Early Breast Cancer Therapy and Cardiovascular Injury

Although recent advances in curative-intent therapies are beginning to produce significant survival gains in early breast cancer, these improvements may ultimately be attenuated by increased risk of long-term cardiovascular mortality. This paper reviews emerging evidence on the cardiovascular effects of breast cancer adjuvant therapy and proposes a new entity that we have labeled the “multiple-hit” hypothesis. The evidence that lifestyle modification, especially exercise therapy, may mitigate these adverse effects is also reviewed. These issues are of considerable practical importance for cardiovascular clinicians, as identification and intervention in those at high risk for cardiovascular complications may reduce a major cause of mortality in women with early breast cancer

Stress Testing for Diastolic Dysfunction: An Old Approach to a New Question

BACKGROUND: Currently, conventional cycle echocardiography is the recommended method for diagnosing diastolic dysfunction in patients with unexplained dyspnea upon exertion. However, this method has several underlying limitations including movement and respiratory artifact. These limitations are often exaggerated in patients who are obese and suffer from exertional dyspnea, and therefore limit its application in clinical diagnosis. Our group recently demonstrated that isometric handgrip echocardiography is a powerful sub-clinical diastolic discriminator that avoids the limitations of conventional cycle echocardiography and that can be easily implemented in the clinic. PURPOSE: However, to date it remains unclear how these two methodologies compare, and thus was the focus of the present investigation. We hypothesized that isometric handgrip echocardiography would be a more robust method for unmasking exercise induced diastolic dysfunction compared to conventional cycle echocardiography, due to its markedly different hemodynamic load. METHODS: To test this hypothesis, we recruited 24 individuals from the community (9 male, 15 female, age range: 18 - 80), who all performed 3 minutes of isometric handgrip echocardiography followed by 3 minutes of dynamic cycle exercise (20 W). At rest and during the final minute of each exercise protocol heart rate (HR), mean arterial pressure (MAP) and Doppler derived E/e’ were recorded. Consistent with our previous work, and that of others, individuals who had a change in E/e’ from rest to exercise of \u3e1.5 (ΔE/e’ \u3e 1.5) were defined as responders, while non-responders were defined as ΔE/e’ \u3c 1.5. RESULTS: Both isometric handgrip and low-intensity cycle exercise resulted in a similar rise in HR (ΔHR: 22 ± 13 vs. 25 ± 7, handgrip vs. cycle exercise, P \u3e 0.05), while isometric handgrip resulted in a larger increase in MAP (ΔMAP: 28 ± 14 vs. 16 ± 12, handgrip vs. cycle exercise, P = 0.0003). Remarkably, the increased afterload stress experienced by the myocardium during isometric handgrip exercise was more robust at unmasking sub-clinical diastolic dysfunction in asymptomatic elderly individuals compared to conventional cycle exercise (handgrip: n = 14 vs. n = 10; and cycle: n = 10 vs. n = 14, responders vs. non-responders). CONCLUSION: Taken together, these data highlight the usefulness of isometric handgrip echocardiography at isolating myocardial diastolic relaxation abnormalities in community dwelling individuals, beyond that of dynamic cycle exercise. Future work should focus on confirming the sensitivity of this method in individuals at risk for or with diagnosed heart failure

Determinants of exercise intolerance in breast cancer patients prior to anthracycline chemotherapy

Women with early‐stage breast cancer have reduced peak exercise oxygen uptake (peak V O2). The purpose of this study was to evaluate peak V O2 and right (RV ) and left (LV ) ventricular function prior to adjuvant chemotherapy. Twenty‐nine early‐stage breast cancer patients (mean age: 48 years) and 10 age‐matched healthy women were studied. Participants performed an upright cycle exercise test with expired gas analysis to measure peak V O2. RV and LV volumes and function were measured at rest, submaximal and peak supine cycle exercise using cardiac magnetic resonance imaging. Peak V O2 was significantly lower in breast cancer patients versus controls (1.7 ± 0.4 vs. 2.3 ± 0.5 L/min, P = 0.0013; 25 ± 6 vs. 35 ± 6 mL/kg/min, P = 0.00009). No significant difference was found between groups for peak upright exercise heart rate (174 ± 13 vs. 169 ± 16 bpm, P = 0.39). Rest, submaximal and peak exercise RV and LV end‐diastolic and end‐systolic volume index, stroke index, and cardiac index were significantly lower in breast cancer patients versus controls (P < 0.05 for all). No significant difference was found between groups for rest and exercise RV and LV ejection fraction. Despite preserved RV and LV ejection fraction, the decreased peak V O2 in early‐stage breast cancer patients prior to adjuvant chemotherapy is due in part to decreased peak cardiac index secondary to reductions in RV and LV end‐diastolic volumes

Near-infrared spectroscopy detects age-related differences in skeletal muscle oxidative function: promising implications for geroscience

Age is the greatest risk factor for chronic disease and is associated with a marked decline in functional capacity and quality of life. A key factor contributing to loss of function in older adults is the decline in skeletal muscle function. While the exact mechanism(s) remains incompletely understood, age-related mitochondrial dysfunction is thought to play a major role. To explore this question further, we studied 15 independently living seniors (age: 72 ± 5 years; m/f: 4/11; BMI: 27.6 ± 5.9) and 17 young volunteers (age: 25 ± 4 years; m/f: 8/9; BMI: 24.0 ± 3.3). Skeletal muscle oxidative function was measured in forearm muscle from the recovery kinetics of muscle oxygen consumption using near-infrared spectroscopy (NIRS). Muscle oxygen consumption was calculated as the slope of change in hemoglobin saturation during a series of rapid, supra-systolic arterial cuff occlusions following a brief bout of exercise. Aging was associated with a significant prolongation of the time constant of oxidative recovery following exercise (51.8 ± 5.4 sec vs. 37.1 ± 2.1 sec, P = 0.04, old vs. young, respectively). This finding suggests an overall reduction in mitochondrial function with age in nonlocomotor skeletal muscle. That these data were obtained using NIRS holds great promise in gerontology for quantitative assessment of skeletal muscle oxidative function at the bed side or clinic

Exercise attenuates cardiotoxicity of anthracycline chemotherapy measured by global longitudinal strain [Letter]

[Extract] Anthracycline-based chemotherapy (AC) is a common treatment for patients with breast cancer and has been associated with a dramatic improvement in breast cancer survivorship. Among patients with early-stage breast cancer, cardiovascular diseases represent the most common cause of mortality, and there is a growing emphasis on strategies for minimizing the toxic effects of breast cancer treatments on the cardiovascular system (1)

Exercise attenuates cardiotoxicity of anthracycline chemotherapy measured by global longitudinal strain [Letter]

[Extract] Anthracycline-based chemotherapy (AC) is a common treatment for patients with breast cancer and has been associated with a dramatic improvement in breast cancer survivorship. Among patients with early-stage breast cancer, cardiovascular diseases represent the most common cause of mortality, and there is a growing emphasis on strategies for minimizing the toxic effects of breast cancer treatments on the cardiovascular system (1)