Clinical features and determinants of VO2peak in de novo heart transplant recipients

doi:10.5500/wjt.v8.i5.188

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World Journal of Transplantation

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2220-3230

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Randomized Clinical Trial

World J Transplantation. Sep 10, 2018; 8(5): 188-197
Published online Sep 10, 2018. doi: 10.5500/wjt.v8.i5.188

Table 1 Clinical characteristics and health-related quality of life of the study population

⁶N = 55-81	Total	Low-capacity group(n = 41)VO_2peak ≤19.4 mL/kg per min	High-capacity group(n = 40)VO_2peak >19.4 mL/kg per min	t(P-value)	Univariate regressionStandardized coefficient Beta [95%CI], PVO_2peak (L/min)	⁷R²
Clinical characteristics
Sex (% men)	73%	66	80	0.152¹	-0.45 [-0.61, -0.23], < 0.001	0.2
Age (yr)	49 ± 13	51 ± 11	46 ± 15	0.08	-0.19 [-0.01, -0.001], 0.093	0.04
Body mass index	25.3 ± 3.7	26.3 ± 3.4	24.2 ± 3.8	0.01	0.28 [0.007, 0.056], 0.013	0.08
Body fat (%)	25.1 ± 8.7	29.0 ± 8.3	21.0 ± 7.1	<0.001	-0.34 [-0.03, -0.006], 0.003	0.11
Donor age (yr)	34 (24, 49)	37 (27, 48)	33 (23, 52)	0.825²	0.09 [-0.004, 0.009], 0.447	0.01
Ischemic time (min)	210 (95, 237)	215 (99, 249)	185 (87, 227)	0.072²	-0.01[-0.001, 0.001], 0.938	8.2^-5
Weeks after HTx	11 ± 1.8	11.3 ± 2	10.9 ± 1.5	0.307	-0.001 [-0.05, 0.05], 0.990	2.0^-5
Duration of HF prior to HTx (yr)	4 (1.5, 10)	4 (1.5, 10.5)	4 (1.0, 9.3)	0.718²	-0.05 [-0.02, 0.01], 0.681	0.002
Time on HTx waiting list (d)	75 (24, 193)	96 (29, 227)	47 (12, 131)	0.06²	-0.14 [-0.001, 1.5-4], 0.202	0.02
Rejections grade 1-2 (% yes)	45	48	43	0.653¹	0.09 [-0.11, 0.27], 0.408	0.01
VO_2peak preHTx (mL/kg per min)	11.6 ± 3.3	11.1 ± 3	12.1 ± 3.5	0.248	0.03 [-0.032, 0.039], 0.826	0.001
LVAD (% yes)	15	22	8	0.067¹	-0.14 [-0.43, 0.097], 0.211	0.02
Preoperative IABP/ECMO (% yes)	16	15	18	0.725¹	0.05 [-0.20, 0.32], 0.637	0.003
Postoperative IABP/ECMO (% yes)	10	15	5	0.264³	-0.26 [-0.68, -0.066], 0.018	0.07
Etiology HF (%)				0.138³
Cardiomyopathy	65	56	75
Ischemic heart disease	25	34	15
Other	10	10	10
Smoking (%) no/yes/ex-smoker	49/0/51	34/0/66	65/0/35	0.005¹	-0.19 [-0.34, 0.03], 0.100	0.03
24 h ambulatory blood pressure
Overall systolic BP	133 ± 12	133 ± 13	132 ± 10	0.672
Overall diastolic BP	81 ± 7	80 ± 8	82 ± 7	0.493
Medication (%)
Ciclosporin	70	63	78	0.165¹
Tacrolimus	28	32	23	0.352¹
Everolimus	34	43	25	0.098¹
Mycophenolate	90	81	100	0.005³	0.29 [0.10, 0.71], 0.009	0.08
Prednisolone	100	100	100
Beta-blocker	28	40	15	0.012¹	-0.19 [-0.39, -0.03], 0.086	0.04
Calcium blocker	25	25	25	1.000¹
ACE inhibitors	3	3	3	1.000³
AII-blocker	9	13	5	0.263³
Diuretics	79	80	78	0.785¹
Statins	99	98	100	1.000³
Blood samples
TG (mmol/L)	1.7 (1.3, 2.5)	2.1 (1.5, 2.8)	1.5 (1.1, 2.2)	0.013²	-0.24 [-0,19, -0.002], 0.045	0.06
LDL (mmol/L)	2.9 ± 1.0	3.0 ± 1.2	2.9 ± 0.7	0.416	0.12 [-0.05, 0.15], 0.308	0.01
HDL (mmol/L)	1.5 ± 0.5	1.5 ± 0.5	1.6 ± 0.5	0.432	0.04 [-0.16, 0.22], 0.755	0.001
Cholesterol (mmol/L)	5.1 ± 1.3	5.3 ± 1.5	5.0 ± 1.0	0.329	0.03 [-0.07, 0.09], 0.830	0.001
Hemoglobin (g/dL)	11.8 ± 1.7	11.3 ± 1.9	12.2 ± 1.4	0.017	0.38 [0.042, 0.15], 0.001	0.14
hs-CRP (mg/L)	2.3 (1.0, 6.1)	2.7 (1.3, 6.7)	1.6 (0.6, 3.9)	0.052²	-0.17 [-0.015, 0.002], 0.125	0.03
NT-proBNP (ng/L)	968.3 (625.8, 1680.8)	1348.9 (765.4,2006.4)	790.7 (522.2, 1351.0)	0.005²	-0.36[-2.7E-4, -6.5^-5], 0.002	0.13
hs-TnT (ng/L)	32.5 (20.0, 61.8)	42.0 (27.8, 66.7)	24.0 (18.0, 50.8)	0.009²	-0.18 [-0.005, 0.001], 0.128	0.03
HbA1c (%)	5.6 ± 0.8	5.8 ± 0.9	5.4 ± 0.7	0.038	-0.15 [-0.19, 0.04], 0.213	0.02
Glucose (mmol/L)	5.9 ± 1.8	6.3 ± 2.1	5.5 ± 1.4	0.046	-0.19 [-0.1, 0.01], 0.109	0.04
Leukocytes (× 10^-9/L)	5.4 ± 2.3	6.0 ± 2.7	4.7 ± 1.6	0.017	-0.06 [-0.05, 0.03], 0.580	0.004
Creatinine (μmol/L)	117.4 ± 31.4	118.0 ± 31.9	116.9 ± 31.3	0.868	-0.05 [-0.004, 0.002], 0.669	0.002
Carbamide (mmol/L)	9.8 ± 3.4	9.9 ± 4.0	9.7 ± 2.7	0.865	-0.003 [-0.03, 0.03], 0.977	1.00E-05
eGFR (mL/min per 1.73 m²)	55 ± 16	54.1 ± 17.0	56.1 ± 15.0	0.586	0.23 [3.9E-5,0.01], 0.049	0.05
Muscle strength and muscular exercise capacity
Muscle strength (Nm)	279 ± 129	231 ± 128	326 ± 113	0.001	0.66 [0.002, 0.003], < 0.001	0.43
Muscular Exercise capacity (J)	3229 ± 1660	2423 ± 1351	4015 ± 1567	< 0.001	0.64 [0.0001, 0.0002], < 0.001	0.41
Spirometry
FEV1 (%)	81 ± 16	74 ± 14	88 ± 16	< 0.001	0.39 [0.004, 0.02], 0.001	0.16
PEF (%)	85 ± 22	79 ± 23	91 ± 20	0.018	0.37 [0.003, 0.01], 0.001	0.14
FVC (%)	86 ± 17	81 ± 16	90 ± 16	0.026	0.17 [-0.002, 0.01], 0.152	0.03
Echocardiography
EF (%)	57.9 ± 5.6	56.2 ± 5.4	59.4 ± 5.4	0.011	0.26 [0.003, 0.04], 0.025	0.07
LVEDD (cm)	4.9 ± 0.5	4.9 ± 0.5	4.9 ± 0.4	0.996	0.42 [0.19, 0.59], < 0.001	0.18
FS (%)	36.7 ± 5.9	35.9 ± 6.8	37.5 ± 4.9	0.242	0.23 [-4.7E-5, 0.03], 0.051	0.05
CO (L/min)	6.1 ± 1.2	6.0 ± 1.2	6.2 ± 1.2	0.467	0.39 [0.06, 0.21], 0.001	0.15
Health-related quality of life
PCS	43 ± 8	41 ± 7	45 ± 8	0.029	0.35 [0.008, 0.03], 0.001	0.13
MCS	54 ± 11	53 ± 10	55 ± 11	0.416	0.17 [-0.002, 0.02], 0.127	0.03
Symptoms of anxiety and depression
HADS-A ≥ 8 (%)⁴	15	17	13	0.562¹	-0.26 [-0.56, -0.05], 0.02	0.07
HADS-D ≥ 8 (%)⁵	5	5	5	1.000³	-0.16 [-0.73, 0.13], 0.165	0.03

Groups are divided according to the median VO_2peak (mL/kg per min). Variables are presented as percentages, mean ± SD or as median (Q1, Q3) where appropriate.

¹χ²;

²Mann Whitney U-test;

³F;

⁴HADS-A score ≥ 8 indicates symptoms of anxiety;

⁵HADS-D score ≥ 8 indicates symptoms of depression;

⁶The actual N varies from 55 to 81 for different variables;

⁷Unadjusted R². ACE: Angiotensin-converting enzyme; ATII: Angiotensin II; BP: Blood pressure; CO: Cardiac output; ECMO: Extracorporeal membrane oxygenation; EF: Ejection fraction; FEV₁: Forced expiratory volume at 1 min; FVC: Forced vital capacity; FS: Fractional shortening; HADS: Hospital anxiety and depression scale; HbA1c: Hemoglobin A1c; HDL: High density lipoprotein; hs-CR: High-sensitive C-reactive protein; hs-TnT: High-sensitive troponin T; HTx: Heart transplantation; IABP: Intra-aortic balloon pump; LVAD: Left ventricle assist device; LVEDD: Left ventricular end diastolic diameter; MCS: Mental component summary; Nm: Newton meter; NT-pro BNP: N-terminal pro brain natriuretic peptide; PEF: Peak expiratory flow; PCS: Physical component summary; Q1: First quartile; Q3: Third quartile; SD: Standard deviation; TG: Triglyceride.

Table 2 Cardiopulmonary responses to exercise of the study population

²N = 63-81	Total	Low-capacity groupVO_2peak ≤ 19.4 mL/kg per min (n = 41)	High-capacity groupVO_2peak > 19.4 mL/kg per min (n = 40)	t(P-value)	Univariate regressionStandardized coefficientBeta [95%CI], PVO_2peak L/min	³R²
VO_2peak (mL/kg per min)	20.4 ± 4.9	16.4 ± 2	24.3 ± 3.6	< 0.001	0.75 [0.05, 0.08], < 0.001	0.56
VO_2peak (L/min)	1.6 ± 0.4	1.3 ± 0.3	1.8 ± 0.4	< 0.001
%expected VO_2peak	55.8 ± 12.4	46.5 ± 7.4	65.3 ± 8.6	< 0.001	0.60 [0.01, 0.03], < 0.001	0.36
RER	1.2 ± 0.1	1.2 ± 0.14	1.2 ± 0.10	0.898
HRrest (echocardiography)	87 ± 10	87 ± 11	86 ± 9	0.85	-0.07 [-0.013, 0.007], 0.551	0.01
Peak systolic BP (mmHg)	188 ± 30	188 ± 31	189 ± 30	0.865	0.19 [-0.001, 0.006], 0.108	0.04
Peak diastolic BP (mmHg)	82 ± 17	82 ± 18	82 ± 16	0.917	0.09 [-0.004, 0.008], 0.467	0.01
VE/VCO_2slope	34.8 ± 7.7	37.3 ± 7.2	32.6 ± 7.6	0.008	-0.42 [-0.035, -0.01], < 0.001	0.18
Vmax (L)	71.4 ± 22.8	60.5 ± 17.5	81.7 ± 22.7	< 0.001	0.76[0.01, 0.02], < 0.001	0.58
O₂ pulse (mL/beat)	12.4 ± 3.3	11.0 ± 3	13.7 ± 3	< 0.001	0.80 [0.08, 0.12], < 0.001	0.65
AT (L/min)	1.08 ± 0.3	0.95 ± 0.2	1.2 ± 0.3	0.001	0.73 [0.74, 1.2], < 0.001	0.53
METS	6.5 ± 1.6	5.4 ± 0.8	7.8 ± 1.3	< 0.001	0.77 [0.16, 0.24], < 0.001	0.59
HRpeak (beats/min)	128 ± 19	121 ± 19	134 ± 17	0.001	0.31 [0.002, 0.01], 0.005	0.1
%HRmax	75 ± 12	72 ± 12	78 ± 11	0.021	0.20 [-0.001, 0.02], 0.071	0.04
HRreserve (beats/min)	43 ± 16	35 ± 13	50 ± 15	< 0.001	0.47 [0.01, 0.02], < 0.001	0.22
CRI	0.51 ± 0.2	0.45 ± 0.18	0.57 ± 0.2	0.004	0.31 [0.20, 1.12], 0.005	0.1
RPE (Borg scale)	18.6 ± 0.8	18.5 ± 1	18.6 ± 0.5	0.638
Test duration (min)	9.5 ± 2.8	7.8 ± 1.5	11.1 ± 2.7	< 0.001
HRrecovery
Beats /min at 2 min	-1.0 (-3.0, 1.0)	-1.0 (-3.0, 1.0)	-2.0 (-3.3, 1.3)	0.697¹

Groups are divided according to the median VO_2peak (mL/kg per min). Variables are presented as mean ± SD or as median (Q1, Q3) where appropriate.

¹Mann Whitney U-test;

²The actual N varies from 63 to 81 for different variables;

³Unadjusted R². BP: Blood pressure; CI, confidence interval; CRI, chronotropic response index; HR, heart rate; METS, metabolic equivalents; Vmax, maximum ventilation; Q1, first quartile; Q3, third quartile; RER, Respiratory Exchange Ratio; RPE, rated perceived exertion; SD, standard deviation.

Table 3 Multiple regression analysis

N = 66	Model 1Standardized coefficient Beta [95% CI]	P-value	Model 2Standardized coefficient Beta [95% CI]	P-value
O₂ pulse (mL/beat)	0.707 [0.075, 0.104]	< 0.001	0.675 [0.069, 0.102]	< 0.001
HRreserve (beats/min)	0.382 [0.007, 0.013]	< 0.001	0.397 [0.008, 0.013]	< 0.001
Muscular exercise capacity (Joule)	0.162 [1.1E-5, 7.1E-5]	0.008	0.155 [8.0^-5, 7.1^-5]	0.015
BMI (kg/m²)			0.067 [-0.004, 0.020]	0.211
Sex			-0.029 [-0.142, 0.086]	0.630
Age (yr)			0.019 [-0.003, 0.004]	0.719
Adjusted R²	0.85		0.84

Dependent variable VO_2peak L/min. Final model for n = 66. BMI: Body mass index; CI: Confidence interval; HR: Heart rate.

Citation: Rolid K, Andreassen AK, Yardley M, Bjørkelund E, Karason K, Wigh JP, Dall CH, Gustafsson F, Gullestad L, Nytrøen K. Clinical features and determinants of VO_2peak in de novo heart transplant recipients. World J Transplantation 2018; 8(5): 188-197
URL: https://www.wjgnet.com/2220-3230/full/v8/i5/188.htm
DOI: https://dx.doi.org/10.5500/wjt.v8.i5.188