The effect of inhaled nitric oxide on maximal oxygen consumption during exercise in acute hypoxia: a randomized double-blind crossover trial.

In moderate hypoxia [partial pressure of inspired oxygen ([Formula: see text]) = 85-111 mmHg], the reduction in maximal oxygen consumption (V̇o2max) has been attributed to arterial desaturation, whereas in severe hypoxia ([Formula: see text] < 85 mmHg), elevated pulmonary artery pressure (PAP) is thought to impair peak cardiac output ([Formula: see text]) and therefore V̇o2max. The purpose of this study was to examine whether reducing PAP with inhaled nitric oxide (iNO, a selective pulmonary vasodilator) would increase V̇o2max in moderate and severe acute hypoxia. Twelve young, healthy participants (mean V̇o2max = 45.3 ± 12.2 mL/kg/min), with normal lung function completed the randomized double-blind crossover study over six sessions. Experimental cardiopulmonary exercise tests (CPET) were completed on separate days with participants under the following conditions: 1) acute moderate hypoxia ([Formula: see text] = 89 mmHg), 2) acute severe hypoxia ([Formula: see text] = 79 mmHg), 3) acute moderate hypoxia with 40 ppm iNO, and 4) acute severe hypoxia with 40 ppm iNO (order randomized). On separate days, rest, and exercise (60 W), echocardiography was conducted to determine right ventricular systolic pressure (RVSP/PAP) under conditions 1-4. Resting RVSP was reduced by 2.5 ± 0.8 mmHg with iNO in moderate hypoxia (P = 0.01) and 1.8 ± 0.2 mmHg in severe hypoxia (P = 0.05); however, iNO had no effect on peak [Formula: see text] or V̇o2max in either hypoxic condition. Despite reducing RVSP with iNO in hypoxia, peak [Formula: see text] and V̇o2max were unaffected, suggesting that iNO may not improve exercise tolerance in healthy participants during hypoxic exercise.NEW & NOTEWORTHY The elevation of pulmonary artery pressure (PAP) with hypoxia may impair peak cardiac output ([Formula: see text]) and therefore V̇o2max. Our novel findings show that despite reducing resting RVSP in acute moderate ([Formula: see text] = 89 mmHg) and severe hypoxia ([Formula: see text] = 79 mmHg) with inspired nitric oxide, peak [Formula: see text], and V̇o2max were unaffected.

Too Little of a Good Thing: Strong Associations Between Cardiac Size and Fitness Among Women.

BACKGROUND: Cardiorespiratory fitness (CRF) is associated with functional impairment and cardiac events, particularly heart failure (HF). However, the factors predisposing women to low CRF and HF remain unclear. OBJECTIVES: This study sought to evaluate the association between CRF and measures of ventricular size and function and to examine the potential mechanism linking these factors. METHODS: A total of 185 healthy women aged >30 years (51 ± 9 years) underwent assessment of CRF (peak volume of oxygen uptake [Vo2peak]) and biventricular volumes at rest and during exercise by using cardiac magnetic resonance (CMR). The relationships among Vo2peak, cardiac volumes, and echocardiographic measures of systolic and diastolic function were assessed using linear regression. The effect of cardiac size on cardiac reserve (change in cardiac function during exercise) was assessed by comparing quartiles of resting left ventricular end-diastolic volume (LVEDV). RESULTS: Vo2peak was strongly associated with resting measures of LVEDV and right ventricular end-diastolic volume (R2 = 0.58-0.63; P < 0.0001), but weakly associated with measures of resting left ventricular (LV) systolic and diastolic function (R2 = 0.01-0.06; P < 0.05). Increasing LVEDV quartiles were positively associated with cardiac reserve, with the smallest quartile showing the smallest reduction in LV end-systolic volume (quartile [Q]1: -4 mL vs Q4: -12 mL), smallest augmentation in LV stroke volume (Q1: +11 mL vs Q4: +20 mL) and cardiac output (Q1: +6.6 L/min vs Q4: +10.3 L/min) during exercise (interaction P < 0.001 for all). CONCLUSIONS: A small ventricle is strongly associated with low CRF because of the combined effect of a smaller resting stroke volume and an attenuated capacity to increase with exercise. The prognostic implications of low CRF in midlife highlight the need for further longitudinal studies to determine whether women with small ventricles are predisposed to functional impairment, exertional intolerance, and HF later in life.

Exercise Leg Blood Flow Is Preserved in Long-term Breast Cancer Survivors Previously Treated With Anthracycline Chemotherapy.

PURPOSE: The objective of this investigation was to compare the acute hemodynamic responses during single-leg knee extension (SLKE) exercise between female breast cancer (BC) survivors previously treated with anthracycline chemotherapy and age- and sex-matched control (CON) subjects. METHODS: Fourteen BC survivors (age: 61 ± 7 yr; time post-anthracycline therapy: 12 ± 6 yr) and nine CON subjects (age: 59 ± 7 yr) performed SLKE exercise at 25%, 50%, and 75% of peak power output during which heart rate, blood pressure (BP), leg blood flow (Doppler ultrasonography), and vascular conductance (leg blood flow/mean BP) were measured. Quadriceps mass was estimated from thigh volume and skinfold measures. RESULTS: Breast cancer survivors had lower quadriceps mass compared with CON subjects (1803 ± 607 vs 2601 ± 1102 g, P = .04). No difference was found between groups for maximal SLKE power output (28 ± 11 vs 34 ± 17 W, P = .35), heart rate (109 ± 14 vs 103 ± 13 bpm, P = .36), or mean arterial BP (122 ± 18 vs 119 ± 26 mm Hg, P = .33). Rest and submaximal exercise mean arterial BP, leg blood flow (indexed to quadriceps muscle mass), and leg vascular conductance were not significantly different between BC survivors and CON subjects. CONCLUSION: Leg blood flow during submaximal SLKE exercise is preserved in long-term BC survivors previously treated with anthracycline chemotherapy.

A single breath of nitric oxide does not alter pulmonary perfusion pressure.

NEW FINDINGS: What is the central question of this study? Is the amount of inhaled nitric oxide (NO) used during a diffusing capacity for inhaled NO manoeuvre sufficient to reduce pulmonary artery systolic pressure (PASP)? What is the main finding and its importance? These findings suggest that a single breath of inhaled NO does not change PASP, and combined with previous correlational work, further validates the use of the diffusing capacity for NO manoeuvre as a technique to determine pulmonary capillary blood volume and membrane diffusing capacity. ABSTRACT: The measurement of diffusing capacity is an important pulmonary function test to evaluate gas exchange. Using both carbon monoxide and nitric oxide (NO), the diffusing capacity for nitric oxide (DL,NO ) technique allows for the partitioning of capillary blood volume and membrane diffusing capacity. However, inhaled NO is known to dilate pulmonary arterioles in both health and disease and therefore could alter the outcomes that the DL,NO technique aims to quantify. The purpose of the study was to determine if a DL,NO manoeuvre alters pulmonary perfusion pressure. Nine participants completed 12 simulated 10-s breath-hold DL,NO manoeuvres (n = 6 placebo inhalations and n = 6 with 40 ppm NO; order randomized) during which tricuspid regurgitant jet velocity was recorded continuously using Doppler ultrasound to estimate pulmonary artery systolic pressure (PASP) as a surrogate for pulmonary perfusion pressure. The PASP was not different between the placebo and NO conditions (P = 0.742). These data indicate that a single DL,NO manoeuvre does not alter PASP and therefore would not be expected to acutely alter pulmonary capillary blood volume or membrane diffusing capacity.

Prescribing Exercise in Early-Stage Breast Cancer During Chemotherapy: A Simple Periodized Approach to Align With the Cyclic Phases of Chemotherapy.

ABSTRACT: Bigaran, A, Howden, EJ, Foulkes, S, Janssens, K, Beaudry, R, Haykowsky, MJ, La Gerche, A, Fraser, SF, and Selig, SE. Prescribing exercise in early-stage breast cancer during chemotherapy: a simple periodized approach to align with the cyclic phases of chemotherapy. J Strength Cond Res 36(10): 2934-2941, 2022-To evaluate whether a periodized aerobic and resistance training plan aligned to the anthracycline chemotherapy (AC) cycles would be well tolerated, feasible, and attenuate the decline in peak oxygen uptake (V̇o2peak) in breast cancer (BC) patients. Twenty-eight women with early-stage BC treated with AC self-selected to undertake exercise training (EX 47 ± 9 years, n = 14) or usual care (53 ± 9 years, n = 14) for 12 weeks as part of a nonrandomized controlled trial. The periodized EX was aligned to the cyclic phases of AC, including AC taper and nontaper weeks. Outcome measures included cardiopulmonary exercise testing. Attendance and adherence variables (relative dose intensity [RDI] and volume load) were calculated to quantify the dose of EX completed relative to the amount of EX prescribed. The mean session attendance was 76% (range 46-88%). The mean ± SD prescribed and completed dose of aerobic training was 332.3 ± 48.7 MET h·wk-1 and 380.6 ± 53.2 MET h·wk-1 (p = 0.02), equating to a mean RDI of 89 ± 17%. For resistance training, the prescribed and completed cumulative dose was 128,264 ± 54,578 and 77,487 ± 26,108 kg (p < 0.001), equating to an RDI of 60 ± 11%. Adherence to the AC taper week RDI (52 ± 14%) for resistance training was significantly lower than the non-AC taper week (72 ± 8%, p = 0.02). The most frequent cause for EX interruption was hospitalization (35%), whereas AC-related illness was the most common cause for missed (57%) or modified EX sessions (64%). This periodized approach was mostly well tolerated for patients with BC. We speculate that a periodized approach may be both more palatable and useful, although this requires further investigation in a randomized controlled trial.

Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls.

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV. Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.

Cardiac mechanisms for low aerobic power in anthracycline treated, older, long-term breast cancer survivors.

Breast cancer survivors have reduced peak aerobic capacity (VO2peak) which may be related to latent or lingering chemotherapy induced cardiac damage. Nine, older (67 ± 3 years), long-term survivors (9.8 years) of anthracycline based chemotherapy and age- and sex-matched healthy controls were recruited and tested to determine whether: i) VO2peak remains reduced in long-term survivorship; and ii) reductions in VO2peak are due to cardiac dysfunction. VO2peak was significantly reduced in breast cancer survivors relative to healthy controls (15.9 ± 2.0 vs 19.9 ± 3.1 ml/kg/min, p = 0.006), however the heart rate and stroke volume responses to exercise were normal (heart rate reserve; 88 ± 9 vs 85 ± 10 bpm, p = 0.62: stroke volume reserve; 13 ± 6 vs 13 ± 9 ml,p = 0.94). These findings indicate low-normal ventricular size in long-term breast cancer survivors, but normal reserve function.

Inhaled nitric oxide does not improve maximal oxygen consumption in endurance trained and untrained healthy individuals.

PURPOSE: Previous work suggests that endurance-trained athletes have superior pulmonary vasculature function as compared to untrained individuals, which may contribute to their greater maximal oxygen uptake ([Formula: see text]O2max). Inhaled nitric oxide (iNO) reduces pulmonary vascular resistance in healthy individuals, which could translate into greater cardiac output and improved [Formula: see text]O2max, particularly in untrained individuals. The purpose of the study was to examine whether iNO improved [Formula: see text]O2max in endurance trained and untrained individuals. METHODS: Sixteen endurance-trained and sixteen untrained individuals with normal lung function completed this randomized double-blind cross-over study over four sessions. Experimental cardiopulmonary exercise tests were completed while breathing either normoxia (placebo) or 40 ppm of iNO, on separate days (order randomized). On an additional day, echocardiography was used to determine pulmonary artery systolic pressure at rest and during sub-maximal exercise (60 Watts) while participants breathed normoxia or iNO. RESULTS: Right ventricular systolic pressure was significantly reduced by iNO during exercise (Placebo: 34 ± 7 vs. iNO: 32 ± 7; p = 0.04). [Formula: see text]O2max was greater in the endurance trained group (Untrained: 3.1 ± 0.7 vs. Endurance: 4.3 ± 0.9 L min-1; p < 0.01), however, there was no effect of condition (p = 0.79) and no group by condition interaction (p = 0.68). Peak cardiac output was also unchanged by iNO in either group. CONCLUSION: Despite a reduction in right ventricular systolic pressure, the lack of change in [Formula: see text]O2max with iNO suggests that the pulmonary vasculature does not limit [Formula: see text]O2max in young healthy individuals, regardless of fitness level.

Cardiac and skeletal muscle predictors of impaired cardiorespiratory fitness post-anthracycline chemotherapy for breast cancer.

This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO2peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy ~ 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO2peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 ± 9 vs 57 ± 10 mL/m2, p = 0.038), GLS (- 30.4 ± 2.2 vs - 28.0 ± 2.5%, p = 0.008), and arteriovenous oxygen difference (16.4 ± 3.6 vs 15.2 ± 3.9 mL/100 mL, p = 0.054). Mediation analysis showed: (1) greater myocardial T1 time (fibrosis) is inversely related to cardiac output and end-systolic volume exercise reserve; (2) greater thigh muscle fatty infiltration is inversely related to arteriovenous oxygen difference; both of which negatively influence VO2peak. Peak SV (R2 = 65%) and thigh muscle fat fraction (R2 = 68%) were similarly strong independent predictors of VO2peak in BCS and matched-CON combined. Post-anthracyclines, myocardial fibrosis is associated with impaired cardiac reserve, and thigh muscle fatty infiltration is associated with impaired oxygen extraction, which both contribute to VO2peak.

Aerobic Fitness Is Related to Myocardial Fibrosis Post-Anthracycline Therapy.

PURPOSE: We evaluated the impact of anthracyclines on left ventricular function and myocardial tissue characteristics using cardiovascular magnetic resonance (CMR) imaging to determine their relationship with V˙O2peak. METHODS: Women with breast cancer who had not yet received treatment (No-AT, n = 16) and had received anthracycline treatment ~1 yr earlier (Post-AT, n = 16) and controls without cancer (CON, n = 16) performed a maximal exercise test and a comprehensive 3T CMR examination, including native myocardial T1 mapping, where elevated T1 times are indicative of myocardial fibrosis. ANOVA and linear regression were used to compare CMR variables between groups and to determine associations with V˙O2peak. Subgroup analysis was performed by categorizing participants as "fit" or "unfit" based on whether their V˙O2peak value was greater or less than 100% of reference value for age, respectively. RESULTS: Left ventricular end-diastolic volume, ejection fraction, and mass were similar between groups. Post-AT, T1 times were elevated (1534 ± 32 vs 1503 ± 28 ms, P < 0.01), and V˙O2peak was reduced (23.1 ± 7.5 vs 29.5 ± 7.7 mL·kg-1⋅min-1, P = 0.02) compared with CON. In No-AT, T1 times and V˙O2peak were similar to CON. In the Post-AT group, T1 time was associated with V˙O2peak (R2 = 64%), whereas in the absence of anthracyclines (i.e., No-AT and CON groups), T1 time was not associated with V˙O2peak. Regardless of group, all fit women had similar T1 times, whereas unfit women Post-AT had higher T1 than unfit CON (1546 ± 22 vs 1500 ± 33 ms, P < 0.01). CONCLUSIONS: After anthracycline chemotherapy, an elevated T1 time suggesting greater extent of myocardial fibrosis, was associated with lower V˙O2peak. However, those who were fit did not have evidence of myocardial fibrosis after anthracycline treatment.

Exercise Intolerance in Anthracycline-Treated Breast Cancer Survivors: The Role of Skeletal Muscle Bioenergetics, Oxygenation, and Composition.

BACKGROUND: Peak oxygen consumption (VO2 ) is reduced in women with a history of breast cancer (BC). We measured leg blood flow, oxygenation, bioenergetics, and muscle composition in women with BC treated with anthracycline chemotherapy (n = 16, mean age: 56 years) and age- and body mass index-matched controls (n = 16). MATERIALS AND METHODS: Whole-body peak VO2 was measured during cycle exercise. 31 Phosphorus magnetic resonance (MR) spectroscopy was used to measure muscle bioenergetics during and after incremental to maximal plantar flexion exercise (PFE). MR imaging was used to measure lower leg blood flow, venous oxygen saturation (Sv O2 ), and VO2 during submaximal PFE, and abdominal, thigh, and lower leg intermuscular fat (IMF) and skeletal muscle (SM). RESULTS: Whole-body peak VO2 was significantly lower in BC survivors versus controls (23.1 ± 7.5 vs. 29.5 ± 7.7 mL/kg/minute). Muscle bioenergetics and mitochondrial oxidative capacity were not different between groups. No group differences were found during submaximal PFE for lower leg blood flow, Sv O2 , or VO2 . The IMF-to-SM ratio was higher in the thigh and lower leg in BC survivors (0.36 ± 0.19 vs. 0.22 ± 0.07, p = .01; 0.10 ± 0.06 vs. 0.06 ± 0.02, p = .03, respectively) and were inversely related to whole-body peak VO2 (r = -0.71, p = .002; r = -0.68, p = .003, respectively). In the lower leg, IMF-to-SM ratio was inversely related to VO2 and O2 extraction during PFE. CONCLUSION: SM bioenergetics and oxidative capacity in response to PFE are not impaired following anthracycline treatment. Abnormal SM composition (increased thigh and lower leg IMF-to-SM ratio) may be an important contributor to reduced peak VO2 during whole-body exercise among anthracycline-treated BC survivors. IMPLICATIONS FOR PRACTICE: Peak oxygen consumption (peak VO2 ) is reduced in breast cancer (BC) survivors and is prognostic of increased risk of cardiovascular disease-related and all-cause mortality. Results of this study demonstrated that in the presence of deficits in peak VO2 1 year after anthracycline therapy, skeletal muscle bioenergetics and oxygenation are not impaired. Rather, body composition deterioration (e.g., increased ratio of intermuscular fat to skeletal muscle) may contribute to reduced exercise tolerance in anthracycline BC survivors. This finding points to the importance of lifestyle interventions including caloric restriction and exercise training to restore body composition and cardiovascular health in the BC survivorship setting.

Curing breast cancer and killing the heart: A novel model to explain elevated cardiovascular disease and mortality risk among women with early stage breast cancer.

Due to advances in prevention, early detection and treatment, early breast cancer mortality has decreased by nearly 40% during the last four decades. Yet, the risk of cardiovascular disease (CVD) mortality is significantly elevated following a breast cancer diagnosis, and it is a leading cause of death in this population. This review will discuss the most recent evidence for risks, pathology, mechanisms, and prevention of CVD morbidity and mortality in women with breast cancer. This evidence will be synthesized into a new model 'the compounding risk and protection model.' This model proposes that the balance between risk factors (i.e., older age, pre-existing traditional CVD risk factors and shared biologic pathways for CVD and cancer such as inflammation, as well as treatment-related and lifestyle toxicity) and potential protection factors (i.e., lifelong non-smoking, regular physical activity, a healthy diet rich in fruits and vegetables, and management of body weight and stress, heart failure therapy) determine the individual risk of CVD morbidity and mortality after diagnosis of early breast cancer.

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 VO2 ). The purpose of this study was to evaluate peak VO2 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 VO2 . RV and LV volumes and function were measured at rest, submaximal and peak supine cycle exercise using cardiac magnetic resonance imaging. Peak VO2 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 VO2 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.

Meta-analysis of Exercise Training on Left Ventricular Ejection Fraction in Heart Failure with Reduced Ejection Fraction: A 10-year Update.

BACKGROUND: The role of exercise training modality to attenuate left ventricular (LV) remodeling in heart failure patients with reduced ejection fraction (HFrEF) remains uncertain. The authors performed a systematic review and meta-analysis of published reports on exercise training (moderate-intensity continuous aerobic, high-intensity interval aerobic, and resistance exercise) and LV remodeling in clinically stable HFrEF patients. METHODS: We searched MEDLINE, Cochrane Central Registry of Controlled Trials, CINAHL, and PubMed (2007 to 2017) for randomized controlled trials of exercise training on resting LV ejection fraction (EF) and end-diastolic and end-systolic volumes in HFrEF patients. RESULTS: 18 trials reported LV ejection fraction (LVEF) data, while 8 and 7 trials reported LV end-diastolic and LV end-systolic volumes, respectively. Overall, moderate-intensity continuous training (MICT) significantly increased LVEF (weighted mean difference, WMD = 3.79%; 95% confidence interval, CI, 2.08 to 5.50%) with no change in LV volumes versus control. In trials ≥6 months duration, MICT significantly improved LVEF (WMD = 6.26%; 95% CI 4.39 to 8.13%) while shorter duration (<6 months) trials modestly increased LVEF (WMD = 2.33%; 95% CI 0.84 to 3.82%). High-intensity interval training (HIIT) significantly increased LVEF compared to control (WMD = 3.70%; 95% CI 1.63 to 5.77%) but was not different than MICT (WMD = 3.17%; 95% CI -0.87 to 7.22%). Resistance training performed alone or combined with aerobic training (MICT or HIIT) did not significantly change LVEF. CONCLUSIONS: In clinically stable HFrEF patients, MICT is an effective therapy to attenuate LV remodeling with the greatest benefits occurring with long-term (≥6 months) training. HIIT performed for 2 to 3 months is superior to control, but not MICT, for improvement of LVEF.

Exercise as a diagnostic and therapeutic tool for the prevention of cardiovascular dysfunction in breast cancer patients.

BACKGROUND: Anthracycline chemotherapy may be associated with decreased cardiac function and functional capacity measured as the peak oxygen uptake during exercise ( V·O2 peak). We sought to determine (a) whether a structured exercise training program would attenuate reductions in V·O2 peak and (b) whether exercise cardiac imaging is a more sensitive marker of cardiac injury than the current standard of care resting left ventricular ejection fraction (LVEF). METHODS: Twenty-eight patients with early stage breast cancer undergoing anthracycline chemotherapy were able to choose between exercise training (mean ± SD age 47 ± 9 years, n = 14) or usual care (mean ± SD age 53 ± 9 years, n = 14). Measurements performed before and after anthracycline chemotherapy included cardiopulmonary exercise testing to determine V·O2 peak and functional disability ( V·O2 peak < 18 ml/min/kg), resting echocardiography (LVEF and global longitudinal strain), cardiac biomarkers (troponin and B-type natriuretic peptide) and exercise cardiac magnetic resonance imaging to determine stroke volume and peak cardiac output. The exercise training group completed 2 × 60 minute supervised exercise sessions per week. RESULTS: Decreases in V·O2 peak during chemotherapy were attenuated with exercise training (15 vs. 4% reduction, P = 0.010) and fewer participants in the exercise training group met the functional disability criteria after anthracycline chemotherapy compared with those in the usual care group (7 vs. 50%, P = 0.01). Compared with the baseline, the peak exercise heart rate was higher and the stroke volume was lower after chemotherapy ( P = 0.003 and P = 0.06, respectively). There was a reduction in resting LVEF (from 63 ± 5 to 60 ± 5%, P = 0.002) and an increase in troponin (from 2.9 ± 1.3 to 28.5 ± 22.4 ng/mL, P < 0.0001), but no difference was observed between the usual care and exercise training group. The baseline peak cardiac output was the strongest predictor of functional capacity after anthracycline chemotherapy in a model containing age and resting cardiac function (LVEF and global longitudinal strain). CONCLUSIONS: The peak exercise cardiac output can identify patients at risk of chemotherapy-induced functional disability, whereas current clinical standards are unhelpful. Functional disability can be prevented with exercise training.

Diastolic Stress Testing Along the Heart Failure Continuum.

PURPOSE OF REVIEW: This review summarizes recent developments highlighting the clinical utility of diastolic stress testing along the heart failure continuum. RECENT FINDINGS: Invasive hemodynamic assessment of cardiac filling pressures during physiological stress is the gold-standard technique for unmasking diastolic dysfunction. Non-invasive surrogate techniques, such as Doppler ultrasound, have shown excellent agreement with invasive approaches and are now recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. While cycle exercise is often advocated, recent evidence supports the use of isometric handgrip as a viable alternative stressor. Diastolic stress testing is a powerful tool to enhance detection of diastolic dysfunction, is able to differentiate between cardiac and non-cardiac pathology, and should be incorporated into routine clinical assessment.

Exercise cardiac magnetic resonance imaging: a feasibility study and meta-analysis.

Cardiac stress testing improves detection and risk assessment of heart disease. Magnetic resonance imaging (MRI) is the clinical gold-standard for assessing cardiac morphology and function at rest; however, exercise MRI has not been widely adapted for cardiac assessment because of imaging and device limitations. Commercially available magnetic resonance ergometers, together with improved imaging sequences, have overcome many previous limitations, making cardiac stress MRI more feasible. Here, we aimed to demonstrate clinical feasibility and establish the normative, healthy response to supine exercise MRI. Eight young, healthy subjects underwent rest and exercise cinematic imaging to measure left ventricular volumes and ejection fraction. To establish the normative, healthy response to exercise MRI we performed a comprehensive literature review and meta-analysis of existing exercise cardiac MRI studies. Results were pooled using a random effects model to define the left ventricular ejection fraction, end-diastolic, end-systolic, and stroke volume responses. Our proof-of-concept data showed a marked increase in cardiac index with exercise, secondary to an increase in both heart rate and stroke volume. The change in stroke volume was driven by a reduction in end-systolic volume, with no change in end-diastolic volume. These findings were entirely consistent with 17 previous exercise MRI studies (226 individual records), despite differences in imaging approach, ergometer, or exercise type. Taken together, the data herein demonstrate that exercise cardiac MRI is clinically feasible, using commercially available exercise equipment and vendor-provided product sequences and establish the normative, healthy response to exercise MRI.

Performance Limitations in Heart Transplant Recipients.

We hypothesize that the reduced peak aerobic power (peak V˙O2) after heart transplantation is due to impaired cardiovascular and skeletal muscle function, and its improvement with short-term (≤1 yr) exercise training is primarily due to favorable skeletal muscle adaptations. Furthermore, the increased peak V˙O2 with long-term (>2 yr) training is primarily mediated by cardiac (sympathetic) reinnervation.