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

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)

Determinants of exercise intolerance in breast cancerpatients prior to anthracycline chemotherapy

Women with early-stage breast cancer have reduced peak exercise oxygenuptake (peakVO2). The purpose of this study was to evaluate peakVO2andright (RV) and left (LV) ventricular function prior to adjuvant chemotherapy.Twenty-nine early-stage breast cancer patients (mean age: 48 years) and 10age-matched healthy women were studied. Participants performed an uprightcycle exercise test with expired gas analysis to measure peakVO2. RV and LVvolumes and function were measured at rest, submaximal and peak supinecycle exercise using cardiac magnetic resonance imaging. PeakVO2was signif-icantly 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 exerciseheart rate (174 13 vs. 169 16 bpm,P=0.39). Rest, submaximal andpeak exercise RV and LV end-diastolic and end-systolic volume index, strokeindex, and cardiac index were significantly lower in breast cancer patients ver-sus controls (P<0.05 for all). No significant difference was found betweengroups for rest and exercise RV and LV ejection fraction. Despite preservedRV and LV ejection fraction, the decreased peakVO2in early-stage breastcancer patients prior to adjuvant chemotherapy is due in part to decreased peak cardiac index secondary to reductions in RV and LV end-diastolic volumes.status: publishe

International Spillovers of Large-Scale Asset Purchases *

Abstract This paper evaluates the international spillover effects of large-scale asset purchases (LSAPs) using a two-country dynamic stochastic general equilibrium model with nominal and real rigidities, and portfolio balance effects. Portfolio balance effects arise from imperfect substitution between short and long-term bond portfolios in each country, as well as between domestic and foreign bonds within these portfolios. We show that LSAPs lower both domestic and foreign long-term yields, and stimulate economic activity in both countries. International spillover effects become larger as foreigners hold a larger share of long-term bonds in their portfolios at the steady state, as the elasticity of substitution between short and long-term bonds decreases, or as the elasticity of substitution between domestic and foreign bonds increases. We also find that U.S. asset purchases that generate the same output effect as U.S. conventional monetary policy have larger international spillover effects. This is because portfolio balance effects appear to be stronger under unconventional policy, and foreigners&apos; U.S. bond holdings are heavily weighted towards long-term bonds