Citations

ABSTRACT Introduction Regional heterogeneity of the human heart plays an important role in left ventricular (LV) and right ventricular (RV) function and may contribute to enhanced myocardial efficiency in the athlete’s heart. Purpose This study comprehensively characterized regional and transmural myocardial tissue deformation (strain) in recreationally active (RA) and endurance-trained (ET) men to determine if regional nonuniformity evolves alongside morphological adaptations associated with endurance training. Methods Echocardiography was used to measure LV and RV global, regional (apical, mid, basal) and transmural (endocardial, epicardial) longitudinal strain in 30 endurance-trained (ET) (age, 31 ± 2 yr; body mass index, 23.1 ± 0.5 kg·m −2 ; V˙O 2peak , 60.2 ± 6.5 mL·kg −1 ·min −1 ) and 30 RA (age: 29 ± 2 yr; body mass index, 23.4 ± 0.4 kg·m −2 ; V˙O 2peak : 42.6 ± 4.6 mL·kg −1 ·min −1 ). Nonuniformity was characterized using apex-to-base and transmural (endocardial-to-epicardial) strain gradients. Results Global longitudinal strain was similar in ET and RA in the left (−17.4% ± 0.4% vs −17.8% ± 0.5%, P = 0.662) and right ventricle (−25.8% ± 0.8% vs 26.4% ± 1.0%, P = 0.717). The apex-to-base strain gradient was greater in ET than RA in the left (−6.5% ± 0.7% vs −2.7% ± 0.8%, P = 0.001) and right ventricle (−9.6% ± 1.8% vs −3.0% ± 1.6%, P = 0.010). The LV transmural strain gradient was greater than RV in both groups, but similar in ET and RA (−4.7% ± 0.2% vs −4.7% ± 0.2%, P = 0.850), whereas RV transmural strain gradient was greater in ET than RA (−3.4% ± 0.3% vs −1.6% ± 0.4%, P = 0.003). RV apex-to-base and transmural strain gradients correlated with RV end-diastolic area ( R = 0.536 & 0.555, respectively, P < 0.01) and V˙O 2peak ( R = 0.415 & 0.677, respectively, P < 0.01). Conclusions Transmural nonuniformity is more pronounced in the left ventricle than the RV free wall; however, RV functional nonuniformity develops markedly after endurance training. Differences in myocardial architecture and exercise-induced wall stress in the left and right ventricles are possible explanations for the marked functional nonuniformity throughout the myocardium and in response to endurance exercise training.

8592 Background: Accrual to NCI clinical trials(CT)is often slower than planned at times mandating premature closure resulting in loss of valuable resources and delay of scientific progress. Methods: The NCI-MYSC AWG identified 10 potential BtA. SWOG, ECOG and Alliance investigators were queried and agreed that these barriers impede accrual (results stratified for academic and community sites). The MYSC AWG developed in collaboration with NCI and FDA strategies to overcome these barriers. Results: Strategies listed for the 3 most often cited BtA: 1. Reimbursement for CT related expenses:increase awareness of improved reimbursement for phase II CT; tailor reimbursement according to CT complexity; request funds from industry and other sources ( http://biqsfp.cancer.gov ) for qualifying ancillary CT components. 2. Spectrum of available treatment options influences CT participation: educate patients and providers about the significance of a new CT using social media, presentations at national meetings and by adding educational material to CT protocol; encourage opinion leaders and advocacy groups not to promote a new therapy as “standard” in the absence of phase III data. 3. Requirement of CT specific therapy at NCI designated sites only: “MYSC AWG Drug Administration Table” describes NCI/FDA approved rules for CT specific drug administration; CT protocol will outline which standard treatment components of a CT can be administered at any site as long as protocol specific guidelines are followed and conduct is supervised by enrolling investigator. Examples of additional strategies to overcome identified BtA: determine feasibility, indication and insurance coverage of CT specific tests during protocol development; discourage narrow eligibility criteria; avoid competing CT; allow up to 1 cycle of commercially available therapy prior to enrollment; CIRB support for phase II CT. Conclusions: The MYSC Accrual Working Group developed in collaboration with NCI and FDA strategies to overcome barriers to myeloma clinical trial accrual. These strategies may be applicable to NCI-sponsored clinical trials evaluating interventions in other diseases.

Abstract Background: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis. Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P &lt; 5 × 10−8) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance–weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI). Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00–1.30) and MZL (OR = 1.09; 95% CI, 1.01–1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83–0.99), all at nominal significance (P &lt; 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99–1.19; P = 0.087). No associations were noteworthy after adjusting for multiple testing. Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes. Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.

Abstract Funding Acknowledgements None Background/Purpose: Anemia is a common condition in patients with cardiovascular disease. The effect of anemia in exercise stress testing has not been evaluated in a large cohort of patients. Methods We performed a retrospective review of patients undergoing exercise stress echocardiography over a 10 year period who had blood hemoglobin assessed within 48 hours of stress testing. World Health Organization cutoffs were used in defining the degree of anemia. The effect of anemia on exercise capacity and stress testing safety outcomes was assessed. Results In 15,652 patients, 90.3% were non-anemic, 7.6% mildly anemic, 2.1% moderately anemic, and 0.1% severely anemic. The incidence of serious supraventricular or ventricular arrhythmias and need to transfer to the hospital was low (0.1%) and did not correlate to anemia severity (p = 0.25). There was an increased incidence of non-sustained SVT or atrial fibrillation with moderate anemia and increased incidence of hypotension with stress testing with mild and moderate anemia. There was a significant reduction in duration of exercise (p &lt; 0.001) and METS (p &lt; 0.001) achieved with worsening anemia. Conclusion Our study demonstrates that exercise stress testing is safe in patients with mild and moderate anemia, albeit with reduced exercise capacity. Low numbers of severely anemic patients despite a large study population limit generalizability of these results in this group. Exercise Capacity Severe Anemia (N = 9) Moderate Anemia (N = 332) Mild Anemia (N = 1183) Non-anemic (N = 14128) P value Resting heart rate 81 ± 13 # 79 ± 14 # 72 ± 14 74 ± 13 &lt;0.001* Peak heart rate 148 ± 22 139 ± 24 # 138 ± 23 # 147 ±22 &lt;0.001* Exercise duration 5.3 ± 2.5 # 6.3 ± 2.1 # 7.2 ± 2.5 # 8.6 ± 2.7 &lt;0.001* METS 6.3 ± 2.5 # 7.1 ± 2.2 # 8.0 ± 2.5 # 9.5 ± 2.7 &lt;0.001* Safety Hypotension with stress 0 (0%) 31 (9.4%) # 94 (8.0%) # 437 (3.1%) &lt;0.001* Mild supraventricular arrhythmia 1 (11.1%) 15 (4.5%) # 20 (1.7%) # 237 (2.3%) 0.04* Severe supraventricular arrhythmia 0 (0%) 0 (0%) 0 (0%) 7 (0.1%) 0.99 Mild ventricular arrhythmia 0 (0%) 20 (6.0%) 74 (6.3%) 756 (5.4%) 0.94 Moderate ventricular arrhythmia 0 (0%) 3 (0.9%) 13 (1.1%) 182 (1.3%) 0.78 Severe ventricular arrhythmia 0 (0%) 1 (0.3%) 2 (0.2%) 1 (0.0%) 0.02 Transfer to hospital 0 (0%) 2 (0.6%) 1 (0.1%) 9 (0.1%) 0.29 Any severe arrhythmia or hospitalization 0 (0%) 2 (0.6%) 3 (0.3%) 17 (0.1%) 0.25 # Multi-comparison adjusted P-value &lt;0.05 compared to non-anemic when group P &lt; 0.05

Abstract Background Noninvasive parameters of LV filling pressure (E/e’) and pulmonary pressures (RVSP) by Doppler echocardiography correlate with functional capacity and outcome in sinus rhythm (SR). Their role in AF is less clear. Elevated left ventricular filling pressures (E/e’) and pulmonary artery systolic pressures (PASP) by Doppler stress echocardiography correlate with impaired functional capacity in patients in sinus rhythm (SR). However, there is limited data in atrial fibrillation (AF). Purpose The aim of this study was to delineate the characteristics of patients with AF referred for exercise stress echocardiography and determine the prevalence and significance of E/e’ and PASP elevations in AF. Methods Subjects were patients referred for exercise treadmill stress echocardiography (n= 14,937) and underwent regional wall motion assessment, Doppler assessment of mitral inflow (E) and early tissue relaxation (e’) velocities and PASP at rest and immediately following maximum symptom limited exercise. Exclusion criteria included significant valvular heart disease (moderate or greater stenosis and/or regurgitation of any cardiac valve or previous valve repair or replacement) (1%), congenital heart disease (&lt;1%) or refusal to participate in research (&lt;1%). Results Patients with AF (n = 310, 2%) were older (71 ± 10 vs 59 ± 13 years, p &lt; 0.001). While resting blood pressure was similar, resting heart rates were higher in AF (80 ± 17 bpm vs 73 ± 13 bpm, p &lt; 0.0001). AF patients achieved lower workloads (6.4 ± 2.4 METS vs 9 ± 2.4 METS, p &lt; 0.001) with lower peak double products (22336 ± 6677 vs 25148 ± 5438, p &lt; 0.001). Rates of resting (27% vs 10%, p &lt; 0.0001) and exercise-induced (37% vs 20%, p &lt; 0.0001) regional wall motion abnormalities were higher in AF. Mean E/e’ was higher in AF at rest (12 ± 5 vs 9 ± 3, p &lt; 0.001) and with exercise (12 ± 5 vs 10 ± 4, p &lt; 0.001), with a higher percentage of patients in AF having E/e’ ≥15 at rest (20% vs 6% in SR, p= &lt;0.001) and with exercise in (23% vs 8%, p &lt; 0.001). PASP was higher in AF at rest (33 ± 8 mm Hg vs 28 ± 6 mm Hg, p &lt; 0.001) and with exercise (48 ± 12 vs 42 ± 11, p &lt; 0.001) compared to SR. E/e’ correlated with exercise capacity in AF and in SR, with an E/e’ cutoff of 11.7 that was best predictive of impaired functional capacity (&lt; 5 METS in women and &lt; 7 METS in men). Conclusions Abnormalities of E/e’ and PASP are more prevalent in patients with AF and correlate with impaired functional capacity. In patients with AF, a medial E/e’ ratio of ≥ 12 immediately following exercise is best associated with impaired functional capacity.

Abstract Aims Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. Methods and results Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58–64%] and 35% (95% CI 31–38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57–65%) and 33% (95% CI 28–37%), respectively; vs. 76% (95% CI 68–82%) and 50% (95% CI 40–59%) in PAH, vs. 71% (95% CI 64–76%) and 49% (95% CI 41–58%) in thromboembolic diseases, vs. 42% (95% CI 35–49%) and 8% (95% CI 4–15%) in CLD (log-rank P &lt; 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD. Conclusion One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.

Abstract Background and Aims We aimed to evaluate the relationship of serum adalimumab trough levels (ATL) with disease activity of inflammatory bowel disease (IBD) patients in a large, well-characterized referral center-based cohort. Methods We compared serum ATL between those with clinical, biochemical, or endoscopic/radiologic disease activity and those without. Results A total of 236 patients with IBD were included. Higher cutoff levels were associated with endoscopic and/or radiologic responses (cutoff value: 5.3 mcg/mL, P = 0.003) compared with improvement in C-reactive protein (cutoff value: 4.3 mcg/mL, P = 0.031). Conclusions Higher cutoff ATL was associated with endoscopic and/or radiologic response.

Abstract Background Cardiac power output-to-mass (CPOM) ratio is a measure of myocardial performance that incorporates both pressure and flow output, normalized to left ventricular (LV) mass generating that cardiac work. Prior small studies have shown that CPOM predicts outcomes in patients with ischemic cardiomyopathy and reduced LV ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise CPOM and power reserve (increase from rest to peak exercise) in patients with normal EF. Methods and results Retrospective study in 24,783 patients (age 59±13 years, 45% females) with EF≥50% and no significant valve disease or right ventricular (RV) dysfunction, undergoing exercise stress echocardiography between 2004–2018. CPOM was calculated as previously described (0.222 x cardiac output x mean blood pressure / LV mass) and expressed in Watts/100g myocardium. Power reserve was calculated as difference in CPOM between peak stress and rest. All-cause mortality was the primary endpoint. Patients were divided into quartiles of power reserve. Patients with higher power reserve were younger, had higher blood pressure and heart rate, lower LV mass, and lower prevalence of prior myocardial infarction. (Table). During follow-up (median (IQR) 3.9 (0.6–8.3) years), 931 (3.8%) patients died. Progressively lower power reserve was associated with increasing mortality (Figure A). Compared to patients with abnormal stress test, patients with the lowest power reserve but otherwise normal stress test had the same survival as those with infarction/cardiomyopathy or ischemia on stress test (Figure B). Resting CPOM had lower predictive value. After adjusting for age, sex, METs achieved, ischemia/infarction on stress test results, and diastolic function grade, both peak exercise CPOM and power reserve were independent predictors of mortality (p<0.0001), incremental to conventional measures. Conclusion Cardiac power output and reserve measured during exercise stress echo provides independent prognostic information in patients with normal resting EF and no significant valve disease or RV dysfunction. The survival of patients with low power reserve but normal stress test was similar to patients with prior infarction/ cardiomyopathy or ischemia on stress test.