Resting pulmonary function and artery pressure and cardiopulmonary exercise testing in chronic heart failure patients in Taiwan − a prospective observational cross-sectional study comparing healthy subjects and interstitial lung disease patients

Figures & data

Figure 1. Flow chart. A total of 234 subjects were assessed for eligibility. Twenty-seven patients with chronic heart failure (CHF), 23 with interstitial lung disease (ILD), and 33 healthy controls were enrolled. All of the subjects underwent lung function tests within 3 months before enrollment. All of the patients with CHF had exertional dyspnea, LVEF <45–50%, and a forced expired volume in one second (FEV₁)/forced vital capacity (FVC) of >0.7. ILD patients were enrolled only if their FEV₁/FVC was >0.7 and their FVC and TLC were <80% predicted. The healthy controls were free of known significant diseases. A total of 151 subjects were excluded due to the reasons shown. For details about the inclusion and exclusion criteria of the participants, please refer to the text. 2D: two-dimensional echocardiography; PFT: pulmonary function testing; CPET: cardiopulmonary exercise testing.

Table 1. Demographic data, blood test, and questionnaire scores in the chronic heart failure (CHF) and interstitial lung disease (ILD) groups and normal subjects.

	CHF (27)		ILD (23)		Normal (33)		CHF vs. ILD	CHF vs. normal
Group (N)	Mean	SE	Mean	SE	Mean	SE	p Value	p Value
Age, years	57.7	1.9	64.5	2.1	61.8	1.7	0.04	NS
Sex, M:F	27:0		9:14		33:0
BMI, kg/m^2	26.6	0.6	23.6	0.6	24.8	0.5	0.001	0.047
Cigarette, pack-year	28.9	3.8	9.8	4.2	2.9	3.5	0.003	<0.0001
Borg score @ rest	0.4	0.1	0.5	0.1	0.0	0.1	NS	0.03
NYHA score, 1–4	1.5	0.1	1.6	0.1	1.0	0.1	NS	0.0001
mMRC score, 0–4	0.5	0.1	0.7	0.1	0.0	0.1	NS	0.006
Leisure activity, 0–4	1.6	0.1	1.8	0.2	1.6	0.1	NS	NS
CAT summed score, 0–40	3.8	0.8	8.7	0.9	0.5	0.7	<0.0001	0.006
OCD score, 0–10 cm	7.5	0.2	6.9	0.2	8.3	0.2	0.05	0.01
NT-proBNP, pg/mL	358.3	60.4	219.9	66.5	45.3	6.3	NS	<0.0001

Abbreviations: CAT: chronic obstructive pulmonary disease assessment test; mMRC: modified Medical Research Council; NYHA: New York Heart Association; OCD: oxygen-cost diagram. Leisure activity was coded 1–4 according to hours of activity per week: 1 = <1 h; 2 = 1–3 h; 3 = 3–6 h; 4 = >6 h. Bolded numbers indicating more advanced or impaired between the disease groups.

Table 2. Echocardiographic and lung function data in the chronic heart failure (CHF) and interstitial lung disease (ILD) groups and normal subjects.

	N	CHF		ILD		Normal		CHF vs. ILD	CHF vs. NORMAL
	CHF:ILD:Normal	Mean	SE	Mean	SE	Mean	SE	p Value	p Value
LVEF, %	27:20:8	41.6	1.3	62.3	1.3	61.3	2.2	<0.0001	<0.0001
Max velocity, TR, cm/s	27:20:8	249.3	6.7	279.7	10.4	227.9	14.1	0.01	NS
Max PG, TR, mmHg	27:19:8	24.2	0.9	31.9	2.6	21.3	2.8	0.003	NS
RVSP, TR, mmHg	27:18:8	34.0	1.9	40.6	3.2	28.8	3.9	0.06	NS
FVC, % predicted	27:23:33	93.4	2.7	67.4	2.9	101.8	2.5	<0.0001	0.06
FEV1, % predicted	27:23:33	94.9	2.6	70.6	2.8	102.7	2.4	<0.0001	0.07
FEV1/FVC, %	27:23:33	81.4	1.1	86.1	1.2	79.8	1.0	0.01	NS
MMEF, % predicted	27:23:33	88.6	5.1	74.3	5.5	92.6	4.6	NS	NS
PEF, % predicted	27:23:33	86.4	3.5	70.0	3.7	104.0	3.1	0.005	0.0007
TLC, % predicted	27:23:33	93.4	2.3	75.7	2.4	97.2	2.0	<0.0001	NS
RV/TLC, %	27:23:33	39.1	1.4	50.9	1.6	38.7	1.3	<0.0001	NS
RV/TLC, % predicted	27:23:33	106.6	3.3	128.0	3.6	101.4	3.0	<0.0001	NS
DLCO, % predicted	27:23:33	89.4	3.1	47.4	3.4	106.2	2.8	<0.0001	0.0002
DLCO/VA, % predicted	27:23:33	104.2	3.5	73.8	3.9	103.7	3.2	<0.0001	NS
VA, % predicted	27:23:33	78.1	2.1	58.4	2.3	86.8	1.9	<0.0001	0.008

Abbreviations: D_LCO: diffusing capacity for carbon monoxide of lung; FEV₁: forced expired volume in one second; FVC: forced vital capacity; LVEF: left ventricular ejection fraction; Max: maximum; MMEF: maximum mid-expiratory flow; PEF: peak expiratory flow; RV: residual volume; RVSP: right ventricular systolic pressure; TLC: total lung capacity; TR: tricuspid valve regurgitation. LVEF in the CHF group including heart failure with reduced and mildly reduced ejection fractions: <30%, n = 3; ≥30%− <40%, n = 4; ≥40%− <50%, n = 20, LVEF in normal controls: n = 8, all >50%, (61.3 ± 2.1%); RVSP = 4 V² + RAP, where V: peak TR jet velocity; RAP: mean right atrial pressure. Bolded numbers indicating more impaired when compared between the disease groups.

Table 3. Cardiopulmonary exercise variables at peak exercise unless specified.

	CHF (27)		ILD (23)		Normal (33)		CHF vs ILD	CHF vs Normal
Group (N)	Mean	SE	Mean	SE	Mean	SE	p Value	p Value
Symptoms
Borg leg fatigue	6.3	0.4	6.9	0.4	6.5	0.4	NS	NS
Borg dyspnea	5.3	0.4	7.2	0.4	5.8	0.4	0.006	NS
Exercise capacity related variables
V̇O2, % predicted	72.9	3.6	74.78	3.8	91.6	3.2	NS	0.0004
Work rate, % predicted	82.0	4.0	84.04	4.3	115.5	3.6	NS	<0.0001
Effort related variables
RER	1.06	0.02	1.05	0.02	1.16	0.02	NS	<0.01
Heart rate, %predicted	83.0	2.2	84.4	2.3	95.2	1.9	NS	0.0001
Pulse pressure, mm Hg	71.7	6.0	83.0	6.3	103.2	5.3	NS	0.0003
Ventilation and its limit related variables
Breathing reserve, %	46.2	3.1	32.1	3.3	39.1	2.7	0.007	NS
V̇E, L/min	57.7	3.4	45.5	3.6	71.4	3.0	0.04	0.01
VT/TI , L/s	2.1	0.1	1.6	0.1	2.6	0.1	0.005	0.02
VT/TE, L/s	1.8	0.1	1.4	0.1	2.2	0.1	0.08	0.01
Ventilation efficiency and gas exchange related variables
SpO2, %	96.8	0.9	87.0	1.0	96.7	0.8	<0.0001	NS
V̇E/V̇O2 @AT	27.6	1.1	32.6	1.2	28.0	1.0	0.008	NS
V̇E/V̇CO2 @AT	33.1	1.1	37.8	1.2	31.7	1.0	0.01	NS
V̇E/V̇O2	34.9	1.3	39.7	1.4	34.4	1.1	0.03	NS
V̇E/V̇CO2	37.2	1.6	42.0	1.7	39.6	1.5	NS	NS
Tidal volume expansion related variables
EELV/TLC	0.51	0.03	0.51	0.03	0.48	0.03	NS	NS
VT-EELV/TLC	0.83	0.02	0.84	0.02	0.81	0.02	NS	NS
VT/TLC	0.32	0.01	0.28	0.01	0.33	0.01	0.05	NS
Breathing time related variables
BF, breath/min	31.6	1.8	41.7	1.9	36.4	1.6	0.001	NS
TI, s	0.91	0.04	0.74	0.04	0.81	0.04	0.008	NS
TE, s	1.09	0.06	0.80	0.06	0.97	0.05	0.002	NS
RSBI, breath/L	18.1	2.3	41.9	2.5	19.3	2.1	<0.0001	NS
IDC	0.46	0.01	0.48	0.01	0.46	0.01	NS	NS
E: I	1.22	0.04	1.10	0.05	1.18	0.04	NS	NS

Abbreviations: AT: anaerobic threshold; B_F: breathing frequency; CHF: chronic heart failure; EELV: end-expiratory lung volume; E:I: expiratory time (T_E) and inspiratory time (T_I) ratio; IDC: inspiratory duty cycle: T_I/breathing cycle time; ILD: interstitial lung disease; O₂P: oxygen pulse: oxygen uptake (V̇O₂) in mL/heart rate in beat/min; RER: respiratory exchange ratio; RSBI: rapid shallow breathing index: B_F/V_T in L; SpO₂: oxyhemoglobin saturation; TLC: total lung capacity; V̇CO₂: CO₂ output; V̇_E: minute ventilation; V_T: tidal volume in L; V_T-EELV: end-inspiratory lung volume. Bolded number indicating more impaired between the disease groups.

Table 4. Correlations of dyspnea score @ peak exercise with breathing pattern and gas exchange at peak exercise or specified otherwise and with echocardiography and lung function at rest in patients with chronic heart failure (CHF) and those with interstitial lung disease (ILD).

	CHF		ILD
	r	p Value	r	p Value
Left ventricular ejection fraction, %		NS		NS
Max velocity, TR, cm/s		NS		NS
Max PG, TR, mmHg	0.42	0.03		NS
FVC%	0.41	0.04		NS
IC%	0.41	0.04		NS
DLCO%		NS		NS
V̇E/V̇O2 @ anaerobic threshold		NS		NS
V̇O2, % predicted		NS		NS
Heart rate, % predicted		NS		NS
SPO2, %		NS		NS
V̇E/V̇CO2		NS		NS
VT/TI, L/s		NS		NS
VT/TE, L/s	0.41	0.04		NS
EILV/TLC	0.35	0.08		NS
EELV/TLC		NS		NS
VT/TLC		NS		NS
Breathing frequency, breath/min		NS		NS
RSBI, breath/L		NS		NS
TE, s		NS		NS
TI, s		NS	−0.40	0.06
I:E		NS	−0.41	0.05
IDC		NS	−0.43	0.04

For abbreviations, please refer to Tables 2 and 3.

Silvestre OM, Nadruz W, Jr.Querejeta Roca G, et al. Declining lung function and cardiovascular risk: the ARIC study. J Am Coll Cardiol. 2018;72(10):1109–1122. doi: 10.1016/j.jacc.2018.06.049.

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Data availability statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.