dysfunction among pediatric OHT recipients within 1-year of transplantation. This is a retrospective cohort study from a single pediatric OHT center. Children under 21 years undergoing cardiac transplantation between 2010 and 2018 were included. Cumulative fluid overload (cFO) was assessed as percent fluid accumulation adjusted for preoperative body weight. Greater than 10% cFO defined those with postoperative cFO and a comparison of postoperative cFO vs. no postoperative cFO (p = 0.04, independent of age and weight. There was no significant relationship between cFO and allograft dysfunction, measured by rates of clinical rejection and cardiopulmonary filling pressures within 1-year of transplant. Early postoperative volume overload is prevalent and associated with increased risk of death at 1-year among pediatric OHT recipients. It may be an important postoperative marker of transplant survival, and this relationship warrants further clinical investigation.

Left ventricular thrombus (LVT) is a recognized complication of acute myocardial infarction which is associated with stroke. There has yet to be a published systematic review that focuses on outcomes for patients with LVT. We conducted a systematic review on treatments, adverse events and thrombus resolution in patients with LVT. Meta-analysis and numerical pooling were used to evaluate the difference in outcomes based on treatment and the presence or absence of LVT. A total of 39 studies were included (5475 patients with LVT and 356 589 patients with no LVT). The use of direct oral anticoagulants (DOACs) was associated with reduced mortality [RR, 0.66; 95% confidence interval (CI), 0.45-0.97; I2 = 9%] and bleeding (RR, 0.64; 95% CI, 0.48-0.85; I2 = 0%) compared to warfarin but there was a nonsignificant reduction in stroke/embolic events (RR, 0.95; 95% CI, 0.76-1.19; I2 = 3%). For patients with any treatment, the rate of stroke/embolic events, bleeding and mortality at follow-up of up to 12 months was 6.4, 3.7 and 7.9%, respectively. Pooled results from six studies that evaluated resolution at 6 months suggest that 80% of LVT were resolved. Apixaban was associated with the highest rate of (93.3%) whereas warfarin exhibited the lowest rate of resolution 73.1%. LVT is best managed with DOAC compared to warfarin therapy. An individualized approach to antithrombotic therapy is warranted as there appears to be no duration of therapy that clearly results in the resolution of all cases of LVT so follow-up imaging after discontinuation of anticoagulant is needed. Left ventricular thrombus (LVT) is a recognized complication of acute myocardial infarction which is associated with stroke. There has yet to be a published systematic review that focuses on outcomes for patients with LVT. We conducted a systematic review on treatments, adverse events and thrombus resolution in patients with LVT. Meta-analysis and numerical pooling were used to evaluate the difference in outcomes based on treatment and the presence or absence of LVT. A total of 39 studies were included (5475 patients with LVT and 356 589 patients with no LVT). The use of direct oral anticoagulants (DOACs) was associated with reduced mortality [RR, 0.66; 95% confidence interval (CI), 0.45-0.97; I2 = 9%] and bleeding (RR, 0.64; 95% CI, 0.48-0.85; I2 = 0%) compared to warfarin but there was a nonsignificant reduction in stroke/embolic events (RR, 0.95; 95% CI, 0.76-1.19; I2 = 3%). For patients with any treatment, the rate of stroke/embolic events, bleeding and mortality at follow-up of up to 12 months was 6.4, 3.7 and 7.9%, respectively. Pooled results from six studies that evaluated resolution at 6 months suggest that 80% of LVT were resolved. Apixaban was associated with the highest rate of (93.3%) whereas warfarin exhibited the lowest rate of resolution 73.1%. LVT is best managed with DOAC compared to warfarin therapy. An individualized approach to antithrombotic therapy is warranted as there appears to be no duration of therapy that clearly results in the resolution of all cases of LVT so follow-up imaging after discontinuation of anticoagulant is needed.

ObjectivesCurrent literature is lacking a comprehensive review of data on dietary interventions in blood pressure (BP) management in sub-Saharan African countries. We assessed the association of dietary and other lifestyle interventions with BP-lowering effects in populations within sub-Saharan Africa.MethodsWe performed a systematic review and random-effects meta-analysis to determine the impact of dietary and lifestyle interventions on SBP and DBP in sub-Saharan Africa. We searched the MEDLINE, EMBASE, and Web of Science databases. We included intervention studies that were randomized and nonrandomized conducted in Africans residing in sub-Saharan Africa investigating diet and other lifestyle, physical activity, weight loss, tobacco, and alcohol cessation modifications. We determined the effect of diet and other lifestyle interventions on SBP and DBP. We expressed effect size as weighted mean difference and 95% confidence interval (CI).Main results: We identified six studies with a total of 1412 individuals, 38% males, mean age of 52.8 years (SD = 11.5). The weighted mean difference of dietary and other lifestyle interventions on SBP and DBP was -7.33 mmHg, (95% CI: -9.90 to -4.76, P

Aims Screening for atrial fibrillation (AF) is recommended in the European Society of Cardiology guidelines. Yields of detection can be low due to the paroxysmal nature of the disease. Prolonged heart rhythm monitoring might be needed to increase yield but can be cumbersome and expensive. The aim of this study was to observe the accuracy of an artificial intelligence (AI)-based network to predict paroxysmal AF from a normal sinus rhythm single-lead ECG. Methods and results A convolutional neural network model was trained and evaluated using data from three AF screening studies. A total of 478 963 single-lead ECGs from 14 831 patients aged ≥65 years were included in the analysis. The training set included ECGs from 80% of participants in SAFER and STROKESTOP II. The remaining ECGs from 20% of participants in SAFER and STROKESTOP II together with all participants in STROKESTOP I were included in the test set. The accuracy was estimated using the area under the receiver operating characteristic curve (AUC). From a single timepoint ECG, the artificial intelligence–based algorithm predicted paroxysmal AF in the SAFER study with an AUC of 0.80 [confidence interval (CI) 0.78–0.83], which had a wide age range of 65–90+ years. Performance was lower in the age-homogenous groups in STROKESTOP I and STROKESTOP II (age range: 75–76 years), with AUCs of 0.62 (CI 0.61–0.64) and 0.62 (CI 0.58–0.65), respectively. Conclusion An artificial intelligence–enabled network has the ability to predict AF from a sinus rhythm single-lead ECG. Performance improves with a wider age distribution.

Aims Literature regarding outcomes associated with atrial fibrillation among cirrhosis patients who had left atrial appendage occlusion (LAAO) device procedure is limited. We aim to evaluate the in-hospital clinical outcomes and 30-day readmissions among LAAO with and without cirrhosis. Methods and results We performed a retrospective study of all hospitalizations associated with the LAAO procedure, using the Nationwide Readmissions Database for the years 2016–19. Primary outcomes were in-hospital clinical outcomes and 30-day readmissions. A total of 54 897 index hospitalizations for LAAO (female 41.8%) were reported. Of these, 905(1.65%) had cirrhosis. Gastrointestinal (GI) bleeding was reported in 44 (4.9%) vs. 1606 (2.97%) and coagulopathy in 21 (2.3%) vs. 521 (0.96%) in cirrhosis and without-cirrhosis groups, respectively. A total of 872 (1.59%) patients needed blood transfusion, 24 (2.7%) vs. 848(1.57%) in cirrhosis vs. without-cirrhosis groups (P = 0.047). Fresh frozen plasma (FFP) transfusion was reported among 888 (1.62%), with cirrhosis 26 (3%) vs. without cirrhosis 862 (1.6%) (P = 0.05). On adjusted multivariate logistic regression analysis, acute kidney injury, coagulopathy, FFP transfusion, and blood transfusion were strongly associated with cirrhosis, and GI bleeding, ischaemic stroke, and intracranial haemorrhage were not associated with cirrhosis. Readmissions in 30 days were 5028 (9.18%), 167 (18.5%) in the cirrhosis group and 4861 (9%) without-cirrhosis group (P = 0.01). On multivariate Cox regression, CHA2DS2-Vasc score of six was significantly associated with 30-day readmission compared with other scores [hazard ratio 2.24; 95% confidence interval (1.58–3.16); P < 0.001]. Conclusion Left atrial appendage occlusion procedure in patients with cirrhosis had relatively similar GI bleeding and stroke rates, however, had higher rates of 30-day readmission. A higher CHA2DS2-Vasc score was more likely to be associated with 30-day readmissions and hence would help in discharge planning. The long-term safety and efficacy of LAAO in the cirrhosis population need to be demonstrated.

Background: Angiotensin receptor-neprilysin inhibitor (ARNI) prescription in the United States remains suboptimal despite strong evidence for efficacy and value in heart failure with reduced ejection fraction. Factors responsible for under prescription are not completely understood. Economic limitations may play a disproportionate role in reduced access for some patients. Methods: This is an analysis of the Get With The Guidelines-Heart Failure registry, supplemented with data from the Distressed Community Index. Data were fit to a mixed-effects regression model to investigate clinical and socioeconomic factors associated with ARNI prescription at hospital discharge. Missing data were handled by multilevel multiple imputation. Results: Of the 136 144 patients included in analysis, 12.6% were prescribed an ARNI at discharge. The dominant determinants of ARNI prescription were ARNI use while inpatient (odds ratio [OR], 72 [95% CI, 58–89]; P P P P P =0.010). The rate of ARNI prescription is increasing with time (OR, 2 [95% CI, 1.8–2.3]; P Conclusions: Multiple medical and socioeconomic factors contribute to low rates of ARNI prescription at hospital discharge. Potential targets for improving ARNI prescription rates include initiating ARNIs during hospitalization and aggressively addressing patients’ access barriers with the support of inpatient social services and pharmacists.

Background: Disproportionate exposure to poor food environments and food insecurity among Black Americans may partially explain critical chronic disease disparities by race and ethnicity. A complex set of structural factors and interactions between Black residents and their food environments, including store types, quantity, proximity, and quality of goods and consumer interactions within stores, may affect nutritional behaviors and contribute to higher cardiovascular and kidney disease risk. Methods: We used the Photovoice methodology to explore the food environment in Baltimore, MD, through the perspectives of Black residents with hypertension between August and November 2019. Twenty-four participants were enrolled in the study (mean age: 65.1 years; 67% female). After a brief photography training, participants captured photos of their food environment, which they discussed in small focus groups over the course of 5 weeks. Discussions were audiotaped and analyzed for emergent themes using a line-by-line inductive approach. Themes were, then, organized into a collective narrative. Results: Findings describe physical and social features of the food environment as well as participants’ perceptions of its origins and holistic and generational health effects. The study illustrates the interrelationships among the broader socio-political environment, the quality and quantity of stores in the food landscape, and the ways in which they engage with the food environment as residents and consumers who have been marginalized due to their race and/or social class. The following meta-themes emerged from the data: (1) social injustice; (2) structural racism and classism; (3) interpersonal racism; (4) generational effects; (5) mistrust; (6) social programs; and (7) community asset-based approaches, including advocacy and civic engagement. Conclusions: Understanding residents’ perceptions of the foundations and effects of the food environment on their health may help stakeholders to cocreate multilevel interventions alongside residents to improve access to healthy food and health outcomes among disparities affected populations.

Background: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied. Methods: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value. Results: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index ( P =0.03, adjusted mean difference [SE] of changes between groups −0.03[0.01]), atrioventricular valve inflow peak E ( P =0.009, 3.95 [1.50]), and A velocities ( P =0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e′ velocity ( P =0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e′ ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s′ and e′ velocity). Conclusions: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort. Registration: URL: https://clinicaltrials.gov ; Unique Identifier: NCT02741115.

Background: Echocardiographic deformation-based ratios and novel multi-parametric scores have been suggested to discriminate transthyretin cardiac amyloidosis (ATTR-CM) from other causes of increased left ventricular wall thickness among patients referred for ATTR-CM evaluation. Their relative predictive accuracy has not been well studied. We sought to (1) identify echocardiographic parameters predictive of ATTR-CM and (2) compare the diagnostic accuracy of these parameters in patients with suspected ATTR-CM referred for technetium-99m-pyrophosphate scintigraphy. Methods: Echocardiograms from 598 patients referred to 3 major amyloidosis centers for technetium-99m-pyrophosphate to detect ATTR-CM were analyzed, including longitudinal strain (LS) analysis. Deformation ratios (septal apex to base ratio, relative apical sparing, ejection fraction to global LS), a multi-center European increased wall thickness score, and Mayo Clinic derived ATTR score (transthyretin cardiac amyloidosis score) were calculated. A logistic regression model was used to identify the parameters that best associated with a diagnosis of ATTR-CM. Comparison of the diagnostic capacity of the parameters was performed by receiver operating characteristic curves and the area under the curve (AUC). Results: Over half of the subjects (54.2%) were diagnosed with ATTR-CM (78% were men, median age of 76 years). Age, inferolateral wall thickness, and basal LS were the strongest predictors of ATTR-CM, AUC of 0.87 (95% CI: 0.83, 0.90), superior to the increased wall thickness score AUC of 0.78 (95% CI: 0.73, 0.83; P =0.004). An inferolateral wall thickness of ≥14 mm (AUC: 0.73) was as accurate as the published cut-offs for transthyretin cardiac amyloidosis score and septal apex to base (AUC: 0.72 and 0.69, P =0.8 and P =0.1, respectively), and was superior to ejection fraction to global LS and relative apical sparing (AUC: 0.64 and 0.53, P P =0.2); outperforming the other indices ( P Conclusion: Inferolateral wall thickness and average basal LS performed as well as or better than more complex echo ratios and multiparametric scores to predict ATTR-CM.

Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. Results: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: 5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (−0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus −1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (−0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). Conclusions: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01178320.

Background: Reducing hospital length of stay (LOS) has been identified as an important lever for minimizing the burden of heart failure hospitalization, yet the impact of social and structural determinants of health on LOS has received little attention. We investigated disparities in LOS across race/ethnicity and their possible drivers. Methods: We analyzed patients hospitalized for heart failure from 2017 to 2020 using the Get With The Guidelines-Heart Failure registry. We characterized LOS differences across race/ethnicity by insurance and disposition, adjusting for demographics, comorbidities, and clinical severity. Effects of hospital-level clustering on LOS across race/ethnicity were assessed using hierarchical mixed-effects models. We evaluated the association between LOS and discharge rates of guideline-directed medical therapy. Results: Three thousand three seven hundred thirty patients hospitalized for heart failure were identified. After excluding inpatient deaths, the adjusted LOS for Black (5.72 days [95% CI, 5.62–5.82]), Hispanic (5.94 days [95% CI, 5.79–6.08]), and Indigenous American/Pacific Islander (6.06 days [95% CI, 5.85–6.27]) patients remained significantly longer compared with non-Hispanic White patients (5.32 days [95% CI, 5.25–5.39]). This pattern was driven by LOS differences among patients discharged to hospice or nursing facilities. After accounting for variability between hospitals, associations of race/ethnicity with LOS either were attenuated or reversed in direction. Guideline-directed medical therapy rates on discharge did not differ significantly across race/ethnicity despite longer LOS for Black, Hispanic, and Indigenous American/Pacific Islander patients. Conclusions: Differences between hospitals drive LOS disparities across race/ethnicity. Longer LOS among Black, Hispanic, and Indigenous American/Pacific Islander patients was not associated with improved quality of care.

The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional–led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single–time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

Background:The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function.Methods:Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants’ sera, or e-cigarette aerosol condensate, on NO and H2O2release and cell permeability in cultured endothelial cells (ECs).Results:E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production.Conclusions:Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.

Binswanger disease is the small vessel form of vascular cognitive impairment and dementia. Deposition of Alzheimer disease proteins can begin in midlife and progress slowly, whereas aging of the vasculature also can begin in midlife, continuing to progress into old age, making mixed dementia the most common type of dementia. Biomarkers facilitate the early diagnosis of dementias. It is possible to diagnose mixed dementia before autopsy with biomarkers for vascular disease derived from diffusor tensor images on magnetic resonance imaging and Alzheimer disease proteins, Aβ (amyloid β), and phosphorylated tau, in cerebrospinal fluid or in brain with positron emission tomography. The presence of vascular disease accelerates cognitive decline. Both misfolded proteins and vascular disease promote inflammation, which can be detected in cerebrospinal fluid by the presence of MMPs (matrix metalloproteinases), angiogenic growth factors, and cytokines. MMPs disrupt the blood-brain barrier and break down myelin, producing Binswanger disease’s 2 main pathological features. Advances in detecting biomarkers in plasma will provide early detection of dementia and aided by machine learning and artificial intelligence, will enhance diagnosis and form the basis for early treatments.

Background: The choroidal vasculature, including the choriocapillaris and vortex veins, is essential for providing nutrients to the metabolically demanding photoreceptors and retinal pigment epithelium. Choroidal vascular dysfunction leads to vision loss and is associated with age-related macular degeneration and the poorly understood pachychoroid diseases including central serous chorioretinopathy and polypoidal choroidal vasculopathy that are characterized by formation of dilated pachyvessels throughout the choroid. Methods: Using neural crest-specific Angpt1 knockout mice, we show that Angiopoietin 1, a ligand of the endothelial receptor TEK (also known as Tie2) is essential for choriocapillaris development and vortex vein patterning. Results: Lacking choroidal ANGPT1, neural crest-specific Angpt1 knockout eyes exhibited marked choriocapillaris attenuation and 50% reduction in number of vortex veins, with only 2 vortex veins present in the majority of eyes. Shortly after birth, dilated choroidal vessels resembling human pachyvessels were observed extending from the remaining vortex veins and displacing the choriocapillaris, leading to retinal pigment epithelium dysfunction and subretinal neovascularization similar to that seen in pachychoroid disease. Conclusions: Together, these findings identify a new role for ANGPT1 in ocular vascular development and demonstrate a clear link between vortex vein dysfunction, pachyvessel formation, and disease.

Background: Mural cells in ascending aortic aneurysms undergo phenotypic changes that promote extracellular matrix destruction and structural weakening. To explore this biology, we analyzed the transcriptional features of thoracic aortic tissue. Methods: Single-nuclear RNA sequencing was performed on 13 samples from human donors, 6 with thoracic aortic aneurysm, and 7 without aneurysm. Individual transcriptomes were then clustered based on transcriptional profiles. Clusters were used for between-disease differential gene expression analyses, subcluster analysis, and analyzed for intersection with genetic aortic trait data. Results: We sequenced 71 689 nuclei from human thoracic aortas and identified 14 clusters, aligning with 11 cell types, predominantly vascular smooth muscle cells (VSMCs) consistent with aortic histology. With unbiased methodology, we found 7 vascular smooth muscle cell and 6 fibroblast subclusters. Differentially expressed genes analysis revealed a vascular smooth muscle cell group accounting for the majority of differential gene expression. Fibroblast populations in aneurysm exhibit distinct behavior with almost complete disappearance of quiescent fibroblasts. Differentially expressed genes were used to prioritize genes at aortic diameter and distensibility genome-wide association study loci highlighting the genes JUN, LTBP4 (latent transforming growth factor beta-binding protein 1), and IL34 (interleukin 34) in fibroblasts, ENTPD1, PDLIM5 (PDZ and LIM domain 5), ACTN4 (alpha-actinin-4), and GLRX in vascular smooth muscle cells, as well as LRP1 in macrophage populations. Conclusions: Using nuclear RNA sequencing, we describe the cellular diversity of healthy and aneurysmal human ascending aorta. Sporadic aortic aneurysm is characterized by differential gene expression within known cellular classes rather than by the appearance of novel cellular forms. Single-nuclear RNA sequencing of aortic tissue can be used to prioritize genes at aortic trait loci.

Many patients exhibit clinically significant depression upon enrollment in cardiac rehabilitation (CR). Antidepressants are a first-line treatment option for depression, but the effectiveness of antidepressants in patients with heart disease is mixed. The purpose of this meta-analysis was to evaluate the efficacy of antidepressants for depression in patients eligible for CR.A meta-analysis was conducted including randomized controlled trials of antidepressants from January 1990 to September 2021 that compared antidepressants with placebo. Random-effects models were used between group effect sizes (Hedges' g ).A total of 13 trials with predominately White (68% ± 12; n =7) male (70% ± 11) samples averaging 61 ± 5 yr compared antidepressants (1128 participants) with placebo (1079 participants). Antidepressants reduced depressive symptoms ( g = 0.17: 95% CI, 0.08-0.27), but the effect was small. Heterogeneity among study effects was low ( I2 = 6.42) and nonsignificant ( Q = 10.75, P = .46), although patients with heart failure ( gHF = 0.05: 95% CI, -0.09 to 0.18) demonstrated smaller effects compared with patients with other cardiovascular disease conditions (g non-HF = 0.22: 95% CI, 0.11-0.32) ( QB [1] = 3.97; Plt; .05). No study reported safety concerns associated with antidepressants.The effect size of antidepressant pharmacotherapy in this population is small. No trials reported on the combined effects of exercise and pharmacotherapy. If the patient is not suicidal, CR staff may consider patient preference and refer patients for additional treatment as necessary.

Background: The United States lacks a timely and accurate nationwide surveillance system for acute ischemic stroke (AIS). We use the Get With The Guidelines-Stroke registry to apply poststratification survey weights to generate national assessment of AIS epidemiology, hospital care quality, and in-hospital outcomes. Methods: Clinical data from the Get With The Guidelines-Stroke registry were weighted using a Bayesian interpolation method anchored to observations from the national inpatient sample. To generate a US stroke forecast for 2019, we linearized time trend estimates from the national inpatient sample to project anticipated AIS hospital volume, distribution, and race/ethnicity characteristics for the year 2019. Primary measures of AIS epidemiology and clinical care included patient and hospital characteristics, stroke severity, vital and laboratory measures, treatment interventions, performance measures, disposition, and clinical outcomes at discharge. Results: We estimate 552 476 patients with AIS were admitted in 2019 to US hospitals. Median age was 71 (interquartile range, 60–81), 48.8% female. Atrial fibrillation was diagnosed in 22.6%, 30.2% had prior stroke/transient ischemic attack, and 36.4% had diabetes. At baseline, 46.4% of patients with AIS were taking antiplatelet agents, 19.2% anticoagulants, and 46.3% cholesterol-reducers. Mortality was 4.4%, and only 52.3% were able to ambulate independently at discharge. Performance nationally on AIS achievement measures were generally higher than 95% for all measures but the use of thrombolytics within 3 hours of early stroke presentations (81.9%). Additional quality measures had lower rates of receipt: dysphagia screening (84.9%), early thrombolytics by 4.5 hours (79.7%), and statin therapy (80.6%). Conclusions: We provide timely, reliable, and actionable US national AIS surveillance using Bayesian interpolation poststratification weights. These data may facilitate more targeted quality improvement efforts, resource allocation, and national policies to improve AIS care and outcomes.

The aim of this investigation was to determine if meeting the 2018 physical activity (PA) time-intensity guidelines was associated with better ambulatory function, health-related quality of life (HRQoL), vascular function, and inflammation than failing to meet the guidelines in patients with peripheral artery disease and claudication. Second, we determined the optimal number of total steps/d and steps taken at moderate cadence needed to meet the PA time-intensity guidelines.Five hundred seventy-two patients were assessed on daily ambulatory activity for 1 wk with a step activity monitor, and were grouped according to whether they achievedlt;150 min/wk of moderate-intensity PA (group 1 = do not meet guidelines; n = 397) or whether they were above this threshold (group 2 = meet guidelines; n = 175).Treadmill peak walking time (mean ± SD) was higher ( Plt; .001) in group 2 (709 ± 359 sec) than in group 1 (427 ± 281 sec). The physical function HRQoL score was higher ( Plt; .001) in group 2 (61 ± 22%) than in group 1 (44 ± 21%). High-sensitivity C-reactive protein was lower ( Plt; .001) in group 2 (3.6 ± 4.5 mg/L) than in group 1 (5.9 ± 6.1 mg/L). Finally, ≥7675 total steps/d and ≥1660 steps/d at moderate cadence were optimal thresholds associated with meeting PA guidelines.Patients with claudication who meet the 2018 PA time-intensity guidelines for US adults had better ambulation, HRQoL, and vascular outcomes than those who failed to meet the PA guidelines. Patients with claudication best achieved the PA time-intensity guidelines by taking ≥7675 total steps/d, and ≥1660 steps/d at a moderate cadence.

ImportanceInternal medicine residents’ professional development preferences were discordant with their perceptions of cardiology in a survey circulated a decade ago; no contemporary data exist. This information is important for effective recruitment and retention of a highly talented and diverse future cardiology workforce.ObjectiveTo identify residents’ professional development preferences and cardiology perceptions, in relation to specialty choice, and compare the findings with those from a decade prior.Design, Setting, and ParticipantsThe original survey from the 2010 study was updated and sent to US internal medicine programs. Respondents (ie, internal medicine residents) rated 38 professional development preferences and 20 cardiology perceptions. Data were collected in 2020 and compared with survey results from the prior 2010 study. Multivariable models were created for specialty choice using scaled independent variables dichotomized using the top 2 options; categorical variables were recoded into binary variables for analysis.Main Outcomes and MeasuresMultivariable models were used to determine the association of demographic characterisitcs and survey responses with prospective career choice. Responses were examined by total group, by gender, by self-reported consideration of entering cardiology as a profession, and by comparison with a decade prior both as a group and by gender.ResultsA total of 840 residents (mean [SD] age, 29.24 [2.82] years; 49.8% male; 55.4% White) completed the survey. The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions, with additional questions on demographic characteristics. The most important professional development preferences by descending Likert score were as follows: positive role models (4.56), stimulating career (3.81), and family friendly (3.78). The cardiology perception statements with the highest agreement were as follows: interferes with family life during training (3.93) and having met positive role models or having positive views of cardiovascular disease as a topic (3.85). Multivariable analysis yielded a 22-element model predicting cardiology as career choice. Compared with the 2010 survey, the findings of this survey indicated increased importance of work-life balance components for both male and female residents, with a greater change in male residents. Contemporary residents were more likely than their predecessors to agree with negative perceptions of cardiology.Conclusions and RelevanceThis survey study found that both male and female residents place a high value on support for optimal work-life balance; these preferences have intensified over the past decade and factor into career choice. Negative perceptions of cardiology persist and, in some aspects, are worsening. Improving the culture of cardiology may make this specialty a more attractive career choice for all.

ImportanceSex-specific differences in the commonly used cardiac biomarkers high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro–brain natriuretic peptide (NT-proBNP) are apparent. There is an absence of medical literature delineating the concentration differences for these biomarkers in transgender individuals without cardiac disease.ObjectiveTo determine the distribution of hs-cTn and NT-proBNP in healthy transgender people.Design, Setting, and ParticipantsIn this cross-sectional prospective study, healthy transgender individuals prescribed testosterone or estradiol for 12 months or more were recruited from internal medicine and primary care clinics that specialize in transgender medical care between November 1, 2017, and July 1, 2018.ExposuresTestosterone or estradiol for 12 months.Main Outcomes and MeasuresConcentrations for hs-cTnI (troponin I), hs-cTnT (troponin T), and NT-proBNP were measured.ResultsTransgender people prescribed testosterone (n = 79; mean [SD] age, 28.8 [7.8] years) or estrogen (n = 93; mean [SD] age, 35.1 [11.7] years) were recruited. The concentration of hs-cTn was significantly higher in transgender men relative to transgender women. For Abbott hs-cTnI levels, the median (IQR) concentration observed in transgender men and women was 0.9 (0.6-1.7) ng/L and 0.6 (0.3-1.0) ng/L, respectively. Results were similar across 2 additional hs-cTn assays. In contrast, NT-proBNP level was higher in transgender women. The median (IQR) NT-proBNP concentration was significantly higher in transgender women ( 49 [32-86] ng/L) than in transgender men (17 [13-27] ng/L).Conclusions and RelevanceFindings of this cross-sectional study suggest that the differences in concentration for hs-cTn and NT-proBNP between transgender men and women were similar to what is observed between cisgender men and women. Sex hormones, rather than sex assigned at birth, may be a stronger driver of the observed concentration differences between healthy men and women for biomarkers of cardiac disease.

Background: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown. Methods: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7–8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using t tests. Results: In cohort A, median (interquartile range) age was 62 years (47–71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4–9). In cohort B, median (interquartile range) age was 59 years (49–71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6–9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance P ≤0.002) and were greater in the high-risk compared with the low-risk category ( P ≤0.002). In cohort B, death or lung transplant occurred in 14 of 54, 23 of 53, and 35 of 54 patients in the lowest, middle, and highest cfDNA tertiles, respectively. cfDNA levels stratified as tertiles (log-rank: P =0.0001) and REVEAL risk groups (log-rank: P P =0.02). Compared with controls, methylation analysis in patients with PAH revealed increased cfDNA originating from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium, and cardiac myocytes (Bonferroni adjusted P P ≤0.02). Conclusions: Circulating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis.