Baseline and Exercise Predictors of V˙O2peak in Systolic Heart Failure Patients: Results from SMARTEX-HF.

PURPOSE: This study aimed to investigate baseline, exercise testing, and exercise training-mediated predictors of change in peak oxygen uptake (V˙O2peak) from baseline to 12-wk follow-up (ΔV˙O2peak) in a post hoc analysis from the SMARTEX Heart Failure trial. METHODS: We studied 215 patients with heart failure with left ventricular ejection fraction (LVEF) ≤35%, and New York Heart Association (NYHA) classes II-III who were randomized to either supervised high-intensity interval training with exercise target intensity of 90%-95% of peak heart rate (HRpeak) or supervised moderate continuous training (MCT) with target intensity of 60%-70% of HRpeak, or who received a recommendation of regular exercise on their own. Predictors of ΔV˙O2peak were assessed in two models: a logistic regression model comparing highest and lowest tertiles (baseline parameters) and a multivariate linear regression model (test/training/clinical parameters). RESULTS: The change in V˙O2peak in response to the interventions (ΔV˙O2peak) varied substantially, from -8.50 to +11.30 mL·kg·min. Baseline NYHA (class II gave higher odds vs III; odds ratio (OR), 7.1 (2.0-24.9); P = 0.002), LVEF (OR per percent, 1.1 (1.0-1.2); P = 0.005), and age (OR per 10 yr, 0.5 (0.3-0.8); P = 0.003) were associated with ΔV˙O2peak.In the multivariate linear regression, 34% of the variability in ΔV˙O2peak was explained by the increase in exercise training workload, ΔHRpeak between baseline and 12-wk posttesting, age, and ever having smoked. CONCLUSION: Exercise training response (ΔV˙O2peak) correlated negatively with age, LVEF, and NYHA class. The ability to increase workload during the training period and increased ΔHRpeak between baseline and the 12-wk test were associated with a positive outcome.

Exercise gas exchange in continuous-flow left ventricular assist device recipients.

Exercise ventilation/perfusion matching in continuous-flow left ventricular assist device recipients (LVAD) has not been studied systematically. Twenty-five LVAD and two groups of 15 reduced ejection fraction chronic heart failure (HFrEF) patients with peak VO2 matched to that of LVAD (HFrEF-matched) and ≥14 ml/kg/min (HFrEF≥14), respectively, underwent cardiopulmonary exercise testing with arterial blood gas analysis, echocardiogram and venous blood sampling for renal function evaluation. Arterial-end-tidal PCO2 difference (P(a-ET)CO2) and physiological dead space-tidal volume ratio (VD/VT) were used as descriptors of alveolar and total wasted ventilation, respectively. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP) and blood urea nitrogen/creatinine ratio were calculated in all patients and used as surrogates of right ventriculo-arterial coupling and circulating effective volume, respectively. LVAD and HFrEF-matched showed no rest-to-peak change of P(a-ET)CO2 (4.5±2.4 vs. 4.3±2.2 mm Hg and 4.1±1.4 vs. 3.8±2.5 mm Hg, respectively, both p >0.40), whereas a decrease was observed in HFrEF≥14 (6.5±3.6 vs. 2.8±2.0 mm Hg, p <0.0001). Rest-to-peak changes of P(a-ET)CO2 correlated to those of VD/VT (r = 0.70, p <0.0001). Multiple regression indicated TAPSE/PASP and blood urea nitrogen/creatinine ratio as independent predictors of peak P(a-ET)CO2. LVAD exercise gas exchange is characterized by alveolar wasted ventilation, i.e. hypoperfusion of ventilated alveoli, similar to that of advanced HFrEF patients and related to surrogates of right ventriculo-arterial coupling and circulating effective volume.

Mineralocorticoid receptor antagonists for heart failure: a real-life observational study.

AIMS: Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population-based analysis, the long-term effects of MRA treatment in HFrEF patients. METHODS AND RESULTS: We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan-Meier, compared by log-rank test and propensity score matching. At 10 years' follow-up, the MRA-untreated group had a significantly lower number of events than the MRA-treated group (P < 0.001). MRA-treated patients had more severe heart failure (higher New York Heart Association class and lower left ventricular ejection fraction, kidney function, and peak VO2 ). At a propensity-score-matching analysis performed on 1587 patients, MRA-treated and MRA-untreated patients showed similar study endpoint values. CONCLUSIONS: In conclusion, MRA treatment does not affect the composite of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation in a real-life setting. A meticulous patient follow-up, as performed in trials, is likely needed to match the positive MRA-related benefits observed in clinical trials.

Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison.

AIMS: Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. METHODS AND RESULTS: We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). CONCLUSION: In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Gait speed has comparable prognostic capability to six-minute walk distance in older patients with cardiovascular disease.

Background Although gait speed and six-minute walk distance are used to assess functional capacity in older patients with cardiovascular disease, their prognostic capabilities have not been directly compared. Methods The study population was identified from the Kitasato University Cardiac Rehabilitation Database and consisted of 1474 patients ≥60 years old with a mean age of 72.2 ± 7.1 years that underwent evaluation of both usual gait speed and six-minute walk distance in routine geriatric assessment between 1 June 2008-30 September 2015. Both gait speed and six-minute walk distance were determined on the same day at hospital discharge. Results Mean gait speed and six-minute walk distance in the whole population were 1.04 m/s and 381 m, respectively, and were strongly positively correlated ( r = 0.80, p < 0.001). A total of 180 deaths occurred during a follow-up of 2.3 ± 1.9 years. After adjusting for confounding factors, both gait speed (adjusted hazard ratio per 0.1 m/s increase: 0.87, 95% confidence interval: 0.81-0.93, p < 0.001) and six-minute walk distance (adjusted hazard ratio per 10-metre increase: 0.96, 95% confidence interval: 0.94-0.97, p < 0.001) were independent predictors of all-cause mortality. There was no significant difference in prognostic capability between gait speed and six-minute walk distance (c-index: 0.64 (95% confidence interval: 0.60-0.69) and 0.66 (95% confidence interval: 0.61-0.70), respectively, p = 0.357). Conclusions Gait speed and six-minute walk distance showed similar prognostic predictive ability for all-cause mortality in older cardiovascular disease patients, indicating the potential utility of gait speed as a simple risk stratification tool in older cardiovascular disease patients.

Pressure injuries in elderly with acute myocardial infarction.

OBJECTIVES: To assess pressure injury (PI) incidence among patients hospitalized for acute myocardial infarction (AMI) in an intensive coronary care unit (ICCU) and to detect the impact of specific risk factors on the development of PI in this clinical setting. PATIENTS AND METHODS: Prospective cohort study in ICCU setting. Patients admitted for AMI: patients mean age 67.5±11.5 years (n=165). Norton Scale, Mini Nutritional Assessment (MNA), demographic, clinical and biochemical data collected at the time of ICCU admission have been tested in a logistic model to assess the odds ratios (ORs) of PI risk development. The jackknifed area under the receiver operating characteristic curve (AUC) and the decision curve analysis have been employed to assess the additive predictive value of a factor. RESULTS: Twenty-seven (16.3%) patients developed PIs. An increased PI risk was associated with advanced age (OR =2.5 every 10-year increase; 95% CI =1.1-5.7), while probability of PI development was reduced in patients with higher left ventricular ejection fraction (LVEF) (OR =0.4 every 5% increase; 95% CI =0.24-0.66), MNA score (OR =0.65 every unit change; 95% CI =0.44-0.95) and Norton Scale score (OR =0.7 every unit change; 95% CI =0.57-0.88). The AUC and the decision curve analysis showed that LVEF inclusion improved the discrimination power and the clinical net benefit of the final model. CONCLUSION: Age, LVEF, Norton Scale and MNA scores have a strong and independent clinical value as predictors of in-hospital PI development in patients with AMI. This finding has the potential to improve the clinical management of patients admitted in ICCU.

Different Determinants of Ventilatory Inefficiency at Different Stages of Reduced Ejection Fraction Chronic Heart Failure Natural History.

BACKGROUND: It is not known whether determinants of ventilation (VE)/volume of exhaled carbon dioxide (VCO2) slope during incremental exercise may differ at different stages of reduced ejection fraction chronic heart failure natural history. METHODS AND RESULTS: VE/VCO2 slope was fitted up to lowest VE/VCO2 ratio, that is, a proxy of the VE/perfusion ratio devoid of nonmetabolic stimuli to ventilatory drive. VE/VCO2 slope tertiles were generated from our database (<27.5 [tertile 1], ≥27.5 to <32.0 [tertile 2], and ≥32.0 [tertile 3]), and 147 chronic heart failure patients with repeated tests yielding VE/VCO2 slopes in 2 different tertiles were selected. Determinants of VE/VCO2 slope changes across tertile pairs 1 versus 2, 2 versus 3, and 1 versus 3 were assessed by exploring changes in VE and VCO2 at lowest VE/VCO2 and those in VE/work rate (W) and VCO2/W slope. Resting and peak cardiac output (CO) were calculated as VO2/estimated arteriovenous O2 difference and the CO/W slope analyzed. Notwithstanding a progressively lower W with increasing tertile, VE at lowest VE/VCO2 and VE/W slope were significantly higher in tertiles 2 and 3 versus tertile 1. Conversely, VCO2 at lowest VE/VCO2 and CO/W slope significantly decreased across tertiles, whereas VCO2/W slope did not. Difference (Δ) in VE/W slope between tertiles accounted for 71% of ΔVE/VCO2 slope variance, with ΔVCO2/W slope explaining an additional 26% (model r=0.99; r2=0.97; P<0.0001). Similar results were obtained substituting ΔVCO2/W slope with ΔCO/W slope. CONCLUSIONS: Ventilatory overactivation is the predominant cause of VE/VCO2 slope increase at initial stages of chronic heart failure, whereas hemodynamic impairment plays an additional role at more-advanced pathophysiological stages.

Cardiopulmonary Exercise Testing: Basics of Methodology and Measurements.

Cardiopulmonary exercise testing adds measurement of ventilation and volume of oxygen uptake and exhaled carbon dioxide to routine physiological and performance parameters obtainable from conventional exercise testing, furnishing an all-around vision of the systems involved in both oxygen transport from air to mitochondria and its use during exercise. Peculiarities of cardiopulmonary exercise testing methodology are the use of ramp protocols and calibration procedures for flow meters and gas analyzers. Among the several parameters provided by this technique, peak oxygen uptake, first and second ventilatory thresholds, respiratory exchange ratio, oxygen pulse, slope of ventilation divided by exhaled carbon dioxide relationship, exercise oscillatory ventilation, circulatory power, and partial pressure of end-tidal carbon dioxide are among the most relevant in the clinical setting. The choice of parameters to be considered will depend on the indication to cardiopulmonary exercise testing in the individual subject or patient, namely, exercise tolerance assessment, prognostic stratification, training prescription, treatment efficacy evaluation, diagnosis of causes of unexplained exercise tolerance reduction, or exercise (patho)physiology evaluation for research purposes. Overall, cardiopulmonary exercise testing is a methodology now widely available and supported by sound scientific evidence. Despite this, its potential still remains largely underused. Strong efforts and future investigations are needed to address these issues and further promote the use of cardiopulmonary exercise testing in the clinical and research setting.

Prognostic role of ß-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database.

AIMS: The use of ß-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared ß-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of ß-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of ß-selectivity and dosage regimens. METHODS AND RESULTS: In 5242 HFrEF patients, we investigated the role of: (i) ß-blocker treatment vs. non-ß-blocker treatment, (ii) ß1-/ß2-receptor-blockers vs. ß1-selective blockers, and (iii) daily ß-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on ß-blockers, while 807 (13.2%) were not. At 5 years, ß-blocker-patients showed a better outcome than non-ß-blocker-subjects [hazard ratio (HR) 0.48, P < 0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the ß1-/ß2-receptor-blocker (n = 2219) vs. ß1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5-25 mg, n = 1431) and low dose (<12.5 mg, n = 1960) (HR 1.97, P < 0.001; HR 1.95, P = 0.001, respectively), with no differences between the last two groups (HR 0.84, P = ns). CONCLUSION: In a large population of chronic HFrEF patients, ß-blockers were associated with a more favourable prognosis without any difference between ß1- and ß2-receptor-blockers vs. ß1-selective blockers. A better outcome was observed in subjects receiving a high daily dose.

High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). METHODS: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. RESULTS: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. CONCLUSIONS: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Heart failure and anemia: Effects on prognostic variables.

BACKGROUND: Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. METHODS: Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively. RESULTS: Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO2 slope was associated with poor prognosis only in patients with low and normal Hb. CONCLUSIONS: Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.

Sex Profile and Risk Assessment With Cardiopulmonary Exercise Testing in Heart Failure: Propensity Score Matching for Sex Selection Bias.

BACKGROUND: In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption (V˙o2): this raises doubt about the accuracy of risk assessment by cardiopulmonary exercise testing (CPET) in women. Accordingly, we aimed to check (1) whether the predictive role of well-known CPET risk indexes, ie, peak V˙o2 and ventilatory response (V˙e/V˙co2 slope), is sex independent and (2) if sex-related characteristics that impact outcome in HF should be considered as associations that may confound the effect of sex on survival. METHODS: The study population consisted of 2985 patients with HF, 498 (17%) of whom were women, from the multicentre Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI): the end point was cardiovascular death within a 3-year period. RESULTS: During the follow-up, 305 (12%) men and 39 (8%) women (P = 0.005) died, and female sex was linked to better survival on univariate analysis (P = 0.008) and independent of peak V˙o2 and V˙e/V˙co2 slope on multivariate analysis. According to propensity score matching for female sex to exclude a sex selection bias and sample discrepancy, 498 men were selected: the standardized percentage bias ranged from 20.8 (P < 0.0001) to 3.3 (P = 0.667). After clinical profile harmonizing, female sex was predictive of HF at univariate analysis. CONCLUSIONS: The low peak V˙o2 and female association with better outcome in HF might be counterfeit: the female prognostic advantage is lost when sex-specific differences are correctly taken into account with propensity score matching, suggesting that for an effective and efficient HF model, adjustment must be made for sex-related characteristics.

The metabolic exercise test data combined with Cardiac And Kidney Indexes (MECKI) score and prognosis in heart failure. A validation study.

BACKGROUND: The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a prognostic model to identify heart failure (HF) patients at risk for cardiovascular mortality (CVM) and urgent heart transplantation (uHT) based on 6 routine clinical parameters: hemoglobin, sodium, kidney function by the Modification of Diet in Renal Disease (MDRD) equation, left ventricle ejection fraction (LVEF), percentage of predicted peak oxygen consumption (VO2) and VE/VCO2 slope. OBJECTIVES: MECKI score must be generalizable to be considered useful: therefore, its performance was validated in a new sequence of HF patients. METHODS: Both the development (MECKI-D) and the validation (MECKI-V) cohorts were composed of consecutive HF patients with LVEF <40% able to perform a symptom-limited cardiopulmonary exercise testing. The CVM or uHT rates were analyzed at one, two and three years in both cohorts: all patients with a censoring time shorter than the scheduled follow-up were excluded, while those with events occurring after 1, 2 and 3 years were considered as censored. RESULTS: MECKI-D and MECKI-V consisted of 2009 and 992 patients, respectively. MECKI-V patients had a higher LVEF, higher peak VO2 and lower VE/VCO2 slope, higher prescription of beta-blockers and device therapy: after the 3-year follow-up, CVM or uHT occurred in 206 (18%) MECKI-D and 44 (13%) MECKI-V patients (p<0.000), respectively. MECKI-V AUC values at one, two and three years were 0.81 ± 0.04, 0.76 ± 0.04, and 0.80 ± 0.03, respectively, not significantly different from MECKI-D. CONCLUSIONS: MECKI score preserves its predictive ability in a HF population at a lower risk.

Intensive cycle ergometer training improves gait speed and endurance in patients with Parkinson's disease: A comparison with treadmill training.

PURPOSE: Cycle ergometer training improves gait in the elderly, but its effect in patients with Parkinson's disease (PD) is not completely known. METHODS: Twenty-nine PD inpatients were randomized to treadmill (n = 13, PD-T) or cycle ergometer (n = 16, PD-C) training for 3 weeks, 1 hour/day. Outcome measures were distance travelled during the 6-min walking test (6MWT), spatio-temporal variables of gait assessed by baropodometry, the Timed Up and Go (TUG) duration, the balance score through the Mini-BESTest, and the score of the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: Sex, age, body mass index, disease duration, Hoehn-Yahr staging, comorbidity and medication did not differ between groups. At end of training, ANCOVA showed significant improvement, of similar degree, in both groups for 6MWT, speed, step length and cadence of gait, TUG, Mini-BESTest and UPDRS. CONCLUSIONS: This pilot study shows that cycle ergometer training improves walking parameters and reduces clinical signs of PD, as much as treadmill training does. Gait velocity is accompanied by step lengthening, making the gait pattern close to that of healthy subjects. Cycle ergometer is a valid alternative to treadmill for improving gait in short term in patients with PD.

Quadriceps Strength as a Predictor of Mortality in Coronary Artery Disease.

BACKGROUND: The purpose of this study was to investigate the prognostic value of quadriceps isometric strength (QIS) in coronary artery disease (CAD). METHODS: The study population consisted of 1314 patients aged >30 years (64.7 ± 10.6 years, 1051 male) with CAD who were hospitalized for acute coronary syndrome or coronary artery bypass grafting. Maximal QIS was evaluated as a marker of leg strength and expressed relative to body weight (% body weight). The primary and secondary endpoints were all-cause death and cardiovascular (CV) death, respectively. RESULTS: During a mean follow-up of 5.0 ± 3.5 years, corresponding to 6537 person-years, there were 118 all-cause deaths and 63 CV deaths. A higher QIS remained associated with decreased all-cause mortality and CV mortality risks (hazard ratio for increasing 10% body weight of QIS 0.77, 95% confidence interval 0.67-0.89, P < .001 for all-cause death; hazard ratio 0.66, 95% confidence interval 0.54-0.82, P < .001 for CV death) after adjustment for other prognostic factors. The inclusion of QIS significantly increased both continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) for all-cause death (cNRI: 0.25, P = .009; IDI: 0.007, P = .030) and CV death (cNRI: 0.34, P = .008; IDI: 0.013, P = .008). CONCLUSIONS: A high level of quadriceps strength was strongly associated with a lower risk of both all-cause and CV mortality in patients with CAD. Evaluation of QIS offered incremental prognostic information beyond pre-existing risk factors.

Hemodynamic, not ventilatory, inefficiency is associated with high VE/VCO2 slope in repaired, noncyanotic congenital heart disease.

BACKGROUND: A high slope of the ventilation vs. carbon dioxide relationship (VE/VCO2 slope) during incremental exercise has been reported in several congenital heart disease (CHD) types, but it is not clear whether the main cause of high VE/VCO2 slope is excessive ventilation or reduced perfusion. METHODS: We studied 169 adolescent and adult patients with repaired, noncyanotic CHD, divided into 2 groups according to VE/VCO2 slope %predicted values (≤120 and >120), and 15 age- and sex-matched normals. VCO2/VE max and VO2/VE max were considered proxies of the perfusion/ventilation relationship, with VCO2 and VO2 as indirect descriptors of cardiac output. RESULTS: VCO2/VE max was significantly and inversely related to VE/VCO2 slope (r=-0.73, p<0.0001), and higher in normals and ≤120 than in >120 (39.6 ± 7.7, 36.1 ± 5.3 and 28.5 ± 4.1, respectively, p<0.0001). Similarly, VCO2 at VCO2/VE max was higher in normals and ≤120 than in >120 (1701 ± 474, 1480 ± 492 and 1169 ± 388 ml/min, respectively, p<0.0001), whereas ventilation at VCO2/VE max showed no changes (43 ± 8, 41 ± 12, 41 ± 11 and 41 ± 9l/min, respectively, p=0.82) between groups. Thus, differences in VCO2/VE max and VE/VCO2 slope between groups were due mostly to changes in VCO2, i.e. in cardiac output, rather than ventilation. The same behavior was observed for VO2/VE max. CONCLUSIONS: A high VE/VCO2 slope observed in patients with repaired, noncyanotic CHD seems not to depend on excessive ventilation but on hypoperfusion due to impaired cardiac output response to incremental exercise. This finding should focus researchers' attention mainly on the heart when addressing exercise pathophysiology of this patient population.