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Understanding the natural history of coronary artery atherosclerosis is necessary to determine prognosis and prescribe effective therapies. Traditional management of coronary artery disease has focused on the treatment of flow-limiting anatomical obstructions that lead to ischaemia. In most scenarios, revascularization of these atherosclerotic plaques has not substantially improved freedom from death or myocardial infarction, questioning the utility of contemporary revascularization strategies to improve prognosis. Advances in non-invasive and invasive imaging techniques have helped to identify the characteristics of obstructive and non-obstructive plaques that are precursors for plaque progression and future acute coronary syndromes as well as cardiac death. These ‘vulnerable plaques’ develop as a consequence of systemic inflammation and are prone to inducing thrombosis. Vulnerable plaques most commonly have a large plaque burden with a well-formed necrotic core and thin fibrous cap and are metabolically active. Perivascular adipose tissue might, in some patients, be used as a surrogate for coronary inflammation and predict future risk of adverse cardiac events. Vulnerable plaques can be identified in their quiescent state, offering the potential for therapeutic passivation. In this Review, we describe the biological and compositional features of vulnerable plaques, the non-invasive and invasive diagnostic modalities to characterize vulnerable plaques, the prognostic utility of identifying vulnerable plaques, and the future studies needed to explore the value of intensified pharmacological and focal treatments of vulnerable plaques.In this Review, the authors describe the features of coronary artery vulnerable plaques as well as non-invasive and invasive diagnostic modalities that can be used to characterize them. They also discuss the prognostic utility of identifying vulnerable plaques and the best current approaches to manage these lesions, and highlight evidence gaps and future directions.

Infective endocarditis (IE), initially described more than 350 years ago, involves infection of the endocardial surface of the heart. The clinical manifestations of IE can involve every organ system, and the cardiac manifestations can include valvular vegetation, abscess, periannular extension of infection, and myopericarditis. Echocardiography is crucial in the diagnosis of IE, but alternative imaging modalities are playing an increasing role in the diagnosis and management of IE. Multidisciplinary care is imperative to the management of IE, often requiring the expertise of cardiologists, cardiothoracic surgeons, infectious diseases specialists, radiologists, and neurologists. We performed a literature search of the PubMed database from January 1st, 2000, to September 30th, 2019, using the terms infective endocarditis, diagnosis, and management to find the most pertinent and highest-quality evidence. This review summarizes key aspects of IE, with a focus on emerging advances in diagnosis. We also highlight growing patient populations at risk for IE, including patients with intracardiac devices and congenital heart disease.

Throughout 2021, the medical and scientific communities have focused on managing the acute morbidity and mortality caused by the coronavirus disease 2019 (COVID-19) pandemic. With the approval of multiple vaccines, there is a light at the end of this dark tunnel and an opportunity to focus on the future, including managing the long-term sequelae in patients who have survived acute COVID-19. In this Perspectives article, we highlight what is known about the cardiovascular sequelae in survivors of COVID-19 and discuss important questions that need to be addressed in prospective studies to understand and mitigate these lasting cardiovascular consequences, including in post-acute COVID-19 syndrome. To provide the greatest benefit to these survivors, prospective studies should begin now, with resources made available to monitor and study this population in the coming years.In this Perspectives article, the authors highlight what is known about cardiovascular sequelae in survivors of COVID-19 and discuss important questions that need to be addressed in prospective studies to understand and mitigate these lasting cardiovascular consequences, including in post-acute COVID-19 syndrome.

Atrial fibrillation is frequently asymptomatic and thus underdetected but is associated with stroke, heart failure, and death. Existing screening methods require prolonged monitoring and are limited by cost and low yield. We aimed to develop a rapid, inexpensive, point-of-care means of identifying patients with atrial fibrillation using machine learning. We developed an artificial intelligence (AI)-enabled electrocardiograph (ECG) using a convolutional neural network to detect the electrocardiographic signature of atrial fibrillation present during normal sinus rhythm using standard 10-second, 12-lead ECGs. We included all patients aged 18 years or older with at least one digital, normal sinus rhythm, standard 10-second, 12-lead ECG acquired in the supine position at the Mayo Clinic ECG laboratory between Dec 31, 1993, and July 21, 2017, with rhythm labels validated by trained personnel under cardiologist supervision. We classified patients with at least one ECG with a rhythm of atrial fibrillation or atrial flutter as positive for atrial fibrillation. We allocated ECGs to the training, internal validation, and testing datasets in a 7:1:2 ratio. We calculated the area under the curve (AUC) of the receiver operatoring characteristic curve for the internal validation dataset to select a probability threshold, which we applied to the testing dataset. We evaluated model performance on the testing dataset by calculating the AUC and the accuracy, sensitivity, specificity, and F1 score with two-sided 95% CIs. We included 180 922 patients with 649 931 normal sinus rhythm ECGs for analysis: 454 789 ECGs recorded from 126 526 patients in the training dataset, 64 340 ECGs from 18 116 patients in the internal validation dataset, and 130 802 ECGs from 36 280 patients in the testing dataset. 3051 (8·4%) patients in the testing dataset had verified atrial fibrillation before the normal sinus rhythm ECG tested by the model. A single AI-enabled ECG identified atrial fibrillation with an AUC of 0·87 (95% CI 0·86–0·88), sensitivity of 79·0% (77·5–80·4), specificity of 79·5% (79·0–79·9), F1 score of 39·2% (38·1–40·3), and overall accuracy of 79·4% (79·0–79·9). Including all ECGs acquired during the first month of each patient's window of interest (ie, the study start date or 31 days before the first recorded atrial fibrillation ECG) increased the AUC to 0·90 (0·90–0·91), sensitivity to 82·3% (80·9–83·6), specificity to 83·4% (83·0–83·8), F1 score to 45·4% (44·2–46·5), and overall accuracy to 83·3% (83·0–83·7). An AI-enabled ECG acquired during normal sinus rhythm permits identification at point of care of individuals with atrial fibrillation. None.

There are limited data on acute kidney injury (AKI) complicating acute myocardial infarction with cardiogenic shock (AMI-CS). This study sought to evaluate 15-year national prevalence, temporal trends and outcomes of AKI with no need for hemodialysis (AKI-ND) and requiring hemodialysis (AKI-D) following AMI-CS. This was a retrospective cohort study from 2000-2014 from the National Inpatient Sample (20% stratified sample of all community hospitals in the United States). Adult patients (>18 years) admitted with a primary diagnosis of AMI and secondary diagnosis of CS were included. The primary outcome was in-hospital mortality in cohorts with no AKI, AKI-ND, and AKI-D. Secondary outcomes included predictors, resource utilization and disposition. During this 15-year period, 440,257 admissions for AMI-CS were included, with AKI in 155,610 (35.3%) and hemodialysis use in 14,950 (3.4%). Older age, black race, non-private insurance, higher comorbidity, organ failure, and use of cardiac and non-cardiac organ support were associated with the AKI development and hemodialysis use. There was a 2.6-fold higher adjusted risk of developing AKI in 2014 compared to 2000. Presence of AKI-ND and AKI-D was associated with a 1.3 and 1.7-fold higher adjusted risk of mortality. Compared to the cohort without AKI, AKI-ND and AKI-D were associated with longer length of stay (9±10, 12±13, and 18±19 days respectively; p<0.001) and higher hospitalization costs ($101,859±116,204, $159,804±190,766, and $265,875 ± 254,919 respectively; p<0.001). AKI-ND and AKI-D are associated with higher in-hospital mortality and resource utilization in AMI-CS.

Key Points First-generation stem cells are comprised of unselected cell mixtures exemplified by unfractionated bone-marrow-derived mononuclear stem cells Initial stem-cell trials have established safety and feasibility, but show limited efficacy in the context of cardiovascular disease The main hurdles to achieving benefit from stem-cell therapy include poorly defined cell populations, quality control in cell processing, and limited efficiency in cell delivery To improve the regenerative effect, investigators have focused on purified cell populations to eliminate nonregenerative cells Next-generation cell therapy ushers a new era in regenerative medicine by targeting organ or disease before implantation The interplay between the diseased heart and regenerative biotherapeutics is critical in achieving repair The use of multipotent stem cells to achieve regeneration in cardiovascular disease has been the subject of continuous evaluation over the past decade. Dr Behfar and colleagues review experience obtained from trials of 'first-generation' cell-based therapy, and discuss the advances that have enabled the development of 'next-generation' stem-cell-based therapies targeting cardiovascular disease. The global impetus to identify curative therapies has been fuelled by the unmet needs of patients in the context of a growing heart failure pandemic. To date, regeneration trials in patients with cardiovascular disease have used stem-cell-based therapy in the period immediately after myocardial injury, in an attempt to halt progression towards ischaemic cardiomyopathy, or in the setting of congestive heart failure, to target the disease process and prevent organ decompensation. Worldwide, several thousand patients have now been treated using autologous cell-based therapy; the safety and feasibility of this approach has been established, pitfalls have been identified, and optimization procedures envisioned. Furthermore, the initiation of phase III trials to further validate the therapeutic value of cell-based regenerative medicine and address the barriers to successful clinical implementation has led to resurgence in the enthusiasm for such treatments among patients and health-care providers. In particular, poor definition of cell types used, diversity in cell-handling procedures, and functional variability intrinsic to autologously-derived cells have been identified as the main factors limiting adoption of cell-based therapies. In this Review, we summarize the experience obtained from trials of 'first-generation' cell-based therapy, and emphasize the advances in the purification and lineage specification of stem cells that have enabled the development of 'next-generation' stem-cell-based therapies targeting cardiovascular disease.

Coronary artery disease is the leading cause of morbidity and mortality worldwide. Selected patients with obstructive coronary artery disease benefit from revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Many (but not all) studies have demonstrated increased survival and greater freedom from adverse cardiovascular events after complete revascularization (CR) than after incomplete revascularization (ICR) in patients with multivessel disease. However, achieving CR after PCI or CABG surgery might not be feasible owing to patient comorbidities, anatomical factors, and technical or procedural considerations. These factors also mean that comparisons between CR and ICR are subject to multiple confounders and are difficult to understand or apply to real-world clinical practice. In this Review, we summarize and critically appraise the evidence linking various types of ICR to adverse outcomes in patients with multivessel disease and stable ischaemic heart disease, non-ST-segment elevation acute coronary syndrome or ST-segment elevation myocardial infarction, with or without cardiogenic shock. In addition, we provide practical recommendations for revascularization in patients with high-risk multivessel disease to optimize their long-term clinical outcomes and identify areas requiring future clinical investigation.In this Review, Stone and colleagues compare the outcomes after complete or incomplete revascularization with PCI or CABG surgery in patients with multivessel disease and stable ischaemic heart disease, NSTE-ACS or STEMI, with or without cardiogenic shock.

Atrial fibrillation (AF) is the most common arrhythmia in adults, and its incidence and prevalence increase with age. The risk of cognitive impairment and dementia also increases with age, and both AF and cognitive impairment or dementia share important risk factors. In meta-analyses of published studies, AF is associated with a 2.4-fold and 1.4-fold increase in the risk of dementia in patients with or without a history of stroke, respectively. This association is independent of shared risk factors such as hypertension and diabetes mellitus. Neuroimaging has illustrated several potential mechanisms of cognitive decline in patients with AF. AF is associated with increased prevalence of silent cerebral infarcts, and more recent data also suggest an increased prevalence of cerebral microbleeds with AF. AF is also associated with a pro-inflammatory state, and the relationship between AF-induced systemic inflammation and dementia remains to be investigated. Preliminary reports indicate that anticoagulation medication including warfarin can reduce the risk of cognitive impairment in patients with AF. Catheter ablation, increasingly used to maintain sinus rhythm in patients with AF, is associated with the formation of new silent cerebral lesions. The majority of these lesions are not detectable after 1 year, and insufficient data are available to evaluate their effect on cognition. Large prospective studies are urgently needed to confirm the association between AF and dementia, to elucidate the associated mechanisms, and to investigate the effect of anticoagulation and rhythm control on cognition.

Remodelling is a response of the myocardium and vasculature to a range of potentially noxious haemodynamic, metabolic, and inflammatory stimuli. Remodelling is initially functional, compensatory, and adaptive but, when sustained, progresses to structural changes that become self-perpetuating and pathogenic. Remodelling involves responses not only of the cardiomyocytes, endothelium, and vascular smooth muscle cells, but also of interstitial cells and matrix. In this Review we characterise the remodelling processes in atherosclerosis, vascular and myocardial ischaemia–reperfusion injury, and heart failure, and we draw attention to potential avenues for innovative therapeutic approaches, including conditioning and metabolic strategies.

Previous atrial fibrillation screening trials have highlighted the need for more targeted approaches. We did a pragmatic study to evaluate the effectiveness of an artificial intelligence (AI) algorithm-guided targeted screening approach for identifying previously unrecognised atrial fibrillation. For this non-randomised interventional trial, we prospectively recruited patients with stroke risk factors but with no known atrial fibrillation who had an electrocardiogram (ECG) done in routine practice. Participants wore a continuous ambulatory heart rhythm monitor for up to 30 days, with the data transmitted in near real time through a cellular connection. The AI algorithm was applied to the ECGs to divide patients into high-risk or low-risk groups. The primary outcome was newly diagnosed atrial fibrillation. In a secondary analysis, trial participants were propensity-score matched (1:1) to individuals from the eligible but unenrolled population who served as real-world controls. This study is registered with ClinicalTrials.gov, NCT04208971. 1003 patients with a mean age of 74 years (SD 8·8) from 40 US states completed the study. Over a mean 22·3 days of continuous monitoring, atrial fibrillation was detected in six (1·6%) of 370 patients with low risk and 48 (7·6%) of 633 with high risk (odds ratio 4·98, 95% CI 2·11–11·75, p=0·0002). Compared with usual care, AI-guided screening was associated with increased detection of atrial fibrillation (high-risk group: 3·6% [95% CI 2·3–5·4] with usual care vs 10·6% [8·3–13·2] with AI-guided screening, p<0·0001; low-risk group: 0·9% vs 2·4%, p=0·12) over a median follow-up of 9·9 months (IQR 7·1–11·0). An AI-guided targeted screening approach that leverages existing clinical data increased the yield for atrial fibrillation detection and could improve the effectiveness of atrial fibrillation screening. Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery.