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Myocardial blood flow (MBF) quantification by positron emission tomography (PET) has diagnostic and prognostic utility in heart transplant (HT) patients. The purpose of this study is to assess the use of PET for early cardiac allograft vasculopathy (CAV) detection and risk stratification. Adult HT recipients, prospectively enrolled from 2 institutions between January 2018-March 2021, underwent evaluation at 3- and 12- months post HT with PET, myocardial biopsy, and intravascular ultrasound (IVUS). Macrovascular CAV was assessed by IVUS maximal intimal thickness (MIT) and percent intimal volume (PIV). Microvascular CAV was assessed by capillary density on myocardial biopsy. Linear regression was performed to determine post HT predictors of CAV progression according to PIV change from 3 to 12 months. Data was analyzed from 74 patients (mean age 51 years, 45% male) who underwent PET, including 69, 67 and 62 patients with examinations at 3-months baseline, 12-months follow-up, and both 3- and 12-months post HT, respectively. Baseline to follow-up IVUS showed median increases of 0.10 mm (IQR 0.10, 0.30) in MIT and 5.6% (IQR 0.9, 10.0) in PIV. Capillary density increased significantly: 485 capillaries/mm2 (IQR 143, 951) at baseline, 607 capillaries/mm2 (IQR 172, 1186), p = 0.04) at follow-up. There were significant correlations between PIV and capillary density at baseline (r = 0.41, p <0.01) and follow-up (r = 0.26, p = 0.04). Flow quantification by PET showed a significant increase from baseline in myocardial flow reserve (2.5 ± 0.7 vs. 2.9 ± 0.8, p <0.01) and stress MBF (2.7 ± 0.6 vs. 2.9 ± 0.6, p = 0.01) without significant change in coronary vascular resistance (47 ± 16 vs. 47 ± 11, p = 0.89). At baseline, there was no association between PET MBF and IVUS or myocardial biopsy. At follow-up, significant correlations were observed between stress MBF (r = -0.35, p <0.01), CVR (r = 0.33, p = 0.01) and PIV with positive correlation trend between CVR and capillary density (r = 0.23, p = 0.07). On linear regression analyses, baseline PET MBF was not associated with 1-year post HT CAV progression. There is significant improvement in graft myocardial blood flow in the first year of transplant. PET MBF at 1-year post transplant is associated with IVUS indices of CAV. Our results suggest potential use of PET for early 1-year post transplant noninvasive assessment of epicardial CAV. [ABSTRACT FROM AUTHOR]

Serum biomarkers may enable noninvasive screening for cardiac allograft vasculopathy (CAV) and may allow for tailored invasive coronary evaluation. We previously identified potential candidate CAV biomarkers using Slow Off-rate Modified Aptamer proteomics. The aim of this study is to validate selected candidate biomarkers for diagnosis of early CAV. Adult heart transplant (HT) recipients from 2 institutions underwent serum biomarker testing during prospective intravascular ultrasound (IVUS) evaluation at 3- and 12-months post-transplant. Enzyme linked immunoassays were used to measure intercellular adhesion molecule 2 (ICAM), receptor tyrosine-protein kinase ErbB3 (ERB), and tissue factor (TF). CAV was assessed on IVUS by percent intimal volume (PIV) and maximal intimal thickness (MIT). An MIT ≥0.5 mm was used to define CAV. : median age 55 years (IQR 44, 61), 59% male. An MIT ≥0.5 mm was present in 42 (51%) and 62 (75%) patients at 3- and 12- months post HT, respectively. There was a significant increase from 3 to 12 months post HT in ICAM (430 ± 178 U/mL vs. 613 ± 249 U/mL, p <0.01), while ERB and TF were unchanged. There were significant negative correlations (all p <0.05) between biomarkers and PIV at 3 months (r = -0.29 for ERB, r = -0.46 for TF) and 12 months (r = -0.27 for ICAM, r = -0.27 for ERB, r= -0.26 for TF). The Figure shows the diagnostic accuracy of individual biomarkers for CAV at 12 months post-transplant. Based on optimal diagnostic thresholds of ICAM <603 U/mL and ERB <4776 pg/mL; combined ICAM and ERB measurements yielded 77% sensitivity (52% specificity) if either biomarker is abnormal and 90% specificity (47% sensitivity) if both biomarkers are abnormal. Serum ICAM and ERB show potential as noninvasive diagnostic biomarkers for early CAV. Due to differing pathogenesis of early and late CAV, these biomarkers should be evaluated in patients with varying CAV disease severity and larger HT populations. [ABSTRACT FROM AUTHOR]

In response to notable increases in tick-associated illnesses in the United States, recent public health policies encouraged multi-sector collaborative approaches to preventing vector-borne diseases. Primary prevention strategies focus on educating the public about risks for tick-borne diseases and encouraging adoption of personal protection strategies. Accurate descriptions of when and where people are at risk for tick-borne diseases aid in the optimization of prevention messaging. Tick and tick-borne pathogen data can be used to fill gaps in epidemiological surveillance. However, the utility of acarological data is limited by their completeness. National maps showing the distribution of medically important tick species and the pathogens they carry are often incomplete or non-existent. Recent policies encourage accelerated efforts to monitor changes in the distribution and abundance of medically important ticks and the presence and prevalence of human pathogens that they carry, and to provide actionable, evidence-based information to the public, health care providers and public health policy makers. In 2018, the Centers for Disease Control and Prevention initiated a national tick surveillance program focused on Ixodes ticks. The national program coordinated and expanded upon existing efforts led by public health departments and academic institutions. Here, we describe experiences of state public health departments engaged in Ixodes tick surveillance, including information on why they initiated Ixodes surveillance programs, programmatic objectives, and strategies for maintaining tick surveillance programs. We share experiences and challenges in interpreting or communicating tick surveillance data to stakeholders and explore how the acarological data are used to complement epidemiological data., (Published by Oxford University Press on behalf of Entomological Society of America 2024.)

Background and Aims: Severe tricuspid regurgitation is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from the surgery., Methods: In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional tricuspid regurgitation (33 centres, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4-5, and high: ≥6)., Results: One thousand and two hundred seventeen were managed conservatively, and 551 underwent isolated tricuspid valve surgery (200 repairs and 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management [41% vs. 36%; hazard ratio (HR) .97; 95% confidence interval (CI) .88-1.08, P = .57]. Surgery improved survival compared with conservative management in the low TRI-SCORE category (72% vs. 44%; HR .27; 95% CI .20-.37, P < .0001), but not in the intermediate (36% vs. 37%; HR 1.17; 95%CI .98-1.40, P = .09) or high categories (20% vs. 24%; HR 1.06; 95% CI .91-1.25, P = .45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR .11; 95% CI .06-.19, P < .0001, and HR .65; 95% CI .47-.90, P = .009). Repair showed benefit in the intermediate category (59% vs. 37%; HR .49; 95% CI .35-.68, P < .0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18-1.72, P = .0002)., Conclusions: Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The safety profile of transcatheter tricuspid valve (TTV) repair techniques is well established, but residual tricuspid regurgitation (TR) remains a concern., Objectives: The authors sought to assess the impact of residual TR severity post-TTV repair on survival., Methods: We evaluated the survival rate at 2 years of 613 patients with severe isolated functional TR who underwent TTV repair in TRIGISTRY according to the severity of residual TR at discharge using a 3-grade (mild, moderate, and severe) or 4-grade scheme (mild, mild to moderate, moderate to severe, and severe)., Results: Residual TR was none/mild in 33%, moderate in 52%, and severe in 15%. The 2-year adjusted survival rates significantly differed between the 3 groups (85%, 70%, and 44%, respectively; restricted mean survival time [RMST]: P = 0.0001). When the 319 patients with moderate residual TR were subdivided into mild to moderate (n = 201, 33%) and moderate to severe (n = 118, 19%), the adjusted survival rate was also significantly different between groups (85%, 80%, 55%, and 44%, respectively; RMST: P = 0.001). Survival was significantly lower in patients with moderate to severe residual TR compared to patients with mild to moderate residual TR (P = 0.006). No difference in survival rates was observed between patients with no/mild and mild to moderate residual TR (P = 0.67) or between patients with moderate to severe and severe residual TR (P = 0.96)., Conclusions: The moderate residual TR group was heterogeneous and encompassed patients with markedly different clinical outcomes. Refining TR grade classification with a more granular 4-grade scheme improved outcome prediction. Our results highlight the importance of achieving a mild to moderate or lower residual TR grade during TTV repair, which could define a successful intervention., Competing Interests: Funding Support and Author Disclosures Dr Dreyfus has received speaker or proctoring fees from Abbott. Dr Kresoja has received consulting fees from Edwards Lifesciences. Dr Taramasso has received consulting or speaker fees from Abbott Vascular, Edwards Lifesciences, Medtronic, Boston Scientific, Shenqi Medical, PiCardia, CoreMedic, VentriMend, MEDIRA, CoreQuest, and HiD Imaging. Dr Iliadis has received consulting fees from Abbott Vascular and Edwards Lifesciences. Dr Nombela-Franco has received consulting or speaker fees from Abbott Vascular, Edwards Lifesciences, and Products and Features. Dr Estevez-Loureiro has received speaker fees from Abbott Vascular, Edwards Lifesciences, Boston Scientific, and Venus Medtech. Dr Hausleiter has received grants and consulting fees from Edwards Lifesciences. Dr Stolz has received consulting or speaker fees from Edwards Lifesciences. Dr Windecker has received research, travel, or educational grants to the institution without personal remuneration from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Farapulse Inc Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, MonarQ, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as an Advisory Board member and/or member of the Steering/Executive Group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave with payments to the institution but no personal payments; and has served as a member of the Steering/Executive Committee Group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Zamorano has received consulting or speaker fees from Novartis, Bayer, and Pfizer. Dr von Bardeleben has received consulting or speaker fees from Abbott Vascular, Edwards Lifesciences, Medtronic, Philips, and Siemens. Dr Tang has received speaker honoraria and has served as a physician proctor, consultant, Advisory Board member, TAVR Publications Committee Member, APOLLO Trial Screening Committee Member, and IMPACT MR Steering Committee member for Medtronic; has received speaker honoraria and has served as a physician proctor, consultant, Advisory Board member, and TRILUMINATE Trial Anatomic Eligibility and Publications Committee member for Abbott Structural Heart; has served as an Advisory Board member for Boston Scientific and JenaValve; has served as a consultant and Physician Screening Committee Member for Shockwave Medical; has served as a consultant for NeoChord, Peija Medical, and Shenqi Medical Technology; and has received speaker honoraria from Siemens Healthineers. Dr Hahn has received speaker fees from Boston Scientific, Edwards Lifesciences, and Philips Healthcare. Dr Webb has received consulting fees from Edwards Lifesciences; and has received research funding from Medtronic, Abbott, Boston Scientific, and Edwards Lifesciences. Dr Lauten has received speaker fees from Boehringer Ingelheim, Medtronic, Amgen, Bayer, Novartis, Sanofi, Chiesi, and AstraZeneca; and is a shareholder of the Devie Medical Drug Eluting Valve for Endocarditis Treatment. Dr Rodés-Cabau has received consulting or speaker fees from Abbott Vascular, Edwards Lifesciences, and Medtronic. Dr Nejjari has received consulting or speaker fees from Abbott Vascular, Medtronic, Edwards Lifesciences, Boston Scientific, and Robocath. Dr Badano has received consulting or speaker fees from Edwards Lifesciences, GE Healthcare, and Philips Medical Systems. Dr Himbert has received proctoring fees from Edwards Lifesciences and Abbott Vascular. Dr Modine has received speaker or consulting fees from Abbott, Edwards Lifesciences, Medtronic, Microport, and GE. Dr Rudolph has received consulting or speaker fees from Abbott Vascular and Edwards Lifesciences. Dr Bax has received lecture fees from Abbott and Edwards Lifesciences. Dr Lurz has received consulting fees from Abbott Medical, Innoventric, and Edwards Lifesciences. Dr Maisano has received grant and/or research institutional support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific Corporation, NVT, Terumo, Venus, and 3mensio; has received consulting fees and personal and institutional honoraria from Abbott, Medtronic, Edwards Lifesciences, Xeltis, Cardiovalve, Occlufit, Simulands, Mtex, Venus, and Squadra; has received royalty income/IP rights from Edwards Lifesciences; and is a shareholder (including share options) in Cardiogard, Cardiovalve, Magenta, SwissVortex, Transseptalsolutions, and 4Tech. Dr Messika-Zeitoun has received research grants from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Positron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant., Objectives: The authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification., Methods: Adults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy., Results: A total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm 2 (95% CI: -6 to 79 capillaries/mm 2 ). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = -0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR., Conclusions: The 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786)., Competing Interests: Funding Support and Author Disclosures This study was funded by a Heart and Stroke Foundation of Canada Grant in Aid (G-17-00018310) and University of Ottawa Heart Institute ORACLE Innovation Cluster Team Grant. Dr Chih is supported by a Tier 2 University of Ottawa Clinical Research Chair in Cardiac Transplantation. Dr Chong has received honoraria from Abbott and is an Abbott Advisory Board member for optical coherence tomography. Dr deKemp has received royalties from rubidium-82 PET technologies licensed to Jubilant Radiopharma and to INVIA Medical Solutions and has also received research funding and honoraria from Jubilant-DraxImage Radiopharma and IONETIX. Dr Beanlands is a University of Ottawa Distinguished Research Chair in Cardiovascular Imaging; and is a consultant for and has received research grant funding from Jubilant-DraxImage, Lantheus Medical Imaging, and General Electric Health Care. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Pulmonary vein isolations (PVI) are being performed using a high-power, short-duration (HPSD) strategy. The purpose of this study was to compare the clinical efficacy and safety outcomes of an HPSD versus low-power, long-duration (LPLD) approach to PVI in patients with paroxysmal atrial fibrillation (AF)., Methods: Patients were grouped according to a HPSD (≥40 W) or LPLD (≤35 W) strategy. The primary endpoint was the 1-year recurrence of any atrial arrhythmia lasting ≥30 s, detected using three 14-day ambulatory continuous ECG monitoring. Procedural and safety endpoints were also evaluated. The primary analysis were regression models incorporating propensity scores yielding adjusted relative risk (RR a ) and mean difference (MD a ) estimates., Results: Of the 398 patients included in the AWARE Trial, 173 (43%) underwent HPSD and 225 (57%) LPLD ablation. The distribution of power was 50 W in 75%, 45 W in 20%, and 40 W in 5% in the HPSD group, and 35 W with 25 W on the posterior wall in the LPLD group. The primary outcome was not statistically significant at 30.1% versus 22.2% in HPSD and LPLD groups with RR a 0.77 (95% confidence interval [CI]) 0.55-1.10; p = .165). The secondary outcome of repeat catheter ablation was not statistically significant at 6.9% and 9.8% (RR a 1.59 [95% CI 0.77-3.30]; p = .208) respectively, nor was the incidence of any ECG documented AF during the blanking period: 1.7% versus 8.0% (RR a 3.95 [95% CI 1.00-15.61; p = .049) in the HPSD versus LPLD group respectively. The total procedure time was significantly shorter in the HPSD group (MD a 97.5 min [95% CI 84.8-110.4)]; p < .0001) with no difference in adjudicated serious adverse events., Conclusions: An HPSD strategy was associated with significantly shorter procedural times with similar efficacy in terms of clinical arrhythmia recurrence. Importantly, there was no signal for increased harm with a HPSD strategy., (© 2023 Wiley Periodicals LLC.)

Background: Early cardiac allograft vasculopathy (CAV) prognostication is needed to improve long-term outcomes after heart transplantation. We characterized first year posttransplant coronary anatomic-physiologic alterations to determine predictors of early CAV progression., Methods: Heart transplant recipients at 2 institutions (enrolled January 2018 to March 2021) underwent prospective evaluation 3 and 12-month posttransplant with angiography and left anterior descending artery intravascular ultrasound, optical coherence tomography, fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance measurements. CAV progression was assessed by intravascular ultrasound change in percentage intimal volume from baseline to 12-month follow-up., Results: Eighty-two patients (mean age, 51 years; 60% men) completed evaluation at mean 13.8 and 56.3 weeks posttransplant. Donor atherosclerosis (baseline intravascular ultrasound maximal intimal thickness, ≥0.5 mm) was evident in 50%. De novo (follow-up maximal intimal thickness, ≥0.5 mm) and rapidly progressive CAV (maximal intimal thickness, ≥0.5-mm increase from baseline) developed in 24% and 13%, respectively. On optical coherence tomography, baseline to follow-up median intimal volume increased 42% (0.58 mm 3 /mm), percentage intimal volume increased 44% (4.6%), vessel volume decreased 4% (-0.50 mm 3 /mm) and lumen volume decreased 9% (-1.02 mm 3 /mm); P <0.05 for all. Fibrotic plaque was the predominant morphology: baseline, 29% and follow-up, 50%. Coronary physiology was abnormal in 41% at baseline and 45% at follow-up, with 1 in 5 patients having microvascular dysfunction (index of microcirculatory resistance, ≥25). On multivariable linear regression analysis, recipient male sex, fibrotic plaque, and index of microcirculatory resistance were independent predictors of coronary disease progression., Conclusions: Fibrotic plaque on optical coherence tomography and index of microcirculatory resistance early posttransplant predict CAV progression in the first year of transplantation., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03217786., Competing Interests: Disclosures Dr Chih is supported by a Heart and Stroke Foundation of Ontario Clinician Scientist Phase I Award and a Tier 2 University of Ottawa Clinical Research Chair in Cardiac Transplantation. Dr Chong has received honorarium from Abbott and is an Abbot advisory board member for optical coherence tomography. Dr Beanlands is a University of Ottawa Distinguished Research Chair in Cardiovascular Imaging. Dr Beanlands is a consultant for and receives research grant funding from Jubilant-DraxImage, Lantheus Medical Imaging, and General Electric Health Care. The other authors report no conflicts.

Introduction: Transradial access (TRA) has rapidly emerged as the preferred vascular access site for coronary angiography and percutaneous coronary intervention. Radial artery occlusion (RAO) remains as an important complication of TRA as it precludes future ipsilateral transradial procedures. While intraprocedural anticoagulation has been studied extensively, the definitive role of postprocedural anticoagulation has not yet been established., Methods and Analysis: The Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion trial is a multicentre, prospective, randomised, open-label, blinded-endpoint design study investigating the efficacy and safety of rivaroxaban to reduce the incidence of RAO. Eligible patients will undergo randomisation to receive either rivaroxaban 15 mg once daily for 7 days or to no additional postprocedural anticoagulation. Doppler ultrasound to assess radial artery patency will be performed at 30 days., Ethics and Dissemination: The study protocol has been approved by the Ottawa Health Science Network Research Ethics Board (approval number 20180319-01H). The study results will be disseminated via conference presentations and peer-reviewed publications., Trial Registration Number: NCT03630055., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Heartland virus (HRTV) disease is an emerging tickborne illness in the midwestern and southern United States. We describe a reported fatal case of HRTV infection in the Maryland and Virginia region, states not widely recognized to have human HRTV disease cases. The range of HRTV could be expanding in the United States.

Importance: Recurrent atrial fibrillation (AF) commonly occurs after catheter ablation and is associated with patient morbidity and health care costs., Objective: To evaluate the superiority of an augmented double wide-area circumferential ablation (WACA) compared with a standard single WACA in preventing recurrent atrial arrhythmias (AA) (atrial tachycardia, atrial flutter, or atrial fibrillation [AF]) in patients with paroxysmal AF., Design, Setting, and Participants: This was a pragmatic, multicenter, prospective, randomized, open, blinded end point superiority clinical trial conducted at 10 university-affiliated centers in Canada. The trial enrolled patients 18 years and older with symptomatic paroxysmal AF from March 2015 to May 2017. Analysis took place between January and April 2022. Analyses were intention to treat., Interventions: Patients were randomized (1:1) to receive radiofrequency catheter ablation for pulmonary vein isolation with either a standard single WACA or an augmented double WACA., Main Outcomes and Measures: The primary outcome was AA recurrence between 91 and 365 days postablation. Patients underwent 42 days of ambulatory electrocardiography monitoring after ablation. Secondary outcomes included need for repeated catheter ablation and procedural and safety variables., Results: Of 398 patients, 195 were randomized to the single WACA (control) arm (mean [SD] age, 60.6 [9.3] years; 65 [33.3%] female) and 203 to the double WACA (experimental) arm (mean [SD] age, 61.5 [9.3] years; 66 [32.5%] female). Overall, 52 patients (26.7%) in the single WACA arm and 50 patients (24.6%) in the double WACA arm had recurrent AA at 1 year (relative risk, 0.92; 95% CI, 0.66-1.29; P = .64). Twenty patients (10.3%) in the single WACA arm and 15 patients (7.4%) in the double WACA arm underwent repeated catheter ablation (relative risk, 0.72; 95% CI, 0.38-1.36). Adjudicated serious adverse events occurred in 13 patients (6.7%) in the single WACA arm and 14 patients (6.9%) in the double WACA arm., Conclusions and Relevance: In this randomized clinical trial of patients with paroxysmal AF, additional ablation by performing a double ablation lesion set did not result in improved freedom from recurrent AA compared with a standard single ablation set., Trial Registration: ClinicalTrials.gov Identifier: NCT02150902.

Objectives: Presentation with ST-segment-elevation myocardial infarction (STEMI) during off-hours may impact timely reperfusion and clinical outcomes. We investigated the association between off-hours presentation, door-to-balloon time, and in-hospital mortality in patients with STEMI referred for primary percutaneous coronary intervention (PCI)., Methods: We included consecutive patients referred for primary PCI at the University of Ottawa Heart Institute between July 2004 and December 2017. The off-hours group included patients presenting on weekends, statutory holidays, or between 18:00 to 07:59 hours on weekdays. The on-hours group included patients presenting between 08:00 and 17:59 hours on weekdays. The primary clinical outcome was the adjusted in-hospital mortality. The primary quality-of-care indicator was door-to-balloon time., Results: A total of 5132 patients were included, with 3152 (61.4%) in the off-hours group and 1980 (38.6%) in the on-hours group. The median door-to-balloon time was longer in the off-hours group compared with the on-hours group (102 minutes vs 77 minutes; P<.001), while the median onset-to-door time was similar (P=.40). There was no difference in the rates of in-hospital mortality (3.5% vs 3.0%; P=.32) or in the adjusted mortality (odds ratio, 1.2; 95% confidence interval, 0.8-1.8; P=.44) between off-hours and on-hours groups. However, door-to-balloon time was an independent predictor of in-hospital mortality (P<.01) and off-hours presentation was an independent predictor of longer door-to-balloon time (P<.001), with an excess of 22.1 minutes., Conclusion: Patients treated with primary PCI during off-hours had longer door-to-balloon times. Treatment during off-hours was an independent predictor of longer door-to-balloon time and longer door-to-balloon times were associated with higher mortality.

Heart failure (HF) is a rising global cardiovascular epidemic driven by aging and chronic inflammation. As elderly populations continue to increase, precision treatments for age-related cardiac decline are urgently needed. Here we report that cardiac and blood expression of IGFBP7 is robustly increased in patients with chronic HF and in an HF mouse model. In a pressure overload mouse HF model, Igfbp7 deficiency attenuated cardiac dysfunction by reducing cardiac inflammatory injury, tissue fibrosis and cellular senescence. IGFBP7 promoted cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and reactive oxygen species (ROS) detoxification, thereby accelerating the progression of HF. In vivo, AAV9-shRNA-mediated cardiac myocyte Igfbp7 knockdown indicated that myocardial IGFBP7 directly regulates pathological cardiac remodeling. Moreover, antibody-mediated IGFBP7 neutralization in vivo reversed IGFBP7-induced suppression of FOXO3a, restored DNA repair and ROS detoxification signals and attenuated pressure-overload-induced HF in mice. Consequently, selectively targeting IGFBP7-regulated senescence pathways may have broad therapeutic potential for HF., (© 2022. The Author(s).)

Background: Alterations in atrial metabolism may play a role in the perpetuation of atrial fibrillation (AF). This study sought to compare 18 F-fluorodeoxyglucose (FDG) uptake on PET, in patients with LV dysfunction versus those without AF., Methods: Seventy-two patients who underwent myocardial viability assessment were evaluated. AF patients (36) had persistent or permanent AF based on history and ECG. Patients without AF (36) were matched to AF patients based on sex, diabetes, age, and LVEF. Maximum and mean FDG Standard Uptake Values (SUV) in the left atrial (LA) wall and right atrial (RA) wall were measured. Tissue-to-blood ratios (TBR) were calculated as atrial wall to blood-pool activity. Atrial volumes were measured by echocardiography., Results: Maximum and mean FDG SUV and TBRs were significantly increased in the RA (but not the LA) of patients with AF compared to those without (P < 0.01). When accounting for changes in atrial volume, the presence of AF remained a significant predictor of higher RA MAX , but not RA MEAN FDG uptake., Conclusion: In patients with LV dysfunction from ischemic cardiomyopathy, LA and RA glucose metabolism are differentially altered in those with persistent atrial fibrillation. Further investigations should elucidate the temporal relationship between AF and glucose metabolic changes, as a potential target for therapy., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Functional mitral regurgitation (MR) is an important clinical consideration in patients with heart failure. Transcatheter edge-to-edge repair (TEER) has emerged as a useful therapeutic tool for patients with chronic heart failure, however the role of TEER in patients with cardiogenic shock (CS) and MR has not yet been studied in a randomized trial. The Transcatheter Mitral Valve Repair for Inotrope Dependent Cardiogenic Shock (CAPITAL MINOS) trial was therefore designed to determine if TEER improves clinical outcomes in the CS population., Methods and Design: The CAPITAL MINOS trial is an open-label, multi-center randomized clinical trial comparing TEER to medical therapy in patients with CS and MR. A total of 144 patients with Society for Cardiovascular Angiography and Interventions (SCAI) class C or D CS and at least 3+ MR will be randomized in a 1:1 ratio to TEER or medical therapy alone. The primary outcome will be a composite of in-hospital all-cause mortality, cardiac transplantation, implantation of durable left ventricular assist device, or discharge on palliative inotropic therapy. Patients will be followed for the duration of their index hospitalization for the primary outcome. Secondary outcomes include 6 month mortality., Implications: The CAPITAL MINOS trial will determine whether TEER improves outcomes in patients with CS and MR and will be an important step in optimizing treatment for this high-risk patient population., Competing Interests: Conflict of interest None reported., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: The main objective was to assess the feasibility of conducting a full randomized controlled trial (RCT) to test the effectiveness of the OA Go Away (OGA) behavioural intervention on adherence to prescribed exercise, level of physical activity, goal attainment, and health outcomes, and to determine the acceptability of the OGA. The OGA is an internal reinforcement tool designed to promote exercise adherence for people with hip or knee OA. Method: This 3-month pragmatic pilot RCT included 40 participants with hip or knee OA who were randomized into the treatment group who used the OGA for three months, or standard care. Results: This pilot RCT which included 37 participants (17 in the treatment group and 20 in the control group) showed that it would be feasible to complete a full RCT of the OGA behavioural intervention with adjustments to the format of the OGA (electronic), inclusion criteria, outcome measures and duration. The OGA was felt to be useful (75%) and motivational (82%) by participants. Conclusions: This pilot RCT justifies a formal RCT of the OGA and shows promising results concerning its acceptability, especially if available in an electronic format., (© Canadian Physiotherapy Association.)

Introduction: There is emerging evidence supporting the use of the radial artery (RA) as a preferred secondary conduit for coronary artery bypass grafting (CABG) as it is associated with higher rates of graft patency at 5 years when compared with saphenous vein grafts (SVG). The modified Allen's test (MAT) is traditionally regarded as the standard of care in the assessment of ulnar artery (UA) patency prior to RA harvesting. Unfortunately, due to high false-positive rates, a substantial number of pre-CABG patients are found to have an abnormal MAT despite normal UA patency, resulting in inappropriate exclusion from RA harvesting. The SVG is generally used in its place when this occurs, resulting in potentially lower rates of long-term graft patency., Methods and Analysis: The CAPITAL iRADIAL-CABG trial is currently enrolling participants 18 years of age or older undergoing CABG for whom the treating physician is considering the use of an RA conduit. Eligible patients will be randomised in a 1:1 fashion to MAT or smartphone-based photoplethysmography application assessment to assess collateral palmar circulation prior to RA harvesting. The primary outcome of the trial is the use of the RA as a conduit during CABG. The primary safety outcome is postoperative palmar ischaemia as determined by clinical assessment or requirement of vascular intervention. Secondary outcomes include vascular complications, early graft failure, need for rescue percutaneous coronary intervention during the index hospitalisation and a composite cardiovascular outcome of myocardial infarction, stroke and cardiovascular death prior to discharge from hospital. A total of 236 participants are planned to be recruited., Ethics and Dissemination: The study was approved by the Ottawa Heart Science Network Research Ethics Board (approval number 20180865-01H). The study results will be disseminated via conference presentations and peer-reviewed publications., Trial Registration Number: NCT03810729., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background The randomized DOREMI (Dobutamine Compared to Milrinone) clinical trial evaluated the efficacy and safety of milrinone and dobutamine in patients with cardiogenic shock. Whether the results remain consistent when stratified by acute myocardial infarction remains unknown. In this substudy, we sought to evaluate differences in clinical management and outcomes of acute myocardial infarction complicated by cardiogenic shock (AMICS) versus non-AMICS. Methods and Results Patients in cardiogenic shock (n=192) were randomized 1:1 to dobutamine or milrinone. The primary composite end point in this subgroup analysis was all-cause in-hospital mortality, cardiac arrest, non-fatal myocardial infarction, cerebrovascular accident, the need for mechanical circulatory support, or initiation of renal replacement therapy (RRT) at 30-days. Outcomes were evaluated in patients with (n=65) and without (n=127) AMICS. The primary composite end point was significantly higher in AMICS versus non-AMICS (hazard ratio [HR], 2.21; 95% CI, 1.47-3.30; P =0.0001). The primary end point was driven by increased rates of all-cause mortality, mechanical circulatory support, and RRT. No differences in other secondary outcomes including cardiac arrest or cerebrovascular accident were observed. AMICS remained associated with the primary composite outcome, 30-day mortality, and RRT after adjustment for age, sex, procedural contrast use, multivessel disease, and inotrope type. Conclusions AMI was associated with increased rates of adverse clinical outcomes in cardiogenic shock along with increased rates of mortality and initiation of mechanical circulatory support and RRT. Contrast administration during revascularization likely contributes to increased rates of RRT. Heterogeneity of outcomes in AMICS versus non-AMICS highlights the need to study interventions in specific subgroups of cardiogenic shock. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03207165.

Importance: Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures., Objective: To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest., Design, Setting, and Participants: Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020., Interventions: Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours., Main Outcomes and Measures: The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit., Results: Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively., Conclusions and Relevance: In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference., Trial Registration: ClinicalTrials.gov Identifier: NCT02011568.

Background: We previously demonstrated high diagnostic accuracy of Rubidium-82 positron emission tomography (PET) myocardial blood flow (MBF) quantification for CAV. The purpose of this study was to validate multiparametric PET detection of CAV by combined rate-pressure-product-corrected myocardial flow reserve (cMFR), stress MBF, and coronary vascular resistance (CVR) assessment., Methods and Results: Diagnostic CAV cut-offs of cMFR < 2.9, stress MBF < 2.3, CVR > 55 determined in a previous study (derivation) were assessed in heart transplant recipients referred for coronary angiography and intravascular ultrasound (IVUS) (validation). CAV was defined as International Society of Heart and Lung Transplantation CAV 1-3 on angiography; and maximal intimal thickness ≥ 0.5 mm on IVUS. Eighty patients (derivation n = 40, validation n = 40) were included: 80% male, mean age 54±14 years, 4.5±5.6 years post transplant. The prevalence of CAV was 44% on angiography and 78% on IVUS. Combined PET cMFR < 2.9, stress MBF < 2.3, CVR > 55 CAV assessment yielded high 88% (specificity 75%) and 83% (specificity 40%) sensitivity for ≥ 1 abnormal parameter and high 88% (sensitivity 59%) and 90% (sensitivity 43%) specificity for 3 abnormal parameters, in the derivation and validation cohorts, respectively., Conclusion: We validate the diagnostic accuracy of multiparametric PET flow quantification by cMFR, stress MBF, and CVR for CAV., (© 2020. American Society of Nuclear Cardiology.)

Background: Catheter ablation is an established therapy for atrial fibrillation but is limited by recurrence; efforts have been made to identify biomarkers that predict recurrence. We investigated the effect of baseline NT-proBNP on AF recurrence following catheter ablation in patients randomized to aggressive (< 120/80 mmHg) or standard blood pressure management (< 140/90 mmHg) in the Substrate Modification with Aggressive Blood Pressure Control trial (SMAC-AF)., Methods: The SMAC-AF study included 173 patients resistant or intolerant to at least one class I or III antiarrhythmic drug. We studied the effect of baseline NT-proBNP on the primary outcome of AF recurrence > 3 months post-ablation., Results: Of the 173 patients, 88 were randomized to the aggressive cohort, and 85 into the standard group. The primary outcome occurred in 61.4% of those in the aggressive arm, versus 61.2% in the standard arm. In the aggressive group, logNT-proBNP predicted recurrence (HR 1.28, p = 0.04, adjusted HR 1.43, p = 0.03), while in the standard cohort, it did not (HR 0.94, p = 0.62, adjusted HR 0.83, p = 0.22). NT-proBNP ≥ 280 pg/mL also predicted occurrence in the aggressive (HR 1.98, p = 0.02) but not the standard cohort (HR 1.00, p = 1.00)., Conclusion: We conclude that pre-ablation NT-proBNP may be useful in predicting recurrence in hypertensive patients and identifying patients who benefit from aggressive blood control and upstream therapies., Trial Registration: NCT00438113, registered February 21, 2007., (© 2021. The Author(s).)

Background: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS., Methods: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters., Results: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization., Conclusions: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165., (© 2021. The Author(s).)