Relationship of Lung Function and Inspiratory Strength with Exercise Capacity and Prognosis in Heart Failure

Ramalho, Sergio Henrique Rodolpho; Lima, Alexandra Correa Gervazoni Balbuena de; Silva, Fabiola Maria Ferreira da; Souza, Fausto Stauffer Junqueira de; Cahalin, Lawrence Patrick; Cipriano, Graziella França Bernardelli; Cipriano Junior, Gerson

Sergio Henrique Rodolpho Ramalho

Programa de Pós-graduação em Ciências e Tecnologias em Saúde - Universidade de Brasília, Brasília, DF - Brazil

https://orcid.org/0000-0001-8444-2655

Alexandra Correa Gervazoni Balbuena de Lima

Programa de Pós-graduação em Ciências e Tecnologias em Saúde - Universidade de Brasília, Brasília, DF - Brazil

Fabiola Maria Ferreira da Silva

Programa de Pós-graduação em Ciências e Tecnologias em Saúde - Universidade de Brasília, Brasília, DF - Brazil

Fausto Stauffer Junqueira de Souza

Programa de Pós-graduação em Ciências e Tecnologias em Saúde - Universidade de Brasília, Brasília, DF - Brazil

Lawrence Patrick Cahalin

Universidade de Miami - Miller School of Medicine, Miami - USA

Graziella França Bernardelli Cipriano

Programa de Pós-graduação em Ciências e Tecnologias em Saúde - Universidade de Brasília, Brasília, DF - Brazil

Programa de Pós-graduação em Ciências da Reabilitação - Universidade de Brasília, Brasília, DF - Brazil

Gerson Cipriano Junior

Programa de Pós-graduação em Ciências e Tecnologias em Saúde - Universidade de Brasília, Brasília, DF - Brazil

Programa de Pós-graduação em Ciências da Reabilitação - Universidade de Brasília, Brasília, DF - Brazil

https://orcid.org/0000-0001-6323-7003

Mailing Address: Sergio Henrique Rodolpho Ramalho • Universidade de Brasília – Faculdade de Ceilândia – Laboratório de Fisiologia - Campus Universitário, Centro Metropolitano – Postal Code 72220-275, Ceilândia Sul, Brasília, DF – Brazil. E-mail: shrramalho@gmail.com

Author Contributions

Conception and design of the research: Ramalho SHR, Lima ACGB, Cipriano GFB, Cipriano Junior G; Acquisition of data: Ramalho SHR, Lima ACGB, Silva FMF, Souza FSJ, Cipriano GFB, Cipriano Junior G; Analysis and interpretation of the data: Ramalho SHR, Cahalin LP, Cipriano GFB, Cipriano Junior G; Statistical analysis: Ramalho SHR; Obtaining financing: Lima ACGB, Cipriano GFB, Cipriano Junior G; Writing of the manuscript: Ramalho SHR; Critical revision of the manuscript for intellectual content: Ramalho SHR, Lima ACGB, Silva FMF, Souza FSJ, Cahalin LP, Cipriano GFB, Cipriano Junior G.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures (3)
Tables (3)

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Figure 1
– Continuous association of FEV₁/FVC (blue) and percent predicted FVC (light red) with FEV₁, LVEF, MIP and VO₂peak at baseline 5 using restricted cubic splines. Models were constructed using restricted cubic splines with 3 knots. *p <0.05 in models further adjusted for age and sex.

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Figure 2
– Continuous associations of FEV1/FVC (blue) and percent predicted FVC (red) at baseline with the composite outcome (cardiovascular death, heart transplant, and left ventricular assist device implant), in a mean follow-up of 2.2±0.7 years (22 events). Models were constructed for the primary exposure variables (FEV₁/FVC and percent predicted FVC) using restricted cubic splines with 3 knots. Linear corresponds to Cox regression analysis. *p <0.05 in models further adjusted for age and sex.

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Figure 3
– Visual abstract of the main findings: FEV₁/FVC and ppFVC differently characterize HF patients. HF: heart failure; LVEF: left ventricular ejection fraction; FEV1: forced expiratory volume in 1 second; ppFVC: percent predicted of forced vital capacity; MIP: maximal inspiratory pressure; CV: cardiovascular; LVAD: left ventricular assist device; HR: hazard ratio. HF: Although ppFVC was associated with other functional variables than the ventilatory reserve, only FEV₁/FVC was associated with a relatively short-term prognosis, particularly for low ejection fraction, suggesting that each marker may add different information regarding HF phenotyping.

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Table 1
– Characteristics of heart failure population at baseline (n=111). Values expressed as mean±SD or n (%)

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Table 2
– Continuous relationship of spirometric patterns (per 10-percentage points increase in each FEV1/FVC and ppFVC) with cardiopulmonary function in heart failure subjects at baseline

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Table 3
– Association of spirometry variables at baseline with incidental composite outcome (cardiovascular mortality, heart transplant or left ventricular assist device implant; 22 events) among heart failure subjects (n=111), with mean follow-up of 2.2±0.7 years

Subjects, n	111
Demographics and clinical characteristics
Age, years	57.4 ± 11.8
Male, n (%)	67 (60%)
Etiology, n (%)
Chagas	32 (29%)
Ischemic	43 (39%)
Idiopathic	23 (21%)
Other	13 (12%)
BMI, kg/m²	26.6 ± 4.8
BMI >30 kg/m²; n (%)	26 (23%)
Medical history
Hypertension, n (%)	63 (57%)
Diabetes, n (%)	20 (18%)
Current smokers, n (%)	29 (26%)
Dyslipidemia, n (%)	44 (40%)
NYHA, n (%)
I	15 (13%)
II	25 (22%)
III	71 (64%)
Medications and devices
Beta-blockers, n (%)	100 (90%)
ACEi/ARB, n (%)	94 (84%)
Spironolactone, n (%)	73 (66%)
Digoxin, n (%)	22 (20%)
Statin, n (%)	70 (63%)
Furosemide, n (%)	67 (60%)
Pacemaker/ICD, n (%)	25 (22%)
Pulmonary function
FEV₁, L	2.3 ± 0.7
FVC, L	3.0 ± 0.9
Percent predicted FVC, %	80 ± 17
Percent predicted FVC <80%	57 (51%)
FEV1/FVC	75 ± 9
FEV₁/FVC ≤70	28 (25%)
MEP, cmH₂O	84.7 ± 40.1
MIP, cmH₂O	75.4 ± 35.4
Low MIP, n (%)	51 (49%)
Echocardiographic characteristics
LVEF, %	38.4 ± 15.0
LVEF >50%, n (%)	24 (23%)
LA volume index, mL/m²	44.7 ± 16.7
Estimated PASP, mmHg	38.9 ± 12.0
Cardiopulmonary test
Peak power, W	80.3 ± 30.6
Peak heart rate, bpm	118 ± 26
Peak systolic pressure, mmHg	151 ± 25
Absolute peak VO₂, mL/min	966 ±401
Relative peak VO₂, mL/kg/min	13.4 ± 4.6
RER	1.23 ± 0.18
Absolute VO₂ at VAT, mL/min	618 ± 281
Relative VO₂ at VAT, mL/kg/min	8.6 ± 3.5
O₂ pulse, mL/beat	8.4 ± 3.1
OUES	1145 ± 465
VE max, (L/min)	45.0 ± 16.6
Ventilatory reserve, %	48 ± 19
VE/VCO2 slope	37.3 ± 8.1
Circulatory power, mmHg.mL/kg/min	2165 ± 1024
Ventilatory power, mmHg	4.3 ± 1.4

Cardiac and pulmonary function		FEV₁/FVC		% Predicted FVC

		Coefficient (95% CI)	p	Coefficient (95% CI)	p
FEV¹, L	Model 1	0.24 (0.10; 0.38)	0.001	0.25 (0.18; 0.31)	<0.001
FEV¹, L	Model 2	0.20 (0.10; 0.31)	<0.001	0.23 (0.19; 0.27)	<0.001
MEP cmH₂O	Model 1	2.7 (-6.6; 11.9)	0.57	-0.9 (-5.8; 4.1)	0.73
MEP cmH₂O	Model 2	0.6 (-7.5;8.8	0.88	-1.5 (-5.8; 2.9)	0.50
MIP, cmH₂O	Model 1	0.9 (-0.6; 8.2)	0.81	4.1 (0.2; 8.1)	0.04
MIP, cmH₂O	Model 2	0.4 (-6.1; 6.9)	0.90	3.8 (0.3; 7.3)	0.031
LV ejection fraction, %	Model 1	1.9 (-1.0; 4.9)	0.20	2.2 (0.6; 3.9)	0.007
LV ejection fraction, %	Model 2	1.6 (-1.4; 4.7)	0.28	2.1 (0.5; 3.8)	0.013
Peak power, W	Model 1	1.5 (-4.6; 7.6)	0.63	4.2 (0.9; 7.5)	0.012
Peak power, W	Model 2	0.3 (-4.3; 4.9)	0.89	3.5 (1.1; 6.0)	0.005
Absolute peak VO₂, mL/min	Model 1	30 (-50; 111)	0.45	35 (-9; 78)	0.11
Absolute peak VO₂, mL/min	Model 2	18 (-49; 86)	0.59	27 (-9; 63)	0.14
Relative peak VO₂, mL/kg/min	Model 1	-0.3 (-1.3; 0.6)	0.47	0.6 (0.1; 1.1)	0.02
Relative peak VO₂, mL/kg/min	Model 2	-0.4 (-1.3; 0.4)	0.30	0.5 (0.1; 1.0)	0.028
Respiratory exchange ratio	Model 1	-0.01 (-0.05; 0.02)	0.48	0.02 (-0.003; 0.04)	0.09
Respiratory exchange ratio	Model 2	-0.01 (-0.05; 0.02)	0.40	0.01 (-0.003; 0.03)	0.10
Absolute VO₂ at VAT, mL/min	Model 1	-8 (-66; 49)	0.77	12 (-20; 44)	0.45
Absolute VO₂ at VAT, mL/min	Model 2	-12 (-67; 44)	0.68	13 (-18; 44)	0.42
Relative VO₂ at VAT, mL/kg/min	Model 1	-0.7 (-1.4; -0.004)	0.05	0.2 (-0.2; 0.6)	0.31
Relative VO₂ at VAT, mL/kg/min	Model 2	-0.7 (-1.4; 0.007)	0.05	0.2 (-0.2; 0.6)	0.25
O₂ pulse, mL/beat	Model 1	0.4 (-0.2; 1.0)	0.21	0.1 (-0.2; 0.5)	0.45
O₂ pulse, mL/beat	Model 2	0.4 (-0.2; 0.9)	0.18	0.1 (0.2; 0.4)	0.47
OUES	Model 1	62 (-31; 155)	0.19	19 (-32; 70)	0.47
OUES	Model 2	48 (-34; 130)	0.25	9 (-36; 54)	0.70
VE max, L/min	Model 1	-0.4 (-3.7; 2.9)	0.82	1.6 (-0.2; 3.4)	0.08
VE max, L/min	Model 2	-0.6 (-3.3; 2.1)	0.68	1.5 (0.02; 2.9)	0.05
Ventilatory reserve, %	Model 1	7.4 (3.9; 10.9)	<0.001	4.6 (2.8; 6.5)	<0.001
Ventilatory reserve, %	Model 2	6.8 (3.3; 10.3)	<0.001	4.3 (2.5; 6.2)	<0.001
VE/VCO₂ slope	Model 1	-0.2 (-2.0; 1.7)	0.87	-0.6 (-1.6; 0.3)	0.19
VE/VCO₂ slope	Model 2	0.2 (-1.6; 2.0)	0.85	-0.5 (-1.5; 0.5)	0.35
Circulatory power, mmHg.mL/kg/min	Model 1	-20 (-202; 163)	0.83	85 (-14; 183)	0.09
Circulatory power, mmHg.mL/kg/min	Model 2	-43 ( -212; 125)	0.61	72 (-19; 163)	0.12
Ventilatory power, mmHg	Model 1	0.08 (-0.20; 0.35)	0.59	0.12 (-0.03; 0.27)	0.11
Ventilatory power, mmHg	Model 2	0.04 (-0.22; 0.31)	0.76	0.10 (-0.04; 0.24)	0.17

	n	Events	Unadjusted HR (95% CI)*	p	Age/sex adjusted HR (95% CI)*	p
FEV ₁ /FVC
Obstructive	28	9	2.45 (1.05-5.77)	p=0.039	2.28 (0.95-5.44)	p=0.064
Non-obstructive	83	13	2.45 (1.05-5.77)	p=0.039	2.28 (0.95-5.44)	p=0.064
Continuous	111	22	1.48 (1.00-2.18)	p=0.050	1.44 (0.97-2.13)	p=0.069
ppFVC
Restrictive	57	14	1.83 (0.77-4.37)	p=0.172	1.86 (0.78-4.44)	p=0.163
Non-restrictive	54	8	1.83 (0.77-4.37)	p=0.172	1.86 (0.78-4.44)	p=0.163
Continuous	111	22	1.16 (0.92-1.46)	p=0.207	1.13 (0.89-1.43)	p=0.306

[1] Mailing Address: Sergio Henrique Rodolpho Ramalho • Universidade de Brasília – Faculdade de Ceilândia – Laboratório de Fisiologia - Campus Universitário, Centro Metropolitano – Postal Code 72220-275, Ceilândia Sul, Brasília, DF – Brazil. E-mail: shrramalho@gmail.com

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Relationship of Lung Function and Inspiratory Strength with Exercise Capacity and Prognosis in Heart Failure

Abstract

Background

Objective

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