Search

Cancer treatment-induced cardiotoxicities are an ongoing concern throughout the cancer care continuum from treatment initiation to survivorship. Several "standard-of-care" primary, secondary, and tertiary prevention strategies are available to prevent the development or further progression of cancer treatment-induced cardiotoxicities and their risk factors. Despite exercise's established benefits on the cardiovascular system, it has not been widely adopted as a nonpharmacologic cardioprotective strategy within cardio-oncology care. In this state-of-the-art review, the authors discuss cancer treatment-induced cardiotoxicities, review the existing evidence supporting the role of exercise in preventing and managing these sequelae in at-risk and affected individuals living after cancer diagnoses, and propose considerations for implementing exercise-based services in cardio-oncology practice.

BackgroundModifiable lifestyle-related factors heighten the risk and severity of coronavirus disease 2019 (COVID-19) in patients with cancer. Whether exercise lowers susceptibility or severity is not known.MethodsWe identified 944 cancer patients from Memorial Sloan Kettering Cancer Center (mean age: 64; 85% female; 78% White) completing an exercise survey before receiving a confirmed positive or negative SARS-CoV-2 test. Exercise was defined as reporting moderate-intensity ≥5 days per week, ≥30 minutes/session or strenuous-intensity ≥3 days per week, ≥20 minutes/session. Multivariable logistic regression was used to determine the relationship between exercise and COVID-19 susceptibility and severity (i.e., composite of hospital admission or death events) with adjustment for clinical-epidemiologic covariates.ResultsTwenty-four percent (230/944) of the overall cohort were diagnosed with COVID-19 and 35% (333/944) were exercisers. During a median follow-up of 10 months, 26% (156/611) of nonexercising patients were diagnosed with COVID-19 compared with 22% (74/333) of exercising patients. The adjusted OR for risk of COVID-19 was 0.65 [95% confidence interval (CI), 0.44-0.96, P = 0.03] for exercisers compared with nonexercisers. A total of 20% (47/230) of COVID-19 positive patients were hospitalized or died. No difference in the risk of severe COVID-19 as a function of exercise status was observed (P > 0.9).ConclusionsExercise may reduce the risk of COVID-19 infection in patients with a history of cancer, but not its severity.ImpactThis study provides the first data showing that exercise might lower the risk of COVID-19 in cancer patients, but further research is required.

We developed and evaluated the Digital Platform for Exercise (DPEx): a decentralized, patient-centric approach designed to enhance all aspects of clinical investigation of exercise therapy. DPEx integrated provision of a treadmill with telemedicine and remote biospecimen collection permitting all study procedures to be conducted in patient's homes. Linked health biodevices enabled high-resolution monitoring of lifestyle and physiological response. Here we describe the rationale and development of DPEx as well as feasibility evaluation in three different cohorts of patients with cancer: a phase 0a development study among three women with post-treatment primary breast cancer; a phase 0b proof-of-concept trial of neoadjuvant exercise therapy in 13 patients with untreated solid tumors; and a phase 1a level-finding trial of neoadjuvant exercise therapy in 53 men with localized prostate cancer. Collectively, our study demonstrates the utility of a fully digital, decentralized approach to conduct clinical trials of exercise therapy in a clinical population. [ABSTRACT FROM AUTHOR]

Pretreatment prognostication, on-treatment monitoring, and early detection of physiological symptoms are considerable challenges in cancer. We describe the feasibility of high-resolution wearable data (steps per day, walking speed) to longitudinally profile physiological trajectories extracted from Apple Health data in three patients with lung cancer from diagnosis through cancer treatment after obtaining informed consent. We used descriptive statistics to describe our approach of building longitudinal physiological profiles. The wearable data monitoring period ranged from 58 to 135 weeks, with between 34,319 and 103,535 distinct digital physiological measures collected during this period--the equivalent to 41 measures per day/patient. Longitudinal profiling revealed that wearable data accurately captured physiological changes linked with clinical events such as surgery and hospitalizations as well as initiation (and cessation) of systemic cancer treatment in all three patients. These findings suggest that wearable devices could play a critical role in the management of lung cancer, although larger studies are needed to confirm these preliminary observations and validate their generalizability. Wearable devices hold significant promise for the development of personalized "digital biomarkers," which may enhance risk stratification and management in oncology. [ABSTRACT FROM AUTHOR]

Background: Body composition may be related to survival in patients with clear-cell renal cell carcinoma (ccRCC), but studies have not simultaneously considered adipose and muscle tissue quantity and radiodensity. Methods: We analyzed data from 1,022 patients with ccRCC who underwent nephrectomy between 2000 and 2020 at Memorial Sloan Kettering Cancer Center. Skeletal muscle, visceral adipose tissue, and subcutaneous adipose tissue indexes (cm2/m2) and radiodensities [Hounsfield units (HU)] were assessed from noncontrast presurgical CT scans; clinical and demographic characteristics were available from the time of surgery. HRs and confidence intervals were estimated for overall (OS) and disease-free survival (DFS) through March 2023 in multivariable models that simultaneously accounted for all body composition measures. Results: The median age of the patients was 58 years, 69% were male, and 90% were White. There were 169 OS events over 8,392 person-years and 253 DFS events over 7,753 person-years of follow-up. In adjusted analyses, poor OS was associated with lower skeletal muscle radiodensity [-10 HU, HR (95% confidence interval), 1.37 (1.05-1.77)] and greater visceral adipose tissue radiodensity [+10 HU, 1.66 (1.06-2.59)], with similar findings for DFS. Poor survival was also associated with greater visceral adipose tissue index [+40 cm2/m2, OS: 1.32 (0.97, 1.79); DFS: 1.33 (1.04, 1.71)]. Associations with skeletal muscle radiodensity were limited to patients with stage 1/2 disease. Conclusions: Radiodensities of skeletal muscle and visceral adipose tissues may be novel presurgical prognostic factors for patients with ccRCC. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Whether structured exercise therapy improves chemotherapy delivery, tolerability, and tumor response is unclear.This was a secondary analysis of a phase 2 trial investigating exercise therapy (n = 72) versus usual care (n = 72) in patients with primary breast cancer. Exercise therapy comprised individualized treadmill walking three times weekly for 20–50 minutes per session at 55%–100% of pretreatment exercise capacity. Chemotherapy delivery was assessed according to the relative dose intensity (RDI), tolerability was assessed according to patient‐reported outcomes and blood laboratory values, and response was assessed based on the pathologic complete response rate in patients who received neoadjuvant chemotherapy.In the exercise therapy group, 51 patients (71%) reached 100% RDI (median, 100%; interquartile range, 100%–100%) compared with 41 patients (57%) in the usual care group (median, 100%; interquartile range, 95%–100%; p = .08). Tolerability was similar in both groups; the rates of grade 3 or higher neutropenia and anemia were 22% versus 39% and 7% versus 10% in the exercise and usual care groups, respectively. In patients who received anthracyclines (n = 104), 41 (77%) had 100% chemotherapy RDI in the exercise therapy group versus 29 (57%) in the usual care group (p = .026). In the neoadjuvant chemotherapy subgroup (n = 51 tumors), the postneoadjuvant therapy (yp) pathologic complete response (ypT0ypN0) rate was 27% (95% confidence interval, 12%–50%) in the exercise therapy group compared with 28% (95% confidence interval, 13%–47%) in the usual care group (p > .9).In patients with primary breast cancer, exercise therapy was associated with improved delivery of anthracycline‐based chemotherapy. Although exercise therapy was not significantly associated with tumor response, effects varied by tumor subtype (trial registration: Clinicaltrials.gov identifier NCT01943695). [ABSTRACT FROM AUTHOR]

Aims The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer. Methods and results Using a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens—concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20–50 min at 55%–100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, −0.88 mL O2·kg−1·min−1; 95% confidence interval (CI): −3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg−1·min−1, P < 0.001). Conclusion There was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials. [ABSTRACT FROM AUTHOR]

Lower body negative pressure (LBNP) is an established and important technique used to physiologically stress the human body, particularly the cardiovascular system. LBNP is most often used to simulate gravitational stress, but it has also been used to simulate hemorrhage, alter preload, and manipulate baroreceptors. During experimentation, the consequences of LBNP and the reflex increases in heart rate and blood pressure can be manipulated and observed in a well-controlled manner, thus making LBNP an important research tool. Numerous laboratories have developed LBNP devices for use in research settings, and a few devices are commercially available. However, it is often difficult for new users to find adequately described design plans. Furthermore, many available plans require sophisticated and expensive materials and/or technical support. Therefore, we have created an affordable design plan for a LBNP chamber. The purpose of this article was to share our design template with others. In particular, we hope that this information will be of use in academic and research settings. Our pressure chamber has been stress tested to 100 mmHg below atmospheric pressure and has been used successfully to test orthostatic tolerance and physiological responses to -50 mmHg.

Early diastolic left ventricular (LV) untwisting has been evaluated as a manifestation of LV recoil, reflecting the release of elastic energy stored during systole. The primary goal of this study was to characterize the relationship between systolic strain (e.g., circumferential strain and the shear strains that comprise twist) with the resulting early diastolic shear strain rates, including the rate of untwisting. A further goal was to characterize these relationships regionally from apical to basal locations. Cardiac magnetic resonance imaging tissue tagging was used to measure circumferential strain, global and regional (apex, mid, basal) twist ([theta]), and circumferential-longitudinal ([[member].sub.CL]) and circumferential-radial ([[member of].sub.CR]) shear strains along with the corresponding untwisting rates (d[theta]/dt and diastolic shear strain rates (d[member of]/dt in 32 healthy males (33 [+ or -] 7 yr). LV untwisting rates and shear strain rates measured during early diastole varied significantly with the measurement location from apex to base (P < 0.001) but demonstrated significant linear correlation with their corresponding preceding systolic strains (P < 0.001). Untwisting rates and diastolic shear strain rates were not significantly correlated with circumferential systolic strain or endsystolic volume (P > 0.05). Normalization of the untwisting rates to the peak twist (d[theta]/[dt.sub.Norm] = -13.6 [+ or -] 2.1 [s.sup.-1]) or shear strain rates to peak systolic shear strain (d[[member of].sub.CL]/[dt.sub.Norm] = -15.0 [+ or -] 5.4 [s.sup.-1], and d[[member of].sub.CR]/[dt.sub.Norm] = -14.2 [+ or -] 7.7 [s.sup.-1]) yielded a uniform measure of early diastolic function that was similar for all shear strain and twist components and for all locations from apex to base. These findings support a linear model of torsional recoil in the healthy heart, where diastolic shear strain rates (e.g., untwisting rates) are linearly related to the corresponding preceding systolic shear stain component. Furthermore, these findings suggest that torsional recoil is uncoupled from end-systolic volumes or the associated strains, such as circumferential strain. relaxation; torsion; untwisting doi: 10.1152/ajpheart.00353.2010.

Left ventricular (LV) active relaxation begins before aortic valve closure and is largely completed during isovolumic relaxation (IVR), before mitral valve opening. During IVR, despite closed mitral and aortic valves, indirect assessments of LV volume have suggested volume increases during this period. The aim of this study is to measure LV volume throughout IVR and to determine the sources of any volume changes. For 10 healthy individuals (26.0 [+ or -] 3.8 yr), magnetic resonance imaging was used to measure time courses of LV volume, principal myocardial strains (circumferential, longitudinal, radial), and LV twist. Mitral leaflet motion was observed using echocardiography. During IVR, LV volume measurements showed an apparent increase of 4.6 [+ or -] 1.5 ml (5.0 [+ or -] 2.0% of the early filling volume change), the LV untwisted by 4.5 [+ or -] 1.9[degrees] (36.6 [+ or -] 18.0% of peak systolic twist), and changes in circumferential, longitudinal, and radial strains were +0.87 [+ or -] 0.64%, +0.93 [+ or -] 0.57%, and - 1.46 [+ or -] 1.66% (4.2 [+ or -] 3.3%, 5.9 [+ or -] 3.3%, and 5.3 [+ or -] 7.5% of peak systolic strains), respectively. The apparent changes in volume correlated (P < 0.01) with changes in circumferential, longitudinal, and radial strains (r = 0.86, 0.69, and -0.37, respectively) and untwisting (r = 0.83). The closed mitral valve leaflets were observed to descend into the LV throughout IVR in all subjects in apical four- and three-chamber and parasternal long-axis views by 6.0 [+ or -] 3.3, 5.1 [+ or -] 2.4, and 2.1 [+ or -] 5.0 mm, respectively. In conclusion, LV relaxation during IVR is associated with changes in principal strains and untwisting, which are all correlated with an apparent increase in LV volume. Since closed mitral and aortic valves ensure true isovolumic conditions, the apparent volume change likely reflects expansion of the LV myocardium and the inward bowing of the closed mitral leaflets toward the LV interior. diastolic function; active relaxation; mitral valve leaflets doi: 10.1152/ajpheart.00131.2010.

The cardiovascular response to exercise in heart transplant recipients (HTR) has been compared with that of healthy individuals matched to the recipient age (RM controls). However, no study has compared HTR with donor age-matched (DM) controls. Moreover, the cardiovascular response to sustained submaximal exercise in HTR requires further evaluation. We therefore examined cardiovascular responses during incremental exercise and sustained (1 h) submaximal aerobic exercise in 9 clinically stable HTR [63 [+ or -] 10 yr of age, 24.2 [+ or -] 10.9 ml.[kg.sup.-1].[min.sup.-1] peak O2 uptake (V[O.sub.2peak)]] and 11 healthy age-matched controls (60 [+ or -] 11 yr of age and 36.3 [+ or -] 10.7 ml.[kg.sup. -1].[min.sup.- V[O.sub.2]peak for 6 RM controls and 35 [+ or -] 8 yr of age and 51.1 [+ or -] 10.4 ml.[kg.sup.-1].[min.sup.-1] V[O.supb.2peak] for 5 DM controls). Heart rate (HR) and left ventricular systolic and diastolic volumes (2-dimensional echocardiography) indexed to body surface area [end-systolic and end-diastolic volume indexes (EDVI and ESVI)], cardiac output (CI), ejection fraction (EF), systemic vascular resistance (SVRI), end-systolic elastance index, and arterial elastance index were determined. Although systolic function was maintained during incremental exercise, peak CI was significantly reduced (6.7 [+ or -] 2.4 vs. 11.6 [+ or -] 1.4 1.[min.sup.-1].[m.sup.-2]), secondary to blunted HR, EDVI, and increased peak SVRI, in HTR compared with DM controls. The lower peak CI in HTR than in RM controls was due to blunted peak EDVI (54.1 [+ or -] 13.2 vs. 68.6 [+ or -] 5.7 ml/[m.sup.2]). During sustained submaximal exercise, HTR exhausted their preload reserve, a response for which changes in ESVI, HR, or EF did not fully compensate. Thus it appears that HTR are limited by impaired preload reserve, HR reserve, and vascular reserve during exercise conditions. exercise capacity; cardiac allograft; hemodynamics