Effect Of Phenotype On Functional Sympatholysis In Patients With Heart Failure With Preserved Ejection Fraction
Bibliographic record
Abstract
Heart failure with preserved ejection fraction (HFpEF) affects 6.5 million adults in the US and results in debilitating exercise intolerance. Using invasive cardiopulmonary exercise testing, our group has identified two phenotypes of exercise intolerance in patients with HFpEF: those who have central limitations to exercise (lower cardiac output (Qc) relative to oxygen uptake [VO2]), and those who have peripheral limitations (i.e., higher Qc/VO2). However, the mechanisms driving exercise intolerance remain unclear. PURPOSE: To investigate sympathetic-mediated vasoconstrictor responses during single leg knee extension (SLKE) exercise (i.e., functional sympatholysis) between the two phenotypes of HFpEF. We hypothesized that functional sympatholysis would be impaired in patients who have peripheral limitations to exercise compared to those with central limitations. METHODS: We recruited 17 patients with HFpEF; six had central limitations (70 ± 5 years; 3 males), and 11 had peripheral limitations (66 ± 6 years; 2 males) to exercise. Heart rate (ECG), beat-by-beat blood pressure (finger photoplethysmography), and common femoral artery blood flow (BF; duplex Doppler ultrasound) were measured continuously during a cold pressor test (CPT) performed at rest and again during submaximal SLKE (5-7.5 W). Leg vascular conductance (LVC) was calculated as leg BF/mean arterial blood pressure (MAP) and presented as a percent change from the preceding baseline. RESULTS: During the resting CPT, MAP increased (central: 12 ± 10 mmHg; peripheral: 19 ± 11 mmHg; p = 0.245) and LVC decreased (central: -10 ± 5%; peripheral: -11 ± 9%; p 0.281) with no differences between groups. During SLKE-CPT the increase in MAP was also not different between phenotypes (central: 10 ± 5 mmHg; peripheral: 11 ± 12 mmHg; p = 0.812). The decrease in LVC to the SLKE-CPT was smaller compared to the resting CPT, but not different between phenotypes (central: 0 ± 7%; peripheral: -6 ± 19%; p = 0.440), suggesting no difference in functional sympatholysis between phenotypes. CONCLUSION: These preliminary data indicate that patients with HFpEF appear to exhibit functional sympatholysis during exercise. However, contrary to our hypothesis, we did not observe any differences between participants with central versus peripheral limitations to exercise.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".