Risk of major adverse cardiovascular events in rural vs urban settings among patients with erectile dysfunction: a propensity-weighted retrospective cohort study of 430 621 men.

BACKGROUND: The relationship between erectile dysfunction (ED) and cardiovascular (CV) events has been postulated, with ED being characterized as a potential harbinger of CV disease. Location of residence is another important consideration, as the impact of rural residence has been associated with worse health outcomes. AIM: To investigate whether men from rural settings with ED are associated with a higher risk of major adverse CV events (MACEs). METHODS: A propensity-weighted retrospective cohort study was conducted with provincial health administrative databases. ED was defined as having at least 2 ED prescriptions filled within 1 year. MACE was defined as the first hospitalization for an episode of acute myocardial infarction, heart failure, or stroke that resulted in a hospital visit >24 hours. We classified study groups into ED urban, ED rural, no ED urban, and no ED rural. A multiple logistic regression model was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score. OUTCOMES: A Cox proportional hazard model was used to examine our primary outcome of time to a MACE. RESULTS: The median time to a MACE was 2731, 2635, 2441, and 2508 days for ED urban (n = 32 341), ED rural (n = 18 025), no ED rural (n = 146 358), and no ED urban (n = 233 897), respectively. The cohort with ED had a higher proportion of a MACE at 8.94% (n = 4503), as opposed to 4.58% (n = 17 416) for the group without ED. As compared with no ED urban, no ED rural was associated with higher risks of a MACE in stabilized time-varying comodels based on inverse probability treatment weighting (hazard ratio, 1.06-1.08). ED rural was associated with significantly higher risks of a MACE vs no ED rural, with the strength of the effect estimates increasing over time (hazard ratio, 1.10-1.74). CLINICAL IMPLICATIONS: Findings highlight the need for physicians treating patients with ED to address CV risk factors for primary and secondary prevention of CV diseases. STRENGTHS AND LIMITATIONS: This is the most extensive retrospective study demonstrating that ED is an independent risk factor for MACE. Due to limitations in data, we were unable to assess certain comorbidities, including obesity and smoking. CONCLUSIONS: Our study confirms that ED is an independent risk factor for MACE. Rural men had a higher risk of MACE, with an even higher risk among those who reside rurally and are diagnosed with ED.

Impact of a Medical Fitness Model on Incident Major Adverse Cardiovascular Events: A Prospective Cohort Study of 11 000 Members.

BACKGROUND: Cardiovascular disease remains the leading cause of disease burden and death in the world. The medical fitness model may be an alternative public health strategy to address cardiovascular risk factors with medical integrated programming. METHODS AND RESULTS: We performed a retrospective cohort study between January 1, 2005, and December 31, 2015. Adults (aged ≥18 years) who did not have a prior major adverse cardiovascular event were included. Controls were assigned a pseudo-index date at random on the basis of the frequency distribution of start dates in the medical fitness facility group. Multivariate Cox proportional hazards regression models were adjusted for age, sex, socioeconomic status, comorbidities, and year of index date. We stratified the medical fitness facility group into low-frequency attenders (≤1 weekly visit) and regular-frequency attenders (>1 weekly visit). Our primary outcome was a hospitalization for nonfatal myocardial infarction and stroke, heart failure, or cardiovascular death. We included 11 319 medical fitness facility members and 507 400 controls in our study. Compared with controls, members had a lower hazard risk of a major adverse cardiovascular event-plus (hazard ratio [HR], 0.88 [95% CI, 0.81-0.96]). Higher weekly attendance was associated with a lower hazard risk of a major adverse cardiovascular event-plus compared with controls, but the effect was not significant for lower weekly attendance (low-frequency attenders: HR, 0.94 [95% CI, 0.85-1.04]; regular-frequency attenders: HR, 0.77 [95% CI, 0.67-0.89]). CONCLUSIONS: Medical fitness facility membership and attendance at least once per week may lower the risk of a major adverse cardiovascular event-plus. The medical fitness model should be considered as a public health intervention, especially for individuals at risk for cardiovascular disease.

A Randomized Trial Examining the Impact of Timing of Intradialytic Cycling on Intradialytic Hypotension.

Introduction: Intradialytic cycling is often performed during the first half of hemodialysis because of concerns regarding increased frequency of intradialytic hypotension (IDH) late in hemodialysis. This increases exercise program resource needs and limits utility of intradialytic cycling to treat dialysis-related symptoms. Methods: This multicenter, randomized, crossover trial compared IDH rate when cycling during the first half versus the second half of hemodialysis in 98 adults on maintenance hemodialysis. Group A cycled during the first half of hemodialysis for 2 weeks and subsequently during the second half for 2 weeks. In group B, the cycling schedule was reversed. Blood pressure (BP) was measured every 15 minutes throughout hemodialysis. Primary outcome was IDH rate (systolic BP [SBP] decrease of >20 mm Hg or SBP <90 mm Hg). Secondary outcomes included symptomatic IDH rate and time to recover post hemodialysis. Data were analyzed using negative binomial and gamma distribution mixed regression. Results: Mean age 64.7 (SD 12.0) and 64.7 (SD 14.2) years in group A (n = 52) and group B (n = 46), respectively. Proportions of females were 33% in group A and 43% in group B. Median time on hemodialysis was 4.1 (interquartile range [IQR] 2.5, 6.1]) years in group A and 3.9 years (IQR 2.5, 6.7) in group B. IDH rate per 100 hemodialysis hours (95% confidence interval [CI]) was 34.2 (26.4, 42.0) and 36.0 (28.9, 43.1) during early and late intradialytic cycling, respectively (P = 0.53). Timing of intradialytic cycling was not associated with symptomatic IDH (relative risk [RR]: 1.07 [0.75-1.53]) or time to recover post hemodialysis (odds ratio: 0.99 [0.79-1.23]). Conclusion: We found no association between the rate of overall or symptomatic IDH and the timing of intradialytic cycling in patients enrolled in an intradialytic cycling program. Increased use of cycling late in hemodialysis may optimize intradialytic cycling program resource use and should be studied as a possible treatment for symptoms common in late hemodialysis.

Association of Membership at a Medical Fitness Facility With Adverse Health Outcomes.

INTRODUCTION: Interventions that increase physical activity behavior can reduce morbidity and prolong life, but long-term effects in large populations are unproven. This study investigates the association of medical fitness facility membership and frequency of attendance with all-cause mortality and rate of hospitalization. METHODS: A propensity weighted retrospective cohort study was conducted by linking individuals who attended medical fitness facilities in Winnipeg, Canada to provincial health administrative databases. Members aged ≥18 years who had ≥1 year of provincial health coverage from their index date between January 1, 2005 and December 31, 2015 were included. Controls were assigned a pseudo-index date at random on the basis of the frequency distribution of index dates in the intervention group. Members were stratified into low-frequency attenders (<1 weekly visit), moderate-frequency attenders (1-3 weekly visits), and high-frequency attenders (>3 weekly visits). The primary outcomes were time to all-cause mortality and rate of hospitalizations. Statistical analyses were performed between 2018 and 2020. RESULTS: Among 19,300 adult members and 515,810 controls, members had a 60% lower risk of all-cause mortality during the first 651 days and 48% after 651 days. Membership was associated with a 13% lower risk of hospitalizations. A dose-response effect was apparent because higher weekly attendance was associated with a lower risk of hospitalizations (low frequency: 9%, moderate frequency: 20%, high frequency: 39%). CONCLUSIONS: Membership at a medical fitness facility was associated with a reduced risk of all-cause mortality and hospitalizations. Healthcare systems should consider the medical fitness model as a preventative public health strategy to encourage physical activity participation.

Change in Physical Activity and Function in Patients with Baseline Advanced Nondialysis CKD.

BACKGROUND AND OBJECTIVES: Although progressive decline in physical activity and function are common in individuals with worsening CKD, little is known about the effect of dialysis initiation on physical activity. We assessed for any association of progression to dialysis in people with advanced CKD with temporal rates of change in physical activity and function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Canadian Frailty Observation and Interventions Trial (CanFIT) participants with an eGFR of <30 ml/min per 1.73 m2 were included. Outcomes included change in physical activity level, measured using the Physical Activity Scale for the Elderly, and physical function, measured using the chair stand, 4-m gait speed, and grip strength tests. Generalized linear regression models were conducted to determine whether dialysis initiation was associated with greater decline in physical activity or function. RESULTS: Of 386 individuals, 162 progressed to dialysis. Both assessments were completed by 98% of individuals for the Physical Activity Scale for the Elderly, 86% for the chair stand test, 84% for the gait speed test, and 91% for the grip strength test. Median (interquartile range) interassessment follow-up was 427 (357-578) days for the "stable advanced CKD" group and 606 (428-1000) days for the "progressed to dialysis" group. Self-reported physical activity and gait speed significantly declined in both groups. Mean (SD) chair stand time increased from 20.8 (17.1) to 24.0 (21.0) seconds among patients with stable advanced CKD, and from 18.5 (15.4) to 27.4 (22.2) seconds among those who progressed to dialysis (adjusted difference in change, 5.2 seconds; 95% confidence interval, 0.8 to 9.7 seconds; P=0.02). CONCLUSIONS: Patients with advanced CKD experience progressive declines in physical activity and function. Transition to dialysis is associated with accelerated decline in physical function, as measured by the chair stand test.

Provider Perception of Frailty Is Associated with Dialysis Decision Making in Patients with Advanced CKD.

BACKGROUND AND OBJECTIVES: Frailty is common in patients with CKD. Little is known about the prevalence of frailty and its effect on prognosis and decisions surrounding dialysis modalities in patients with advanced CKD (eGFR<30 ml/min per 1.73 m2). Our objective was to determine the agreement between different frailty measures and physical function and their association with dialysis modality choice (home based versus in-center) and all-cause mortality in patients with advanced CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study was a prospective, multicenter, cohort study. In 603 patients with advanced CKD, we collected demographics, comorbidities, and laboratory results in addition to objective (Fried frailty criteria) and subjective measures of frailty (physician and nurse impressions) and physical function (Short Physical Performance Battery). Logistic regression and Cox proportional hazards models were used to evaluate the association of frailty with dialysis modality choice and all-cause mortality, respectively. RESULTS: The prevalence of frailty varied with assessment tool used (Fried frailty criteria, 34%; Short Physical Performance Battery, 55%; physician impression, 44%; nurse impression, 36%). The agreement between all frailty and physical function measures was poor. We had 227 patients reach kidney failure and decide on a dialysis therapy, and 226 patients died during a mean follow-up of 1455 days. After adjusting for age, sex, and comorbid conditions, the Fried criteria and Short Physical Performance Battery were associated with a two-fold higher risk of all-cause mortality (hazard ratio, 1.96; 95% confidence interval, 1.47 to 2.61 and hazard ratio, 1.96; 95% confidence interval,1.42 to 2.76, respectively). Patients deemed as frail by physician and nurse frailty impressions were three to four times more likely to choose in-center dialysis (odds ratio, 3.41; 95% confidence interval, 1.56 to 7.44; odds ratio, 3.87; 95% confidence interval, 1.76 to 8.51, respectively). CONCLUSIONS: We found that the agreement between objective and subjective measures of frailty and physical function was poor. Objective measures of frailty and physical function were associated with mortality, and subjective measures of frailty were associated with dialysis modality choice.

Association of Physical Activity and Poor Health Outcomes in Patients With Advanced CKD.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is associated with declining physical function and activity. In the general population, lower physical activity is associated with poorer quality of life and greater all-cause mortality. The aim of this study was to assess if lower physical activity levels are associated with adverse health outcomes in patients with advanced CKD. STUDY DESIGN: A multicenter prospective cohort study. SETTING & PARTICIPANTS: 579 adult patients with CKD glomerular filtration rate categories 4 and 5 (G4-G5) treated at 4 Canadian multidisciplinary kidney health clinics between 2012 and 2018. EXPOSURE: Patient-reported measures of physical activity using the Physical Activity Scale for the Elderly (PASE) questionnaire and subsequently stratified PASE scores into tertiles. OUTCOME: All-cause mortality, progression to kidney failure, and future falls. ANALYTICAL APPROACH: Outcomes were analyzed using time-dependent proportional hazards models and logistic regression models. RESULTS: In 1,193 days of follow-up observation, 118 patients died, 204 progressed to dialysis, and 129 reported a fall. When compared with low physical activity, higher levels of physical activity were associated with a 52% lower all-cause mortality (adjusted HR, 0.48; 95% CI, 0.27-0.85) in models adjusted for age, sex, and comorbidity. No associations were detected between higher levels of physical activity and either slower progression to kidney failure or a lower rate of future falls. LIMITATIONS: Physical activity and falls were self-reported. Our population was of limited racial/ethnic diversity, which may affect generalizability. Findings were observational and do not indicate whether interventions targeting physical activity may affect adverse health outcomes. CONCLUSIONS: Higher levels of physical activity were associated with about 50% lower all-cause mortality in the advanced CKD population. These findings are consistent with a potential benefit from maintained physical activity as patients approach kidney failure.

The Impact of Frailty on Technique Failure and Mortality in Patients on Home Dialysis.

Background:Patients on home dialysis therapies experience technique failure, which is associated with morbidity and mortality. Reasons for technique failure are complex, and often related to functional decline in the patient or caregiver. Frailty is associated with an increased risk of adverse health outcomes. We investigated the impact of frailty on technique failure and mortality in a prospective cohort of patients on home dialysis therapies.Methods:We collected objective (Fried criteria and Short Physical Performance Battery [SPPB]), and subjective (physician and nurse impression) measures of frailty from 109 prevalent home dialysis patients. Our primary outcome was a composite of technique failure, defined as a permanent unplanned transition (> 30 days in duration) to facility-based hemodialysis or all-cause death. The association between different frailty assessment tools and the primary composite outcome was evaluated using Cox models.Results:Fried criteria and physician impression was associated with a greater than 2-fold increase in risk of our composite outcome (HR: 2.10 [95% CI 1.09 - 3.99], 2.15 [95% CI 1.15 - 4.00, respectively] in adjusted analyses. Weakness and weight loss subdomains of the Fried criteria were both associated with an increased risk of our composite outcome in adjusted analyses (HR: 2.16 [95% CI 1.23 - 3.78], 2.69 [95% CI 1.39 - 5.40], respectively).Conclusions:Objective and subjective measures of frailty are associated with a more than 2-fold higher risk of technique failure or death in patients undergoing home dialysis. Assessing frailty as part of the clinical evaluation for home dialysis therapies may be useful for prognostication and clinical management.

Intradialytic exercise preconditioning: an exploratory study on the effect on myocardial stunning.

BACKGROUND: Exercise preconditioning provides immediate protection against cardiac ischemia in clinical/preclinical studies in subjects without chronic kidney disease. In individuals requiring renal replacement therapy, hemodialysis (HD) results in significant circulatory stress, causing acute ischemia with resultant recurrent and cumulative cardiac injury (myocardial stunning). Intradialytic exercise (IDE) has been utilized to improve functional status in individuals receiving HD. The objective of this study was to explore the role of IDE as a preconditioning intervention and assess its effect on HD-induced myocardial stunning. METHODS: We performed a single-center cross-sectional exploratory study in adults on chronic HD participating in a clinical IDE program. HD-induced cardiac stunning was evaluated over two HD sessions within the same week: a control visit (no exercise) and an exposure visit (usual intradialytic cycling). Echocardiography was performed at the same three time points for each visit. Longitudinal strain values for 12 left ventricular segments were generated using speckle-tracking software to assess the presence of HD-induced regional wall motion abnormalities (RWMAs), defined as a ≥20% reduction in strain; two or more RWMAs represent myocardial stunning. RESULTS: A total of 19 patients were analyzed (mean age 57.2 ± 11.8 years, median dialysis vintage 3.8 years). The mean number of RWMAs during the control visit was 4.5 ± 2.6, falling to 3.6 ± 2.7 when incorporating IDE (a reduction of -0.95 ± 2.9; P = 0.17). At peak HD stress, the mean number of RWMAs was 5.8 ± 2.7 in the control visit versus 4.0 ± 1.8 during the exposure visit (a reduction of -1.8 ± 2.8; P = 0.01). CONCLUSION: We demonstrated for the first time that IDE is associated with a significant reduction in HD-induced acute cardiac injury.

Cognitive Impairment in Advanced Chronic Kidney Disease: The Canadian Frailty Observation and Interventions Trial.

BACKGROUND: Chronic kidney disease (CKD) affects more than one third of older adults, and is a strong risk factor for vascular disease and cognitive impairment. Cognitive impairment can have detrimental effects on the quality of life through decreased treatment adherence and poor nutrition and results in increased costs of care and early mortality. Though widely studied in hemodialysis populations, little is known about cognitive impairment in patients with pre-dialysis CKD. METHODS: Multicenter, cross-sectional, prospective cohort study including 385 patients with CKD stages G4-G5. Cognitive function was measured with a validated tool called the Montreal Cognitive Assessment (MoCA) as part of a comprehensive frailty assessment in the Canadian Frailty Observation and Interventions Trial. Cognitive impairment was defined as a MoCA score of ≤24. We determined the prevalence and risk factors for cognitive impairment in patients with CKD stages G4-G5, not on dialysis. RESULTS: Two hundred and thirty seven participants (61%) with CKD stages G4-G5 had cognitive impairment at baseline assessment. When compared to a control group, this population scored lower in all domains of cognition, with the most pronounced deficits observed in recall, attention, and visual/executive function (p < 0.01 for all comparisons). Older age, recent history of falls and history of stroke were independently associated with cognitive impairment. CONCLUSIONS: Our study uncovered a high rate of unrecognized cognitive impairment in an advanced CKD population. This impairment is global, affecting all aspects of cognition and is likely vascular in nature. The longitudinal trajectory of cognitive function and its effect on dialysis decision-making and outcomes deserves further study.

Frailty and physical function in chronic kidney disease: the CanFIT study.

BACKGROUND: Frailty, a manifestation of unsuccessful aging, is highly prevalent in people with chronic kidney disease (CKD) and is associated with comorbid conditions in cross-sectional studies. Longitudinal studies investigating the progression of frailty in those with advanced non-dialysis CKD are lacking. OBJECTIVES: Canadian Frailty Observation and Interventions Trial (CanFIT). To determine the natural history, prevalence of perceived and measured frailty and its association with dialysis treatment choices and adverse outcomes in patients with advanced CKD. DESIGN: Longitudinal observational study, designed to collect data from 600 participants over 2 years. SETTING: Interprofessional non-dialysis CKD clinics at four tertiary health care centres in central Canada. PATIENTS: People with CKD stage 4 and 5 (eGFR <30 ml/min/1.73 m(2)) who are not on dialysis at enrollment. MEASUREMENTS: Multiple Frailty Definitions: Short Physical Performance Battery (SPPB), Fried Frailty Criteria, Frailty Index. Dialysis start: In-Centre Hemodialysis, Home Hemodialysis or Peritoneal Dialysis Outcomes: Death, Opt-out or Lost to follow up. METHODS: We will perform physical and cognitive assessments annually. We plan to analyze the relationships between frailty, treatment choices and patient centered outcomes. RESULTS: We have recruited 217 participants in 2 centres; of these, 56 % had reduced physical function at baseline, as defined by the SPPB. Risk of reduced physical function was 8 fold higher in those with diabetes after adjusting for age, gender, eGFR and comorbidities. LIMITATIONS: Referred population, use of SPPB as a measure of frailty, inter-operator variability in measurement of hand grip and gait speed, cross-sectional analysis of baseline data in the subset recruited to date. CONCLUSIONS: People with advanced CKD have a high burden of reduced physical function, especially those with diabetes. We will continue enrollment into the CanFIT study to further understand the clinical history of CKD and frailty in this population.

CONTEXTE: La fragilité, une manifestation du vieillissement malheureux, est très répandue chez les personnes atteintes d'insuffisance rénale chronique (IRC) et est associée à des conditions de comorbidité dans les études transversales. Rares sont les études longitudinales destinées à étudier la progression de la fragilité chez les personnes atteintes d'IRC avancée qui ne reçoivent pas de dialyse. OBJECTIFS: Canadian Frailty Observation and Interventions Trial (CanFIT). Déterminer l'évolution naturelle, la prévalence de la fragilité perçue et mesurée, de même que son association avec les options de traitement à la dialyse et les effets indésirables sur les patients atteints d'IRC avancée. TYPE D'ÉTUDE: Étude longitudinale d'observation visant à recueillir les données de 600 patients sur deux ans. CONTEXTE: Des unités interprofessionnelles d'IRC qui ne pratiquent pas la dialyse dans quatre centres de soins tertiaires du centre du Canada. PARTICIPANTS: Des personnes atteintes d'IRC de stade 4 et 5 (R-EGF <30 ml/min/1,73 m2) qui ne recevaient pas de dialyse au moment de l'inscription. MESURES: Diverses définitions de la fragilité : le Short Physical Performance Battery (SPPB), les critères de fragilité de Fried et l'indice de fragilité. Le lieu de l'amorce de la dialyse : la dialyse en centre, la dialyse à domicile; ou les résultats de la dialyse péritonéale : le décès, le refus ou la perte de suivi. MÉTHODES: Nous effectuerons des examens physiques et cognitifs sur une base annuelle. Nous planifions analyser la relation entre la fragilité, le choix du traitement et les résultats axés sur le patient. RÉSULTATS: Nous avons recruté 217 participants dans 2 centres; parmi ceux-ci, 56 % présentaient d'entrée de jeu une réduction des fonctions physiques, telles que définies par le SPPB. Les risques de subir une réduction des fonctions physiques étaient 8 fois supérieurs chez les patients souffrant de diabète, après ajustement selon l'âge, le sexe, le R-EGF et les comorbidités. LIMITES DE L'ÉTUDE: La population désignée, le recours au SPPB pour mesurer la fragilité, la variabilité des intervenants dans la mesure de la vitesse de préhension et de marche, l'analyse transversale des données de référence du sous-ensemble recruté jusqu'à maintenant. CONCLUSIONS: Les personnes atteintes d'IRC avancée sont accablées d'une forte réduction de la fonction physique, et particulièrement celles qui sont atteintes de diabète. Nous poursuivrons l'inscription à l'étude de CanFIT afin d'approfondir les connaissances au sujet de l'évolution clinique de l'IRC et la fragilité des personnes atteintes.

Urinary, Plasma, and Serum Biomarkers' Utility for Predicting Acute Kidney Injury Associated With Cardiac Surgery in Adults: A Meta-analysis.

BACKGROUND: Early accurate detection of acute kidney injury (AKI) occurring after cardiac surgery may improve morbidity and mortality. Although several novel biomarkers have been developed for the early detection of AKI, their clinical utility in the critical intraoperative and immediate postoperative period remains unclear. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adult patients having cardiac surgery. SELECTION CRITERIA FOR STUDIES: EMBASE, CINAHL, Cochrane Library, Scopus, and PubMed from January 1990 until January 2015 were systematically searched for cohort studies reporting the utility of novel biomarkers for the early diagnosis of AKI after adult cardiac surgery. Reviewers extracted data for study design, population, timing of biomarker measurement and AKI occurrence, biomarker performance (area under the receiver operating characteristic curve [AUROC]), and risk of bias. INDEX TESTS: Novel urine, plasma, and serum AKI biomarkers, measured intraoperatively and in the early postoperative period (<24 hours). REFERENCE TESTS: AKI was defined according to the RIFLE, AKIN, or 2012 KDIGO criteria. RESULTS: We found 28 studies reporting intraoperative and/or early postoperative measurement of urine (n=23 studies) or plasma or serum (n=12 studies) biomarkers. Only 4 of these studies measured biomarkers intraoperatively. Overall, intraoperative discrimination by the urine biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury marker 1 (KIM-1) demonstrated AUROCs<0.70, whereas N-acetyl-ß-d-glucosaminidase (NAG) and cystatin C had AUROCs<0.75. In the immediate 24-hour postoperative period, the urine biomarkers NGAL (16 studies), KIM-1 (6 studies), and liver-type fatty acid binding protein (6 studies) exhibited composite AUROCs of 0.69 to 0.72. The composite AUROCs for postoperative urine cystatin C, NAG, and interleukin 18 were ≤0.70. Similarly, the composite AUROCs for postoperative plasma NGAL (6 studies) and cystatin-C (5 studies) were <0.70. LIMITATIONS: Heterogeneous AKI definitions. CONCLUSIONS: In adults, known urinary, plasma, and serum biomarkers of AKI possess modest discrimination at best when measured within 24 hours of cardiac surgery.