Gabriele Valli

Cardiopulmonary exercise testing in the functional and prognostic evaluation of patients with pulmonary diseases.

Exercise testing is increasingly utilized to evaluate the level of exercise intolerance in patients with lung and heart diseases. Cardiopulmonary exercise testing (CPET) is considered the gold standard to study a patient’s level of exercise limitation and its causes. The 2 CPET protocols most frequently used in the clinical setting are the maximal incremental and the constant work rate tests. The aim of this review is to focus on the main respiratory diseases for which exercise tolerance is indicated; for example, chronic obstructive pulmonary disease, interstitial lung disease, primary pulmonary hypertension and cystic fibrosis. This review also focuses on the variables/indices that are utilized in the functional and prognostic evaluation. The recognition of abnormal response patterns of ventilatory, cardiac and metabolic limitation to exercise may help in the diagnostic evaluation. In addition, CPET indexes can provide important functional and prognostic information regarding patients with pulmonary disease. Exercise indices, such as peak oxygen uptake (V’O2 peak), ventilatory equivalents for carbon dioxide production (V’E-/V’CO2) and arterial oxygen saturation (SpO2), have in fact proven to be better predictors of prognosis than lung function measurements obtained at rest. Moreover, useful information on the effects of therapeutic interventions may be obtained by CPET by studying the changes in endurance capacity during high-intensity constant work rate protocols.

Prognostic factors in severe pulmonary hypertension patients who need parenteral prostanoid therapy: The impact of late referral

BACKGROUND Oral drugs have made the treatment of pulmonary hypertension (PH) feasible in non-expert centers, which could delay patient access to prostanoid therapy. METHODS Fifty-seven consecutive patients with precapillary PH received a prostanoid in our center. Data at prostanoid initiation included modality of center referral, medical history, New York Heart Association [NYHA] class, exercise capacity, echocardiographic parameters, and hemodynamics. RESULTS Overall survival at 1, 2, and 3 years was 85%, 69%, 55%, respectively. Non-survivors had worse NYHA class III/IV (17/12) than survivors (27/1; p < 0.01) and exercise capacity on 6-minute-walk distance (254 ± 114 vs 354 ± 91 meters; p < 0.01). Non-survivors were more frequently referred on oral therapy (83% vs 36%; p < 0.01) and had a higher rate of urgent prostanoid treatment (69% vs 17%; p < 0.0001). Multivariate analysis (hazard ratio [95% confidence interval]) found the independent prognostic factors were urgent prostanoid therapy (2.0 [1.1-3.9]) and NYHA class (3.5 [1.5-8.2]). Survivors had a significant response to prostanoid, improving NYHA class from 2.8 ± 0.4 to 2.3 ± 0.5 (p = 0.002), 6-minute walk distance from 354 ± 91 to 426 ± 82 meters (p = 0.0001), and pulmonary hemodynamics (pulmonary artery pressure from 56 ± 13 to 44 ± 18 mm Hg [p < 0.05]; cardiac index from 2.0 ± 1.2 to 3.1 ± 1.2 liters/min/m(2) [p = 0.002], and pulmonary vascular resistance from 17 ± 10 to 8 ± 6 WU [p = 0.001]). CONCLUSIONS Referral of patients on oral treatment to a tertiary PH center is delayed and significantly affects prognosis.

Cardiopulmonary exercise testing (CPET) in pulmonary emphysema.

In patients affected by chronic obstructive pulmonary disease (COPD), cardiopulmonary response to exercise was never related to the severity of emphysema (E) measured by high resolution computed tomography (HRCT). Sixteen patients (age=65±8 yrs; FEV(1)=54±18%pred; RV=160±28%pred) with moderate to severe E (quantified by lung HRCT as % voxels <-910 HU) were exercised on a cycle-ergometer to exhaustion. Oxygen uptake (V˙(O2)), carbon dioxide output (V˙(CO2)), ventilation (V˙(E)), tidal volume (V(T)), and end-tidal P(CO2) (PET(CO2)) derived variables were measured breath-by-breath. The % of E correlated with: (1) the ratio V(Tpeak) (r=0.74; p=0.001); (2) the V˙(E)/V˙(CO2) slope (r=-0.77; p=0.0004); (3) PET(CO2) values at peak exercise (r=0.80; p=0.0001). Also, the %E was strongly predicted by the following exercise equation: %E(EST) = 58.1 + 11.9 × ΔV˙(E)/V˙(CO2) (r=0.94; p<0.0001). A V(Tpeak)/FEV1 ratio>1 is typically observed in severe E patients; furthermore, the V˙(E)/V˙(CO2) slope and the PET(CO2peak) values decrease and increase respectively as more as the emphysema is severe.

Right intraventricular dyssynchrony in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension: Clinical impact and reversibility

OBJECTIVES The aim of this study was to determine the prevalence of right intraventricular dyssynchrony, its determinants and prognostic impact in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension. BACKGROUND Right ventricular dyssynchrony has been described in pulmonary arterial hypertension, but no evidence is available on its prognostic impact and evolution after therapy. METHODS In 83 consecutive therapy-naïve patients, right ventricular dyssynchrony was evaluated by 2-dimensional speckle-tracking echocardiography calculating the standard deviation of the times to peak-systolic strain for the 4 mid-basal right ventricular segments (RV-SD4). After baseline (World Health Organization [WHO] class, pulmonary hemodynamics, 6-min walk test [6 MWT]), a second assessment was performed after 12 months or when clinical worsening occurred. RESULTS Patients with right ventricular dyssynchrony (RV-SD4 >18 ms) had advanced WHO class, worse 6 MWT, right ventricular remodeling, and hemodynamic profile compared with patients ≤ 18 ms. Determinants of dyssynchrony included pulmonary vascular resistance, QRS duration, and right ventricular end-diastolic area (r(2) = 0.38; p < 0.000001). At 12 months, 32.5% of patients presented clinical worsening (actuarial rates: 19% at 6 months, 31% at 1 year). Multivariable models for clinical worsening prediction showed that the addition of RV-SD4 to clinical and hemodynamic variables (WHO IV, 6 MWT, and cardiac index) significantly increased the prognostic power of the model (0.74 vs. 0.81; p = 0.005, 95% confidence interval [CI]: 0.02 to 0.11). Receiver operating characteristic analysis identified RV-SD4 ≥ 23 ms as the best cutoff value for clinical worsening prediction (95% negative predictive value). At 12 months, normalization of dyssynchrony was achieved in patients with a large reduction of pulmonary vascular resistance (-42 ± 4%). CONCLUSIONS Right ventricular dyssynchrony is frequent in pulmonary arterial hypertension, is an independent predictor of clinical worsening, and might regress during effective treatments.

Pulmonary arterial dilatation in pulmonary hypertension: prevalence and prognostic relevance.

Objectives: Pulmonary arterial dilatation is considered a consequence of chronic pulmonary hypertension (PH), but despite its relatively common detection, its prevalence and prognostic impact have not yet been systematically investigated. The aim of the study was to investigate these factors in a relatively large cohort of severe PH patients. Methods: One hundred and forty-one consecutive patients diagnosed with PH were monitored for a mean of 957 days. Data including functional class, exercise capacity, invasive hemodynamics and pulmonary artery (PA) echo/CT scan measurement were performed and outcomes prospectively collected. Results: PA dilatation is a common feature, present in the 76.6% of cases in this cohort of severe PH patients. Survival at 1, 2 and 3 years was 83, 71 and 58%, respectively. On univariate analysis, the baseline variables associated with a poor outcome were related to pulmonary arterial hypertension associated with connective tissue disease (CDT-PAH), New York Heart Association (NYHA) functional class, 6-min walk test and right atrial pressure. On multivariate analysis only CDT-PAH and NYHA functional class remained independently associated with poor survival. Conclusions: PA dilatation is commonly detected in severe PH patients and is not associated with an increased risk of death.

The hypoxic profile during trekking to the Pyramid Laboratory.

UNLABELLED The oxygen saturation values reported in the high altitude literature are usually taken during a few minutes of measurement either at rest or during exercise. We aimed to investigate the daily hypoxic profile by monitoring oxygen saturation for 24 h in 8 lowlanders (4 females, ages 26 to 59) during trekking from Lukla (2850 m) to the Pyramid Laboratory (5050 m). Oxygen saturation was measured (1) daily at each altitude (sm), (2) for 24-h during ascent to 3500 m, 4200 m, and on day 1 at 5050 m (lm), and (3) during a standardized exercise (em). RESULTS (1) the sm and lm values were 90.9% (+/-0.5) and 86.4% (+/-1.1) at 3500 m; 85.2%(+/-1.1), and 80% (+/-1.9) at 4200 m; 83.8%(+/-1) and 77% (+/-1.7) at 5050 m (p < or = 0.05); (2) the daily time spent with oxygen saturation < or =90% was 56.5% at 3500 m, 81% at 4200 m, and 95.5% at 5050 m; (3) during exercise, oxygen saturation decreased by 10.58%, 13.43%, and 11.24% at 3500, 4200, and 5050 m, respectively. In conclusion, our data show that the level of hypoxemia during trekking at altitude is more severe than expected on the basis of a short evaluation at rest and should be taken into account.

Relationship between individual ventilatory response and acute renal water excretion at high altitude

We tested the hypothesis that the individual ventilatory adaptation to high altitude (HA, 5050 m) may influence renal water excretion in response to water loading. In 8 healthy humans (33+/-4 S.D. years) we studied, at sea level (SL) and at HA, resting ventilation (VE), arterial oxygen saturation (SpO2), urinary output after water loading (WL, 20 mL/kg), and total body water (TBW). Ventilatory response to HA was defined as the difference in resting VE over SpO2 (DeltaVE/DeltaSpO2) from SL to HA. At HA, a significant increase in urinary volume after the first hour from WL (%WLt0-60) was observed. Significant correlations were found between DeltaVE/DeltaSpO2 versus %WLt0-60 at HA and versus changes in TBW, from SL to HA. In conclusion, in healthy subjects the ventilatory response to HA influences water balance and correlates with kidney response to WL. A higher ventilatory response at HA, allowing a more efficient water renal handling, is likely to be a protective mechanisms from altitude illness.

Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension

Survival in patients with pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to afterload. How altered RV function impacts on exercise capacity in PAH is not exactly known. 104 idiopathic PAH (IPAH) patients aged 52±14 years underwent a diagnostic right heart catheterisation, a comprehensive echocardiography including two-dimensional speckle tracking for RV dyssynchrony evaluation and a cardiopulmonary exercise test. Multivariate analyses were performed to identify independent predictors of peak oxygen uptake (peak V′O2). A first multivariate analysis of only resting haemodynamic variables identified cardiac index, right atrial (RA) pressure and pulmonary arterial compliance as independent predictors, with low predictive capacity (r2=0.31; p<0.001). A second multivariate analysis model which considered only echocardiographic parameters but without RV dyssynchrony, identified RV fractional area change (FAC) and RA area as independent predictors with still low predictivity (r2=0.35; p<0.001). Adding RV dyssynchrony to the second model increased its predictivity (r2=0.48; p<0.001). Repetition of the three multivariate analyses in patients with preserved RVFAC confirmed that inclusion of RV dyssynchrony results in the highest predictive capability of peak V′O2 (r2=0.53; p=0.001). A comprehensive echocardiography with speckle tracking-derived assessment of the heterogeneity of RV contraction improves the prediction of aerobic exercise capacity in IPAH. Speckle tracking assessment of RV dyssynchrony improves the prediction of aerobic exercise capacity in IPAH http://ow.ly/yHyh30bedtD

A Simplified Approach for the Estimation of the Ventilatory Compensation Point

UNLABELLED Incremental cardiopulmonary exercise test with gas exchange measurement is the gold standard for the identification of the ventilatory compensation point (VCP). It has previously been demonstrated that the change in the slope of increment of minute ventilation over HR (ΔV˙E/ΔHR) can be used alternatively to the ventilatory equivalent for CO₂ (V˙E/V˙CO₂) method for detection of VCP in healthy subjects undergoing cycle ergometer (C) incremental exercise. The same evaluation during treadmill (T) incremental exercise and comparison between C and T have not yet been performed. PURPOSE We analyzed, during both C and T incremental exercises, the V˙E/HR and the respiratory rate (RR)/HR relationships, expressed either as slope or as an absolute value. We hypothesized that changes in the slope of increment of the two relationships could represent a reliable method for VCP detection, regardless of exercise mode and protocol. METHODS Fourteen healthy male subjects (age = 31 ± 7 yr (mean ± SD)) underwent two T incremental exercises--fast (FT) and slow (ST) protocols (8 km·h⁻¹, 2% (F(T)) and 1% (S(T)) grade per minute)--and one C incremental exercise (30 W·min⁻¹). O₂ uptake (V˙O₂), V˙CO₂, V˙E, HR, and RR were measured breath by breath. RESULTS A good between-method agreement in the detection of VCP by the ΔV˙(E)/ΔV˙CO₂, ΔV˙(E)/ΔHR, and the ΔRR/ΔHR slope changes was found in both T protocols and C. No differences (C vs T and F(T) vs S(T)) were found in the slope of the ΔV˙(E)/ΔHR and ΔRR/ΔHR relationships after the VCP and in the V˙(E)/HR and RR/HR absolute values at VCP. CONCLUSIONS In healthy young males, the ΔV˙E/ΔHR and ΔRR/ΔHR relationships during T and C incremental exercises can be reliably used to detect the VCP as an alternative to the ventilatory equivalent method.

Minute ventilation and heart rate relationship for estimation of the ventilatory compensation point at high altitude: a pilot study

BackgroundThe ventilatory compensation point (VCP) is an exercise threshold which has been used in the design of training programs in sports medicine and rehabilitation. We recently demonstrated that changes in the slope of the minute ventilation to heart rate relationship (ΔV˙E/ΔHR) can be utilized for estimation of the VCP during incremental exercise at sea level (SL). We hypothesized that in hypoxic conditions, such as high altitude (HA), VCP can be also reliably estimated by ΔV˙E/ΔHR.MethodsAt SL and on immediate ascent to HA (5,050 m), six healthy subjects (42 ± 14 SD years) performed a maximal incremental exercise test on a cycle ergometer; O2 uptake (V˙O2), CO2 output (V˙CO2), V˙E, and HR were measured breath-by-breath. The ΔV˙E/ΔHR method for VCP estimation was compared to the standard method using the ventilatory equivalent for CO2 (V˙E/V˙CO2) and end-tidal PCO2 (PETCO2). The ΔV˙E/ΔHR slope values below (S1) and above (S2) VCP were computed by linear regression analysis.ResultsA significant difference between S1 and S2 was observed, at SL and HA, for both the ΔV˙E/ΔHR and V˙E/V˙CO2 methods for VCP estimation. A good agreement between the two methods (ΔV˙E/ΔHR vs. V˙E/V˙CO2) was found for both environmental conditions; the mean difference ± 2 SD of V˙O2 at VCP (VCP-V˙O2) was −22 ± 112 ml/min at SL and 39 ± 81 ml/min at HA. The VCP-V˙O2 was significantly lower at HA compared to SL; in addition, S1 and S2 mean values were significantly higher at HA compared to SL.ConclusionAt HA, VCP may be reliably estimated by the ΔV˙E/ΔHR method.