Do Heart Failure Biomarkers Influence Heart Failure Treatment Response?

PURPOSE OF REVIEW: Heart failure (HF) is one of the leading causes of cardiac morbidity and mortality around the world. Our evolving understanding of the cellular and molecular pathways of HF has led to the identification and evaluation of a growing number of HF biomarkers. Natriuretic peptides remain the best studied and understood HF biomarkers, with demonstrated clinical utility in the diagnosis and prognostication of HF. Less commonly understood is the utility of HF biomarkers for guiding and monitoring treatment response. In this review, we outline the current HF biomarker landscape and identify novel biomarkers that have potential to influence HF treatment response. RECENT FINDINGS: An increasing number of biomarkers have been identified through the study of HF mechanisms. While these biomarkers hold promise, they have not yet been proven to be effective in guiding HF therapy. A more developed understanding of HF mechanisms has resulted in an increased number of available pharmacologic HF therapies. In the past, biomarkers have been useful for the diagnosis and prognostication of HF. Future evaluation on their use to guide pharmacologic therapy is ongoing, and there is promise that biomarker-guided therapy will allow clinicians to begin personalizing treatment for their HF patients.

Clinical Phenotypes in Patients With Type 2 Diabetes Mellitus: Characteristics, Cardiovascular Outcomes and Treatment Strategies.

PURPOSE OF REVIEW: With recent advances in the pharmacological management of type 2 diabetes mellitus (T2DM), there is a growing need to understand which patients optimally benefit from these novel therapies. Various clinical clustering methodologies have emerged that utilise data-agnostic strategies to categorise patients that have similar clinical characteristics and outcomes; broadly, this characterisation is termed phenotyping. In patients with T2DM, we aimed to describe patient characteristics from phenotype studies, their cardiovascular risk profiles and the impact of antihyperglycemic treatment. RECENT FINDINGS: Numerous phenotypic studies have been undertaken that have utilised a combination of clinical, biochemical, imaging and genetic variables. Each of these has produced phenotypes that display a spectrum of cardiovascular risk. Studies that aimed to describe pathophysiological phenotypes generally identified five phenotypes: autoimmune phenotype, insulin-related phenotypes (including permutations of insulin deficiency and resistance), obesity phenotype, ageing phenotype, and a sex-related phenotype. Studies examining risk profiles have demonstrated that across such phenotypes there is a spectrum of risk for diabetic complications. Few studies have examined treatment effects across these phenotypes, and thus provide little insights towards making phenotype-guided treatment decisions Clustering analyses in patients with T2DM have identified distinct phenotypes with unique risk profiles. Further studies are needed that harness the use of clinical, biochemical, imaging and genetic data to explore therapeutic heterogeneity and response to antihyperglycemic treatment across the spectrum of patient phenotypes.

Update on the diagnosis and management of acute heart failure.

PURPOSE OF REVIEW: To highlight the advances in the diagnosis and management of acute heart failure (AHF) from recent clinical trials and observational studies. RECENT FINDINGS: We highlight date from recent studies examining the use of novel biomarkers (micro RNAs, osteopontin, insulin-like growth-factor binding protein-7) for the diagnosis of AHF. In addition, we summarize the evidence for novel pharmacological therapies including: serelaxin, ularitide, clevidipine, urocortins, BMS-986231, TRB027, vericiguat, omecamtiv, and torsemide. Finally, we explore the evidence behind the use of novel management algorithms. SUMMARY: Despite many advances in understanding the pathophysiology of AHF, there is currently insufficient evidence to suggest changes to standards of care.

Case report and review of nonischemic spontaneous papillary muscle rupture reports between 2000 and 2015.

Spontaneous papillary muscle rupture (PMR) is a rare cardiovascular emergency. We present a 63-year-old male who presents with acute dyspnea who was found to have an anterior PMR, with no evidence of coronary artery disease, infection, or trauma. A review of cases of nonischemic spontaneous PMR published in 2000-2015 identified 11 additional cases of spontaneous PMR. Posterior and anterior papillary muscles involvement was identified in 54.5% and 45.5% of cases, respectively. Rapid identification due to advances in imaging modalities and improved surgical management has led to optimal outcomes in patients with spontaneous PMR.

Virtual sorting hat™ technology for the matching of candidates to residency training programs.

BACKGROUND: The matching of medical students and trainees to appropriate training programmes poses many challenges, including financial cost and applicant stress. There are few studies that have examined alternatives to the current process of matching candidates to specialist training. Case reports from Hogwarts School of Witchcraft and Wizardry™ have suggested that wearable technology may be used to assign individuals with particular sets of skills and virtues to an appropriate house. METHODS: Investigators developed a modified sorting hat in the form of an online, cross-sectional survey. The virtual sorting hat was delivered to medical students at the National University of Ireland, Galway, and medical practitioners practising in the associated hospitals and communities. Pearson's chi-square was used to demonstrate correlations between the allocation of participants to Hogwarts' houses by virtual sorting hat technology and expressed higher specialist training preference. RESULTS: Virtual sorting hat technology, applied to medical undergraduates and postgraduates, allocated most participants to Hufflepuff™ (44%) and Ravenclaw™ (32%). Allocation to Gryffindor was associated with preference for surgery and allocation to Slytherin™ with preference for psychiatry. CONCLUSION: Virtual sorting hat technology requires significant refinement before application to medical muggles™ .

Ireland's medical brain drain: migration intentions of Irish medical students.

BACKGROUND: To provide the optimum level of healthcare, it is important that the supply of well-trained doctors meets the demand. However, despite many initiatives, Ireland continues to have a shortfall of physicians, which has been projected to persist. Our study aimed to investigate the migration intentions of Irish medical students and identify the factors that influence their decisions in order to design appropriate interventions to sustain the supply of trained doctors in order to maintain a viable medical system. METHODS: An online cross-sectional survey was undertaken of all Irish medical students studying in the Republic of Ireland. The survey included nominal, ordinal, and scale items to determine migration intentions, factors influencing their decisions, and understanding of the Irish healthcare system. RESULTS: A total of 2 273 medical students responded (37% response rate), of whom 1 519 were classified as Irish medical students (having completed secondary school in Ireland). Of these, 88% indicated they were either definitely migrating or contemplating migrating following graduation or completion of the pre-registration intern year. Forty percent expressed an intention of returning to Ireland within 5 years. The factors most influencing their decision to leave were career opportunities (85%), working conditions (83%), and lifestyle (80%). CONCLUSION: The migration intentions expressed in this study predict an immediate and severe threat to the sustainability of the Irish healthcare service. Urgent interventions such as providing information about career options and specialty training pathways are required. These must begin in the undergraduate phase and continue in postgraduate training and are needed to retain medical school graduates.

Cardiovascular pathology, inheritance and prognosis in a familial cohort of Loeys-Dietz type III.

INTRODUCTION: Loeys-Dietz syndrome (LDS) is a heritable disease that is the result of dysregulation of the transforming growth factor beta (TGFß) pathway. The pathogenic variants associated with the condition are linked to aortic aneurysms and dissections along with other cardiovascular and non-cardiovascular abnormalities. LDS type III is associated with pathogenic variants in the SMAD3 gene responsible for signally in the TGFß pathway. Most of the current knowledge of LDS stems from studies of LDS I and II patient with limited data on large cohorts of LDS III patients. We sought to identify the prevalence and course of cardiovascular diseases in a large familial cohort of LDS III patients and also to compare these findings with a previously described cohort of similar size with the identical pathogenic variant. METHODS: The cohort was identified by systematic genetic screening of a familial cohort identified through a single proband. Data was collected from retrospective chart review of patients identified to be affected by the syndrome. RESULTS: Screening of 97 patients identified 19 patients (16 through genetic testing and 3 through phenotypic screening of untested direct descendants of genetically positive individuals). The prevalence of cardiovascular abnormalities was 84%. There was significant intrafamilial phenotypic variability within the cohort with the predominant cardiovascular abnormality being mitral valve disease followed by aortic disease. 92% of patients >18 years of age had osteoarthritis which is a further hallmark of LDS III. CONCLUSION: LDS III sets itself apart from the more widely studied LDS types I and II cardiovascular phenotypes by presenting later in life and tending to be more strongly associated with mitral valve disease.

Applicability and impact of the COMPASS trial in a Canadian population of patients with atherosclerotic disease.

BACKGROUND AND AIMS: In the COMPASS trial, low-dose rivaroxaban with aspirin improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the potential clinical implications of this therapy in a generalizable population. METHODS AND RESULTS: A retrospective cohort of adults with ASVCD was formed using healthcare administrative databases in Alberta, Canada (population 4.4 million). Patients with a new diagnosis between 2008 and 2019 formed the epidemiological cohort (n = 224,600) and those with long-term follow-up (>5 years) formed the outcomes cohort (n = 232,460). The primary outcome of major adverse cardiovascular events (MACE) was assessed and categorized based on the COMPASS trial eligibility. In the outcomes cohort, 77% had only coronary artery disease, 15% had only peripheral artery disease, and 8% had both. Of those, 37% met the COMPASS trial eligibility criteria, 36% met exclusion criteria and 27% did not meet inclusion criteria. Over a median of 7.8 years, the COMPASS exclusion group demonstrated the highest rate of MACE (5.9 per 100 person-years), following by the eligible group and the group that did not meet COMPASS inclusion criteria (3.1 and 1.4 per 100 person-years respectively). The expected net clinical benefit of antithrombotic therapy in the eligible group was 5.6 fewer events per 1000 person-years. CONCLUSIONS: In a real-world population of 4.4 million adults, there are roughly 20,000 new cases of ASVCD diagnosed yearly, with ∼40% being eligible for the addition of low-dose rivaroxaban therapy to antiplatelet therapy. The theoretical implementation of dual antithrombotic treatment in this population could result in a substantial reduction in cardiovascular morbidity and mortality.

Outcomes of management strategies in patients with prior coronary artery bypass grafting presenting with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass grafting (CABG) presenting with an acute coronary syndrome (ACS) have poor outcomes and the optimal treatment strategy for this population is unknown. METHODS: Using linked administrative databases, we examined patients with an ACS between 2008 and 2019, identifying patients with prior CABG. Patients were categorized by ACS presentation type and treatment strategy. Our primary outcome was the composite of death and recurrent myocardial infarction at one year. RESULTS: Of 54,641 patients who presented with an ACS, 1670 (3.1%) had a history of prior CABG. Of those, 11.0% presented with an ST-elevation myocardial infarction (STEMI) of which, 15.3% were treated medically, 31.1% underwent angiography but were treated medically, 22.4% with fibrinolytic therapy and 31.1% with primary PCI. The primary outcome rate was the highest (36.8%) in patients who did not undergo angiography and was similar in the primary PCI (20.8%) and fibrinolytic group (21.9%). In patients presenting with a non-ST elevation acute coronary syndrome (NSTE-ACS) (89.0%), 33.2% were treated medically, 38.5% underwent angiography but were treated medically and 28.2% were treated with PCI. Compared to those who underwent PCI, patients treated conservatively demonstrated a higher risk of the composite outcome (14.8% vs 27.3%; adjusted hazard ratio 1.70, 95% confidence interval 1.22-2.37). CONCLUSIONS: Patients with prior CABG presenting with an ACS are often treated conservatively without PCI, which is associated with a higher risk of adverse events.

Utilizing Quality of Life Adjusted Days Alive and Out of Hospital in Heart Failure Clinical Trials.

BACKGROUND: In heart failure (HF) trials, there has been an emphasis on utilizing more patient-centered outcomes, including quality of life (QoL) and days alive and out of hospital. We aimed to explore the impact of QoL adjusted days alive and out of hospital as an outcome in 2 HF clinical trials. METHODS: Using data from 2 trials in HF (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT] and Study of Dietary Intervention under 100 mmol in Heart Failure [SODIUM-HF]), we determined treatment differences using percentage days alive and out of hospital (%DAOH) adjusted for QoL at 18 months as the primary outcome. For each participant, %DAOH was calculated as a ratio between days alive and out of hospital/total follow-up. Using a regression model, %DAOH was subsequently adjusted for QoL measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score. RESULTS: In the GUIDE-IT trial, 847 participants had a median baseline Kansas City Cardiomyopathy Questionnaire Overall Summary Score of 59.0 (interquartile range, 40.8-74.3), which did not change over 18 months. %DAOH was 90.76%±22.09% in the biomarker-guided arm and 88.56%±25.27% in the usual care arm. No significant difference in QoL adjusted %DAOH was observed (1.09% [95% CI, -1.57% to 3.97%]). In the SODIUM-HF trial, 796 participants had a median baseline Kansas City Cardiomyopathy Questionnaire Overall Summary Score of 69.8 (interquartile range, 49.3-84.3), which did not change over 18 months. %DAOH was 95.69%±16.31% in the low-sodium arm and 95.95%±14.76% in the usual care arm. No significant difference was observed (1.91% [95% CI, -0.85% to 4.77%]). CONCLUSIONS: In 2 large HF clinical trials, adjusting %DAOH for QoL was feasible and may provide complementary information on treatment effects in clinical trials.

Canadian Cardiovascular Society 2023 Guidelines on the Fitness to Drive.

Cardiovascular conditions are among the most frequent causes of impairment to drive, because they might induce unpredictable mental state alterations via diverse mechanisms like myocardial ischemia, cardiac arrhythmias, and vascular dysfunction. Accordingly, health professionals are often asked to assess patients' fitness to drive (FTD). The Canadian Cardiovascular Society previously published FTD guidelines in 2003-2004; herein, we present updated FTD guidelines. Because there are no randomized trials on FTD, observational studies were used to estimate the risk of driving impairment in each situation, and recommendations made on the basis of Canadian Cardiovascular Society Risk of Harm formula. More restrictive recommendations were made for commercial drivers, who spend longer average times behind the wheel, use larger vehicles, and might transport a larger number of passengers. We provide guidance for individuals with: (1) active coronary artery disease; (2) various forms of valvular heart disease; (3) heart failure, heart transplant, and left ventricular assist device situations; (4) arrhythmia syndromes; (5) implantable devices; (6) syncope history; and (7) congenital heart disease. We suggest appropriate waiting times after cardiac interventions or acute illnesses before driving resumption. When short-term driving cessation is recommended, recommendations are on the basis of expert consensus rather than the Risk of Harm formula because risk elevation is expected to be transient. These recommendations, although not a substitute for clinical judgement or governmental regulations, provide specialists, primary care providers, and allied health professionals with a comprehensive list of a wide range of cardiac conditions, with guidance provided on the basis of the level of risk of impairment, along with recommendations about ability to drive and the suggested duration of restrictions.

Harnessing Electronic Medical Records in Cardiovascular Clinical Practice and Research.

The use of electronic medical records has rapidly been adopted world-wide, which has resulted in multiple new opportunities for cardiovascular research. These include the following: (1) the development and assessment of clinical decision tools, meant to increase quality of care; (2) harnessing data linkages to examine genetic, epidemiological, and pharmacological associations on an unprecedented scale; and (3) harnessing electronic medical records to facilitate the conduct of cardiovascular clinical trials. While these opportunities promise to revolutionize cardiovascular care and research, enthusiasm should be tempered while further assessment of true clinical utility has been undertaken.

Sex differences in post-operative outcomes following non-cardiac surgery.

It is uncertain whether sex is an independent risk factor for poor outcomes after non-cardiac surgery. We examined sex differences in short- and long-term mortality and morbidity in patients undergoing non-cardiac surgery in Alberta, Canada. Using linked administrative databases, we identified patients undergoing one of 45 different non-cardiac surgeries who were hospitalized between 2008 and 2019. Adjusted odds ratios (95% CI) were reported for mortality at 30-days, 6-months, and 1-year stratified by sex. Secondary outcomes including all-cause hospitalization, hospitalization for heart failure (HF), hospitalization for acute coronary syndrome (ACS), hospitalization for infection, hospitalization for stroke, and hospitalization for bleeding were also analyzed. Multivariate logistic regression was adjusted for age, sex, surgery type, the components of the Charlson Comorbidity Index, and the Revised Cardiac Risk Index. We identified 552,224 unique patients who underwent non-cardiac surgery of which 304,408 (55.1%) were female. Male sex was a predictor of mortality at 30-days (aOR 1.25 (1.14, 1.38), p<0.0001), 6-months (aOR 1.26 (1.20, 1.33), p<0.0001), and 1-year (aOR 1.25 (1.20, 1.31), p<0.0001). Similarly, male sex was a predictor of hospital readmission at 30-days (1.12 (1.09, 1.14), p<0.0001), 6-months (aOR 1.11 (1.10, 1.13), p<0.0001), and 1-year (aOR 1.06 (1.04, 1.07), p<0.0001). When the results were stratified by age, the effect of male sex on clinical outcome diminished for age ≥ 65years compared to younger patients. In conclusion, male patients undergoing non-cardiac surgery have higher risks of all-cause mortality and readmission after adjustment for baseline risk factor differences, particularly in those under 65-years-old. The overall incidence of readmission for stroke, bleeding, HF and ACS after non-cardiac surgery was low. The impact of male sex on clinical outcomes decreases with increasing age, suggesting the importance of considering the effect of both sex and age on clinical outcomes after non-cardiac surgery.

The Challenges of Identifying Patients With Peripheral Artery Disease Utilizing Administrative Databases.

Peripheral artery disease (PAD) carries a high burden of morbidity when identified in patients with coronary artery disease (CAD). However, identification of patients with concomitant CAD and PAD remains challenging. Using linked administrative databases of 207,026 individuals with CAD between 2002 and 2019 (median follow-up, 4.7 years), a model for PAD was applied to identify baseline PAD and the development of PAD during follow-up. Both baseline PAD and future PAD models demonstrated poor calibration and discrimination (c-statistic 0.618 and 0.583). In the absence of additional variables, the present models are unable to identify patients with concomitant CAD and PAD.

La maladie artérielle périphérique (MAP) impose un lourd fardeau de morbidité lorsqu'elle est diagnostiquée chez les patients atteints de coronaropathie. Toutefois, il reste difficile de repérer les patients atteints à la fois de coronaropathie et de MAP. À partir de bases de données administratives liées comptant 207 026 personnes atteintes de coronaropathie entre 2002 et 2019 (suivi médian de 4,7 ans), un modèle pour la MAP a été appliqué afin de repérer une MAP initiale et l'apparition d'une MAP au cours du suivi. Les modèles de MAP initiale et de MAP future ont tous deux été associés à un calibrage et à une capacité de distinction insatisfaisants (statistique C de 0,618 et 0,583). En l'absence d'autres variables, les modèles actuels sont incapables de repérer les patients atteints de coronaropathie et de MAP concomitantes.

Anticoagulation in type 2 myocardial infarctions: Lessons learned from the rivaroxaban in type 2 myocardial infarctions feasibility trial.

Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population. Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period. Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial. Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only ∼1 in every 20 screened individuals being a candidate for study recruitment.

Exploring the pragmatic-explanatory spectrum across cardiovascular clinical trials.

Clinical trials are a cornerstone of modern medicine and form the backbone of evidence that is used to create evidence-based guidelines. Contemporary clinical trials have tended to be quite explanatory, assessing an intervention in ideal conditions with highlyprotocolized interventions, strict inclusion/exclusion criteria, high resource utilization and with frequent (and often specialized) follow-up. In conjunction with decreased event-rates due to the improvement of cardiovascular care, this has resulted in increasingly complex, large, clinical trials that are associated with exponentially increasing costs. This has led to a strong push for streamlined trials that more truly represent "real world" settings and conduct. Such pragmatic trials emphasize "real world" conduct, including broader inclusion criteria that lead to more typical and less carefully selected patient populations, and more realistic trial setting and execution elements. We explore the spectrum of pragmatism across cardiovascular clinical trials, highlighting novel innovations and trends over the past decade.

Clinical features and complications of Loeys-Dietz syndrome: A systematic review.

INTRODUCTION: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor ß signalling pathway. Due to the recent discovery of the underlying genetic mutations leading to LDS, the spectrum of characteristics and complications is not fully understood. METHODS: Our search included five databases (Pubmed, SCOPUS, Web of Science, EMBASE and google scholar) and included variations of "Loeys-Dietz Syndrome" as search terms, using all available data until February 2021. All study types were included. Three reviewers screened 1394 abstracts, of which 418 underwent full-text review and 392 were included in the final analysis. RESULTS: We identified 3896 reported cases of LDS with the most commonly reported features and complications being: aortic aneurysms and dissections, arterial tortuosity, high arched palate, abnormal uvula and hypertelorism. LDS Types 1 and 2 share many clinical features, LDS Type 2 appears to have a more aggressive aortic disease. LDS Type 3 demonstrated an increased prevalence of mitral valve prolapse and arthritis. LDS Type 4 and 5 demonstrated a lower prevalence of musculoskeletal and cardiovascular involvement. Amongst 222 women who underwent 522 pregnancies, 4% experienced an aortic dissection and the peripartum mortality rate was 1%. CONCLUSION: We observed that LDS is a multisystem connective tissue disorder that is associated with a high burden of complications, requiring a multidisciplinary approach. Ongoing attempts to better characterise these features will allow clinicians to appropriately screen and manage these complications.

Beyond the revised cardiac risk index: Validation of the hospital frailty risk score in non-cardiac surgery.

Frailty is an established risk factor for adverse outcomes following non-cardiac surgery. The Hospital Frailty Risk Score (HFRS) is a recently described frailty assessment tool that harnesses administrative data and is composed of 109 International Classification of Disease variables. We aimed to examine the incremental prognostic utility of the HFRS in a generalizable surgical population. Using linked administrative databases, a retrospective cohort of patients admitted for non-cardiac surgery between October 1st, 2008 and September 30th, 2019 in Alberta, Canada was created. Our primary outcome was a composite of death, myocardial infarction or cardiac arrest at 30-days. Multivariable logistic regression was undertaken to assess the impact of HFRS on outcomes after adjusting for age, sex, components of the Charlson Comorbidity Index (CCI), Revised Cardiac Risk Index (RCRI) and peri-operative biomarkers. The final cohort consisted of 712,808 non-cardiac surgeries, of which 55·1% were female and the average age was 53·4 +/- 22·4 years. Using the HFRS, 86.3% were considered low risk, 10·7% were considered intermediate risk and 3·1% were considered high risk for frailty. Intermediate and high HFRS scores were associated with increased risk of the primary outcome with an adjusted odds ratio of 1·61 (95% CI 1·50-1.74) and 1·55 (95% CI 1·38-1·73). Intermediate and high HFRS were also associated with increased adjusted odds of prolonged hospital stay, in-hospital mortality, and 1-year mortality. The HFRS is a minimally onerous frailty assessment tool that can complement perioperative risk stratification in identifying patients at high risk of short- and long-term adverse events.

Long-Term Outcomes for Patients With Acute Coronary Syndrome and Nonvalvular Atrial Fibrillation.

Short-term outcomes are worse for patients with acute coronary syndrome (ACS) with a history of nonvalvular atrial fibrillation (NVAF). However, long-term prognosis remains unclear. We linked administrative health databases to identify patients hospitalized with ACS (ST-elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], and unstable angina) between 2008 and 2019 in Alberta, Canada. Patients were stratified according to history of NVAF before hospitalization. The primary outcome was a composite of all-cause mortality, hospitalization for myocardial infarction, or stroke at 3 years. Cox models were constructed to estimate the association between ACS, NVAF, and outcomes. Of 54,309 ACS hospitalizations, 6,351 patients (11.7%) had a history of NVAF. Compared with patients without NVAF, patients with previous NVAF were older (75.6 ± 11.6 vs 64.9 ± 13.4 years), women (35.1% vs 30.0%), had higher comorbid burden (Charlson co-morbidity index 3.0 vs 1.0), and more often presented with NSTEMI (57.5% vs 49.0%). The primary outcome occurred in 37.0% of patients with previous NVAF and 17.4% without (p <0.001). In the multivariable analysis, there was a 1.14-fold (95% confidence interval [CI] 1.09 to 1.20) higher risk of the primary outcome in patients with previous NVAF. There was a significant association with STEMI (adjusted harazard ratio [aHR] 1.24, 95% CI 1.12 to 1.36) and NSTEMI (aHR 1.12, 95% CI 1.06 to 1.19) but not with unstable angina (aHR 1.04, 95% CI 0.90 to 1.22). In conclusion, in this population-based study, we identified that a history of NVAF at ACS presentation is associated with worse long-term prognosis, particularly for STEMI and NSTEMI.