Schmidt, Tyler

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.

Introduction: Cardiac sarcoidosis (CS) is a non-ischemic disease which can present with right ventricular (RV) dysfunction, but there is a paucity of research describing RV function and natural history in CS. Methods: We queried a registry of 512 CS patients for those with baseline and follow-up echocardiography (TTE). Demographics, medications, and baseline/follow-up TTE data were collected. RV-pulmonary arterial (RV-PA) coupling was approximated by ratio of tricuspid annular plane systolic excursion to estimated pulmonary artery systolic pressure (TAPSE:ePASP). Results: Our query yielded 343 CS patients with mean age 56y (σ=12y), who were predominantly male (67%) and white (90%) with a median follow-up 4y (interquartile range 4.1y). Most had pulmonary sarcoidosis (68%). Baseline TTE data showed left ventricular ejection fraction 48% (σ=14), abnormal RV function with RV systolic pressure (ePASP) 34 mmHg (σ=11), TAPSE 21mm (σ=5), RV S′ 0.14 m/s (σ=0.07), and RV-PA uncoupling (TAPSE:ePASP 0.69 mm/mm Hg, σ=0.25). Baseline RV function parameters did not differ by pulmonary involvement of sarcoidosis. 92% received immunosuppression and 65% received neurohormonal blockade. In long-term follow-up, the overall cohort demonstrated a trend towards worsening of both RV S’ and RV-PA coupling (P=.02 and P=.003 for linear trend, respectively) but stable ePASP (P=.11). Trends in both non-invasive ePASP and RV-PA coupling were similar in patients with and without pulmonary involvement (P=.48 and P=.79, respectively). Conclusions: In our large CS cohort with extensive follow-up, metrics of RV function and RV-PA coupling are often abnormal at CS diagnosis. Echocardiographic measures of PASP tend to remain stable but markers of RV dysfunction, including RV-PA coupling, tend to worsen throughout the disease course irrespective of pulmonary sarcoidosis. More granular phenotyping of pulmonary hypertension in CS is required to better understand this relationship.

A 104-year-old woman presented with dyspnoea. Workup revealed normal troponins, elevated D-dimer at 2285 with subsequent chest CT angiogram negative for pulmonary embolism. NT-pro BNP elevated to 5208 pg/mL. Chest X-ray revealed mild cardiac enlargement with bilateral pleural effusions. ECG revealed accelerated junctional rhythm. The initial plan was to obtain transthoracic echocardiogram and start diuresis for presumed heart failure. Given her specific cardiac history, pacemaker interrogation was ordered which revealed her pacemaker mode changed from DDDR to VVI. She underwent pacemaker battery exchange with complete resolution in her symptoms and ability to return to prior functional status. Overall, dyspnoea in centenarians could be multifactorial. Pacemaker elective replacement mode secondary to end of life battery can present as non-specific cardio respiratory symptoms. As the pacemaker population ages to the survival beyond the battery life, pacemaker aetiology behind heart failure symptoms needs to be highly considered by medical providers.

To our knowledge, natural history has not been reported for cardiac sarcoidosis (CS) diagnosed by pathologic evaluation of the apical core at left ventricular assist device (LVAD) implantation or cardiac transplantation. We retrospectively identified 232 consecutive patients meeting CS criteria. Of these patients, 54 were diagnosed by pathologic confirmation of CS, 10 after evaluation of the apical core (LVAD implant) or explanted heart (transplant). We compared clinical characteristics at initial evaluation and outcomes for these 10 patients with those of 10 patients with known CS before LVAD implant/transplant. In the study group, five patients (50%) had confirmed extracardiac sarcoidosis before LVAD implant/transplant; five had not been diagnosed with sarcoidosis. Mean (standard deviation) left ventricular ejection fraction at initial evaluation was 23% (16%), and left ventricular end-diastolic dimension was 61 (10) mm. Four patients died during follow-up; however, no survival difference was found for the 10 patients diagnosed incidentally and the group with a previous diagnosis or institutional LVAD/transplant cohorts. Patients diagnosed with CS on pathological examination of the apical core/explanted heart may have severe dilated cardiomyopathy as the initial presentation. Outcomes for patients with CS after advanced heart failure therapies may be comparable with those of non-CS patients.

Abstract Background Cardiac sarcoidosis (CS) is an infiltrative inflammatory condition defined by infiltration of noncaseating granulomas into the heart. Based on the location of sarcoid lesion involvement, patients can present with symptoms of congestive heart failure, arrhythmias, and even sudden cardiac death. Purpose Diagnosis of CS has been somewhat challenging, with the Heart Rhythm Society (HRS) and Japanese Ministry of Health and Welfare (JMHW) being the 2 widely accepted diagnostic guidelines. Endomyocardial biopsy is the gold standard to prove definite CS but has a low sensitivity. Imaging studies have been helpful as non-invasive methods to diagnose probable CS but these can be logistically difficult and expensive. Thus, investigating for laboratory biomarkers that can act as both diagnostic and prognostic can be crucial in how we diagnose and manage CS in the future. Methods Patients meeting HRS for CS were evaluated at a single institution (n=217). Biomarkers of interest included angiotensin-converting enzyme (ACE), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin-T, 1,25 dihydroxyvitamin D (1,25-OHVit-D), and creatinine. Biomarkers were stratified by clinical variables of interest and their association with prognosis was examined. The primary endpoint was LVAD implantation, transplantation, or death. Results Mean values on presentation were: ACE 32.9±28, ESR 12±13, CRP 7.4±19, NT-proBNP 1630±2923, Troponin-T 0.03±0.1, 1,25-OHVit-D 55.5±20, and creatinine 1.12±0.3. None of the biomarkers differed by sex, definite or probable CS, or a history of immunosuppression. ACE levels were associated with the presence of cardiac fibrosis on cardiac MRI (mean difference 14.7, p=0.032). Troponin-T (p=0.006; HR 1.06 per 0.01 ng/mL), NT-proBNP (p=0.0003; HR 1.31 per 1,000 pg/mL), and creatinine (p=0.01; HR 4.02 per mg/dL) were each associated with the primary endpoint (52/217 patients). Biomarkers associated with long term outcomes in patients with cardiac sarcoidosis Biomarker Hazard ratio P value Troponin-T 1.06 (1.02–1.11)* 0.006 NT-pro BNP 1.31 (1.15–1.48)** 0.0003 Creatinine 4.02 (1.41–9.94)*** 0.01 *Per 0.01 ng/mL change; 99th percentile upper reference limit <0.01 ng/mL; **per 1,000 pg/mL change; ***per 1 mg/dL change. Conclusion Troponin-T, NT-proBNP, and creatinine at presentation predict outcomes in patients with CS. Further investigation on the utility of biomarkers for assessment of disease activity and treatment response is warranted.