Myocardial flow reserve recovery in patients with Takotsubo syndrome: insights from positron emission tomography.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been implicated in the pathogenesis of Takotsubo syndrome (TTS). Positron emission tomography (PET) plays a key role in the assessment of CMD through myocardial flow reserve (MFR). However, there is limited information on the temporal progression of MFR and its relationship to coronary artery disease (CAD) in TTS patients. METHODS: This study evaluated patients with TTS who underwent cardiac catheterization and PET within one year of hospitalization. Patients were categorized into acute (≤10 days), subacute (11-30 days), and chronic (≥31 days) stages based on post-onset time of PET assessment. MFR values and prevalence of abnormal MFR (<2.0) were compared between stages. Temporal MFR changes in patients with obstructive CAD (≥70% stenosis by coronary angiography), non-obstructive CAD, and normal coronaries were compared. RESULTS: Of the 88 patients studied (mean age 70; 96% female), 52 (59%) were in the acute, 17 (19%) in the subacute, and 19 (22%) in the chronic stage. Median MFR in the acute stage was 2.0 (1.5-2.3), with 58% of patients showing abnormal MFR. A significant time-dependent improvement in MFR was observed (p=0.002), accompanied by a decreased prevalence of abnormal MFR (p=0.016). While patients with normal coronaries showed significant MFR improvement over time (p=0.045), patients with obstructive or non-obstructive CAD demonstrated no improvement across three stages (p=0.346 and 0.174, respectively). CONCLUSIONS: PET-derived MFR was impaired in TTS patients during the acute phase, with improvement suggesting potential recovery from CMD over time. The concurrent presence of obstructive CAD might impede this recovery process.

RAFF-5 Study to Improve the Quality and Safety of Care for Patients Seen in the Emergency Department With Acute Atrial Fibrillation and Flutter.

BACKGROUND: We sought to improve the immediate and subsequent care of emergency department (ED) patients with acute atrial fibrillation (AF) and flutter (AFL) by implementing the principles of the Canadian Association of Emergency Physicians AF/AFL Best Practices Checklist. METHODS: This cohort study included 3 periods: before (7 months), intervention introduction (1 month), and after (7 months), and was conducted at a major academic centre. We included patients who presented with an episode of acute AF or AFL and used multiple strategies to support ED adoption of the Canadian Association of Emergency Physicians checklist. We developed new cardiology rapid-access follow-up processes. The main outcomes were unsafe and suboptimal treatments in the ED. RESULTS: We included 1108 patient visits, with 559 in the before and 549 in the after period. In a comparison of the periods, there was an increase in use of chemical cardioversion (20.6% vs 25.0%; absolute difference [AD], 4.4%) and in electrical cardioversion (39.2% vs 51.2%; AD, 12.0%). More patients were discharged with sinus rhythm restored (66.9% vs 75.0%; AD, 8.1%). The proportion seen in a follow-up cardiology clinic increased from 24.2% to 39.9% (AD, 15.7%) and the mean time until seen decreased substantially (103.3 vs 49.0 days; AD, -54.3 days). There were very few unsafe cases (0.4% vs 0.7%) and, although there was an increase in suboptimal care (19.5% vs 23.1%), overall patient outcomes were excellent. CONCLUSIONS: We successfully improved the care for ED patients with acute AF/AFL and achieved more frequent and more rapid cardiology follow-up. Although cases of unsafe management were uncommon and patient outcomes were excellent, there are opportunities for physicians to improve their care of acute AF/AFL patients. GOV IDENTIFIER: NCT05468281.

Machine and deep learning models for accurate detection of ischemia and scar with myocardial blood flow positron emission tomography imaging.

BACKGROUND: Quantification of myocardial blood flow (MBF) is used for the noninvasive diagnosis of patients with coronary artery disease (CAD). This study compared traditional statistics, machine learning, and deep learning techniques in their ability to diagnose disease using only the rest and stress MBF values. METHODS: This study included 3245 rest and stress rubidium-82 positron emission tomography (PET) studies and matching diagnostic labels from perfusion reports. Standard logistic regression, lasso logistic regression, support vector machine, random forest, multilayer perceptron, and dense U-Net were compared for per-patient detection and per-vessel localization of scars and ischemia. RESULTS: Receiver-operator characteristic area under the curve (AUC) of machine learning models was significantly higher than those of traditional statistics models for per-patient detection of disease (0.92-0.95 vs. 0.87) but not for per-vessel localization of ischemia or scar. Random forest showed the highest AUC = 0.95 among the different models compared. On the final hold-out set for generalizability, random forest showed an AUC of 0.92 for detection and 0.89 for localization of perfusion abnormalities. CONCLUSIONS: For per-vessel localization, simple models trained on segmental data performed similarly to a convolutional neural network trained on polar-map data, highlighting the need to justify the use of complex predictive algorithms through comparison with simpler methods.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW.

OBJECTIVES: The objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). BACKGROUND: 15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. METHODS: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. CONCLUSIONS: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. CLINICAL TRIAL REGISTRATION INFORMATION: Clinical-Trials.gov (#NCT05134012).

The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE: The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN: CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION: Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER: NCT04181996.

Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy.

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/mm2 (95% CI: -6 to 79 capillaries/mm2). 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).

Flurpiridaz F-18 PET Myocardial Perfusion Imaging in Patients With Suspected Coronary Artery Disease.

BACKGROUND: Flurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. OBJECTIVES: The purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). METHODS: In this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. RESULTS: A total of 578 patients (age 63.7 ± 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index ≥30 kg/m2, and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flurpiridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated. CONCLUSIONS: This second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273).

Sex Differences in Systemic and Coronary Arterial Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) predominantly affects females. Systemic and coronary arterial abnormalities are present in HFpEF and may contribute to HFpEF in females. We performed a cross-sectional study of 32 participants with HFpEF and 26 controls. Arterial hemodynamics were noninvasively assessed by combining arterial tonometry with echocardiography. Coronary microvascular function was assessed by rubidium-82 positron emission tomography as the myocardial flow reserve. Coronary vascular resistance (CVR) at rest and vasodilator stress were calculated using positron emission tomography. CVR reserve was calculated as stress - rest CVR. Multivariable linear regression assessed the associations of female sex with arterial hemodynamics in participants with and without HF, and the association of HF with arterial hemodynamics within each sex stratum. Demographics and left ventricular systolic and diastolic function were similar between males and females. Among those with HFpEF, females had a higher steady and pulsatile arterial load and more impaired (less negative) CVR reserve than males. Conversely, in controls, females had similar hemodynamics to males. We then divided the sample based on sex. Femaleswith HFpEF had a higher pulsatile arterial load and higher stress CVR than control females. Among males, arterial hemodynamics were similar, regardless of HFpEF status. The measures of early pulsatile arterial load were independently associated with higher E/e' and lower myocardial flow reserve in females only. In conclusion, despite similar left ventricular function between sexes, older females with HFpEF are characterized by additional systemic and coronary arterial hemodynamic abnormalities compared with males with HFpEF and similarly aged females without HFpEF.

Pharmacological and metabolic parameters of [18F]flubrobenguane in clinical imaging populations.

BACKGROUND: Cardiac sympathetic nervous system molecular imaging has demonstrated prognostic value. Compared with meta-[11C]hydroxyephedrine, [18F]flubrobenguane (FBBG) facilitates reliable estimation of SNS innervation using similar analytical methods and possesses a more convenient physical half-life. The aim of this study was to evaluate pharmacokinetic and metabolic properties of FBBG in target clinical cohorts. METHODS: Blood sampling was performed on 20 participants concurrent to FBBG PET imaging (healthy = NORM, non-ischemic cardiomyopathy = NICM, ischemic cardiomyopathy = ICM, post-traumatic stress disorder = PTSD). Image-derived blood time-activity curves were transformed to plasma input functions using cohort-specific corrections for plasma protein binding, plasma-to-whole blood distribution, and metabolism. RESULTS: The plasma-to-whole blood ratio was 0.78 ± 0.06 for NORM, 0.64 ± 0.06 for PTSD and 0.60 ± 0.14 for (N)ICM after 20 minutes. 22 ± 4% of FBBG was bound to plasma proteins. Metabolism of FBBG in (N)ICM was delayed, with a parent fraction of 0.71 ± 0.05 at 10 minutes post-injection compared to 0.53 ± 0.03 for PTSD/NORM. While there were variations in metabolic rate, metabolite-corrected plasma input functions were similar across all cohorts. CONCLUSIONS: Rapid plasma clearance of FBBG limits the impact of disease-specific corrections of the blood input function for tracer kinetic modeling.

Incidence of Atrial Fibrillation as the Initial Manifestation of Cardiac Sarcoidosis: Insights From a Catheter Ablation Registry.

Background: Cardiac sarcoidosis (CS) is a rare form of arrhythmogenic cardiomyopathy; a delayed diagnosis can lead to significant consequences. Patients with clinically manifest CS often have minimal extracardiac involvement and thus frequently present initially to cardiology. Indeed, certain specific arrhythmic scenarios should trigger investigations for undiagnosed CS. Atrial fibrillation (AF) has been described as one of the presenting features of CS; however, the incidence of this presentation is not known. Methods: At our institution, cardiac computerized tomography is routinely performed prior to catheter ablation for AF. Noncardiac incidental findings are described by radiologists and are followed-up by interval investigations. We systematically reviewed noncardiac reports from 1574 consecutive patients in our prospective AF ablation registry. Specifically, we used text-scraping techniques to search on the following keywords: "adenopathy" and "sarcoidosis." Detailed chart review of identified cases was then performed to evaluate results of interval investigations and assess long-term outcomes. Results: Twenty of 1574 patients (1.3%) had noncardiac reports containing "adenopathy" and/or "sarcoidosis." After interval imaging and a follow-up period averaging 60 ± 35 months, only 2 patients of 1574 (0.13%) were diagnosed with CS. Four of 20 (20%) had a previous history of extracardiac sarcoidosis, and another 1 of 20 (5%) was subsequently diagnosed with extracardiac sarcoidosis. However, none of these 5 patients had evidence of cardiac involvement. Conclusions: CS is a rare finding among patients undergoing a first-time AF ablation. Our findings suggest that AF is an uncommon initial presentation of CS. Thus, investigations for CS in patients with AF are not warranted routinely, unless additional suggestive clinical features are present.

Contexte: La sarcoïdose cardiaque (SC) est une forme rare de cardiomyopathie arythmogène; un retard dans le diagnostic peut entraîner d'importantes conséquences. Les patients qui présentent une SC cliniquement manifeste ont souvent une atteinte extracardiaque minime, et consultent donc souvent d'abord en cardiologie. En effet, certains scénarios arythmiques précis devraient déclencher la recherche de signes d'une SC non diagnostiquée. La fibrillation auriculaire (FA) a été décrite comme un signe indicateur de SC; on ne connaît toutefois pas l'incidence de ce signe. Méthodologie: Dans notre établissement, la tomodensitométrie cardiaque est souvent réalisée avant une ablation par cathéter de la FA. Les découvertes non cardiaques fortuites sont décrites par les radiologues, puis font l'objet d'un suivi par des examens d'imagerie réalisés à intervalles déterminés. Nous avons systématiquement évalué les éléments non cardiaques signalés chez 1 574 patients consécutifs dans notre registre prospectif sur l'ablation de la FA. Nous avons utilisé des techniques de dépouillement du texte pour trouver les mots-clés suivants : « adenopathy ¼ (adénopathie) et « sarcoidosis ¼ (sarcoïdose). Un examen du dossier médical complet des cas retenus a été réalisé pour évaluer les résultats des examens de suivi et évaluer les résultats à long terme. Résultats: Parmi les 1 574 patients, 20 (1,3 %) présentaient des notes non cardiaques contenant les termes « adenopahy ¼ (adénopathie) ou « sarcoidosis ¼ (sarcoïdose). Après l'examen d'imagerie et une période de suivi d'une durée moyenne de 60 ±35 mois, seuls deux patients (0,13 %) ont reçu un diagnostic de SC. Quatre des 20 patients visés (20 %) présentaient des antécédents de sarcoïdose extracardiaque, et un patient sur 20 (5 %) a reçu un diagnostic de sarcoïdose extracardiaque à la suite de l'intervention. Toutefois, aucun de ces cinq patients ne montrait de signes d'atteinte cardiaque. Conclusions: La SC est une occurrence rare chez les patients qui subissent une première ablation de la FA. Nos constats indiquent que la FA est une présentation initiale peu commune de la SC. Aussi, la recherche de la SC chez les patients atteints de FA n'est pas justifiée dans une procédure de routine, à moins que d'autres caractéristiques cliniques pointant vers cette affection ne soient présentes.

Cost-Effectiveness of Colchicine for Recurrent Cardiovascular Events.

Background: Colchicine is an anti-inflammatory therapy with a low associated cost that has been shown in 2 large studies to reduce cardiovascular (CV) events, but its use is associated with side effects. The main objective for this analysis is to determine whether colchicine therapy is cost-effective for the prevention of recurrent CV events in patients who have suffered a myocardial infarction (MI). Methods: A decision model was developed to estimate the healthcare costs in Canadian dollars and the clinical outcomes among patients who have suffered an MI and are treated with colchicine. Probabilistic Markov modelling was used in combination with Monte Carlo simulation to derive expected lifetime costs and quality-adjusted life-years, which permitted the calculation of incremental cost-effectiveness ratios. Models were derived for both short-term (20 months) and long-term (lifelong) colchicine use in this population. Results: Long-term colchicine use was dominant over standard of care, with lower average lifetime costs per patient (CAD$91,552.80 vs $97,085.84) and a higher average number of quality-adjusted life-years per patient (19.92 vs 19.80). Short-term colchicine use also dominated over standard of care. Results were consistent over a range of scenario analyses. Conclusions: Based on 2 large randomized controlled trials, treatment of patients post-MI with colchicine appears cost-effective, compared to the standard of care at the current price. Based on these studies and currently accepted willingness-to-pay thresholds in Canada, healthcare payers could consider funding long-term colchicine therapy for CV secondary prevention while we await results from ongoing trials.

Contexte: La colchicine est un traitement anti-inflammatoire peu coûteux qui, selon deux grandes études, réduit le taux d'événements cardiovasculaires (CV), mais son utilisation est également associée à des effets secondaires. L'objectif principal de cette analyse était de déterminer si le traitement par la colchicine présente un rapport coût-efficacité intéressant en prévention des événements CV récurrents chez les patients ayant subi un infarctus du myocarde (IM). Méthodologie: Un modèle décisionnel a été mis au point pour estimer les coûts des soins de santé en dollars canadiens et les issues cli-niques chez les patients qui ont subi un IM et qui sont traités par la colchicine. Un modèle probabiliste de Markov a été utilisé en association avec une simulation de Monte-Carlo pour obtenir le coût attendu pendant la vie et le nombre d'années de vie ajustées en fonction de la qualité, données qui ont permis de calculer les rapports coût-efficacité différentiels. Les modèles ont été adaptés pour l'utilisation de la colchicine à court terme (20 mois) et à long terme (à vie) dans la même population. Résultats: L'utilisation de colchicine à long terme donnait de meilleurs résultats que le traitement de référence, avec un coût moyen à vie par patient plus faible (91 552,80 $ CA c. 97 085,84 $ CA) et un plus grand nombre moyen d'années de vie ajustées selon la qualité (19,92 c. 19,80). L'utilisation à court terme de la colchicine donnait aussi de meilleurs résultats que le traitement de référence. Ces résultats ont été observés pour un éventail de scénarios analysés. Conclusions: Selon deux grands essais randomisés contrôlés, le traitement par la colchicine des patients ayant subi un IM semble avoir un meilleur rapport coût-efficacité que le traitement de référence en fonction des coûts actuels. Selon ces études et les seuils de propension à payer actuellement acceptés au Canada, les payeurs pourraient envisager de financer le traitement à long terme par la colchicine en prévention d'événements CV secondaires, jusqu'à l'obtention des résultats des essais en cours.

Fibrotic Plaque and Microvascular Dysfunction Predict Early Cardiac Allograft Vasculopathy Progression After Heart Transplantation: The Early Post Transplant Cardiac Allograft Vasculopathy Study.

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 mm3/mm), percentage intimal volume increased 44% (4.6%), vessel volume decreased 4% (-0.50 mm3/mm) and lumen volume decreased 9% (-1.02 mm3/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.

Exponential dosing to standardize myocardial perfusion image quality with rubidium-82 PET.

BACKGROUND: 82Rb PET is commonly performed using the same injected activity in all patients, resulting in lower image quality in larger patients. This study compared 82Rb dosing with exponential vs proportional functions of body weight on the standardization of myocardial perfusion image (MPI) quality. METHODS: Two sequential cohorts of N = 60 patients were matched by patient weight. Rest and dipyridamole stress 82Rb PET was performed using 0.1 MBq·kg-2 exponential and 9 MBq·kg-1 proportional dosing. MPI scans were compared qualitatively with visual image quality scoring (IQS) and quantitatively using the myocardium-to-blood contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as a function of body weight. RESULTS: Average (min-max) patient body weight was 81 ± 18 kg (46-137 kg). Proportional dosing resulted in decreasing CNR, SNR, and visual IQS with increasing body weight (P < 0.05). Exponential dosing eliminated the weight-dependent decreases in these image quality metrics that were observed in the proportional dosing group. CONCLUSION: 82Rb PET dosing as an exponential (squared) function of body weight produced consistent stress perfusion image quality over a wide range of patient weights. Dramatically lower doses can be used in lighter patients, with the equivalent population dose shifted toward the heavier patients to standardize diagnostic image quality.