Sympathetic vasoconstrictor constraint on exercise capacity in heart failure: does biological sex matter?
Bibliographic record
Abstract
Abstract Background/Introduction Exercise intolerance in heart failure (HF) predicts both quality of life and survival. Female patients often present with more disabling symptoms. We discovered, in HF, regardless of left ventricular ejection fraction (LVEF), a ‘paradoxical’ reflex increase in vasoconstrictive muscle sympathetic nerve activity (MSNA) during 1-leg cycling exercise in patients across the spectrum, absent in healthy individuals, and an inverse relationship between MSNA during cycling and exercise capacity (peak oxygen uptake; V̇O2peak). Purpose Our present aim was to test the hypothesis that females with HF display a greater ‘paradoxical’ muscle sympatho-excitatory response than males. Methods We investigated 15 female (68±8 yrs; LVEF: 40±16%, range 20-67; BMI: 30±9 kg/m2) and 41 male (64±9 yrs; LVEF: 38±15%, range 15-73; BMI: 29±5 kg/m2) patients with chronic, stable HF, treated for such with contemporary guideline-based medical therapy. In the seated position, we measured heart rate (HR), blood pressure (BP), and MSNA (microneurography) during 2 minutes of baseline rest and 4 minutes of 1-leg cycling (2 minutes each at mild [0 load] and moderate [~30-40% V̇O2peak] intensity). V̇O2peak was obtained by open circuit spirometry during a standard, symptom-limited incremental cycling test (15 W·min-1). Results Resting HR (64±10 vs. 63±10 beats·min-1; P=0.89), systolic BP (115±19 vs. 105±16 mmHg; P=0.09), and diastolic BP (65±12 vs. 64±10 mmHg; P=0.84) did not differ between females and males, respectively. Resting MSNA also was not different between females and males (51±11 vs. 50±11 bursts·min-1; P=0.70), whereas V̇O2peak was lower in females (15±5 vs. 21±8 ml·kg-1·min-1; P<0.01). During 1-leg cycling exercise, HR (+12±6 vs. +10±6 beats·min-1 at moderate cycling) and diastolic BP (+13±10 vs. +7±8 beats·min-1 at moderate cycling) increased similarly in females and males, respectively (both P>0.05), whereas the systolic BP response during moderate cycling was greater in females (+25±22 vs. +15±9 mmHg; P=0.03). Similarly, compared to baseline rest, MSNA increased during mild and moderate cycling in both sexes (all P<0.05), yet the magnitude of response during moderate cycling was greater in females than males (+9±6 vs. +4±10 bursts·min-1; P=0.03). In both sexes, the level of MSNA during moderate intensity cycling related inversely to V̇O2peak, explaining 42% of the variance in females (P<0.01), yet only 10% in males (P=0.05). Conclusions In patients with HF, the ‘paradoxical’ muscle sympathetic vasoconstrictor response to dynamic exercise is more pronounced in females than in males, which likely constrains to a larger extent, skeletal muscle blood flow and increases resistance, thereby contributing to the more severe exercise intolerance observed in female patients. Our findings may help inform novel, female-specific therapeutic strategies designed to reverse such sympathetic disturbances, alleviate symptoms, and improve exercise capacity.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.008 | 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".