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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]

Background: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown., Methods: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin., Results: Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P <0.03) but attenuated, relative to controls (4.80±0.63; P =0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort ( P <0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P <0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P <0.05, all comparisons)., Conclusions: Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis., Competing Interests: None.

Electro-mechanical noise from the interaction of multiple coronary wires can inhibit pacing with a risk of asystole in pacemaker-dependent patients. Awareness of this phenomenon is important to guide prompt management with adjustment of device sensitivity, asynchronous pacing, removal of a coronary wire or insertion of a temporary pacing system., Competing Interests: Authors declare no conflict of interests for this article., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

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.)

Background: The prognostic significance of Q waves and T-wave inversions (TWI) combined and separately in STEMI patients undergoing primary PCI has not been well established in previous studies., Methods: We included 7,831 patients from the TOTAL trial and divided the patients into categories based on Q waves and TWIs in the presenting ECG. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock or new or worsening NYHA class IV heart failure within one year. The study evaluated the effect of Q waves and TWI on the risk of primary outcome and all-cause death, and whether patient benefit of aspiration thrombectomy differed between the ECG categories., Results: Patients with Q+TWI+ (Q wave and TWI) pattern had higher risk of primary outcome compared to patients with Q-TWI- pattern [33 (10.5%) vs. 221 (4.2%); adjusted hazard ratio (aHR) 2.10; 95% CI, 1.45-3.04; p<0.001] within 40-days' period. When analyzed separately, patients with Q waves had a higher risk for the primary outcome compared to patients with no Q waves in the first 40 days [aHR 1.80; 95% CI, 1.48-2.19; p<0.001] but there was no additive risk after 40 days. Patients with TWI had a higher risk for primary outcome only after 40 days when compared to patients with no TWI [aHR 1.63; 95% CI, 1.04-2.55; p=0.033]. There was a trend towards a benefit of thrombectomy in patients with the Q+TWI+ pattern., Conclusions: Q waves and TWI combined (Q+TWI+ pattern) in the presenting ECG is associated with unfavourable outcome within 40-days. Q waves tend to affect short-term outcome, while TWI has more effect on long-term outcome., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: In-stent restenosis (ISR) is the most common cause of stent failure. Although the rate of ISR is significantly lower with contemporary drug-eluting stents (DES), it remains a challenging clinical entity to treat., Recent Findings: In this review, we focus on a practical approach to management of DES ISR with intravascular imaging at its core, as supported by several recently published articles. This facilitates assessment of the underlying mechanism(s) essential to the successful treatment of ISR allowing for a tailored selection of treatment modalities., Summary: The successful treatment of DES ISR requires identification of the causative mechanism(s). Individualized treatment may include high-pressure balloon angioplasty alone, cutting or scoring balloons, intravascular lithotripsy, atheroablative therapies and a selection of either repeat DES implantation or drug-coated balloon treatment., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking., Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves., Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days., Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave., Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization., Competing Interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Ms Behrouzi has received research grant support to her institutions from Boehringer Ingelheim, Lilly, and Sanofi-Aventis, outside the submitted work. Dr Farkouh has received research grants from Amgen, Novartis, and Novo Nordisk, outside the submitted work. Dr Goodman reports research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from: Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, 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 Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, TIMI Study Group (Brigham Health). Dr Udell has received research grant support to his institutions from AstraZeneca, Novartis, and Sanofi; reported service as a consultant for Amgen, Boehringer Ingelheim, Janssen, Merck, Novartis, Novavax, and Sanofi; and received honoraria from Boehringer Ingelheim and Janssen outside the submitted work. No other disclosures were reported. This study received funding from a 10.13039/501100000024Canadian Institutes for Health Research (CIHR) Strategy for Patient-Oriented Research Innovative Clinical Trial Multi-year grant (MYG-151211), a Ted Rogers Centre for Heart Research Innovation Fund - COVID-19 Award, and in part by the Peter Munk Cardiac Centre Innovation Fund. Ms Behrouzi is supported by a 10.13039/501100000024CIHR Canada Graduate Scholarship – Doctoral (CGS D) award, a 10.13039/501100003579University of Toronto MD/PhD studentship, and a Ted Rogers Centre for Heart Research Doctoral Award. Dr Atzema is supported by Mid-Career Investigator Awards from the 10.13039/100004411Heart and Stroke Foundation, Sunnybrook Health Sciences Centre, and 10.13039/100012665ICES. Dr Kapral holds the Lillian Love Chair in Women’s Health from the University Health Network/University of Toronto. Dr Kaul holds a CIHR Sex and Gender Science Chair and a Heart and Stroke Foundation Chair in Cardiovascular Research. Dr Goodman was supported by the 10.13039/100004411Heart and Stroke Foundation of Ontario/10.13039/501100003579University of Toronto Polo Chair. Dr Austin is supported by a Mid-Career Investigator Award from the 10.13039/100004411Heart and Stroke Foundation. Dr McAlister holds the Alberta Health Services Chair in Cardiovascular Outcomes Research. Dr Lee is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. Dr Udell is supported by a 10.13039/100013873Government of Ontario Early Researcher Award (ER15-11-037), a Clinician Scientist Merit Award, Department of Medicine, University of Toronto, Peter Munk Cardiac Centre, Women’s College Research Institute and Department of Medicine, Women’s College Hospital. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical outcomes after STEMI has not been clearly investigated., Objectives: The aim of this study was to assess the sex-related differences in TB and its clinical implications in patients with STEMI., Methods: Individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration were analyzed, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year., Results: Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death: 1.52; 95% CI: 1.10-2.12; P = 0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, the risk for 1-year CV death was higher only in women with HTB (HR: 1.23; 95% CI: 1.18-1.28; P < 0.001), who also had an increased risk for all-cause death and ST than men., Conclusions: In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for ST, CV, and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB., Competing Interests: Funding Support and Author Disclosures Dr Manzi has received a research grant from the European Society of Cardiology during the conduct of this study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)