P1110Role of an extensive diagnostic work-up in the detection of concealed cardiomyopathies in athletes with complex ventricular arrhythmias and implications for sports" eligibility assessment

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Dello Russo ◽  
M Casella ◽  
F Guerra ◽  
P Compagnucci ◽  
A Gasperetti ◽  
...  

Abstract Background ventricular Arrhythmias (VAs) are a common clinical problem and a critical issue with regards to sports" eligibility in athletes. Although VAs can be considered a benign feature of the athlete’s heart adaptive phenotype, they may also be the only clinical manifestation of a concealed cardiomyopathy, potentially heralding sudden cardiac death (SCD) during sports activity. Purpose to evaluate the diagnostic contribution and the implications for sports eligibility assessment of a thorough non-invasive and invasive work-up including electrophysiology study (EPS), electroanatomical mapping (EAM) and endomyocardial biopsy (EMB) in athletes with complex VAs and to derive a multiparametric risk score in order to easily predict structural heart diseases’ diagnosis. Methods we conducted a prospective, single-arm, open-label single center, observational study. All consecutive athletes presenting for evaluation at our institution after being disqualified from participating in sports due to complex VAs were enrolled. The athletes underwent a baseline non-invasive diagnostic protocol with transthoracic echocardiogram and gadolinium enhanced cardiac magnetic resonance imaging (cMRI). Subsequently EPS, EAM and EAM-guided EMB were performed if deemed necessary. Sports eligibility status was re-assessed at 6 months’ follow-up. A multivariable logistic regression model was built, considering cMRI as the gold standard exam. Results after diagnostic evaluation, 55 subjects (26.4%) had a diagnosis of heart disease, most commonly myocarditis (n = 27) and arrhythmogenic right ventricular cardiomyopathy (ARVC, n = 16). After 6 months, 100 athletes (48.1%) were judged eligible to participate in competitive sports and 46 subjects (22.1%) were deemed eligible to participate in non-competitive sports. On multivariable logistic-regression analysis, abnormalities on ECG (OR 5.3) or on echocardiogram (OR 3.7), sustained VA inducibility on EPS (OR 17.7) and low-voltage areas on EAM (OR 7.7) proved all predictive of concealed structural heart diseases’ diagnosis. We derived two simple risk scores: a 40-points risk score and an 8-points risk score (obtained by weighing each variable according to the regression model’s ORs). Both these risk scores’ performance proved very good (AUC = 0.856 for the 40-points score and AUC = 0.852 for the 8-points score, figure 1). Conclusions approximately 1/4 of athletes presenting with complex VAs have a concealed heart disease, most commonly myocarditis or ARVC. ECG, echocardiogram and EAM abnormalities and sustained VAs inducibility on EPS are predictive of structural heart diseases’ detection. Therefore, these diagnostic tests should be routinely included in the evaluation of athletes with complex VAs. A risk score including the results of these tests can greatly help in the prediction of concealed structural heart diseases’ diagnosis. More than 2/3 of subjects were judged eligible to participate in sports at 6 months’ follow-up. Abstract Figure 1. ROC curves for diagnosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Compagnucci ◽  
M Casella ◽  
F Guerra ◽  
A Gasperetti ◽  
G Volpato ◽  
...  

Abstract Background Premature ventricular complexes (PVCs) are a common clinical problem and a critical issue with regard to sports eligibility in sportsmen. Although PVCs can be considered a benign feature of the athlete's heart adaptive phenotype, they may also be the only clinical manifestation of a concealed cardiomyopathy, potentially heralding sudden cardiac death (SCD) during sports activity. The optimal diagnostic evaluation of athletes with PVCs is currently uncertain. Purpose To evaluate the diagnostic contribution and the implications for sports eligibility assessment of a thorough non-invasive and invasive work-up including electroanatomical mapping (EAM) and endomyocardial biopsy (EMB) in athletes with PVCs. Methods We conducted a prospective, single-arm, open-label double center study. All consecutive athletes presenting for evaluation at our institution after being disqualified from participating in sports due to PVCs were included in our study. These athletes underwent a baseline non-invasive diagnostic protocol with transthoracic echocardiogram and gadolinium enhanced cardiac magnetic resonance imaging (cMRI). Subsequently, an invasive diagnostic work-up was performed, including EPS with programmed electrical stimulation, EAM and EAM-guided EMB if deemed necessary. When clinically indicated, catheter ablation was performed. Sports eligibility status was re-assessed at six months' follow-up according to Italian sports medicine guidelines. Results After diagnostic evaluation, 20 subjects out of 107 (19%) had a diagnosis of heart disease, most commonly myocarditis (n=8), arrhythmogenic right ventricular cardiomyopathy (ARVC, n=7) or dilated cardiomyopathy (DCM, n=2). On multivariate logistic-regression analysis, QRS complex/T wave abnormalities on ECG (OR 23), non left bundle branch block and inferior axis PVC morphology (OR 13), echocardiogram abnormalities (OR 24) and low-voltage areas on EAM (OR 33) were significantly associated with diagnosis of a concealed cardiac disease. Nondiagnostic abnormalities on cMRI were common in this population of athletes, prevalently involving the right ventricle. EAM-guided EMB was performed in 12 subjects (11%) and catheter ablation in 56 (52.3%). After six months, 63 athletes (59%) were judged eligible to participate in competitive sports and 23 subjects (21%) were deemed eligible to participate in non-competitive sports. Conclusions Almost one fifth of sportsmen presenting with PVCs have a concealed heart disease, most commonly myocarditis or ARVC. Non-outflow tract PVCs' morphology and abnormalities on ECG, echocardiogram and EAM are predictive of structural heart disease's detection, whereas nondiagnostic findings on cMRI can be misleading in athletes. Invasive diagnostic tests, including EAM and EAM-guided EMB, play a critical role in case of diagnostic uncertainty. More than ¾ of subjects were judged eligible to participate in sports at 6 months' follow-up. Funding Acknowledgement Type of funding source: None


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2396-2396
Author(s):  
Carrie A. Thompson ◽  
Sophia Wang ◽  
Matthew J. Maurer ◽  
Thomas M. Habermann ◽  
Richard K. Severson ◽  
...  

Abstract Small lymphocytic lymphoma (SLL) is an incurable indolent lymphoma, and there are relatively few prognostic biomarkers for this important NHL subtype. We evaluated the hypothesis that inherited variability in cytokine and immune-related genes was associated with overall survival in SLL. We genotyped 73 SNPs in 44 candidate genes in 140 SLL patients aged 20–70 years who participated in a population-based case-control study conducted from 1998–2000 through the Surveillance, Epidemiology, and End Results (SEER) cancer registries in Detroit, Seattle, Iowa, and Los Angeles. DNA was extracted from a venous blood sample or mouthwash buccal cell sample. All genotyping was conducted at the National Cancer Institute Core Genotyping Facility using the Taqman platform. Histology, stage, presence of B-symptoms, first course of therapy, date of last follow-up, and vital status were derived from linkage to registry databases at each study site in the spring of 2005. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) and 95% confidence interval for the association between individual SNPs and overall survival, adjusted for age, demographic and clinical factors. Multiple simultaneous modeling strategies were used to identify the best summary multi-SNP risk score to predict survival. At last follow-up, there were 45 deaths in 140 patients (32%). The median follow-up of the 95 surviving patients was 58 months (range 24–75 months). In multivariate modeling, SNPs in IL13 (rs1800925; HRCC=2.36, 1.24–4.49), IL7R (rs1494555; HRGG =2.20, 0.84–5.76), and TNF-alpha (rs1800630; HRAC/AA=1.73, 0.95–3.17) were the strongest and most robust predictors of survival. Two or more deleterious genotypes from these three SNPs increased the risk of death (HR=2.2, 1.2–4.1) compared with one or fewer deleterious genotypes (p=0.009). Three groups (low, intermediate, and high risk) were defined by combining the SNP score and a clinical/demographic score. The 5-year Kaplan-Meier survival estimates for these groups were 85%, 65%, and 11%, respectively. Compared to patients with a low risk score, patients with intermediate (HR=2.5, 1.2–5.1) or high (HR=11, 4.3–27.7) risk scores had poorer overall survival (p=3.9 x 10−8). Our preliminary results suggest that SNPs in IL13, IL7R, and TNF-alpha alone and in combination predict overall survival in SLL, lending support to the hypothesis that host genetic background is a promising class of prognostic biomarkers in SLL.


2021 ◽  
Vol 4 ◽  
pp. 70
Author(s):  
Sinéad Flynn ◽  
Seán Millar ◽  
Claire Buckley ◽  
Kate Junker ◽  
Catherine Phillips ◽  
...  

Background: Type 2 diabetes (T2DM) is a significant cause of morbidity and mortality, thus early identification is of paramount importance. A high proportion of T2DM cases are undiagnosed highlighting the importance of effective detection methods such as non-invasive diabetes risk scores (DRSs). Thus far, no DRS has been validated in an Irish population. Therefore, the aim of this study was to compare the ability of nine DRSs to detect T2DM cases in an Irish population. Methods: This was a cross-sectional study of 1,990 men and women aged 46–73 years. Data on DRS components were collected from questionnaires and clinical examinations. T2DM was determined according to a fasting plasma glucose level ≥7.0 mmol/l or a glycated haemoglobin A1c level ≥6.5% (≥48 mmol/mol). Receiver operating characteristic curve analysis assessed the ability of DRSs and their components to discriminate T2DM cases. Results: Among the examined scores, area under the curve (AUC) values ranged from 0.71–0.78, with the Cambridge Diabetes Risk Score (AUC=0.78, 95% CI: 0.75–0.82), Leicester Diabetes Risk Score (AUC=0.78, 95% CI: 0.75–0.82), Rotterdam Predictive Model 2 (AUC=0.78, 95% CI: 0.74–0.82) and the U.S. Diabetes Risk Score (AUC=0.78, 95% CI: 0.74–0.81) demonstrating the largest AUC values as continuous variables and at optimal cut-offs. Regarding individual DRS components, anthropometric measures displayed the largest AUC values. Conclusions: The best performing DRSs were broadly similar in terms of their components; all incorporated variables for age, sex, BMI, hypertension and family diabetes history. The Cambridge Diabetes Risk Score, had the largest AUC value at an optimal cut-off, can be easily accessed online for use in a clinical setting and may be the most appropriate and cost-effective method for case-finding in an Irish population.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Ahmad Nanaa ◽  
Rama Nana ◽  
Zhuoer Xie ◽  
Dragan Jevremovic ◽  
Phuong L. Nguyen ◽  
...  

Background: Clonal cytopenias of Undetermined Significance (CCUS) have a higher risk of progression to myeloid neoplasm (MN) compared to idiopathic cytopenias of undetermined significance (ICUS) (Malcovati et al., Blood, 2017). The implementation of flow cytometric (FC) immune-phenotyping and next generation sequencing (NGS) in clinical practice has improved the diagnosis of these entities but the clinical significance and interaction of these abnormal results are still unknown. In this study we investigated predictive factors that play role in survival and progression to MN in patients with ICUS/CCUS. Methods: Patients (Pts) who had undergone evaluation for unexplained cytopenia and had undergone FC and bone marrow morphological assessment between 3/2015-3/2020 at Mayo Clinic Rochester were included. Pts were excluded if a malignant hematological disorder was diagnosed prior to the time of FC. FC included evaluation of the following parameters: Abnormal expression of HLA-DR/CD13, CD2, CD7, CD45, and CD56 on blasts; and abnormal CD13/CD16 expression and side scatter on granulocytic cells. NGS panel up to 2018 included 34 genes, ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA1, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, MPL, MYD88, NOTCH1, NPM1, NRAS, PHF6, PTPN11, RUNX1, SETBP1, SF3B1, TERT, TET2, TP53, U2AF1, WT1, and ZRSR2; in 2018, BRAF was omitted and 12 genes were added, ANRD26, DDX41, ELANE, ETNK1, KDM6A, MYD88, NOTCH1, RAD21, SH2B3, SRP72, SMC3, and STAG2. Results: Characteristics: Of 490 consecutive pts, 238 (median age 69 years (range 19-92), 66% males) met our inclusion criteria as ICUS. 86 (36%) pts had CCUS (abnormal cytogenetics and/or tested positive for pathogenic mutations on NGS). After a median follow-up of 28 months (95% CI: 20 to 31 months), 21 (25%) patients developed MN and 23 (27%) died during follow-up. Comparing ICUS vs CCUS: upon comparing CCUS pts to ICUS, several factors were found to be significantly different: CCUS pts were older (p= .02); majority male (p= .04), had more abnormal HLA-DR/CD13 (p <.0001), more side-scattered light by FC (p <.0001), more pancytopenia on follow up (p= .02) and more morphologic atypia (<.0001). Overall survival (OS) outcomes in CCUS: Several covariates were significant in univariate models, and model selection was used to generate a risk score based on abnormal CD7, abnormal CD13/CD16, abnormal HLA-DR/CD13, splenomegaly and history of prior chemotherapy or radiotherapy (range: 0 - 4; HR=2.58, [95 CI: 1.69 - 3.94], p<.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score=2+), with estimated 2-yr-OS of 95%, 84%, 40%, respectively (Figure 1). An extended risk score model including NGS factors added ASXL1 and IDH1 mutation status to the previous model (range: 0 - 6; HR=2.72, [95 CI 1.82 - 4.06], p<0.0001). MN-free survival (MNFS) in CCUS: 37 pts either progressed to MN and/or died with a median follow up time for MNFS of 22.4 months. Similar for OS, model selection approaches yielded a composite risk score: splenomegaly, BCOR mutation status, mutation in RAS signaling pathway, abnormal expression of flow markers CD13/CD16, HLA-DR/CD13 or CD7 (HR=3.23, [95 CI: 1.90 - 5.49], p=<0.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score ≥ 2), with estimated 1-yr MNFS of 84%, 74%, and 31%, respectively (Figure 2). Conclusion: CCUS has unique features compared to ICUS. Several factors, including clinical characteristics, immune-phenotyping by FC, and somatic mutations have important impact on risk of progression to MN and on overall survival. Our findings serve as proof-of-concept that such integrated models could help identify CCUS patients at higher risks for progression to MN or death. They can guide treatment accordingly and should be evaluated further. Disclosures Shah: Dren Bio: Consultancy.


Author(s):  
Itzhak Kronzon ◽  
Juan Manuel Monteagudo ◽  
Francesco F. Faletra ◽  
Priti Mehla ◽  
Muhamed Saric

Repairing structural heart diseases without surgery has been a major challenge. The title ‘The Father of Interventional Cardiology’ belongs to William J. Rushkind (1922–1986) who performed atrial balloon septostomy in newborn babies with D-transposition as early as 1968. He also designed devices for the transcatheter closure of atrial defects and of patent ductus arteriosus. The introduction of better devices and skilled operators led to successful procedures which are less traumatic, shorter, and in many cases significantly less expensive. The various modalities of cardiac imaging have become a crucial ingredient of the preprocedural diagnosis, procedural guidance, and the assessment of procedural results and follow-up. This chapter will demonstrate and discuss the role of imaging in several catheter-based procedures that are now commonly practised by the current generation of interventional cardiologists who are involved in structural heart disease.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Paul C Cremer ◽  
Yuping Wu ◽  
Lee Pierson ◽  
Danielle Brennan ◽  
Leslie Cho

Background: Cardiovascular mortality has declined with advances in primary and secondary prevention, yet risk assessment for patients undergoing exercise treadmill testing is generally still based upon the Duke Treadmill Score (DTS). We hypothesized that a new risk score would perform better than the DTS. Methods: We studied 59,877 consecutive patients who had exercise testing between Januray 1, 2000 and October 27, 2011 with the sample divided equally into derivation and validation cohorts. The primary outcome was all-cause mortality. Risk scores for men and women were developed from Cox proportional hazards models. The DTS was compared to new risk scores in the validation cohort with C-statistics, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: Over a median follow-up of 8 years, there were 2,521 deaths. In the multivariable model, age, exercise capacity, heart rate recovery, weight, and renal disease were associated with mortality in men and women. Diabetes mellitus and history of smoking were associated with mortality in women whereas heart failure, current smoking, and hypertension were associated with mortality in men. C-statistics, NRI, and IDI were all improved with the new risk scores (Table). In particular, the new risk scores correctly reclassified patients with events, especially in women. Patients in the highest tertile of risk score also had substantial mortality during follow-up (Figure). Conclusions: We have developed new risk scores for men and women that perform better than the DTS, particularly in patients at the highest risk for all-cause mortality.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 530-530
Author(s):  
Julia Elizabeth McGuinness ◽  
Vicky Ro ◽  
Simukayi Mutasa ◽  
Richard Ha ◽  
Katherine D. Crew

530 Background: The standard of care for early-stage hormone receptor (HR)-positive breast cancer (BC) is 5-10 years of adjuvant endocrine therapy (ET), which leads to a 50-60% relative risk reduction in BC recurrence. However, 10-40% of patients may relapse up to 20 years (y) after diagnosis, and there is a need for biomarkers of response to ET. We developed a novel, fully-automated convolutional neural network (CNN)-based mammographic evaluation that accurately predicts BC risk, which is being evaluated as a pharmacodynamic response biomarker to adjuvant ET. Methods: We conducted a retrospective cohort study among women with HR-positive stage I-III unilateral BC diagnosed at Columbia University Irving Medical Center from 2007-2017, who received adjuvant ET and had at least 2 mammograms of the contralateral breast (baseline and annual follow-up). Demographics, clinical characteristics, BC treatments, and relapse status were extracted from the electronic health record and New York-Presbyterian Hospital Tumor Registry. We performed CNN analysis of mammograms at baseline (start of ET) and annual follow-up. Our primary endpoint was change in CNN risk score, expressed as a continuous variable (range, 0-1). We used two-sample t-tests to assess for differences in mean CNN scores between patients who relapsed or remained in remission. We evaluated if CNN score at baseline and change from baseline were associated with relapse using logistic regression, with adjustment for known prognostic factors. Results: Among 870 evaluable women, mean age at diagnosis was 59.5y (standard deviation [SD], 12.4); 60.3% had stage I tumors, 72.6% underwent lumpectomy, and 45.8% received chemotherapy. With a median follow-up of 4.9y, there were 68 (7.9%) breast cancer relapses (36 distant, 26 local, 6 new primary). Median number of evaluable mammograms per patient was 5 (range, 2-13). Mean baseline CNN risk scores were significantly higher among women who relapsed compared to those in remission (0.258 vs 0.237, p = 0.022), which remained significant after adjustment for known prognostic factors. There was a significant difference in mean absolute change in CNN risk score from baseline to 1y follow-up between those who relapsed vs. remained in remission (0.001 vs. -0.022, p = 0.027), but this was no longer significant in multivariable analysis. Conclusions: We demonstrated that higher baseline CNN risk score was an independent predictor of BC relapse. A greater decrease in mean CNN risk scores at 1-year follow-up after initiating adjuvant ET was seen among BC patients who remained in remission compared to those who relapsed. Therefore, baseline CNN risk scores may identify patients at high-risk for breast cancer recurrence to target for more intensive adjuvant treatment. Early changes in CNN risk scores may be used to predict response to long-term ET in the adjuvant setting.


2019 ◽  
Vol 75 (5) ◽  
pp. 980-986 ◽  
Author(s):  
Ming-Tuen Lam ◽  
Chor-Wing Sing ◽  
Gloria H Y Li ◽  
Annie W C Kung ◽  
Kathryn C B Tan ◽  
...  

Abstract Background To evaluate whether the common risk factors and risk scores (FRAX, QFracture, and Garvan) can predict hip fracture in the oldest old (defined as people aged 80 and older) and to develop an oldest-old-specific 10-year hip fracture prediction risk algorithm. Methods Subjects aged 80 years and older without history of hip fracture were studied. For the derivation cohort (N = 251, mean age = 83), participants were enrolled with a median follow-up time of 8.9 years. For the validation cohort (N = 599, mean age = 85), outpatients were enrolled with a median follow-up of 2.6 years. A five-factor risk score (the Hong Kong Osteoporosis Study [HKOS] score) for incident hip fracture was derived and validated, and its predictive accuracy was evaluated and compared with other risk scores. Results In the derivation cohort, the C-statistics were .65, .61, .65, .76, and .78 for FRAX with bone mineral density (BMD), FRAX without BMD, QFracture, Garvan, and the HKOS score, respectively. The category-less net reclassification index and integrated discrimination improvement of the HKOS score showed a better reclassification of hip fracture than FRAX and QFracture (all p < .001) but not Garvan, while Garvan, but not HKOS score, showed a significant over-estimation in fracture risk (Hosmer–Lemeshow test p < .001). In the validation cohort, the HKOS score had a C-statistic of .81 and a considerable agreement between expected and observed fracture risk in calibration. Conclusion The HKOS score can predict 10-year incident hip fracture among the oldest old in Hong Kong. The score may be useful in identifying the oldest old patients at risk of hip fracture in both community-dwelling and hospital settings.


2012 ◽  
Vol 27 (1_suppl) ◽  
pp. 10-15 ◽  
Author(s):  
R D Malgor ◽  
N Labropoulos

Chronic venous disease (CVD) is very prevalent and causes a significant financial burden in Western societies. Accurate diagnosis is mandatory to define the anatomy and pathophysiology involved in the disease process. Duplex ultrasound (DU) is a well-established non-invasive tool used for varicose veins work-up that, most recently, has also been utilized for follow-up after endovenous procedures such as endovenous laser or radiofrequency ablation and foam sclerotherapy. Insightful information on how DU is performed during varicose veins work-up and the rationale of DU utilization for endovenous procedures are discussed.


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