Screening tools for the detection of clinically silent cardiac sarcoidosis.

BACKGROUND: clinically silent cardiac sarcoidosis (CS) may be associated with adverse outcomes, hence the rationale for screening patients with extracardiac sarcoidosis. The optimal screening strategy has not been clearly defined. METHODS: patients with extra-cardiac sarcoidosis were prospectively included and underwent screening consisting of symptom history, electrocardiography (ECG), transthoracic echocardiogram, Holter, and signal-averaged ECG (SAECG). Cardiac magnetic resonance (CMR) was performed in all patients. Clinically silent CS was defined as CMR demonstrating late gadolinium enhancement (LGE) in a pattern compatible with CS according to a majority of independent and blinded CMR experts. Significant cardiac involvement was defined as the presence of LGE ≥6% and/or a positive fluorodeoxyglucose-positron emission tomography. RESULTS: among the 129 patients included, clinically silent CS was diagnosed in 29/129 (22.5%), and 19/129 patients (14.7%) were classified as CS with significant cardiac involvement. There was a strong association between hypertension and CS (p < 0.05). Individual screening tools provided low diagnostic yield; however, combination of tests performed better, for example, a normal Holter and a normal SAECG had negative predictive values of 91.7%. We found consistently better diagnostic accuracy for the detection of CS with significant cardiac involvement. CONCLUSION: clinically silent CS and CS with significant cardiac involvement were found in 22.5% and 14.7% of patients with extra-cardiac sarcoidosis. The association with hypertension raises the possibility that some cases of hypertensive cardiomyopathy may be mistaken for CS. Screening with readily available tools, for example Holter and SAECG, may help identifying patients without CS where additional CMR is not needed.

Does E-learning Facilitate Medical Education in Pediatric Neurology?

BACKGROUND: E-learning has become commonplace in medical education. Incorporation of multimedia, clinical cases, and interactive elements has increased its attractiveness over textbooks. Although there has been an expansion of e-learning in medicine, the feasibility of e-learning in pediatric neurology is unclear. This study evaluates knowledge acquisition and satisfaction using pediatric neurology e-learning compared to conventional learning. METHODS: Residents of Canadian pediatrics, neurology, and pediatric neurology programs and medical students from Queens University, Western University, and the University of Ottawa were invited to participate. Learners were randomly assigned two review papers and two ebrain modules in a four-topic crossover design. Participants completed pre-tests, experience surveys, and post-tests. We calculated the median change in score from pre-test to post-test and constructed a mixed-effects model to determine the effect of variables on post-test scores. RESULTS: In total, 119 individuals participated (53 medical students; 66 residents). Ebrain had a larger positive change than review papers in post-test score from pre-test score for the pediatric stroke learning topic but a smaller positive change for Duchenne muscular dystrophy, childhood absence epilepsy, and acute disseminated encephalomyelitis. Learning topics showed statistical relationship to post-test scores (p = 0.04). Depending on topic, 57-92% (N = 59-66) of respondents favored e-learning over review article learning. CONCLUSIONS: Ebrain users scored higher on post-tests than review paper users. However, the effect is small and it is unclear if it is educationally meaningful. Although the difference in scores may not be substantially different, most learners preferred e-learning. Future projects should focus on improving the quality and efficacy of e-learning modules.

Negative Association of Smoking History With Clinically Manifest Cardiac Sarcoidosis: A Case-Control Study.

Background: The etiology of sarcoidosis is still unknown and is likely related to a genetic susceptibility to unidentified environmental trigger(s). Our group and others have extensively described a specific phenotype of primarily Caucasian patients who have clinically manifest cardiac sarcoidosis (CS). In this study, we sought to explore whether smoking is associated with this specific phenotype of sarcoidosis. Methods: We performed a case-control study. Cases with clinically manifest CS were prospectively enrolled in the Cardiac Sarcoidosis Multi-Center Prospective Cohort Study (CHASM-CS registry; NCT01477359) and answered a standardized smoking history questionnaire. Cases were matched 10:1 with controls from the Ontario Health Study. Pretreatment positron emission tomography scans with 18F-fluorodeoxyglucose were compared for smokers vs nonsmokers. Results: Eighty-seven cases met the inclusion criteria. A total of 82 of 87 (94.3%) answered the questionnaire and were matched with 820 controls. A clear negative association of sarcoidosis and smoking was found, with 23 of 82 CS cases (28.0%) being current or ex-smokers, vs 392 of 820 controls (47.8%; P = 0.0006). CS patients with a smoking history had significantly less lifetime consumption (8.31 ± 9.20 pack-years) than the controls (15.34 ± 10.84 pack-years; P < 0.003). On 18F-fluorodeoxyglucose-positron emission tomography scan, the mean standardized uptake value of the left ventricle was 4.2 ± 8.98 in lifetime nonsmokers vs 2.89 ± 2.07 in patients with a smoking history (P < 0.0001). Conclusions: We describe a strong negative association between smoking history and clinically manifest CS. Nonsmokers had more severe myocardial inflammation (greater mean standardized uptake value of the left ventricle) than did patients with a smoking history. Further research is needed to understand these associations and whether they have therapeutic potential.

Introduction: L'étiologie de la sarcoïdose est encore inconnue et est possiblement liée à une susceptibilité génétique à un ou des déclencheurs environnementaux inconnus. Notre groupe et d'autres groupes ont exposé sous tous ses aspects un phénotype particulier chez des patients principalement blancs qui ont une sarcoïdose cardiaque (SC) manifeste sur le plan clinique. Dans la présente étude, nous avons cherché à explorer si le tabagisme est associé à ce phénotype particulier de la sarcoïdose. Méthodes: Nous avons réalisé une étude cas témoins. Les cas qui avaient une SC manifeste sur le plan clinique ont été inscrits de façon prospective à l'étude CHASM-CS (Cardiac Sarcoidosis Multi-Center Prospective Cohort Study, registre CHASM-CS; NCT01477359) et ont répondu à un questionnaire standardisé sur les antécédents de tabagisme. Les cas ont été appariés 10:1 aux témoins de l'Étude sur la santé Ontario. Nous avons comparé avant le traitement la tomographie par émission de positons au 18F-fluorodéoxyglucose des fumeurs vs des non-fumeurs. Résultats: Quatre-vingt-sept cas répondaient aux critères d'inclusion. Un total de 82 sur 87 (94,3 %) cas ont rempli le questionnaire et ont été appariés à 820 témoins. Nous avons observé une association négative claire entre la sarcoïdose et le tabagisme, soit 23 sur 82 cas de SC (28,0 %) qui fumaient actuellement ou étaient des ex-fumeurs vs 392 sur 820 témoins (47,8 % ; P = 0,0006). Les patients atteints de SC qui avaient des antécédents de tabagisme avaient une consommation significativement moindre durant leur vie (8,31 ± 9,20 paquets-années) que les témoins (15,34 ± 10,84 paquets-années ; P < 0,003). À la tomographie par émission de positons au 18F-fluorodéoxyglucose, la valeur moyenne de fixation normalisée du ventricule gauche était de 4,2 ± 8,98 chez les non-fumeurs de toujours vs 2,89 ± 2,07 chez les patients qui avaient des antécédents de tabagisme (P < 0,0001). Conclusions: Nous démontrons une forte association négative entre les antécédents de tabagisme et la SC manifeste sur le plan clinique. Les non-fumeurs avaient plus d'inflammation myocardique grave (une plus grande valeur moyenne de fixation normalisée du ventricule gauche) que les patients qui avaient des antécédents de tabagisme. D'autres recherches sont nécessaires pour comprendre ces associations et savoir s'ils ont un potentiel thérapeutique.

Age, Not Sex, Modifies the Effect of Frailty on Long-term Outcomes After Cardiac Surgery.

OBJECTIVE: To examine the prevalence of frailty in surgical patients and determine whether age and sex modify the relationship between frailty and long-term mortality. BACKGROUND: Frailty is a complex and prevalent clinical syndrome. The cardiac surgery literature consists mostly of small, single-center studies, and the epidemiology of frailty remains to be fully elucidated in a real-world surgical population. METHODS: This retrospective cohort study included patients who underwent coronary artery bypass grafting, and/or aortic, mitral or tricuspid valve surgery in Ontario, Canada, between 2008 and 2016. The primary outcome was all-cause mortality. Survival probabilities were calculated using the Kaplan-Meier method, and the association of covariates with the hazard of death was assessed using multivariable Cox proportional hazard models. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. RESULTS: Of 72,824 patients, 11,685 (16%) were frail. At median 5 ±â€Š2 years of follow-up, 2921 (25.0%) frail patients and 8637 (14.1%) non-frail patients had died [adjusted hazard ratio 1.60; 95% confidence interval (CI), 1.53-1.68]. The adjusted hazard ratio was highest in patients who underwent isolated mitral (2.18; 95% CI, 1.71-2.77) and mitral + aortic valve surgery (1.85; 95% CI, 1.33-2.58) and lowest after coronary artery bypass grafting + mitral valve surgery (1.38; 95% CI, 1.11-1.70). Age, but not sex, modified the effect of frailty on mortality; such that the rate of death decreased linearly with increasing patient age. CONCLUSIONS: We observed a high prevalence of frailty in patients undergoing cardiac surgery, and a statistically significant association between frailty and long-term mortality after cardiac procedures. Importantly, the rate of death was inversely proportional to age, such that frailty had a stronger adverse impact on younger patients. Our findings highlight the need to incorporate frailty into the preoperative risk stratification and investigate strategies to support younger patients who are frail.

Exploring Occupational, Recreational, and Environmental Associations in Patients With Clinically Manifest Cardiac Sarcoidosis.

BACKGROUND: Sarcoidosis is a condition of unknown etiology. A number of occupational, recreational, and environmental exposures have been associated with the development of extra-cardiac sarcoidosis. Patients with clinically manifest cardiac sarcoidosis (CS) have a distinct clinical phenotype. We sought to explore the exposures associated with clinically manifest CS. METHODS: Two groups of patients were recruited in a prospective registry: cases (patients with clinically manifest CS) and controls (patients without sarcoidosis and who had similar cardiac presentations to cases). A validated survey, previously used in other sarcoidosis phenotypes, was sent to all patients. RESULTS: A total of 113 patients met the inclusion criteria and were sent the survey, of whom 79 of 113 (69.9%) completed the survey. We found 3 environmental associations. First, we found a negative association of CS with smoking, with 8 of 43 (18.6%) CS patients being current or ex-smokers compared to 17 of 36 (47.2%) of the controls. Second, we found a positive association with mold exposure, with 21 of 43 (48.8%) CS patients having a prior history of mold exposure compared to 9 of 36 (25.0%) of the controls. After multivariable analysis, there remained significant associations between CS and smoking (odds ratio 0.14 [95% confidence interval 0.04-0.51], P = 0.002) and mold exposure (odds ratio 5.69 [95% confidence interval 1.68-19.25], P = 0.005). Finally, patients with CS and self-reported acne had a significantly longer duration of active acne (7.82 ± 3.97 years) than did control patients 2.67 ± 1.03 years (P = 0.006). CONCLUSIONS: We found a negative association between smoking history and the diagnosis of CS. We also found a significant 5-fold increase in mold exposure and a positive association with duration of acne in patients with CS compared to controls.

CONTEXTE: Les causes de la sarcoïdose demeurent inconnues. Un certain nombre de facteurs de risque professionnels, récréatifs et environnementaux ont toutefois été associés à la survenue de la sarcoïdose extracardiaque. Les patients qui sont atteints d'une sarcoïdose cardiaque cliniquement manifeste ont un phénotype clinique particulier. Nous nous sommes penchés sur les facteurs de risque associés à cette maladie. MÉTHODOLOGIE: Nous avons recruté deux groupes de patients à partir d'un registre de données prospectives : des cas de sarcoïdose cardiaque (présentant les manifestations cliniques de la sarcoïdose cardiaque) et des cas témoins (patients sans sarcoïdose, mais qui présentaient des signes et des symptômes cardiaques similaires à ceux des patients atteints de sarcoïdose cardiaque). Nous avons envoyé à l'ensemble des participants un questionnaire validé et déjà utilisé auprès de patients présentant d'autres phénotypes de sarcoïdose. RÉSULTATS: Au total, 113 patients répondaient aux critères d'inclusion. Nous avons envoyé le questionnaire à ces 113 patients, et 79 d'entre eux (69,9 %) y ont répondu. Nous avons détecté trois facteurs environnementaux. Nous avons d'abord noté une association négative entre la sarcoïdose cardiaque et le tabagisme : 8 patients atteints de sarcoïdose cardiaque sur 43 (18,6 %) fumaient ou avaient déjà fumé, comparativement à 17 témoins sur 36 (47,2 %). Nous avons ensuite observé une association positive avec l'exposition aux moisissures : 21 patients atteints de sarcoïdose cardiaque sur 43 (48,8 %) avaient des antécédents d'une telle exposition, comparativement à 9 des 36 témoins (25,0 %). Les associations entre la sarcoïdose cardiaque et le tabagisme et l'exposition aux moisissures sont demeurées significatives après une analyse multivariée (risque relatif approché [RRA] pour le tabagisme : 0,14 [intervalle de confiance {IC} à 95 % : 0,04-0,51], p = 0,002; RRA pour l'exposition aux moisissures : 5,69 [IC à 95 % : 1,68-19,25], p = 0,005). Finalement, chez les patients atteints de sarcoïdose cardiaque et d'acné autodéclarée, la durée de l'acné était significativement plus longue (7,82 ± 3,97) que celle relevée chez les témoins (2,67 ± 1,03; p = 0,006). CONCLUSIONS: Nous avons détecté une association négative entre les antécédents de tabagisme et le diagnostic de sarcoïdose cardiaque. Nous avons également observé que l'exposition aux moisissures était 5 fois plus élevée et que l'acné est présente plus longtemps chez les patients atteints de sarcoïdose cardiaque que chez les témoins.

Atrial Arrhythmias in Clinically Manifest Cardiac Sarcoidosis: Incidence, Burden, Predictors, and Outcomes.

Background Recent data have suggested a substantial incidence of atrial arrhythmias (AAs) in cardiac sarcoidosis (CS). Our study aims were to first assess how often AAs are the presenting feature of previously undiagnosed CS. Second, we used prospective follow-up data from implanted devices to investigate AA incidence, burden, predictors, and response to immunosuppression. Methods and Results This project is a substudy of the CHASM-CS (Cardiac Sarcoidosis Multicenter Prospective Cohort Study; NCT01477359). Inclusion criteria were presentation with clinically manifest cardiac sarcoidosis, treatment-naive status, and implanted with a device that reported accurate AA burden. Data were collected at each device interrogation visit for all patients and all potential episodes of AA were adjudicated. For each intervisit period, the total AA burden was obtained. A total of 33 patients met the inclusion criteria (aged 56.1±7.7 years, 45.5% women). Only 1 patient had important AAs as a part of the initial CS presentation. During a median follow-up of 49.1 months, 11 of 33 patients (33.3%) had device-detected AAs, and only 2 (6.1%) had a clinically significant AA burden. Both patients had reduced burden after CS was successfully treated and there was no residual fluorodeoxyglucose uptake on positron emission tomography scan. Conclusions First, we found that AAs are a rare presenting feature of clinically manifest cardiac sarcoidosis. Second, AAs occurred in a minority of patients at follow-up; the burden was very low in most patients. Only 2 patients had clinically significant AA burden, and both had a reduction after CS was treated. Registration URL: https://www.clini​caltr​ials.gov; unique identifier NCT01477359.

Reproducibility of cardiac magnetic resonance imaging in patients referred for the assessment of cardiac sarcoidosis; implications for clinical practice.

Cardiac sarcoidosis (CS) is an increasingly recognized condition, but cardiac magnetic resonance (CMR) image interpretation in these patients may be challenging as findings are often non-specific. The main objective of this study was to investigate the inter-reader agreement for the overall interpretation of CMR for the diagnosis of CS in an experienced reference center and investigate factors that may lead to discrepancies between readers. Consecutive patients undergoing CMR imaging to investigate for CS were included. CMR images were independently reviewed by two readers, blinded to all clinical, imaging and demographic information. The readers classified each scan as "consistent with cardiac sarcoidosis", "not consistent with cardiac sarcoidosis" or "indeterminate". Inter-reader agreement was assessed using κ-statistics. When there was disagreement on the overall interpretation, a third reader reviewed the images. Also, two readers independently commented on the presence of edema, presence of LGE (both ventricles) and quantified the extent of left ventricular LGE. 87 patients (43 women, mean age 54.3 ± 12.2 years) were included in the study. There was agreement regarding the overall interpretation in 72 of 87 (83%) CMR scans. The κ value was 0.64, indicating moderate agreement. There was similar moderate agreement in the interpretation of LGE parameters. In an experienced referral center, we found moderate agreement between readers in the interpretation of CMR in patients with suspected CS. Physicians should be aware of this inter-observer variability in interpretation of CMR studies in patients with suspected CS.

Treatment with corticosteroids is associated with an increase in ventricular arrhythmia burden in patients with clinically manifest cardiac sarcoidosis: Insights from implantable cardioverter-defibrillator diagnostics.

INTRODUCTION: We sought to explore the relationship between ventricular tachycardia (VT) and premature ventricular complex (PVC) burden (from implantable cardioverter-defibrillator diagnostics), before and during corticosteroid use in patients with newly diagnosed clinically manifest cardiac sarcoidosis (CS). METHODS: A single-centre, prospective cohort study was performed in consecutive patients who met all of the following criteria: (1) presentation with clinically manifest CS, (2) abnormal myocardial fluoro-deoxyglucose (FDG) uptake on positron emission tomography scan, (3) plan for implantation with implantable cardioverter-defibrillator device that reports accurate PVC count, (4) plan to initiate corticosteroids after the device healing period. Data were collected during each device interrogation visit for all patients in the study. For each inter-visit period the total number of episodes of VT-sustained and nonsustained, and the number of PVCs was obtained. Each inter-visit period was classified into one of the following three periods: (1) New diagnosis of treatment-naive active disease without corticosteroids during the period. (2) Known treatment-naive active disease with corticosteroids initiated during the inter-visit period. (3) On corticosteroid therapy during the entire period. RESULTS: A total of 20 patients with a mean age of 59.7 ± 7.7 years were recruited and 82 inter-visit periods were analyzed. All patients were corticosteroid responders based on FDG uptake. The maximum left ventricular standardized uptake value was 11.14 ± 5.19 before corticosteroid initiation and 4.07 ± 0.88 after (p < .001). Patients with active untreated CS had an average of 496.4 ± 879.1 PVCs per day. After treatment with corticosteroids, the average PVC count increased to 1332.4 ± 1865.7/day during Period 2 (p = .036) and to 1590.1 ± 2362.2 per day during Period 3 (p = .008). There was also a statistically significant increase in episodes of nonsustained ventricular tachycardia (NSVT) before and after treatment with corticosteroids (p = .017). There were too few episodes of sustained ventricular arrhythmia to analyze. Overall, 18 out of 20 patients (90%) had an increase in PVC burden after corticosteroid initiation. CONCLUSION: This study demonstrated, on average, a threefold increase in daily PVC count in clinically manifest CS patients during treatment with corticosteroids compared to pretreatment. There was also a significant increase in episodes of NSVT. Clinicians and patients with active manifest CS should be aware that corticosteroids are unlikely to lead to a reduction in the burdens of PVC and NSVT.

Prevalence of left atrial appendage thrombus detected by transoesophageal echocardiography before catheter ablation of atrial fibrillation in patients anticoagulated with non-vitamin K antagonist oral anticoagulants.

AIMS: There is ongoing controversy about the need for routine transoesophageal echocardiography (TOE) prior to atrial fibrillation (AF) ablation. Recently, the debate was reignited by the publication of a large series of patients showing a prevalence of left atrial appendage thrombus (LAAT) on TOE of 4.4%. We sought to assess the prevalence of LAAT on TOE before AF ablation at our institution. METHODS AND RESULTS: Consecutive patients scheduled for AF ablation at our institution between January 2009 and December 2016 were included. All patients were on oral anticoagulation for at least 4 weeks prior to TOE. Transoesophageal echocardiographies were performed 3-5 days prior to scheduled AF ablation. Data were collected utilizing a prospective database. In all, 668 patients and 943 AF ablation procedures were included. Mean age was 64 ± 11 years, 72% were male, average CHADS2 score was 1.0 ± 1.0, and 72% of the patients had paroxysmal AF. At the time of ablation, 496 (53%) were on non-vitamin K antagonist oral anticoagulants (NOACs) and 447 (47%) were on Warfarin. There were three cases with LAAT (3/943, 0.3%), all of whom had persistent AF and were on Warfarin. Two patients underwent surgical ablation and the third patient did not undergo ablation. CONCLUSION: In our experience, the prevalence of LAAT in patients on anticoagulation therapy undergoing TOE before catheter ablation of AF is 0.3%, which was much lower than recently reported. None of the patients with paroxysmal AF or on NOACs were found to have LAAT. Rather than routine use of TOE prior to AF ablation, a risk-based approach should be considered.

The Psychometric Properties of a Self-Administered, Open-Source Module for Valuing Metastatic Epidural Spinal Cord Compression Utilities.

INTRODUCTION: Web surveys are often used for utility valuation. Typically, custom utility valuation tools that have not undergone psychometric evaluation are used. OBJECTIVES: This study aimed to determine the psychometric properties of a metastatic epidural spinal cord compression (MESCC) module run on a customizable open-source, internet-based, self-directed utility valuation platform (Self-directed Online Assessment of Preferences [SOAP]). METHODS: Individuals accompanying patients to the emergency department waiting room in Ottawa, Canada, were recruited. Participants made SOAP MESCC health state valuations in the waiting room and 48 h later at home. Validity, agreement reliability, and responsiveness were measured by logical consistency of responses, smallest detectable change, the interclass correlation coefficient, and Guyatt's responsiveness index, respectively. RESULTS: Of 285 participants who completed utility valuations, only 113 (39.6%) completed the re-test. Of these 113 participants, 92 (81.4%) provided valid responses on the first test and 75 (66.4%) provided valid responses on the test and re-test. Agreement for all groups of health states was adequate, since their smallest detectable change was less than the minimal clinically important difference. The mean interclass correlation coefficients for all health states were > 0.8, indicating at least substantial reliability. Guyatt's responsiveness indices all exceeded 0.80, indicating a high level of responsiveness. CONCLUSIONS: To our knowledge, this is the first validated open-source, web-based, self-directed utility valuation module. We have demonstrated the SOAP MESCC module is valid, reproducible, and responsive for obtaining ex ante utilities. Considering the successful psychometric validation of the SOAP MESCC module, other investigators can consider developing modules for other diseases where direct utility valuation is needed.

Bi-atrial fibrosis detected using three-dimensional late gadolinium enhancement magnetic resonance imaging in a patient with cardiac sarcoidosis.

Presented is the case of a 62-year old male with a history of sarcoidosis and sinus node dysfunction, who underwent late gadolinium enhancement magnetic resonance imaging, which demonstrated left ventricular hyperenhancement and bi-atrial fibrosis.

Three-year outcomes and reconnection patterns after initial contact force guided pulmonary vein isolation for paroxysmal atrial fibrillation.

BACKGROUND AND OBJECTIVE: Contact force (CF) sensing is a novel technology used for catheter ablation of atrial fibrillation (AF). We compared the single procedure success of CF-guided pulmonary vein isolation (PVI) with that of non-CF guided PVI during a 3-year (1,095 days) follow up period and analyzed the pattern of pulmonary vein (PV) reconnection. METHODS: A cohort of 167 subjects (68 CF vs. 99 non-CF) with paroxysmal AF were included in the study. Atrial arrhythmia (AA) recurrence was defined as documented AF, atrial flutter, or atrial tachycardia lasting >30 seconds and occurring after 90 days. RESULTS: Subjects in the CF group showed a statistically nonsignificant improvement in AA free survival compared to those in the non-CF group (66.2% vs. 51.5%; P value: 0.06). A greater propensity for reconnection was noted around the right-sided PVs compared to left-sided PVs related in both catheter ablation groups. For example, in the CF group 36% of right-sided segments reconnected compared to 16% of left-sided segments (P value <0.01). CONCLUSIONS: A greater propensity for reconnection was noted around the right sided PV segments in both the CF and non-CF groups. The explanation for this finding was related to greater catheter instability around the right sided veins. Further research is needed to explore the utility of a "real-time" composite indicator that includes RF energy, CF and catheter stability in predicting transmural lesion formation during catheter ablation.