Introduction
Methods
Ethics approval
Participants
Clinical assessment
Definition of PRc
Follow-up
Statistical analysis
Results
Missing
N
| HeFREF (N = 1420) | HeFNEF (N = 1094) | Not HF (N = 1150) |
P value HeFREF vs. Not HF |
P value HeFREF vs. HeFNEF |
P value HeFNEF vs. Not HF |
P value All groups | |
---|---|---|---|---|---|---|---|---|
Age (years) | – | 71 (63–78) | 76 (70–82) | 68 (60–75) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Men (%) | – | 1005 (71) | 516 (47) | 584 (51) |
< 0.001
|
< 0.001
| 0.156 |
< 0.001
|
NYHA class (%) | 2/17/161 | |||||||
I | 212 (15) | 325 (30) | 488 (49) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
| |
II | 708 (50) | 493 (46) | 369 (37) | |||||
III | 457 (32) | 244 (23) | 124 (13) | |||||
IV | 41 (3) | 15 (1) | 8 (1) | |||||
Diabetes (%) | 2/3/4 | 356 (25) | 287 (26) | 259 (23) | 0.12 | 0.36 | 0.06 | 0.13 |
Ischaemic heart disease (%) | 2/7/15 | 932 (66) | 476 (44) | 244 (22) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Cerebrovascular disease (%) | 2/7/15 | 100 (7) | 68 (6) | 40 (4) |
< 0.001
|
< 0.001
|
0.01
|
0.001
|
Body surface area (m2) | 6/7/4 | 1.91 (1.73–2.08) | 1.85 (1.71–2.04) | 1.95 (1.78–2.11) |
< 0.001
|
0.01
|
< 0.001
|
< 0.001
|
Systolic BP (mmHg) | 13/3/21 | 129 (114–147) | 149 (131–167) | 147 (132–162) |
< 0.001
|
< 0.001
| 0.06 |
< 0.001
|
Diastolic BP (mmHg) | 13/3/21 | 76 (66–84) | 78 (70–88) | 83 (75–91) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Heart rate (bpm) | – | 73 (63–86) | 68 (59–78) | 69 (60–79) |
< 0.001
|
< 0.001
| 0.18 |
< 0.001
|
QRS (ms) | 6//1/4 | 112 (96–140) | 92 (84–106) | 90 (82–98) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
QRS ≥ 150 ms (%) | 6//1/4 | 249 (18) | 51 (5) | 18 (2) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
PR (ms) | – | 172 (154–194) | 168 (152–192) | 162 (148–180) |
< 0.001
| 0.53 |
< 0.001
|
< 0.001
|
PRc (ms) | – | 174 (157–196) | 168 (151–192) | 163 (147–179) |
< 0.001
| 0.03 |
< 0.001
|
< 0.001
|
QT (ms) | 19/19/6 | 413 (380–446) | 406 (384–431) | 396 (372–416) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
QTc (ms) | 19/19/6 | 453 (422–483) | 429 (410–452) | 418 (401–441) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
TSH (mIU/L) | 117/91/196 | 1.6 (1.0–2.5) | 1.7 (1.1–2.5) | 1.6 (1.0–2.3) |
0.04
| 0.37 |
0.01
|
0.02
|
eGFR (1.73 mL/min/m2) | 3/2/12 | 62 (47–77) | 61 (47–75) | 75 (63–88) |
< 0.001
| 0.15 |
< 0.001
|
< 0.001
|
NT-ProBNP (ng/L) | 436/8/139 | 1319 (583–3378) | 547 (321–1171) | 86 (46–140) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Ejection fraction by Simpson’s | 564/523/491 | 33 (27–37) | 54 (48–61) | 59 (54–64) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
LV systolic dysfunction (%) | – | |||||||
Normal–trivial | 0 | 820 (75) | 1151 (100) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
| |
Mild | 0 | 274 (25) | 0 | |||||
Mild–moderate | 849 (60) | 0 | 0 | |||||
>Moderate | 571 (40) | 0 | 0 | |||||
Mitral regurgitation > mild (%) | 27/17/161 | 447 (32) | 124 (13) | 27 (2) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Medication at initial visit | ||||||||
β-blocker (%) | 14/18/55 | 862 (61) | 550 (51) | 285 (26) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
ACE-I (%) | 14/18/55 | 1019 (72) | 532 (49) | 325 (30) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
ARB (%) | 14/18/55 | 133 (9) | 161 (15) | 128 (12) | 0.07 |
< 0.001
|
0.02
|
< 0.001
|
MRA (%) | 14/18/55 | 422 (30) | 95 (9) | 22 (2) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Amiodarone (%) | 6/18/36 | 66 (5) | 19 (2) | 6 (0.5) |
< 0.001
|
0.001
|
< 0.001
|
< 0.001
|
Digoxin no. (%) | 6/18/36 | 118 (8) | 40 (4) | 9 (0.8) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Loop Diuretic (%) | 8/18/3 | 993 (70) | 557 (52) | 249 (22) |
< 0.001
|
< 0.001
|
< 0.001
|
< 0.001
|
Ivabradine (%) | 14/18/55 | 5 (0.4) | 2 (0.2) | 0 | 0.07 | 0.35 | 0.5 | 0.14 |
1 year mortality (%) | – | 171 (12) | 76 (10) | 8 (1) |
< 0.001
| 0.13 |
< 0.001
|
< 0.001
|
PRc Q1 N = 355 | PRc Q2 N = 355 | PRc Q3 N = 355 | PRc Q4 N = 355 |
P value | |
---|---|---|---|---|---|
Age (years) | 70 (61–77) | 70 (61–77) | 71 (63–78) | 73 (65–79) |
< 0.001
|
Men, no. (%) | 225 (63) | 236 (67) | 259 (72) | 285 (81) |
< 0.001
|
NYHA class, no. (%) | |||||
I | 59 (17) | 51 (14) | 54 (15) | 47 (13) |
0.002
|
II | 193 (54) | 180 (51) | 171 (48) | 164 (46) | |
III | 96 (27) | 114 (32) | 122 (35) | 125 (36) | |
IV | 7 (2) | 9 (3) | 6 (2) | 19 (5) | |
Diabetes, no. (%) | 64 (18) | 83 (23) | 96 (27) | 113 (32) |
0.001
|
Ischaemic heart disease, no. (%) | 232 (65) | 232 (65) | 228 (64) | 240 (68) | 0.64 |
Cerebrovascular disease, no. (%) | 17 (5) | 30 (8) | 28 (8) | 28 (8) | 0.19 |
Body surface area (m2) | 1.86 (1.67–2.05) | 1.90 (1.71–2.08) | 1.91 (1.75–2.07) | 1.95 (1.78–2.11) |
< 0.001
|
Systolic BP (mmHg) | 130 (115–147) | 129 (115–147) | 130 (115–147) | 128 (112–147) | 0.69 |
Diastolic BP (mmHg) | 75 (67–83) | 75 (66–84) | 78 (69–87) | 75 (65–83) | 0.89 |
Heart rate (bpm) | 70 (60–84) | 74 (64–87) | 72 (62–86) | 73 (62–86) | 0.34 |
QRS (ms) | 104 (92–134) | 106 (96–136) | 114 (98–142) | 120 (104–148) |
< 0.001
|
QRS ≥ 150 ms (%) | 44 (12) | 51 (14) | 69 (19) | 88 (25) |
< 0.001
|
PR (ms) | 144 (134–151) | 164 (160–168) | 182 (176–188) | 210 (200–222) | – |
PRc (ms) | 146 (136–152) | 166 (162–170) | 184 (178–189) | 212 (203–224) | – |
QT (ms) | 417 (382–446) | 406 (374–440) | 412 (385–449) | 418 (384–452) | 0.15 |
QTc (ms) | 447 (419–478) | 453 (421–482) | 454 (422–486) | 456 (424–484) |
0.01
|
Thyroid stimulating hormone (mIU/L) | 1.5 (1.0–2.4) | 1.5 (1.0–2.3) | 1.7 (1.0–2.6) | 1.7 (1.1–2.7) |
0.01
|
eGFR (1.73 mL/min/m2) | 66 (50–81) | 63 (48–79) | 61 (46–77) | 58 (44–71) |
< 0.001
|
NT-ProBNP (ng/L) | 1311 (582–3045) | 1048 (446–3331) | 1400 (548–3350) | 1751 (811–3915) |
0.50
|
Ejection fraction by Simpson’s | 32 (27–38) | 33 (27–38) | 33 (27–37) | 32 (25–37) | 0.19 |
Left ventricular dysfunction, no. (%) |
0.02
| ||||
Normal–trivial | – | – | – | – | |
Mild | 0 | 0 | 0 | 0 | |
Mild–moderate | 227 (64) | 213 (60) | 213 (60) | 196 (55) | |
>Moderate | 128 (36) | 142 (40) | 142 (40) | 159 (45) | |
Mitral regurgitation > mild | 108 (31) | 100 (29) | 124 (36) | 115 (33) | 0.23 |
β-blocker, no. (%) | 208 (60) | 222 (63) | 214 (61) | 218 (61) | 0.57 |
ACE-I, no. (%) | 259 (74) | 254 (72) | 251 (71) | 255 (73) | 0.72 |
ARB, no. (%) | 31 (9) | 37 (10) | 26 (7) | 39 (11) | 0.59 |
MRA, no. (%) | 87 (25) | 109 (31) | 115 (32) | 111 (32) |
0.05
|
Amiodarone, no. (%) | 14 (4) | 9 (3) | 14 (4) | 29 (8) |
0.005
|
Digoxin, no. (%) | 20 (6) | 28 (8) | 32 (9) | 38 (11) |
0.01
|
Loop diuretic, no. (%) | 234 (67) | 237 (67) | 246 (70) | 276 (78) | 0.001 |
Ivabradine, no. (%) | 3 (0.8) | 1 (0.3) | 0 | 1 (0.3) | 0.16 |
1 year mortality, no. (%) | 36 (10) | 49 (14) | 36 (11) | 49 (13) | 0.34 |
Variables associated with a long PR interval
Univariable model | Multivariable model | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HeFREF
N = 1420 | HeFNEF
N = 1094 | No HF
N = 1150 | HeFREF (R
2 = 0.12)
N = 976 | HeFNEF (R
2 = 0.15)
N = 1046 | Not HF (R
2 = 0.16)
N = 884 | ||||||||
P
|
P
| Unstandardized coefficient B (95% CI) |
P
| Standardized coefficient | Unstandardized coefficient B (95% CI) |
P
| Standardized coefficient | Unstandardized coefficient B (95% CI) |
P
| Standardized coefficient | |||
Age | Per decade increase |
< 0.001
|
< 0.001
|
< 0.001
| 4.94 (2.87, 7.01) |
< 0.001
| 0.18 | 8.83 (6.30, 11.36) |
< 0.001
| 0.23 | 4.79 (2.88, 6.71) |
< 0.001
| 0.19 |
Sex | Men vs. women |
< 0.001
|
< 0.001
|
< 0.001
| 10.41 (5.64, 15.17) |
< 0.001
| 0.15 | 8.83 (4.16, 14.01) |
< 0.001
| 0.12 | 2.57 (−1.42, 6.56) | 0.20 | 0.05 |
QRS | Per 10 ms increase |
< 0.001
|
< 0.001
|
< 0.001
| 1.53 (0.86, 2.21) |
< 0.001
| 0.14 | 2.64 (1.78, 3.510) |
< 0.001
| 0.18 | 2.75 (1.67, 3.83) |
< 0.001
| 0.17 |
BSA | Per m2 increase |
< 0.001
|
< 0.001
|
< 0.001
| 16.86 (7.14, 26.57) |
0.001
| 0.14 | 23.68 (13.33, 34.03) |
< 0.001
| 0.17 | 19.27 (11.27, 27.27) |
< 0.001
| 0.17 |
Diabetes | Yes vs. no |
< 0.001
| 0.20 |
< 0.001
| 3.73 (−0.88, 8.35) | 0.13 | 0.05 | 1.14 (−3.73, 6.02) | 0.65 | 0.01 | 6.52 (2.43, 10.61) |
0.002
| 0.10 |
NYHA | III/IV vs. I/II |
0.004
| 0.08 | 0.34 | 2.86 (−1.31, 7.04) | 0.17 | 0.04 | 1.84 (−3.25, 6.94) | 0.48 | 0.02 | 1.33 (−3.65, 6.31) | 0.54 | 0.02 |
Log[NT-ProBNP] | Per Log[NT-ProBNP] increase |
0.04
|
0.01
| 0.56 | 2.10 (−1.79, 6.00) | 0.27 | 0.04 | 4.06 (−1.65, 9.77) | 0.16 | 0.05 | −4.42 (−10.27, 1.43) | 0.14 | −0.05 |
Systolic BP | Per 5 mmHg increase | 0.89 | 0.94 | 0.01 | −0.20 (−0.63, 0.23) | 0.38 | −0.03 | 0.04 (−0.38, 0.45) | 0.86 | 0.01 | 0.10 (−0.33, 0.52) | 0.64 | 0.02 |
eGFR | Per 5 mL/min/1.73 m2
|
< 0.001
|
0.01
|
< 0.001
| 0.12 (−0.46, 0.69) | 0.70 | 0.01 | 0.13 (−0.46, 0.72) | 0.67 | 0.01 | −0.79 (−1.41, −0.17) |
0.01
| −0.09 |
Digoxin | Yes vs. no |
0.01
| 0.08 | 0.32 | 10.36 (3.12, 17.59) | 0.01 | 0.09 | 6.69 (−4.63, 18.01) | 0.25 | 0.03 | 9.72 (−8.96, 28.40) | 0.31 | 0.04 |
Amiodarone | Yes vs. no |
< 0.001
| 0.07 | 0.94 | 10.94 (1.93, 19.95) |
0.01
| 0.08 | −2.29 (−17.84, 13.26) | 0.77 | −0.01 | −11.24 (−34.22, 11.73) | 0.37 | −0.03 |
Loop diuretic | Yes vs. no |
0.03
|
0.049
| 0.09 | 2.85 (−1.53, 7.23) | 0.18 | 0.04 | −2.60 (−7.19, 2.00) | 0.27 | −0.04 | −1.35 (−5.48, 2.78) | 0.52 | −0.02 |
ARB | Yes vs. no |
0.04
| 0.41 | 0.08 | 2.42 (−5.03, 9.87) | 0.51 | 0.02 | 2.87 (−3.32, 9.05) | 0.36 | 0.03 | −2.05 (−7.41, 3.31) | 0.45 | −0.03 |
MRA | Yes vs. no |
0.02
| 0.23 |
0.03
| 0.60 (−3.93, 5.14) | 0.79 | 0.01 | 2.31 (−5.41, 10.04) | 0.56 | 0.02 | 5.69 (−5.22, 17.12) | 0.29 | 0.03 |
ACE-I | Yes vs. no | 0.27 | 0.23 |
0.003
| −0.54 (−5.62, 4.55) | 0.85 | −0.01 | 1.14 (−3.41, 5.69) | 0.62 | 0.02 | 2.02 (−1.39, 6.53) | 0.20 | 0.04 |
β-blocker | Yes vs. no | 0.70 |
0.003
|
0.003
| −0.47 (−0.4.56, 3.63) | 0.82 | −0.01 | 4.68 (0.41, 8.95) | 0.03 | 0.06 | 4.78 (0.80, 8.77) |
0.02
| 0.08 |
One-year follow-up in patients with HeFREF
Cox regression | HeFREF N = 975 | HeFNEF N = 1040 | Not HF N = 873 | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Variable | Hazard ratio representation | Hazard ratio (95% CI) |
P value | Wald | Hazard ratio (95% CI) |
P value | Wald | Hazard ratio (95% CI) |
P value | Wald |
Log[NT-ProBNP] | Per Log[NT-ProBNP] increase | 2.23 (1.78, 2.77) |
< 0.001
| 50.27 | 2.12 (1.63, 2.75) |
< 0.001
| 31.39 | 1.91 (0.98, 3.73) |
0.06
| 3.56 |
Age | Per decade increase | 1.44 (1.26, 1.65) |
< 0.001
| 28.01 | 1.69 (1.48, 1.95) |
< 0.001
| 55.10 | 1.64 (1.33, 2.02) |
< 0.001
| 21.58 |
Diastolic BP | Per 5 mmHg increase | 0.91 (0.87, 0.95) |
< 0.001
| 20.53 | 0.99 (0.95, 1.03) | 0.58 | 0.31 | 0.94 (0.87, 1.00) | 0.06 | 3.53 |
NYHA | III/IV vs. I/II | 1.39 (1.12, 1.72) |
0.003
| 8.95 | 1.45 (1.15, 1.83) |
0.001
| 10.12 | 1.80 (1.19, 2.73) |
0.006
| 7.68 |
Digoxin | Yes vs. no | 1.45 (1.02, 2.07) |
0.03
| 4.33 | 1.78 (1.17, 2.71) |
0.01
| 7.32 | 4.05 (1.67, 9.80) |
0.002
| 9.60 |
eGFR | Per 5 mL/min/1.73 m2 increase | 0.97 (0.94, 1.00) |
0.03
| 4.67 | 0.99 (0.96, 1.02) |
0.43
| 0.62 | 0.99 (0.93, 1.05) | 0.66 | 0.19 |
β-blocker | Yes vs. no | 0.85 (0.68, 1.07) | 0.16 | 1.97 | 0.82 (0.65, 1.03) | 0.09 | 2.87 | 0.61 (0.37, 1.00) | 0.05 | 3.84 |
Loop diuretic | Yes vs. no | 1.21 (0.95, 1.55) | 0.13 | 2.30 | 1.69 (1.35, 2.11) |
< 0.001
| 21.52 | 1.59 (1.12, 2.27) |
0.01
| 6.48 |
Ischaemic heart disease | Yes vs. no | 1.17 (0.93, 1.46) | 0.17 | 1.85 | 0.90 (0.73, 1.12) | 0.34 | 0.90 | 1.17 (0.79, 1.72) | 0.44 | 0.60 |
Body surface area | Per m2 increase | 0.62 (0.35, 1.10) | 0.10 | 2.69 | 0.52 (0.31, 0.87) |
0.01
| 6.08 | 0.75 (0.33, 1.67) | 0.47 | 0.51 |
Sex | Men vs. women | 1.16 (0.90, 1.50) | 0.26 | 1.26 | 1.61 (1.27, 2.03) |
< 0.001
| 15.70 | 2.17 (1.48, 3.21) |
< 0.001
| 15.59 |
Diabetes | Yes vs. no | 1.16 (0.90, 1.50) | 0.25 | 1.32 | 1.38 (1.08, 1.76) |
0.01
| 6.83 | 1.22 (0.77, 1.92) | 0.38 | 0.76 |
PR | Per 10 ms increase | 1.01 (0.98, 1.05) | 0.40 | 0.70 | 0.99 (0.96–1.03) | 0.69 | 0.16 | 0.92 (0.85, 0.98) |
0.02
| 5.69 |
Baseline heart rate | Per 10 beats per minute increase | 1.03 (0.96, 1.10) | 0.48 | 0.51 | 1.17 (1.08, 1.26) |
< 0.001
| 15.12 | 1.17 (1.03, 1.33) |
0.02
| 5.42 |
Amiodarone | Yes vs. no | 1.13 (0.71, 1.79) | 0.61 | 0.26 | 1.55 (0.84, 2.86) | 0.16 | 1.94 | 1.99 (0.60, 6.70) | 0.26 | 1.26 |
QRS | Per 10 ms increase | 0.99 (0.96, 1.03) | 0.77 | 0.09 | 1.01 (0.96, 1.05) | 0.76 | 0.09 | 0.96 (0.86, 1.08) | 0.47 | 0.50 |
CVA/TIA | Yes vs. no | 1.02 (0.71, 1.46) | 0.92 | 0.01 | 1.10 (0.77, 1.58) | 0.60 | 0.28 | 1.55 (0.79, 3.03) | 0.20 | 1.63 |