Search

Heart failure (HF) is often associated with pulmonary congestion, reduced lung function, abnormal gas exchange, and dyspnea. We tested whether pulmonary congestion is associated with expanded vascular beds or an actual increase in extravascular lung water (EVLW) and how airway caliber is affected in stable HF Subsequently we assessed the influence of an inhaled short acting beta agonist (SABA). Thirty-one HF (7F; age, 62 ± 11 years; ht. 175 ± 9 cm; wt. 91 ± 17 kg; LVEF, 28 ± 15%) and 29 controls (11F; age; 56 ± 11 years; ht. 174 ± 8 cm; wt. 77 ± 14 kg) completed the study. Subjects performed PFTs and a chest computed tomography (CT) scan before and after SABA CT measures of attenuation, skew, and kurtosis were obtained from areas of lung tissue to assess EVLW Airway luminal areas and wall thicknesses were also measured : CT tissue density suggested increased EVLW in HF without differences in the ratio of airway wall thickness to luminal area or luminal area to TLC (skew: 2.85 ± 1.08 vs. 2.11 ± 0.79, P < 0.01; Kurtosis: 15.5 ± 9.5 vs. 9.3 ± 5.5 P < 0.01; control vs. HF). PFTs were decreased in HF at baseline (% predicted FVC:101 ± 15% vs. 83 ± 18%, P < 0.01;FEV1:103 ± 15% vs. 82 ± 19%, P < 0.01;FEF25-75: 118 ± 36% vs. 86 ± 36%, P < 0.01; control vs. HF). Airway luminal areas, but not CT measures, were correlated with PFTs at baseline. The SABA cleared EVLW and decreased airway wall thickness but did not change luminal area. Patients with HF had evidence of increased EVLW, but not an expanded bronchial circulation. Airway caliber was maintained relative to controls, despite reductions in lung volume and flow rates. SABA improved lung function, primarily by reducing EVLW., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Patients with heart failure (HF) display numerous derangements in ventilatory function, which together serve to increase the work of breathing (W(b)) during exercise. However, the extent to which the resistive and elastic properties of the respiratory system contribute to the higher W(b) in these patients is unknown. We quantified the resistive and elastic W(b) in patients with stable HF (n = 9; New York Heart Association functional class I-II) and healthy control subjects (n = 9) at standardised levels of minute ventilation (V'(E)) during graded exercise. Dynamic lung compliance was systematically lower for a given level of V'(E) in HF patients than controls (p<0.05). HF patients displayed slightly higher levels of inspiratory elastic W(b) with greater amounts of ventilatory constraint and resistive W(b) than control subjects during exercise (p<0.05). Our data indicates that the higher W(b) in HF patients is primarily due to a greater resistive, rather than elastic, load to breathing. The greater resistive W(b) in these patients probably reflects an increased hysteresivity of the airways and lung tissues. The marginally higher inspiratory elastic W(b) observed in HF patients appears related to a combined decrease in the compliances of the lungs and chest wall. The clinical and physiological implications of our findings are discussed.

Circulation time (the transit time for a bolus of blood through the circulatory system) is a potential index of cardiac dysfunction in chronic heart failure (HF). In healthy subjects, circulation time falls as cardiac output (Q) rises during exercise, however little is known about this index in HF. In this study we examined the relationship between lung-to-lung circulation time (LLCT) during exercise in ten HF (53 +/- 14 year, resting ejection fraction = 23 +/- 8%) and control subjects (51 +/- 18 year). We hypothesized that HF patients would have slower LLCT times during exercise when compared to control subjects. Each subject completed two identical incremental exercise tests during which LLCT was measured in one test and Q measured in the other. Q was measured using the open circuit C(2)H(2) washin technique and circulation time measured using an inert gas technique. In HF patients and control subjects, LLCT decreased and Q increased from rest (HF:LLCT = 53.6 +/- 8.2 s, Q = 4.3 +/- 1.1 l min(-1); control: LLCT = 55.3 +/- 10.9 s, Q = 4.5 +/- 0.5 l min(-1)) to peak exercise (HF:LLCT = 20.6 +/- 3.9* s, Q = 8.8 +/- 2.5* l min(-1); control:LLCT = 14.9 +/- 2.4 s, Q = 16.5 +/- 1.2 l min(-1); *P < 0.05 vs control). LLCT was significantly (P < 0.05) slower for the HF group when compared to the control group during submaximal exercise and at peak exercise. However, at a fixed Q the HF subjects had a faster LLCT. We hypothesize that the faster LLCT at a fixed Q for HF patients, may be the result of a more intensive peripheral vasoconstriction of non-active beds and a better redistribution of blood flow.

Background: Peak exercise capacity (VO2peak) is a measure of the severity of chronic heart failure (CHF); however, few indices of resting cardiopulmonary function have been shown to predict VO2peak. A prolonged circulation time has been suggested as an index of increased severity of CHF. The aim of this study was to investigate the relationship between resting lung-to-lung circulation time (LLCT) and VO2peak in CHF., Methods and Results: Thirty CHF patients (59 +/- 13 years, New York Heart Association: 1.9 +/- 1.0) undertook the study. Each subject completed resting pulmonary and echocardiography measures and an incremental exercise test. LLCT was measured using the reappearance of end-tidal acetylene (P(ET),C2H2) after a single inhalation. Univariate and multivariate stepwise linear regression was used to determine the predictors of VO2peak. Univariate correlates of VO2peak (group mean 1.53 +/- 0.44 L/min(-1)) included LLCT (r = -0.75), inspiratory capacity (r = 0.41), ejection fraction (r = 0.33), peak early flow velocity (r = -0.39), and the ratio of early to late flow velocity (r = -0.31). LLCT was the only independent predictor where VO(2peak) = 3.923-0.045 (LLCT); r2 = 54%., Conclusions: These results suggest that resting LLCT determined using the soluble inert gas technique represents a simple, noninvasive method that provides additional information regarding exercise capacity in CHF.

Background: This study examined the influence of increased cardiac size on maximal lung volumes, forced expiratory airflows, and the diffusing capacity of the lungs in heart failure (HF) patients compared with controls., Methods and Results: Forty-one HF patients of New York Heart Association (NYHA) class: Group A = class I/II (n = 26) and Group B = class III/IV (n = 15) and an equal number matched controls (CTL) were recruited. Participants underwent echocardiography, spirometry, and posteroanterior and lateral chest radiographic evaluation (RAD) for volumetric estimation of the total thoracic cavity (TTC), diaphragm, heart, and lungs. Analysis of variance demonstrated no difference between groups for TTC volume (P = .63). RAD cardiac volumes (% TTC volume) were significantly different among all groups (P < .001). Echocardiograms determined left ventricular mass was elevated in the HF groups compared with the CTL group (P < .001) with no difference between HF groups. Lung volume (% TTC volume) was reduced as a function of disease severity (P < .001). RAD measures of cardiac volume demonstrated the strongest relationship with restrictive lung alterations (t-statistic = -5.627, P < .001 and t-statistic = -4.378, P < .001 for forced vital capacity and forced expiratory volume in 1 second, respectively)., Conclusions: These results suggest cardiac size may pose significant constraints on the lungs and likely plays a major role in the restrictive breathing patterns often reported in HF patients.

Background: Patients with heart failure (HF) display a number of breathing abnormalities including periodic breathing (PB) at rest. Although the mechanism(s) contributing to PB remain unclear, we examined whether changes in pulmonary wedge pressure (PWP) and pulmonary vascular resistance (PVR) alter PB in patients with established HF., Methods: We studied 12 male patients with HF (age, 50 +/- 11 years; ejection fraction, 18.3 +/- 3.8 %; New York Heart Association class, 3.2 +/- 0.4), with PB at rest, who are undergoing right heart catheterization with infusion of nitroprusside., Results: At baseline, patients with HF displayed minute ventilation (V(E)) oscillations with amplitude of 5.5 +/- 2.7 L/min (57 +/- 34% of the average V(E)) and cycle length of 61 +/- 18 seconds. Cardiac index (CI), PVR, and mean PWP averaged 2.0 +/- 0.4 L min(-1) m(-2), 281.9 +/- 214.9 dyne/s per cm(-5), and 28.3 +/- 5.4 mm Hg, respectively. During nitroprusside infusion, CI increased to 3.1 +/- 0.6 L min(-1) m(-2), PVR decreased to 163.9 +/- 85.2 dyne/s per cm(-5), and PWP fell to 10.0 +/- 4.2 mm Hg. Nitroprusside reduced the amplitude (2.6 +/- 2.4 L/min, 23 +/- 21% of average V(E); P < .01) and cycle length (41.4 +/- 28.8 seconds; P < .01) of V(E) oscillations while abolishing oscillations in 3 patients. Although average V(E) and PaCO2 remained unchanged, there was a significant increase in the ratio of tidal volume to inspiratory time (V(T)/T(I); P < .01), suggesting an increase in ventilatory drive. The change in the amplitude of V(E) oscillations was positively correlated with the change in PWP (r = 0.75; P < .01), negatively correlated with the change in PVR (r = 0.63; P < .05), and not correlated with the change in CI., Conclusions: These data suggest that PWP (left atrial pressure) may play a direct role in the PB observed in HF at rest.

Background: The purpose of this study was to determine the influence of changes in cardiac size on total lung volume in patients with chronic heart failure compared to control subjects., Methods: Forty-four patients and age-, gender-, and height-matched control participants were recruited. All participants underwent posteroanterior and lateral chest radiography for volumetric estimations of the total thoracic cavity (TTC), diaphragm, heart, and lungs. To assess the relationship between chronic heart failure severity and cardiac enlargement, patients with chronic heart failure were classified into groups based on New York Heart Association class, as follows: class I and II, n = 26 (group A); class III and IV, n = 18 (group B)., Results: There was no difference between the groups for TTC volume (TTCV) [p = 0.56]. Cardiac volumes were significantly different between all groups for both the absolute volumes (p < 0.001) were calculated as a percentage of TTCV (p < 0.001), with the largest cardiac volumes in group B (twice the volume of healthy control subjects). When expressed as a percentage of TTCV, there also was a clear reduction in lung volumes as a function of disease severity (p < 0.001)., Conclusions: The present study demonstrates a close relationship between the severity of heart failure and cardiac size. These changes in cardiac size within a closed thoracic cavity may pose significant constraints on the lungs, resulting in reductions in lung volumes that likely play a major role in the restrictive breathing patterns often reported in patients with chronic heart failure.

Background: Patients with chronic heart failure (CHF) have reduced pulmonary diffusing capacity for carbon monoxide (DLCO). Acute pulmonary congestion also causes reduction of DLCO, which is reversible. We hypothesized for patients with CHF that the rate of rise of exercise DLCO is reduced compared to healthy controls and falls near end-exercise consistent with progressive interstitial edema., Methods and Results: DLCO and pulmonary blood flow (QC)) were measured by a rebreathe technique in CHF subjects (n = 11) and controls (n = 8) at rest, during constant workload exercise, and after exercise. DLCO of CHF subjects was less than controls at rest (16.5 +/- 1 vs. 21.9 +/- 2 mL/min/mm Hg, P < .01). CHF subjects exercised 11 +/- 2 minutes to 90% peak VO2, whereas controls exercised 17 +/- 2 minutes, reaching 88% peak VO2. In CHF subjects, DLCO increased to 19 +/- 2 mL/min/mm Hg and for controls to 38 +/- 3 mL/min/mm Hg. During the final 3 minutes of exercise, DLCO increased 5% in controls while decreasing 5% in CHF subjects (DLCO/Q(C)) was lower in CHF subjects at rest and progressively lower throughout exercise (P < .01)., Conclusion: In patients with CHF, DLCO has reduced rate of rise with exercise and falls near end-exercise consistent with limitation of alveolar-capillary recruitment and progressive interstitial edema.

Background: The gene encoding ACE exhibits an insertion/deletion polymorphism resulting in 3 genotypes (DD, ID, and II), which affects serum and tissue ACE activity as well as other vasoactive substances. Pulmonary function is frequently abnormal in patients with congestive heart failure (CHF), the mechanism of which has not been completely characterized. ACE inhibition has been shown to improve diffusion across the alveolar-capillary membrane and to improve exercise capacity and gas exchange in CHF. The aim of the current study was to determine if ACE genotype is associated with altered pulmonary function and exercise intolerance in patients with treated CHF., Methods and Results: Fifty-seven patients (stratified according to ACE genotype as 17 DD, 28 ID, 12 II) with ischemic and dilated cardiomyopathy, left ventricular ejection fraction (LVEF) <35%, and <10 pack-years of smoking history were studied. All patients were receiving standard therapy for left ventricular systolic dysfunction. Pulmonary function, LVEF, serum ACE, plasma angiotensin II, atrial natriuretic peptide, and brain natriuretic peptide were measured at baseline. Peak VO2 and gas exchange measurements were assessed with graded exercise. Resting LVEF was similar among the genotype groups (25% to 28%), and no differences were observed in diastolic function or pulmonary artery pressures (P>0.05). Mean peak VO2 and forced vital capacity (% Pred) were significantly reduced (P<0.05), whereas mean serum ACE activity and plasma angiotensin II concentration were highest in DD homozygotes. Subjects homozygous for the D-allele also demonstrated higher mean ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise (P<0.05)., Conclusions: ACE DD genotype is associated with decreased exercise tolerance in CHF, possibly mediated by altered pulmonary function. Pharmacological strategies effecting more complete inhibition of serum and tissue ACE and/or potentiation of bradykinin may improve exercise capacity in patients with CHF and ACE DD genotype.

We examined the degree of ventilatory constraint in patients with a history of chronic heart failure (CHF; n = 11; mean +/- SE age, 62 +/- 4 years; cardiac index [CI], 2.0 +/- 0.1; and ejection fraction [EF], 24 +/- 2%) and in control subjects (CTLS; n = 8; age, 61 +/- 5 years; CI, 2.6 +/- 0.3) by plotting the tidal flow-volume responses to graded exercise in relationship to the maximal flow-volume envelope (MFVL). Inspiratory capacity (IC) maneuvers were performed to follow changes in end-expiratory lung volume (EELV) during exercise, and the degree of expiratory flow limitation was assessed as the percent of the tidal volume (VT) that met or exceeded the expiratory boundary of the MFVL. CHF patients had significantly (p < 0.05) reduced baseline pulmonary function (FVC, 76 +/- 4%; FEV(1), 78 +/- 4% predicted) relative to CTLS (FVC, 99 +/- 4%; FEV(1), 102 +/- 4% predicted). At peak exercise, oxygen consumption (VO(2)) and minute ventilation (V(E)) were lower in CHF patients than in CTLS (VO(2), 17 +/- 2 vs 32 +/- 2 mL/kg/min; VE, 56 +/- 4 vs 82 +/- 6 L/min, respectively), whereas VE/carbon dioxide output was higher (42 +/- 4 vs 29 +/- 5). In CTLS, EELV initially decreased with light exercise, but increased as VE and expiratory flow limitation increased. In contrast, the EELV in patients with CHF remained near residual volume (RV) throughout exercise, despite increasing flow limitation. At peak exercise, IC averaged 91 +/- 3% and 79 +/- 4% (p < 0.05) of the FVC in CHF patients and CTLS, respectively, and flow limitation was present over > 45% of the VT in CHF patients vs < 25% in CTLS (despite the higher VE in CTLS). The least fit and most symptomatic CHF patients demonstrated the lowest EELV, the greatest degree of flow limitation, and a limited response to increased inspired carbon dioxide during exercise, all consistent with VE constraint. We conclude that patients with CHF commonly breathe near RV during exertion and experience expiratory flow limitation. This results in VE constraint and may contribute to exertional intolerance.