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.     

Association Between Physical Activity Measurements and Key Parameters of Cardiopulmonary Exercise Testing in Patients With Heart Failure

BackgroundA hallmark characteristic of heart failure (HF) is reduced physical activity (PA) patterns. The relationship between key cardiopulmonary exercise testing (CPX) variables and PA patterns has not been investigated. Therefore, we evaluated PA patterns in patients with ischemic HF and its relationship to peak oxygen consumption (VO₂), the minute ventilation/carbon dioxide production (VE/VCO₂) slope, and the oxygen uptake efficiency slope (OUES).Methods and ResultsSixteen patients with HF wore an accelerometer for six days to measure total steps/day as well as percentage of time at light, moderate, and vigorous PA. Symptom-limited CPX was performed on a treadmill using a ramping protocol. Total steps correlated with VO₂ (r = 0.64 P < .05), the VE/VCO₂ slope (r = ?0.72; P < .05), and the OUES (0.63; P < .05). The percentage of time at light-intensity PA correlated with the VE/VCO₂ slope (r = 0.58; P < .05) and the OUES (r = ?0.51; P < .05). The percentage of time at vigorous-intensity PA correlated with peak VO₂ (r = 0.55; P < .05) and the VE/VCO₂ slope (r = ?0.52; P < .05).ConclusionsPA assessed by accelerometer is significantly associated with key CPX variables in patients with HF.     

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.     

Cardiopulmonary Exercise Testing as a Diagnostic Tool for the Detection of Left-sided Pulmonary Hypertension in Heart Failure

BackgroundRecently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly ominous consequence of left-sided heart failure (HF). The primary aim of this investigation was to assess the ability of key cardiopulmonary exercise testing (CPX) variables to detect elevated pulmonary pressures in a HF cohort.MethodsThis was a retrospective analysis of a prospectively collected database. Two hundred ninety-three subjects with HF (63 ± 10 years old, 79% male) underwent Doppler echocardiography to estimate resting pulmonary artery systolic pressure (PASP). Peak oxygen consumption (VO₂), the minute ventilation/carbon dioxide production (VE/VCO₂) slope, peak partial pressure of end-tidal CO₂ (P_ETCO₂) and exercise oscillatory ventilation (EOV) were determined.ResultsForty-six percent (n = 134) of the subjects presented with a PASP ≥40 mm Hg. A VE/VCO₂ slope </≥36.0 was the best predictor of a PASP ≥40 mm Hg (odds ratio [OR] 12.1, 95% confidence interval [CI] 6.8–21.4; P < .001). Peak P_ETCO₂ ≤34 mm Hg (OR 3.8, 95% CI 1.3–11.2; P < .001) and the presence of EOV (OR 3.2, 95% CI 1.8–5.8; P < .001) added significant diagnostic value.ConclusionsAlthough CPX is an established prognostic assessment in the HF population, the results of the present investigation indicate that it may also have important diagnostic utility for PH.     

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.     

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.     

Abnormalities in Cardiopulmonary Exercise Testing Ventilatory Parameters in Heart Failure: Pathophysiology and Clinical Usefulness

Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction, derangement of multiple organ systems and poor outcome. Out of several markers of severity, abnormalities in exercise ventilation (VE) offer relevant insights into the pathophysiology of dyspnea, lung gas exchange, and control of ventilation and are now recognized as meaningful indicators of disease severity and prognosis. Ventilation inefficiency, identified as an increased slope of VE vs carbon dioxide production (VCO₂) recognizes as major determinants an increased waste ventilation due to enhanced dead space, early occurrence of lactic acidosis, and an abnormal chemoreflex and/or metaboreflex activity. In some cases of HF, especially associated with advanced hemodynamic and neural deregulation, an exercise oscillatory ventilatory (EOV) pattern may occur. According to an increasing number of studies, EOV identifies the 15–30 % of higher-risk HF patients requiring aggressive treatment and provides an even more robust prediction of outcome compared to VE/VCO₂ slope. Overall, a refined prevalence definition and more comprehensive use of these markers in a clinical environment and in future interventional trials seem challenging for the years to come.     

Peak VO2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison

Background

Exercise testing with ventilatory expired gas analysis has proven to be a valuable tool for assessing patients with heart failure (HF). Peak oxygen consumption (peak VO₂) continues to be considered the gold standard for assessing prognosis in HF. The minute ventilation − carbon dioxide production relationship (VE/VCO₂ slope) has recently demonstrated prognostic significance in patients with HF, and in some studies, it has outperformed peak VO₂.

Methods

Two hundred thirteen subjects, in whom HF was diagnosed, underwent exercise testing between April 1, 1993, and October 19, 2001. The ability of peak VO₂ and VE/VCO₂ slope to predict cardiac-related mortality and hospitalization was examined.

Results

Peak VO₂ and VE/VCO₂ slope were demonstrated with univariate Cox regression analysis both to be significant predictors of cardiac-related mortality and hospitalization (P <.01). Multivariate analysis revealed that peak VO₂ added additional value to the VE/VCO₂ slope in predicting cardiac-related hospitalization, but not cardiac mortality. The VE/VCO₂ slope was demonstrated with receiver operating characteristic curve analysis to be significantly better than peak VO₂ in predicting cardiac-related mortality (P <.05). Although area under the receiver operating characteristic curve for the VE/VCO₂ slope was greater than peak VO₂ in predicting cardiac-related hospitalization (0.77 vs 0.73), the difference was not statistically significant (P = .14).

Conclusions

These results add to the present body of knowledge supporting the use of cardiopulmonary exercise testing in HF. Consideration should be given to revising clinical guidelines to reflect the prognostic importance of the VE/VCO₂ slope in addition to peak VO₂.     

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 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.

     

Prognostic value of a new cardiopulmonary exercise testing parameter in chronic heart failure: oxygen uptake efficiency at peak exercise - comparison with oxygen uptake efficiency slope

IntroductionA growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O₂ consumption (VO₂) and minute ventilation (VE) in patients with chronic heart failure (CHF).ObjectiveTo evaluate the prognostic value of a new CPET parameter — peak oxygen uptake efficiency (POUE) — and to compare it with OUES in patients with CHF.MethodsWe prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy — 153 male, aged 53.3 ± 13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7 ± 8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone — who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverterdefibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up.Peak VO₂, percentage of predicted peak VO₂, VE/VCO₂ slope, OUES and POUE were analyzed. OUES was calculated using the formula VO₂ (l/min) = OUES (log₁₀VE) + b. POUE was calculated as pVO₂ (l/min) / log₁₀peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE.ResultspVO₂: 20.5 ± 5.9; percentage of predicted peak VO₂: 68.6 ± 18.2; VE/VCO₂ slope: 30.6 ± 8.3; OUES: 1.85 ± 0.61; POUE: 0.88 ± 0.27. During a mean follow-up of 33.1 ± 14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37).ConclusionPOUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.     

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.     

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.     

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.     

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,Impedance Cardiography,and Reclassification of Risk in Patients Referred for Heart Failure Evaluation

BackgroundAn impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which impedance cardiography (ICG) during exercise in combination with cardiopulmonary exercise test (CPX) responses reclassified risk for adverse events in patients with HF.Methods and ResultsCPX and ICG were performed in 1236 consecutive patients (48±15 years) evaluated for HF. Clinical, ICG and CPX variables were acquired at baseline and subjects 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. Net reclassification improvement (NRI) was calculated to quantify the impact of adding hemodynamic responses to a model including established CPX risk markers on reclassifying risk. There were 422 events. Among CPX variables, peak VO₂ and indices of ventilatory inefficiency (VE/VCO₂ slope, oxygen uptake efficiency slope) were significant predictors of risk for adverse events. Among hemodynamic variables, change in cardiac index, peak cardiac time interval, and peak left cardiac work index were the strongest predictors of risk. Having 5 impaired CPX and ICG responses to exercise yielded a sevenfold higher risk for adverse events compared with having no abnormal responses. Combining ICG responses to CPX resulted in NRIs ranging between 0.34 and 0.89, attributable to better reclassification of events.ConclusionCardiac hemodynamics determined by ICG complement established CPX measures in reclassifying risk among patients with HF.     

Aerobic exercise effect on prognostic markers for systolic heart failure patients: a systematic review and meta-analysis

From previous systematic reviews and meta-analyses, there is consensus about the positive effect of exercise training on exercise capacity for systolic heart failure (HF); however, the effect on actual prognostic markers such as NTproBNP and minute ventilation/carbon dioxide production (VE/VCO₂) slope has not been evaluated. The primary aim of the proposed study is to determine the effect of aerobic exercise training (AEX) on the VE/VCO₂ slope and NTproBNP. The following databases (up to February 30, 2013) were searched with no language limitations: CENTRAL (The Cochrane Library 2013, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), and Physiotherapy Evidence Database (PEDro) (from January 1929). We screened reference lists of articles and also conducted an extensive hand search of the literature. Randomized controlled trials of exercise-based interventions with 2-month follow-up or longer compared to usual medical care or placebo were included. The study population comprised adults aged between 18 and 65 years, with evidence of chronic systolic heart failure (LVEF < 45 % and baseline NTproBNP > 300 pg/ml). Two review authors independently extracted data on study design, participants, interventions, and outcomes. We assessed the risk of bias using PEDro scale. We calculated mean differences (MD) or standardized mean differences between intervention and control groups for outcomes with sufficient data; for other outcomes, we described findings from individual studies. Eight studies involving a total of 408 participants met the inclusion criteria across the NTproBNP (5 studies with 191 patients) and VE/VCO₂ slope (4 studies with 217 patients). Aerobic exercise significantly improved NTproBNP by a MD of ?817.75 [95 % confidence interval (CI) ?929.31 to ?706.19]. Mean differences across VE/VCO₂ slope were ?6.55 (95 % CI ?7.24 to ?5.87). Those patients’ characteristics and exercise were similar (frequency = 3–5 times/week; duration = 20–50 min/day; intensity = 60–80 % of VO₂ peak) on the included studies. Moreover, the risk of bias across all studies was homogeneous (PEDro scale = 7–8 points). However, based on the statistical analysis, the heterogeneity among the studies was still high, which is related to the variable characteristics of the studies. Aerobic exercise may be effective at improving NTproBNP and the VE/VCO₂ slope in systolic HF patients, but these effects are limited to a specific HF population meeting specific inclusion criterion in a limited number of studies. Future randomized controlled studies including diastolic and HF overleap with pulmonary diseases are needed to better understand the exact influence of AEX.     

Prognostic value of brain natriuretic peptide and enhanced ventilatory response to exercise in patients with chronic heart failure

Whether brain natriuretic peptide (BNP), combined with a cardiopulmonary exercise test (CPx) parameters or echocardiography improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is currently unclear. In 156 consecutive stable outpatients with mild to moderate HF and left ventricular ejection fraction (LVEF) <40%, we assessed the impact of BNP assay, Doppler echocardiography and CPx on survival. Median BNP plasma levels were 207 [90–520] pg/mL. Mean LVEF was 33 ± 7%. Left bundle branch block (LBBB) was present in 52 patients (33%) and a restrictive filling pattern in 35 (22%). The slope of the relation between minute ventilation and carbon dioxide production (VE/VCO₂ slope) averaged 35 ± 8; an enhanced ventilatory response (EVR) to exercise (VE/VCO₂ slope >35) was found in 67 patients (43%). During 759 ± 346 days of follow-up, 24 patients died. By multivariate analysis, the strongest independent predictors of all-cause death among clinical, echocardiographic variables and BNP were LBBB and beta-blocker treatment. When CPx variables were added, the best predictors of mortality were LBBB, beta-blockade and VE/VCO₂ slope. This study highlights the value of a sequential approach, based on clinical, laboratory and functional data to identify high-risk HF patients. BNP assay might constitute a simple alternative tool for patients with an inability or with clinical contraindications to exercise, advanced physical deconditioning and unreliable CPx results. However, whenever feasible, CPx with assessment of EVR is recommended for a more accurate prediction of prognosis.     

Ventilation Dispersion Index as an Objective Evaluation Tool of Exercise Oscillatory Ventilation in Patients With Heart Failure

BackgroundExercise oscillatory ventilation (EOV) is related to worse prognosis in patients with heart failure (HF). However, its determination is subjective and there is no standard measure to identify it. The aim of the study was to evaluate and characterize the EOV of patients with HF using the ventilation dispersion index (VDI).Methods and ResultsPatients underwent cardiopulmonary exercise testing (CPX), EOV was assessed by 2 reviewers and the VDI was calculated. The receiver operator curve analysis was used to assess the ability of the VDI to predict EOV. Pearson's correlation test was performed to determine the relationship between VDI and CPX variables. Forty-three patients with HF underwent CPX and were divided into 2 groups: with a VDI of less than 0.601 and a VDI of 0.601 or greater. An area under the curve of 0.759 was observed in the receiver operator curve analysis between VDI and EOV (P = .008). The VDI showed a significant correlation with the ventilatory CPX variables. According to the cut-off point obtained on the receiver operator curve, patients with a VDI of 0.601 or greater had lower left ventricular ejection fraction and higher values of resting minute ventilation and peak minute ventilation.ConclusionsThe VDI proved to be a good predictor of EOV in patients with HF.