scholarly journals Exercise Training Preserves Myocardial Strain and Improves Exercise Tolerance in Doxorubicin-Induced Cardiotoxicity

2021 ◽  
Vol 8 ◽  
Author(s):  
Igor L. Gomes-Santos ◽  
Camila P. Jordão ◽  
Clevia S. Passos ◽  
Patricia C. Brum ◽  
Edilamar M. Oliveira ◽  
...  

Doxorubicin causes cardiotoxicity and exercise intolerance. Pre-conditioning exercise training seems to prevent doxorubicin-induced cardiac damage. However, the effectiveness of the cardioprotective effects of exercise training concomitantly with doxorubicin treatment remains largely unknown. To determine whether low-to-moderate intensity aerobic exercise training during doxorubicin treatment would prevent cardiotoxicity and exercise intolerance, we performed exercise training concomitantly with chronic doxorubicin treatment in mice. Ventricular structure and function were accessed by echocardiography, exercise tolerance by maximal exercise test, and cardiac biology by histological and molecular techniques. Doxorubicin-induced cardiotoxicity, evidenced by impaired ventricular function, cardiac atrophy, and fibrosis. Exercise training did not preserve left ventricular ejection fraction or reduced fibrosis. However, exercise training preserved myocardial circumferential strain alleviated cardiac atrophy and restored cardiomyocyte cross-sectional area. On the other hand, exercise training exacerbated doxorubicin-induced body wasting without affecting survival. Finally, exercise training blunted doxorubicin-induced exercise intolerance. Exercise training performed during doxorubicin-based chemotherapy can be a valuable approach to attenuate cardiotoxicity.

Author(s):  
Agata Nowak-Lis ◽  
Tomasz Gabryś ◽  
Zbigniew Nowak ◽  
Paweł Jastrzębski ◽  
Urszula Szmatlan-Gabryś ◽  
...  

The presence of a well-developed collateral circulation in the area of the artery responsible for the infarction improves the prognosis of patients and leads to a smaller area of infarction. One of the factors influencing the formation of collateral circulation is hypoxia, which induces angiogenesis and arteriogenesis, which in turn cause the formation of new vessels. The aim of this study was to assess the effect of endurance training conducted under normobaric hypoxia in patients after myocardial infarction at the level of exercise tolerance and hemodynamic parameters of the left ventricle. Thirty-five patients aged 43–74 (60.48 ± 4.36) years who underwent angioplasty with stent implantation were examined. The program included 21 training units lasting about 90 min. A statistically significant improvement in exercise tolerance assessed with the cardiopulmonary exercise test (CPET) was observed: test duration (p < 0.001), distance covered (p < 0.001), HRmax (p = 0.039), maximal systolic blood pressure (SBPmax) (p = 0.044), peak minute ventilation (VE) (p = 0.004) and breathing frequency (BF) (p = 0.044). Favorable changes in left ventricular hemodynamic parameters were found for left ventricular end-diastolic dimension LVEDD (p = 0.002), left ventricular end-systolic dimension LVESD (p = 0.015), left ventricular ejection fraction (LVEF) (p = 0.021), lateral e’ (p < 0.001), septal e’ (p = 0.001), and E/A (p = 0.047). Endurance training conducted in hypoxic conditions has a positive effect on exercise tolerance and the hemodynamic indicators of the left ventricle.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
NPD Cunha ◽  
I Aguiar-Ricardo ◽  
T Rodrigues ◽  
P Silverio Antonio ◽  
S Couto Pereira ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction A number of randomized controlled trials have examined the effect of exercise training on left ventricle (LV) remodeling in individuals with cardiovascular disease. However, the results of these trials have been inconclusive.  Purpose Evaluation of the impact of a cardiac rehabilitation program (CRP) on left ventricle remodelling evaluated by echocardiogram.  Methods Observational single centre study including consecutive patients, undergoing structured CRP since June 2016 until February 2020. Phase II CRP included 3 months of exercise training, aerobic and strength exercise, individually prescribed, 3 times a week, 60 minutes sessions. All patients were submitted to a clinical evaluation, echocardiogram, and cardiopulmonary exercise test before and after the CRP. Results 205 patients (62.6 ± 11 years, 83.4% men, 82.3% ischemic disease) were included in a phase II CRP. Most patients had ischemic disease (82.3%) and 23.5% of patients had left ventricular ejection fraction (LVEF) &lt;40%. Of the cardiovascular risk factors, hypertension was the most prevalent (76%), followed by dyslipidaemia (67.4%), active smoking (45.9%) and diabetes (26.9%).  After the CRP, there was a significant improvement of LVEF (from 48.3 ± 13 to 52 ± 11.6 %, p = 0.001) and a significant reduction of LV volumes (LV end-diastolic volume, LVEDV , decreased from 140 ± 81 to 121 ± 57, p = 0.002; LV end-systolic volume , LVESV , reduced from 80 ± 75 to 64 ± 48, p = 0.004). Considering only the patients with LVEF &lt; 40% (n = 38), the improvement was even greater: LVEF increased from 30 ± 8 to 39 ± 13 (p = 0.002); LVEDV reduced from 206 ± 107 to 159 ± 81 (p = 0.001) and LVESV reduced from 142 ± 99 to 101 ± 66 (p = 0.002). 63.6%(n = 14) of these patients improved at least 10% of LVEF and only 1 of them had a cardiac resynchronization therapy device.  Conclusions A phase II CR program was associated with significant improvements in left ventricular reverse remodelling irrespective of baseline EF classification. Those with reduced baseline EF derived an even greater improvement, highlighting the great importance of CR in this subgroup of patients.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcus Sandri ◽  
Stephan Gielen ◽  
Norman Mangner ◽  
Volker Adams ◽  
Sandra Erbs ◽  
...  

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.


2018 ◽  
Vol 25 (18) ◽  
pp. 1937-1946 ◽  
Author(s):  
Erik H Van Iterson ◽  
Chul-Ho Kim ◽  
Katelyn Uithoven ◽  
Thomas P Olson

Background Exercise intolerance, obesity, and low hemoglobin (hemoglobin<13 and <12 g/dl, men/women, respectively) are common features of heart failure. Despite serving as potent contributors to metabolic dysfunction, the impact of obesity and low hemoglobin on exercise intolerance is unknown. This study tested the hypotheses, compared with non-obese (NO) heart failure with normal hemoglobin, (a) counterparts with low hemoglobin and obesity or non-obesity will demonstrate reduced peak exercise oxygen uptake; (b) obese with normal hemoglobin will demonstrate decreased peak exercise oxygen uptake; (c) compared across stratifications, obese with low hemoglobin will demonstrate the sharpest decrement in peak exercise oxygen uptake. Methods Adults with heart failure ( n = 315; left ventricular ejection fraction≤40%; 77% men) (Group 1: normal hemoglobin and non-obese, n = 137; Group 2: low hemoglobin and non-obese, n = 51; Group 3: normal hemoglobin+obesity, n = 89; Group 4, n = 38: low hemoglobin+obesity; body mass index = 26 ± 3, 26 ± 2, 34 ± 4, 34 ± 4 kg/m2, respectively) completed treadmill cardiopulmonary exercise testing as part of routine clinical management. Peak exercise oxygen uptake was measured via standard metabolic system. Results There were no group-wise differences for heart failure class, gender, left ventricular ejection fraction, and resting cardiopulmonary function. Group 1 demonstrated increased peak exercise oxygen uptake versus Groups 2–4 (20 ± 6 versus 17 ± 6, 17 ± 5, 13 ± 4 ml/kg/min, respectively; all p < 0.001); whereas Group 4 peak exercise oxygen uptake was reduced versus all groups ( p < 0.001). Additionally, both body mass index (R2 = 0.10) and hemoglobin (R2 = 0.12) were significant predictors of peak exercise oxygen uptake in Group 1; which were relationships not mirrored for Groups 2–4. Conclusion These data suggest obesity together with low hemoglobin are potent contributors to impaired peak exercise oxygen uptake and, hence, oxidative metabolic capacity. In diverse populations of heart failure where obesity and/or low hemoglobin are present, it is important to consider these features together when interpreting peak exercise oxygen uptake and underlying exercise limitations.


2021 ◽  
Vol 5 (7) ◽  
Author(s):  
Shiavax Rao ◽  
Arjun Kanwal ◽  
Sriram Padmanabhan

Abstract Background Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and exercise intolerance. It is often considered to be a paediatric disease, owing to most cases being diagnosed during childhood and mortality being the highest during the first few years of life. Case summary We report a case of dilated cardiomyopathy due to BTHS in a 27-year-old adult male patient, who initially presented with lightheadedness, dyspnoea, orthopnoea, and bilateral lower extremity oedema. Key findings from investigations included leukopenia, prolonged QTc interval, reduced left ventricular ejection fraction (LVEF), global enlargement of all heart chambers, patent coronary arteries, and mild pulmonary hypertension. The patient was diuresed to euvolemia and discharged with a LifeVest. Guideline-directed medical therapy was initiated and uptitrated as an outpatient. A repeat echocardiogram 2 years after initial presentation showed marked improvement in LVEF. Discussion It is possible that there are adult patients with idiopathic cardiomyopathy, which may be attributable to BTHS. In the absence of an obvious underlying cause, with the appropriate historical information, clinical exam, laboratory investigations, and imaging findings, BTHS should be considered as a likely cause of non-ischaemic cardiomyopathy.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Adolfo G Mauro ◽  
Stefano Toldo ◽  
Ross B Mikkelsen ◽  
Asim Alam ◽  
Elisabeth Weiss ◽  
...  

Introduction: Radiation therapy (XRT) used for the treatment of cancer, can expose the heart to the radiation beam causing cardiac injury. However, fatigue and exercise intolerance are common symptoms in patients treated with XRT for different types of cancer, in which the XRT field does not involve the heart. Hypothesis: We hypothesize that impaired cardiac reserve may occur even when the XRT field is distant from the heart (‘out of target effect’). Methods: C57BL/6J female mice underwent two different radiation treatments (20 Gray, single dose) using a Small Animal Radiation Research Platform: a) the isocenter was pointed to the right lung sparing the heart (‘out of target’) and b) the heart was chosen as isocenter, as positive control. An additional group of mice were sham-irradiated, as negative control. Transthoracic echocardiography was used to assess the left ventricular ejection fraction (LVEF) at baseline and the contractile reserve expressed as percentage change in the LVEF measured at rest (LVEFr) and 3 minutes after intraperitoneal administration of the β-adrenergic agonist, isoproterenol (LVEFi)[(LVEFi-LVEFr)/LVEFr]*100]. Results: Three days after radiation treatment irradiated and sham mice showed normal LVEF at rest. However, the ‘out of target’ irradiation group showed a significant impairment in cardiac contractile reserve compared with sham, and similar to the ‘on target’ group (Figure). Conclusions: ‘Out of target’ radiation therapy leads to impaired cardiac contractile reserve in the mouse.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A Ovchinnikov ◽  
A V Potekhina ◽  
A A Borisov ◽  
N M Ibragimova ◽  
E N Yushchyuk ◽  
...  

Abstract Background Diagnosis of early heart failure with preserved ejection fraction (HFpEF) may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and indicators of volume overload may be absent at rest. We aimed to characterize the contribution of abnormal left atrial (LA) mechanical properties to exercise intolerance in early HFpEF (normal left ventricular filling pressures at rest but elevated during exercise). Methods Diastolic stress testing (DST) was performed in 104 patients with left ventricular ejection fraction ≥50%, in sinus rhythm, and no more than LV diastolic dysfunction grade I, referred for assessment of exertional dyspnoea. Patients exercised supine cycle ergometry at 60 rpm starting with a 3-min period of low-level 25-W workload followed by 25-W increments in 3-minute stages to maximum tolerated levels. According to DST, 43 patients were diagnosed with HFpEF (average mitral E-to-annular e′ ratio [E/e′] &gt; 14, and peak TR velocity &gt;2.8 m/sec at maximal exertion) and 61 as non-cardiac dyspnea (NCD). During the test, two-dimensional images, mitral E/e′, peak tricuspid regurgitation (TR) velociry, and two-dimensional LA mechanical parameters (longitudinal LA strain [LASR] and strain rate [LASRR] during reservoir phase and LA stiffness assessed as a ratio of mitral E/e′ ratio to LASR) were analysed at baseline, and at peak. Results HFpEF and NCD patients were similar in regard to the LA volume index (34.4 [30.2;39.4] vs. 33.6 [28.4;37.1] ml/m2), and NT-proBNP level (132 [80;238] vs. 129 [80;197] pg/ml). As compared with NCD patients, HFpEF patients displayed reduced LA reservoir function assessed by LASR (22.3 [18.9;25.6] vs. 24.2 [21.2;29.8] % at rest, and 25.3 [21.4;30.2] vs. 29.0 [24.2;33.3] % with exercise) and LASRR (0.78 [0.58;0.96] vs. 0.90 [0.68;1.12] /s at rest, and 1.10 [0.79;1.31] vs. 1.24 [1.03;1.56] s–1 with exercise) with increased LA stiffness (0.57 [0.44;0.70] vs. 0.42 [0.30;0.49] mmHg/% at rest, and 0.61 [0.46;0.74] vs. 0.40 [0.32;0.51] mmHg/% with exercise, all P &lt; 0.05). Additionally, HFpEF patients showed smaller exercise elevation in LASRR (+31 [-5;77] vs. +47 [12;85] % as compared with resting values, P &lt; 0.05). Exercised LA stiffness and reservoir strain correlated with exercise LV filling pressures estimated by mitral E/e′ ratio (r = 0.72 and r =–0.35, P &lt; 0.001). LA stiffness showed a good diagnostic accuracy (area under the curve 0.75), and LA stiffness &gt; 0.46 mmHg/% demonstrated reasonable sensitivity (79%) and specificity (71%) to diagnose HFpEF. Neither LV global longitudinal strain and ejection fraction at rest nor their exercise-induced elevation differed between HFpEF and NCD. Conclusion Impaired LA reservoir function and increased stiffness are associated with exercise intolerance in patients with early HFpEF, while LV systolic function seems preserved in this stage of the disease. LA stiffness provides HFpEF diagnostic potential in ambulatory patients with dyspnea


2016 ◽  
Vol 130 (24) ◽  
pp. 2239-2244 ◽  
Author(s):  
Mark J. Haykowsky ◽  
Rhys Beaudry ◽  
R. Matthew Brothers ◽  
Michael D. Nelson ◽  
Satyam Sarma ◽  
...  

Breast cancer (BC) survival rates have improved during the past two decades and as a result older BC survivors are at increased risk of developing heart failure (HF). Although the HF phenotype common to BC survivors has received little attention, BC survivors have a number of risk factors associated with HF and preserved ejection fraction (HFPEF) including older age, hypertension, obesity, metabolic syndrome and sedentary lifestyle. Moreover, not unlike HFPEF, BC survivors with preserved left ventricular ejection fraction (BCPEF) have reduced exercise tolerance measured objectively as decreased peak oxygen uptake (peak VO2). This review summarizes the literature regarding the mechanisms of exercise intolerance and the role of exercise training to improve peak VO2 in BCPEF.


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