Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 15, Number 1, February 2024, pages 18-28

Hemodynamic Response to Exercise Training in Heart Failure With Reduced Ejection Fraction Patients

Figure 1. Flowchart of the study. CPET: cardiopulmonary exercise testing; HFrEF: heart failure with reduced ejection fraction; ICG: impedance cardiography.

Figure 2. Radar changes in peak hemodynamic parameters in responders (R) and non-responders (NR). CO: cardiac output; DBP: diastolic blood pressure; HR: heart rate; SBP: systolic blood pressure.

Figure 3. Receiver operating characteristic curves for discrimination between responder and non-responder HFrEF patients. CO: cardiac output; HFrEF: heart failure with reduced ejection fraction; SVR: systemic vascular resistance; V̇O₂oxygen uptake.

**Table 1.** Baseline Characteristics of HFrEF Patients According to Their Training Response Status
Variable	All patients (n = 76)	Non-responders (n = 38) (ΔV̇O_2peak ≤ 2.2 mL/min/kg)	Responders (n = 38) (ΔV̇O_2peak > 2.2 mL/min/kg)
Data are expressed as mean ± SD for parametric data or as n (%) for dichotomous variables. AF: atrial fibrillation; BM: body mass; BMI: body mass index; BNP: brain natriuretic peptide; Coro: coronaropathy; DCM: dilated cardiomyopathy; F: female; HFrEF: heart failure with reduced ejection fraction; ICD: implantable cardioverter-defibrillator; M: male; SD: standard deviation.
Sex ratio (F/M)	11/65 (14/86)	6/32 (16/84)	5/33 (13/77)
Age (years)	57 ± 12	59 ± 13	56 ± 12
Height (cm)	173.27 ± 9.28	172.03 ± 8.18	174.49 ± 10.19
BM (kg)	72.93 ± 16.61	72.79 ± 13.64	73.06 ± 13.26
BMI (kg/m²)	24.17 ± 4.54	24.54 ± 4.12	23.80 ± 4.95
Blood analysis
Hemoglobin (g/dL)	12.79 ± 1.94	12.84 ± 1.96	12.73 ± 1.92
Creatinine (µmol/L)	101 ± 32.86	101 ± 41.32	100 ± 24.40
Median of BNP values (pg/mL)	384	396	372
Cardiovascular risk factors
DCM	26 (34)	14 (37)	12 (32)
Coro	24 (32)	13 (34)	11 (29)
Hypertension	17 (22)	7 (18)	10 (26)
AF	7 (9)	5 (13)	2 (5)
ICD	17 (22)	11 (29)	6 (16)
Type 2 diabetes	7 (9)	5 (13)	2 (5)
Baseline medication
Bisoprolol	58 (76)	31 (82)	27 (71)
Ramipril	53 (70)	26 (68)	27 (71)
Eplerenone	51 (67)	27 (71)	24 (63)
Entresto	15 (20)	7 (18)	8 (21)
Furosemide	56 (74)	29 (76)	27 (71)

Table 1. Baseline Characteristics of HFrEF Patients According to Their Training Response Status

Variable

All patients (n = 76)

Non-responders (n = 38) (ΔV̇O_2peak ≤ 2.2 mL/min/kg)

Responders (n = 38) (ΔV̇O_2peak > 2.2 mL/min/kg)

Data are expressed as mean ± SD for parametric data or as n (%) for dichotomous variables. AF: atrial fibrillation; BM: body mass; BMI: body mass index; BNP: brain natriuretic peptide; Coro: coronaropathy; DCM: dilated cardiomyopathy; F: female; HFrEF: heart failure with reduced ejection fraction; ICD: implantable cardioverter-defibrillator; M: male; SD: standard deviation.

Sex ratio (F/M)

11/65 (14/86)

6/32 (16/84)

5/33 (13/77)

Age (years)

57 ± 12

59 ± 13

56 ± 12

Height (cm)

173.27 ± 9.28

172.03 ± 8.18

174.49 ± 10.19

BM (kg)

72.93 ± 16.61

72.79 ± 13.64

73.06 ± 13.26

BMI (kg/m²)

24.17 ± 4.54

24.54 ± 4.12

23.80 ± 4.95

Blood analysis

Hemoglobin (g/dL)

12.79 ± 1.94

12.84 ± 1.96

12.73 ± 1.92

Creatinine (µmol/L)

101 ± 32.86

101 ± 41.32

100 ± 24.40

Median of BNP values (pg/mL)

384

396

372

Cardiovascular risk factors

DCM

26 (34)

14 (37)

12 (32)

Coro

24 (32)

13 (34)

11 (29)

Hypertension

17 (22)

7 (18)

10 (26)

7 (9)

5 (13)

2 (5)

ICD

17 (22)

11 (29)

6 (16)

Type 2 diabetes

7 (9)

5 (13)

2 (5)

Baseline medication

Bisoprolol

58 (76)

31 (82)

27 (71)

Ramipril

53 (70)

26 (68)

27 (71)

Eplerenone

51 (67)

27 (71)

24 (63)

Entresto

15 (20)

7 (18)

8 (21)

Furosemide

56 (74)

29 (76)

27 (71)

**Table 2.** Hemodynamic Parameters at Rest and at Peak
Variable	Pre	Post	P-value
Data are expressed as mean ± SD. P ≤ 0.05; P ≤ 0.01; P ≤ 0.001; **P ≤ 0.0001. CO: cardiac output; DBP: diastolic blood pressure; HR: heart rate; SBP: systolic blood pressure; SD: standard deviation; SV: stroke volume; SVR: systemic vascular resistance; V̇_E: ventilation; V̇_E/V̇O₂: minute ventilation/oxygen production; V̇_E/V̇CO₂: minute ventilation/carbon dioxide production; V̇O₂: oxygen uptake.
V̇O₂ (mL/min/kg)	5.31 ± 1.99	13.42 ± 3.53	5.04 ± 1.60	15.72 ± 4.82	0.3264	< 0.0001****
HR (bpm)	78.95 ± 14.34	108.51 ± 22.52	73.60 ± 12.80	113.55 ± 24.24	0.0003***	0.0056**
SV (mL)	61.56 ± 19.37	81.72 ± 25.10	65.37 ± 16.93	89.29 ± 26.18	0.0496*	0.0157*
CO (L/min)	4.93 ± 1.40	8.80 ± 3.32	4.76 ± 1.19	10.08 ± 3.91	0.1857	0.0012**
SBP (mm Hg)	97.94 ± 19.39	125.19 ± 37.38	98.56 ± 18.17	134.13 ± 36.19	0.7989	0.0690
DBP (mm Hg)	64.82 ± 16.50	69.42 ± 19.67	63.10 ± 11.31	74.08 ± 18.78	0.3414	0.0474*
V̇_E (L/min)	15.31 ± 4.79	47.29 ± 13.94	14.49 ± 4.20	54.81 ± 16.64	0.1917	< 0.0001****
V̇_E/V̇O₂	41.84 ± 8.71	50.73 ± 11.51	41.43 ± 9.75	50.29 ± 11.78	0.7277	0.6618
V̇_E/V̇CO₂	49.05 ± 9.33	45.30 ± 10.32	48.30 ± 10.11	43.58 ± 9.28	0.4893	0.0319*
SVR (dyn.s/cm⁵)	1,250.18 ± 255.69	809.79 ± 280.00	1,246.38 ± 247.72	744.21 ± 271.85	0.9111	0.0417*

Table 2. Hemodynamic Parameters at Rest and at Peak

Variable

Pre

Post

P-value

At rest

At peak

At rest

At peak

At rest

At peak

Data are expressed as mean ± SD. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001. CO: cardiac output; DBP: diastolic blood pressure; HR: heart rate; SBP: systolic blood pressure; SD: standard deviation; SV: stroke volume; SVR: systemic vascular resistance; V̇_E: ventilation; V̇_E/V̇O₂: minute ventilation/oxygen production; V̇_E/V̇CO₂: minute ventilation/carbon dioxide production; V̇O₂: oxygen uptake.

V̇O₂ (mL/min/kg)

5.31 ± 1.99

13.42 ± 3.53

5.04 ± 1.60

15.72 ± 4.82

0.3264

< 0.0001****

HR (bpm)

78.95 ± 14.34

108.51 ± 22.52

73.60 ± 12.80

113.55 ± 24.24

0.0003***

0.0056**

SV (mL)

61.56 ± 19.37

81.72 ± 25.10

65.37 ± 16.93

89.29 ± 26.18

0.0496*

0.0157*

CO (L/min)

4.93 ± 1.40

8.80 ± 3.32

4.76 ± 1.19

10.08 ± 3.91

0.1857

0.0012**

SBP (mm Hg)

97.94 ± 19.39

125.19 ± 37.38

98.56 ± 18.17

134.13 ± 36.19

0.7989

0.0690

DBP (mm Hg)

64.82 ± 16.50

69.42 ± 19.67

63.10 ± 11.31

74.08 ± 18.78

0.3414

0.0474*

V̇_E (L/min)

15.31 ± 4.79

47.29 ± 13.94

14.49 ± 4.20

54.81 ± 16.64

0.1917

< 0.0001****

V̇_E/V̇O₂

41.84 ± 8.71

50.73 ± 11.51

41.43 ± 9.75

50.29 ± 11.78

0.7277

0.6618

V̇_E/V̇CO₂

49.05 ± 9.33

45.30 ± 10.32

48.30 ± 10.11

43.58 ± 9.28

0.4893

0.0319*

SVR (dyn.s/cm⁵)

1,250.18 ± 255.69

809.79 ± 280.00

1,246.38 ± 247.72

744.21 ± 271.85

0.9111

0.0417*

**Table 3.** Hemodynamic Parameters at Peak for Responders and Non-Responders
Variable	Non-responders (n = 38) (ΔV̇O_2peak/kg ≤ 2.2 mL/min/kg)	Responders (n = 38) (ΔV̇O_2peak/kg > 2.2 mL/min/kg)	P-value
Data are expressed as mean ± SD. ^aOverall time P-value in case of a non-significant group × time interaction. ^bP-value Δ (post - pre) within group. P ≤ 0.05; P ≤ 0.01; P ≤ 0.001; **P ≤ 0.0001. CO: cardiac output; DBP: diastolic blood pressure; HR: heart rate; SBP: systolic blood pressure; SD: standard deviation; SVR: systemic vascular resistance; V̇_E: ventilation; V̇_E/V̇O₂: minute ventilation/oxygen production; V̇_E/V̇CO₂: minute ventilation/carbon dioxide production; V̇O₂oxygen uptake.
SBP (mm Hg)
Pre	128.13 ± 39.53	122.33 ± 35.43	0.1186	0.9414	0.0485*
Post	130.18 ± 32.26	137.97 ± 39.98
Δ (post - pre)	2.05 ± 39.86	15.64 ± 44.43
P-value Δ (post - pre)^b	0.9441	0.0265*
DBP (mm Hg)
Pre	68.66 ± 18.03	70.15 ± 21.36	0.2766	0.4334	0.0259*
Post	71.34 ± 16.26	76.74 ± 20.82
Δ (post - pre)	2.68 ± 15.72	6.59 ± 24.00
P-value Δ (post - pre)	0.6495	0.0392*
V̇_E (L/min)
Pre	47.84 ± 12.76	46.74 ± 15.15	< 0.0001****	0.1422	< 0.0001****
Post	48.84 ± 14.17	60.62 ± 16.99
Δ (post - pre)	1.00 ± 7.63	13.87 ± 10.79
P-value Δ (post - pre)	0.7563	< 0.0001****
V̇O₂ (mL/min/kg)
Pre	13.23 ± 3.66	13.59 ± 3.45	< 0.0001****	0.0017**	< 0.0001****
Post	13.05 ± 3.04	18.33 ± 4.82
Δ (post - pre)	-0.18 ± 2.28	4.73 ± 2.62
P-value Δ (post - pre)	0.8457	< 0.0001****
HR (bpm)
Pre	108.42 ± 23.37	108.59 ± 21.96	0. 0311*	0. 4129	0. 0040**
Post	109.76 ± 22.96	117.23 ± 25.17
Δ (post - pre)	1.34 ± 13.79	8.64 ± 16.41
P-value Δ (post - pre)	0. 8299	0. 0010***
V̇_E/V̇O₂
Pre	52.31 ± 11.41	49.18 ± 11.54	0.6131	0.1839	0.7062
Post	52.45 ± 11.58	48.20 ± 11.74
Δ (post - pre)	0.13 ± 8.97	-0.98 ± 8.45
P-value Δ (post - pre)	0.9947	0.7817
V̇_E/V̇CO₂
Pre	46.51 ± 10.15	44.11 ± 10.47	0.3726	0.1879	0.0359*
Post	45.52 ± 9.06	41.69 ± 9.21
Δ (post - pre)	-0.99 ± 6.52	-2.43 ± 7.26
P-value Δ (post - pre)	0.6196	0.0691
CO (L/min)
Pre	9.02 ± 3.39	8.59 ± 3.28	0.0185*	0.4963	0.0011**
Post	9.39 ± 3.76	10.75 ± 3.98
Δ (post - pre)	0.37 ± 3.25	2.16 ± 3.22
P-value Δ (post - pre)	0.7309	0.0002***
SVR (dyn.s/cm⁵)
Pre	799.16 ± 278.65	820.15 ± 284.55	0.5407	0.9637	0.0515
Post	755.29 ± 254.44	733.41 ± 290.73
Δ (post - pre)	-43.87 ± 264.61	-86.74 ± 291.99
P-value Δ (post - pre)	0.5615	0.1363

Table 3. Hemodynamic Parameters at Peak for Responders and Non-Responders

Variable

Non-responders (n = 38) (ΔV̇O_2peak/kg ≤ 2.2 mL/min/kg)

Responders (n = 38) (ΔV̇O_2peak/kg > 2.2 mL/min/kg)

P-value

Group × time interaction

Group

Time^a

Data are expressed as mean ± SD. ^aOverall time P-value in case of a non-significant group × time interaction. ^bP-value Δ (post - pre) within group. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001. CO: cardiac output; DBP: diastolic blood pressure; HR: heart rate; SBP: systolic blood pressure; SD: standard deviation; SVR: systemic vascular resistance; V̇_E: ventilation; V̇_E/V̇O₂: minute ventilation/oxygen production; V̇_E/V̇CO₂: minute ventilation/carbon dioxide production; V̇O₂oxygen uptake.

SBP (mm Hg)

Pre

128.13 ± 39.53

122.33 ± 35.43

0.1186

0.9414

0.0485*

Post

130.18 ± 32.26

137.97 ± 39.98

Δ (post - pre)

2.05 ± 39.86

15.64 ± 44.43

P-value Δ (post - pre)^b

0.9441

0.0265*

DBP (mm Hg)

Pre

68.66 ± 18.03

70.15 ± 21.36

0.2766

0.4334

0.0259*

Post

71.34 ± 16.26

76.74 ± 20.82

Δ (post - pre)

2.68 ± 15.72

6.59 ± 24.00

P-value Δ (post - pre)

0.6495

0.0392*

V̇_E (L/min)

Pre

47.84 ± 12.76

46.74 ± 15.15

< 0.0001****

0.1422

< 0.0001****

Post

48.84 ± 14.17

60.62 ± 16.99

Δ (post - pre)

1.00 ± 7.63

13.87 ± 10.79

P-value Δ (post - pre)

0.7563

< 0.0001****

V̇O₂ (mL/min/kg)

Pre

13.23 ± 3.66

13.59 ± 3.45

< 0.0001****

0.0017**

< 0.0001****

Post

13.05 ± 3.04

18.33 ± 4.82

Δ (post - pre)

-0.18 ± 2.28

4.73 ± 2.62

P-value Δ (post - pre)

0.8457

< 0.0001****

HR (bpm)

Pre

108.42 ± 23.37

108.59 ± 21.96

0. 0311*

0. 4129

0. 0040**

Post

109.76 ± 22.96

117.23 ± 25.17

Δ (post - pre)

1.34 ± 13.79

8.64 ± 16.41

P-value Δ (post - pre)

0. 8299

0. 0010***

V̇_E/V̇O₂

Pre

52.31 ± 11.41

49.18 ± 11.54

0.6131

0.1839

0.7062

Post

52.45 ± 11.58

48.20 ± 11.74

Δ (post - pre)

0.13 ± 8.97

-0.98 ± 8.45

P-value Δ (post - pre)

0.9947

0.7817

V̇_E/V̇CO₂

Pre

46.51 ± 10.15

44.11 ± 10.47

0.3726

0.1879

0.0359*

Post

45.52 ± 9.06

41.69 ± 9.21

Δ (post - pre)

-0.99 ± 6.52

-2.43 ± 7.26

P-value Δ (post - pre)

0.6196

0.0691

CO (L/min)

Pre

9.02 ± 3.39

8.59 ± 3.28

0.0185*

0.4963

0.0011**

Post

9.39 ± 3.76

10.75 ± 3.98

Δ (post - pre)

0.37 ± 3.25

2.16 ± 3.22

P-value Δ (post - pre)

0.7309

0.0002***

SVR (dyn.s/cm⁵)

Pre

799.16 ± 278.65

820.15 ± 284.55

0.5407

0.9637

0.0515

Post

755.29 ± 254.44

733.41 ± 290.73

Δ (post - pre)

-43.87 ± 264.61

-86.74 ± 291.99

P-value Δ (post - pre)

0.5615

0.1363