Anti-inflammatory effect of biologic therapy in patients with psoriatic disease: A prospective cohort FDG PET study.

AIM: The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by 82Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3). METHODS AND RESULTS: Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBRmax) was measured to assess vascular inflammation. 82Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBRmax: - .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBRmax: .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response. CONCLUSION: In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.

Anti-inflammatory effect of rosuvastatin in patients with HIV infection: An FDG-PET pilot study.

AIMS: This study aimed to evaluate markers of systemic as well as imaging markers of inflammation in the ascending aorta, bone marrow, and spleen measured by 18F-FDG PET/CT, in HIV+ patients at baseline and following therapy with rosuvastatin. METHODS AND RESULTS: Of the 35 HIV+ patients enrolled, 17 were randomized to treatment with 10 mg/day rosuvastatin and 18 to usual care for 6 months. An HIV- control cohort was selected for baseline comparison of serum inflammatory markers and monocyte markers of inflammation. 18F-FDG-PET/CT imaging of bone marrow, spleen, and thoracic aorta was performed in the HIV+ cohort at baseline and 6 months. While CD14++CD16- and CCR2 expressions were reduced, serum levels of IL-7, IL-8, and MCP-1 were elevated in the HIV+ population compared to the controls. There was a significant drop in FDG uptake in the bone marrow (TBRmax), spleen (SUVmax) and thoracic aortic (TBRmax) in the statin-treated group compared to the control group (bone marrow: - 10.3 ± 16.9% versus 5.0 ± 18.9%, p = .0262; spleen: - 9.8 ± 20.3% versus 11.3 ± 28.8%, p = .0497; thoracic aorta: - 19.1 ± 24.2% versus 4.3 ± 15.4%, p = .003). CONCLUSIONS: HIV+ patients had significantly markers of systemic inflammation including monocyte activation. Treatment with low-dose rosuvastatin in the HIV+ cohort significantly reduced bone marrow, spleen and thoracic aortic FDG uptake.

Radiolabeled Thioflavin-T Derivative PET Imaging for the Assessment of Cardiac Amyloidosis.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) is an often under-recognized cause of heart failure with preserved ejection fraction. The goal of the current paper was to review imaging modalities available for detecting cardiac amyloidosis. We wished to determine what modalities are available for the diagnosis of cardiac amyloidosis and what modalities could be utilized in the future. RECENT FINDINGS: Early and delayed planar imaging of the chest currently plays a central role in the workup and diagnosis of CA. However, novel positron emission tomography (PET) tracers could play a large role in CA imaging in the future. There is an increasing body of literature supporting the use of targeted amyloid-binding PET radiotracers such as 11C-Pittsburgh compound B (11C-PIB), 18F-florbetapir, -flutemetamol, and -florbetaben for the detection of cardiac amyloid. While planar imaging currently plays a large role in the workup of CA, PET imaging could play an increasing important role in the future. The quantitative abilities of novel PET tracers could theoretically allow for the serial monitoring of patients and detection of response to therapy, and the sensitive nature of the tracers could allow for even earlier disease detection. Further work with large randomized controlled trial data is needed in the development and validation of PET tracers for cardiac amyloid and represents an exciting development within the realm of nuclear cardiology.

Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.

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.

Association between prehospital arterial hypercapnia and mortality in acute heart failure: a retrospective cohort study.

BACKGROUND: Acute Heart Failure (AHF) is a potentially lethal pathology and is often encountered in the prehospital setting. Although an association between prehospital arterial hypercapnia in AHF patients and admission in high-dependency and intensive care units has been previously described, there is little data to support an association between prehospital arterial hypercapnia and mortality in this population. METHODS: This was a retrospective study based on electronically recorded prehospital medical files. All adult patients with AHF were included. Records lacking arterial blood gas data were excluded. Other exclusion criteria included the presence of a potentially confounding diagnosis, prehospital cardiac arrest, and inter-hospital transfers. Hypercapnia was defined as a PaCO2 higher than 6.0 kPa. The primary outcome was in-hospital mortality, and secondary outcomes were 7-day mortality and emergency room length of stay (ER LOS). Univariable and multivariable logistic regression models were used. RESULTS: We included 225 patients in the analysis. Prehospital hypercapnia was found in 132 (58.7%) patients. In-hospital mortality was higher in patients with hypercapnia (17.4% [23/132] versus 6.5% [6/93], p = 0.016), with a crude odds-ratio of 3.06 (95%CI 1.19-7.85). After adjustment for pre-specified covariates, the adjusted OR was 3.18 (95%CI 1.22-8.26). The overall 7-day mortality was also higher in hypercapnic patients (13.6% versus 5.5%, p = 0.044), and ER LOS was shorter in this population (5.6 h versus 7.1 h, p = 0.018). CONCLUSION: Prehospital hypercapnia is associated with an increase in in-hospital and 7-day mortality in patient with AHF.

The echocardiographic assessment of the right ventricle in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared with athletes and matched controls.

BACKGROUND: There are discrepancies in the quantitative echocardiographic criteria for the right ventricle (RV) between the revised task force criteria (TFC) for Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) and the guidelines for RV assessment endorsed by American Society of Echocardiography (ASE). Importantly, these criteria do not take into account potential adaptation of the RV to exercise. The goal of this study was to compare the revised TFC quantitative echocardiographic parameters in patients with ARVC/D, athletes and matched controls. METHODS: Echocardiographic parameters of the RV were retrospectively collected in patients who fulfilled the TFC for ARVC/D, an age- matched, sex-matched, and body surface area-matched control population, and athletes (defined as individuals who exercised for more than 7 hours per week). Patients with structural heart disease were excluded in the control and athlete groups. RESULTS: Twenty patients with ARVC/D, 11 athletes and 20 matched controls were included. There was no significant difference between ARVC/D patients and athletes with the exception of the parasternal long axis right ventricular outflow tract diameter. All parameters were significantly different between ARVC/D patients and the control group. Furthermore, when subjects were categorized into meeting 1 major revised TFC/abnormal ASE criteria or not, only ASE criteria were able to differentiate ARVC/D from control population. Both were unable to differentiate ARVC/D from athletes. CONCLUSIONS: Right ventricle quantitative echocardiographic criteria in the revised TFC are not specific for ARVC/D. Care should be taken in applying these criteria in athletes.

Right Heart Function During and After Community-Acquired Pneumonia in Adults.

BACKGROUND: New-onset or worsening heart failure is the most common extra-pulmonary complication of community-acquired pneumonia (CAP) during the first 30 days after diagnosis. METHODS: We evaluated the changes in the right ventricular function amongst adult CAP survivors from the time of acute infection to its resolution. We performed comprehensive transthoracic echocardiographic examinations to assess right heart function during the acute illness and the convalescent period (4 to 6 weeks after hospital discharge). RESULTS: Twenty-six patients underwent acute measurements, of which convalescent measurements were completed in 19 subjects. There was no significant change in any of the right heart function parameters from the acute to convalescent stage of CAP. CONCLUSIONS: Our results suggest that right ventricular function does not meaningfully change in the transition from the acute to convalescent stage of CAP in non-critically ill adult CAP survivors.

Infective Endocarditis: The role of PET imaging in diagnosis and management.

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) has recently emerged as an increasingly used alternative and supplementary imaging modality for the diagnosis of infective endocarditis. 18F-FDG PET/CT imaging for IE is given a Class I recommendation (level of evidence B) and is therefore recommended in cases of possible prosthetic valve IE to both detect valvular lesions, as well as confirm the diagnosis of IE. They have also given a class I recommendation (level of evidence B) for brain and whole-body 18F-FDG PET/CT and/or MRI imaging to detect peripheral lesions for patients with either native or prosthetic valve IE. Molecular imaging is playing an increasingly important role in the diagnosis and management of patients with IE. The important role of 18F-FDG PET/CT imaging has been acknowledged by recent guideline updates. These advanced imaging tests are not supplanting the role of echocardiography in the diagnostic pathway for IE. Rather, they are additional tools that are available where the diagnosis is complicated, difficult, or uncertain.

Canadian Cardiovascular Society/Canadian Women's Heart Health Alliance Clinical Practice Update on Myocardial Infarction With No Obstructive Coronary Artery Disease (MINOCA).

Myocardial infarction with no obstructive coronary artery disease (MINOCA) represents 6%-15% of all acute coronary syndromes, and women are disproportionately represented. MINOCA is an encompassing preliminary diagnosis, and emerging evidence supports a more expansive comprehensive diagnostic and therapeutic clinical approach. The current clinical practice update summarizes the latest evidence regarding the epidemiology, clinical presentation, and diagnostic evaluation of MINOCA. A cascaded approach to diagnostic workup is outlined for clinicians, for noninvasive and invasive diagnostic pathways, depending on clinical setting and local availability of diagnostic modalities. Evidence concerning the nonpharmacological and pharmacological treatment of MINOCA are presented and summarized according to underlying cause of MINOCA, with practical tips on the basis of expert opinion, outlining a real-life, evidence-based, comprehensive approach to management of this challenging condition.

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.

Aortic Stenosis Progression: A Systematic Review and Meta-Analysis.

BACKGROUND: Aortic valve stenosis is a progressive disorder with variable progression rates. The factors affecting aortic stenosis (AS) progression remain largely unknown. OBJECTIVES: This systematic review and meta-analysis sought to determine AS progression rates and to assess the impact of baseline AS severity and sex on disease progression. METHODS: The authors searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 1, 2020, for prospective studies evaluating the progression of AS with the use of echocardiography (mean gradient [MG], peak velocity [PV], peak gradient [PG], or aortic valve area [AVA]) or computed tomography (calcium score [AVC]). Random-effects meta-analysis was performed to evaluate the rate of AS progression for each parameter stratified by baseline severity, and meta-regression was performed to determine the impact of baseline severity and of sex on AS progression rate. RESULTS: A total of 24 studies including 5,450 patients (40% female) met inclusion criteria. The pooled annualized progression of MG was +4.10 mm Hg (95% CI: 2.80-5.41 mm Hg), AVA -0.08 cm2 (95% CI: 0.06-0.10 cm2), PV +0.19 m/s (95% CI: 0.13-0.24 m/s), PG +7.86 mm Hg (95% CI: 4.98-10.75 mm Hg), and AVC +158.5 AU (95% CI: 55.0-261.9 AU). Increasing baseline severity of AS was predictive of higher rates of progression for MG (P < 0.001), PV (P = 0.001), and AVC (P < 0.001), but not AVA (P = 0.34) or PG (P = 0.21). Only 4 studies reported AS progression stratified by sex, with only PV and AVC having 3 studies to perform a meta-analysis. No difference between sex was observed for PV (P = 0.397) or AVC (P = 0.572), but the level of confidence was low. CONCLUSIONS: This study provides progression rates for both hemodynamic and anatomic parameters of AS and shows that increasing hemodynamic and anatomic baseline severity is associated with faster AS progression. More studies are needed to determine if sex differences affect AS progression. (Aortic Valve Stenosis Progression Rate: A Systematic Review and Meta-Analysis; CRD42021207726).

Influence of preoperative frailty on quality of life after cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Frailty has emerged as an important prognostic marker of increased mortality after cardiac surgery, but its association with quality of life (QoL) and patient-centered outcomes is not fully understood. We sought to evaluate the association between frailty and such outcomes in older patients undergoing cardiac surgery. METHODS: This systematic review included studies evaluating the effect of preoperative frailty on QoL outcomes after cardiac surgery amongst patients 65 years and older. The primary outcome was patient's perceived change in QoL following cardiac surgery. Secondary outcomes included residing in a long-term care facility for 1 year, readmission in the year following the intervention, and discharge destination. Screening, inclusion, data extraction, and quality assessment were performed independently by two reviewers. Meta-analyses based on the random-effects model were conducted. The evidential quality of findings was assessed with the GRADE profiler. RESULTS: After the identification of 3105 studies, 10 observational studies were included (1580 patients) in the analysis. Two studies reported on the change in QoL following cardiac surgery, which was higher for patients with frailty than for patients without. Preoperative frailty was associated with both hospital readmission (pooled odds ratio [OR] 1.48 [0.80-2.74], low GRADE level) as well as non-home discharge (pooled OR 3.02 [1.57-5.82], moderate GRADE level). CONCLUSION: While evidence in this field is limited by heterogeneity of frailty assessment and non-randomized data, we demonstrated that baseline frailty may possibly be associated with improved QoL, but with increased readmission as well as discharge to a non-home destination following cardiac surgery. These patient-centered outcomes are important factors when considering interventional options for older patients. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).

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.

Cost-Effectiveness of Canakinumab From a Canadian Perspective for Recurrent Cardiovascular Events.

Background: Cardiovascular (CV) disease is a condition with high levels of morbidity and mortality. Canakinumab is a novel monoclonal antibody therapy that has been shown to reduce CV events but is associated with side effects and high cost. The main objective for this analysis is to determine whether canakinumab use is cost-effective for the prevention of recurrent CV events. Methods: A decision model was developed to estimate the direct costs and outcomes among patients who have suffered a myocardial infarction and are treated with canakinumab. A lifetime study horizon was used to analyze the base-case costs and utilities from the perspective of the Canadian publicly funded healthcare system. Markov modeling was used in combination with Monte Carlo simulation to derive expected values for costs and quality-adjusted life years (QALYs), permitting the calculation of incremental cost-effectiveness ratios. Results: Canakinumab was associated with higher average lifetime costs per patient ($457,982 vs $82,565) and higher average QALYs per patient (14.90 vs 14.20), compared with standard of care. Thus, the incremental cost per QALY gained for canakinumab treatment vs standard-of-care therapy was $535,365. The probability that canakinumab treatment is cost-effective was 0%. Results were consistent over a range of scenario analyses. Conclusions: Treatment of patients post-myocardial infarction with canakinumab is not cost-effective, compared with standard-of-care therapy at the current price. Based on currently accepted willingness-to-pay thresholds in Canada, a reduction in price of 91% is required to yield a cost per patient that would be considered appropriate.

Introduction: La maladie cardiovasculaire (CV) est une affection à forts taux de morbidité et de mortalité. Le canakinumab est un nouveau traitement par anticorps monoclonaux qui s'est avéré diminuer les événements CV, mais qui est associé à des effets secondaires et des coûts élevés. Le principal objectif de la présente analyse est de déterminer si l'utilisation du canakinumab est rentable dans la prévention des événements CV récidivants. Méthodes: Nous avons élaboré un modèle de prise de décision pour estimer les coûts directs et les résultats chez les patients qui ont souffert d'un infarctus du myocarde et qui sont traités par canakinumab. Nous avons utilisé un horizon d'étude sur la vie entière pour l'analyse coût-utilité de référence selon la perspective du système de soins de santé du Canada financé par l'État. La modélisation de Markov qui a été utilisée en combinaison avec la simulation Monte Carlo pour obtenir les valeurs attendues des coûts et des années de vie ajustées en fonction de la qualité (AVAQ) a permis le calcul des ratios coûts-efficacité différentiels. Résultats: Le canakinumab a été associé à des coûts moyens sur la vie entière plus élevés par patient (457 982 $ vs 82 565 $) et une AVAQ moyenne plus élevée par patient (14,90 vs 14,20) que le traitement selon la norme de soins. Par conséquent, le coût différentiel par AVAQ obtenu avec le traitement par canakinumab vs le traitement selon la norme de soins était de 535 365 $. La probabilité que le traitement par canakinumab soit rentable était de 0 %. Les résultats étaient cohérents dans un éventail d'analyses de scénarios. Conclusions: Le traitement des patients après un infarctus du myocarde par canakinumab n'est pas rentable comparativement au traitement selon la norme de soins au prix actuel. Selon les seuils de propension à payer actuellement acceptés au Canada, une réduction du prix de 91 % est requise pour obtenir un coût par patient qui serait considéré comme approprié.

Estimated Aortic Pulse Wave Velocity Is Associated With Faster Thoracic Aortic Aneurysm Growth: A Prospective Cohort Study With Sex-Specific Analyses.

BACKGROUND: Thoracic aortic aneurysm (TAA) is associated with high morbidity and mortality, and there is a critical need for improved tools for risk assessment and prognostication. We have previously shown that aortic stiffness, measured from arterial tonometry (carotid-femoral pulse wave velocity [cfPWV]), is independently associated with TAA expansion. To increase clinical applicability, we sought to determine the association of mathematically estimated aortic pulse wave velocity (e-PWV) with TAA expansion. METHODS: One-hundred and five consecutive unoperated subjects with TAA were recruited. We used arterial tonometry to measure cfPWV and used mean arterial pressure and age to calculate e-PWV according to validated equations. Multivariable linear regression assessed associations of baseline e-PWV with future aneurysm growth. Given sex differences in TAA outcomes, sex-stratified analyses were performed. RESULTS: Seventy-eight percent of subjects were men. Mean ± standard deviation (SD) age, baseline aneurysm size, and follow-up time were 62.6 ± 11.4 years, 46.2 ± 3.8 mm, and 2.9 ± 1.0 years, respectively. Aneurysm growth was 0.43 ± 0.37 mm per year; e-PWV was independently associated with future aneurysm expansion (ß ± SE: 0.240 ± 0.085, P = 0.006). In sex-specific analyses, e-PWV was associated with aneurysm growth in both men (ß ± standard error (SE) : 0.076 ± 0.022, P = 0.001) and women (ß ± SE : 0.145 ± 0.050, P = 0.012), but the strength of association nearly twice as strong in women as in men. CONCLUSIONS: Greater aortic stiffness reflects worse aortic health and provides novel insights into disease activity; e-PWV is independently associated with TAA growth. This finding increases clinical applicability, as e-PWV can be estimated simply, quickly, and free of cost without the need for specialized equipment.

Investigating the treatment phenotypes of cardiac sarcoidosis: A prospective cohort study.

Introduction: Data indicates there are 4 main pulmonary sarcoidosis duration/treatment phenotypes: asymptomatic, acute (disease duration <1-2 years), chronic and advanced. There are no data about disease duration/treatment phenotypes of cardiac sarcoidosis patients. Our study had 2 main aims (i) to assess the response to corticosteroids and (ii) to assess the incidence of relapse after a one-year course of corticosteroids (thereby classifying patients as acute or chronic treatment phenotype). Methods: Consecutive, treatment naive patients with CS were prospectively recruited and treated with 0.5 mg/kg prednisone, to a maximum dose of 40 mg/day. Patients had a follow-up PET after 3-6 months of therapy (PET 2). In the responders (PET definition of response) the prednisone was then weaned and stopped after 12 months. Three months after stopping, the PET was repeated to look for disease relapse (PET 3). Results: Twenty-one consecutive patients were included, and all patients showed a reduction in cardiac FDG uptake after 3-6 months and 19/21 (90.5 %) met the PET definition of response. Of these, 12/19 (63.1 %) relapsed after prednisone was stopped. There were no serious adverse effects during the trial of therapy cessation and there were no later relapses in the 7 non-relapsers during over 4 years of subsequent follow-up. Conclusion: The initial response rate to prednisone was high with all patients showing a reduction in FDG uptake and 19/21 meeting a PET definition of >25 % response. Secondly, a trial of therapy discontinuation was able to classify 7/19 patients as acute treatment phenotype and 12/19 as chronic.

Examining anti-inflammatory therapies in the prevention of cardiovascular events: protocol for a systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Inflammation is emerging as an important risk factor for atherosclerotic cardiovascular disease and has been a recent target for many novel therapeutic agents. However, comparative evidence regarding efficacy of these anti-inflammatory treatment options is currently lacking. METHODS AND ANALYSIS: This systematic review will include randomised controlled trials evaluating the effect of anti-inflammatory agents on cardiovascular outcomes in patients with known cardiovascular disease. Studies will be retrieved from Medline, Embase, the Cochrane Central Register of Controlled Trials, as well as clinical trial registry websites, Europe PMC and conference abstract handsearching. No publication date or language restrictions will be imposed. Eligible interventions must have some component of anti-inflammatory agent. These include (but are not limited to): non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, prednisone, methotrexate, canakinumab, pexelizumab, anakinra, succinobucol, losmapimod, inclacumab, atreleuton, LP-PLA2 (darapladib) and sPLA2 (varespladib). The primary outcomes will include major adverse cardiac events (MACE), and each individual component of MACE (myocardial infarction, stroke and cardiovascular death). Key secondary outcomes will include unstable angina, heart failure, all-cause mortality, cardiac arrest and revascularisation. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Network meta-analysis based on the random effects model will be conducted to compare treatment effects both directly and indirectly. The quality of the evidence will be assessed with appropriate tools including the Grading of Recommendations, Assessment, Development and Evaluation profiler or Confidence in Network Meta-Analysis tool. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review. The findings will be disseminated through a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022303289.

Influence of preoperative frailty on quality of life after cardiac surgery: Protocol for a systematic review and meta-analysis.

BACKGROUND: Frailty has emerged as an important prognostic marker of adverse outcomes after cardiac surgery, but evidence regarding its ability to predict quality of life after cardiac surgery is currently lacking. Whether frail patients derive the same quality of life benefit after cardiac surgery as patients without frailty remains unclear. METHODS: This systematic review will include interventional studies (RCT and others) and observational studies evaluating the effect of preoperative frailty on quality-of-life outcomes after cardiac surgery amongst patients 65 years and older. Studies will be retrieved from major databases including the Cochrane Central Register of Controlled Trials, Embase, and Medline. The primary exposure will be frailty status, independent of the tool used. The primary outcome will be change in quality of life, independent of the tool used. Secondary outcomes will include readmission during the year following the index intervention, discharge to a long-term care facility and living in a long-term care facility at one year. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Meta-analysis based on the random-effects model will be conducted to compare the outcomes between frail and non-frail patients. The evidential quality of the findings will be assessed with the GRADE profiler. CONCLUSION: The findings of this systematic review will be important to clinicians, patients and health policy-makers regarding the use of preoperative frailty as a screening and assessment tool before cardiac surgery. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).