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.

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.

Non-invasive measurement of stroke volume during exercise in heart failure patients.

The objective of the present study was to determine the variability of the arterio-venous O(2) concentration difference [C(a-v)O(2)] at anaerobic threshold and at peak oxygen uptake (VO(2)) during a progressively increasing cycle ergometer exercise test, with the purpose of assessing the possible error in estimating stroke volume from measurements of VO(2) alone. We sampled mixed venous and systemic arterial blood every 1 min during a progressively increasing cycle ergometer exercise test and measured, in each blood sample, haemoglobin concentration and blood gas data. Ventilation, VO(2) and CO(2) uptake were also measured continuously. We studied 40 patients with normal haemoglobin concentrations and with stable heart failure due to ischaemic or idiopathic cardiomyopathy. Mean values (+/-S.D.) for C(a-v)O(2) were 7.8+/-2.6, 13.0+/-2.4 and 15. 0+/-2.7 ml/100 ml at rest, anaerobic threshold and peak VO(2) respectively. The patients with heart failure were divided into classes according to their peak VO(2). Classes A, B and C contained patients with peak VO(2) values of>20, 15-20 and 10-15 ml.min(-1). kg(-1) respectively. At anaerobic threshold, C(a-v)O(2) was 12.3+/-1. 3, 13.1+/-2.7 and 13.5+/-2.6 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P<0.05). At peak exercise C(a-v)O(2) was 13.6+/-1.4, 15.6+/-2.5 and 15.4+/-3.2 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P<0.05). Stroke volume was estimated for each subject using the mean values of the measured C(a-v)O(2) in each functional class and individual values of VO(2) and heart rate using the Fick formulation. The average difference between the stroke volume estimated from mean C(a-v)O(2) and that obtained using the patient's actual C(a-v)O(2) value was 9.2+/-9.7, 1.0+/-8.8 and -0.2+/-6.1 ml at anaerobic threshold, and -1.9+/-11.3, 0.9+/-10.0 and -2.3+/-8.5 ml at peak exercise, in classes A, B and C respectively. Among the various classes, the most precise estimation of stroke volume was observed for class C patients. We conclude that stroke volume during exercise can be estimated with the accuracy needed for most purposes from measurement of VO(2) at the anaerobic threshold and at peak exercise, and from population-estimated mean values for C(a-v)O(2) in heart failure patients.

Exercise-induced hemoconcentration in heart failure due to dilated cardiomyopathy.

Exercise-induced hemoconcentration is a useful mechanism, particularly in heart failure, because it increases oxygen content of blood, perfusing the working muscles; in 50 normal subjects and 50 patients with congestive heart failure, hemoglobin at peak exercise increased by 7 +/- 3% and 5 +/- 3%, respectively. Hemoconcentration was due to fluid flux out of the vascular bed, likely through oncotic forces related to intracellular lactate accumulation and not to red blood cell recruitment from other organs (spleen), because hemoglobin increase, as a percentage, was similar to plasma protein increase.

[Periodic breathing during physical exercise: expression of a form of ventricular interdependence?]. / Respiro periodico durante esercizio fisico: espressione di una diversa forma di interdipendenza ventricolare?

Periodic breathing may be observed in patients with severe congestive heart failure during exercise. We describe a patient with such a breathing pattern. We noted that nadir of oxygen consumption cycles slightly preceded the nadir of ventilation cycles, suggesting that this breathing pattern is due to cardiac output periodic changes, possibly through an interplay among the two ventricles and the pulmonary blood reservoir.

[Effects of cardiomegaly on the anatomical and functional state of the lung in chronic heart failure]. / Influenza della cardiomegalia sullo stato anatomico e funzionale del polmone nello scompenso cardiaco cronico.

Heart and lungs might compete for the intrathoracic space in case of heart enlargement (as in heart failure). Therefore, the pulmonary abnormalities observed in patients with chronic heart failure (restrictive pattern and reduction of diffusion capacity) might be at least in part related to cardiomegaly. In 53 patients (11 women, 42 men, mean age 65 +/- 8 years) with stable heart failure and cardiac enlargement (cardiothoracic ratio-Ctr > or = 50%) we measured carbon monoxide lung diffusion (DLCO), lung tissue content (VT, single breath, expiratory regression of acetylene), alveolar volume (Va, single breath, expiratory regression of methane) and vital capacity (VC). In 16 patients the two subcomponents of DLCO, i.e. alveolar-capillary membrane diffusion (Dm) and diffusion related to capillary volume (Cv), were analyzed. Patients were grouped for Ctr (> or = 60%, Group 1, n = 28 and < 60%, Group 2, n = 25): VT (Group 1 0.62 +/- 0.2 l; Group 2 0.76 +/- 0.2 l, p < 0.01); Va (Group 1 4.21 +/- 0.97 l; Group 2 5.37 +/- 1.12 l, p < 0.0001); VC (Group 1 2.3 +/- 0.6 l; Group 2 3.1 +/- 0.6 l, p < 0.0001); DLCO (Group 1 16.15 +/- 3.95 ml/min x mmHg; Group 2 22.24 +/- 6.57 ml/min x mmHg, p < 0.0001). An inverse correlation was observed between Dm and Ctr (r = -0.47, p < 0.02), which disappeared when Va was accounted for Dm/Va (r = -0.12, NS). Cv was lower in Group 1 vs Group 2. In conclusion, in patients with Ctr > or = 60% (Group 1) "anatomy" (VT, Va, VC and Cv) and function (DLCO) of the lungs are impeded. This is likely due to reduction of space available for the lungs in the thorax by an enlarged heart (no correlation between Dm/Va vs Ctr).

[Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure]. / Meccanismi di facilitazione della cessione di ossigeno durante esercizio nel paziente con scompenso cardiaco cronico]

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.

[Acetylsalicylic acid antagonism vs ACE inhibitor in congestive heart failure as shown by a diminished respiratory and exercise capacity]. / Antagonismo di acido acetilsalicilico vs ACE-inibitore nell'insufficienza cardiaca congestizia rivelato da una diminuita capacità respiratoria e di esercizio.

Our hypothesis is that regulation of the lung vessel tone and microvascular permeability may be disrupted in chronic heart failure (CHF) and angiotensin converting enzyme (ACE) inhibition may contribute to their readjustment. This hypothesis is based on the fact that KII-ACE, the same enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the luminal surface of the lung vessels and its blockade in CHF may reduce their exposure to an excess of angiotensin II and augment the action of prostaglandins and nitric oxide (NO) deriving from local kinin hyperconcentration. We probed whether ACE-inhibitors influence the pulmonary function; this is peculiar of CHF; they act as KII- or ACE-blockers. Aspirin was utilized as a prostaglandin synthesis inhibitor. We investigated 16 CHF patients and 16 age- and sex-matched normal volunteers or mild untreated hypertensives. All were non-smokers, not taking ACE-inhibitors, aspirin or other cyclooxygenase inhibitors. Pulmonary function tests, exercise testing with respiratory gases and echocardiography were performed in the run-in and repeated at the end of placebo, enalapril (10 mg t.i.d.), enalapril plus aspirin (325 mg/day) and aspirin given in random order and double-blind fashion for 15 days each. Enalapril, as compared to placebo, caused an increase in mean voluntary ventilation (MVV) and alveolar-capillary diffusing capacity for carbon monoxide (DLCO) in CHF, that were counteracted by the addition of aspirin. Aspirin alone was not effective. Enalapril and aspirin were ineffective on the pulmonary function of controls. As to the functional capacity, enalapril increased exercise tolerance time, oxygen consumption (VO2p), minute ventilation (VEp) tidal volume (VTp) and reduced the ratio of volume of dead space gas (VDp) to VTp (VD/VTp), at peak exercise in CHF patients. These effects all were inhibited by the combination of aspirin and were not observed in controls. In CHF VO2p changes from placebo correlated with those in DLCO (r = 0.80, p < 0.0001) and not with those in ejection fraction. This correlation was abolished by aspirin and was not seen in controls. Variations in VD/VTp in CHF patients while on enalapril were related to those in DLCO (r = -0.69, p = 0.003). In CHF the ventilatory equivalent for carbon dioxide production per minute at 1 liter was diminished with enalapril and not in combination with aspirin. Derangements related to CHF are the substrate for benefits of ACE-inhibition on pulmonary function and exercise capacity. Pulmonary diffusion limitation is an important mediator of exercise impairment and its improvement with enalapril goes in parallel with VD/VT, MVV, VT, VE to VCO2 relationship and not with ejection fraction. These patterns reflect changes occurring within the lung that are not related to left ventricular function. The counteracting influence of aspirin on these affects bespeaks a substantial participation of prostaglandins that might readjust capillary permeability and lung interstitial fluid content or alveolar capillary membrane diffusing capacity.

Evaluation of the dead space/tidal volume ratio in patients with chronic congestive heart failure.

Dead space/tidal volume ratio (VD/VT) evaluation is currently performed in patients with respiratory and cardiac disorders, and includes measurement of arterial CO2 partial pressure (PaCO2). PaCO2 is generally derived from either PETCO2 (end-expiratory CO2 pressure) or PJCO2 (calculated as PJCO2 = 5.5 + 0.9 PETCO2 - 2.1 VT). The applicability of these methods may be questionable in chronic heart failure due to its frequent association with lung dysfunction. In 63 patients with congestive heart failure, the authors compared PaCO2 versus PETCO2 and PJCO2 and VD/VT measured with PaCO2 versus VD/VT estimated with PETCO2 (estimation 1) or PJCO2 (estimation 2). Comparisons were made at rest, at submaximal exercise, and at peak exercise. Considering all 326 measurements, there was a strong correlation, but not an identity, between PaCO2 and PETCO2 (PaCO2 = 7.25 + 0.80 PETCO2, r = .84, P < .0001) and between PaCO2 and PJCO2 (PaCO2 = 6.18 + 0.84 PJCO2, r = .85, P < .0001). Results were comparable concerning PaCO2 versus PJCO2. Measured VD/VTs also strongly correlated with estimated VD/VTs (VD/VT measured = -0.03 + 1.11 VD/VT [estimation 1], r = .90, P < .0001, and VD/VT measured = 0.03 + 0.92 VD/VT [estimation 2], r = .90, P < .0001). However, only at rest and, solely for estimation 1, at submaximal exercise were the slopes and y intercepts of measured versus estimated VD/VT not different from 1 and 0, respectively; in this regard, lung dysfunction was more influential than the severity of cardiac failure. Although PaCO2 strongly correlates with PETCO2 and PJCO2, these measurements may not be reliable for a noninvasive calculation of VD/VT in chronic congestive heart failure.

[Measurement of dead space/tidal volume ratio during exercise in patients with heart failure]. / Calcolo del rapporto spazio morto/volume corrente nello scompenso cardiaco durante esercizio.

Dead space (VD)/tidal volume (VT) ratio is an indirect index of ventilation/perfusion matching. Therefore, it is currently evaluated in patients with congestive heart failure to detect the organ system limiting the exercise tolerance. The VD/VT calculation requires measurement of arterial CO2 partial pressure (PaCO2). For practical reasons, the software of most metabolic carts substitutes the PaCO2 with the end-expiratory CO2 (PETCO2) or the PJCO2 (calculated as PJCO2 = 5.5 +/- 0.9 PETCO2-2.1 VT). Nonetheless, the applicability of these methods in congestive heart failure is unknown. We compared in 63 patients with congestive heart failure 326 measurements of PaCO2 versus PETCO2 and PJCO2 and VD/VT measured with PaCO2 versus VD/VT estimated with PETCO2 (estimation 1) or PJCO2 (estimation 2). Comparisons were made at rest (Phase 1), during submaximal exercise (Phase 2), and at peak exercise (Phase 3). We found a strong correlation, but not an identity, between PaCo2 and PETCO2 (PaCO2 = 7.25 +/- 0.80 PETCO2, r = 0.84; p < 0.0001); similarly for PaCO2 and PETCO2. Several observations were out of 95% confidence interval, and some measurements exceeded mean +/- 2 SD when the differences between PaCo2 and PETCO2 or PJCO2 were plotted against the averages from the two (Bland and Altman method). Measured VD/VTs also strongly correlated with the estimated ones (VD/VT measured = -0.03 +/- 1.11 VD/VT estimated 1 r = 0.90; p < 0.0001 e VD/VT measured = 0.03 +/- 0.92 VD/VT estimated 2 r = 0.90; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)