Role of cardiopulmonary exercise test in the prediction of hemodynamic impairment in patients with pulmonary arterial hypertension.

Periodic repetition of right heart catheterization (RHC) in pulmonary arterial hypertension (PAH) can be challenging. We evaluated the correlation between RHC and cardiopulmonary exercise test (CPET) aiming at CPET use as a potential noninvasive tool for hemodynamic burden evaluation. One hundred and forty-four retrospective PAH patients who had performed CPET and RHC within 2 months were enrolled. The following analyses were performed: (a) CPET parameters in hemodynamic variables tertiles; (b) position of hemodynamic parameters in the peak end-tidal carbon dioxide pressure (PETCO2) versus ventilation/carbon dioxide output (VE/VCO2) slope scatterplot, which is a specific hallmark of exercise respiratory abnormalities in PAH; (c) association between CPET and a hemodynamic burden score developed including mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and right atrial pressure. VE/VCO2 slope and peak PETCO2 significantly varied in mPAP and PVR tertiles, while peak oxygen uptake (peak VO2) and O2 pulse varied in the tertiles of all hemodynamic parameters. PETCO2 versus VE/VCO2 slope showed a strong hyperbolic relationship (R 2 = 0.7627). Patients with peak PETCO2 > median (26 mmHg) and VE/VCO2 slope < median (44) presented lower mPAP and PVR (p < 0.005) than patients with peak PETCO2 < median and VE/VCO2 slope > median. Multivariate analysis individuated peak VO2 (p = 0.0158) and peak PETCO2 (p = 0.0089) as hemodynamic score independent predictors; the formula 11.584 - 0.0925 × peak VO2 - 0.0811 × peak PETCO2 best predicts the hemodynamic score value from CPET data. A significant correlation was found between estimated and calculated scores (p < 0.0001), with a precise match for patients with mild-to-moderate hemodynamic burden (76% of cases). The results of the present study suggest that CPET could allow to estimate the hemodynamic burden in PAH patients.

Subclinical pulmonary edema in endurance athletes.

Strenuous exercise may cause progressive and proportional haemodynamic overload damage to the alveolar membrane, even in athletes. Despite the high incidence of arterial desaturation reported in endurance athletes has been attributed, into other factors, also to the damage of the alveolar-capillary membrane this evidence is equivocal. Some studies demonstrated flood of the interstitial space and consequent increase in pulmonary water content, but most of them were able to show this through indirect signs of interstitial oedema. The present review illustrates the literature's data in favour or against pulmonary interstitial edema due to intense exercise in athletes.

Exhaled nitric oxide and exercise performance in heart failure.

BACKGROUND: In heart failure abnormalities of pulmonary function are frequently observed particularly during exercise, which is characterized by hyperpnea, low tidal volume, early expiratory flow limitation and reduced lung compliance. Exhaled nitric oxide (NO) is increased in asthma. We evaluated whether a correlation between exhaled NO and lung mechanics exists during exercise in heart failure. METHODS: We studied 33 chronic heart failure patients and 11 healthy subjects with: a) standard pulmonary function, b) lung diffusion for carbon monoxide (DLCO) including its subcomponents, capillary volume and membrane resistance and eNO both at rest and during light exercise, c) maximal cycloergometer cardiopulmonary exercise test. RESULTS: Forced expiratory volume in 1 second (FEV1) was reduced in heart failure patients (83 +/- 17% of predicted) as was DLCO (75 +/- 18% of predicted) due to reduced membrane resistance (32.6 +/- 10.3 ml/mmHg/min vs. 39.9 +/- 6.9 in patients vs. controls, p < 0.02). eNO was lower in patients vs. controls (9.7 +/- 5.4 ppm vs. 14.4 +/- 6.4, p < 0.05) and was, during exercise, constant in patients and reduced in controls. No significant correlation was found between eNO and lung function. Vice-versa eNO changes during exercise were correlated with peak exercise oxygen consumption (r = 0.560, p < 0.001). CONCLUSIONS: The hypothesis of a link between eNO and lung function in heart failure was not proved. The correlation between eNO changes during exercise and peak VO2 might be due to hemoglobin oxygenation which binds NO to hemoglobin.

Does lung diffusion impairment affect exercise capacity in patients with heart failure?

OBJECTIVE: To determine whether there is a relation between impairment of lung diffusion and reduced exercise capacity in chronic heart failure. DESIGN: 40 patients with heart failure in stable clinical condition and 40 controls participated in the study. All subjects underwent standard pulmonary function tests plus measurements of resting lung diffusion (carbon monoxide transfer, TLCO), pulmonary capillary volume (VC), and membrane resistance (DM), and maximal cardiopulmonary exercise testing. In 20 patients and controls, the following investigations were also done: (1) resting and constant work rate TLCO; (2) maximal cardiopulmonary exercise testing with inspiratory O2 fractions of 0.21 and 0.16; and (3) rest and peak exercise blood gases. The other subjects underwent TLCO, DM, and VC measurements during constant work rate exercise. RESULTS: In normoxia, exercise induced reductions of haemoglobin O2 saturation never occurred. With hypoxia, peak exercise uptake (peak O2) decreased from (mean (SD)) 1285 (395) to 1081 (396) ml/min (p < 0.01) in patients, and from 1861 (563) to 1771 (457) ml/min (p < 0.05) in controls. Resting TLCO correlated with peak O2 in heart failure (normoxia < hypoxia). In heart failure patients and normal subjects, TLCO and peak O2 correlated with O2 arterial content at rest and during peak exercise in both normoxia and hypoxia. TLCO, VC, and DM increased during exercise. The increase in TLCO was greater in patients who had a smaller reduction of exercise capacity with hypoxia. Alveolar-arterial O2 gradient at peak correlated with exercise capacity in heart failure during normoxia and, to a greater extent, during hypoxia. CONCLUSIONS: Lung diffusion impairment is related to exercise capacity in heart failure.

Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failure.

OBJECTIVES: We sought to investigate the possibility that lung diffusing capacity reduction observed in chronic heart failure is reversible in the short term. BACKGROUND: Mechanical properties of the lung usually ameliorate with antifailure treatment including drugs, ultrafiltration and heart transplantation, whereas lung diffusion rarely improves. METHODS: We studied the mechanical properties of the lung (pulmonary function tests with determination of alveolar volume, extravascular lung fluids and lung tissue), lung diffusion for carbon monoxide (DLco), including membrane diffusing capacity (Dm), pulmonary capillary blood volume (Vc) and pulmonary hemodynamics, in 28 patients with stable chronic heart failure, before a single session of extracorporeal ultrafiltration (3,973 +/- 2200 ml) and four days thereafter. Lung mechanics and diffusion were also evaluated in 18 normal subjects. RESULTS: Vital capacity, forced expiratory volume (1 s) and maximal voluntary ventilation were lower in patients when compared with normal subjects, and increased after ultrafiltration from 2.1 +/- 0.7 to 2.5 +/- 0.7(1)*, 1.7 +/- 0.5 to 2.0 +/- 0.6(1)* and 67 +/- 25 to 79 +/- 26 (1/min)*, respectively (* p < 0.02 vs. pre-ultrafiltration). Post-ultrafiltration alveolar volume was augmented, while lung tissue, body weight (approximately 6 kg), chest X-ray extravascular lung water score and pulmonary vascular pressure were reduced. Heart dimensions (echocardiography) remained unchanged. DLco, Dm and Vc were 29.0 +/- 5.0 ml/min/mm Hg, 47.0 +/- 11.0 ml/min/mm Hg, 102 +/- 20 ml in normal subjects and 17.1 +/- 4.0#, 24.1 +/- 6.5#, 113 +/- 38 and 17.0 +/- 5.0#, 24.8 +/- 7.9#, 100 +/- 39 in patients before and after ultrafiltration, respectively (# = p < 0.01 vs. controls). CONCLUSIONS: In chronic heart failure, ultrafiltration improves volumes and mechanical properties of the lung by reducing lung fluids. Diffusion is unaffected by ultrafiltration, suggesting that, in chronic heart failure, the alveolar-capillary membrane abnormalities are fluid-independent.

Effects of simulated altitude-induced hypoxia on exercise capacity in patients with chronic heart failure.

PURPOSE: Patients with stable heart failure often wish to spend time at altitudes above those of their residence. However, it is not known whether they can safely tolerate ascent to high altitudes or what its effects on work capacity may be. SUBJECTS AND METHODS: We studied 14 normal subjects and 38 patients with clinically stable heart failure, 12 of whom had normal workload [peak exercise oxygen consumption (VO(2)) greater than 20 mL/min/kg], 14 of whom had slightly diminished workload (peak VO(2) 20 to 15 mL/min/kg), and 12 of whom had markedly diminished workload (peak VO(2) less than 15 mL/min/kg) at baseline. All performed cardiopulmonary exercise tests with inspired oxygen fractions equal to those at 92, 1,000, 1,500, 2,000, and 3,000 m, and maximum achieved work rates (mean +/- SD) were measured. RESULTS: All subjects completed the trial; no test was interrupted because of arrhythmia, angina, or ischemia. Maximum work rate decreased in parallel with increasing simulated altitude. The percentage decrease was greater for patients with heart failure and was most marked among those with the lowest workload at baseline. Maximum achieved work rate declined by 3% +/- 4% per 1,000 m in normal subjects, by 5% +/- 3% (P <0.01) in patients with heart failure with normal workload, by 5% +/- 4% (P <0.01) in patients with slightly diminished workload, and by 11% +/- 5% (P <0.01 vs normal subjects and vs the other patients with heart failure) in patients with markedly reduced workload. CONCLUSION: Patients with stable heart failure who ascend to higher altitudes should expect to have a reduction in maximum physical activity in proportion to their exercise capacity at sea level.

Cardiomegaly as a possible cause of lung dysfunction in patients with heart failure.

BACKGROUND: Our hypothesis is that an enlarged heart may compete for space with the lungs, causing a restrictive pattern that is often seen in patients with chronic heart failure. METHODS: Eighty patients with stable congestive heart failure in New York Heart Association classes II and III participated in the study. We measured cardiothoracic index (chest radiography), FEV1, vital capacity, alveolar volume, lung diffusion capacity for carbon monoxide (DLCO), and its 2 subcomponents alveolar-capillary membrane diffusion (DM), and pulmonary capillary blood volume. RESULTS: Reliable measurements were obtained in 72 of 80 participants enrolled. Cardiothoracic index averaged 57% +/- 7%. FEV1, vital capacity, alveolar volume, DLCO, and DM were inversely related to the cardiothoracic index (r = -0.514, -0.557, -0.522, -0.475, and -0.480, respectively). However, the relations of DLCO and DM with the cardiothoracic index were lost when DLCO and DM were adjusted for alveolar volume. A significant correlation (P < .01) was found between alveolar volume and vital capacity, FEV1, and DLCO (r = 0.799, 0.705, and 0.614, respectively). At multivariate analysis, cardiothoracic index, FEV1, and pulmonary capillary blood volume were independent predictors of DLCO, whereas alveolar volume, FEV1, and left ventricular ejection fraction were independent predictors of DM. CONCLUSIONS: Cardiac enlargement in chronic heart failure appears to be involved in causing restrictive lung pattern and a reduced alveolar volume that disturbs carbon monoxide diffusion.

Impeded alveolar-capillary gas transfer with saline infusion in heart failure.

The microvascular pulmonary endothelium barrier is critical in preventing interstitial fluid overflow and deterioration in gas diffusion. The role of endothelium in transporting small solutes in pathological conditions, such as congestive heart failure (CHF), has not been studied. Monitoring of pulmonary gas transfer during saline infusion in CHF was used to probe this issue. Carbon monoxide diffusion (DL(CO)), its membrane diffusion (D(M)) and capillary blood volume (V(C)) subcomponents, and mean right atrial (rap) and mean pulmonary wedge (wpp) pressures after saline or 5% D-glucose solution infusions were compared with baseline in 26 moderate CHF patients. Saline was also tested in 13 healthy controls. In patients, 750 mL of saline lowered DL(CO) (-8%, P<0.01 versus baseline), D(M) (-10%, P<0.01 versus baseline), aldosterone (-29%, P<0.01 versus baseline), renin (-52%, P<0.01 versus baseline), and hematocrit (-6%, P<0.05 versus baseline) and increased V(C) (20%, P<0.01 versus baseline), without changing rap and wpp. Saline at 150 mL produced qualitatively similar results regarding DL(CO) (-5%, P<0.01 versus baseline), D(M) (-7%, P<0.01 versus baseline), V(C) (9%, P<0.01 versus baseline), rap, wpp, aldosterone (-9%, P<0.05 versus baseline), and renin (-14%, P<0.05 versus baseline). Glucose solution (750 mL), on the contrary, increased DL(CO) (5%, P<0.01 versus 750 mL of saline) and D(M) (11%, P<0.01 versus 750 mL of saline) and decreased V(C) (-9, P<0.01 versus 750 mL of saline); aldosterone (-40%), renin (-41%), hematocrit (-3%), rap, and wpp behaved as they did after saline infusion. In controls, responses to both saline amounts were similar to responses in CHF patients regarding aldosterone, renin, hematocrit, rap, and wpp, whereas DL(CO), D(M), and V(C) values tended to rise. Hindrance to gas transfer (reduced DL(CO) and D(M)) with salt infusion in CHF, despite an increase in V(C) and no variations in pulmonary hydrostatic forces, indicates an upregulation in sodium transport from blood to interstitium with interstitial edema. Redistribution of blood from the lungs, facilitating interstitial fluid reabsorption, or sodium uptake from the alveolar lumen by the sodium-glucose cotransport system might underlie the improved alveolar-capillary conductance with glucose.

Oxygen consumption.

It gets more and more frequent to use oxygen consumption (VO2) to evaluate exercise capacity and response to treatment in heart failure patients. The amount of VO2 is due to ventilation, oxygen transport and muscle activity. No one of these single steps can define by itself VO2, but all these physiological functions are integrated each other. In this paper we examine the modifications of cardiac output, arteriovenous oxygen content difference, and the temporal behavior of their variations during exercise in heart failure. We specifically describe changes in VO2 during simulated altitude; we also contemplate mechanisms governing oxygen diffusion from capillary bed to mitochondria and critical capillary PO2 concept.

Evidence of multifocal activity of coronary disease in patients with acute myocardial infarction.

BACKGROUND: Destabilization of the fibrous cap facilitates plaque rupture, thrombus formation, and myocardial infarction. Because systemic stimuli, such as lipoproteins, infectious agents, and autoantigens, may incite this reaction, one may wonder whether disruption mechanisms are only local or systemic and infarction is caused by an arbitrary plaque event or by a systemic, acute activity of the coronary disease. METHODS AND RESULTS: Early (3 to 5 days) and late (1 month) peri-infarction coronary angiographic data in 23 patients with first infarction were compared with that in 23 similar patients, with angiography performed because of stable angina and repeated after 1 month before angioplasty. Nonculprit lesion changes at the narrowest point defined progression or regression when exceeding 0.27 mm. In patients with recent infarction we found that 16 had progression, 4 had regression, 1 had both, 2 were steady (values in patients with stable angina being 2 [P<.0011, 1 [NS], 0 [NS], and 20 [P<.001]); 27 lesions were infarct related; 17 of the 45 nonculprit lesions progressed and 5 regressed (values in stable angina being 2 [P<.001] and 1 [P<.05] out of 78); minimal diameter reduction of progressing stenoses averaged 0.39 mm; lumen increase of regressing lesions averaged 0.30 mm; 3 patients developed interim rest angina associated with progression of a nonculprit lesion. CONCLUSIONS: A greater proportion of subjects and lesions with progression or regression (in infarction versus stable angina) supports the hypothesis that infarction is a hallmark of systemic coronary disease activity. Changes might vary according to the "maturation" stage of an atheroma, and maximal expression would be at the level of the offending plaque. Shrinkage, thrombolysis, or vascular remodeling would determine the residual plaque morphology.

[Peri-infarct angiographic behavior of "non-culprit" coronary infarct lesions]. / Comportamento angiografico perinfartuale delle lesioni coronariche "non colpevoli" di infarto.

Because systemic factors, such as lipoproteins, autoantigens, infectious agents, may facilitate plaque rupture, thrombus formation and coronary occlusion, the question may arise of whether thrombosis be only a local plaque event or the consequence of an acute activity of the entire coronary tree. Taking changes at the narrowest point of non culprit lesions as reflecting progression or regression of the disease when > 0.27 mm, early (within a few days) and late (within 1 month) coronarographic findings in 23 patients with first infarction were compared with those of patients with stable angina, in whom coronary angiography was performed for diagnostic purposes and was repeated 1 month later, before angioplasty. Sixteen infarction patients had progression, 4 had regression, 1 had both, and 2 had steadiness; corresponding values in stable angina group were 2 (p < 0.001), 1 (NS), 0 (NS) and 20 (p < 0.001). In the infarction group, 17 out of the 45 non culprit lesions progressed and 5 regressed; corresponding figures in stable angina group were 2 (p < 0.001) and 1 (p < 0.05). Three of the infarction patients developed interim angina at rest that was associated with progression of a culprit lesion in each of them. These results support the hypothesis that in a number of cases infarction may not reflect an arbitrary plaque event but rather a systemic coronary disease activity with maximal expression at the level of the offending plaque.