Quantifying Improvement in V˙ o2peak and Exercise Thresholds in Cardiovascular Disease Using Reliable Change Indices.

PURPOSE: Improving aerobic fitness through exercise training is recommended for the treatment of cardiovascular disease (CVD). However, strong justifications for the criteria of assessing improvement in key parameters of aerobic function including estimated lactate threshold (θ LT ), respiratory compensation point (RCP), and peak oxygen uptake (V˙ o2peak ) at the individual level are not established. We applied reliable change index (RCI) statistics to determine minimal meaningful change (MMC RCI ) cutoffs of θ LT , RCP, and V˙ o2peak for individual patients with CVD. METHODS: Sixty-six stable patients post-cardiac event performed three exhaustive treadmill-based incremental exercise tests (modified Bruce) ∼1 wk apart (T1-T3). Breath-by-breath gas exchange and ventilatory variables were measured by metabolic cart and used to identify θ LT , RCP, and V˙ o2peak . Using test-retest reliability and mean difference scores to estimate error and test practice/exposure, respectively, MMC RCI values were calculated for V˙ o2 (mL·min -1. kg -1 ) at θ LT , RCP, and V˙ o2peak . RESULTS: There were no significant between-trial differences in V˙ o2 at θ LT ( P = .78), RCP ( P = .08), or V˙ o2peak ( P = .74) and each variable exhibited excellent test-retest variability (intraclass correlation: 0.97, 0.98, and 0.99; coefficient of variation: 6.5, 5.4, and 4.9% for θ LT , RCP, and V˙ o2peak , respectively). Derived from comparing T1-T2, T1-T3, and T2-T3, the MMC RCI for θ LT were 3.91, 3.56, and 2.64 mL·min -1. kg -1 ; 4.01, 2.80, and 2.79 mL·min -1. kg -1 for RCP; and 3.61, 3.83, and 2.81 mL·min -1. kg -1 for V˙ o2peak . For each variable, MMC RCI scores were lowest for T2-T3 comparisons. CONCLUSION: These MMC RCI scores may be used to establish cutoff criteria for determining meaningful changes for interventions designed to improve aerobic function in individuals with CVD.

Probing Evidence of Cerebral White Matter Microstructural Disruptions in Ischemic Heart Disease Before and Following Cardiac Rehabilitation: A Diffusion Tensor MR Imaging Study.

BACKGROUND: Ischemic heart disease (IHD) is linked to brain white matter (WM) breakdown but how age or disease effects WM integrity, and whether it is reversible using cardiac rehabilitation (CR), remains unclear. PURPOSE: To assess the effects of brain aging, cardiovascular disease, and CR on WM microstructure in brains of IHD patients following a cardiac event. STUDY TYPE: Retrospective. POPULATION: Thirty-five IHD patients (9 females; mean age = 59 ± 8 years), 21 age-matched healthy controls (10 females; mean age = 59 ± 8 years), and 25 younger controls (14 females; mean age = 26 ± 4 years). FIELD STRENGTH/SEQUENCE: 3 T diffusion-weighted imaging with single-shot echo planar imaging acquired at 3 months and 9 months post-cardiac event. ASSESSMENT: Tract-based spatial statistics (TBSS) and tractometry were used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in cerebral WM between: 1) older and younger controls to distinguish age-related from disease-related WM changes; 2) IHD patients at baseline (pre-CR) and age-matched controls to investigate if cardiovascular disease exacerbates age-related WM changes; and 3) IHD patients pre-CR and post-CR to investigate the neuroplastic effect of CR on WM microstructure. STATISTICAL TESTS: Two-sample unpaired t-test (age: older vs. younger controls; IHD: IHD pre-CR vs. age-matched controls). One-sample paired t-test (CR: IHD pre- vs. post-CR). Statistical threshold: P < 0.05 (FWE-corrected). RESULTS: TBSS and tractometry revealed widespread WM changes in older controls compared to younger controls while WM clusters of decreased FA in the fornix and increased MD in body of corpus callosum were observed in IHD patients pre-CR compared to age-matched controls. Robust WM improvements (increased FA, increased AD) were observed in IHD patients post-CR. DATA CONCLUSION: In IHD, both brain aging and cardiovascular disease may contribute to WM disruptions. IHD-related WM disruptions may be favorably modified by CR. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Do Clinical Exercise Tests Permit Exercise Threshold Identification in Patients Referred to Cardiac Rehabilitation?

BACKGROUND: To evaluate the feasibility of "threshold-based" aerobic exercise prescription in cardiovascular disease, we aimed to quantify the proportion of patients whose clinical cardiopulmonary exercise test (CPET) permit identification of estimated lactate threshold (θLT) and respiratory compensation point (RCP) and to characterize the variability at which these thresholds occur. METHODS: Breath-by-breath CPET data of 1102 patients (65 ± 12 years) referred to cardiac rehabilitation were analyzed to identify peak O2 uptake (V˙O2peak; mL·min-1 and mL·kg-1·min-1) and θLT and RCP (reported as V˙O2, %V˙O2peak, and %peak heart rate [%HRpeak]). Patients were grouped by the presence or absence of thresholds: group 0: neither θLT nor RCP; group 1: θLT only; and group 2: both θLT and RCP. RESULTS: Mean V˙O2peak was 1523 ± 627 mL·min-1 (range: 315-3789 mL·min-1) or 18.0 ± 6.5 mL·kg-1·min-1 (5.2-46.5 mL·kg-1·min-1) and HRpeak was 123 ± 24 beats per minute (bpm) (52 bpm-207 bpm). There were 556 patients (50%) in group 0, 196 (18%) in group 1, and 350 (32%) in group 2. In group 1, mean θLT was 1240 ± 410 mL·min-1 (580-2560 mL·min-1), 75% ± 8%V˙O2peak (52%-92%V˙O2peak), or 84% ± 6%HRpeak (64%-96%HRpeak). In group 2, θLT was 1390 ± 360 mL·min-1 (640-2430 mL·min-1), 70% ± 8%V˙O2peak (41%-88%V˙O2peak), or 78% ± 7%HRpeak (52%-96%HRpeak), and RCP was 1680 ± 440 mL·min-1 (730-3090 mL·min-1), 84% ± 7%V˙O2peak (54%-99%V˙O2peak), or 87% ± 6%HRpeak (59%-99%HRpeak). Compared with group 1, θLT in group 2 occurred at a higher V˙O2 but lower %V˙O2peak and %HRpeak (P < 0.05). CONCLUSIONS: Only 32% of CPETs exhibited both θLT and RCP despite flexibility in protocol options. Commonly used step-based protocols are suboptimal for "threshold-based" exercise prescription.

Importance of Completing Hybrid Cardiac Rehabilitation for Long-Term Outcomes: A Real-World Evaluation.

Community-based hybrid cardiac rehabilitation (CR) programs offer a viable alternative to conventional centre-based CR, however their long-term benefits are unknown. We conducted a secondary analysis of the CR Participation Study conducted in London, Ontario, between 2003 and 2006. CR eligible patients hospitalized for a major cardiac event, who resided within 60 min, were referred to a hybrid CR program; 381 of 544 (64%) referred patients initiated CR; an additional 1,498 CR eligible patients were not referred due to distance. For the present study, CR participants were matched using propensity scores to CR eligible non-participants who resided beyond 60 min, yielding 214 matched pairs. Subjects were followed for a mean (standard deviation, SD) of 8.56 (3.38) years for the outcomes of mortality or re-hospitalization for a major cardiac event. Hybrid CR participation was associated with a non-significant 16% lower event rate (Hazard Ratio [HR]: 0.84, 95% CI: 0.59⁻1.17). When restricting to pairs where CR participants achieved a greater than 0.5 metabolic equivalent exercise capacity increase (123 pairs), CR completion was associated with a 51% lower event rate (HR: 0.49, 95% CI: 0.29⁻0.81). Successful completion of a community-based hybrid CR program may be associated with decreased long-term mortality or recurrent cardiac events.

Smoking cessation and the cardiovascular specialist: Canadian Cardiovascular Society position paper.

Tobacco addiction is the leading cause of preventable disease, disability, and death in Canada and is the most significant of the modifiable cardiovascular risk factors. Tobacco addiction is a principal contributor to the development of coronary artery disease (CAD) and its consequences, including sudden cardiac death, acute myocardial infarction, and heart failure. Its prevention and treatment should be accorded high priority. In fact, 30% of all CAD deaths are attributable to smoking. The identification and documentation of the smoking status of all patients, and the provision of cessation assistance, should be a priority in every cardiovascular setting. Systematic approaches to the identification and treatment of smokers can dramatically enhance the likelihood of cessation-the most cost-effective of all the interventions to prevent the development or progression of CAD. It is the view of the Canadian Cardiovascular Society that all patients in every medical setting-private office, outpatient clinic, or hospital-should have their smoking status systematically identified and documented and be offered specific assistance in initiating a cessation attempt. The provision of unambiguous, nonjudgemental advice regarding the importance of cessation and assistance with the initiation of a smoking cessation attempt should be seen as a fundamental responsibility of any cardiovascular clinician who encounters smokers in any setting. All cardiovascular specialists should be familiar with the principles and practice of smoking cessation. It is important for cardiovascular specialists to be as familiar with the initiation of smoking-cessation pharmacotherapy as they are with the pharmacological management of hypertension and hyperlipidemia.

The effects of exercise training on insulin resistance in patients with coronary artery disease.

BACKGROUND: It is unclear whether the beneficial effects of habitual exercise on insulin resistance are due to concomitant weight loss, changes in diet or whether they are simply related to the transient effects of the last bout of exercise. Moreover, patients with coronary artery disease (CAD) have not been studied. DESIGN: Randomized controlled trial. METHODS: To determine the effects of exercise training on insulin resistance (i.e. low insulin sensitivity) in CAD patients without diabetes independent of changes in weight, diet or the effect of acute exercise, 29 patients were randomized to 12 weeks of supervised exercise training and 26 to usual activity. Insulin sensitivity was determined at 72 h following their last bout of exercise using the minimal model technique. Weight was held constant by adjusting caloric intake. RESULTS: Following the intervention, peak oxygen uptake increased by 0.18+/-0.14 l/min in the exercise training group, which was significantly higher (P<0.0001) than that in the usual activity group (0.02+/-0.14 l/min). Insulin sensitivity did not change significantly within or between groups during the study [exercise training -0.24+/-1.15 x 10(4)/min and usual activity 0.06+/-0.67 x 10(4)/min/(microU/ml)]. CONCLUSIONS: Twelve weeks of moderate exercise training in the absence of weight loss did not result in significant change in insulin resistance in patients with CAD.

Recurrent hepatocellular carcinoma after transplantation: use of a pathological score on explanted livers to predict recurrence.

Milan and University of California at San Francisco (UCSF) criteria are used to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). Recurrent HCC is a significant cause of death. There is no widely accepted pathological assessment strategy to predict recurrent HCC after transplantation. This study compares the pathology of patients meeting Milan and UCSF criteria and develops a pathological score and nomogram to assess the risk of recurrent HCC after transplantation. All explanted livers with HCC from our center over the 18-yr period 1985 to 2003 were assessed for multiple pathological features and relevant clinical data were recorded; multivariate analysis was performed to determine features associated with recurrent HCC. Using pathological variables that independently predicted recurrent HCC, a pathological score and nomogram were developed to determine the probability of recurrent HCC. Of 75 cases analyzed, 50 (67%) met Milan criteria, 9 (12%) met only UCSF criteria and 16 (21%) met neither criteria based on explant pathology. There were 20 cases of recurrent HCC and the mean follow-up was 8 yr. Recurrent HCC was more common (67 vs. 12%; P < 0.001) and survival was lower (15 vs. 83% at 5 yr; 15 vs. 55% at 8 yr; P < 0.001) with those who met only UCSF criteria, compared to those who met Milan criteria. Cryptogenic cirrhosis (25 vs. 5%; P = 0.015), preoperative AFP >1,000 ng/mL (20 vs. 0%; P < 0.001) and postoperative OKT3 use (40 vs. 15%; P = 0.017) were more common among patients with recurrent HCC. While microvascular invasion was the strongest pathological predictor of recurrent HCC, tumor size >or=3 cm (P = 0.004; odds ratio [OR] = 7.42), nuclear grade (P = 0.044; OR = 3.25), microsatellitosis (P = 0.020; OR = 4.82), and giant/bizarre cells (P = 0.028; OR = 4.78) also predicted recurrent HCC independently from vascular invasion. The score and nomogram stratified the risk of recurrent HCC into 3 tiers: low (<5%), intermediate (40-65%), and high (>95%). In conclusion, compared to patients meeting Milan criteria, patients who meet only UCSF criteria have a worse survival and an increased rate of recurrent HCC with long-term follow-up, as well as more frequent occurrence of adverse histopathological features, such as microvascular invasion. Application of a pathological score and nomogram could help identify patients at increased risk for tumor recurrence, who may benefit from increased surveillance or adjuvant therapy.

Eosinophilic esophagitis in adults: distinguishing features from gastroesophageal reflux disease: a study of 41 patients.

Eosinophilic esophagitis in adults is a recently described entity occurring in young males with dysphagia, in whom esophageal biopsies show eosinophilic infiltration. This study defines the clinical and histological features of patients with eosinophilic esophagitis, distinguishing it from gastroesophageal reflux disease. Esophageal biopsies from patients with dysphagia or esophagitis were reviewed blindly, and assessed for: epithelial eosinophil counts, presence of eosinophilic microabscesses, edema, basal zone hyperplasia, lamina propria papillae elongation, eosinophils and fibrosis. Clinical and endoscopic findings were obtained. Eosinophilic esophagitis was diagnosed with epithelial eosinophils > or = 15 in > or = 2 high-power fields (hpfs) or > or = 25 in any hpf. Analysis was performed with Mann-Whitney, chi2 and ANOVA tests. Of 157 cases, 41 had eosinophilic esophagitis. Male gender (81%) and age < or = 45 (54%) were commoner in patients with eosinophilic esophagitis (P = 0.001, 0.010, respectively). Dysphagia was more common in eosinophilic esophagitis patients (63%, P < 0.001); heartburn was more common in noneosinophilic esophagitis patients (53%, P < 0.001). Endoscopic rings were more common in eosinophilic esophagitis patients (27%, P = 0.023); hiatus hernia was more common in noneosinophilic esophagitis patients (11%, P = 0.022). Eosinophils were more numerous in eosinophilic esophagitis biopsies (mean 39/hpf, P < or = 0.001). Only eosinophilic esophagitis biopsies had eosinophilic microabscesses (42%, P < or = 0.001). Edema, basal zone hyperplasia, lamina propria papillae elongation and lamina propria eosinophils were commoner in eosinophilic esophagitis (P < or = 0.001-0.002), while lamina propria fibrosis was specific for eosinophilic esophagitis (39%, P < 0.001). Eosinophilic esophagitis is a disease with a predilection for young males with dysphagia and rings on endoscopy. Biopsies in eosinophilic esophagitis have high epithelial eosinophil counts, averaging nearly 40/hpf. Increased awareness of eosinophilic esophagitis is necessary, since treatment with allergen elimination or anti-inflammatory therapy may be more effective than acid suppression.