Objective Measures Of Functional Capacity Research Articles

SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure

The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported. To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF. The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023. Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included. Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted. Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS). In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes. These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.

A Comparison of the 6-Minute Walk Test to Treadmill Exercise Test as a Tool to Evaluate Functional Capacity in Healthy ManilaMed Employees: The CoST TET Study

INTRODUCTION: Functional capacity is a strong predictor of mortality and nonfatal cardiovascular outcomes in both men and women with and without coronary artery disease. This study aimed to compare the distance traveled of the 6-minute walk test (6MWT) to the metabolic equivalent (MET) of the treadmill exercise test (TET) as a measure of functional capacity among healthy ManilaMed (Medical Center Manila) employees and to determine and compare the distance traveled in 6MWT and the MET of TET according to general characteristics such as age, sex, height, weight, and body mass index (BMI) as determinants of maximal walking distance and the cause of the early termination of the TET. METHODS: This was a single-center prospective cross-sectional study done at a private tertiary hospital. All participants underwent TET and 6MWT. Metabolic equivalent of TET, distance traveled in 6MWT, and the computed MET of the distance traveled were recorded and analyzed. RESULTS: Fifty healthy employees performed both the 6MWT and the TET to measure their functional capacity. Twenty-two were males, and 28 were females. The mean age was 31.80 ± 7.17 years, and the mean ± SD for BMI was 25.05 ± 4.32 kg/m2. Using 400 m as predictor of good functional capacity, the farther the distance traveled (&gt;400 m), the higher the MET they achieved in the TET, and the lower the distance traveled (&lt;400 m), the lower the MET achieved in the TET (t test P = 0.0125). This study also showed that more than or equal to 400- m distance traveled in the 6MWT can be used as a measure of good functional capacity in this population. However, there was a significant difference (t test P = 0.006) in the computed MET in the 6MWT in relation to the MET achieved in TET. In this study age, sex, and BMI were the predictors of the distance traveled in the 6MWT (P = 0.0049) and in the TET. CONCLUSION: The distance traveled in meters in the 6MWT can be used as an objective measure of functional capacity in healthy population, and &gt;400-m distance can be used as a parameter of good functional capacity. The formula used to compute MET in the 6MWT is not comparable with the MET achieved in TET. Age, sex, and BMI significantly influenced the performance in the 6MWT and TET.

Changes in functional health status following open abdominal aortic aneurysm repair and the role of exercise-based rehabilitation: protocol for a systematic review and meta-analysis

Background and objectives: The aim of this systematic review is to explore the current evidence surrounding the changes in functional status following open or endovascular abdominal aortic aneurysm (AAA) repair and the role of postoperative exercise-based rehabilitation programmes. Methods: The proposed study will incorporate two separate systematic reviews within it, one to assess changes in functional status (component 1) and another to consider the role of exercise-based rehabilitation for improving functional status (component 2), both following AAA repair. The Medline, EMBASE and Cochrane CENTRAL databases will be searched using two separate search strategies including the terms “aortic aneurysm”, “functional capacity”, “functional decline” and” exercise therapy”. We plan to include all prospective randomised and non-randomised trials that have considered the impact of AAA repair on functional status and/or the effect of exercise-based rehabilitation following AAA repair. For component 1, the primary outcome will be changes in objective measures of functional capacity or physical function following AAA repair and, for component 2, it will be changes in physical function or functional capacity following exercise-based rehabilitation after AAA repair. The extracted data will include study characteristics – ie, sample size, a description of the intervention and control conditions (where applicable), outcome measures, length of follow-up and main findings related to outcome measures. For both components a narrative synthesis will be produced, supported by a summary table. We intend to conduct quantitative meta-analyses for both components. For each selected outcome we plan to evaluate the certainty of evidence based on the GRADE approach and risk of bias of included studies will be assessed using the Cochrane tool. Conclusions: Based on a lack of current evidence, we present a protocol for a systematic review to investigate the functional changes associated with open and endovascular AAA repair and the potential value of postoperative exercise rehabilitation.

Reassessing the NYHA classification for heart failure: a comparison between classes I and II using cardiopulmonary exercise testing

Abstract Background The New York Heart Association (NYHA) functional classification has evolved to become a major determinant of eligibility to medical interventions and clinical trials, but its reliability to discriminate patients with mild heart failure (HF) has been questioned by studies that demonstrated a major overlap in self-reported symptoms and laboratory markers between NYHA classes I and II. Purpose To assess the reliability of NYHA classification by comparing cardio-pulmonary exercise test (CPET) results and its overlap between HF patients classified as NYHA I and II. Methods We retrospectively analyzed data from HF patients who underwent CPET in 3 medical centers in Brazil. NYHA class was defined as recorded on CPET day or during the previous clinical visit. Inclusion criteria were diagnosis of HF, age ≥16, and NYHA class I or II. We analyzed overlap between kernel density estimations for the percent-predicted peak VO2, minute ventilation/carbon dioxide production (VE/VCO2) slope, and oxygen uptake efficiency slope (OUES) in patients in NYHA classes I and II. Categorical variables were compared using chi-square tests. Results We included 684 patients, of which 42% (284) were classified as NYHA I. Mean age was 56.1 years; 44% (303) were female and mean left ventricular ejection fraction was 36% (±14.2%). Regarding CPET measures, mean global percent-predicted peak VO2 was 56.6% (±26.1%), VE/VCO2 slope was 38.8 (±10.2), and OUES was 1.50 (±0.59). Kernel density overlap between NYHA classes I and II was considerable: 83% for percent-predicted peak VO2, 89% for VE/VCO2 slope, and 85% for OUES (Figure 1). There was no significant difference between NHYA I and II in CPET indicators of poor prognosis: percent-predicted peak VO2 &amp;lt;50% was present in 53% vs. 48% of patients classified as NYHA I and II, respectively (p=0.15); VE/VCO2 slope &amp;gt;36 in 54% vs. 57% (p=0.39); and OUES &amp;lt;1.4 in 46% vs. 48% (p=0.51). Conclusions HF patients classified as NYHA I and II overlap substantially in objective measures of functional capacity assessed by CPET. These findings suggest that NYHA classification is a poor discriminator of cardiopulmonary capacity among patients with mild HF, and raise questions about its use as a benchmark to guide HF therapy. Funding Acknowledgement Type of funding sources: None. Figure 1

A randomized controlled trial of motivational interviewing as a tool to enhance secondary prevention strategies in cardiovascular disease (MICIS study)

Background Physical activity/exercise has consistently been shown to improve objective measures of functional capacity, enhance quality of life, improve coronary risk profile, and reduce mortality for individuals with coronary heart disease. Despite the gains achieved by those who attend cardiac rehabilitation (CR) many individuals fail to maintain lifestyle changes. Aim(s) The aims of this study were to evaluate the effectiveness of motivational interviewing as a strategy for promoting maintenance of cardiac risk factor modification in patients who had participated in standard, 6-week outpatient CR programs. Methods In a randomized controlled trail, participants in usual care and intervention group (Motivational interviewing supplemental to a standard 6-week CR program) were followed up at 6-weeks and 12-months. The primary outcome was distance walked on the six-minute walk test (6MWT), used as both an indicator of functional capacity and habitual physical activity. Secondary outcomes included modifiable coronary risk factors (smoking, self-reported physical activity, waist circumference, body mass index and medication adherence), psychological status (depression, anxiety, stress, perceived cardiac control, perceived social support, exercise self-efficacy) and quality of life. Results Total 110 patients, usual care (n = 58) and intervention (n = 52), consented to participate in the study. Overall, demographic and clinical characteristics did not differ between groups at baseline. Motivational interviewing was no more likely to promote maintenance of cardiac risk factor modification (both primary and secondary outcomes) than a standard CR program alone. Both intervention and control groups maintained the gains achieved during CR at the 12-month follow-up except for weight loss. Conclusions Although both groups maintained the gains achieved during CR for physical activity, there was no effect of the intervention on maintenance of cardiac risk factor modification on both primary and secondary outcomes.

The Prognostic Importance of the 6-Minute Walk Test in AL Amyloidosis

Background The six-minute walk test (6MWT) is an easy-to-implement objective measure of functional capacity. This standardised reproducible measure of individual function may have value in systemic AL amyloidosis to provide an additional objective measure of fitness for chemotherapy, impact of chemotherapy and, within the clinical trial setting, both as a potential clinical endpoint and exclusion criteria. We aim to validate its prognostic value in AL amyloidosis. Methods All patients from a prospective observational study of newly diagnosed AL amyloidosis, (ALchemy) over a 5-year period, were studied. Six-minute walk testing was performed at baseline and 6, 12, 18, 24, 36 and 48-month follow up. Both the median 6MWT and percentage predicted for age, sex, height and weight were analysed. Results In total, 799 evaluable patients were included of whom 564 (70.6%) had cardiac involvement. Baseline 6MWT distance was 418.5 metres (m) / 80.5% predicted, and diminished with increasing cardiac Mayo stage (p&amp;lt;0.0001). A baseline 6MWT ≥300m was independent of Mayo staging in predicting survival (Mayo II Hazard ratio [HR] 2.21 [1.35-3.64], p=0.002; Mayo IIIa HR 3.92 [2.42-6.34], p&amp;lt;0.0001; Mayo IIIb HR 6.08 [3.63-10.12], p&amp;lt;0.0001; 6MWT ≥300m HR 2.97 [2.38-3.72], p&amp;lt;0.0001). Baseline 6MWT correlated strongly with other prognostic factors including Eastern Cooperative Oncology Group (ECOG) performance status (p&amp;lt;0.0001) and New York Heart Association (NYHA) Classification of Heart Failure (p=0.008). Patients were followed up for a median of 32 (1-90) months following diagnosis. Median overall survival (OS) was 70.0 (56.8-83.2) months. The median OS of patients achieving ≥300m on baseline 6MWT was not reached whilst those achieving &amp;lt;300m had a median OS of 25.0 (18.1-31.9) months. Patients unable to attempt the test had a median OS of 5.0 (2.8-7.2) months (p&amp;lt;0.0001). Patients achieving ≥300m at any time point had a significantly better OS (at 6, 12, 24 and 36 months p&amp;lt;0.0001 whilst at 48 months p=0.03). Patients unable to attempt a 6MWT at any point in time has a median OS of 10 (6.4-13.6) months from that point. In patients with Mayo IIIb disease, the 6MWT remained prognostic (≥300m: 61 [4.2-117.8] months vs. &amp;lt;300m: 4.0 [1.3-6.9] months vs. unable to walk: 1.0 [0.3-1.7] months, p&amp;lt;0.0001). The 6MWT fell significantly by 6 months (391.0m/73.5%, p=0.0002) then rose again by 12 months (median 415.0m/78.0%, p=0.02). There was no significant change in 6MWT thereafter. When stratified by haematological response and censoring deaths before 12 months, only patients in a complete response (CR) improved at 12 months (431.0m/83.0% vs. 437.0m/85%, p=0.001) whilst those with a lesser haematological response got worse (Very good partial response [VGPR]: 403.5m/75.0% to 395.5m/76.5%, p=0.02; Partial Response [PR]: 413.0m/79.0% to 362.5m/74.0%, p=0.0007; Nil response [NR]: 437.0m/83.0% to 355.0m/70%, p=0.0002). A 33m improvement in 6MWT, a value reported to be clinically meaningful in cardiopulmonary disorders, was independent of haematological response in predicting survival (CR [reference], VGPR: HR 2.02 [1.08-3.80], p=0.03; PR: HR 3.51 [1.83-6.73], p&amp;lt;0.0001; NR: HR 5.61 [2.88-10.92], p&amp;lt;0.0001; 6MWT improvement ≥33m: HR 1.61 [1.01-2.59], p=0.047). Patients in whom 6MWT improved by ≥33m at 12 months survived longer although median OS was not reached in either category (p=0.01). In patients who achieved a baseline 6MWT of &amp;lt;300m but improved by ≥33m at 12 months, median OS was superior to those who improved by &amp;lt;33m (not reached vs. 35.0 [25.7-44.3] months, p=0.006). Among patients with Mayo stage IIIb disease and censoring all deaths within 12 months, those who improved by ≥33m at 12 months lived longer (OS NR vs. 70.0 [51.4-88.6] months, p&amp;lt;0.0001). Conclusion The 6MWT is prognostic in AL amyloidosis at multiple time points and a baseline distance of ≥300m is independent of current Mayo stage criteria in predicting survival. Inability to undertake a 6MWT at baseline is an extremely poor prognostic indicator. At 12 months, improvement in 6MWT of ≥33m predicts survival independent of haematological response. The 6MWT is a useful prognostic indicator in systemic AL amyloidosis and could be used as an inclusion/exclusion criterion in the clinical trial setting. Disclosures Wechalekar: Celgene: Honoraria; Takeda: Honoraria, Other: Travel; Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory.

Assessment of oxygen-uptake efficiency slope in healthy children and children with heart disease: Generation of appropriate reference values for the OUES variable.

Oxygen-uptake efficiency slope (OUES) is an objective measure of functional capacity that does not require a maximal effort but is considerably dependent on anthropometric variables and requires the generation of an appropriate reference value in children. This study aimed to establish normal reference values for OUES/kg in children with and without congenital heart diseases. Besides that, reference values are presented secondarily for OUES per body surface area (OUES/BSA). Cross-sectional. Six hundred and seventy-six children and adolescents performed a maximal cardiopulmonary exercise test (305 healthy controls and 371 individuals with congenital heart defect), between four and 21 years old (481 males and 195 females, with a mean age of 12 years). The OUES reference value for the classification of children and adolescents with normal functional capacity (>80% of predicted maximum oxygen uptake) was 34.63 (sensitivity 77% and specificity 83%, p < 0.05). Regarding the body surface area, considering healthy patients and those with heart disease, the cutoff value of the OUES/BSA was 1151 with sensitivity of 79% and specificity of 79%. OUES/kg may be an important marker tool in the differentiation between preserved or abnormal functional capacity in children and adolescents with and without congenital heart disease, even at the submaximal level of exercise.

PS02.180: THE ROLE OF CARDIOPULMONARY EXERCISE TESTING IN OESOPHAGO-GASTRIC CANCER SURGERY: EVALUATION OF A SINGLE-CENTRE EXPERIENCE

Abstract Background Cardiopulmonary exercise testing (CPEX) is an objective measure of functional capacity adapted to predict post-operative morbidity. CPEX may also identify optimisable cardio-respiratory comorbidity, prompting treatment modification or specialist referral. The role of CPEX in patient optimisation before oesophago-gastrectomy is yet to be evaluated. This study aims to assess the utility of CPEX in altering management and optimising patients prior to oesophago-gastrectomy. Methods All patients who underwent pre-operative CPEX testing and two phase oesophago-gastrectomy (January 2012 to January 2018) were included. All changes in patient management brought about by CPEX findings were evaluated. In addition, the role of validated risk-stratifying CPEX parameters (anaerobic threshold (AT), VO2 peak and FEV1) in predicting post-operative complications was assessed. Results 236 patients underwent surgery. Median AT and VO2 peak were 11.95(7–24)ml/kg/min and 773(403–1552)ml/min/m2 respectively. 46% (109/236) of patients (VO2 peak &gt; 800ml/min/m2) were graded ‘low risk’, 42% (99/236) ‘intermediate risk’ (VO2 peak = 600–800ml/min/m2), and 12% (28/236) ‘high risk’ (VO2 peak &lt; 600ml/min/m2) for developing post-operative cardio-pulmonary complications. Based on CPEX findings, management plans were altered in 84 patients (36%). Cardiac comorbidity was identified in 55 patients (23%) with immediate alteration of cardiac medications in 9% (21/236) and another 11% (27/236) requiring specialist cardiology review. Medication for respiratory optimisation was initiated in 3% (7/236) and formal respiratory review sought in 5% (12/236). ‘Intermediate’ and ‘high risk’ patients had similar rates of overall complication (63% vs 63%, P = 1.00), cardio-pulmonary complication (48% vs 47%, P = 0.17), anastomotic leak (11% vs 15%, P = 0.33) and 90-day mortality (6% vs 4%, P = 0.40) compared with ‘low risk’ groups. CPEX variables (AT, VO2 peak, FEV1) did not predict complications, length of critical care or overall stay on Receiver Operating Characteristic curves (AUROC &lt; 0.5) and multivariate logistic regression models. Conclusion CPEX findings changed management in 36% of patients, enabling optimisation before oesophago-gastrectomy. ‘Confounding by intention’ is a bias reducing the strength of association between test results and post-operative complications due to the propensity to medically intervene on the basis of the test findings. This study highlights the possibility that the high intervention rate may explain the poor correlation between test results and post-operative outcome. Disclosure All authors have declared no conflicts of interest.

Effect of Spironolactone on Myocardial Fibrosis and Other Clinical Variables in Patients with Hypertrophic Cardiomyopathy

BackgroundMyocardial fibrosis has proved to be an important marker and determinant in the pathogenesis of hypertrophic cardiomyopathy. In particular, scar formation, if substantial, can promote ventricular tachyarrhythmias or progressive heart failure in the absence of left ventricular outflow obstruction. Therefore, an intervention to mitigate myocardial fibrosis would be potentially advantageous to hypertrophic cardiomyopathy patients. MethodsEligible hypertrophic cardiomyopathy patients were randomized 1:1 in a prospective double-blind fashion to spironolactone 50 mg or placebo to be taken over a 12-month period. The primary endpoint was the effect of mineralocorticoid receptor blockade on serum markers of collagen synthesis and degradation. A number of other functional and morphologic variables and biomarkers comprised secondary exploratory measures. ResultsFifty-three hypertrophic cardiomyopathypatients (41 ± 13 years old; 72% men) were randomized; demographic and clinical variable were well matched at baseline. Absolute change between baseline and 12 months did not differ between hypertrophic cardiomyopathy patients treated with spironolactone and those receiving placebo with respect to serum markers of collagen synthesis or degradation, fibrosis by late gadolinium enhancement on cardiac magnetic resonance imaging, or other clinical variables, including objective measure of functional capacity (peak VO2), New York Heart Association functional class, left ventricular wall thickness, mass and volume, and left atrial size, as well as assessment of diastolic function (P = .4-1.0). ConclusionsThese findings do not support the use of spironolactone in hypertrophic cardiomyopathy to improve left ventricular remodeling by mitigating myocardial fibrosis or altering clinical course.

Clinical utility of the UCSD Performance-Based Skills Assessment-Brief (UPSA-B) in adults living with HIV: Associations with neuropsychological impairment and patient-reported everyday functioning difficulties.

ObjectiveRequiring only 10–15 minutes to complete, the UCSD Performance-Based Skills Assessment (UPSA-B) has high clinical utility as a brief measure of functional capacity. This study aimed to validate the UPSA-B in adults living with HIV/AIDS (HIV+), and identify whether the UPSA-B can be used as an indicator of functional dependence in this population.MethodOne hundred and three HIV+ adults and 91 HIV- adults completed a comprehensive neuropsychological and neuromedical battery, including a self-report measure of functional status (IADL Dependence vs. IADL Independence), an objective measure of functional capacity (UPSA-B), and a self-report measure of mood states including a subscale related to cognitive difficulties (Profile of Mood States [POMS]-Confusion/Bewilderment subscale).ResultsHIV+ participants had significantly lower UPSA-B scores than their HIV- counterparts (p = 0.02), although this fell to a trend (p = 0.08) when including covariates. Among the HIV+ group, higher UPSA-B scores were related to better neuropsychological ability, but unrelated to self-reported functional independence. Conversely, UPSA-B scores were unrelated to participant-reported cognitive difficulties on the POMS Confusion/Bewilderment subscale. An ROC curve was generated to determine the optimal UPSA-B value for discriminating between normal neuropsychological functioning versus neuropsychological impairment, with results indicating an optimal cutoff of 79. The UPSA-B identified HIV+ persons with cognitive impairment with 70.9% accuracy.ConclusionsThe UPSA-B was able to differentiate neuropsychological impairment from no impairment among HIV+ participants and holds promise as a clinical screening tool in this population. However, indicators of functional disability among adults living with HIV is still not well understood and is likely multifactorial in nature. These data highlight the complex interplay between objective functional capacity, neurocognitive ability, subjective cognitive symptoms, and functional dependence.

Vortioxetine: A Review in Cognitive Dysfunction in Depression.

Vortioxetine (Brintellix®; Trintellix®), a generally efficacious and well tolerated antidepressant agent, is approved in the EU and USA for the treatment of major depressive disorder (MDD) in adults. The drug has a distinctive pharmacological profile (combining inhibition of the serotonin transporter with modulation of multiple serotonin receptors) and has been shown to enhance cognitive performance in various animal models and clinical trials. Across three large, placebo-controlled studies in adults with recurrent MDD, short-term treatment with vortioxetine almost always resulted in statistically significant and clinically meaningful improvements in performance on two objective measures (the Digit Symbol Substitution Test and Rey Auditory Verbal Learning Test) that together cover a broad range of cognitive domains, including executive function, attention, processing speed, learning and memory. Vortioxetine also significantly improved a subjective measure of cognitive function (the Perceived Deficits Questionnaire) and an objective measure of functional capacity (the University of San Diego performance-based skills assessment). In general, the beneficial effects of vortioxetine on these measures were largely independent of its effect on improving depressive symptoms. Based on the available data, therefore, vortioxetine is a useful treatment option in patients with MDD where impaired cognitive function is apparent.

Use of the 6-Min Walk Distance to Identify Variations in Treatment Benefits From Implantable Cardioverter-Defibrillator and Amiodarone: Results From the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)

The purpose of this study was to determine if 6-min walk test data assists in treatment decisions for patients withheart failure. In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), a pre-specified subgroup analysis showed that patients with New York Heart Association functional class III symptoms did not benefit from implantable cardioverter-defibrillator (ICD) therapy and appeared to be harmed by amiodarone, whereas New York Heart Association functional class II patients obtained significant survival benefit from ICD. We postulated that a more objective measure of functional capacity, such as 6-min walk (6MW) distance, might provide a better tool for selecting these preventive therapies. A 6MW test was performed before randomization in 2,397 patients. Median follow-up was 45.5 months. All-causemortality was the primary endpoint, with cause-specific mortality (heart failure, arrhythmic) examined insecondary analyses. The hazard ratios (HRs) for ICD therapy compared to placebo were estimated within tertiles of baseline 6MW distance: HR: 0.42 (95% confidence interval [CI]: 0.26 to 0.66) for 6MW distance >386 m (top tertile); HR: 0.57 (95% CI: 0.39 to 0.83) for 6MW distance 288 to 386 m (middle tertile); and HR: 1.02 (95% CI: 0.75 to 1.39) for 6MW distance<288 m (bottom tertile). The corresponding HRs for amiodarone compared to placebo were 0.68 (95% CI: 0.46 to 1.02) for the top, 0.86 (95% CI: 0.61 to 1.21) for the middle, and 1.56 (95% CI: 1.17 to 2.09) for the bottom tertile. The 6MW distance was inversely related to heart failure-related mortality but not to arrhythmic mortality. ICD therapy reduced arrhythmic mortality in the top 2 tertiles of 6MW, but had no effect on heart failure mortality. A baseline 6MW distance<288 m identified a subgroup of SCD-HeFT patients who were harmed by amiodarone therapy and did not benefit from ICD. (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609).

The RIME trial: Are we closer to the answer of when to repair ischemic mitral regurgitation?

BACKGROUND The development of mitral valve regurgitation as a result of left ventricular remodelling following myocardial infarction carries adverse implications on survival and quality of life (QOL). There is uncertainty whether mitral valve repair at the time of surgical revascularization improves survival and quality of life and enhances left ventricular reverse remodelling in patients with moderate ischemic mitral regurgitation (IMR). The Randomized Ischemic Mitral Evaluation (RIME) trial investigators tried to address this issue by studying whether repairing moderate IMR at the time of surgical revascularization can lead to more favourable outcomes compared with surgical revascularization only. Results of this multicentre, randomized, controlled trial were recently published in Circulation. 1 RIME was conducted in 6 centres in the UK and one in Poland. Out of 172 patients referred for CABG with moderate IMR, the RIME investigators randomized 73 eligible patients to receive either CABG alone (CABG group; n ¼ 39 patients) or CABG with mitral valve repair (Repair group; n ¼ 34 patients) The primary end-point was oxygen consumption at maximal exercise (VO2Max) measured by cardiopulmonary exercise testing, as an objective measure of functional capacity, at one year. The secondary end-points were left ventricular end-systolic volume indexed to body surface area (LVESVI) and mitral regurgitation volume as well as plasma B-type natriuretic peptide (BNP). All measurement were performed before enrollment and at one year postoperatively. Moderate IMR was defined by echocardiographically derived quantitative measures – namely regurgitant orifice area, regurgitant volume and vena contracta width – as per the ACC/AHA/ASE Valvular Heart Disease Guidelines. Patients were considered eligible if they met any of the above criteria whether at rest or during exercise. 2 Patients were excluded if they had ejection fraction ,30%, structural mitral valve disease (including papillary muscle rupture), significant aortic valve disease, previous or active endocarditis, previous cardiac surgery, unstable angina, symptoms of advanced heart failure or cardiogenic shock or significant comorbidities like liver or renal impairment and chronic obstructive airway disease. All CABG procedures utilized the left internal mammary artery to graft the left anterior descending coronary artery All technically graftable, significantly narrowed coronary arteries were addressed. Mitral repair was performed using a complete annuloplasty ring with the aim of achieving a leaflet coaptation length of at least 8mm and no or trace mitral regurgitation at the end of the operation. Both groups received similar number of grafts but the repair group expectedly had longer bypass and cross clamp times compared to the CABG group. The trial met all its end points with high statistical significance at the proposed follow up period of one year. The primary end point of change in peak oxygen consumption (Peak VO2) showed significant improvement at 1 year. The Peak VO2 in the repair group increased by 22% (from 14.8 ^ 3.2 to 18.1 ^ 2.9mL/kg/min) while the CABG group only increased by 5% (from 15.1 ^ 3.3 to

Correlations between physician-perceived functional status, patient-perceived health status, and cardiopulmonary exercise results in hypertrophic cardiomyopathy

Dyspnea and the resulting functional impairment are a common complication in hypertrophic cardiomyopathy (HCM). The relationship between physician-perceived functional status, patient-perceived health status, and objective exercise test results has not been evaluated in this condition. To evaluate the correlation between the Kansas City Cardiomyopathy Questionnaire (KCCQ) and (1) physician's perceived (NYHA class) and (2) objective measurement (cardiopulmonary exercise test) of functional capacity in patients with HCM. In 24 outpatients with HCM at a single, referral center, the KCCQ instrument was administered and cardiopulmonary exercise testing (CPX) was performed. Severity of symptoms as determined by physician (NYHA classification) and patient (KCCQ instrument) was obtained before exercise test results were known. Pearson correlation was used to assess the independent correlation between KCCQ score and the various exercise parameters; Spearman correlation was used to assess correlation between KCCQ score and NYHA class. KCCQ results demonstrated moderate reductions in all domains, with greatest reduction in quality-of-life domain. CPX testing showed reduction in peak oxygen consumption (mean absolute VO2 20.5±7.8ml/kg/min and percent predicted VO2 76.8±4.1%). There were negative correlations between NYHA class and all KCCQ components except the self-efficacy score. The strongest correlations were between NYHA class and the overall summary score (r=-0.623, p=0.001) as well as the physical limitation score (r=-0.604, p=0.002). Similarly, there were statistically significant positive correlations between the KCCQ components and percent predicted peak VO2. The strongest correlation was between percent predicted peak VO2 and the physical limitation score (r=0.474, p=0.019), but there was also correlation between percent predicted peak VO2 and the quality-of-life score (r=0.456, p=0.025), the functional status score (r=0.455, p=0.025), and the clinical summary score (r=0.444, p=0.030). The multiple domains of the KCCQ provide data on patient-perceived health status, which correlate with physician-perceived and objective measurement of functional capacity in HCM. Additional studies are needed to evaluate the sensitivity of the KCCQ to changes in functional capacity over time or in response to therapies for this condition.

Exercise in Hypertrophic Cardiomyopathy

The risk of sudden cardiac death (SCD) associated with vigorous athletic competition in individuals with hypertrophic cardiomyopathy (HCM) is well documented, and is the basis for recommended exclusion from competitive sports independent of other risk factors. Although SCD risk with recreational exercise is less well defined, published guidelines for participation in recreational sports, based on a consensus of expert opinion, offer a valuable framework for counseling patients. Exercise stress testing is an important diagnostic and prognostic tool in the evaluation of HCM patients, providing an objective measure of functional capacity, physiologic hemodynamic responses to stress, presence of ischemia, and provocable left ventricular outflow tract obstruction. The value of cardiopulmonary exercise testing in HCM is less well studied than in the heart failure population, but can be used to set a safe target for exercise intensity as part of an individualized exercise prescription. The long-term effects of exercise on HCM pathophysiology are largely theoretical at this stage. Potential harmful effects of fatiguing exercise include prolonged contractile dysfunction resulting from microvascular ischemia and energetic compromise. Conversely, several animal studies have shown that voluntary exercise prevents or reverses many pathologic features of HCM, including those related to apoptosis and energetics. Substantial evidence for health-promoting benefits of exercise in the general population, in addition to promising safety and efficacy data in patients with chronic heart failure, emphasizes the need to attain a reasonable balance between potential risks and benefits of aerobic fitness in individuals with HCM.

CALGB 140803—Association between cardiorespiratory fitness and overall survival in operable lung cancer patients: Ancillary analysis of protocol 9238

7518 Background: Cardiorespiratory fitness is a well-established independent predictor of all-cause mortality in a broad range of adult populations. The association between cardiorespiratory fitness and mortality has not been investigated among individuals diagnosed with cancer. We examined the association between cardiorespiratory fitness and all-cause mortality in 398 patients with non-small cell lung cancer (NSCLC). Methods: Using a prospective, observational design, patients with known or suspected NSCLC enrolled in CALGB 9238 were studied. Prior to pulmonary resection, all participants performed an incremental exercise test with expired gas analysis to assess cardiorespiratory fitness (i.e., peak oxygen consumption; VO2peak) and were observed for death or until June 2008. Cox proportional hazards models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO2peak (&lt;0.96 / 0.96–1.29 / &gt;1.29 L.min-1) with adjustment for age, gender, and performance status. Results: Of the 398 patients, 335 underwent surgical resection and 63 were deemed not eligible for resection. Median follow-up was 30.8 months, 294 deaths were reported during this period. For the entire sample, mortality rates declined across increasing VO2peak categories (adjusted Ptrend= 0.012). Compared with patients achieving a VO2peak &lt;0.96 L.min-1, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% CI, 0.46 to 0.88) for a VO2peak of 0.96–1.29 L.min-1, and 0.56 (95% CI, 0.39 to 0.80) for a VO2peak of &gt;1.29 L.min-1. The corresponding HRs for surgical patients were 0.65 (95% CI, 0.44 to 0.96) and 0.62 (95% CI, 0.42 to 0.90) relative to the lowest VO2peak category (ptrend=0.03), respectively. For non-surgical patients, the HRs were 0.74 (95% CI, 0.32 to 1.75) and 0.43 (95% CI, 0.18 to 1.00) relative to the lowest category (ptrend&lt;0.04). Conclusions: Low VO2peak is associated with poorer survival among surgical candidates with NSCLC. Further work is required to investigate the prognostic value of objective measures of functional capacity in NSCLC and other cancer populations. No significant financial relationships to disclose.

Prognostic value of time-related changes of cardiopulmonary exercise testing indices in stable chronic heart failure: a pragmatic and operative scheme

Although peak oxygen consumption (VO2) is an objective measurement of functional capacity linked to survival, most clinicians use clinical history to monitor changes over time of functional disability. The aim was to verify the prognostic value of time-related changes (Delta) of symptom-limited cardiopulmonary exercise testing (CPX) indices in stable chronic heart failure (CHF). We studied 231 stable CHF patients (200 men) with left ventricular ejection fraction (LVEF) of 24 +/- 8% and peak VO2 of 14.3 +/- 8 ml/kg per min, who performed two symptom-limited CPX over time. The two incremental CPX were separated by a mean interval of 258 +/- 42 days; 59 (26%) suffered cardiovascular death or underwent urgent heart transplantation during the follow-up (1167 +/- 562 days). Peak VO2, LVEF (measured at second evaluation), Deltapeak VO2 and DeltaNYHA (New York Heart Association classification) were selected as independent predictors in the total population, and LVEF, Deltapeak VO2, and NYHA in patients with peak VO2 of 14 ml/kg per min or less (106 patients); no Delta parameter was selected in patients with preserved exercise tolerance. Survival analysis was performed taking into consideration the inter-test variability of peak VO2 (6%): true fall: more than 6% decrease, decline within the measurement variability; less than 6% decrease, improvement within the measurement variability; less than 6% increase and true rise; more than 6% increase: total mortality rate was 51, 23, 19 and 14% (P < 0.0001), respectively. Deltapeak VO2 is a useful outcome index; a combination of static (single) and time-related functional variables can enhance the prognostication process in stable CHF patients.

Relationship Of Six Minute Walk Distance To Maximal Oxygen Consumption In Older Diastolic And Systolic Heart Failure

PURPOSE Maximal oxygen consumption (VO2max) is considered the most objective measure of functional capacity and prognosis in heart failure (HF) patients. However, 6-minute walk distance test (6-MWT) has become widely used as a safe, well tolerated, and inexpensive indicator provided prognostic and functional performance information in patients with HF. Therefore, the aims of the present investigation were: to evaluate the relationship between 6-MWT and VO2max in older HF patients, at baseline tests and, to examine the relationship between the change in 6-MWT and VO2max after 16-week of exercise training. METHODS We studied 97 older (>65 years), 58 women and 39 male, with systolic and diastolic HF, during upright bicycle ergometer with an incremental protocol to maximal effort, breath-by-breath expired gas analysis, and continuous electrocardiograph monitoring. Patients also performed 6-MWT along a measured inside corridor walking from end to end at their own pace while attempting to cover as much ground as possible in six minutes. During 16-week, exercise group (EG) performed a training program, keeping the exercise cycling and walking intensity between 50 and 70% of the VO2max by monitoring heart rate. RESULTS At baseline test, there was significantly moderate correlation (r = 0.53) between 6-MWT and VO2max when all patients were pooled together. At follow-up 6-MWT was significantly higher than that at the baseline tests in EG and control group (CG). VO2max values were significant increased only in EG after training period. Mean change of variables (difference between follow-up and baseline) was significantly higher in VO2max for EG and no difference was found in 6-MWT between groups. After exercise training weak correlation (r = 0.19) was found between the mean change in 6-MWT and VO2max in EG and CG. CONCLUSIONS 6-MWT is not a useful predictor of VO2max. While VO2max demonstrated a training effect after 16-week training program in elderly HF patients, 6-MWT had only a practice effect. 6-MWT does not appear to be surrogate for VO2max in elderly HF patients.

Long-Term Healthcare and Cost Outcomes of Disease Management in a Large, Randomized, Community-Based Population With Heart Failure

Because of the prevalence and expense of congestive heart failure (CHF), significant efforts have been made to develop disease management (DM) programs that will improve clinical and financial outcomes. The effectiveness of such programs in a large, heterogeneous population of CHF patients remains unknown. We randomized 1069 patients (aged 70.9+/-10.3 years) with systolic (ejection fraction 35+/-9%) or echocardiographically confirmed diastolic heart failure (HF) to assess telephonic DM over an 18-month period. Data were collected at baseline and at 6-month intervals. Survival analysis was performed by Kaplan-Meier and Cox regression methods. Healthcare utilization was defined after extensive record review, with an attempt to account for all inpatient and outpatient visits, medications, and diagnostic tests. We obtained data on 92% of the patients, from nearly 53,000 health-related encounters. Total cost per patient was defined by adding estimated costs for the observed encounters, excluding the cost of the DM. Kaplan-Meier analysis showed that DM patients had a reduced mortality rate (P=0.037), with DM patients surviving an average of 76 days longer than controls. Subgroup analysis showed that DM had beneficial outcomes in patients with systolic HF (hazard ratio 0.62; P=0.040), which was more pronounced in NYHA classes III and IV. Although improvements in NYHA class were more likely with DM (P<0.001), 6-minute walk data from 217 patients in whom data were available at each visit showed no significant benefit from DM (P=0.08). Total and CHF-related healthcare utilization, including medications, office or emergency department visits, procedures, or hospitalizations, was not decreased by DM. Repeated-measures ANOVA for cost by group showed no significant differences, even in the higher NYHA class groups. Participation in DM resulted in a significant survival benefit, most notably in symptomatic systolic HF patients. Although DM was associated with improved NYHA class, 6-minute walk test results did not improve. Healthcare utilization was not reduced by DM, and it conferred no cost savings. DM in HF results in improved life expectancy but does not improve objective measures of functional capacity and does not reduce cost.

Impact of cardiopulmonary exercise testing on patient selection for cardiac resynchronisation therapy

In patients with systolic heart failure the assessment of peak oxygen consumption during cardiopulmonary exercise (CPX) testing provides an objective measure of functional capacity and important prognostic information. Several studies in pacemaker therapy and in cardiac resynchronization therapy (CRT) have used peak oxygen uptake as an endpoint. This article reviews the impact of CPX testing on patient selection for CRT.