Citations

Introduction: The COVID-19 pandemic imposed significant constraints to delivery of cardiac rehabilitation (CR) with many programs relying on delivery of home-based cardiac rehabilitation (HBCR). We sought to compare the effects of HBCR vs conventional center-based CR (CBCR) on clinical metrics, health-related quality of life, and modifiable risk factors in CR patients. Methods: Retrospective cohort study comparing 511 HBCR patients (March 2020-April 2021; COVID-19 pandemic) and 765 age and sex matched CBCR patients (Jan 2018-Jan2020; immediately pre-pandemic) from the Mayo Clinic Health System. We assessed changes in clinical outcomes before and after CR. HBCR included 12 sessions (one in-person assessment + weekly education and exercise monitoring phone/video calls). Conventional CBCR included 36 sessions (3 sessions per week for 12 weeks). Continuous data were described as mean±SD, and comparisons of change between groups were assessed with linear regression adjusting for baseline value, in complete cases. Results: HBCR and CBCR patients were 65±14 yrs old (68% male) and 65±14 yrs old (67% male) respectively. HBCR patients demonstrated greater improvement in exercise days/week whereas CBCR patients had greater improvement in exercise min/day. HBCR patients had greater improvement in blood glucose with a trend towards greater improvement in non-HDL cholesterol. Both groups demonstrated similar improvement on nutrition, depression, health-related quality of life surveys and total, LDL and HDL cholesterol, as well as HbA1c between the groups. Conclusions: Collecting clinical metrics during the COVID-19 pandemic proved challenging due to the initial closure of out-patient services. For patients in whom data was captured, HBCR appears to be similarly effective at improving several intermediate outcomes compared to CBCR. HBCR may be an effective alternative for improving clinical outcomes in patients who are unable to participate in CBCR.

TPS3640 Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients (pts) with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated it as a primary endpoint. Collaborating with a multidisciplinary oncology team and pt groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation and improve quality of life for pts. Methods: In this Alliance for Clinical Trials in Oncology randomized phase II trial (1:1), up to 312 pts with microsatellite stable LARC, clinical stage T4N0, any T, N+ or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Pts will be randomized to receive neoadjuvant long course CRT (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks (w) + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Pts will undergo assessment 8-12 w post-TNT completion for the primary endpoint of cCR per previously validated criteria and recommended WW and surveillance if cCR is achieved or TME if an incomplete response is noted. Secondary objectives include time-to event outcomes (disease-free and overall survival, organ preservation time and time to distant metastasis) and adverse effects. Statistical power, based on cCR, incorporates a one-sided alpha = 0.048 and power = 90% yielding 312 patients (156 per arm). Biospecimens including archival tumor tissue, matched / normal blood samples and serial rectal MRI will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and is actively recruiting. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov ID: NCT05610163 Clinical trial information: NCT05610163 .

Background: Heart failure patients with preserved ejection fraction (HFpEF) exhibit exercise intolerance and exertional dyspnea. The underlying pathophysiology is complex and involves multiple physiological systems. To this point, HFpEF patients exhibit pulmonary abnormalities at rest and during exercise. For example, HFpEF patients have higher work of breathing during exercise due to greater inspiratory and expiratory resistive work of breathing. Importantly, this greater resistive work of breathing is not associated with higher inspiratory and expiratory flow rates suggesting pulmonary resistance is elevated in HFpEF patients. One potential explanation for the increase in resistive work of breathing during exercise in HFpEF patients is smaller luminal area of the airways. Purpose: The purpose of this study was to determine if differences exist in the luminal area of the large conducting airways in HFpEF patients compared to controls. We hypothesized that HFpEF patients will exhibit smaller luminal areas of the large conducting airways compared to controls. Methods: HFpEF patients (n=9; 67±7 yrs; 30±3 kg/m2) and controls (n=8; 62±9 yrs; 24±3 kg/m2) were enrolled. All participants performed pulmonary function testing and a thoracic computerized tomographic (CT) scan (assessed at total lung capacity). The airway luminal area was quantified from three-dimensional reconstructions from the high-resolution CT scans. The luminal areas of the large conducting airways were measured at three discreet points (corresponding to the beginning, middle, and end of the airway), averaged, and indexed to height. Results: The luminal area of the trachea was not different between groups (p=0.95). HFpEF patients had smaller luminal area of the right main bronchus (control: 1.38±0.21 vs. HFpEF: 1.18±0.13 mm2/cm) and left main bronchus (control: 0.98±0.20 vs. HFpEF: 0.79±0.15 mm2/cm) (both, p<0.04) than controls. HFpEF patients also had smaller luminal area of the bronchus intermedius (control: 0.82±0.14 vs. HFpEF: 0.67±0.15 mm2/cm) and left lower lobe bronchus (control: 0.48±0.13 vs. HFpEF: 0.36±0.07 mm2/cm) compared to controls (both, p<0.04). No differences were present between groups in the right and left upper lobe bronchi (both, p>0.40). Conclusion: HFpEF patients have smaller luminal areas of some, but not all large conducting airways compared to controls. These findings provide support for smaller large conducting airways in HFpEF contributing to the pulmonary abnormalities during exercise in these patients. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The diaphragm muscle is important in both sustaining ventilation and performing higher-force behaviors necessary for maintaining airway patency. Ventilatory behaviors (i.e., eupnea and response to hypoxia-hypercapnia) require only ~20% of maximal force generation, whereas coughing requires forces ~60% of maximal. Existing techniques to measure the full range of forces generated by respiratory muscles are limited by their invasiveness (e.g., balloon manometry for transdiaphragmatic pressure (Pdi) measurements), requirements for training, supervision and subjectivity (e.g., maximal inspiratory and expiratory pressures). Ultrasound-based shear-wave elastography (SWE) assesses muscle stiffness and has shown promising results in being used as a surrogate for Pdi to evaluate diaphragm muscle force. Previous literature has demonstrated a correlation between diaphragm SWE and Pdi at lower force behaviors and the goal of the present study was to evaluate the efficacy of SWE-based measurements of the diaphragm in correlating with Pdi measurements across the range of forces generated by the diaphragm. In this pilot study, we recruited 6 male and 5 female healthy volunteers. Subjects were positioned in a seated position with their torso unsupported. Pdi was measured during graded inspiratory threshold loading trials using a POWERbreathe Plus commercial inspiratory loading device, as well as during maximal inspiratory pressure (MIP). Simultaneously, SWE was performed at the zone of apposition in the right anterior axillary line, and diaphragm Young’s modulus and shear wave speed were subsequently measured. The average Pdi during MIP testing was 149 ± 66 cm H2O. Pdi during inspiratory loading at a low resistance was 39 ± 14 cm H2O and at a high resistance was 78 ± 29 cm H2O. Subjects were able to generate an average Pdi range of 39 ± 19 cm H2O across the graded resistance levels, and the average percent of MIP obtained was 54 ± 13%. Average Young’s modulus as measured with SWE during inspiratory loading at a low resistance was 46 ± 19 kPa and at a high resistance was 104 ± 19 kPa. From low to high resistance, Pdi, Young’s modulus, and shear wave speed increased by an average of 100%, 126%, and 59%, respectively. Taken together, SWE is a promising method of non-invasive assessment of diaphragm muscle forces across a range of voluntary behaviors. Support from NIH grant R21 DA055848 and the Mayo Clinic. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract Funding Acknowledgements Type of funding sources: None. Background Falls are the leading cause of injury-related morbidity and mortality among older adults in the United States, including those with cardiovascular disease. Cardiac rehabilitation (CR) helps to optimize functional capacity, strength, and balance in patients with cardiovascular disease and, in theory, may reduce the risk of falls. However, little evidence has been published in this regard. Purpose The purpose of this study was to assess the association between CR participation and risk of falls in a community-based sample of individuals 65 years of age and older with cardiovascular disease who were eligible for CR participation. Methods Individuals from Southeastern MN and Western WI, USA, 65 years of age and older who had experienced a cardiovascular event that qualified them for CR (MI, PCI, CABG, Valve Surgery, Transplant) between January 1, 2000, and December 31, 2018, were included in this study. Participation in CR (≥1 sessions, CR-group) and subsequent falls (moderate or severe, using the Campbell classification system) were ascertained using the Rochester Epidemiology Project records-linkage system. Logistic model to create propensity weighting were used to test the association between CR participation and falls after adjustment for potentially confounding factors. Results A total of 5004 individuals met inclusion criteria for the study, with 2183 (44%) included in the CR group and 2821 (56%) in the non-CR group (CR was indicated, but the individual did not participate). Overall, 1122 patients experienced a fall within the first 5 years (16% of those in the CR-group, 23% of those in the non-CR group). After adjustment, CR participation was not associated with falls, but older individuals, females, and those with a history of falls were more likely to have had a fall, compared to young individuals, males, and those without a history of a fall. Conclusions While CR is beneficial for patients with cardiovascular disease, our study did not find evidence of an association between CR participation and fall risk in individuals 65 years of age and older who have cardiovascular disease. Additional research is needed to evaluate the role of CR components that may potentially reduce modifiable risk factors for falls and thereby reduce the risk of falls.

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac rehabilitation (CR) is a key component in the continuum of care for patients with CVD that reduces mortality, morbidity and rehospitalization. Clinical practice guidelines strongly recommend and encourage CR participation for eligible patients with CVD. Although there are multiple studies on barriers and solutions to improve the initiation rates of CR, a limited number of studies have explored the barriers and solutions to increase the degree of adherence to CR. Purpose The aim of this study was to define those characteristics that predict adherence to CR with special focus on women and employed patients, since these groups are generally understudied. Methods We performed a retrospective electronic medical record review of the Mayo Clinic CR program, Rochester to identify patients who had started the Mayo Clinic program between January 1, 2014 and September 30, 2015. Among patients who met the inclusion criteria, we conducted a telephone survey with the aim of defining barriers to participation and possible solutions proposed by patients to increase CR adherence. The survey included factors previously identified in the literature as possible barriers, as well as other hypothetical factors; including closed and open-ended questions. The study was approved by the Mayo Clinic institutional review board. Results 376 patients met the inclusion criteria. 257 patients completed the survey. 240 (63.8%) returned the HIPAA (Health Information Use Authorization) document. 72 (30%) were women with a mean age of 66.4 ±12.4 years. Forty-seven percent (n = 113) of the participants did not complete the recommended course of 36 sessions of CR. Among the most important barriers, we found that schedule conflicts were more frequently noted to be a barrier to CR participation among employed patients compared to non-employed patients (p=0.04). Lack of motivation and an inadequate awareness of the importance of completing CR were significantly reported as barriers from employed and non-employed patients. Among the proposed solutions, the participants suggested the potential benefit of alternative delivery models for CR programs; as well efforts to improve awareness of the importance of CR adherence among patients and professionals. Conclusions This study has great relevance because it addressed barriers and potential solutions to CR adherence. Barriers such as mental stress and motivation, as well as a lack of knowledge about CR benefits highlight the role of patient counseling and education as keys to help improve CR adherence. Alternative CR delivery models are attractive options to help facilitate participation, with special focus on the employed population and women, as they more frequently report logistical barriers to CR compared to non-employed patients and men. Further research and advocacy work are needed to help identify and implement strategies that address barriers to CR adherence and completion.

ABSTRACT Introduction Measurement of the work of breathing (Wb) during exercise provides useful insights into the energetics and mechanics of the respiratory muscles across a wide range of minute ventilations. The methods and analytical procedures used to calculate the Wb during exercise have yet to be critically appraised in the literature. Purpose The aim of this systematic review was to evaluate the quality of methods used to measure the Wb during exercise in the available literature. Methods We conducted an extensive search of three databases for studies that measured the Wb during exercise in adult humans. Data were extracted on participant characteristics, flow/volume and pressure devices, esophageal pressure (P oes ) catheters, and methods of Wb analysis. Results A total of 120 articles were included. Flow/volume sensors used were primarily pneumotachographs ( n = 85, 70.8%), whereas the most common pressure transducer was of the variable reluctance type ( n = 63, 52.5%). Esophageal pressure was frequently obtained via balloon-tipped catheters ( n = 114, 95.0%). Few studies mentioned calibration, frequency responses, and dynamic compensation of their measurement devices. The most popular method of measuring the Wb was pressure–volume integration ( n = 51, 42.5%), followed by the modified Campbell ( n = 28, 23.3%) and Dean & Visscher diagrams ( n = 26, 21.7%). Over one-third of studies did not report the methods used to process their pressure–volume data, and the majority (60.8%) of studies used the incorrect Wb units and/or failed to discuss the limitations of their Wb measurements. Conclusions The findings of this systematic review highlight the need for the development of a standardized approach for measuring Wb, which is informative, practical, and accessible for future researchers.

Abstract Over 50 years ago, John Wahren and Lennart Jorfeldt published a manuscript in Clinical Science where they detailed a series of studies of leg blood flow during exercise. They used a novel approach to indicator dye dilution: continuous arterial infusions of dye using venous samples. This technique allowed them to describe for the first time the fundamental relationships between large muscle group exercise, muscle blood flow, and pulmonary and muscle oxygen uptake. They also defined mechanical efficiency, a key measurement of muscle function. This paper formed the basis for research into muscle blood flow and exercise in health and disease and continued to be cited by modern research. In this commentary, we describe the innovations they made, the key observations that came out of their results, and the importance of this manuscript to current research.

Respiratory muscle dysfunction is thought to contribute to exercise intolerance in heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are unknown. In the present study, patients with HFpEF had greater increases in leg muscle vascular resistance index and greater decreases in leg muscle blood flow index compared with controls during inspiratory resistive breathing (to activate the metaboreflex). Furthermore, respiratory muscle blood flow index responses normalized to pressure generation during inspiratory resistive breathing were exaggerated in HFpEF compared with controls.