Kopecky, Stephen L.

Introduction: Diabetes affected 529 million people globally by 2021, largely due to rising obesity contributing to Type 2 diabetes (DM2). In the U.S., it is the seventh leading cause of death and closely linked to cardiovascular disease, the leading cause of mortality in this population. Effective, low-cost strategies to improve glycemic and cardiometabolic health are essential. Psyllium, a viscous soluble fiber, has been shown to lower LDL cholesterol and improve glycemic indices, whereas non-viscous fibers like wheat dextrin lack similar benefits. Emerging lipid markers such as ceramides are associated with cardiometabolic risk but have not been studied in response to fiber. The interaction between fiber and GLP-1 agonists is also unclear. Hypothesis: Psyllium supplementation will improve cardiometabolic markers more than wheat dextrin in people with DM2. Methods: In this randomized trial at Mayo Clinic, adults with DM2 (HbA1c 6.5–10%) were randomized to psyllium or wheat dextrin for 12 weeks. Participants were recruited via electronic health records. Key exclusions: GI disease, bariatric surgery, steroid use, and pregnancy. Follow-up visits occurred at weeks 4, 8, and 12. Primary endpoints were changes in HbA1c and fasting glucose; secondary endpoints included lipids, ceramides, hsCRP, and BMI. An ex post facto analysis evaluated GLP-1 use. Primary analysis was intention-to-treat. Adherence = ≥85% dose completion. Results: Ninety-eight participants enrolled (Psyllium n=50, Dextrin n=48) with similar baseline characteristics. At 12 weeks, psyllium significantly reduced HbA1c (-0.38 ± 0.69, p=0.002). Among adherent users, HbA1c dropped further (-0.41 ± 0.70, p=0.001) with reduced fasting glucose (-14.5 ± 38.2, p=0.013). Wheat dextrin showed no benefit. In subgroup analysis, GLP-1 users on psyllium saw greater HbA1c reductions than non-users (-0.45 vs. -0.23), while GLP-1 users on dextrin had no change (+0.06). No significant changes were found in ceramides, lipids, or BMI in any analysis. CRP trended lower in adherent psyllium users (p=0.055). Conclusion: Psyllium significantly reduced HbA1c over 12 weeks in DM2, especially in adherent and GLP-1–treated groups. Effects may be attributed to psyllium's ability to form a gel in the gastrointestinal tract, modulating nutrient absorption. No effects were seen on ceramides or lipids, likely due to low baseline levels in the latter. Psyllium appears to be a safe, accessible adjunct for glycemic control in DM2.

Abstract Background Erectile dysfunction (ED) is a known precursor and sequela of cardiovascular disease (CVD), with ED severity predicting CVD severity. Aim This study aimed to evaluate the utility of ceramide levels in patients with ED. Methods We initiated ceramide testing in all patients with ED. We retrospectively analyzed ceramide levels from electronic records and stratified by severity of symptoms using the erectile function domain of the International Index of Erectile Function (IIEF). Outcomes The study aimed to determine whether abnormal ceramide levels were associated with ED severity and increased cardiovascular risk. Results Three hundred and fifty-four patients were reviewed, of whom 253 (71.5%) had moderate or higher ED. A statistically significant difference in abnormal ceramide values was found in patients with moderate to severe symptoms, and the odds of getting an abnormal ceramide test were increased based on the IIEF scoring alone (odds ratio [OR] 2.3 [1.04-5.12]; P-value = .034). Clinical Implications Serum ceramide testing could be beneficial in identifying cardiovascular risk in men with ED, potentially prompting cardiac referrals and lifestyle modifications. Strengths and Limitations The strengths of this study include a large sample size and the use of a well-established scale, while the limitations include the retrospective nature of the study and the need for further research to validate the findings. Conclusion Patients undergoing management for ED may benefit from serum ceramide testing and subsequent cardiac referral.

Background: Cardiac rehabilitation (CR) is essential to secondary cardiovascular disease prevention and management of cardiac patients. Despite its proven benefits, CR remains underutilized with enrollment and completion rates ranging from 10-30% in the US. Yet, there is a scarcity of nationally representative data among diverse populations on socioeconomic differences in barriers and beliefs of CR participation and delivery mode preferences. Hypothesis: The perceptions (barriers, beliefs), CR delivery mode preferences, and CR utilization (prior enrollment) varies by socioeconomic status (SES) among CR-eligible individuals. Methods: We conducted an anonymous national electronic survey from March 2023 to January 2024 of individuals self-reporting a prior CR-eligible diagnosis. The 22-item CR Barriers Scale assessed perceived barriers to CR enrollment and participation using a 5-point Likert scale (strongly disagree to strongly agree). A 13-item, validated questionnaire assessed 4 subscales pertaining to patients’ beliefs about CR, each rated on a 5-point Likert scale (strongly disagree to strongly agree): perceived necessity, concerns about exercise, practical barriers and perceived suitability. CR delivery mode preferences were ascertained (eg, virtual, at-home, etc.). Mean barriers and belief scores as well as delivery mode preferences were stratified by SES. Low SES was defined as ≤ high school education, Medicaid insurance, or uninsured. High SES was defined as > high school education and non-Medicaid health insurance. Responses were analyzed using descriptive statistics with R software. Results: A total of 466 participants completed the survey (38.1% women, 30.6% minoritized racial/ethnic group, 29.6% low SES, 95% response rate) ( Table 1 ). The majority indicated prior enrollment in CR (81.5%) with no difference by SES. CR barrier scores did not differ significantly by SES (p=0.331) ( Table 2 ). Beliefs about CR perceived necessity and perceived suitability differed by SES (p<0.001 and p=0.025), but beliefs regarding concerns about exercise and practical barriers did not. The low SES group reported a higher preference for completely at-home CR compared to the high SES group (33.6% vs 7.4%, p<0.001). Conclusion: Our findings suggest that CR beliefs varied by SES while utilization did not. For CR-eligible patients experiencing socioeconomic disadvantage, at-home CR may be a preferred alternative to center-based CR to increase CR participation and adherence.

Background Innovative restructuring of cardiac rehabilitation (CR) delivery remains critical to reduce barriers and improve access to diverse populations. Destination Cardiac Rehab is a novel virtual world technology‐based CR program delivered through the virtual world platform, Second Life, which previously demonstrated high acceptability as an extension of traditional center‐based CR. This study aims to evaluate efficacy and adherence of the virtual world–based CR program compared with center‐based CR within a community‐informed, implementation science framework. Methods Using a noninferiority, hybrid type 1 effectiveness‐implementation, randomized controlled trial, 150 patients with an eligible cardiovascular event will be recruited from 6 geographically diverse CR centers across the United States. Participants will be randomized 1:1 to either the 12‐week Destination Cardiac Rehab or the center‐based CR control groups. The primary efficacy outcome is a composite cardiovascular health score based on the American Heart Association Life's Essential 8 at 3 and 6 months. Adherence outcomes include CR session attendance and participation in exercise sessions. A diverse patient/caregiver/stakeholder advisory board was assembled to guide recruitment, implementation, and dissemination plans and to contextualize study findings. The institutional review board–approved randomized controlled trial will enroll and randomize patients to the intervention (or control group) in 3 consecutive waves/year over 3 years. The results will be published at data collection and analyses completion. Conclusions The Destination Cardiac Rehab randomized controlled trial tests an innovative and potentially scalable model to enhance CR participation and advance health equity. Our findings will inform the use of effective virtual CR programs to expand equitable access to diverse patient populations. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05897710.

Background There is a scarcity of validated rapid dietary screening tools for patient use in the clinical setting to improve health and reduce cardiovascular risk. The Healthy Eating Index (HEI) 2015 measures compliance with the 2015 to 2020 Dietary Guidelines for Americans but requires completion of an extensive diet assessment to compute, which is time consuming and impractical. The authors hypothesize that a 19‐item dietary survey assessing consumption of common food groups known to affect health will be correlated with the HEI‐2015 assessed by a validated food frequency questionnaire and can be further reduced without affecting validity. Methods and Results A 19‐item Eating Assessment Tool (EAT) of common food groups was created through literature review and expert consensus. A cross‐sectional survey was then conducted in adult participants from a preventive cardiology clinic or cardiac rehabilitation and in healthy volunteers (n=661, mean age, 36 years; 76% women). Participants completed an online 156‐item food frequency questionnaire, which was used to calculate the HEI score using standard methods. The association between each EAT question and HEI group was analyzed by Kruskal‐Wallis test. Linear regression models were subsequently used to identify univariable and multivariable predictors for HEI score for further reduction in the number of items. The final 9‐item model of Mini‐EAT was validated by 5‐fold cross validation. The 19‐item EAT had a strong correlation with the HEI score ( r =0.73) and was subsequently reduced to the 9 items independently predictive of the HEI score: fruits, vegetables, whole grains, refined grains, fish or seafood, legumes/nuts/seeds, low‐fat dairy, high‐fat dairy, and sweets consumption, without affecting the predictive ability of the tool ( r =0.71). Conclusions Mini‐EAT is a 9‐item validated brief dietary screener that correlates well with a comprehensive food frequency questionnaire. Future studies to test the Mini‐EAT's validity in diverse populations and for development of clinical decision support systems to capture changes over time are needed.

Introduction: Limited validated rapid dietary screening tools are available for patient use for actionable goal setting to improve health and reduce cardiovascular risk. The Healthy Index (HEI) Score measures compliance with the 2015-2020 Dietary Guidelines for Americans but requires completion of an extensive food frequency questionnaire (FFQ) to compute, which is time consuming and impractical. Hypothesis: A 19-item dietary survey that assesses consumption of common food groups known to affect health is correlated to the gold standard FFQ and HEI score and can be further reduced without affecting validity. Methods: An evidence-based 19-item Eating Assessment Tool (EAT™) of common food groups was created through literature review and expert consensus. We then conducted a cross-sectional survey of adult patients from a preventive cardiology clinic or cardiac rehabilitation and of healthy volunteers (n=628, mean age= 37 y, 76% women). Participants completed an online 156-item FFQ which was used to calculate the HEI score using standard methods. The association between each EAT™ question and HEI score category was analyzed by Kruskal-Walis test. Linear regression models were used to identify univariable and multivariable predictors for HEI score. The final model of Mini-EAT™ was validated by 5-fold cross validation. Results: The 19-item EAT™ had good correlation with the HEI (r=0.77) and was subsequently reduced to the 8 items independently predictive of the HEI score: fruits, vegetables, whole grains, refined grains, legumes/nuts/seeds, low-fat dairy, high-fat dairy, and sweets consumption, without affecting the predictive ability of the tool (r=0.76). Conclusions: Mini-EAT™ is an 8-item validated brief dietary screener that correlates well with a comprehensive FFQ. Future studies to test the Mini-EAT™’s validity in diverse populations and for development of clinical decision support systems to capture changes over time are needed.

ABSTRACT Introduction Erectile dysfunction (ED) is a known precursor and sequelae to diagnosed cardiovascular disease (CVD). ED AUA guidelines recommend evaluating standard CV risk factors including serum lipids and penile doppler to help stratify CV risk, but few patients are referred for further evaluation. Plasma ceramides are metabolic byproducts that are novel predictors of adverse cardiovascular events resulting from unstable atherosclerotic plaque. CVD risk conferred by ceramide levels has been shown to be independent of conventional risk factors such as LDL and hsCRP levels. Thus, Plasma MI-Heart Ceramide is a new test that useful for evaluating shorter term major adverse cardiovascular events (MACE) in the next 1 to 5 years. Objective We sought to evaluate the utility of ceramide levels in ED patients Methods We initiated ceramide testing in all patients with ED in late 2019 (in addition to lipids and Hgba1c). We queried our electronic medical record for ceramide levels and men with a diagnosis of ED. Ceramide levels stratified patients in normal, moderate, high, and very high risk. Twenty eight patients additionally had penile duplex ultrasound (DUS). Left and right peak systolic velocity values were averaged and a value of &lt;25 cm/s was defined as penile arterial insufficiency. Results 245 men with ED and ceramide levels were analyzed. 44% (n=107) were normal, 42% (n=103) were moderate risk, 12% (n=29) were high risk and 2% (n=6) were very high risk. As result of their ceramide and office evaluation, 42% (15/35) of high/very high risk patients were referred for cardiac evaluation. Comparing ceramide scores in men with penile arterial insufficiency (16.7 cm/sec) vs patients without (43.2 cm/sec), we found no significant difference (p=1). Similarly, when comparing DUS results between ceramide risk categories, we found no significant differences (p=1). Conclusions One in 7 men presenting to an ED clinic had a high or very high ceramide risk. DUS results did not correlate with ceramide risk. Patients undergoing DUS (even without arterial insufficiency) may benefit from additional ceramide testing and possible cardiac referral. Further study is warranted to optimize utility of ceramide in men with ED and potentially decrease peri-procedural IPP cardiac morbidity. Disclosure No

Background: CHA2DS2-VASc score has been shown to predict occurrences of incident stroke in patients with history of atrial fibrillation (A-Fib)/ Flutter. However, data on whether if CHA2DS2-VASc score would predict incidence of stroke in patients without A-Fib/ Flutter is less clear. Methods: From 1993 through 2010, all patients undergoing a clinically indicated treadmill exercise test (TMET) at the Mayo Clinic, Rochester, MN were identified (N= 76,857). From this, Olmsted and neighboring counties residents were selected (N=14,095). From this, patients with age <18 years; prior history of valvular heart disease or A-Fib/ Flutter were excluded. Patient undergoing only Bruce or accelerated Naughton protocols on TMET were considered. Patients were stratified into 4 groups at baseline based on CHA2DS2-VASc score as determined at the time of TMET; group-0 score=0; group-I=1; group-2=2; group-3≥3. Patients were prospectively followed from the date of TMET until end of January 2016 for occurrence of incident stroke (ischemic and hemorrhagic). Stroke diagnosis was ascertained through retrospective chart review. Traumatic intracranial bleed was not considered. Proportional hazard regression modeling was done to assess relationship of CHA2DS2-VASc score with the stroke outcome while adjusting for METs achieved, sex, obesity, smoking status, and other relevant risk factors. Results: Final study population comprised of 12,624 patients with female comprising 37% of the cohort. Mean age in our study group was 52.2 ± 12.8 years. During an overall median follow-up of 14 (8 to 17) years, 1,255 (9.9%) patients developed incident stroke. While using CHA2DS2-VASc group-3 as referent, patients in CHA2DS2-VASc group-0 [0.18(0.14-0.23, p<.001)], group-1[0.33 (0.28-0.39, p<.001)], and group-2 [0.50 (0.43-0.58, p<.001)] were at significantly lower risk of developing stroke. Each increase of one point on the CHA2DS2-VASc scale was associated with a 51% [1.51(1.45-1.58, p<.001)] increase in incidence of stroke. Conclusion: CHA2DS2-VASc score predicts incidence of stroke in patients without history of A-Fib/ Flutter.

Background: We conducted this study to assess the safety of symptom-limited cardiopulmonary exercise testing (CPX) in patients with varying severity of aortic stenosis (AS). We hypothesized that exercise testing would be safe, as defined by a rates for all-cause death of <0.01% and rate of nonfatal major cardiovascular (CV) events <0.1% within 24 hours of CPX. Secondary purpose of this study was to determine the frequency of complications during CPX. Methods: This cohort study was carried out with 308 consecutive patients with varying degree of AS (as determined by standard echocardiographic criteria) with no or equivocal symptoms who were referred for clinically indicated cardiopulmonary testing between 1994 and 2009. We did not include patients with pending or completed heart transplant, or ventricular assist device implantation. These patients underwent standard symptom limited CPX, and continuous monitoring of heart rate, blood pressure, and electrocardiogram was performed. Complications recorded included death, non-fatal major CV events (cardiac arrest, symptomatic and sustained ventricular or atrial tachycardia, and syncope), and minor events such as hypotension, non-sustained atrial and ventricular arrhythmias, positive exercise ECG and anginal pain. Results: The mean age of patients was 66 ± 14 years, and 252 (82%) were males. The number of patients with mild, moderate and severe AS were 44 (14%), 138 (49%), and 126 (41%) respectively. No death or major CV event occurred during or within 24 hours of CPX. Eleven patients developed supraventricular arrhythmias without compromising hemodynamic status, and one had asymptomatic non-sustained ventricular tachycardia. Detailed description of complications is presented in the Table 1 . Conclusion: Our results show that symptom-limited CPX is safe among AS patients with no or equivocal symptoms based on no deaths or major CV events in our cohort. Minor complications occurred in 110 patients (36%). Table 1 Mild AS (n=44) Moderate AS (n=138) Severe AS (n=126) Age 61.7 ± 15.3 66.5 ± 13.86 67.89 ± 12.74 Males 36 (81%) 128 (83%) 96 (85%) Test protocol O2 protocol 39 (86%) 123 (89%) 104 (82%) Other 5 15 22 Reason for termination Symptom-limited 41 (93%) 114 (82%) 96 (76%) Other 3 24 30 Chest pain None 41 (93%) 122 (88%) 117 (93%) Non-cardiac 0 2 0 Non-anginal 0 2 0 Anginal 2 14 9 Treadmill ECG interpretation Negative 27 (61%) 67 (49%) 45 (37%) Non-diagnostic 14 48 58 Positive 3 23 23 Ventricular arrhythmia None 42 (95%) 134 (97%) 122 (97%) 3-5 beats VT 2 3 4 NSVT 0 1 0 Supraventricular arrhythmia None 42 (95%) 135 (97%) 120 (95%) SVT ≤ 30 sec 2 3 4 SVT > 30 sec 0 0 1 Afib 0 0 1 BP response Normal 41 (93%) 117 (85%) 93 (74%) Hypotensive 3 21 33 AS = Aortic Stenosis, ECG = Electrocardiogram, VT = Ventricular tachycardia, NSVT = Non-sustained ventricular tachycardia, SVT = Supraventricular tachycardia, Afib = Atrial fibrillation, BP = Blood pressure