Adel, Fadi W

BACKGROUND: Although diabetes is a known driver of heart failure with preserved ejection fraction, whether antecedent hyperinsulinemia drives preclinical diastolic dysfunction (DD) progression before overt hyperglycemia remains unknown. Therefore, we investigated whether elevated endogenous insulin and insulin resistance independently predict longitudinal DD progression and adverse cardiovascular outcomes. METHODS: In a community-based cohort study, we evaluated 1191 participants from the Olmsted County Heart Function Study (median age, 58.7 [interquartile range, 52.4–66.6 years]) who underwent echocardiography at baseline and after 4 years. Fasting insulin and homeostatic model assessment of insulin resistance were assessed. The primary end point was DD progression. Secondary outcomes (mortality, heart failure) were assessed in 2030 participants followed for a median of 10.97 (95% CI, 10.90–11.05) years for heart failure and a median of 18.1 (95% CI, 18.0–18.2) years for mortality. RESULTS: DD progression occurred in 7.5% of participants. Baseline fasting insulin and homeostatic model assessment of insulin resistance strongly predicted progression ( P <0.001). In multivariable analysis, every 1-SD increase in log-transformed insulin was associated with 65% increased odds of progression (odds ratio, 1.65 [95% CI, 1.33–2.07]; P <0.001), adjusting for age, creatinine, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Similar results were observed for homeostatic model assessment of insulin resistance (odds ratio, 1.66 [95% CI, 1.34–2.08]; P <0.001). In secondary analyses, elevated insulin independently predicted all-cause (hazard ratio, 1.11 per 1-SD [95% CI, 1.02–1.21]) and cardiovascular mortality (hazard ratio, 1.16 [95% CI, 1.02–1.33]). Homeostatic model assessment of insulin resistance was similarly predictive of all-cause (hazard ratio, 1.11 [95% CI, 1.03–1.20]) and cardiovascular mortality (hazard ratio, 1.16 [95% CI, 1.02–1.32]). CONCLUSIONS: Elevated endogenous insulin and insulin resistance are predictors of progressive DD and long-term mortality, even after accounting for body mass index. Metabolic dysregulation may drive myocardial stiffening before diabetes onset, identifying a potential early therapeutic window for heart failure with preserved ejection fraction prevention.

Gross anatomy is now delivered in curricula that are increasingly compressed and integrated with other areas of medical training. At the same time, digital resources and physical models have become more common as supplementary tools in anatomy education. These shifts have renewed interest in the distinctive educational value of donor-based learning and in how preservation methods should be aligned with clinically meaningful learning objectives. This narrative review examines the use of fresh human donor tissue in anatomy teaching and clinically oriented procedural training. It focuses on unembalmed, non-fixed, and fresh-frozen tissue, while soft-preserved tissue is considered mainly as contextual and comparative evidence. Literature searches were conducted in MEDLINE, Scopus, Web of Science, and ERIC databases for English-language human studies published from 2015 through early 2026, with backward citation to identify older landmark comparator papers. Because the preservation-explicit educational literature was limited and heterogenous, findings were synthesized narratively. Across the included literature, fresh tissue appears most educationally valuable when learning objectives depend on functional tissue behavior, including tissue palpation, percussion, tissue-plane recognition, ultrasound-guided anatomy, or realistic procedural handling. Available studies suggest benefits in selected knowledge and performance outcomes, especially in clinically oriented examination and postgraduate refresher courses. Comparator evidence indicates that soft-preserved tissue may provide a pragmatic alternative when programs need repeated access or broader curricular integration while still preserving more realistic handling than formal fixed donors. Formalin fixed tissue remains useful for durable structural teaching despite reduced functional realism. Overall, preservation methods should be treated as a curricular design decision rather than a neutral technical detail. Fresh tissue therefore has a defensible place in competency-based anatomy education when used selectively for tasks requiring high functional fidelity, although stronger evidence for long-term clinical transfer remains limited.

Abstract Aims Define the relationship between N‐terminal atrial natriuretic peptide (NT‐ANP) levels and incident metabolic syndrome and type 2 diabetes mellitus (‘metabolic disease’) in healthy adults and develop a risk prediction score. Materials and Methods Retrospective cohort study of Olmsted County Heart Function Study participants, a random sampling of county residents aged 45 years and older ( n = 2042). Clinical data were collected during enrolment between 1997 and 2000 and upon follow‐up 4 years later. Outcomes were followed for 8 years. We studied 715 subjects without metabolic disease at enrolment who completed follow‐up, assessing incident metabolic disease as the primary outcome. Youden's index was used to identify optimal cut‐points and develop the risk score. Results Upon multivariate analysis adjusting for age gender, HDL and triglycerides, higher baseline serum NT‐ANP levels were associated with a lower risk of metabolic disease (OR: 0.65, CI 0.49–0.85, p = 0.002). Higher baseline serum insulin and aldosterone levels were associated with higher risk of incident metabolic disease (OR: 2.04, CI 1.57–2.65, p < 0.001; OR: 1.43, CI 1.14–1.81, p = 0.002, respectively). Baseline serum NT‐ANP < 3337 pg/mL was 96.6% sensitive for future development of metabolic disease. A weighted score including all three biomarkers was 78.6% sensitive and 77.3% specific. Conclusions In healthy adults aged 45 years or older, higher baseline NT‐ANP levels are associated with a lower four‐year risk of developing metabolic disease. Serum NT‐ANP levels are a sensitive biomarker of future risk of metabolic disease and have screening utility when combined with insulin and aldosterone levels into a composite score.

Abstract Aims Gender-affirming hormone therapy (GAHT) is used by some transgender individuals (TG), who comprise 1.4% of US population. However, the effects of GAHT on electrocardiogram (ECG) remain unknown. The objective is to assess the effects of GAHT on ECG changes in TG. Methods and results Twelve-lead ECGs of TG on GAHT at the Mayo Clinic were inspected using a validated artificial intelligence (AI) algorithm. The algorithm assigns a patient’s ECG male pattern probability on a scale of 0 (female) to 1 (male). In the primary analysis, done separately for transgender women (TGW) and transgender men (TGM), 12-lead ECGs were used to estimate the male pattern probability before and after GAHT. In a subanalysis, only patients with both pre- and post-GAHT EGCs were included. Further, the autopopulated PR, QRS, and QTc intervals were compared before and after GAHT. Among TGW (n = 86), the probability (mean ± SD) of an ECG male pattern was 0.84 ± 0.25 in the pre-GAHT group, and it was lowered to 0.59 ± 0.36 in the post-GAHT group (n = 173, P &lt; 7.8 × 10−10). Conversely, among TGM, male pattern probability was 0.16 ± 0.28 (n = 47) in the pre-GAHT group, and it was higher at 0.41 ± 0.38 in the post-GAHT group (n = 53, P &lt; 2.4×10−4). The trend persisted in the subanalysis. Furthermore, both the PR (P = 5.68 × 10−4) and QTc intervals (P = 6.65×10−6) prolonged among TGW. Among TGM, the QTc interval shortened (P = 4.8 × 10−2). Conclusion Among TG, GAHT is associated with ECG changes trending towards gender congruence, as determined by the AI algorithm and ECG intervals. Prospective studies are warranted to understand GAHT effects on cardiac structure and function.

Background Phosphodiesterase V (PDEV) is upregulated in heart failure, leading to increased degradation of cGMP and impaired natriuresis. PDEV inhibition improves the renal response to B‐type natriuretic peptide in animal models. We tested the hypothesis that long‐term PDEV inhibition would improve renal function and cardiorenal response after short‐term volume load in subjects with pre–heart failure. Methods and Results A total of 20 subjects with pre–heart failure (defined as an ejection fraction ≤45% without previous diagnosis of heart failure) and renal impairment were randomized in a 2:1 manner to tadalafil or placebo. Baseline echocardiography and renal clearance study were performed, followed by a short‐term saline load and repeated echocardiography and renal clearance study. Subjects then received either tadalafil at a goal dose of 20 mg daily or placebo, and the study day was repeated after 12 weeks. Long‐term tadalafil did not improve glomerular filtration rate (median increase of 2.0 mL/min in the tadalafil group versus 13.5 mL/min in the placebo group; P =0.54). There was no difference in urinary sodium or cGMP excretion with PDEV inhibition following short‐term saline loading. Conclusions Glomerular filtration rate and urinary sodium/cGMP excretion were not significantly different after 12 weeks of tadalafil compared with placebo. These results do not support the use of PDEV inhibition to improve renal response in patients with pre–heart failure. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01970176.