Search

In the previous paper, theoretical consideration of the tracer gas experimental method that uses dynamic steady state concentration was made. In this study, the feasibility of the tracer gas experimental method was examined based on a laboratory experiment. It was confirmed that a dynamic steady state concentration in case of negative generation of tracer gas corresponds to the age of air in an open-air system. The sum of dynamic steady state concentrations in case of positive generation of tracer gas and that for negative generation in the air recirculating part of a room is similar to the steady state concentration in an open air system.

Background: Although they are fast-growing populations in the United States, little is known about survival outcomes of Hispanic and Asian patients after in-hospital cardiac arrest., Methods and Results: In Get With The Guidelines-Resuscitation, we identified Asian, Hispanic, and White adults with in-hospital cardiac arrest during 2005 to 2023. Using multivariable models, we compared rates of survival to discharge separately for Asian and Hispanic patients versus White patients, as well as rates of sustained return of spontaneous circulation for ≥20 minutes and favorable neurologic survival as secondary outcomes. Of 189 557 in-hospital cardiac arrests, 167 640 (88.4%), 16 800 (8.9%), and 5117 (2.7%) patients were White, Hispanic, and Asian, respectively. Compared with the survival rate to discharge for White patients (22.0%), rates were lower for Hispanic (19.4%; adjusted odds ratio [OR], 0.93 [95% CI, 0.89-0.97]; P <0.001) and Asian patients (17.8%; adjusted OR, 0.90 [95% CI, 0.83-0.97]; P =0.008), and these differences were attenuated after accounting for the hospital at which patients received care (adjusted OR: Hispanic patients, 0.95 [95% CI, 0.91-1.00]; Asian patients, 0.91 [95% CI, 0.84-0.99]). Although there were no differences in rates of return of spontaneous circulation between White (68.7%), Hispanic (69.0%), and Asian patients (69.7%), both Asian and Hispanic patients were less likely to have favorable neurologic survival (White: 18.3%; Hispanic: 15.4%; adjusted OR, 0.88 [95% CI, 0.84-0.93]; Asian: 13.2%; adjusted OR, 0.80 [95% CI, 0.73-0.87]). These differences were also attenuated after accounting for hospital site., Conclusions: Compared with White patients, Hispanic and Asian patients with in-hospital cardiac arrest had lower rates of overall survival and favorable neurologic survival. Some of these differences were associated with the hospital at which patients received care.

Background: Prior studies of patients presenting with acute myocardial infarction (AMI) without Standard Modifiable Risk Factors (SMuRFs), such as diabetes, dyslipidemia, hypertension, and smoking, reported higher in-hospital but lower long-term mortality than those with SMuRFs. However, the impact of SMuRFs on health status outcomes (patients' symptoms, function, and quality of life) after a first AMI are unknown., Methods: Data from two prospective registries, PREMIER and TRIUMPH, were used to identify patients with no prior history of coronary disease hospitalized at 31 U.S. hospitals for AMI between 2003-2008. Serial health status over 12 months was collected using the Seattle Angina Questionnaire (SAQ) Summary Score. Changes in SAQ over 12 months were compared between patients with and without SMuRFs using hierarchical linear mixed models with sequential adjustments for baseline SAQ scores, clinical, and sociodemographic characteristics., Results: Among 4076 patients with a first AMI (mean age 58.4±12.4, 34% female, 22% Black), 569 (14.0%) presented without SMuRFs. Compared with patients with SMuRFs, those without SMuRFs were more likely to be male, White, have higher income and education, fewer depressive symptoms, and higher baseline SAQ Summary Scores (83.5±13.2 vs. 79.6±16.5). After adjusting for baseline SAQ scores, patients without SMuRFs had larger SAQ Summary Score improvements at 12 months than those with SMuRFs (adjusted difference between groups = 2.61 points, 95%CI: 1.29-3.93), but sequential adjustment for clinical and socioeconomic characteristics attenuated this difference (1.69 points, 95% CI 0.40-1.97)., Conclusions: Among AMI patients, those without modifiable risk factors had similar health status at 12-months as compared with those having modifiable cardiovascular risk factors, which should provide reassurance to those with less targets for secondary prevention., Competing Interests: Declaration of competing interest none, (Copyright © 2024. Published by Elsevier Inc.)

Importance: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a commonly used outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean treatment effects do not necessarily reflect the clinical benefit experienced by individual patients., Objective: To evaluate the association between mean KCCQ treatment effects and the proportions of patients experiencing clinically important improvements across a range of clinical trials and heart failure etiologies., Design, Setting, and Participants: A patient-level analysis of 11 randomized clinical trials, including 9977 patients, was performed to examine the association between mean treatment effects and the KCCQ Overall Summary Score (OSS) and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate to large (≥10 points) improvements. There was no target date range, and included studies were those for which patient-level data were available. Validation was performed in 7 additional trials. The data were analyzed between July 1 and September 15, 2023., Main Outcomes and Measures: Proportion of patients experiencing an improvement of 5 or more and 10 or more points in their KCCQ score (with each domain transformed to a range of 0 to 100 points, where higher scores represent better health status)., Results: Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI], 4.0%-8.1%) in the proportion of patients improving 5 or more points and 5.0% (95% PI, 3.1%-7.0%) in the proportion improving 10 or more points, corresponding to a number needed to treat of 17 (95% PI, 12-25) and 20 (95% PI, 14-33), respectively., Conclusions and Relevance: Inferences about clinical impacts based on population-level mean treatment effects may be misleading, since even small between-group differences may reflect clinically important treatment benefits for individual patients. Results of this study suggest that clinical trials should explicitly describe the distributions of KCCQ change at the patient level within treatment groups to support the clinical interpretation of their results.

Competing Interests: Disclosures MSK, MAJ, CFS, and ELO are supported by the National Heart, Lung and Blood Institutes of Health under Award Number T32H110837. NI received an unrestricted research grant for the Department of Cardiology, Keio University School of Medicine from Bristol Myer Squibb. JAS owns the copyright to the Kansas City Cardiomyopathy Questionnaire and provides consulting services to Abbott, Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Meyers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, and Imbria on patient-reported outcomes.

Background: Pursuing initial invasive or conservative management of chronic coronary disease (CCD) is a preference-sensitive decision that should include shared decision-making. Communicating the benefits of either approach is challenging, as individual patients rarely achieve the population-averaged outcomes reported in clinical trials. Our objective was to develop a patient decision aid (PDA) with patient-specific estimates of outcomes for initial invasive versus conservative management of CCD, based on the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches)., Methods: This was a multiphase mixed-methods study using focus groups of outpatients with CCD, caregivers, clinicians, and researchers. Focus groups were held in Kansas City, MO and New York City, NY between September 2021 and June 2022. Patients with CCD were included if they had a positive stress test within 1 year. Phase 1 focused on patient priorities for outcomes to guide treatment decisions. Phase 2 involved PDA development and refinement. Phase 3 involved further refinement and member checking. Key themes involving shared decision-making and treatment preferences were elicited from focus groups using a deductive approach to develop a PDA representing the outcomes most important to patients., Results: Of 46 patient and caregiver participants, the mean age was 63.5 years, 53% were female, 61% were White, 24% were Black, and 9% were Hispanic. When deciding between treatments, participants valued shared decision-making but generally deferred decisions to clinicians. The outcomes most important to participants were survival and quality of life, followed by physical functioning and symptoms. To represent these outcomes, participants favored simple visualizations, such as a speedometer or health meter. When deciding between treatment options, participants preferred to use the PDA collaboratively with a clinician instead of as a stand-alone tool., Conclusions: Our novel, patient-centered approach to developing a PDA for CCD with patient-specific outcomes has the potential to rapidly translate clinical trial results to individual patients and support shared decision-making., Competing Interests: Dr Spertus reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; personal fees from Bayer, Novartis, AstraZeneca, Amgen, Janssen, and United Healthcare; and grants from the American College of Cardiology, outside the submitted work. In addition, Dr Spertus has a patent copyright to SAQ (Seattle Angina Questionnaire) with royalties paid, and is on the Board of Directors for Blue Cross Blue Shield of Kansas City, and reports equity in Health Outcomes Sciences. Mr. Jones reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Maron reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Hochman is the principal investigator for the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular, Medtronic, Inc, Abbott Laboratories (formerly St. Jude Medical Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp & Dohme Corp, Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc, Espero BioPharma, and Amgen, Inc, and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. The other authors report no conflicts.

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) demonstrated greater health status benefits with an initial invasive strategy, as compared with a conservative one, for patients with chronic coronary disease and moderate or severe ischemia. Whether these benefits vary globally is important to understand to support global adoption of the results., Methods: We analyzed participants' disease-specific health status using the validated 7-item Seattle Angina Questionnaire (SAQ: >5-point differences are clinically important) at baseline and over 1-year follow-up across 37 countries in 6 international regions. The average effect of initial invasive versus conservative strategies on 1-year SAQ scores was estimated using Bayesian proportional odds regression and compared across regions., Results: Considerable regional variation in baseline health status was observed among 4617 participants (mean age=64.4±9.5 years, 24% women), with the mean SAQ summary scores of 67.4±19.5 in Eastern Europe participants (17% of the total), 71.4±15.4 in Asia-Pacific (18%), 74.9±16.7 in Central and South America (10%), 75.5±19.5 in Western Europe (26%), and 78.6±19.2 in North America (28%). One-year improvements in SAQ scores were greater in regions with lower baseline scores with initial invasive management (17.7±20.9 in Eastern Europe and 11.4±19.3 in North America), but similar in the conservative arm. Adjusting for baseline SAQ scores, similar health status benefits of an initial invasive strategy on 1-year SAQ scores were observed (ranging from 2.38 points [95% CI, 0.04-4.50] in North America to 4.66 points [95% CI, 2.46-6.94] in Eastern Europe), with an 88.3% probability that the difference in benefit across regions was <5 points., Conclusions: In patients with chronic coronary disease and moderate or severe ischemia, initial invasive management was associated with a consistent health status benefit across regions, with modest regional variability, supporting the international generalizability of health status benefits from invasive management of chronic coronary disease., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522., Competing Interests: Dr Ikemura received an unrestricted research grant for the Department of Cardiology, Keio University School of Medicine from Bristol Myer Squibb. Dr Spertus discloses providing consultative services on patient-reported outcomes and evidence evaluation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Meyers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare. He holds research grants from Bristol Meyers Squibb, Abbott Vascular, and Janssen. He owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. Dr Nguyen is currently supported by the National Heart, Lung, and Blood Institute under Award Number T32HL110837. Dr Reynolds reports grants from National Heart, Lung, and Blood Institute, during the conduct of the study, she received support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study) and Biotelemetry Inc (donation of telemetry monitors for an unrelated research study). Dr Bangalore reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study; grants and personal fees from Abbott Vascular; personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Bhargava reports grants from the National Heart, Lung and Blood Institute, during the conduct of the study. Dr Senior reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study and speaker fees from Bracco, Lantheus Medical Imaging Boston USA, and Philips Healthcare outside the submitted work. A. Elghamaz reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Goodman reports research grant support (eg, steering committee or data and safety monitoring committee) and speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, CYTE Ltd., Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma; and salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Failure Society, Canadian Heart Research center and MD Primer, Canadian VIGOUR center, Cleveland Clinic Coordinating Center for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating center, PERFUSE Research Institute, TIMI Study Group (Brigham Health). Dr Lopes reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; other from Bayer and Boehringer Ingelheim; grants and other from Bristol-Myers Squibb; other from Daiichi Sankyo; grants and other from GlaxoSmithKline and Medtronic; other from Merck; grants and other from Pfizer; other from Portola; and grants and other from Sanofi, outside the submitted work. Dr Pracon reports grants from National Heart, Lung, and Blood Institute, during the conduct of the study and research grant honoraria from NYU. Dr Lopez-Sendon reports grants from National Heart, Lung and Blood Institute, during the conduct of the study; other from Bayer, other from Boehringer Ingleheim, grants and other from Bristol-Myers Squibb, other from Daiichi Sankyo, grants and other from Glaxo Smith Kline, grants and other from Medtronic, other from Merck, grants and other from Pfizer, other from Portola, grants and other from Sanofi, outside the submitted work. Dr Maggioni reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and personal fees from Bayer, AstraZeneca, Sanofi and Novartis, outside the submitted work. Dr Kohsaka has received grant support paid to the institution and fees from Novartis and AstraZeneca. Dr White has received grant support paid to the institution and fees for serving on Steering Committees of the ODYSSEY trial from Sanofi and Regeneron Pharmaceuticals, the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) and MINT study from the National Institutes of Health, the STRENGTH trial from Omthera Pharmaceuticals, the HEART-FID study from American Regent, the DAL-GENE study from DalCor Pharma UK Inc., the AEGIS-II study from CSL Behring, the CLEAR OUTCOMES study from Esperion Therapeutics Inc, and the SOLIST-WHF and SCOREDS trials from Sanofi Aventis Australia Pty Ltd. Dr Mavromatis reports grants from the National Heart, Lung, and Blood Institute; grants from National Heart, Blood, and Lung Institute (CV Inflammation Reduction Trial and GMCSF in PAD-3 Trial), grants from CSL Behring, St Jude’s Medical, Medtronic, DalCor Pharmaceuticals, AstraZeneca, Novartis, Regeneron, and Member of American College of Cardiology and Society of Cardiovascular Angiography and Interventions. Dr Boden reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study; grants from Abbvie, grants from Amarin, grants from Amgen, personal fees from Amgen, personal fees from Cleveland Clinic Clinical Coordinating Center, personal fees from Janssen, outside the submitted work. Dr Fatima Rodriguez reports consulting fees from Novartis, NovoNordisk, AstraZeneca, and Health Pals, and research support from the National Institutes of Health, the American Heart Association, and the Doris Duke Foundation. Dr Hochman is PI for the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular; Medtronic Inc.; Abbott Laboratories (formerly St. Jude Medical Inc); Royal Philips NV (formerly Volcano Corporation); Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Merck Sharp & Dohme Corp.; Omron Healthcare Inc, and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. She is also the PI for ISCHEMIA-EXTEND. Dr Maron reports grants from National Heart, Lung, and Blood Institute, during the conduct of the study. The other authors report no conflicts.

Background: Various treatment approaches for atrial fibrillation (AF) have demonstrated improved health status, yet the significance of these therapeutic interventions in individual patients remains unclear., Objective: This study aimed to evaluate health status changes in patients with early AF, focusing on those who experience clinically significant deterioration after treatment initiation., Methods: We analyzed data from a multicenter, prospective registry of newly diagnosed patients with AF. One-year changes in health status across different treatment strategies were assessed by the Atrial Fibrillation Effect on QualiTy-of-life Overall Summary (AFEQT-OS) score. Clinically relevant deterioration and improvement in health status were defined as ≥5-point decrease and increase in AFEQT-OS score, respectively; no change was -5 to 5 points., Results: Overall, 1960 patients with AF were evaluated. Mean AFEQT-OS scores at baseline and 1-year follow-up were 76.7 ± 17.7 and 85.4 ± 14.8, respectively. Although most patients (53.9%) experienced clinically important improvement, a considerable proportion had no change (28.7%) or deterioration (17.4%) in their health status. Proportions of patients with no change or deterioration varied by treatment strategy: 59.9%, 53.9%, and 32.0% in rate control, antiarrhythmic drug, and catheter ablation groups, respectively. The multivariable model identified older age, female sex, heart failure, coronary artery disease, and higher baseline AFEQT-OS score as independent predictors of worsening health status, regardless of treatment strategy., Conclusion: Many patients with early AF experience worsening or no change in health status irrespective of treatment strategy. Standardizing patients' health status assessment, especially for patients with comorbidities, may aid in patients' selection and their outcomes., Competing Interests: Disclosures Dr Ikemura received an unrestricted research grant from the Department of Cardiology, Keio University School of Medicine, Bristol-Myers Squibb, Japan. Dr Kohsaka received an unrestricted research grant from the Department of Cardiology at Keio University School of Medicine from Bayer Pharmaceutical and Daiichi Sankyo, grants from Bayer Yakuhin, Ltd and Daiichi Sankyo, and personal fees from Bristol-Myers Squibb. Dr Kimura received grants from Bayer Yakuhin Ltd. Dr Takatsuki received grants and personal fees from Bayer and personal fees from Daiichi Sankyo. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Aims: The purpose of this study is to utilize patient-reported outcomes to determine the percentage of patients concerned about mild to moderate bleeding side effects of anticoagulants., Methods and Results: We consecutively enrolled 3312 newly diagnosed or referred patients for atrial fibrillation (AF) management from 11 sites within the Keio interhospital Cardiovascular Studies-Atrial Fibrillation registry between September 2012 and May 2018. Of these patients, 2636 (79.5%) were taking oral anticoagulants at enrollment. Using the Atrial Fibrillation Effect on Quality-of-life questionnaire (AFEQT), the patients who responded '1: not at all bothered' or '2: hardly bothered' on the seven-point scale regarding bleeding side effects were classified as the 'no OAC concern' group while those responding '3: a little bothered' to '7: extremely bothered' were classified as the 'OAC concern' group. On baseline analysis, 29.3% (n = 772) were 'concerned' about bleeding side effects. The proportion of women and patients with AF-related symptoms was higher in the oral anticoagulant (OAC) concern vs. no OAC concern group (36.9% vs. 29.8%, P < 0.0004 and 66.2% vs. 56.7%, P < 0.0001, respectively). The CHADS2 scores ≥ 2 were comparable between groups. Of the 430 patients in the 1-year follow-up analysis, the proportion of the continued OAC concern group (1 year from enrollment) was 41.6%. The dabigatran, rivaroxaban, and apixaban usage rates were comparable between the two groups in baseline and 1-year follow-up analysis., Conclusion: Approximately one-third of all patients with AF on anticoagulant therapy were concerned regarding bleeding from short- and long-term anticoagulant use., Competing Interests: Conflict of interest: I.U.’s stipend is paid indirectly by Daiichi Sankyo. S.K. received an unrestricted research grant for the Department of Cardiology at Keio University School of Medicine from Novartis and AstraZeneca, as well as personal fees from Bristol-Myers Squibb. N.I. received grants from Bristol-Myers Squibb. T.K. received grants from Bayer Yakuhin, Ltd. S.T. received grants from Bayer Pharmaceuticals and Japan Lifeline along with personal fees from Daiichi Sankyo, Bayer Pharmaceuticals, Bristol-Myers Squibb, Abbott, Medtronic, and Boston Scientific. D.K. belongs to the endowment department supported by AMED under grant number JP22lk0201701. The other authors report no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Quantifying guideline-directed medical therapy (GDMT) intensity is foundational for improving heart failure (HF) care. Existing measures discount dose intensity or use inconsistent weighting., Methods: The Kansas City Medical Optimization (KCMO) score is the average of total daily to target dose percentages for eligible GDMT, reflecting the percentage of optimal GDMT prescribed (range, 0-100). In Change the Management of Patients With HF, we computed KCMO, HF collaboratory (0-7), and modified HF Collaboratory (0-100) scores for each patient at baseline and for 1-year change in established GDMT at the time (mineralocorticoid receptor antagonist, β-blocker, ACE [angiotensin-converting enzyme] inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor). We compared baseline and 1-year change distributions and the coefficient of variation (SD/mean) across scores., Results: Among 4532 patients at baseline, mean KCMO, HF collaboratory, and modified HF Collaboratory scores were 38.8 (SD, 25.7), 3.4 (1.7), and 42.2 (22.2), respectively. The mean 1-year change (n=4061) for KCMO was -1.94 (17.8); HF collaborator, -0.11 (1.32); and modified HF Collaboratory, -1.35 (19.8). KCMO had the highest coefficient of variation (0.66), indicating greater variability around the mean than the HF collaboratory (0.49) and modified HF Collaboratory (0.53) scores, reflecting higher resolution of the variability in GDMT intensity across patients., Conclusions: KCMO measures GDMT intensity by incorporating dosing and treatment eligibility, provides more granularity than existing methods, is easily interpretable (percentage of ideal GDMT), and can be adapted as performance measures evolve. Further study of its association with outcomes and its usefulness for quality assessment and improvement is needed., Competing Interests: Disclosures Drs Khan and Sherrod are supported by the National Heart, Lung, and Blood Institute under award T32H110837. Dr Ikemura received an unrestricted research grant for the Department of Cardiology, Keio University School of Medicine from Bristol Myer Squibb. Dr Sauer reports industry relationships with Abbott, Boston Scientific, Biotronik, Bayer, Amgen, CSL Vifor, Acorai, Story Health, General Prognostics, Impulse Dynamics, and Edwards Lifesciences. He also serves as advisory board member and owns stock in ISHI digital health company. Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Butler reports consulting for Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, and Vifor. Dr DeVore reports research funding through his institution from Biofourmis, Bodyport, Cytokinetics, American Regent Inc, the National Institutes of Health and the National Heart, Lung, and Blood Institute, Novartis, and Story Health. He also provides consulting services for and/or receives honoraria from Abiomed, Cardionomic, LivaNova, Natera, NovoNordisk, Story Health, and Zoll. Dr Lund is supported by Karolinska Institutet, the Swedish Research Council (grant 523-2014-2336), the Swedish Heart Lung Foundation (grants 20150557 and 20190310), and the Stockholm County Council (grants 20170112 and 20190525). Dr Lund reports the following relationships with industry: grants, consulting, honoraria: Abbot, Alleviant, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Edwards, Merck/MSD, Novartis, Novo Nordisk, OrionPharma, Owkin, Pharmacosmos, Vifor Pharma; stock ownership: AnaCardio. Dr Chan is supported by the National Heart, Lung, and Blood Institute under award R01HL160734 and is a consultant for Optum Rx. Dr Spertus has provided consultative services on patient-reported outcomes and evidence evaluation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Myers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare; holds research grants from Bristol Myers Squibb, Abbott Vascular, and Janssen; owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire; and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. The other authors report no conflicts.

Introduction: The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects., Methods and Analysis: In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint., Ethics and Dissemination: The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses., Trial Registration Number: UMIN000045229., Competing Interests: Competing interests: Dr Shiraishi reports consulting fee from Otsuka Pharmaceutical and lecture fees from Otsuka Pharmaceutical, Novartis, AstraZeneca, Ono Pharmaceutical, Boehringer Ingelheime, and Bayer.Dr. Ikemura reports an unrestricted research grant from Bristol Myer Squibb.Dr Kohsaka received an unrestricted research grant from Novartis and honoraria from Pfizer Japan. The remaining authors have no conflict of interest to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: A primary objective in managing atrial fibrillation (AF) is to optimize patients' health status, which can be done only if physicians accurately quantify the outcomes associated with AF in patients' lives., Objective: To explore physicians' estimation of the health status of patients with AF and its association with subsequent care and outcomes., Design, Setting, and Participants: A multicenter, prospective cohort study was conducted in 2 outpatient practices in Tokyo, Japan. Participants included patients with newly diagnosed AF or those referred for initial treatment of AF at outpatient practices and treating physicians from November 8, 2018, to April 1, 2020. Data analysis was performed from December 22, 2022, to July 7, 2023., Exposures: Participating patients completed the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire, a 20-item tool covering 4 domains with a 7-point Likert scale; 3 domains (symptoms, daily activities, and treatment concerns) were used in this study. Blinded to patients' responses, treating physicians answered a 3-item questionnaire quantifying each patient's AFEQT domain with a single item. Patients' mean Likert scale responses within each AFEQT domain were subtracted from the physicians' assessments so that higher scores (≥0.5 points) indicate physician underestimation, while lower scores (≤0.5 points) indicate physician overestimation of the health status of patients with AF., Main Outcomes and Measures: The independent association of physician-patient concordance with treatment escalation (alteration or initiation of antiarrhythmic drugs, cardioversion, or catheter ablation) and 1-year adjusted changes in AFEQT scores., Results: Among 330 patients (238 [72.1%] men; mean [SD] age, 67.9 [11.9] years; 163 [49.4%] with paroxysmal AF), physicians correctly estimated health status in 112 patients (33.9%), underestimated it in 42 patients (12.7%), and overestimated it in 176 patients (53.3%). Treatment escalation occurred in 63.6% of patients whose health status was correctly estimated, 47.6% of those whose health status was underestimated, and 66.3% of patients whose health status was overestimated. After multivariable adjustment, underestimation of health status was independently associated with less treatment escalation (adjusted odds ratio, 0.43; 95% CI, 0.20-0.90) and less frequent AFEQT overall summary score improvement at 1 year (underestimated, 2.5 [95% CI, -1.6 to 6.7] vs correctly and overestimated health status, 8.4 [95% CI, 7.0-9.9] points; P = .01)., Conclusions and Relevance: In this cohort study, physician underestimation of the health status of patients with AF was common and associated with less aggressive treatment and less health status improvement at 1 year.

Background: Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in a broader range of patients., Methods: Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g., documented history of HF, left ventricular ejection fraction ≤ 40%, or BNP levels ≥ 100 pg/mL). Participants, aged 61 ± 10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year., Results: A lower baseline BNP correlated with reduced AFEQT scores. Post CA, all groups showed significant AFEQT score improvements. The lower-BNP group displayed notable enhancements (18.2 ± 1.2, 15.0 ± 1.1, 12.6 ± 1.2, 13.6 ± 1.2, p < 0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/mL) exhibited significant QOL improvements. Comparing paroxysmal AF (PAF) and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements., Conclusions: This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvements.

Aims: The discontinuation of oral anticoagulants (OACs) remains as a significant concern in the management of atrial fibrillation (AF). The discontinuation rate may vary depending on management strategy, and physicians may also discontinue OACs due to concerns about patient satisfaction with their care. We aimed to assess the incidence of OAC discontinuation and its relationship to patients' health in an outpatient AF registry., Methods and Results: From a multicenter registry for newly recognized AF patients ( n = 3313), we extracted 1647 (49.7%) patients with OACs and a CHA 2 DS 2 -Vasc score of ≥2. Discontinuation was defined as sustained cessation of OACs within a 1-year follow-up. We examined predictors associated with discontinuation and its relations to health status defined by the AFEQT questionnaire. Of the 1647 patients, 385 (23.6%) discontinued OACs after 1 year, with discontinuation rates varying across treatment strategies (15.3% for catheter ablation, 4.9% for rhythm control with antiarrhythmic drugs, and 3.0% for rate control). Successful rhythm control was associated with discontinuation in the catheter ablation (OR 6.61, 95% CI 3.00-14.6, p < 0.001) and antiarrhythmic drugs (OR 6.47, 95% CI 2.62-15.9, p < 0.001) groups, whereas the incidence of bleeding events within 1 year was associated with discontinuation in the rate control group. One-year AFEQT scores did not significantly differ between patients who discontinued OACs and those who did not in each treatment strategy group., Conclusions: OAC discontinuation was common among AF patients with significant stroke risk but varied depending on the chosen treatment strategy. This study also found no significant association between OAC discontinuation and patients' health status.

Background Catheter ablation (CA) for atrial fibrillation (AF) is preferred for paroxysmal AF (PAF) but selectively performed in patients with persistent AF (PersAF). This study aimed to investigate the prognostic differences and consequences of CA based on the AF type. Methods and Results Data from a multicenter AF cohort study were analyzed, categorizing patients as PAF or PersAF according to AF duration (≤7 or >7 days, respectively). A composite of all-cause death, heart failure hospitalization, stroke, and bleeding events during 2-year follow-up and changes in the Atrial Fibrillation Effect on Quality-of-life score were compared. Additionally, propensity score matching was performed to compare clinical outcomes of patients with and without CA in both AF types. Among 2788 patients, 51.6% and 48.4% had PAF and PersAF, respectively. Patients with PersAF had a higher incidence of the composite outcome (12.8% versus 7.2%; P <0.001) and smaller improvements in Atrial Fibrillation Effect on Quality-of-life scores than those with PAF. After adjusting for baseline characteristics, PersAF was an independent predictor of adverse outcomes (adjusted hazard ratio, 1.35 [95% CI, 1.30-1.78], P =0.031) and was associated with poor improvements in Atrial Fibrillation Effect on Quality-of-life scores. Propensity score matching analysis showed that the CA group had significantly fewer adverse events than the medication group among patients with PAF (odds ratio, 0.31 [95% CI, 0.18-0.68]; P =0.002). Patients with PersAF showed a similar but nonsignificant trend. Conclusions PersAF is a risk factor for worse clinical outcomes, including patients' health status. CA is associated with fewer adverse events, although careful consideration is required based on the AF type.

Background: Clinical practice guidelines recommend optimizing the health status of patients with atrial fibrillation (AF) as a primary treatment goal. Whether disease-specific health status is associated with subsequent clinical events is unknown., Objectives: The aim of this study was to investigate the association between health status and subsequent clinical events among patients with AF., Methods: Using a prospective cohort study of patients with new-onset AF referred to 11 hospitals (n = 3,313, 68.4% men, mean age 67.8 ± 11.6 years), data were extracted from 3,296 patients (99.4%) who completed the disease-specific Atrial Fibrillation Effects on Quality-of-Life (AFEQT) questionnaire between 2012 and 2018. Factors associated with baseline AFEQT overall summary (OS) score and associations between major adverse cardiovascular or neurologic events (MACNE; a composite of all-cause death, stroke, or new-onset heart failure hospitalization) over 2 years were investigated., Results: Overall, 517 participants (15.6%) had poor to fair health status (AFEQT OS <60), and 1,035 (31.2%) had fair to good health status (AFEQT OS 60 to <80) at baseline. Female sex, younger age, family history of AF, higher baseline heart rate, paroxysmal AF, initial visit to the emergency department, and history of heart failure were associated with lower AFEQT OS scores. Of those, 226 participants (6.8%) experienced MACNE; restricted cubic spline analysis with adjustment for factors associated with baseline AFEQT score showed a nonlinear increase in the risk for MACNE with AFEQT OS score <80. The strongest associations were observed for baseline AFEQT daily activity scores (for AFEQT daily activity score of <80 vs ≥80, HR: 1.65; 95% CI: 1.21-2.25)., Conclusions: Diminished health status in patients with AF is common and is independently associated with subsequent adverse cardiovascular events., Competing Interests: Funding Support and Author Disclosures This study was funded by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grants 20H03915, 20J01755, and 21K16069) and by an unrestricted research grant from Bayer Yakuhin. Dr Ikemura has received an unrestricted research grant for the Department of Cardiology, Keio University School of Medicine, from Bristol Myers Squibb. Dr Kohsaka has received an unrestricted research grant to the Department of Cardiology at Keio University School of Medicine from Bayer, Novartis, and Daiichi Sankyo; and has received personal fees from Bristol Myers Squibb. Dr Kimura has received grants from Bayer Yakuhin. Dr Takatsuki has received grants and personal fees from Bayer; and has received personal fees from Daiichi Sankyo and Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Clinical congestion is the most frequent reason for hospital admission in patients with acute heart failure (AHF). However, few studies have investigated the patterns and prognostic implication of the physical congestion using unbiased and robust statistical methods., Methods: A hierarchical agglomerative clustering analysis was performed in the multicenter Japanese AHF registry (N = 3151) with the distance calculated by Jaccard's distance for jugular vein distention (JVD), leg edema, S3, crackles, and orthopnea. The primary outcome was a composite of cardiac death and heart failure readmission within 1-year., Results: At the time of admission, the median number of prevalent congestive signs was 2. We identified three phenogroups: 'no physical congestions' (N = 251); 'congestion without JVD' (N = 1415); and 'congestion with JVD' (N = 1495). Patients in 'no physical congestion' were the youngest (median 75 [62, 83] years) with the lowest systolic blood pressure (122 [106, 142] mmHg). Patients in 'congestion without JVD', and 'congestion with JVD' were similar in terms of age (77 [67, 84] vs. 78 [69, 84] years) and systolic blood pressure (138 [118, 160] vs. 137 [118, 158] mmHg). While 30-day mortality was similar (4.0%, 3.7%, and 4.3% in 'no physical congestion,' 'congestion without JVD,' and 'congestion with JVD', respectively), the patients in 'congestion with JVD' were at the highest risk for the primary outcome (adjusted hazard ratio 1.79, 95% CI 1.26-2.55 when 'no physical congestion' was a reference)., Conclusions: Our clustering analysis demonstrated that congestion signs, particularly JVD, allowed identification of AHF phenogroups with distinct clinical characteristics and long-term outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: The usefulness of catheter ablation (CA) for atrial fibrillation (AF) across a broad spectrum of heart failure (HF) patients remains to be established. We assessed the association of CA with both health-related quality of life (QoL) and cardiovascular events among HF patients with reduced and preserved left ventricular ejection fraction (LVEF) in an 'all-comer' outpatient-based AF registry., Methods and Results: Of 3303 patients with AF consecutively enrolled in a retrospective multicentre registry that mandated the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire at registration and 1-year follow-up, we extracted data from 530 patients complicating clinical HF. The association between CA and both 1-year change in AFEQT Overall Summary (AFEQT-OS) scores and 2-year composite clinical outcomes (including all-cause death, stroke, and HF hospitalization) was assessed by multivariable analyses. The median duration of AF was 108 days (52-218 days), and 83.4% had LVEF >35%. Overall, 75 patients (14.2%) underwent CA for AF within 1-year after registration. At 1-year follow-up, 67.2% in the ablation group showed clinically meaningful improvements of ≥ 5 points in AFEQT-OS score than 47.8% in the non-ablation group {adjusted odds ratio, 2.03 [95% confidence interval (CI): 1.13-3.64], P = 0.017}. Furthermore, the composite endpoint of all-cause death, stroke, and HF hospitalization occurred less frequently in the ablation group than the non-ablation group [adjusted hazard ratio, 0.27 (95% CI: 0.09-0.86), P = 0.027]., Conclusion: Among AF-HF patients, CA was associated with improved QoL and lower risk of cardiovascular events against drug therapy alone, even for patients with mildly reduced and preserved LVEF., Competing Interests: Conflict of interest: Y.S. is affiliated with a department endowed by Nippon Shinyaku Co., Ltd., Medtronic Japan Co., Ltd., and BIOTRONIK JAPAN Inc., and received honoraria from Otsuka Pharmaceuticals Co., Ltd. and Ono Pharmaceuticals Co., Ltd. S.K. received an unrestricted research grant from the Department of Cardiology at Keio University School of Medicine from Bayer Pharmaceutical and Daiichi Sankyo, received grants from Bayer Yakuhin, Ltd. and Daiichi Sankyo, and received personal fees from Bristol-Myers Squibb. N.I. received grants from Bristol-Myers Squibb. T.K. received grants from Bayer Yakuhin, Ltd. S.T. received grants and personal fees from Bayer and received personal fees from Daiichi Sankyo and Bristol-Myers Squibb. The remaining authors have no conflicts of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The advances in the integrated management of patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) have reduced subsequent cardiovascular events. Nonetheless, sudden cardiac death (SCD) remains a major concern. Therefore, we aimed to investigate the time trend in SCD incidence after PCI and to identify the clinical factors contributing to SCD. From a prospective, multicenter cohort registry in Japan, 8,723 consecutive patients with coronary artery disease undergoing PCI between 2009 and 2017 were included. We evaluated the SCD incidence 2 years after PCI; all death events were adjudicated, and SCD was defined as unexpected death without a noncardiovascular cause in a previously stable patient within 24 hours from the onset. The Fine and Gray method was used to identify the factors associated with SCD. Overall, the mean age of the patients was 68.3 ± 11.3 years, and 1,173 patients (13.4%) had heart failure (HF). During the study period, the use of second-generation drug-eluting stents increased. The 2-year cumulative incidence of all-cause mortality and SCD was 4.29% and 0.45%, respectively. All-cause mortality remained stable during the study period (p for trend = 0.98), whereas the crude incidence of SCD tended to decrease over the study period (p for trend = 0.052). HF was the strongest predictor associated with the risk of SCD (crude incidence [vs non-HF] 2.13% vs 0.19%; p <0.001). In conclusion, the incidence of SCD after PCI decreased over the last decade, albeit the high incidence of SCD among patients with HF remains concerning., Competing Interests: Disclosures Dr Kohsaka reports investigator-initiated grant funding from Bayer and Daiichi Sankyo. The remaining authors have no conflicts of interest to declare. Dr. Ikemura received an unrestricted research grant for the Department of Cardiology, Keio University School of Medicine from Bristol Myer Squibb., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Early detection of atrial fibrillation (AF) is important. Japan has a universal screening system, and regular health screening (HS) is available to support AF detection without a hospital visit. However, health-related outcomes and other characteristics of HS-detected and conventionally diagnosed AF remain unknown., Hypothesis: That the characteristics and health-related outcomes of patients with HS-detected AF may differ from those of patients whose AF was detected by other procedures., Methods: In total, 3318 consecutive newly referred AF cases were enrolled; demographic characteristics and health-related and clinical outcomes were compared between two groups created based on the mode of AF detection (the HS and non-HS groups). Health-related outcomes were assessed using the AF Effect on QualiTy-of-life (AFEQT) questionnaire at baseline and after 1 year of follow-up., Results: AF was detected by HS in 25.0% of patients; these patients had lower CHADS 2 scores (1.01 vs. 1.50, p < .001), higher prevalence of persistent AF (odds ratio, 95% confidence interval; 2.21, 1.88-2.60) and asymptomatic presentation (3.19, 2.71-3.76), and better baseline QoL scores (83.6 vs. 75.0; p < .001). Catheter ablation was more frequently performed in the HS group at follow-up (44.4% vs. 34.1%; p < .001). At 1-year follow-up, the AFEQT scores of the HS group were significantly better in most subdomains., Conclusions: In the Japanese registry, AF was detected via HS in 25% of patients referred to specialty centers for management. Notably, the overall health status of patients with HS-detected AF improved after medical interventions, including catheter ablations., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Recent randomized clinical trials have demonstrated that applying rhythm control during the early stage of atrial fibrillation (AF) may lead to improved clinical outcomes. However, the effects of this modality on health-related quality of life (HRQoL) have not been fully investigated. We aimed to assess the association between the AF stage, determined by the time between AF diagnosis and referral to the cardiology clinic, and HRQoL outcomes., Methods: Using an outpatients-based multicenter AF registry (n = 3,313), we analyzed 2,070 patients with AF diagnosed within 5 years. The patients were divided into 2 groups according to AF stage: early and late AF (AF duration ≤1 and >1 year, respectively). All patients had HRQoL information collected at baseline and 1 year after their initial treatment (assessed via the Atrial Fibrillation Effect on Quality-of-Life-overall summary [AFEQT-OS] score, with higher scores reflecting better HRQoL). The change in AFEQT-OS was adjusted for patient characteristics using a generalized linear mixed model., Results: The early AF group (n = 1,644) was older (early, 68.5 ± 11.1, late, 64.4 ± 10.6 years, P < .001) and had more heart failure (early, 19.9%, late, 12.7%, P < .001) than the late AF group (n = 426). At 1 year after treatment, the adjusted changes in AFEQT-OS were similar in patients with rhythm (adjusted difference [SE], early, 8.4 [1.2], late, 7.2 [1.4], P = .15) or rate (early, 4.0 [0.7], late, 2.3 [1.4], P = .16) control, regardless of AF stage. Furthermore, the improvement in HRQoL was similar between early and late AF in patients undergoing catheter ablation (early, 10.2 [2.1], late, 9.8 [2.4], P = .78), whereas a significant difference was observed in those receiving antiarrhythmic drug therapy alone (early, 10.2 [1.4], late, 3.5 [2.2], P < .001)., Conclusions: Rhythm control therapy provided clinically meaningful improvements in HRQoL, regardless of AF stage. For patients with impaired HRQoL, AF duration should not be a deterrent to treatment, especially catheter ablation., (Copyright © 2022. Published by Elsevier Inc.)

Decoy receptor proteins that trick viruses to bind to them should be resistant to viral escape because viruses that require entry receptors cannot help but bind decoy receptors. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for coronavirus cell entry. Recombinant soluble ACE2 was previously developed as a biologic against acute respiratory distress syndrome (ARDS) and verified to be safe in clinical studies. The emergence of COVID-19 reignited interest in soluble ACE2 as a potential broad-spectrum decoy receptor against coronaviruses. In this review, we summarize recent developments in preclinical studies using various high-affinity mutagenesis and Fc fusion approaches to achieve therapeutic efficacy of recombinant ACE2 decoy receptor against coronaviruses. We also highlight the relevance of stimulating effector immune cells through Fc-receptor engagement and the potential of using liquid aerosol delivery of ACE2 decoy receptors for defense against ACE2-utilizing coronaviruses., Competing Interests: Declaration of interests A.H., J.T., and T.O. are the inventors on a patent filed by Kyoto Prefectural University of Medicine and Osaka University (ACE2 mutant protein, PCT/JP2021/031372)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Early identification of atrial fibrillation (AF) patients at risk for heart failure (HF) remains critical for improving their outcomes. We aimed to investigate whether indices of left ventricular diastolic dysfunction (LVDD) can stratify AF patients without clinical history of HF. Methods: We extracted 1775 patients’ data from a prospective cohort that consecutively recruited recently recognized AF patients with ejection fraction ≥50%. We categorized patients as LVDD grade 0 (none) to 3 (severe) based on mitral deceleration time and E/e’ per the American Society of Echocardiography recommendation. The primary outcome was a composite of all-cause death, stroke, and HF hospitalization during the 2-year follow-up. We also investigated the Atrial Fibrillation Effects on QualiTy-of-Life (AFEQT) scores. Results: Overall, 857 (48.3%) had mild or higher LVDD. Incidence of primary outcomes increased in parallel with LVDD grading (1.8%, 2.8%, 6.5%, and 8.1% for grades 0−3, respectively, p < 0.001), and the presence of grade 3 LVDD was an independent predictor of the primary outcome (adjusted HR 2.28 (vs. grade 0), 95%CI 1.13−4.60). Furthermore, patients with LVDD had lower AFEQT scores at the enrollment and 1-year follow-up. Conclusions: LVDD indices were associated with adverse clinical outcomes and patients’ perceived health status in a recently diagnosed AF cohort without HF.

Patients with atrial fibrillation (AF) at the highest risk of progression to heart failure (HF) need to be identified. We investigated whether QRS duration can stratify patients with AF at risk for poor clinical outcomes, including health-related quality of life (HR-QoL). We analyzed data from a multicenter registry-based cohort study of patients with AF. Patients were grouped according to the QRS duration (narrow: <120 ms; wide: ≥120 ms) at registration (baseline). The primary outcome was a composite of all-cause death and HF hospitalizations during a 2-year follow-up. In addition, the AF effect on the quality-of-life overall summary score was compared between the groups. In 3,269 patients, 302 (9.2%) had a wide QRS; these patients were more likely to be older, male, and have higher CHA 2 DS 2 -VASc scores than those with a narrow QRS. The incidence of the composite outcome was higher in patients with a wide QRS than those with a narrow QRS (13.1% vs 4.9%, p <0.001). After adjustment, a wide QRS was an independent predictor of the primary outcome (adjusted hazard ratio 1.58, 95% confidence interval 1.09 to 2.29, p = 0.016), and the results persisted after the exclusion of patients with bundle branch block or cardiac implantable electronic devices. Regarding HR-QoL outcomes, patients with a wide QRS were less likely to improve AF effect on quality-of-life overall summary scores at 1 year than those with a narrow QRS (adjusted difference -2.31, 95% confidence interval -4.06 to -0.57, p = 0.009). QRS prolongation, even for a nonspecific conduction disturbance, was an independent predictor of adverse outcomes and worse HR-QoL in patients with AF., Competing Interests: Disclosures Dr. Kohsaka received an unrestricted research grant for the Department of Cardiology at Keio University School of Medicine from Bayer Pharmaceutical and Daiichi Sankyo; received grants from Bayer Yakuhin, Ltd. and Daiichi Sankyo; and received personal fees from Bristol-Myers Squibb. Dr. Kimura received grants from Bayer Yakuhin, Ltd. Dr. Takatsuki received grants and personal fees from Bayer and received personal fees from Daiichi Sankyo and Bristol-Myers Squibb. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Recently, a denture adhesive that is easy to clean and contain moisturizing ingredients have been developed for patients with dry mouth. Although the retentive force produced by conventional denture adhesives and oral moisturizers have been compared on models, no study has reported their comparison in the oral cavity. In this study, we aimed to clarify the effects of different directions of traction and loads at the time of pressure contact on the retentive force on a palatal plate made from a dentulous jaw model., Methods: A palatal plate was fabricated with thermoplastic resin on a dentulous jaw model, and a loop-shaped traction device was attached to the centre of the palate. The test samples were a cream-type denture adhesive, a denture adhesive for dry mouth, an oral moisturizer, and a denture moisturizer. The specimens were applied to the inner surface of the plate, which was then mounted under vertical pressure. Then, the retentive force was measured, using a digital force gauge, while the plate was pulled in different directions and with different loads., Results: No significant difference in retentive force was observed in any of the test samples when the direction of traction was between 45° and 60°. The retentive force of the denture adhesive for dry mouth was significantly higher with a direction of traction of 90° than that of 45° or 60°. The retentive force when oral moisturizer was used was significantly higher in the 90° traction direction than in the 45° direction. There was no significant difference between a force of 4.0 kgf or 5.5 kgf when using a denture adhesive for dry mouth. Comparing the four load size conditions, the larger the load, the higher was the retentive force. Similar results were obtained for the cream-type denture adhesive and denture moisturizer. Significantly higher retentive force was observed for larger loads when oral moisturizer was used., Conclusions: The results suggest that the direction of traction and the pressure load affect the retentive force on a palatal plate., (© 2022. The Author(s).)

Background: Recent trials on novel heart failure (HF) treatments (angiotensin receptor-neprilysin inhibitor, sodium-glucose cotransporter 2 inhibitor, and ivabradine) emphasize the use of conventional medical therapy (angiotensin-converting enzyme inhibitors, beta-blockers [BB], and mineral corticosteroid receptor antagonists). We aimed to evaluate the prescription rate of conventional medical therapy and its association with long-term outcomes in patients eligible for recent trials., Methods: We examined 1295 consecutive patients with HF with reduced ejection fraction (HFrEF) from a multicenter registry (WET-HF registry). We assessed conventional medical therapy implementation among patients meeting the PARADIGM-HF/DAPA-HF and SHIFT enrollment criteria. We also examined the association between conventional medical therapy use and long-term outcomes within each enrollment criterion., Results: Overall, 62.2% and 35.3% of HFrEF patients met the enrollment criteria of the PARADIGM-HF/DAPA-HF and SHIFT trials. Only 33.9% and 31.9% received full conventional medical therapy within each patient subset. Notably, 84.2% of patients who met the SHIFT enrollment criteria were on BB, and only 23.0% and 4.4% were on ≥50% or the full recommended dose, respectively. Implementation of full conventional medical therapy use was associated with lower 2-year mortality and HF readmission rates in the PARADIGM-HF/ DAPA-HF eligible group (HR 0.68, 95% CI 0.50-0.92). The use of BB at ≥50% of the recommended dose was associated with lower 2-year mortality and HF readmission rates in the SHIFT-eligible group (HR 0.50, 95% CI 0.30-0.84)., Conclusions: Conventional medical therapy was underutilized among patients eligible for novel trials within a Japanese HF registry. Further efforts to optimize conventional medical therapy are needed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Catheter ablation is widely used as first-line therapy for patients with impaired quality of life; however, whether catheter ablation improves survival and other outcomes in atrial fibrillation (AF) cases remains unclear., Objective: The purpose of this study was to evaluate whether catheter ablation reduces adverse clinical outcomes and improves patients' quality of life using data from a contemporary Japanese multicenter registry of patients with early-stage AF., Methods: The Keio Interhospital Cardiovascular Studies-Atrial Fibrillation registered 3318 patients with AF newly diagnosed at or referred to participating hospitals between 2014 and 2018. Propensity score matching based on 47 demographic variables was performed. We extracted 823 pairs who underwent catheter ablation or medical therapy alone. The primary outcome was the composite of all-cause death, stroke, bleeding events, and heart failure hospitalization during a 2-year follow-up period. Additionally, the Atrial Fibrillation Effect on QualiΤy-of-Life scores at baseline and 1-year follow-up were evaluated., Results: Within the matched cohort, the median time since AF diagnosis was 0.3 years (interquartile range [IQR] 0.1‒2.3 years), age was 67.0 years (IQR 59.0‒73.0 years), and the CHA 2 DS 2 -VASc score was 2.0 (IQR 1.0‒2.0). During a median follow-up period of 730 days (IQR 366‒731 days), patients who underwent catheter ablation had a lower risk of primary outcomes (hazard ratio 0.49; 95% confidence interval 0.30‒0.79; P = .004), with a significantly lower risk of heart failure hospitalization (hazard ratio 0.33; 95% confidence interval 0.14-0.77; P = .010) and improved Atrial Fibrillation Effect on QualiΤy-of-Life scores, than did those who received medical therapy., Conclusion: In patients with propensity score-matched, early-stage, real-world AF, catheter ablation was associated with a lower risk of adverse clinical events and improved quality of life as compared with medical therapy., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The Omicron (B.1.1.529) SARS-CoV-2 variant contains an unusually high number of mutations in the spike protein, raising concerns of escape from vaccines, convalescent serum, and therapeutic drugs. Here, we analyzed the degree to which Omicron pseudo-virus evades neutralization by serum or therapeutic antibodies. Serum samples obtained 3 months after two doses of BNT162b2 vaccination exhibited 18-fold lower neutralization titers against Omicron than parental virus. Convalescent serum samples from individuals infected with the Alpha and Delta variants allowed similar frequencies of Omicron breakthrough infections. Domain-wise analysis using chimeric spike proteins revealed that this efficient evasion was primarily achieved by mutations clustered in the receptor binding domain but that multiple mutations in the N-terminal domain contributed as well. Omicron escaped a therapeutic cocktail of imdevimab and casirivimab, whereas sotrovimab, which targets a conserved region to avoid viral mutation, remains effective. Angiotensin-converting enzyme 2 (ACE2) decoys are another virus-neutralizing drug modality that are free, at least in theory, from complete escape. Deep mutational analysis demonstrated that an engineered ACE2 molecule prevented escape for each single-residue mutation in the receptor binding domain, similar to immunized serum. Engineered ACE2 neutralized Omicron comparably to the Wuhan strain and also showed a therapeutic effect against Omicron infection in hamsters and human ACE2 transgenic mice. Similar to previous SARS-CoV-2 variants, some sarbecoviruses showed high sensitivity against engineered ACE2, confirming the therapeutic value against diverse variants, including those that are yet to emerge.

Background Atrial fibrillation and heart failure (HF) possess mutual risk factors and share a common pathophysiological pathway. Tricuspid regurgitation (TR) is a known predictor of adverse events in patients with HF. However, its implications on patients with atrial fibrillation in its early stage remain unknown. Methods and Results Data of 2211 patients without previous HF diagnosis were extracted from a prospective, multicenter registry of newly diagnosed patients with atrial fibrillation. TR was categorized as absent, mild, moderate, and severe based on the American Society of Echocardiography recommendations. The primary outcome was time to first hospitalization for HF after enrollment. The Atrial Fibrillation Effects on Quality-of-Life scores were compared. Overall, 1107 patients (50.1%) had TR (42.3%, 7.2%, and 0.6% for mild, moderate, and severe, respectively). During follow-up (median 730 [interquartile range, 366-731] days), 44 patients (2.0%) experienced HF hospitalization, and the incidence increased with severity of TR ( P <0.001). TR was an associated predictor of the primary outcome (hazard ratio [HR]: 2.51, P =0.050; HR: 6.19, P =0.008; for moderate and severe TR versus no TR). Changes in AFEQT overall score were negatively related to TR severity (8.7±17.5 versus 8.5±17.0 versus 3.1±17.5 versus 1.4±11.8, absent versus mild versus moderate versus severe TR, respectively), although it was not an independent predictor after adjustments. Conclusions TR severity at atrial fibrillation diagnosis was an associated predictor of subsequent hospitalization for HF, which may warrant the need for a more intensive follow-up and HF-related management.

An accurate prediction of major adverse events after percutaneous coronary intervention (PCI) improves clinical decisions and specific interventions. To determine whether machine learning (ML) techniques predict peri-PCI adverse events [acute kidney injury (AKI), bleeding, and in-hospital mortality] with better discrimination or calibration than the National Cardiovascular Data Registry (NCDR-CathPCI) risk scores, we developed logistic regression and gradient descent boosting (XGBoost) models for each outcome using data from a prospective, all-comer, multicenter registry that enrolled consecutive coronary artery disease patients undergoing PCI in Japan between 2008 and 2020. The NCDR-CathPCI risk scores demonstrated good discrimination for each outcome (C-statistics of 0.82, 0.76, and 0.95 for AKI, bleeding, and in-hospital mortality) with considerable calibration. Compared with the NCDR-CathPCI risk scores, the XGBoost models modestly improved discrimination for AKI and bleeding (C-statistics of 0.84 in AKI, and 0.79 in bleeding) but not for in-hospital mortality (C-statistics of 0.96). The calibration plot demonstrated that the XGBoost model overestimated the risk for in-hospital mortality in low-risk patients. All of the original NCDR-CathPCI risk scores for adverse periprocedural events showed adequate discrimination and calibration within our cohort. When using the ML-based technique, however, the improvement in the overall risk prediction was minimal., (© 2022. The Author(s).)

Background: Measuring the quality of care has been central for improving the outcomes of patients undergoing percutaneous coronary intervention (PCI). This study described the performance rates and regional variations in quality metrics for PCI using a representative national Japanese registry., Methods: Overall, 760,854 patients across 714 institutions (2016-2018) were analysed. Quality metrics included preprocedural antiplatelet therapy use, door-to-balloon time ≤90 min for ST-elevation myocardial infarction, transradial approach, and preprocedural noninvasive stress testing for elective cases in 47 Japanese prefectures. Coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) were also evaluated. Factors associated with preprocedural testing rates were evaluated using multivariable linear regression., Findings: Rates of preprocedural antiplatelet therapy use were high with low variations (96·4% [94·7-97·2%]), but there was still substantial room for improvement in the rates of door-to-balloon time (74·7% [71·2-78·9%]) and transradial approach use (70·9% [65·1-73·4%]). Rates of preprocedural noninvasive stress testing were low with substantial variation (36·6% [27·1-49·7%]). Additionally, we found substantial variations in CCTA (50·0% [39·5-55·1%]) and FFR measurement (15·7% [113·-18·3%]) rates. The number of scintigraphy scanners/ prefecture was associated with the performance of noninvasive stress testing (13·4% [95% CI, 2·45-24·4%] increase for every 1/100,000 population increase in scanners)., Interpretations: We observed substantial regional variation in the use of preprocedural testing, and its performance was directly related to nuclear-scanner availability. These findings suggest the need for targeted efforts in improving testing rates, whether by optimising resource allocation or additional education or feedback mechanisms., Funding: This study was funded by the Japan Society for the Promotion of Science (Grant Nos. 20H03915, 16H05215, 16KK0186, and 20K22883) and by the Ministry of Health, Labor and Welfare Grants-in-Aid for Scientific Research Program (Grant No. 21FA1015). The J-PCI registry is led and supported by the Japanese Association of Cardiovascular Intervention and Therapeutics., Competing Interests: Kohsaka has received investigator-initiated grant funding from Daiichi-Sankyo and Bristol-Myers Squibb and has received personal fees from Bristol-Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Author(s).)

Aims: The impact of worsening renal function (WRF) on the prognosis of patients with acute heart failure (AHF) remains controversial. We aimed to identify phenotypically distinct subgroups among individuals with both AHF and WRF using cluster analysis., Methods and Results: Overall, the data of 483 patients with both AHF and WRF enrolled in the West Tokyo Heart Failure Registry were analysed. Using cluster analysis, we identified three phenotypically distinct subgroups (phenogroups 1, 2, and 3). We assessed the impact of WRF on the prognosis of each phenogroup by comparing the incidence of composite endpoints, including all-cause death and re-hospitalization due to heart failure, with those of a propensity score-matched, non-WRF control group. Participants in phenogroup 1 (N = 122) were the youngest (69.3 ± 13.7 years), had relatively preserved estimated glomerular filtration rate (eGFR, 70.0 ± 27.7 mL/min/1.73 m 2 ), and reduced left ventricular ejection fraction (LVEF) (41.8 ± 13.7%). Conversely, participants in phenogroup 3 (N = 122) were the oldest (81.7 ± 8.5 years), had the worst eGFR (33.0 ± 20.9 mL/min/1.73 m 2 ), and had preserved LVEF (51.7 ± 14.8%). The characteristics of the participants in phenogroup 2 (N = 239) were between those of phenogroups 1 and 3. The propensity score matching analysis showed that WRF was associated with a higher incidence of composite endpoints in phenogroup 1, whereas this association was not observed in phenogroups 2 and 3., Conclusions: Using cluster analysis, we revealed three phenotypically distinct subgroups of patients with both AHF and WRF. WRF was associated with worse clinical outcomes in the subgroup of younger patients with reduced LVEF and preserved renal function., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)