Urothelium-derived prostanoids enhance contractility of urinary bladder smooth muscle and stimulate bladder afferent nerve activity in the mouse.

The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder contents and the inner layers of the bladder wall. The urothelium, however, is not simply a passive barrier, as it can produce signaling factors, such as ATP, nitric oxide, prostaglandins, and other prostanoids, that can modulate bladder function. We investigated whether substances produced by the urothelium could directly modulate the contractility of the underlying urinary bladder smooth muscle. Force was measured in isolated strips of mouse urinary bladder with the urothelium intact or denuded. Bladder strips developed spontaneous tone and phasic contractions. In urothelium-intact strips, basal tone, as well as the frequency and amplitude of phasic contractions, were 25%, 32%, and 338% higher than in urothelium-denuded strips, respectively. Basal tone and phasic contractility in urothelium-intact bladder strips were abolished by the cyclooxygenase (COX) inhibitor indomethacin (10 µM) or the voltage-dependent Ca2+ channel blocker diltiazem (50 µM), whereas blocking neuronal sodium channels with tetrodotoxin (1 µM) had no effect. These results suggest that prostanoids produced in the urothelium enhance smooth muscle tone and phasic contractions by activating voltage-dependent Ca2+ channels in the underlying bladder smooth muscle. We went on to demonstrate that blocking COX inhibits the generation of transient pressure events in isolated pressurized bladders and greatly attenuates the afferent nerve activity during bladder filling, suggesting that urothelial prostanoids may also play a role in sensory nerve signaling.NEW & NOTEWORTHY This paper provides evidence for the role of urothelial-derived prostanoids in maintaining tone in the urinary bladder during bladder filling, not only underscoring the role of the urothelium as more than a barrier but also contributing to active regulation of the urinary bladder. Furthermore, cyclooxygenase products greatly augment sensory nerve activity generated by bladder afferents during bladder filling and thus may play a role in perception of bladder fullness.

Anxiety Predicts Worse Cardiorespiratory Fitness Outcomes in Cardiac Rehabilitation for Lower Socioeconomic Status Patients.

PURPOSE: The purpose of this study was to show that patients in cardiac rehabilitation (CR) with lower socioeconomic status (SES) have worse clinical profiles and higher rates of psychiatric difficulties and they have lower cardiorespiratory fitness (CRF) improvements from CR than their counterparts with higher SES. Improvement in CRF during CR predicts better long-term health outcomes. Research suggests that higher anxiety impairs CRF in structured exercise regimes and is overrepresented among patients with lower SES. However, no study has determined whether this relationship holds true in CR. METHODS: This study is a secondary analysis of a randomized controlled trial to improve CR attendance among patients with lower SES. Anxiety (ASEBA ASR; Achenbach System of Empirically Based Assessment, Adult Self Report) and CRF measures (metabolic equivalent tasks [METs peak ]) were collected prior to CR enrollment and 4 mo later. Regression was used to examine the association of anxiety with CRF at 4 mo while controlling for other demographic and clinical characteristics. RESULTS: Eight-eight participants were included in the analyses, 31% of whom had clinically significant levels of anxiety ( T ≥ 63). Higher anxiety significantly predicted lower exit CRF when controlling for baseline CRF, age, sex, qualifying diagnosis, and number of CR sessions attended ( ß =-.05, P = .04). Patients with clinically significant levels of anxiety could be expected to lose >0.65 METs peak in improvement. CONCLUSIONS: The results from this study suggest that anxiety, which is overrepresented in populations with lower SES, is associated with less CRF improvement across the duration of CR. The effect size was clinically meaningful and calls for future research on addressing psychological factor in CR.

Carbon monoxide monitoring to objectively measure smoking status in cardiac rehabilitation.

OBJECTIVE: Participation in cardiac rehabilitation (CR) is associated with reduced morbidity and mortality. However, most programs rely on self-report measures when assessing the critical risk factor of smoking. This study examined smoking status using self-report versus objective measurement using expired carbon monoxide (CO) and compared patient characteristics by CO level. METHOD: Patients were screened for smoking status when entering CR by self-report and by objectively measured CO. Measures of aerobic fitness, educational attainment, depressive symptoms, and self-reported physical function were also collected. The discrepancy between smoking status based on self-report and objective measurement was examined and patient characteristics by CO measurement were compared. RESULTS: Of the 853 patients screened, 62 self-reported current smoking and 112 had a CO of ≥ 4 ppm. Using a cut-off of ≥ 4 ppm encompassed almost all self-reported smokers (specificity: 98.5%) and identified 61 patients (not reporting current smoking) needing further screening. Further questioning yielded an additional 21 patients with combusted use (tobacco/cannabis), six nonsmoking patients with environmental CO exposure, and 34 where the reason for elevated CO was unknown. CO ≥ 4 ppm patients were younger (62.2 vs. 67.7, p < .01), had higher depression scores (5.6 vs. 3.7, Patient Health Questionairre-9, p < .01), had lower educational attainment (59.0% ≤ high school vs. 31.3%, p < .01), had lower levels of fitness (after controlling for clinical characteristics, p < .01), and completed fewer CR sessions (18 vs. 22, p < .01). CONCLUSIONS: A substantial number of patients who are actively smoking may be misclassified by relying on patient report alone. CO monitoring provides a simple and objective method of systematically screening patients. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Assessment of the Early Disabling Effects of Coronary Artery Bypass Graft Surgery Using Direct Measures of Physical Function.

PURPOSE: Coronary artery bypass graft (CABG) surgery is an important treatment option in patients with coronary artery disease. Despite its beneficial effects, CABG surgery and its subsequent hospitalization may reduce physical functional capacity in patients, contributing to physical disability. Our objective was to assess the early disabling effects of CABG surgery and its subsequent hospitalization using direct measurements of physical function. METHODS: Patients (n = 44) were assessed pre-surgery and at hospital discharge for physical function using the Short Physical Performance Battery (SPPB) and self-reported physical and mental health by questionnaire. RESULTS: The total SPPB score (P < .001) and all of its components (P < .01-.001) decreased markedly following CABG surgery and hospitalization, with greater reductions in total SPPB score (P < .05) and gait speed (P < .01) in patients with higher body mass index. While CABG surgery and hospitalization reduced patient-reported physical function, changes in these indices largely did not correlate with changes in SPPB outcomes. CONCLUSION: Our results show the early disabling effects of CABG surgery and hospitalization on directly measured physical function, and that patients with higher body mass index had greater reductions. In addition, our results underscore the need to perform direct measurements of physical function to describe reductions in physiological functional capacity. These findings suggest the need for inpatient rehabilitation or early mobility programs to address this decline in physical function.

Benchmarking Depressive Symptoms in Cardiac Rehabilitation.

PURPOSE: Depression affects cardiac health and is important to track within cardiac rehabilitation (CR). Using two depression screeners within one sample, we calculated prevalence of baseline depressive symptomology, improvements during CR, and predictors of both. METHODS: Data were drawn from the University of Vermont Medical Center CR program prospectively collected database. A total of 1781 patients who attended between January 2011 and July 2019 were included. Two depression screeners (Geriatric Depression Scale-Short Form [GDS-SF] and Patient Health Questionnaire-9 [PHQ-9]) were compared on proportion of the sample categorized with ≥ mild or moderate levels of depressive symptoms (PHQ-9 ≥5, ≥10; GDS-SF ≥6, ≥10). Changes in depressive symptoms by screener were examined within patients who had completed ≥9 sessions of CR. Patient characteristics associated with depressive symptoms at entry, and changes in symptoms were identified. RESULTS: Within those who completed ≥9 sessions of CR with exit scores on both screeners (n = 1201), entrance prevalence of ≥ mild and ≥ moderate depressive symptoms differed by screener (32% and 9% PHQ-9; 12% and 3% GDS-SF; both P< .001). Patients who were younger, female, with lower cardiorespiratory fitness (CRF) scores were more likely to have ≥ mild depressive symptoms at entry. Most patients with ≥ mild symptoms decreased severity by ≥1 category by exit (PHQ-9 = 73%; GDS-SF = 77%). Nonsurgical diagnosis and lower CRF were associated with less improvement in symptoms on the PHQ-9 (both P< .05). CONCLUSION: Our results provide initial benchmarks of depressive symptoms in CR. They identify younger patients, women, patients with lower CRF, and those with nonsurgical diagnosis as higher risk groups for having depressive symptoms or lack of improvement in symptoms.

Improvement in Physical Function After Coronary Artery Bypass Graft Surgery Using a Novel Rehabilitation Intervention: A RANDOMIZED CONTROLLED TRIAL.

PURPOSE: Cardiorespiratory and skeletal muscle deconditioning occurs following coronary artery bypass graft surgery and hospitalization. Outpatient, phase 2 cardiac rehabilitation (CR) is designed to remediate this deconditioning but typically does not begin until several weeks following hospital discharge. Although an exercise program between discharge and the start of CR could improve functional recovery, implementation of exercise at this time is complicated by postoperative physical limitations and restrictions. Our objective was to assess the utility of neuromuscular electrical stimulation (NMES) as an adjunct to current rehabilitative care following postsurgical discharge and prior to entry into CR on indices of physical function in patients undergoing coronary artery bypass graft surgery. METHODS: Patients were randomized to 4 wk of bilateral, NMES (5 d/wk) to their quadriceps muscles or no intervention (control). Physical function testing was performed at hospital discharge and 4 wk post-discharge using the Short Physical Performance Battery and the 6-min walk tests. Data from 37 patients (19 control/18 NMES) who completed the trial were analyzed. The trial was registered at ClinicalTrials.gov (NCT03892460). RESULTS: Physical function measures improved from discharge to 4 wk post-surgery across our entire cohort (P < .001). Patients randomized to NMES, however, showed greater improvements in 6-min walk test distance and power output compared with controls (P < .01). CONCLUSION: Our results provide evidence supporting the utility of NMES to accelerate recovery of physical function after coronary artery bypass graft surgery.

Response to Exercise Training During Cardiac Rehabilitation Differs by Sex.

PURPOSE: Directly measured peak aerobic capacity or oxygen uptake is a powerful predictor of prognosis in individuals with cardiovascular disease. Women enter phase 2 cardiac rehabilitation (CR) with lower and their response to training, compared with men, is equivocal. We analyzed at entry and exit in patients participating in CR and improvements by diagnosis to assess training response. We also identified sex differences that may influence change in . METHODS: The cohort included consecutive patients enrolled in CR between January 1996 and December 2015 who performed entry exercise tolerance tests. Data collected included demographics, index diagnosis, , and exercise training response. RESULTS: The cohort consisted of 3925 patients (24% female). There was a significant interaction between baseline and diagnosis (P < .001), with percutaneous coronary intervention and myocardial infarction greater than other diagnoses. Surgical patients demonstrated greater improvement in than nonsurgical diagnoses (n = 1789; P < .001). Women had lower than men for all diagnoses (P < .02) and demonstrated less improvement (13 vs 17%, P < .001). Percent improvement using estimated metabolic equivalents of task (METs) were similar for women and men (33 vs 31%, P = NS). Despite overall increases in , 18% of patients (24% women, 16% men) failed to demonstrate any improvement (exit ≤ entry ). CONCLUSIONS: While there were no differences in training effect estimated by METs, directly measured showed a significantly lower training response for women despite adjusting for covariates. In addition, 18% of patients did not see any improvement in . Alternatives to traditional CR exercise programming need to be considered.

Financial Incentives to Increase Cardiac Rehabilitation Participation Among Low-Socioeconomic Status Patients: A Randomized Clinical Trial.

OBJECTIVES: This study sought to examine the efficacy of financial incentives to increase Medicaid patient participation in and completion of cardiac rehabilitation (CR). BACKGROUND: Participation in CR reduces morbidity, mortality, and hospitalizations while improving quality of life. Lower-socioeconomic status (SES) patients are much less likely to attend and complete CR, despite being at increased risk for recurrent cardiovascular events. METHODS: A total of 130 individuals enrolled in Medicaid with a CR-qualifying cardiac event were randomized 1:1 to receive financial incentives on an escalating schedule ($4 to $50) for completing CR sessions or to receive usual care. Primary outcomes were CR participation (number of sessions completed) and completion (≥30 sessions completed). Secondary outcomes included changes in sociocognitive measurements (depressive/anxious symptoms, executive function), body composition (waist circumference, body mass index), fitness (peak VO2) over 4 months, and combined number of hospitalizations and emergency department (ED) contacts over 1 year. RESULTS: Patients randomized to the incentive condition completed more sessions (22.4 vs. 14.7, respectively; p = 0.013) and were almost twice as likely to complete CR (55.4% vs. 29.2%, respectively; p = 0.002) as controls. Incentivized patients were also more likely to experience improvements in executive function (p < 0.001), although there were no significant effects on other secondary outcomes. Patients who completed ≥30 sessions had 47% fewer combined hospitalizations and ED visits (p = 0.014), as reflected by a nonsignificant trend by study condition with 39% fewer hospital contacts in the incentive condition group (p = 0.079). CONCLUSIONS: Financial incentives improve CR participation among lower-SES patients following a cardiac event. Increasing participation among lower-SES patients in CR is critical for positive longer-term health outcomes. (Increasing Cardiac Rehabilitation Participation Among Medicaid Enrollees; NCT02172820).

Cardiac Rehabilitation Participation Rates and Outcomes for Patients With Heart Failure.

PURPOSE: Exercise training has been shown to reduce combined cardiovascular mortality and hospitalizations in patients with chronic heart failure (CHF) with reduced ejection fraction (HFrEF). Whereas there are extensive data on exercise training for individuals with HFrEF in a research setting, the experience of delivering cardiac rehabilitation (CR) services in the clinical setting has not been well described. With little knowledge regarding the number of qualifying patients with HFrEF in the United States, we described our 18-month experience recruiting hospitalized inpatients and stable outpatients into phase 2 CR. METHODS: Patients hospitalized with CHF HFrEF were tracked for enrollment in CR. Exercise training response was described for patients identified as inpatients and for stable HFrEF outpatients referred from cardiology clinic or heart failure clinic. RESULTS: The cohort included 83 patients hospitalized with CHF and 36 outpatients. Only 17% (14/83) of eligible HFrEF inpatients enrolled in CR following CHF hospitalization compared with 97% (35/36) outpatient referrals. Improvements in aerobic capacity for the total cohort were observed whether expressed as estimated metabolic equivalents (n = 19, 4.6 ± 1.6 to 6.2 ± 2.4, P < .0001) or (Equation is included in full-text article.)O2peak (n = 14, 14.4 ± 3.5 to 16.4 ± 4.6 mL/kg/min, P = .02) for those who completed CR. CONCLUSION: Significant barriers to recruiting and enrolling patients with HFrEF were observed and only 17% of inpatients attended CR. Systematic in-hospital referral with close followup in the outpatient setting has the potential to capture more eligible patients. The participation of referred stable outpatients with HFrEF was much higher. Regardless of the referral source, patients with HFrEF completing CR can expect improvements in aerobic capacity, muscle strength, and depressive symptoms.

Directly Measured Physical Function in Cardiac Rehabilitation.

PURPOSE: The Short Physical Performance Battery (SPPB) is a strong predictor for risk of physical disability in older adults. Roughly half of individuals participating in phase II cardiac rehabilitation (CR) are 65 years or older, many presenting with low aerobic capacities and may be at increased risk for physical disability. METHODS: The cohort consisted of 196 consecutive patients (136 men), aged 65 years or older, entering CR who were prospectively evaluated by the SPPB. Data were also obtained for age, self-reported physical function (Medical Outcomes Study Short Form-36 questionnaire), and peak aerobic capacity. Measures were repeated upon completion of CR for those individuals who completed the program. RESULTS: The average age of patients was 74 ± 0.5 years. At baseline, total SPPB score was 9.7 ± 0.2 (out of 12). Followup data were obtained on 133 (68%) patients, with a mean improvement of 0.8 ± 0.1 (P < .0001), which was not clinically significant (≥1 point). Focusing on patients with a low baseline SPPB score, 72 subjects scored ≤9 (7.1 ± 0.2), with 45 completing exit measures. Improvements were found in gait speed (0.5 ± 0.1, P < .0001), chair-stand (1.0 ± 0.1, P < .0001), and total SPPB (1.6 ± 0.3, P < .0001) in this more disabled group. Measures of (Equation is included in full-text article.)O2peak were significantly reduced in the low SPPB group (13.5 ± 0.4 vs 17.5 ± 0.4 mL/kg/min, P < .0001). Measured (Equation is included in full-text article.)O2peak (R = 26%, P < .0001) and self-reported physical function score (R = 5%, P = .02) were the only multivariate predictors of baseline SPPB. CONCLUSION: For patients who enter CR with low SPPB scores (37%), significant improvements in physical function were noted, largely explained by improved walking speed and leg strength (chair-stand).

Patient Characteristics Predictive of Cardiac Rehabilitation Adherence.

PURPOSE: Cardiac rehabilitation (CR) is a program of structured exercise and interventions for coronary risk factor reduction that reduces morbidity and mortality rates following a major cardiac event. Although a dose-response relationship between the number of CR sessions completed and health outcomes has been demonstrated, adherence with CR is not high. In this study, we examined associations between the number of sessions completed within CR and patient demographics, clinical characteristics, smoking status, and socioeconomic status (SES). METHODS: Multiple logistic regression and classification and regression tree (CART) modeling were used to examine associations between participant characteristics measured at CR intake and the number of sessions completed in a prospectively collected CR clinical database (n = 1658). RESULTS: Current smoking, lower SES, nonsurgical diagnosis, exercise-limiting comorbidities, and lower age independently predicted fewer sessions completed. The CART analysis illustrates how combinations of these characteristics (ie, risk profiles) predict the number of sessions completed. Those with the highest-risk profile for nonadherence (<65 years old, current smoker, lower SES) completed on average 9 sessions while those with the lowest-risk profile (>72 years old, not current smoker, higher SES, surgical diagnosis) completed 27 sessions on average. CONCLUSIONS: Younger individuals, as well as those who report smoking or economic challenges or have a nonsurgical diagnosis, may require additional support to maintain CR session attendance.

Financial incentives to promote cardiac rehabilitation participation and adherence among Medicaid patients.

PURPOSE: Cardiac rehabilitation (CR) improves medical outcomes after myocardial infarction or coronary revascularization. Lower socioeconomic status (SES) patients are less likely to participate in and complete CR. The aim of this study was to test whether financial incentives may increase participation and adherence to CR among lower-SES patients. METHODS: Patients eligible to participate in CR with Medicaid insurance coverage were approached for inclusion. Patients were placed on an escalating incentive schedule of financial incentives contingent upon CR attendance. CR participation was compared to a usual care group of 101 Medicaid patients eligible for CR in the 18months prior to the study. Attendance (participating in ≥one CR sessions) and adherence (sessions completed out of 36) were compared between groups. The study was conducted in Vermont, USA, 2013-2015. RESULTS: Of 13 patients approached to be in the study and receive incentives, 10 (77%) agreed to participate. All 10 patients completed at least one session of CR, significantly greater than the 25/101 (25%) in the control condition (p<0.001). Of patients in both groups who attended at least one session of CR, adherence was higher in the intervention group (average of 31.1 sessions completed vs. 13.6 in the control group, p<0.001). CR completion rates were also higher during the intervention with 8 of 10 (80%) intervention patients completing all 36 sessions compared to only 2 of 25 (8%) control patients (p<0.001). CONCLUSIONS: Financial incentives may be an efficacious strategy for increasing CR participation and adherence among Medicaid patients.

Skeletal muscle ultrastructure and function in statin-tolerant individuals.

INTRODUCTION: Statins have well-known benefits on cardiovascular mortality, though up to 15% of patients experience side effects. With guidelines from the American Heart Association, American College of Cardiology, and American Diabetes Association expected to double the number of statin users, the overall incidence of myalgia and myopathy will increase. METHODS: We evaluated skeletal muscle structure and contractile function at the molecular, cellular, and whole tissue levels in 12 statin tolerant and 12 control subjects. RESULTS: Myosin isoform expression, fiber type distributions, single fiber maximal Ca(2+) -activated tension, and whole muscle contractile force were similar between groups. No differences were observed in myosin-actin cross-bridge kinetics in myosin heavy chain I or IIA fibers. CONCLUSIONS: We found no evidence for statin-induced changes in muscle morphology at the molecular, cellular, or whole tissue levels. Collectively, our data show that chronic statin therapy in healthy asymptomatic individuals does not promote deleterious myofilament structural or functional adaptations.

Cardiac Rehabilitation After Heart Valve Surgery: COMPARISON WITH CORONARY ARTERY BYPASS GRAFT PATIENTS.

PURPOSE: Coronary artery bypass graft (CABG) surgery patients participating in cardiac rehabilitation (CR) experience improvements in aerobic fitness, but there has been little study of outcomes for heart valve (HV) surgical patients. The primary aims of this study were to evaluate baseline peak aerobic capacity for HV patients participating in CR and to compare outcomes between HV and CABG patients. METHODS: Five hundred seventy-six consecutive patients who underwent HV surgery (n = 125), HV plus CABG surgery (n = 57), or CABG surgery (n = 394), all with classic sternotomy and enrolled in CR, were prospectively studied. Changes in outcomes were assessed for individuals who completed CR (n = 313). RESULTS: HV patients were significantly older and had a greater percentage of females than the CABG-only group. Combining HV and HV + CABG groups, valvular disorders included 134 mitral, 39 aortic, and 8 combined abnormalities (mitral and aortic). For the entire cohort, the mean number of CR exercise sessions attended was 23.6 ± 11.7. Peak oxygen uptake ((Equation is included in full-text article.)) increased 19.5% from 17.4 ± 4.4 to 20.8 ± 5.5 mLO2·kg(-1)·min(-1) (P < .0001). Improvement in peak (Equation is included in full-text article.)with CR exercise training was similar between the 3 groups of patients. Within the group of patients who had HV surgery, percentage change in peak (Equation is included in full-text article.)was not significantly different between the 3 types of valvular abnormalities (ie, mitral [19.2%], aortic [24.4%], and mitral + aortic [21.9%]). CONCLUSIONS: HV surgery patients achieve similar improvement in aerobic fitness from participating in CR exercise training as individuals who had CABG. The observed improvements in aerobic fitness are similar, regardless of the type of valve abnormality or whether CABG was performed concurrently.