Right Ventricular Function and Prognosis in Stable Heart Failure Patients

BackgroundRight ventricular ejection fraction (RVEF) is a mortality predictor in heart failure (HF) patients. There are controversial results regarding the influence of RVEF on other important prognostic variables. The purpose of this study was to investigate the effect of RVEF on exercise parameters obtained during cardiopulmonary exercise testing (CPET), creatinine and B-type natriuretic peptide (BNP) levels, and a composite outcome of death, heart transplantation, or ventricular assist device implantation in ambulatory HF patients.Methods and ResultsThis retrospective cohort study included 246 ambulatory HF patients with CPET and RVEF evaluated with the use of first-pass radionuclide angiography. We analyzed the impact of RVEF on other prognostic factors with the use of multivariable linear regression. The mean age was 49 ± 12 years. The mean peak VO₂ was 16.4 ± 5.7 mL kg⁻¹ min⁻¹, mean peak VE/VCO₂ 34.1 ± 9.1, mean creatinine 1.17 ± 0.40 mg/dL, and median BNP 158 pg/mL (interquartile range 374 pg/mL). The mean left ventricular ejection fraction was 35 ± 12% and the mean RVEF 38 ± 10%. For every 10% decrease in RVEF, peak VO₂ decreased 0.97 mL kg⁻¹ min⁻¹ (P < .05), creatinine increased 0.12 mg/dL (P < .01), and log BNP increased 0.26 (P < .05).ConclusionsWe found an independent association between RVEF and prognostic markers in HF patients. Worsening RV function may exert its negative effect on prognosis through increasing congestion (elevated BNP), affecting renal blood flow (increased creatinine) and limiting left ventricular preload, thereby reducing exercise tolerance.     

Why Levosimendan Improves the Clinical Condition of Patients With Advanced Heart Failure: A Holistic Approach

BackgroundIn advanced heart failure (HF), levosimendan increases peak oxygen uptake (VO₂). We investigated whether peak VO₂ increase is linked to cardiovascular, respiratory, or muscular performance changes.Methods and ResultsTwenty patients hospitalized for advanced HF underwent, before and shortly after levosimendan infusion, 2 different cardiopulmonary exercise tests: (a) a personalized ramp protocol with repeated arterial blood gas analysis and standard spirometry including alveolar–capillary gas diffusion measurements at rest and at peak exercise, and (b) a step incremental workload cardiopulmonary exercise testing with continuous near-infrared spectroscopy analysis and cardiac output assessment by bioelectrical impedance analysis.Levosimendan significantly decreased natriuretic peptides, improved peak VO₂ (11.3 [interquartile range 10.1–12.8] to 12.6 [10.2–14.4] mL/kg/min, P < .01) and decreased minute ventilation to carbon dioxide production relationship slope (47.7 ± 10.7 to 43.4 ± 8.1, P < .01). In parallel, spirometry showed only a minor increase in forced expiratory volume, whereas the peak exercise dead space ventilation was unchanged. However, during exercise, a smaller edema formation was observed after levosimendan infusion, as inferable from the changes in diffusion components, that is, the membrane diffusion and capillary volume. The end-tidal pressure of CO₂ during the isocapnic buffering period increased after levosimendan (from 28 ± 3 mm Hg to 31 ± 2 mm Hg, P < .01). During exercise, cardiac output increased in parallel with VO₂. After levosimendan, the total and oxygenated tissue hemoglobin, but not deoxygenated hemoglobin, increased in all exercise phases.ConclusionsIn advanced HF, levosimendan increases peak VO₂, decreases the formation of exercise-induced lung edema, increases ventilation efficiency owing to a decrease of reflex hyperventilation, and increases cardiac output and muscular oxygen delivery and extraction.     

Enhanced Echo Intensity of Skeletal Muscle Is Associated With Exercise Intolerance in Patients With Heart Failure

BackgroundSkeletal muscle is quantitatively and qualitatively impaired in patients with heart failure (HF), which is closely linked to lowered exercise capacity. Ultrasonography (US) for skeletal muscle has emerged as a useful, noninvasive tool to evaluate muscle quality and quantity. Here we investigated whether muscle quality based on US-derived echo intensity (EI) is associated with exercise capacity in patients with HF.Methods and ResultsFifty-eight patients with HF (61 ± 12 years) and 28 control subjects (58 ± 14 years) were studied. The quadriceps femoris echo intensity (QEI) was significantly higher and the quadriceps femoris muscle thickness (QMT) was significantly lower in the patients with HF than the controls (88.3 ± 13.4 vs 81.1 ± 7.5, P= .010; 5.21 ± 1.10 vs 6.54 ±1.34 cm, P< .001, respectively). By univariate analysis, QEI was significantly correlated with age, peak oxygen uptake (VO₂), and New York Heart Association class in the HF group. A multivariable analysis revealed that the QEI was independently associated with peak VO₂ after adjustment for age, gender, body mass index, and QMT: β-coefficient = −11.80, 95%CI (−20.73, −2.86), P= .011.ConclusionEnhanced EI in skeletal muscle was independently associated with lowered exercise capacity in HF. The measurement of EI is low-cost, easily accessible, and suitable for assessment of HF-related alterations in skeletal muscle quality.     

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.     

Association of muscular fitness with rehospitalization for heart failure with reduced ejection fraction

BackgroundLimited information is available regarding the prognostic potential of muscular fitness parameters in heart failure (HF) with reduced ejection fraction (HFrEF).HypothesisWe aimed to investigate the predictive potential of knee extensor muscle strength and power on rehospitalization and evaluate the correlation between exercise capacity and muscular fitness in patients newly diagnosed with HFrEF.MethodsNinety nine patients hospitalized with a new diagnosis of HF were recruited (64 men; aged 58.7 years [standard deviation (SD), 13.2 years]; 32.3% ischemic; ejection fraction, 28% [SD, 8%]). The inclusion criteria were left ventricular ejection fraction <40% and sufficient clinical stability to undergo exercise testing. Aerobic exercise capacity was measured with cardiopulmonary exercise testing. Knee extensor maximal voluntary isometric contraction (MVIC) and muscle power (MP) were measured using the Baltimore therapeutic equipment system. The clinical outcome was HF rehospitalization.ResultsOver a mean follow‐up period of 1709 ± 502 days, 39 patients were rehospitalized due to HF exacerbation. HF rehospitalization was more probable for patients with diabetes and lower oxygen uptake at peak exercise (peak VO₂), knee extensor MVIC, and MP. The Kaplan–Meier survival analysis revealed significantly different cumulative HF rehospitalization rates according to the tertiles of peak VO₂ (P = 0.005) and MP (P = 0.002). Multivariable Cox proportional hazard model showed that the lowest tertiles of peak VO₂ (hazard ratio (HR), 6.26; 95% confidence interval (CI), 1.93–20.27); and MP (HR, 5.29; 95% CI, 1.05–26.53) were associated with HF rehospitalization. Knee extensor muscle power was an independent predictor for rehospitalization in patients with HFrEF.ConclusionKnee extensor muscle power was an independent predictor for rehospitalization in patients with HFrEF.     

Diastolic Intra–Left Ventricular Pressure Difference During Exercise: Strong Determinant and Predictor of Exercise Capacity in Patients With Heart Failure

Background

Although the enhancement of early-diastolic intra–left ventricular pressure difference (IVPD) during exercise is considered to maintain exercise capacity, little is known about their relationship in heart failure (HF).

Age-Related Maximum Heart Rate Among Ischemic and Nonischemic Heart Failure Patients Receiving β-Blockade Therapy

BackgroundEquations to predict maximum heart rate (HR_max) in heart failure (HF) patients receiving β-adrenergic blocking (BB) agents do not consider the cause of HF. We determined equations to predict HR_max in patients with ischemic and nonischemic HF receiving BB therapy.Methods and ResultsUsing treadmill cardiopulmonary exercise testing, we studied HF patients receiving BB therapy being considered for transplantation from 1999 to 2010. Exclusions were pacemaker and/or implantable defibrillator, left ventricle ejection fraction (LVEF) >50%, peak respiratory exchange ratio (RER) <1.00, and Chagas disease. We used linear regression equations to predict HR_max based on age in ischemic and nonischemic patients. We analyzed 278 patients, aged 47 ± 10 years, with ischemic (n = 75) and nonischemic (n = 203) HF. LVEF was 30.8 ± 9.4% and 28.6 ± 8.2% (P = .04), peak VO₂ 16.9 ± 4.7 and 16.9 ± 5.2 mL kg^?1 min^?1 (P = NS), and the HR_max 130.8 ± 23.3 and 125.3 ± 25.3 beats/min (P = .051) in ischemic and nonischemic patients, respectively. We devised the equation HR_max = 168 ? 0.76 × age (R² = 0.095; P = .007) for ischemic HF patients, but there was no significant relationship between age and HR_max in nonischemic HF patients (R² = 0.006; P = NS).ConclusionsOur study suggests that equations to estimate HR_max should consider the cause of HF.     

A comparison of finger and forehead pulse oximeters in heart failure patients during maximal exercise

BackgroundPulse oximeters, clinically used to measure oxygen saturation (SpO₂), rely on adequate perfusion of the tissues over which they are placed. Heart failure (HF) patients can have impaired peripheral perfusion which may compromise the accuracy of a peripherally placed pulse oximeter. This decrease in peripheral perfusion may be especially apparent during exercise. The objective of this study was to determine if pulse oximeter accuracy is dependent on location in heart failure patients during peak exercise.Methods20 participants with HF (7F, age 64.±11 yr) and 9 participants with coronary artery disease as controls (CAD: 3F, age 66±5 yr) performed a maximal exertion treadmill exercise stress test while wearing both finger and forehead pulse oximeters.ResultsAt peak exercise, the two pulse oximeters measurements of SpO₂ differed from each other by 3.8 ± 3.3% in the HF group (p<0.01) and 2.0 ± 1.4% in the CAD group (p = 0.065). The difference between the pulse rate from the pulse oximeters and the heart rate from the 12-lead ECG in the HF group was 12±20 BPM (p<0.01) for the finger pulse oximeter, and 2 ± 3 BPM (p = 0.162) for the forehead pulse oximeter.ConclusionsForehead pulse oximeters may be more reliable compared to finger pulse oximeters in obtaining SpO₂ measurements in HF patients during a treadmill maximal exercise test.     

Acetazolamide and Inhaled Carbon Dioxide Reduce Periodic Breathing During Exercise in Patients With Chronic Heart Failure

BackgroundPeriodic breathing (PB) during sleep and exercise in heart failure (HF) is related to respiratory acid-base status, CO₂ chemosensitivity, and temporal dynamics of CO₂ and O₂ sensing. We studied inhaled CO₂ and acetazolamide to alter these factors and reduce PB.Methods and ResultsWe measured expired and arterial gases and PB amplitude and duration in 20 HF patients during exercise before and after acetazolamide given acutely (500 mg intravenously) and prolonged (24 hours, 2 g orally), and we performed overnight polysomnography. We studied CO₂ inhalation (1%–2%) during constant workload exercise. PB disappeared in 19/20 and 2/7 patients during 2% and 1% CO₂. No changes in cardiorespiratory parameters were observed after acute acetazolamide. With prolonged acetazolamide at rest: ventilation +2.04 ± 4.0 L/min (P = .001), tidal volume +0.11 ± 1.13 L (P = .003), respiratory rate +1.24 ± 4.63 breaths/min (NS), end-tidal PO₂ +4.62 ± 2.43 mm Hg (P = .001), and end-tidal PCO₂ −2.59 ± 9.7 mm Hg (P < .001). At maximum exercise: Watts −10% (P < .02), VO₂ −61 ± 109 mL/min (P = .04) and VCO₂ 101 ± 151 mL/min (P < .02). Among 20 patients, PB disappeared in 1 and 7 subjects after acute and prolonged acetazolamide, respectively. PB was present 80% ± 26, 65% ± 28, and 43% ± 39 of exercise time before and after acute and prolonged acetazolamide, respectively. Overnight apnea/hypopnea index decreased from 30.8 ± 83.8 to 21.1 ± 16.9 (P = .003).ConclusionsIn HF, inhaled CO₂ and acetazolamide reduce exercise PB with additional benefits of acetazolamide on sleep PB.     

Wearable Patch-Based Estimation of Oxygen Uptake and Assessment of Clinical Status during Cardiopulmonary Exercise Testing in Patients With Heart Failure

BackgroundTo estimate oxygen uptake (VO₂) from cardiopulmonary exercise testing (CPX) using simultaneously recorded seismocardiogram (SCG) and electrocardiogram (ECG) signals captured with a small wearable patch. CPX is an important risk stratification tool for patients with heart failure (HF) owing to the prognostic value of the features derived from the gas exchange variables such as VO₂. However, CPX requires specialized equipment, as well as trained professionals to conduct the study.Methods and ResultsWe have conducted a total of 68 CPX tests on 59 patients with HF with reduced ejection fraction (31% women, mean age 55 ± 13 years, ejection fraction 0.27 ± 0.11, 79% stage C). The patients were fitted with a wearable sensing patch and underwent treadmill CPX. We divided the dataset into a training–testing set (n = 44) and a separate validation set (n = 24). We developed globalized (population) regression models to estimate VO₂ from the SCG and ECG signals measured continuously with the patch. We further classified the patients as stage D or C using the SCG and ECG features to assess the ability to detect clinical state from the wearable patch measurements alone. We developed the regression and classification model with cross-validation on the training–testing set and validated the models on the validation set. The regression model to estimate VO₂ from the wearable features yielded a moderate correlation (R² of 0.64) with a root mean square error of 2.51 ± 1.12 mL · kg^–1 · min^–1 on the training–testing set, whereas R² and root mean square error on the validation set were 0.76 and 2.28 ± 0.93 mL · kg^–1 · min^–1, respectively. Furthermore, the classification of clinical state yielded accuracy, sensitivity, specificity, and an area under the receiver operating characteristic curve values of 0.84, 0.91, 0.64, and 0.74, respectively, for the training–testing set, and 0.83, 0.86, 0.67, and 0.92, respectively, for the validation set.ConclusionsWearable SCG and ECG can assess CPX VO₂ and thereby classify clinical status for patients with HF. These methods may provide value in the risk stratification of patients with HF by tracking cardiopulmonary parameters and clinical status outside of specialized settings, potentially allowing for more frequent assessments to be performed during longitudinal monitoring and treatment.     

Left Atrial Stiffness Index Independently Predicts Exercise Intolerance and Quality of Life in Older,Obese Patients With Heart Failure With Preserved Ejection Fraction

BackgroundHeart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life. Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO₂), physical function (distance walked in 6 minutes [6MWD]) and quality of life (Kansas City Cardiomyopathy Questionnaire).Methods and ResultsWe compared 75 older, obese, patients with HFpEF with 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its 3 distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. The LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’, by Doppler ultrasound examination) and LA reservoir strain. HFpEF had a decreased reservoir strain (16.4 ± 4.4% vs 18.2 ± 3.5%, P = .018), lower conduit strain (7.7 ± 3.3% vs 9.1 ± 3.4%, P = .028), and increased stiffness index (0.86 ± 0.39 vs 0.53 ± 0.18, P < .001), as well as decreased peak VO₂, 6MWD, and lower quality of life. Increased LA stiffness was independently associated with impaired peak VO₂ (β = 9.0 ± 1.6, P < .001), 6MWD (β = 117 ± 22, P = .003), and Kansas City Cardiomyopathy Questionnaire score (β = –23 ± 5, P = .001), even after adjusting for clinical covariates.Conclusions: LA stiffness is independently associated with impaired exercise tolerance and quality of life and may be an important therapeutic target in obese HFpEF.RegistrationNCT00959660     

The relationship between resting lung-to-lung circulation time and peak exercise capacity in chronic heart failure patients

BackgroundPeak exercise capacity (VO_2peak) is a measure of the severity of chronic heart failure (CHF); however, few indices of resting cardiopulmonary function have been shown to predict VO_2peak. A prolonged circulation time has been suggested as an index of increased severity of CHF. The aim of this study was to investigate the relationship between resting lung-to-lung circulation time (LLCT) and VO_2peak in CHF.Methods and ResultsThirty CHF patients (59 ± 13 years, New York Heart Association: 1.9 ± 1.0) undertook the study. Each subject completed resting pulmonary and echocardiography measures and an incremental exercise test. LLCT was measured using the reappearance of end-tidal acetylene (P_ET,C₂H₂) after a single inhalation. Univariate and multivariate stepwise linear regression was used to determine the predictors of VO_2peak. Univariate correlates of VO_2peak (group mean 1.53 ± 0.44 L/min⁻¹) included LLCT (r = −0.75), inspiratory capacity (r = 0.41), ejection fraction (r = 0.33), peak early flow velocity (r = −0.39), and the ratio of early to late flow velocity (r = −0.31). LLCT was the only independent predictor where VO_2peak = 3.923–0.045 (LLCT); r² = 54%.ConclusionsThese results suggest that resting LLCT determined using the soluble inert gas technique represents a simple, noninvasive method that provides additional information regarding exercise capacity in CHF.     

Effects of gender on peak oxygen consumption and the timing of cardiac transplantation.

OBJECTIVES: This study examines the gender effects on peak exercise oxygen consumption (VO2) and survival in heart failure (HF) patients and their implications for cardiac transplantation. BACKGROUND: The predictive value of peak VO2 in women HF patients is poorly established but is one of the indicators used to optimally time cardiac transplantation in women. METHODS: A total of 594 ambulatory HF patients (mean age 52 +/- 12 years, 28% women, mean left ventricular ejection fraction 26 +/- 12%, 73% on beta-blocker) underwent symptom-limited exercise tests with breath-by-breath expired gas analyses using ramped treadmill protocols. Kaplan-Meier survival curves were generated for each gender and compared using log-rank tests. RESULTS: Women had a significantly lower peak VO2 than men (14.0 +/- 4.9 ml/kg/min vs. 16.6 +/- 7.1 ml/kg/min; p < 0.0001), despite being younger (48.9 +/- 11.5 years vs. 53.2 +/- 12.4 years; p < 0.0001) and having a higher left ventricular ejection fraction (29 +/- 13% vs. 25 +/- 11%; p < 0.0003). However, the one-year transplant-free survival was significantly lower for men than for women (81% vs. 94%, p < 0.0001), a finding seen across each Weber class. Cox regression analyses confirmed the protective effects of female gender on transplant-free survival when controlling for peak VO2, age, race, beta-blocker use, and type of cardiomyopathy. The peak VO2 associated with 85% one-year transplant-free survival was significantly higher in men than in women (11.5 vs. 10.0 ml/kg/min). CONCLUSIONS: Women had a significantly lower peak Vo(2) than men, but had better survival at all levels of exercise capacity. The current practice of uniform application of peak VO2 as an aid to determine cardiac transplantation timing should be re-examined.     

Caffeine prolongs exercise duration in heart failure

BackgroundCaffeine increases submaximal exercise performance in healthy young subjects; its effects on exercise tolerance in heart failure (HF) have not been characterized.Methods and ResultsTo determine whether caffeine increases exercise tolerance in HF, caffeine (4 mg/kg intravenously, equivalent to 2 cups of coffee) or vehicle were infused into 10 treated HF patients (left ventricular ejection fraction 25 ± 2 %), and 10 age-matched normal subjects (N) on 2 separate days in a double-blind, randomized, crossover design. We measured heart rate, blood pressure, and ventilation at rest and during graded cycling (15 W/minute) to peak effort. Peak oxygen consumption was unaffected in either group. Mean exercise time was unchanged in N (1013 ± 87 versus 988 ± 107 seconds; P = .86) but was significantly increased by caffeine in HF (from 511 ± 28 to 560 ± 37 seconds; P = .004) despite an increase in peak minute ventilation (P < .05). Resting and peak blood pressures were higher after caffeine (P < .05) in HF, not N.ConclusionCaffeine allows HF patients to exercise longer at peak effort.     

B-type natriuretic peptide kinetics and cardiopulmonary exercise testing in heart failure

BackgroundIn patients with chronic heart failure (CHF), B-type natriuretic peptide (BNP) is related to peak oxygen consumption (peak VO₂) and the relationship between minute ventilation and carbon dioxide production (VE/VCO₂ slope). However, the exercise response depends on the mode of exercise. This study sought to compare peak treadmill and bicycle exercise responses with respect to their relationship with BNP and to assess whether BNP measured at rest or during exercise could identify patients with greater functional impairment and ventilatory inefficiency.MethodsTwenty-three patients with mild-to-moderate stable systolic CHF (age 72 ± 8 years, left ventricular ejection fraction 32 ± 7%) underwent treadmill and bicycle cardiopulmonary exercise testing within 5 (interquartile range 3–7) days. BNP was measured at rest and at peak exercise.ResultsBNP at rest was an independent multivariate predictor of both peak VO₂ and the VE/VCO₂ slope for both exercise modes. However, the proportion of variance explained univariately and multivariately was ≤ 0.55, indicating that BNP did not strongly explain the variation of peak VO₂ and the VE/VCO₂ slope. The exercise-induced rise in circulating BNP did not differ between the test modes [treadmill: 50 (24–89) pg/ml vs. bicycle: 46 (15–100) pg/ml; p = 0.73]. BNP levels at peak exercise were strongly related to resting values, but did not provide additional information on peak VO₂ or the VE/VCO₂ slope.ConclusionsIn typical CHF patients, BNP measured at rest or at peak exercise does not strongly predict peak VO₂ or the VE/VCO₂ slope regardless of the exercise mode, and is therefore not a sufficiently accurate surrogate for cardiopulmonary exercise testing.     

Circuit resistance training in chronic heart failure improves skeletal muscle mitochondrial ATP production rate--a randomized controlled trial

BackgroundWe aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF).Methods and ResultsThirteen CHF patients (New York Heart Association functional class 2.3 ± 0.5; Left ventricular ejection fraction 26 ± 8%; age 70 ± 8 years) underwent testing for peak total body oxygen consumption (VO_2peak), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO_2peak and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO_2peak, P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO_2peak) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO_2peak.ConclusionsThese findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.     

Association of functional and health status measures in heart failure

BackgroundA wide variety of instruments have been used to assess the functional capabilities and health status of patients with chronic heart failure (HF), but it is not known how well these tests are correlated with one another, nor which one has the best association with measured exercise capacity.Methods and ResultsForty-one patients with HF were assessed with commonly used functional, health status, and quality of life measures, including maximal cardiopulmonary exercise testing, the Duke Activity Status Index (DASI), the Veterans Specific Activity Questionnaire (VSAQ), the Kansas City Cardiomyopathy Questionnaire (KCCQ), and 6-minute walk distance. Pretest clinical variables, including age, resting pulmonary function tests (forced expiratory volume in 1 s and forced vital capacity), and ejection fraction (EF) were also considered. The association between performance on these functional tools, clinical variables, and exercise test responses including peak VO₂ and the VO₂ at the ventilatory threshold, was determined. Peak oxygen uptake (VO₂) was significantly related to VO₂ at the ventilatory threshold (r = 0.76, P < .001) and estimated METs from treadmill speed and grade (r = 0.72, P < .001), but had only a modest association with 6-minute walk performance (r = 0.49, P < .01). The functional questionnaires had modest associations with peak VO₂ (r = 0.37, P < .05 and r = 0.26, NS for the VSAQ and DASI, respectively). Of the components of the KCCQ, peak VO₂ was significantly related only to quality of life score (r = 0.46, P < .05). Six-minute walk performance was significantly related to KCCQ physical limitation (r = 0.53, P < .01) and clinical summary (r = 0.44, P < .05) scores. Among pretest variables, only age and EF were significantly related to peak VO₂ (r = −0.58, and 0.46, respectively, P < .01). Multivariately, age and KCCQ quality of life score were the only significant predictors of peak VO₂, accounting for 72% of the variance in peak VO₂.ConclusionCommonly used functional measures, symptom tools, and quality of life assessments for patients with HF are poorly correlated with one another and are only modestly associated with exercise test responses. These findings suggest that exercise test responses, non-exercise test estimates of physical function, and quality of life indices reflect different facets of health status in HF and one should not be considered a surrogate for another.     

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.     

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.     

Chronotropic competence in endurance trained heart transplant recipients: heart rate is not a limiting factor for exercise capacity

Objectives. The purpose of this study was to show that the chronotropic potential of the well trained heart transplant recipient (HTR) does not limit exercise capacity.Background. Chronotropic incompetence is considered to be the main limiting factor of the functional capacity of heart transplant recipients. However, no systematic study had been published on patients who had spontaneously undergone heavy endurance training for several years.Methods. Heart rate (HR) and respiratory gas exchanges (VO₂, VCO₂, VE) were measured in 14 trained HTRs (T-HTRs) during exercise tests on a bicycle, on a treadmill and by Holter electrocardiography during a race.Results. Peak values observed in T-HTRs during the treadmill test were higher than those reached during the bicycle test (VO_2peak:39.8 ± 6.9 vs. 32.5 ± 7.8 ml·kg⁻¹·min⁻¹, p < 0.001; HR_peak: 169 ± 14 vs. 159 ± 16 bpm, p < 0.01). During treadmill exercise VO_2peakand HR_peakvalues observed were very close to the mean predicted VO_2pmaxand HR_pmax. The maximum heart rate during the race (HR_race) was greater than HR_peakvalues during the treadmill test (179 ± 14 vs 169 ± 14 bpm, p < 0.01) and slightly above the mean predicted values (HR_race/HR_pmax× 100 = 101 ± 10%). The treadmill exercise test yields more reliable data than does the bicycle test.Conclusions. Extensive endurance training enables heart transplant recipients to reach physical fitness levels similar to those of normal sedentary subjects; heart rate does not limit their exercise capacity.