Exercise limitations in heart failure with preserved ejection fraction and obesity: is the issue the engine or chassis?
Bibliographic record
Abstract
Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome characterized by reduced peak oxygen uptake (VO2peak) secondary to central and peripheral limitations. Obesity is a well-established risk factor for HFpEF and has garnered considerable interest as a therapeutic target, particularly in the context of the obese-HFpEF phenotype. However, the impact of obesity on VO2peak and its Fick determinants in HFpEF remains unclear. Purpose To understand the impact of obesity on VO2peak and it’s central and peripheral determinants in individuals with HFpEF. Methods Patients referred to a multi-disciplinary unexplained dyspnea clinic with an established HFpEF diagnosis were included (n=448), and sub-grouped based on body mass index (BMI, ≥30 kg/m2 or <30) into HFpEF with- (HFpEFObese, n=138; BMI=34.3±3.7 kg/m2; 68% female; 71±9 yrs) or without obesity (HFpEFNon-Obese, n=310; BMI=24.9±3.0 kg/m2; 60% female; 74±9 yrs.). Patients underwent maximal cardiopulmonary exercise testing with simultaneous echocardiography (CPETecho) to assess VO2peak, exercise hemodynamics (cardiac output, CO; stroke volume, SV; heart rate, HR, mean pulmonary artery pressure, mPAP) and the arterio-venous oxygen difference (a-vO2diff). HFpEF sub-groups were compared using ANCOVA with adjustment for age and sex. Comparison was made using absolute values and values adjusted for bodyweight (peak VO2) or body surface area (BSA; CO, SV) . Pooled HFpEF sub-groups were also compared using ANCOVA (adjusted for age and sex) to controls (CON, n=153; BMI: 23.1±2.7 kg/m2, 41% female; 62±5 yrs) without HFpEF to elucidate the impact of HFpEF, versus HFpEF plus obesity on VO2peak and its determinants. Results HFpEFObese and HFpEFNon-Obese had comparable absolute VO2peak, peak exercise HR and a-vO2diff, while HFpEFObese had higher CO at peak exercise secondary to a larger SV. Resting and exercise mPAP and mPAP-CO slopes were higher in HFpEF vs CON (P<0.001 for all; Fig. 2), with no differences seen between HFpEF obesity phenotypes (P>0.50 for all). In contrast, bodyweight-adjusted peak VO2 was markedly lower in HFpEFObese (Fig. 1B), despite comparable peak exercise cardiac index and stroke volume index. Regardless of HFpEF sub-group, peak VO2, central (CO, HR, mPAP) and peripheral factors (a-vO2diff) were markedly impaired in HFpEF versus CON (Fig. 1). Conclusions Obese HFpEF patients demonstrate a higher stroke volume reserve while maintaining oxygen extraction. However, these adaptations are insufficient to sustain weight-adjusted peak VO2 at the levels of their non-obese counterparts. This suggests that obesity induces adaptive cardiac and peripheral muscle remodeling. Accordingly, HFpEF patients achieving weight reduction should be supported with adjuvant exercise training programs to preserve cardiac and peripheral muscle performance as the load of excess body mass is alleviated, thereby enhancing exercise tolerance.Fig 1.Differences in VO2 determinantsFig 2.Differences in mPAP and CO
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".