Although cardiopulmonary exercise testing (CPET) parameters have known prognostic value in adults after Fontan palliation, there are limited data correlating treadmill CPET with invasive exercise hemodynamics. Furthermore, the invasive hemodynamic underpinnings of exercise limitations have not been thoroughly investigated. This is a retrospective analysis of 55 adults (age ≥18 years) with prior Fontan palliation who underwent treadmill CPET before invasive exercise hemodynamic testing using a supine cycle protocol between November 2018 and April 2023. The median age was 32.2 (IQR 24.1; 37.2) years. The peak heart rate (HR) was 139.7 ± 28.1 beats per minute and the peak oxygen consumption (VO2) was 19.1 ± 5.7 ml/kg/min (47.4 ± 13.5% predicted). VO2/HR was directly related to exercise stroke volume index (r = 0.50, p = 0.0002), whereas no association was seen with exercise arterio-mixed venous O2 content difference (r = 0.14, p = 0.32). Peak HR was inversely related to exercise pulmonary artery (PA) pressures (r = -0.61, p <0.0001) and PA wedge pressures (PAWP) (r = -0.61, p <0.0001). Moreover, %predicted VO2 was inversely related to exercise PA pressures (r = -0.50, p <0.0001) and PAWP (r = -0.55, p <0.0001). Peak VO2 ≤19.1 ml/kg/min had a sensitivity of 81% and a specificity of 76% (area under the curve 0.82) for predicting a ΔPAWP/ΔQs ratio >2 mmHg/L/min and/or a ΔPA/ΔQp >3 mmHg/L/min, whereas a predicted peak VO2 ≤48% had a sensitivity of 74% and a specificity of 81% (area under the curve 0.79) for the same parameters. In summary, lower peak HR and peak VO2 were associated with higher exercise PAWP and PA pressure. Peak VO2 ≤48% predicted provided the optimal cutoff for predicting increased indexed exercise PAWP or PA pressures; therefore, low peak VO2 should alert clinicians of abnormal underlying hemodynamics.

A high minute ventilation/rate of carbon dioxide production (V̇E/V̇co2) slope during exercise is prognostic for cardiovascular death. Recent data indicate that adults with either controlled or untreated primary hypertension, but not those with uncontrolled hypertension, exhibit a higher V̇E/V̇co2 slope during exercise. However, the sample sizes were modest. Therefore, we used the Fitness Registry and the Importance of Exercise National Database to determine whether adults with hypertension, particularly those with controlled or untreated hypertension, exhibit higher V̇E/V̇co2 slopes compared with adults without hypertension.

Using the Fitness Registry and the Importance of Exercise National Database, we isolated primary hypertension by excluding those with any disease other than hypertension or taking any medications other than antihypertension medications. We also excluded current smokers and those with obesity. The V̇E/V̇co2 slope was determined during a peak cycling exercise test. All data are presented as median [interquartile range]. We compared groups using linear regression adjusted for age, male/female, and body mass index. The characteristics of the entire sample (n=4109) were age, 42 [18] years; 48% women; body mass index, 26 [4] kg/m2. The V̇E/V̇co2 slope did not differ between adults with hypertension (n=1940; 24.7 [3.7]) compared with those without hypertension (n=2169; 24.9 [3.8]) (hypertension versus no hypertension, P=0.31; overall model: R2=0.07, F4,4104=73.0; P<0.001). Further, the V̇E/V̇co2 slope did not differ between adults with medication-controlled hypertension (n=107; 24.4 [3.0]), untreated hypertension (n=1626; 24.8 [3.9]), uncontrolled hypertension (n=207; 24.8 [3.0]), or those without hypertension (n=2169; 24.9 [3.8]) (hypertension subgroup versus no hypertension, P≥0.06; overall model: R2=0.07, F6,4102=49.6, P<0.001).

Primary hypertension is not associated with V̇E/V̇co2 slope in the Fitness Registry and the Importance of Exercise National Database.

This study aimed to highlight the ventilatory and circulatory determinants of changes in ˙VO2peak after exercise-based cardiac rehabilitation (ECR) in patients with coronary heart disease (CHD). Eighty-two CHD patients performed, before and after a 3-month ECR, a cardiopulmonary exercise testing (CPET) on a bike with gas exchanges measurements (˙VO2peak, minute ventilation, i. e., ˙VE), and cardiac output (Q˙c). The arteriovenous difference in O2 (C(a-v¯)O2) and the alveolar capillary gradient in O2 (PAi-aO2) were calculated using Fick's laws. Oxygen uptake efficiency slope (OUES) was calculated. A 5.0% cut off was applied for differentiating non- (NR: ˙VO2<0.0%), low (LR: 0.0≤ ∆˙VO2<5.0%), moderate (MR: 5.0≤∆˙VO2 < 10.0%), and high responders (HR: ∆˙VO2≥10.0%) to ECR. A total of 44% of patients were HR (n=36), 20% MR (n=16), 23% LR (n=19), and 13% NR (n=11). For HR, the ˙VO2peak increase (p<0.01) was associated with increases in ˙VE (+12.8±13.0 L/min, p<0.01), (+1.0±0.9 L/min, p<0.01), and C(a-v¯)O2 (+2.3±2.5 mLO2/100 mL, p<0.01). MR patients were characterized by+6.7±19.7 L/min increase in ˙VE (p=0.04) and+0.7±1.0 L/min of Q˙c (p<0.01). ECR induced decreases in ˙VE (p=0.04) and C(a-v¯)O2 (p<0.01) and a Q˙c increase in LR and NR patients (p<0.01). Peripheral and ventilatory responses more than central adaptations could be responsible for the ˙VO2peak change with ECR in CHD patients.

Background An elevated ventilatory efficiency slope during exercise (minute ventilation/volume of expired CO2; VE/VCO2 slope) is a strong prognostic indicator in heart failure. It is elevated in people with heart failure with preserved ejection, many of whom have hypertension. However, whether the VE/VCO2 slope is also elevated in people with primary hypertension versus normotensive individuals is unknown. We hypothesize that there is a spectrum of ventilatory inefficiency in cardiovascular disease, reflecting an increasingly abnormal physiological response to exercise. The aim of this study was to evaluate the VE/VCO2 slope in patients with hypertension compared with age-, peak oxygen consumption-, and sex-matched healthy subjects. Methods and Results Ramped cardiovascular pulmonary exercise tests to peak oxygen consumption were completed on a bike ergometer in 55 patients with primary hypertension and 24 normotensive controls. The VE/VCO2 slope was assessed from the onset of exercise to peak oxygen consumption. Data were compared using unpaired Student t test. Age (mean±SD, 66±6 versus 64±6 years; P=0.18), body mass index (25.4±3.5 versus 24±2.4 kg/m2; P=0.13), and peak oxygen consumption (23.2±6.6 versus 24±7.3 mL/min per kg; P=0.64) were similar between groups. The VE/VCO2 slope was elevated in the hypertensive group versus controls (31.8±4.5 versus 28.4±3.4; P=0.002). Only 27% of the hypertensive group were classified as having a normal VE/VCO2 slope (20-30) versus 71% in the control group. Conclusions Ventilatory efficiency is impaired people with hypertension without a diagnosis of heart failure versus normotensive individuals. Future research needs to establish whether those patients with hypertension with elevated VE/VCO2 slopes are at risk of developing future heart failure.

Heart failure with preserved ejection fraction (HFpEF) is associated with cardiopulmonary abnormalities that may increase physiological dead space to tidal volume (VD/VT) during exercise. However, studies have not corrected VD/VT for apparatus mechanical dead space (VDM), which may confound the accurate calculation of VD/VT. We evaluated whether calculating physiological dead space with (VD/VT_VDM) and without (VD/VT) correcting for VDM impacts the interpretation of gas exchange efficiency during exercise in HFpEF. Fifteen HFpEF (age: 69 ± 6 yr; V̇o_2peak: 1.34 ± 0.45 L/min) and 12 controls (70 ± 3 yr; V̇o_2peak: 1.70 ± 0.51 L/min) were studied. Pulmonary gas exchange and arterial blood gases were analyzed at rest, submaximal (20 W for HFpEF and 40 W for controls), and peak exercise. VD/VT was calculated as [Formula: see text] - [Formula: see text]/[Formula: see text]. VD/VT_VDM was calculated as [Formula: see text] - [Formula: see text]/[Formula: see text] - VDM/VT. VD/VT decreased from rest (HFpEF: 0.54 ± 0.07; controls: 0.32 ± 0.07) to submaximal exercise (HFpEF: 0.46 ± 0.07; controls: 0.25 ± 0.06) in both groups (P < 0.05), but remained stable (P > 0.05) thereafter to peak exercise (HFpEF: 0.46 ± 0.09; controls: 0.22 ± 0.05). In HFpEF, VD/VT_VDM did not change (P = 0.58) from rest (0.29 ± 0.07) to submaximal exercise (0.29 ± 0.06), but increased (P = 0.02) thereafter to peak exercise (0.33 ± 0.06). In controls, VD/VT_VDM remained stable such that no change was observed (P > 0.05) from rest (0.17 ± 0.06) to submaximal exercise (0.14 ± 0.06), or thereafter to peak exercise (0.14 ± 0.05). Calculating physiological dead space with and without a VDM correction yields quantitively and qualitatively different results, which could have impact on the interpretation of gas exchange efficiency in HFpEF. Further investigation is required to uncover the clinical consequences and the mechanism(s) explaining the increase in VD/VT_VDM during exercise in HFpEF.NEW & NOTEWORTHY Calculating VD/VT with and without correcting for VDM yields quantitively and qualitatively different results, which could have an important impact on the interpretation of V/Q mismatch in HFpEF. The finding that V/Q mismatch and gas exchange efficiency worsened, as reflected by an increase in VD/VT_VDM during exercise, has not been previously demonstrated in HFpEF. Thus, further studies are needed to investigate the mechanisms explaining the increase in VD/VT_VDM during exercise in patients with HFpEF.

Cardiopulmonary exercise testing (CPX) is the gold standard approach for the assessment of cardiorespiratory fitness (CRF). The primary aim of the current study was to determine reference standards for the minute ventilation/carbon dioxide production (V˙E/V˙co2) slope in a cohort from the "Fitness Registry and the Importance of Exercise: A National Database" (FRIEND) Registry.

The current analysis included 2512 tests from 10 CPX laboratories in the United States. Inclusion criteria included CPX data on apparently healthy men and women: (1) age ≥20 yr; and (2) with a symptom-limited exercise test performed on a treadmill. Ventilation and V˙co2 data, from the initiation of exercise to peak, were used to calculate the V˙E/V˙co2 slope via least-squares linear regression. Reference values were determined for men and women by decade of life.

On average, V˙E/V˙co2 slope values were lower in men and increased with age independent of sex. Fiftieth percentile values increased from 27.1 in the second decade to 33.9 in the eighth decade in men and from 28.5 in the second decade to 33.7 in the eighth decade in women. In the overall group, correlations with baseline characteristics and the V˙E/V˙co2 slope were statistically significant (P < .05) although generally weak, particularly for age and body mass index.

The results of the current study establish reference values for the V˙E/V˙co2 slope when treadmill testing is performed, and all exercise data are used for the slope calculation. These results may prove useful in enhancing the interpretation of CPX results when assessing CRF.

Patients with cardiovascular diseases frequently experience exertional dyspnea. However, the relationship between respiratory muscle strength including its fatigue and cardiovascular dysfunctions remains to be clarified.The maximal inspiratory pressure/maximal expiratory pressure (MIP/MEP) before and after cardiopulmonary exercise testing (CPX) in 44 patients with heart failure and ischemic heart disease were measured. Respiratory muscle fatigue was evaluated by calculating MIP (MIPpost/MIPpre) and MEP (MEPpost/MEPpre) changes.The mean MIPpre and MEPpre values were 67.5 ± 29.0 and 61.6 ± 23.8 cm H2O, respectively. After CPX, MIP decreased in 25 patients, and MEP decreased in 22 patients. We evaluated the correlation relationship between respiratory muscle function including respiratory muscle fatigue and exercise capacity evaluated by CPX such as peak VO2 and VE/VCO2 slope. Among MIP, MEP, change in MIP, and change in MEP, only the value of change in MIP had an association with the value of VE/VCO2 slope (R = -0.36, P = .017). In addition, multivariate analysis for determining factor of change in MIP revealed that the association between the change in MIP and eGFR was independent from other confounding parameters (beta, 0.40, P = .017). The patients were divided into 2 groups, with (MIP change < 0.9) and without respiratory muscle fatigue (MIP change > 0.9), and a significant difference in peak VO2 (14.2 ± 3.4 [with fatigue] vs 17.4 ± 4.7 [without fatigue] mL/kg/min; P = .020) was observed between the groups.Respiratory muscle fatigue demonstrated by the change of MIP before and after CPX significantly correlated with exercise capacity and renal function in patients with cardiovascular disease.

Autonomic dysfunction (AD) and dynamic hyperinflation (DH) have been implicated as pathophysiological mechanisms of heart failure with preserved ejection fraction (HFpEF) in chronic obstructive pulmonary disease (COPD) patients. Their association, however, remains elusive: The aims of the study were: (1) to determine the prevalence of AD and DH in non-severe COPD patients, with exertional dyspnea, without clinically overt cardio-vascular (CV) comorbidities; (2) to analyze the correlation and clinical significance between DH, AD, and maksed HFpEF.

We applied CPET in 68 subjects. Echocardiography was performed before CPET and 1-2 min after peak exercise. IC manoeuvres were applied. Patients were divided into two groups: patients with and without masked HFpEF. Wilkoff method calculated the meatabolic - chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined.

The prevalence of CI was 77 vs. 52% in patients with/without masked HFpEF; of abnormal HRR - 98 vs. 62% respectively; of DH - 53 vs. 29%. ICdyn was associated with AD. Univariate regression showed association between masked HFpEF, ICdyn, HRR, oxygenuptake ('VO₂), 'VO₂ at anaerobic threshold, oxygen (O₂) pulse and 'VE/'VCO₂ slope. None of these parameters is an independent predictor for masked HFpEF.

DH, AD, and masked HFpEF are prevalent in non-severe COPD patients, who complain of exertional dyspnea and are free of clinically overt CV comorbidities. DH is independently associated with AD. Neither AD, nor DH and CPET are independent predictors for masked HFpEF.

Background: Ventilatory inefficiency during exercise assessed using the lowest minute ventilation/carbon dioxide production (V̇E/V̇CO₂) ratio was recently proven to be a strong prognostic marker of heart failure (HF) regardless of left ventricular ejection fraction (LVEF). Its physiological background, however, has not been elucidated. Methods and Results: Fifty-seven HF patients underwent cardiopulmonary exercise testing and exercise-stress echocardiography. The lowest V̇E/V̇CO₂ ratio was assessed on respiratory gas analysis. Echocardiography was obtained at rest and at peak exercise. LVEF was measured using the method of disks. Cardiac output (CO) and the ratio of transmitral early filling velocity (E) to early diastolic tissue velocity (e') were calculated using the Doppler method. HF patients were divided into preserved EF (HFpEF) and reduced EF (HFrEF) using the LVEF cut-off 40% at rest. Twenty-four patients were classified as HFpEF and 33 as HFrEF. In HFpEF, age (r=0.58), CO (r=-0.44), e' (r=-0.48) and E/e' (r=0.45) during exercise correlated with the lowest V̇E/V̇CO₂ ratio (P<0.05 for all). In contrast, in HFrEF, age (r=0.47) and CO (r=-0.54) during exercise, but not e' and E/e', correlated with the lowest V̇E/V̇CO₂ ratio. Conclusions: Loss of CO augmentation was associated with ventilatory inefficiency in HF regardless of LVEF, although lung congestion determined ventilatory efficiency only in HFpEF.

Autonomic dysfunction (AD) and cardiopulmonary exercise testing (CPET) parameters have been associated with masked heart failure with preserved ejection fraction (HFpEF) in the general population. Their clinical significance for masked HFpEF in chronic obstructive pulmonary disease (COPD) is however elusive.

The aim of the study was to determine the prevalence, correlation and clinical significance of AD and CPET with masked HFpEF, in non-severe COPD patients, complaining of exertional dyspnoea, without clinically overt cardio-vascular (CV) comorbidities.

We applied CPET and echocardiography in 68 COPD subjects. Echocardiography was performed before CPET and 1-2 min after peak exercise. Patients were divided into two groups: patients with and without masked HFpEF. Peak E/e' - 15 was applied as a cut-off. Chronotropic incompetence (CI) was assumed if both failure to reach the target heart rate (HR) on exercise and diminished heart rate reserve <80% occurred. Abnormal HR recovery (HRR) was taken if the decline is <12 beats within the first minute after exercise cessation. Univariate regression showed association between masked HFpEF, HRR, VO2, VO2 at AT, oxygen pulse and VE/VCO2 slope. The multivariate regression demonstrated HRR as the only independent predictor of masked HFpEF - (OR 10.28; 95% CI (3.55-29.80)).

Abnormal HRR is the only independent predictor of masked HFpEF in non-severe COPD patients. Despite of being associated with masked HFpEF, the lower VO2, lower oxygen pulse, higher VE/VCO2 slope and lower exercise load seem to be the consequences, rather than the triggers for it.

The heart and lungs are intimately linked. Hence, impaired function of one organ may lead to changes in the other. Accordingly, heart failure is associated with airway obstruction, loss of lung volume, impaired gas exchange, and abnormal ventilatory control. Cardiopulmonary exercise testing is an excellent tool for evaluation of gas exchange and ventilatory control. Indeed, many parameters routinely measured during cardiopulmonary exercise testing, including the level of minute ventilation per unit of carbon dioxide production and the presence of exercise oscillatory ventilation, have been found to be strongly associated with prognosis in patients with heart failure.

Exercise ventilation efficiency index in cardiopulmonary exercise testing (CPET) is elevated in patients with heart failure providing useful information on disease progression and prognosis. Few data, however, exist for ventilation efficiency index among cystic fibrosis (CF) patients.

To assess ventilation efficiency index (ΔVE/ΔVCO₂ or V'E/V'CO₂ slope) and intercept of ventilation (VE-intercept) in CF patients with mild, moderate, and severe cystic fibrosis (CF) lung disease. To assess possible correlations with ventilation inhomogeneity and structural damages as seen on high resolution computed tomography (HRCT).

CF patients with mild (FEV₁  > 80%, n = 47), moderate (60% < FEV₁  < 80%, n = 21), and severe (FEV₁  < 60%, n = 9) lung disease, mean age 14.9 years participated. Peak oxygen uptake (VO₂ peak), pulmonary ventilation at peak exercise (VE), respiratory equivalent ratios for oxygen and carbon dioxide at peak exercise (VE/VO₂ , VE/VCO₂ ), end-tidal CO₂ (PetCO₂ ), and ΔVE/ΔVCO₂ , ΔVE/ΔVO₂ in a maximal CPET along with spirometry and multiple breath washout indices were examined. HRCT scans were performed and scored using Bhalla score.

Mean ΔVE/ΔVCO₂ showed no significant differences among the three groups (P = .503). Mean VE_int discriminated significantly among the different groups (p ² < 0.001). Ventilation efficiency index did not correlate either with LCI or Bhalla score. However, VE together with ΔVE/ΔVCO₂ slope could predict Bhalla score (r ²  = 0.869, P = .006).

No significant differences were found regarding ΔVE/ΔVCO₂ slope levels between the three groups. Ventilation intercept (VE_int ) was elevated significantly as disease progresses reflecting increased dead space ventilation. CF patients retain their ventilation efficiency to exercise even as lung function deteriorates by adopting a higher respiratory rate along with increased dead space ventilation.

Respiratory muscle weakness causes fatigue in these muscles during exercise and thereby increases dead-space ventilation ratio with decreased tidal volume. However, it remains unclear whether respiratory muscle weakness aggravates ventilation-perfusion mismatch through the increased dead-space ventilation ratio. In ventilation-perfusion mismatch during exercise, minute ventilation versus carbon dioxide production (VE/VCO₂ ) slope > 34 is an indicator of poor prognosis in patients with chronic heart failure (CHF). We examined the relationship of respiratory muscle weakness with dead-space ventilation ratio and ventilation-perfusion mismatch during exercise and clarified whether respiratory muscle weakness was a clinical predictor of VE/VCO₂ slope > 34 in patients with CHF.

Maximal inspiratory pressure (PI_max ) was measured as respiratory muscle strength 2 months after hospital discharge in 256 compensated patients with CHF. During cardiopulmonary exercise test, we assessed minute dead-space ventilation versus VE (VD/VE ratio) as dead-space ventilation ratio and VE/VCO₂ slope as ventilation-perfusion mismatch. Patients were divided into low, moderate and high PI_max groups based on the PI_max tertile. We investigated determinants of VE/VCO₂ slope > 34 among these groups.

The low PI_max group showed significantly higher VD/VE ratios at 50% of peak workload and at peak workload and higher VE/VCO₂ slope than the other two groups (P < 0.001, respectively). PI_max was a significant independent determinant of VE/VCO₂ slope > 34 (odds ratio (OR): 0.67, 95% CI: 0.54-0.82) with area under the receiver operating characteristic curve of 0.812 (95% CI: 0.750-0.874).

Respiratory muscle weakness was associated with an increased dead-space ventilation ratio aggravating ventilation-perfusion mismatch during exercise in patients with CHF.

Wave intensity (WI) is a novel noninvasive index of circulatory dynamics that reflects ventriculo-arterial coupling. It is calculated as the product of the first derivative of blood pressure and that of flow velocity measured by carotid echocardiography. This study aimed to clarify the clinical implications of WI and its relation with carbon dioxide production (VE/VCO₂ slope). Twenty-one healthy volunteers (control group) and 21 patients with hypertension (HT group) underwent cardiopulmonary exercise testing (CPX) and exercise stress echocardiography. WI was assessed in the right carotid artery using an ultrasound system. The first peak of WI (W₁) during the early ejection phase was measured at baseline and mitral annular velocity was assessed by tissue Doppler imaging. Ventilatory kinetics during exercise was assessed using the relation of minute ventilation to VE/VCO₂ slope. VE/VCO₂ slope, W₁, and E/E' were greater in the HT group than in the control group. PeakVO₂ and VO₂ at the anaerobic threshold were lower in the HT group than in the control group. VE/VCO₂ slope was significantly correlated with W₁ (r = 0.58, p < 0.01) and E/E' (r = 0.44, p < 0.01). Stepwise multivariate analysis revealed that W₁ was an independent determinant of VE/VCO₂ slope (β = 0.43, p < 0.01). In conclusion, W₁ might be able to predict the severity of heart failure without the need for CPX. Moreover, WI may be a useful modality in assessing heart failure pathophysiology based on ventriculo-arterial coupling.

The minute ventilation-carbon dioxide production (VE/VCO2) slope, obtained during exercise testing, possesses prognostic value in heart failure (HF). The VE-VCO2 relationship is generally linear thereby hypothetically producing similar slope values regardless of the exercise-test time interval used for calculation.

This study assesses the ability of the VE/VCO2 slope, calculated at different time intervals throughout a progressive exercise test, to predict 1-year cardiac-related hospitalization and mortality in subjects with HF.

Seventy-two subjects underwent symptom-limited exercise testing with ventilatory expired gas analysis. Mean age and left ventricular ejection fraction for 44 male and 28 female subjects were 51.2 years (+/-13.0) and 27.0% (+/-12.3) respectively. The VE/VCO2 slope was calculated from time 0 to 25, 50, 75 and 100% of exercise time and subsequently used to create five randomly selected VE/VCO2 slope categories.

(The intraclass correlation coefficient found calculation of the VE/VCO2 slope, when divided into quartiles, to be a reliable measure (alpha=0.94, P<0.0001). Univariate Cox regression analysis revealed all VE/VCO2 slope categories (25-100% and random selections) were significant predictors of cardiac-related hospitalization and mortality over a 1-year period. Multivariate Cox regression analysis revealed all VE/VCO2 slope categories outperformed peak oxygen consumption (VO2) in predicting hospitalization and mortality at 1 year.

Although the different classification schemes were not identical, these results suggest VE/VCO2 slope maintains prognostic significance regardless of exercise-test time interval. Calculation of VE/VCO2 slope may therefore still be valuable in subjects putting forth a sub-maximal effort while effort-dependent measures, such as peak VO2, are not.

Heart failure with preserved ejection fraction (HFpEF) is commonly associated with hypertension (HTN). However, resting echocardiography (ECHO) can underestimate the severity of disease. Exercise stress echocardiography (ESE) and the cardiopulmonary exercise testing (CPX) appeared to be useful tests in dynamic assessment of HFpEF. The value of combined exercise stress echocardiography cardiopulmonary testing (ESE-CPX) in the identification of masked HFpEF is still undetermined.

The purpose of this study was to analyse the value of the combined ESE-CPX in the identification of masked HFpEF in patients with HTN, dyspnoea and normal resting left ventricular (LV) systolic and diastolic function.

We studied 87 patients with HTN, exertional dyspnoea and normal resting LV function. They all underwent ESE-CPX testing (supine bicycle, ramp protocol, 15 W/min). ECHO measurements were performed at rest, and at peak load. Achievement of peak E/e' ratio>15 was a marker for masked HFpEF.

Increase of E/e'>15 occurred in 8/87 patients (9.2%) during ESE-CPX. Those patients had the lower peak VO2 (p = 0.012), the lower VO2 at anaerobic threshold (p = 0.025), the lower workload (p = 0.026), the lower peak partial pressure end tidal carbon dioxide (PetCO2) (p < 0.0001), and the higher VE/VCO2 slope (p < 0.0001) which was an independent multivariate predictor of HFpEF (p = 0.021), with the cut-off value of 32.95 according to the receiver-operator characteristic (ROC) curve (sensitivity (Sn) 100%, specificity (Sp) 90%).

The combined ESE-CPX test is feasible and reliable test that can unmask HFpEF and may become an important aid in the early diagnosis of HFpEF, excluding the other causes of exertional dyspnoea.

Patients with late-stage chronic obstructive pulmonary disease (COPD) are prone to CO2 retention, a condition which has been often attributed to increased ventilation-perfusion mismatch particularly during oxygen therapy. However, patients with mild-to-moderate COPD or chronic heart failure (CHF) also suffer similar ventilatory inefficiency but they remain near-normocapnic at rest and during exercise with an augmented respiratory effort to compensate for the wasted dead space ventilation. In severe COPD, the augmented exercise ventilation progressively reverses as the disease advances, resulting in hypercapnia at peak exercise as ventilatory limitation due to increasing expiratory flow limitation and dynamic lung hyperinflation sets in. Submissive hypercapnia is an emerging paradigm for understanding optimal ventilatory control and cost/benefit decision-making under prohibitive respiratory chemical-mechanical constraints, where the need to maintain normocapnia gives way to the mounting need to conserve the work of breathing. In severe/very severe COPD, submissive hypercapnia epitomizes the respiratory controller's 'can't breathe, so won't breathe' say-uncle policy when faced with insurmountable ventilatory limitation. Even in health, submissive hypercapnia ensues during CO2 breathing/rebreathing when the inhaled CO2 renders normocapnia difficult to restore even with maximal respiratory effort, hence the respiratory controller's 'ain't fresh, so won't breathe' modus operandi. This 'wisdom of the body' with a principled decision to tolerate hypercapnia when faced with prohibitive ventilatory or gas exchange limitations rather than striving for untenable normocapnia at all costs is analogous to the notion of permissive hypercapnia in critical care, a clinical strategy to minimize the risks of ventilator-induced lung injury in patients receiving mechanical ventilation.

While patients with heart failure who achieve a peak oxygen uptake (peak VO2) of 10 mL·kg(-1)·min(-1) or less are often considered for intensive surveillance or intervention, those achieving 14 mL·kg(-1)·min(-1) or more are generally considered to be at lower risk. Among patients in the "intermediate" range of 10.1 to 13.9 mL·kg(-1)·min(-1), optimally stratifying risk remains a challenge.

Patients with heart failure (N = 1167) referred for cardiopulmonary exercise testing were observed for 21 ± 13 months. Patients were classified into 3 groups of peak VO2 (≤10, 10.1-13.9, and ≥14 mL·kg(-1)·min(-1)). The ability of heart rate recovery at 1 minute (HRR1) and the minute ventilation/carbon dioxide output (VE/VCO2) slope to complement peak VO2 in predicting cardiovascular mortality were determined.

Peak VO2, HRR1 (<16 beats per minute), and the VE/VCO2 slope (>34) were independent predictors of mortality (hazard ratio 1.6, 95% CI: 1.2-2.29, P = .006; hazard ratio 1.7, 95% CI: 1.1-2.5, P = .008; and hazard ratio 2.4, 95% CI: 1.6-3.4, P < .001, respectively). Compared with those achieving a peak VO2 ≥ 14 mL·kg(-1)·min(-1), patients within the intermediate range with either an abnormal VE/VCO2 slope or HRR1 had a nearly 2-fold higher risk of cardiac mortality. Those with both an abnormal HRR1 and VE/VCO2 slope had a higher mortality risk than those with a peak VO2 ≤ 10 mL·kg(-1)·min(-1). Survival was not different between those with a peak VO2 ≤ 10 mL·kg(-1)·min(-1) and those in the intermediate range with either an abnormal HRR1 or VE/VCO2 slope.

HRR1 and the VE/VCO2 slope effectively stratify patients with peak VO2 within the intermediate range into distinct groups at high and low risk.

Excess ventilation during exercise with accompanying dyspnea is characteristic of chronic heart failure (CHF), and these patients often exhibit increased Ve relative to the Vco(2) compared with normal subjects. This can be measured in several ways, including using such variables as the slope of Ve versus Vco(2), the lowest ratio of Ve/Vco(2), and the ratio of Ve/Vco(2) at the lactic acidosis threshold or peak exercise. There is now considerable evidence that the degree of excess ventilation during exercise in patients with CHF is a robust predictor of outcome and identifies higher-risk patients requiring aggressive treatment, including heart transplantation. The mechanism of excess ventilation in patients with CHF during exercise is not completely understood. It may be related to enhanced output of chemoreceptors or peripheral muscle ergoreceptors, increased dead space/Vt ratio due to increased contribution of high ventilation-perfusion lung regions or rapid shallow breathing caused by earlier onset of lactic acidosis, or likely resulting from a combination of these causes.

Despite recent advances in the management of chronic heart failure (CHF), the prognosis of many of these patients remains dire. The need for an accurate prognosis in these patients has led to the identification of several indicators purported to represent the impact of the disease. Such indicators often are obtained at rest and are not always accurate at determining the clinical status of CHF patients. As a result, the relationship between prognostic indicators and clinical outcomes is frequently weak. On the other hand, physiological responses to acute exercise may unmask patients with the worst clinical status and identify those at increased risk of poor outcomes. Therefore, the present review appraises the value of several prognostic indicators for patients with CHF collected at rest and in response to exercise. In particular, it contrasts the value and accuracy of predictors of mortality widely used in clinical settings, such as oxygen uptake, ventilatory efficiency, and left ventricular ejection fraction, with new and more direct indicators of ventricular systolic and diastolic function.

The heart rate increase during exercise (DeltaHR) and heart rate recovery (HRR) have demonstrated prognostic value in several investigations, but its application in the heart failure (HF) population is limited, particularly in a beta-blocked (BB) cohort.

Five-hundred and twenty subjects with HF underwent cardiopulmonary exercise testing to determine peak oxygen consumption (VO(2)), the minute ventilation/carbon dioxide production (VE/VCO(2)) slope, DeltaHR and HRR at 1 min (HRR(1)).

There were 79 cardiac-related deaths during the tracking period. A HRR(1) threshold of </>or=16 beats/min was a significant prognostic marker in the overall group (hazard ratio: 4.6, 95% CI: 2.8-7.5, p<0.001) as well as no-BB (hazard ratio: 9.1, 95% CI: 4.1-20.2, p<0.001) and BB (hazard ratio: 2.9, 95% CI: 1.6-5.4, p<0.001) subgroups. The DeltaHR was a significant univariate predictor in the overall group and no-BB subgroup only. Multivariate Cox regression analysis revealed HRR(1) was the strongest prognostic marker (chi-square: 39.9, p<0.001). The VE/VCO(2) slope (residual chi-square: 21.8, p<0.001) and LVEF (residual chi-square: 9.6, p=0.002) were also retained in the regression.

These results indicate that HRR maintains prognostic value in HF irrespective of BB use. The routine inclusion of HRR in the prognostic assessment of patients with HF may be warranted.

The Weber classification system is a well established method for categorizing patients according to peak oxygen consumption (VO(2)), but it is unknown whether ventilatory efficiency adds prognostic value. The purpose of the current study was to assess the added prognostic value of the minute ventilation/carbon dioxide production (VE/VCO(2)) slope to the Weber classification system in patients diagnosed with heart failure (HF).

Five hundred and forty-eight subjects with HF participated in this analysis. Mean left ventricular ejection fraction was 32.9+/-13.3%. Subjects were tracked for cardiac-related mortality following the exercise test.

The numbers of subjects in Weber Classes A-D were 144, 119, 212 and 71, respectively. One hundred and eight major cardiac events (91 deaths, 10 emergent heart transplants and 7 LVAD implantations) occurred during a mean tracking period of 33.8+/-28.6 months. Receiver operating characteristic (ROC) curve analysis revealed the VE/VCO(2) slope prognostic classification schemes were significant in each of the four Weber classes (A: area=0.84, optimal threshold=31.3, 79% sensitivity/90% specificity, p<0.01; B: area=0.66, optimal threshold=33.9, 73% sensitivity/67% specificity, p<0.05; C: area=0.71, optimal threshold=36.0, 65% sensitivity/68% specificity, p<0.01; D: area=0.66, optimal threshold=41.8, 68% sensitivity/58% specificity, p<0.05).

These results indicate that the VE/VCO(2) slope improves the identification of individuals at higher risk for mortality within each Weber class. These findings further support the routine clinical application of ventilatory efficiency in the HF population.

Ventilatory 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.

A 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 slope(50) or OUES(50)) and 100% (VE/VCO2 slope(100) or OUES(100)) 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: > or = 0.74, P < .001). Area under the ROC curve for the VE/VCO2 slope(100) was, however, significantly greater than OUES(50), OUES(100), and peak VO2 (P < .05).

Although 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.

Ventilatory efficiency is commonly defined as the level of ventilation V(E) at a given carbon dioxide output (V(CO(2) )). The slope of the V(E) versus V(CO(2) ) relationship and the lowest V(E)/V(CO(2) ) are two ventilatory efficiency indices that can be measured during cardiopulmonary exercise testing (CPET). A possible CPET mode dependency for these indices was evaluated in healthy men and women. Also evaluated was the relationship between these two indices as, in theory, V(E)/V(CO(2) ) falls hyperbolically towards an asymptote that numerically equals the V(E) versus V(CO(2) ) slope at exercise levels below the ones that cause respiratory compensation for metabolic acidosis. Twenty-eight healthy subjects (14 men) underwent treadmill and cycle ergometer CPET on different days. Ventilation and the gas fractions for oxygen and CO(2) were measured with a vacumed metabolic cart. In men, paired t-test analysis failed to find a mode difference for either ventilatory efficiency index but the opposite was true in the women as each woman had higher values for both indices on the treadmill. For men, the lowest V(E)/V(CO(2) ) was larger than the V(E) versus V(CO(2) ) slope by 1.3 on the treadmill and 0.8 on the cycle ergometer. The corresponding values for women were 1.7 and 1.4. We conclude that in healthy subjects, women, but not men, demonstrate a mode dependency for the two ventilatory efficiency indices investigated in this study. Furthermore, our results are consistent with the theoretical expectation that the lowest V(E)/V(CO(2) ) has a numerical value just above the asymptote of the V(E)/V(CO(2) ) versus V(CO(2) ) relationship.

The level of ventilation (VE)) at a given carbon dioxide output (CO2) determines ventilatory efficiency. During cardiopulmonary exercise testing (CPET), ventilatory efficiency can be measured as the slope of the (VE) versus VCO2 relationship or the lowest VE/VCO2. We evaluated the test-retest reliability of these two ventilatory efficiency indices in 29 healthy subjects (14 males). Each subject performed duplicate cycle ergometer tests on different days. Ventilation and the gas fractions for oxygen and CO2 were measured with a Vacumed metabolic cart. Linear regression analysis of the VE versus VCO2 slope for the duplicate tests in the males, females, and both sexes combined yielded correlation coefficients of 0.822, 0.942, and 0.910, respectively. The corresponding correlation coefficients for the lowest VE/VCO2 were 0.745, 0.929, and 0.884. A comparison of the test-retest correlation coefficients between the two ventilatory efficiency measures for the men, women, and both sexes combined revealed that they were not significantly different and, for a given index, there were no sex differences. The bias (mean of difference scores between tests) and 95% limits of agreement for the VE versus VCO2 slope in the males, females, and both sexes combined were -0.05 +/- 2.41, -0.57 +/- 1.92, and -0.32 +/- 2.20, respectively. The bias and 95% limits of agreement for the lowest VE/VCO2 were very similar with values of 0.06 +/- 2.45, -0.22 +/- 2.03, and -0.10 +/- 2.27. We conclude that the test-retest reliability for the VE versus VCO2 slope and the lowest VE/VCO2 is the same and that there is no sex difference in reliability for either index of ventilatory efficiency.

The rate in which heart rate recovers from exercise has recently been shown to be a strong predictor of mortality in patients suspected of having coronary disease, but its prognostic value in patients with heart failure (HF) has not been explored. We sought to assess the prognostic utility of heart rate recovery (HRR) in patients with HF.

Eighty-seven subjects diagnosed with compensated HF underwent cardiopulmonary exercise testing (CPX). Mean age and ejection fraction were 50.0 (+/-13.9) years and 28.1% (+/-13.6%), respectively. Heart rate at 1-minute post-CPX was subtracted from maximal heart rate during the exercise test to produce a measure of HRR1 in beats per minute. Subjects were followed for a combined death/hospitalization end point for 1-year after CPX.

The mean peak respiratory exchange ratio, peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2) slope, and HRR1 were 1.06 (+/-0.11), 14.8 (+/-4.7) mL.kg(-1).min(-1), 36.6 (+/-8.6), and 11.0 (+/-10.4) beat/min, respectively. Although all three variables were significant univariate predictors of the composite end point (P < .001), multivariate Cox regression analysis only retained the VE/VCO2 slope (chi2 = 33.5, P < .001) and HRR1 (residual chi2 = 15.0, P < .001) in the equation. The hazard ratio for subjects having both an abnormal VE/VCO2 slope (> 34.4) and HRR1 (< 6.5 beat/min) value was 9.2 (95% CI 4.5-18.5, P < .0001).

These results indicate that HRR provides additional prognostic information in patients with HF undergoing CPX. Moreover, given the independent prognostic value of HRR, this variable alone may provide valuable clinical information when ventilatory expired gas analysis is not available.

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.

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.

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/VCO(2) 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).

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.

The minute ventilation (VE)-carbon dioxide output (VCO(2)) relationship has recently been demonstrated to have prognostic significance in the heart failure (HF) population. However, the method by which the VE/VCO(2) slope is expressed has been inconsistent.

One hundred eighty-eight subjects, who had received diagnoses of HF, underwent exercise testing. Two VE/VCO(2) slope calculations were made, one using exercise data prior to the ventilatory threshold (VT), and one using all data points from rest to peak exercise. Four separate peak exercise VE/VCO(2) slope calculations also were derived with unaveraged, 10-s, 30-s, and 60-s ventilatory expired gas sampling intervals.

Although univariate Cox regression analysis demonstrated pre-VT and peak VE/VCO(2) slope calculations to both be significant predictors of cardiac-related mortality and hospitalization (p < 0.001), the peak classification scheme was significantly better (p < 0.01). The ventilatory expired gas-sampling interval that was used did not impact the predictive ability of the peak VE/VCO(2) slope.

Although both the pre-VT and peak VE/VCO(2) slope calculations were prognostically significant, the peak expression was superior. The sampling interval did not appear to have a significant impact on prognostic utility. We hope that the results of the present study will contribute to the standardization of the VE/VCO(2) slope and will enhance its clinical application.

This study investigates the relationship between ventilatory expired gas and cardiac parameters measured during exercise testing in patients with heart failure.

Twenty-five subjects (12 male, 13 female) diagnosed with compensated heart failure underwent symptom-limited exercise testing with ventilatory expired gas analysis. Metabolic and cardiac measures of interest were collected during testing.

Mean peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2) slope, percentage of age predicted maximal heart rate achieved during exercise testing (%APMHR), and peak respiratory exchange ratio were 14.7 +/- 4.7 mL O2/kg/min-1, 33.8 +/- 9.8, 76% +/- 15%, and 1.1 +/- 0.11, respectively. The VE/VCO2 slope was significantly correlated with the following: %APMHR (r = -0.81, P < 0.001), peak VO2 (r = -0.83, P < 0.001), VO2 at ventilatory threshold (r = -0.70, P < 0.001), and the dead space to tidal volume ratio (VD/Vt) (r = 0.65, P < 0.001). The ability of peak VO2 and %APMHR to predict the VE/VCO2 slope was significant (r = 0.86, r2 = 0.72, P < 0.0001).

This study demonstrates the importance of analyzing multiple exercise test parameters, including metabolic measures, in patients with heart failure.

Left ventricular enlargement with normal systolic function is common in asymptomatic relatives of patients with familial dilated cardiomyopathy, many of whom progress to overt dilated cardiomyopathy at follow up.

To examine maximal and submaximal gas exchange variables of cardiopulmonary exercise testing in asymptomatic relatives with left ventricular enlargement.

Controlled evaluation of metabolic exercise performance of patients with dilated cardiomyopathy and asymptomatic relatives with left ventricular enlargement identified through prospective family screening in a cardiomyopathy outpatient clinic.

23 relatives with left ventricular enlargement, 33 normal controls, 29 patients with dilated cardiomyopathy, and 10 elite athletes with echocardiographic criteria of left ventricular enlargement ("physiological" enlargement) underwent symptom limited upright cycle ergometry using a ramp protocol.

Peak oxygen consumption (pVO(2); mean (SD)) was significantly reduced in relatives with left ventricular enlargement (78 (16.3)%) v normal controls (96%, p < 0.01) and athletes (152%, p < 0.001), but was higher than in patients with dilated cardiomyopathy (69%, p < 0.01). pVO(2) was less than 80% of predicted in 75% of patients, 58% of relatives, 22% of controls, and none of the athletes. Oxygen pulse (pVO(2)/heart rate) was less than 80% of predicted in 69% of patients, 35% of relatives, 6% of controls, and none of the athletes. The slope of minute ventilation v CO(2) production (DeltaVE/DeltaVCO(2)) was > 30 in 68% of patients, 50% of relatives, and in none of the controls or athletes. Anaerobic threshold, occurring in relatives at 37 (14)% of the predicted VO(2), was higher than in the patients (32%, p < 0.01) and lower than in the controls (45%, p < 0.05) or in the athletes (55%, p < 0.001).

Maximal and submaximal cardiopulmonary exercise test variables are abnormal in asymptomatic relatives with left ventricular enlargement, in spite of normal systolic function. This provides further evidence that left ventricular enlargement represents subclinical disease in relatives of patients with dilated cardiomyopathy. Metabolic exercise testing can complement echocardiography in identifying relatives at risk for the development of dilated cardiomyopathy.

To investigate the relationship of the BP response to the Valsalva maneuver (VM) to parameters of congestive heart failure (CHF) other than hemodynamic measures.

Comparison of neurohormones (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], norepinephrine [NE]), parameters of spiroergometry, and clinical parameters with BP response to the VM.

Tertiary care center.

Forty-five patients with stable CHF (ejection fraction, 28 +/- 7%).

Pulse amplitude ratio (PAR) calculated between the end and the beginning of the VM using the last two and the first three beats of the straining phase. Failure of the systolic BP to fall below the resting level during the VM.

Patients in the New York Heart Association class III (n = 15) had a higher PAR than those in class II (0.82 +/- 0.21 vs 0.63 +/- 0.20; p < 0.01). There was a close correlation between PAR and ANP (r = 0.76) and BNP (r = 0.62), whereas other parameters were less well correlated (eg, for peak f1.gif" BORDER="0">O(2), r = -0.35; p < 0.05). Patients with failure of the systolic BP to fall below the resting level (n = 24) had higher neurohormones (mean ANP, 246 +/- 158 vs 84 +/- 43 pg/mL; mean BNP, 282 +/- 289 vs 81 +/- 85 pg/mL; p < 0.001; mean NE, 3.9 +/- 1.7 vs 3.4 +/- 1.5 nmol/L; nanosecond), lower exercise capacity (19.8 +/- 5.2 vs 23.0 +/- 3.7 mL/kg/min; p < 0.05), and their quality of life (Minnesota questionnaire) was more compromised (31 +/- 19 vs 18 +/- 15; p < 0. 05).

The BP response to the VM is related to a broad range of clinical and neurohumoral parameters of CHF. Whether or not it is also related to prognosis remains to be determined. Nevertheless, this easily applicable test should be part of the assessment of patients with CHF.

To examine the submaximal and maximal indices of the exercise response of patients with hypertrophic cardiomyopathy.

Prospective examination of cardiopulmonary responses to ramp exercise test of a consecutive group of patients with hypertrophic cardiomyopathy attending a cardiomyopathy outpatient clinic.

50 patients aged 12 to 76 years (mean (SD) 35 (14)) with diagnosis of hypertrophic cardiomyopathy performed incremental cycle ergometry; 22 sedentary volunteers (seven female, 15 male) aged 14 to 58 years (mean (SD) 31 (12)) served as controls. Respiratory gas was continuously sampled from the mouth-piece, and its concentration profile phase aligned to the respired air flow signals. Following analogue to digital conversion, gas exchange variables were computed breath by breath and the data were averaged every 30 seconds for graphic display. A 12 lead ECG was monitored continuously and recorded every three minutes during the exercise.

Both the peak oxygen uptake attained on the test (VO2 peak) and anaerobic threshold were reduced in patients with hypertrophic cardiomyopathy compared with the control group (p < 0.0001). In 29 patients (59%) the VO2 peak was less than 60% and only two patients achieved a peak above 80% of their predicted values. The anaerobic threshold was below 60% of the predicted value in 31 patients and above 80% in only three patients. The slope of oxygen uptake/work rate relation (delta VO2/delta WR) was decreased in 16 patients (32%). The maximum oxygen pulse (VO2/HR) was reduced as a percentage of the predicted value, and became flat at high work rates in 32 patients. There was a significant correlation between anaerobic threshold and VO2 peak (p < 0.0001), work efficiency (p < 0.0001), and maximum oxygen pulse (p < 0.0001). The slope of change in ventilation against change in carbon dioxide output (delta VE/delta VCO2) for the subanaerobic threshold range was increased in 36 patients (72%) and was inversely correlated with anaerobic threshold (p < 0.0002).

There were severe abnormalities in maximal and submaximal indices of pulmonary gas exchange in a cohort of hypertrophic cardiomyopathy patients attending a referral cardiovascular clinic. The pattern of the abnormalities suggests that a reduced stroke volume response, ventilation/perfusion mismatch, and abnormal peripheral oxygen utilisation are the possible mechanisms of exercise intolerance.

The purpose of this study was to analyse the ventilatory efficiency for carbon dioxide (CO2) in the assessment of exercise tolerance in patients with pulmonary hypertension. Two groups of patients were studied. One group consisted of 37 patients with normal pulmonary artery pressure who underwent surgical closure of a left-to-right shunt. Another group was composed of 10 patients with pulmonary hypertension. Both patient groups were compared with the mean value of an age-matched pool of normal control subjects. Aerobic exercise performance was assessed by determination of the ventilatory threshold. The ventilatory efficiency for CO2 was assessed by calculating the slope of ventilation over carbon dioxide below the ventilatory threshold. The slope of ventilation vs. carbon dioxide output in patients with pulmonary hypertension (48 +/- 12) was steeper than the slope (31.3 +/- 7.0) in patients with normal pulmonary artery pressure (P < 0.05). Significant correlations (P < 0.05) were found between the pulmonary artery pressure and the slope of pulmonary ventilation over carbon dioxide (r = 0.92) and also with the physiological dead space-tidal volume ratio at maximal exercise (r = 0.55). This was associated with a severe reduction in exercise performance in patients with pulmonary hypertension, whereas in patients with normal pulmonary artery pressure it was only slightly below the lower limit of normal. These results demonstrate that patients with pulmonary hypertension have an inefficient ventilatory response to metabolically produced CO2 during exercise, which severely limits exercise tolerance.

The ventilatory response to exercise in patients with chronic heart failure (HF) is greater than normal for a given metabolic rate. The objective of the present study was to determine the mechanism(s) for the high ventilatory output in patients with chronic HF.

Centers in Germany, Italy, Japan, and the United States participated in this study. Each center contributed studies on patients and normal subjects of similar age and sex. One hundred thirty patients with chronic HF and 52 healthy subjects participated. Spirometric and breath-by-breath gas exchange measurements were made during rest and increasing cycle exercise. Arterial blood was sampled for measurement of pH, PaCO2, PaO2, and lactate during exercise in 85 patients. Resting forced expiratory volume in 1 second (FEV1) and vital capacity (VC) were proportionately reduced at all levels of impairment. Patients with more severe HF had greater tachypnea and a smaller tidal volume (VT) at a given exercise expired volume per unit time (VE). This was associated with an expiratory flow pattern characteristic of lung restriction. VE and VCO2 as a function of VO2 were increased during exercise in HF patients. The increases were greater the lower the peak VO2 per kilogram of body weight. The ratio of VD (physiological dead space) to VT and the difference between arterial and end tidal PCO2 at peak VO2 also increased inversely with peak VO2/kg. In contrast, the difference between alveolar and arterial PO2 and PaCO2 were both normal, on average, at peak VO2 regardless of the level of impairment. The more severe the exercise limitation, the higher the lactate and the lower the HCO3- at a given VO2, although pH was tightly regulated.

The increase in VE in chronic HF patients is caused by an increase in VD/VT due to high ventilation/perfusion mismatching, an increase in VCO2 relative to VO2 resulting from HCO3- buffering of lactic acid, and a decrease in PaCO2 due to tight regulation of arterial pH. With regard to the excessive VE in HF patients, the increases in VD/VT and VCO2 relative to VO2 are more important as the patient becomes more exercise limited. Regional hypoperfusion but not hypoventilation typifies lung gas exchange in HF. This and other mechanisms might account for the restrictive changes leading to exercise tachypnea in HF patients.

Cardiac Syndrome X (microvascular angina) and the more recently described metabolic Syndrome X (an epidemiological association between insulin resistance and atheroma, dyslipidaemia, and hypertension) may have more in common than the chance of their common sobriquet, in view of evidence that microvascular angina too is characterised by insulin resistance and endothelial dysfunction. The implications are discussed.

Exertional dyspnoea is a limiting symptom in many patients with mitral stenosis but its causes remain incompletely understood. Ventilation during exercise is abnormal in chronic heart failure of all causes and there is increased ventilatory cost of carbon dioxide production.

23 patients with rheumatic mitral stenosis undergoing percutaneous balloon dilatation of the mitral valve were studied to investigate exercise ventilation.

Treadmill exercise tests with respiratory gas analysis were performed before and 1 day, 7 days, and 10 weeks after balloon dilatation of the mitral valve. The relation between ventilation (VE) and production (VCO2) was analysed by linear regression.

The VE/VCO2 slope was linear in all patients and before balloon dilatation of the mitral valve it correlated inversely with peak minute oxygen consumption (VO2) (rs = -0.47, P < 0.05), exercise duration (rs = -0.66, P < 0.01), and mitral valve area (rs = -0.5, P < 0.05). The VE/VCO2 slope declined acutely after balloon dilatation of the mitral valve (n = 10) (mean (SD) 41 (4) v 36 (2.9), P < 0.05) and did not change again thereafter. At 10 weeks (n = 23) exercise duration (460 (230) v 630 (240) s, P < 0.01) and peak VO2 (12.7 (4.3) v 14.9 (4.8) ml/kg/min, P < 0.05) increased significantly.

Patients with rheumatic mitral stenosis have a similar increase in the VE/VCO2 slope to that of patients with heart failure from other causes. Successful balloon dilatation of the mitral valve is associated with an acute reduction in the exercise VE/VCO2 slope.