Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD

Figures & data

Table 1. Subjects’ main characteristics and pharmacological treatment.

	Controls (n = 12)	COPD (n = 16)	Heart failure (n = 15)	Overlap (n = 16)
Demographic/anthropometric
Age, yrs	68.7 ± 8.0 ^a	69.3 ± 7.4^a	67.5 ± 9.2 ^a	70.9 ± 7.6^a
Height, cm	171.2 ± 5.4^a	169.8 ± 9.9^a	170.9 ± 6.2^a	168.6 ± 8.3^a
Weight, kg	79.8 ± 13.7^a	78.3 ± 16.9^a	77.0 ± 11.0^a	81.3 ± 9.3^a
Body mass index, kg/m^2	25.8 ± 3.6^a	26.6 ± 4.5^a	24.4 ± 7.3^a	27.1 ± 6.0^a
mMRC dyspnea score (2/3/4)	–	4/10/2	3/9/3	3/9/4
NYHA functional class (2/3)	–	11/5	11/4	12/4
Ejection Fraction (%)	65.9 ± 9.7^a	64.1 ± 10.3^a	31.3 ± 8.1^b	32.5 ± 6.9^b
Estimated pulmonary systolic arterial pressure (mmHg) ^*	–	37.8 ± 19.8^a	41.4 ± 20.1^a	40.6 ± 28.1^a
Smoking, never/ex/current	12/0/0	0/13/3	9/3/3	0/15/1
pack-yrs	0	51.3 ± 15.8^a	40.4 ± 16.0^b	55.1 ± 21.6^a
Main co-morbidities
Hypertension	6^a	10^b	9^b	9^b
Type II diabetes	5^a	8^b	9^b	8^b
Hypercolesterolemia	3^a	12^b	13^b	12^b
Depression	3^a	6^b	5^b	7^b
Main medications
Long-acting β2 agonists	0^a	14^b	0^a	10^b
Long-acting anti-muscarinics	0^a	15^b	0^a	14^b
Inhaled steroids	0^a	12^b	0^b	11^b
Diuretics	0^a	2^a	15^b	16^b
Selective β-blockers	0^a	0^a	15^b	16^b
Angiotensin-conversor enzyme inhibitors	0^a	2^a	9^b	8^b

P < 0.05: Statistically-significant differences are indicated by different letters. Values are mean±SD or frequency (N). ^* N = 0, 9, 11, and 12 for controls, COPD, heart failure and overlap, respectively (participants with Dopppler-detectable tricuspide regurgitation jet).

Table 2. Resting lung function and responses to incremental exercise.

	Controls (n = 12)	COPD (n = 16)	Heart failure (n = 15)	Overlap (n = 16)
Lung Function
FVC,%pred	103.8 ± 9.7^a	78.3 ± 10.0^b	82.4 ± 10.0^b	74.5 ± 11.2^b
FEV1,%pred	94.1 ± 8.2^a	54.1 ± 13.9^b	79.3 ± 11.2^c	56.9 ± 15.9^b
FEV1/FVC	0.75 ± 0.03^a	0.57 ± 0.09^b	0.82 ± 0.05 ^c	0.62 ± 0.08^b
TLC,%pred	101.1 ± 10.8^a	120.1 ± 14.3^b	89.9 ± 10.1^c	108.1 ± 9.9^a
RV,%pred	96.1 ± 9.3^a	181.3 ± 30.9^b	90.5 ± 13.8^a	121.5 ± 15.7^c
DLCO,%pred	111.1 ± 14.7^a	50.5 ± 10.9^b	70.9 ± 15.8^c	59.9 ± 11.1^d
PaO2, mmHg	–	65.6 ± 3.9^a	72.0 ± 5.3^b	67.6 ± 5.1^a
PaCO2, mmHg	–	42.5 ± 3.6^a	35.6 ± 3.1^b	38.9 ± 3.3^c
Incremental Exercise Test
Work rate,%pred	89.5 ± 6.2^a	54.8 ± 9.4^b	56.1 ± 8.7^b	52.7 ± 10.3^b
O2 uptake,%pred	92.1 ± 9.9^a	60.1 ± 10.3^b	50.3 ± 8.7^c	46.3 ± 7.3^c
ΔO2/Δwork rate, mL/min/W	10.1 ± 1.2^a	9.7 ± 2.0^b	7.8 ± 1.8^c	7.4 ± 1.7^c
Ventilation/MVV	0.52 ± 0.10^a	0.89 ± 0.11^b	0.64 ± 0.12^c	0.86 ± 0.09^b
Heart rate, bpm	152 ± 15^a	138 ± 10^b	119 ± 12^c	120 ± 11^c
Heart rate,%pred	102.5 ± 5.9^a	87.3 ± 9.9^b	70.1 ± 7.8^c	70.4 ± 6.3^c
SpO2,%	95 ± 3^a	88 ± 5^b	94 ± 3^a	93 ± 4^a
Dyspnea score	3 (2–5)^a	7.5 (5–10)^b	5 (4–8)^c	7 (5–10)^d
Leg effort score	6 (4–10)^a	5 (3–7)^b	7.5 (5–10)^c	7.5 (6–10)^c
Dyspnea as limiting symptom	0/12^a	14/16^b	7/15^c	8/16^c
Leg effort as limiting symptom	12/12^a	8/16^b	13/15^a	14/16^a

P<0.05: Statistically-significant differences are indicated by different letters. Values are mean ± SD or median (range).

FVC = forced expiratory volume; FEV₁ = forced expiratory volume in 1 s; TLC = total lung capacity; RV = residual volume; DL_CO = lung diffusing capacity; PaO₂ = arterial partial pressure for oxygen; PaCO₂ = arterial partial pressure for carbon dioxide; MVV = maximal voluntary ventilation; SpO₂ = oxygen saturation by pulse oximetry.

Table 3. Physiological and sensorial responses to constant work rate exercise test at 80% peak.

	Controls (n = 12)	COPD (n = 16)	Heart failure (n = 15)	Overlap (n = 16)
Tlim, s	1040 (743–1200)^a	332 (215–414)^b	315 (197–401)^b	202 (98–301)^c
O2 uptake, mL/min	1528 ± 289^a	1180 ± 195^b	1131 ± 178^b	1095 ± 215^b
CO2 output, mL/min	1747 ± 215^a	1215 ± 208^b	1334± 221^c	1400± 249^c
Respiratory exchange ratio	1.14 ± 0.09^a	1.03 ± 0.07^b	1.18 ± 0.10^c	1.20 ± 0.11^c
Heart rate, bpm	146 ± 12^a	132 ± 11^b	112 ± 10^c	110 ± 13^c
Heart rate,%pred	97.3 ± 6.1^a	81.5 ± 10.1^b	68.9 ± 8.8^c	66.9 ± 8.4^c
Ventilation/MVV	0.45 ± 0.12^a	0.88 ± 0.10^b	0.59 ± 0.14^c	0.85 ± 0.10^b
Ventilation /CO2 output ratio	30 ± 4^a	31 ± 4^a	40 ± 5^b	41 ± 4^b
End-tidal CO2, mmHg	30 ± 3^a	40 ± 5 ^b	34 ± 4^c	33 ± 5^c
End-exercise – rest PartO2, mmHg	4.3 ± 2.1^a	−10.9 ± 7.9^b	1.5 ± 4.7^c	−2.3 ± 3.9^c
End-exercise – rest SpO2,%	3 ± 2^a	−6 ± 2^b	2 ± 3^a	3 ± 3^a
End-exercise – rest PartCO2, mmHg	−6.1 ± 3.5^a	6.4 ± 4.3^b	−4.9 ± 3.0^c	−5.3 ± 4.4^c
Dyspnea score	2 (1–4)^a	7 (5–10)^b	4.5 (3–7)^c	5.5 (4–8)^c
Leg effort score	6 (4–8)^a	4 (2–6)^b	7 (5–9)^c	8 (5–10)^c
Leg effort-dyspnea	4 (1–6)^a	−3 (−6–1)^b	2.5 (−1–5)^c	3.5 (1–6) ^c

P < 0.05: Statistically significant differences are indicated by different letters. Values are mean ± SD or median (range).

Tlim, time to fatigue; MVV = maximal voluntary ventilation; art = arterialized; SpO₂ = oxygen saturation by pulse oximetry.

Figure 1. Central (panels a and b) and peripheral (panels c and d) hemodynamic responses as a function of exercise intensity and their relationship (panels e and f) in healthy controls and patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and COPD-CHF (overlap). “Δ“ is the difference between 20% and 80% peak work rate.

Figure 2. Blood lactate concentration and muscle deoxygenation (HHb) as a function of exercise intensity in healthy controls and patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and COPD-CHF (overlap). “Δ“ is the difference between 20% and 80% peak work rate.

Figure 3. Relationship between time to exercise intolerance (Tlim) and changes in muscle blood flow and oxygen uptake () in healthy controls and patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and COPD-CHF (overlap). “Δ“ is the difference between 20% and 80% peak work rate.