Mechanisms of reduced exercise capacity in breast cancer survivors compared to patients with HFpEF and controls: insights from comprehensive cardiopulmonary exercise testing
Bibliographic record
Abstract
Abstract Background The risk of heart failure with reduced ejection fraction in breast cancer survivors (BCS) has been well characterized. Emerging evidence suggests BCS may also be at an increased risk of heart failure with preserved ejection fraction (HFpEF). Exercise intolerance – quantified objectively as reduced peak oxygen uptake (VO2) – is a cardinal manifestation of HFpEF and is also commonly reported by BCS. However, the mechanisms contributing to reduced peak VO2 in BCS with preserved left-ventricular ejection fraction (LVEF), and phenotypic overlap with HFpEF, have not been definitively established. Purpose To compare variables measured during cardiopulmonary exercise testing with invasive hemodynamic monitoring (iCPET) among BCS, non-cancer controls (CON), and HFpEF patients referred for exertional dyspnea evaluation. Methods We investigated consecutive female BCS (n=33, 67±9 years old, BMI: 26.9±6.1 kg/m2) who underwent iCPET (10.3±6.2 years post-diagnosis) at a single institution and performed 1:1 propensity-matching on the basis of age, sex, BMI, and presence of hypertension, to patients with confirmed HFpEF (n=33; 66±12 yrs old, BMI: 26.5±5.1 kg/m2), and CON (n=33; 65±9 yrs old, BMI: 27.9±5.0 kg/m2). Maximal upright iCPET with right-heart and radial arterial catheters was performed on an upright cycle ergometer to quantify arterio-venous oxygen content difference (Ca-vO2diff), pulmonary capillary wedge pressure (PCWP), Fick cardiac output (CO), stroke volume (SV), and diffusive muscle O2 conductance (DmO2). Radionuclide ventriculography was used to assess LVEF. Results Relative to CON, both BCS and HFpEF patients had markedly reduced peak VO2 (Fig 1) with a similar degree of impairment between BCS and HFpEF. The lower peak VO2 in BCS and HFpEF was related to comparable deficits in peak exercise oxygen delivery vs CON (Fig 2). In BCS compared to CON, the lower CO was primarily driven by a lower maximal HR (Fig 1E), while in HFpEF this was more-so a result of lower SV (Fig 1F). Peak exercise Ca-vO2diff was similar between all three groups (Fig 1C) but given the increased transit time stemming from lower CO, DmO2 was also impaired in BCS and HFpEF (Fig 2). Compared to CON (1.0±0.4 mmHg/L/min) and HFpEF (3.2±2.0 mmHg/L/min), BCS showed a trend for an intermediate PCWP/CO slope (2.0±2.1 mmHg/L/min; P=0.056 vs CON; P<0.021 vs HFpEF). Seventeen BCS (52%) met diagnostic criteria for HFpEF (supine resting PCWP ≥15 mmHg and/or PCWP/CO slope values >2.0 mmHg/L/min). Conclusions BCS with preserved LVEF can present with marked exercise intolerance, secondary to impairments in central (impaired CO and O2 delivery, increased PCWP at rest and/or exercise) and peripheral factors (reduced DmO2) that show significant overlap with HFpEF pathophysiology. This highlights the importance of considering HFpEF as a cause of exercise intolerance in BCS and the utility of exercise assessments such as iCPET in the evaluation of these patients.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 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".