Recovery kinetics of oxygen uptake is prolonged in adults with an atrial septal defect and improves after transcatheter closure

Background

In adults with an atrial septal defect (ASD) transcatheter closure leads to an improvement of peak oxygen uptake (VO₂), but the kinetics of recovery of VO₂ after maximal exercise in this patient population and the impact of transcatheter ASD closure have never been investigated.

Methods

Twenty consecutive patients underwent a maximal cardiopulmonary exercise test both the day before and 6 months after transcatheter ASD closure. For comparison, an age- and sex-matched group consisting of 53 healthy adults was built. The constant decay of VO₂, CO₂ production (VCO₂), minute ventilation (VE), and heart rate (HR), expressed as the first-degree slope of a single linear relation, were calculated for the first minute of recovery.

Results

Patients with an ASD had a prolonged VO₂ slope (P = .0012), VCO₂ slope (P = .0003), and VE slope (0.013) when compared with control subjects. Six months after transcatheter ASD closure, significant improvements of VO₂ slope (P = .0043) and of VCO₂ slope (P = .0022) were recorded, so that no difference was found when compared with those of the control group (P = .1 and P = .06, respectively). The VE slope and HR slope did not change after closure. A significant association between VO₂ slope and peak VO₂in the group of patients with ASD was shown by the Spearman correlation, both before (r = 0.67, P = .0012) and after ASD closure (r = 0.71, P = .0004).

Conclusions

A limited cardiopulmonary reserve in adults with no symptom who have an ASD appears to affect not only maximal exercise responses but also the recovery phase. Transcatheter ASD closure induces a significant improvement of the ability of recovering from maximal exercise and eliminates the difference with a healthy population.     

Comparison of ventilatory expired gas parameters used to predict hospitalization in patients with heart failure

Background Several ventilatory expired gas measures obtained during exercise testing demonstrate prognostic value in the heart failure (HF) population. Comparison of prognostic efficacy between pertinent measures is sparse. Methods The ability of various expressions of peak oxygen consumption (VO₂), the relationship between minute ventilation (VE) and carbon dioxide production (VCO₂), and the partial pressure of end-tidal carbon dioxide (P_ETCO₂) were assessed to determine which measure(s) best predicted cardiac-related hospitalization over a 1-year period in subjects diagnosed with HF. Results Univariate Cox regression analysis found that several expressions of peak VO₂, VE-VCO₂ relationship, and P_ETCO₂ were significant predictors of hospitalization. Multivariate Cox regression analysis revealed that the VE/VCO₂ slope significantly predicted hospitalization (χ² = 29.1, P < .00001). Peak VO₂ and P_ETCO₂ did not provide additional predictive value. Conclusions The prognostic superiority of the VE/VCO₂ slope over peak VO₂ may be a result of the latter measure's partial dependence on subject effort and skeletal muscle function. (Am Heart J 2002;143:427-32.)     

Cardiopulmonary exercise testing is equally prognostic in young, middle-aged and older individuals diagnosed with heart failure

Background

Previous research has demonstrated the prognostic value of cardiopulmonary exercise testing (CPX) in elderly patients with heart failure (HF). Investigations that have comprehensively examined the value of CPX across different age groups are lacking. The purpose of the present investigation was to evaluate the prognostic value of CPX in young, middle-aged and older patients with HF.

Methods

A total of 1605 subjects (age: 59.2 ± 13.7 years, 78% male) underwent CPX and were subsequently tracked for major cardiac events. Ventilatory efficiency (VE/VCO₂ slope) and peak oxygen consumption (VO₂), both absolute and percent-predicted, were determined. The prognostic value of these CPX variables was assessed in ≤ 45, 46-65 and ≥ 66 year subgroups.

Results

The three year event rates for major cardiac events in the ≤ 45, 46-65 and ≥ 66 year subgroups were 8.8%, 6.0% and 5.7%, respectively. The VE/VCO₂ slope (Hazard ratio ≥ 1.07, p < 0.001), peak VO₂ (Hazard ratio ≤ 0.87, p < 0.001) and percent-predicted peak VO₂ (Hazard ratio ≤ 0.98, p < 0.001) were all significant prognostic markers in each age subgroup. While the VE/VCO₂ slope carried the greatest prognostic strength, peak VO₂ and percent-predicted peak VO₂ were retained in multivariate analyses (Residual Chi-Square ≥ 5.2, p < 0.05). With respect to peak VO₂, the actual value was the more robust prognostic marker in the ≤ 45 and ≥ 66 year subgroups while the percent-predicted expression provided better predictive resolution in subjects who were 46-65 years old.

Conclusions

These results indicate that, irrespective of a patient's age at presentation, CPX provides valuable prognostic information in the HF population.     

The minute ventilation/carbon dioxide production slope is prognostically superior to the oxygen uptake efficiency slope

BackgroundVentilatory efficiency, commonly assessed by the minute ventilation (VE)-carbon dioxide production (VCO₂) slope, has proven to be a strong prognostic marker in the heart failure (HF) population. Recently, the oxygen uptake efficiency slope (OUES) has demonstrated prognostic value, but additional comparisons to established cardiopulmonary exercise test (CPET) variables are required.Methods and ResultsA total of 341 subjects were diagnosed with HF participated in this analysis. The VE/VCO₂ slope and the OUES were calculated using 50% (VE/VCO₂ slope₅₀ or OUES₅₀) and 100% (VE/VCO₂ slope₁₀₀ or OUES₁₀₀) of the exercise data. Peak oxygen consumption (VO₂) was also determined. There were 47 major cardiac-related events during the 3-year tracking period. Receiver operating characteristic (ROC) curve analysis demonstrated the classification schemes for both VE/VCO₂ slope and OUES calculations as well as peak VO₂ were statistically significant (all areas under the ROC curve: ≥0.74, P < .001). Area under the ROC curve for the VE/VCO₂ slope₁₀₀ was, however, significantly greater than OUES₅₀, OUES₁₀₀, and peak VO₂ (P < .05).ConclusionsAlthough the OUES was a significant predictor of mortality, the VE/VCO₂ slope maintained optimal prognostic value. An elevated VE/VCO₂ slope may be the single best indicator of increased risk for adverse events.     

Measures of exercise capacity in adults with congenital heart disease

Background

Exercise capacity in grown-ups with congenital heart disease (GUCH) is mostly reported by peak oxygen consumption (peak VO₂). Our aim was to evaluate the maximal character of exercise tests, and to investigate submaximal measures of exercise capacity.

Methods

Adults with Coarctation of the Aorta (COA, n = 155), Tetralogy of Fallot (TOF, n = 98), dextro-Transposition of the Great Arteries (dTGA, n = 68) and Univentricular Heart (UVH, n = 10), and 122 healthy adults performed cardiopulmonary exercise testing until exhaustion. Gas exchange was measured breath by breath. The maximal performance of the test was evaluated by respiratory exchange ratio (RER), ventilatory equivalent for oxygen and Borg scale. Oxygen uptake efficiency slope (OUES), VE/VCO₂ slope and VO₂/WR slope were calculated and ventilatory anaerobic threshold (VAT) was defined. Correlations of these measures with peak VO₂ were calculated.

Results

GUCH showed significantly lower peak VO₂ than controls (p < 0.001), declining from 80% in COA, 74% in TOF, 64% in dTGA, to 55% in UVH. Compared to suggested criteria, mean peak RER and median Borg scale indicated a maximal effort in GUCH, however these results were significantly lower than controls (p < 0.05). OUES, VO₂/WR slope and VAT were significantly lower in patients compared to controls. OUES (r = 0.853) and VAT (r = 0.840) correlated best with peak VO₂; VO₂/WR slope (r = 0.551) and VE/VCO₂ slope (r = −0.421) correlated to a lesser degree (p < 0.001).

Conclusion

The investigated GUCH show reduced exercise tolerance compared to controls, related to the underlying heart defect. Different expressions of exercise tolerance clearly reveal the same differences in exercise capacity across groups of GUCH.     

The clinical and research applications of aerobic capacity and ventilatory efficiency in heart failure: an evidence-based review

A hallmark symptom of heart failure (HF) is exercise intolerance, typically evidenced by excessive shortness of breath, and/or fatigue with exertion. In recent years, the physiologic response to progressive exercise using direct measures of ventilation and gas exchange, commonly termed the cardiopulmonary exercise test (CPX), has evolved into an important clinical tool in the management of patients with HF. There is currently debate regarding the optimal CPX response to apply when stratifying risk for mortality, hospitalization, or other outcomes in patients with HF. Early studies in this area focused on the application of peak VO₂ in predicting outcomes in patients considered for transplantation. More recently, the focus of these studies has shifted to an emphasis on ventilatory inefficiency, in lieu of or in combination with peak VO₂, in estimating risk. The most widely studied index of ventilatory inefficiency has been the minute ventilation/carbon dioxide production (VE/VCO₂) slope. A growing body of studies over the last decade has demonstrated that among patients with HF, the VE/VCO₂ slope more powerfully predicts mortality, hospitalization, or both, than peak VO₂. A number of investigations have also simultaneously examined the diagnostic importance of peak VO₂ and the VE/VCO₂ slope as well as their respective response to various interventions. This review examines the body of evidence which has used aerobic capacity and ventilatory efficiency as prognostic and diagnostic markers as well as endpoints in interventional trials. Based on this evidence, recommendations for future clinical and research applications of these CPX variables are provided.     

Corrélation entre fonction atriale et capacité fonctionnelle chez les sportifs de haut niveau

Aim

The aim of the study is to show the relationship existing between tissular Doppler imaging (TDI) parameters and functional capacity in highly trained subjects.

Methods and patients

We therefore studied 46 patients including 22 untrained and 24 trained subjects. Each subject had pulsed TDI recording of systolic (S) and diastolic (E and A) longitudinal myocardial velocities in the basal portion of the RV free wall (RV), the septum (sep) and the LV free wall (LV) from apical 4C view. Athletes underwent the same day a cardiopulmonary test during which we measured peak VO₂ (ml/kg/min) and anaerobic threshold (AT, ml/kg/min) and calculated VE/VCO₂ slope. We studied differences between echocardiographic parameters in the two groups using Student test. Coefficients of correlations were calculated using the Spearman method.

Results

Differences between two groups concerned Tei index of right (RV) and left ventricle (LV), telediastolic diameter of LV, and A waves on each wall. In athletes RV, sep and LV S waves did not correlate with VO₂, AT or VE/VCO₂ RV, sep and LV A waves correlated significantly and negatively with VO₂, RV and sep A waves negatively with AT, and sep and LV A waves positively with VE/VCO₂.

Conclusion

In athletes, atrial function shows a negative relationship with cardiopulmonary exercise parameters: the lower the proportion of LV filling due to atrial contraction, the better the level of functional capacity. This is probably due to myocardial structure, which allows more efficient early filling in hypertrophic athlete's heart.     

Exercise oscillatory breathing and NT-proBNP levels in stable heart failure provide the strongest prediction of cardiac outcome when combining biomarkers with cardiopulmonary exercise testing

BackgroundN-Terminal pro–brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET)–derived variables are gold standards for assessing prognosis in heart failure (HF) patients. We sought to refine cardiac events prediction by performing a combined analysis of NT-proBNP with markers of exercise ventilatory efficiency.Methods and ResultsA total of 260 stable HF patients underwent measurements of plasma NT-proBNP levels before, at peak exercise, and at 1-minute CPET recovery phase along with peak oxygen uptake (VO₂), ventilation to CO₂ production (VE/VCO₂) slope, and exercise periodic breathing (EPB) determinations. After a median follow-up period of 20.6 months, there were 54 cardiac-related deaths. Univariate analysis including NT-proBNP at rest, at peak exercise, and at 1 minute recovery, peak VO₂, VE/VCO₂ slope, and EPB showed NT-proBNP to be the strongest independent predictor with equivalent performance for rest, peak, and recovery levels. Thus, only NT-proBNP at rest was considered (Harrel C 0.783, 95% confidence interval [CI] 0.722–0.844) with VE/VCO₂ slope (Harrel C 0.720, 95% CI 0.646–0.794), EPB (Harrel C 0.685, 95% CI 0.619–0.751), and peak VO₂ (Harrel C 0.618, 95% CI 0.533–0.704). With bivariate stepwise analyses, NT-proBNP along with EPB emerged as the strongest prognosticators (Harrel C 0.800, 95% CI 0.737–0.862).ConclusionsIn the refinement for robust outcome predictors in HF patients, NT-proBNP levels together with EPB led to the most powerful definition. VE/VCO₂ slope and peak VO₂ did not provide any prognostic adjunct. A biomarker/CPET approach seems very promising to warrant the continuous implementation in the prognostic work-up of HF patients.     

A neural network approach to predicting outcomes in heart failure using cardiopulmonary exercise testing

Objectives

To determine the utility of an artificial neural network (ANN) in predicting cardiovascular (CV) death in patients with heart failure (HF).

Background

ANNs use weighted inputs in multiple layers of mathematical connections in order to predict outcomes from multiple risk markers. This approach has not been applied in the context of cardiopulmonary exercise testing (CPX) to predict risk in patients with HF.

Methods

2635 patients with HF underwent CPX and were followed for a mean of 29 ± 30 months. The sample was divided randomly into ANN training and testing sets to predict CV mortality. Peak VO₂, VE/VCO₂ slope, heart rate recovery, oxygen uptake efficiency slope, and end-tidal CO₂ pressure were included in the model. The predictive accuracy of the ANN was compared to logistic regression (LR) and a Cox proportional hazards (PH) score. A multi-layer feed-forward ANN was used and was tested with a single hidden layer containing a varying number of hidden neurons.

Results

There were 291 CV deaths during the follow-up. An abnormal VE/VCO₂ slope was the strongest predictor of CV mortality using conventional PH analysis (hazard ratio 3.04; 95% CI 2.2–4.2, p < 0.001). After training, the ANN was more accurate in predicting CV mortality compared to LR and PH; ROC areas for the ANN, LR, and PH models were 0.72, 0.70, and 0.69, respectively. Age and BMI-adjusted odds ratios were 4.2, 2.6, and 2.9, for ANN, LR, and PH, respectively.

Conclusion

An ANN model slightly improves upon conventional methods for estimating CV mortality risk using established CPX responses.     

Oxygen uptake efficiency slope, a new submaximal parameter in evaluating exercise capacity in chronic heart failure patients

Background

The oxygen uptake efficiency slope (OUES) is a new submaximal parameter which objectively predicts the maximal exercise capacity in children and healthy subjects. However, the usefulness of OUES in adult patients with and without advanced heart failure remains undetermined. The present study investigates the stability and the usefulness of OUES in adult cardiac patients with and without heart failure.

Methods

Forty-five patients with advanced heart failure (group A) and 35 patients with ischemic heart disease but normal left ventricular ejection fraction (group B) performed a maximal exercise test. PeakVO₂ and percentage of predicted peakVO₂ were markers of maximal exercise capacity, whereas OUES, ventilatory anaerobic threshold (VAT), and slope VE/VCO₂ were calculated as parameters of submaximal exercise.

Results

Group A patients had lower peakVO₂ (P < .001), lower percentage of predicted peakVO₂ (P = .001), lower VAT (P < .05), steeper slope VE/VCO₂ (P < .001), and lower OUES (P < .02). Within group A, significant differences were found for VAT, slope VE/VCO₂, and OUES (all P < .01) between patients with peakVO₂ above and below 14 mL O₂/kg/min. Of all the submaximal parameters, VAT correlated best with peakVO₂ (r =.814, P < .01) followed by OUES/kg (r = .781, P < .01), and slope VE/VCO₂ (r = −.492, P < .001). However, VAT could not be determined in 18 (23%) patients.

Conclusions

OUES remains stable over the entire exercise duration and is significantly correlated with peakVO₂ in adult cardiac patients with and without impaired LVEF. Therefore, OUES could be helpful to assess exercise performance in advanced heart failure patients unable to perform a maximal exercise test. Further studies are needed to confirm our hypothesis.     

A flattening oxygen consumption trajectory phenotypes disease severity and poor prognosis in patients with heart failure with reduced,mid‐range,and preserved ejection fraction

Background

In heart failure (HF), a flattening oxygen consumption (VO₂) trajectory during cardiopulmonary exercise test (CPET) reflects an acutely compromised cardiac output. We hypothesized that a flattening VO₂ trajectory is helpful in phenotyping disease severity and prognosis in HF with either reduced (HFrEF), mid‐range (HFmrEF), or preserved (HFpEF) ejection fraction.

Methods and results

Overall, 319 HF patients (198 HFrEF, 80 HFmrEF, and 41 HFpEF) underwent CPET. A flattening VO₂ trajectory was tracked and defined as an inflection of VO₂ linearity as a function of work rate with a second slope downward inflection >35% extent of the first one. Peak VO₂, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, and the presence of exercise oscillatory ventilation (EOV) were also determined. Pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE) were measured by echocardiography. A flattening VO₂ occurred in 92 patients (28.8%). PASP and TAPSE at rest were significantly higher and lower (P < 0.001), respectively. The primary outcome was the combination of all‐cause death, heart transplantation and left ventricular assist device implantation. The secondary outcome was the primary outcome plus hospitalization for cardiac reasons. In the multivariate model including peak VO₂, VE/VCO₂ slope, EOV and VO₂ trajectory, a flattening VO₂ trajectory and EOV were retained in the regression for primary (X² = 35.78, and 36.36, respectively; P < 0.001) and secondary (X² = 12.45 and 47.91, respectively; P < 0.001) outcomes.

Conclusions

Results point to a flattening VO₂ trajectory as a likely new and strong predictor of events in HF with any ejection fraction. Given the relation of right‐sided cardiac dysfunction to pulmonary hypertension, this oxygen pattern might suggest a real‐time decrease in pulmonary blood flow to the left heart.

     

Ventilatory response to exercise improves risk stratification in patients with chronic heart failure and intermediate functional capacity

Background Peak oxygen consumption (VO₂) has an important prognostic role in chronic heart failure (CHF), but its discriminatory power is limited in patients with intermediate exercise capacity (peak VO₂ between 10-18 mL/kg/min). Thus, supplementary exertional indexes are greatly needed. Methods Six hundred patients with CHF with left ventricular ejection fraction (LVEF) ≤40% who performed a symptom-limited cardiopulmonary exercise testing were screened and followed up for 780 ± 450 days. Results Eighty-seven patients had major cardiac events (77 cardiac deaths and 10 urgent heart transplantations). Multivariate analysis revealed the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO₂ slope) (χ², 79.3, P < .0001), LVEF (χ², 24.6, P < .0001), and peak VO₂ (χ², 9.4, P < .0001) as independent and additional predictors of major cardiac events. VE/VCO₂ slope was the strongest independent predictor of outcome (χ², 20.9, P = .0001) in patients with intermediate peak VO₂ (n = 403), and the best cutoff value was 35 (χ², 25.8; relative risk = 3.2, 95% CI 2.0-5.1, P < .0001). Total mortality rate was 30% in patients with VE/VCO₂ slope ≥35 (n = 103, 26%) and 10% in those with VE/VCO₂ slope <35 (n = 300, 74%) (P < .0001). Patients with VE/VCO₂ slope ≥35 had a similar total mortality rate to those with peak VO₂ ≤10 mL/kg/min (30% vs 37%, P not significant). Conclusions A rational and pragmatic risk stratification process with symptom-limited cardiopulmonary exercise testing in CHF should include both peak VO₂ and VE/VCO₂ slope, the latter index effectively predicting outcome in almost one fourth of patients with intermediate exercise capacity. (Am Heart J 2002;143:418-26.)     

The Lowest VE/VCO2 Ratio During Exercise as a Predictor of Outcomes in Patients With Heart Failure

BackgroundThe lowest minute ventilation (VE) and carbon dioxide production (VCO₂) ratio during exercise has been suggested to be the most stable and reproducible marker of ventilatory efficiency in patients with heart failure (HF). However, the prognostic power of this index is unknown.Methods and ResultsA total of 847 HF patients underwent cardiopulmonary exercise testing (CPX) and were followed for 3 years. The associations between the lowest VE/VCO₂ ratio, maximal oxygen uptake (peak VO₂), the VE/VCO₂ slope, and major events (death or transplantation) were evaluated using proportional hazards analysis; adequacy of the predictive models was assessed using Akaike information criterion (AIC) weights. There were 147 major adverse events. In multivariate analysis, the lowest VE/VCO₂ ratio (higher ratio associated with greater risk) was similar to the VE/VCO₂ slope in predicting risk (hazard ratios [HR] per unit increment 2.0, 95% CI 1.1–3.4, and 2.2, 95% CI 1.3–3.7, respectively; P < .01), followed by peak VO₂ (HR 1.6, 95% CI 1.1–2.4, P = .01). Patients exhibiting abnormalities for all 3 responses had an 11.6-fold higher risk. The AIC weight for the 3 variables combined (0.94) was higher than any single response or any combination of 2. The model including all 3 responses remained the most powerful after adjustment for β-blocker use, type of HF, and after applying different cut points for high risk.ConclusionsThe lowest VE/VCO₂ ratio adds to the prognostic power of conventional CPX responses in HF.     

Muscle sympathetic nerve activity and ventilation during exercise in subjects with and without chronic heart failure

BACKGROUND:

Changes within skeletal muscle, including augmentation of its capacity to elicit reflex increases in both efferent muscle sympathetic nerve activity (MSNA) and ventilation during work, contribute significantly to exercise intolerance in heart failure (HF). Previously, we demonstrated that peak oxygen uptake (pVO₂) in HF relates inversely to MSNA at rest and during exercise.

OBJECTIVE:

To test the hypothesis that there is an independent positive relationship between resting MSNA and the ratio of ventilation to carbon dioxide output during exercise (VE/VCO₂) that is augmented in HF.

METHODS:

MSNA at rest and VE/VCO₂ during stationary cycling were measured in 30 patients (27 men) with HF (mean ± SD ejection fraction 20±6%) and in 31 age-matched controls (29 men).

RESULTS:

MSNA was higher in HF patients than in controls (51.5±14.3 bursts/min versus 33.0±11.1 bursts/min; P<0.0001). The VE/VCO₂ slope was also higher in HF patients than in controls (33.7±5.7 versus 26.0±3.5; P<0.0001), whereas pVO₂ was lower in HF patients than in controls (18.6±6.6 versus 31.4±8.4 mL/kg/min; P<0.0001). There were significant relationships between MSNA and VE/VCO₂ in both HF (r=0.50; P=0.005) and control subjects (r=0.36; P=0.046). The slope of this regression equation was steeper in HF (0.20 versus 0.11 × MSNA; P=0.001). An analysis of covariance for main effects, including age and pVO₂, identified a significant independent relationship between MSNA burst frequency and VE/VCO₂ (P=0.013) that differed between HF and controls (P<0.01).

CONCLUSIONS:

The magnitude of resting sympathetic activity correlates positively with the VE/VCO₂ slope. Augmentation of this relationship in HF patients is consistent with the concept that enhanced mechanoreceptor reflex activity exaggerates their ventilatory response to exercise.     

Comparison of the Seattle Heart Failure Model and Cardiopulmonary Exercise Capacity for Prediction of Death in Patients With Chronic Ischemic Heart Failure and Intracoronary Progenitor Cell Application

Background:

Despite many therapeutic advances, the prognosis of patients with chronic heart failure (CHF) remains poor. Therefore, reliable identification of high‐risk patients with poor prognosis is of utmost importance. Cardiopulmonary exercise testing (CPET) provides important prognostic information by peak O₂ uptake (peak VO₂), maximal oxygen pulse (O₂ Pmax), O₂ uptake efficiency slope (OUES), and VE/VCO₂ slope (VE/VCO₂). A different approach for prognostic assessment is the Seattle Heart Failure Model (SHFM), which is based on clinical data and calculates the estimated annual mortality.

Hypothesis:

Comparison of the prognostic value of the Seattle Heart Failure Score and cardiopulmonary excercis testing in patients with chronic heart failure.

Methods:

One hundred fifty‐seven patients with ischemic heart failure and recent intracoronary progenitor cell application were analyzed for mortality during a follow‐up of 4 years. CPET (peak VO₂, O₂ Pmax, OUES, VE/VCO₂) was performed in all patients at baseline. The SHFM score was calculated for every patient, with data obtained at the time of CPET.

Results:

During follow‐up, 24 patients died (15.2%). Nonsurvivors had significantly worse initial CPET results and a higher SHFM score compared to survivors. Receiver operating characteristics curve analysis of sensitivity and specificity revealed the largest area under the curve value for the SHFM score, followed by VE/VCO₂ slope. Kaplan Meier analysis using cutoff points of SHFM and VE/VCO₂ slope with highest sensitivity and specificity resulted in significant discrimination of survivors and nonsurvivors. By multivariate analysis, only the SHFM score persisted as independent predictor of mortality in these patients.

Conclusions:

These data indicate superior prognostic power of the SHFM score compared to CPET in patients with chronic ischemic heart failure. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO₂), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO₂ (7,319), VE/VCO₂ slope (5,044), EOV (1,617), and OUES (584). Peak VO₂, the VE/VCO₂ slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO₂ and the VE/VCO₂ slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.     

Development of a cardiopulmonary exercise prognostic score for optimizing risk stratification in heart failure: the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE) study

BackgroundCardiopulmonary exercise testing (CPET) provides powerful information on risk of death in heart failure (HF). We sought to define the relative and additive contribution of the 3 landmark (CPET) prognostic markers—peak oxygen consumption (VO₂), minute ventilation/carbon dioxide production (VE/VCO₂) slope, and exercise periodic breathing (EPB)—to the overall risk of cardiac death and to develop a prognostic score for optimizing risk stratification in HF patients.Methods and ResultsA total of 695 stable HF patients (average LVEF: 25 ± 8%) underwent a symptom-limited CPET maximum test after familiarization and were prospectively tracked for cardiac mortality. At multivariable Cox analysis EPB emerged as the strongest prognosticator. Using a statistical bootstrap technique (5000 data resamplings), point estimates, and 95% confidence intervals were obtained. Thirty-two configurations were adopted to classify patients into a given cell, according to EPB presence or absence and values of the 2 other covariates. Configurations without EPB and with VE/VCO₂ slope ≤30 were not significantly different from 0 (reference value). Statistical power of configurations increased with higher VE/VCO₂ slope and lower peak VO₂. This prompted us to formulate a score including EPB as a discriminating variable, the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE), which ranges between -1 and 1, with zero as reference configuration, that would help to optimize the prognostic accuracy of CPET-derived variables. The greatest PROBE score impact was provided by EPB, followed by VE/VCO₂ slope, whereas peak VO₂ added minimal prognostic power.ConclusionsEPB with an elevated VE/VCO₂ slope leads to the highest and most precise PROBE score, whereas no additional risk information emerges when EPB is present with a peak VO₂ ≤10 mL O₂·kg^?1·min^?1. PROBE score appears to provide a step forward for optimizing CPET use in HF prognostic definition.     

Cardiopulmonary and Noninvasive Hemodynamic Responses to Exercise Predict Outcomes in Heart Failure

BackgroundAn impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which noninvasive estimates of cardiac hemodynamics during exercise in combination with cardiopulmonary exercise test (CPX) responses improved the estimation of risk for adverse events in patients with HF.Methods and ResultsCPX and impedance cardiography were performed in 639 consecutive patients (mean age 48 ± 14 years), evaluated for HF. Clinical, hemodynamic, and CPX variables were acquired at baseline and subjects were followed for a mean of 460 ± 332 days. Patients were followed for the composite outcome of cardiac-related death, hospitalization for worsening HF, cardiac transplantation, and left ventricular assist device implantation. Cox proportional hazards analyses including clinical, noninvasive hemodynamic, and CPX variables were performed to determine their association with the composite endpoint. There were 113 events. Among CPX variables, peak oxygen uptake (VO₂) and the minute ventilation (VE)/carbon dioxide production (VCO₂) slope were significant predictors of risk for adverse events (age-adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.05–1.11 for both; P < .001). Among hemodynamic variables, peak cardiac index was the strongest predictor of risk (HR 1.08, 95% CI 1.0–1.16; P = .01). In a multivariate analysis including CPX and noninvasively determined hemodynamic variables, the most powerful predictive model included the combination of peak VO₂, peak cardiac index, and the VE/VCO₂ slope, with each contributing significantly and independently to predicting risk; an abnormal response for all 3 yielded an HR of 5.1 (P < .001).ConclusionsThese findings suggest that noninvasive indices of cardiac hemodynamics complement established CPX measures in quantifying risk in patients with HF.     

Multivariable analysis of heart rate recovery after cycle ergometry in heart failure: exercise in heart failure

Purpose

The purpose of this study was to investigate the association between impairment in heart rate recovery (HR_rec) after cycle ergometry and prognostic markers in patients with heart failure (HF) compared with healthy controls.

Methods

Fifty patients with chronic HF (systolic HF, N = 30; diastolic HF, N = 20; mean age = 62 ± 12 years) and 50 healthy controls (N = 50; mean age = 66 ± 13 years) underwent 2-dimensional and M-mode echocardiography followed by cardiopulmonary exercise testing. Independent predictors of HR_rec at 1 and 2 minutes after exercise were analyzed by univariable and multivariable regression analyses, and receiver operating characteristics were performed to obtain area under the curve.

Results

In HF, left ventricular end-diastolic diameter (millimeters), left ventricular ejection fraction (%), N-terminal pro-brain natriuretic peptide (picograms/milliliter), peak oxygen uptake (VO₂peak [milliliters/kilogram/min]), and peak heart rate (HR_peak) showed a significant association with HR_rec (beats/min) in univariate regression analyses (P < .001), but only VO₂peak remained independently predictive of both HR_rec1 (P = .034) and HR_rec2 (P = .008) in the multivariable regression analyses. In controls, VO₂peak (P = .035) and HR_peak (P = .032) were significantly associated with HR_rec2 in univariate analyses only. Optimal cutoff values for discriminating HF versus non-HF based on HR_rec were 17.5 beats/min (sensitivity 92%; specificity 74%) for HR_rec1 and 31.5 beats/min (sensitivity 94%; specificity 86%) for HR_rec2. Optimal cutoff values for discriminating systolic HF versus diastolic HF were 12.5 beats/min (sensitivity 78%; specificity 80%) for HR_rec1 and 24.5 beats/min (sensitivity 82%; specificity 90%) for HR_rec2.

Conclusion

Impairment in after exercise HR_rec is significantly and independently associated with VO2peak in HF and thus might constitute a useful tool for assessing the degree of functional status during exercise rehabilitation.     

Prognostic impact of the addition of ventilatory efficiency to the Seattle heart failure model in patients with heart failure

BackgroundThe Seattle Heart Failure Model (SHFM) is a multivariable model with proven prognostic value. Cardiopulmonary exercise testing (CPX) and neurohormonal markers (eg, B-type natriuretic peptide [BNP]) are also well accepted assessment techniques in the HF population and have both demonstrated robust prognostic value. The purpose of this investigation was to assess the combined prognostic value of the SHFM and CPX.Methods and ResultsThis study included all 453 patients enrolled in the Multicenter In-Sync Randomized Clinical Evaluation (MIRACLE) trial. Baseline SHFM and CPX were used. Both peak oxygen consumption (VO₂) and ventilatory efficiency (VE/VCO₂) were determined. In a univariate Cox proportional model analysis, SHFM and log-transformed peak VE/VCO₂ were stronger predictors of 6-month mortality (both P < .001) than log-transformed BNP (P = .013) or peak VO₂ (P = .066). In a multivariable Cox proportional hazards model, neither peak VO₂ nor BNP were independent predictors when added to the SHFM (P > .1). Conversely, peak VE/VCO₂ was a strong independent predictor when added to the SHFM, with an increase in the Cox proportional hazards model Wald χ² from 22.7 for SHFM alone to 33.8 with inclusion of log-transformed peak VE/VCO₂ (P < .0001) and significant changes in the net reclassification improvement and integrated discrimination index (both P < .002).ConclusionsThese results indicate that the SHFM and peak VE/VCO₂ work synergistically to improve prognostic resolution. Further investigation is needed to continue to optimize multivariable prognostic models in patients with HF, a chronic disease population that continues to suffer from a high adverse event rate despite advances in medical care.