Introduction
Methods
The PURSUIT-HFpEF registry
Study population
Plasma osmolality, nutrition status, plasma volume estimation and echocardiographic measurements
Follow-up and endpoints
Statistical analysis
Results
Characteristics of the study population
All patients (n = 960) | Q1 (n = 318) Osm < 293.2 | Q2 (n = 322) 293.2 ≤ Osm < 300.3 | Q3 (n = 320) 300.3 ≤ Osm | P-value | |
---|---|---|---|---|---|
Age, years | 83 (77–87) | 83 (77–87) | 83 (77–87) | 83 (77–87) | 0.9761 |
Female | 524 (55) | 178 (56) | 179 (56) | 167 (52) | 0.5709 |
Prior HF hospitalization | 244 (26) | 63 (20)‡ | 84 (26) | 97 (31)* | 0.0089 |
Comorbidities | |||||
Hypertension | 809 (85) | 254 (80)‡ | 272 (85) | 183 (89)* | 0.0112 |
Diabetes | 314 (33) | 87 (28)‡ | 93 (29)‡ | 134 (42)*,† | < 0.0001 |
Dyslipidemia | 393 (41) | 111 (35)‡ | 128 (40) | 154 (48)* | 0.0036 |
COPD | 73 (8) | 25 (8) | 21 (7) | 27 (9) | 0.6247 |
CKD | 384 (40) | 97 (31)‡ | 118 (37)‡ | 169 (53)*,† | < 0.0001 |
Malignancy | 112 (12) | 36 (12) | 33 (10) | 43 (14) | 0.4165 |
General condition on admission | |||||
BMI, kg/m2 | 23.8 (21.0–26.9) | 23.2 (20.6–26.5)‡ | 23.7 (20.9–26.8) | 24.6 (21.9–27.7)* | 0.0022 |
SBP, mmHg | 147 (128–170) | 146 (129–166) | 149 (127–167) | 149 (128–175) | 0.3444 |
DBP, mmHg | 80 (66–93) | 82 (69–92) | 80 (67–94) | 76 (64–93) | 0.2598 |
Heart rate | 82 (67–100) | 82 (68–102) | 82 (68–99) | 82 (65–100) | 0.7596 |
AF | 444 (46) | 153 (48) | 154 (48) | 137 (43) | 0.3187 |
GNRI | 98 (90–106) | 96 (89–103)‡ | 98 (90–106) | 100 (92–107)* | 0.0110 |
Laboratory examination on admission | |||||
Hemoglobin, g/dL | 11.1 (9.8–12.5) | 11.5 (10.1–12.7)‡ | 11.4 (10.1–12.7)‡ | 10.7 (9.4–12.3)*,† | < 0.0001 |
Hematocrit, % | 34 (30–38) | 35 (31–38)‡ | 35 (31–38)‡ | 33 (29–38)*,† | 0.0033 |
Serum total protein, g/dL | 6.7 (6.3–7.1) | 6.7 (6.3–7.2) | 6.7 (6.3–7.2) | 6.7 (6.2–7.1) | 0.3454 |
Serum albumin, g/dL | 3.5 (3.2–3.8) | 3.5 (3.1–3.8) | 3.5 (3.2–3.9) | 3.5 (3.1–3.8) | 0.3340 |
BUN, mg/dL | 22 (16–32) | 18 (14–24)†,‡ | 21 (15–27)*,‡ | 31 (23–43)*,† | < 0.0001 |
Creatinine, mg/dL | 1.1 (0.8–1.5) | 1.0 (0.7–1.2)†,‡ | 1.0 (0.8–1.3)*,‡ | 1.4 (0.9–2.0)*,† | < 0.0001 |
eGFR, mL/min/1.73m2 | 45 (30–58) | 51 (38–65)†,‡ | 45 (33–59)*,‡ | 33 (21–50)*,† | < 0.0001 |
Serum sodium, mEq/L | 140 (137–142) | 137 (134–138)†,‡ | 141 (139–142)*,‡ | 142 (140–144)*,† | < 0.0001 |
Serum potassium, mEq/L | 4.1 (3.7–4.5) | 4.2 (3.8–4.5)† | 4.0 (3.7–4.4)*,‡ | 4.2 (3.7–4.6)† | 0.0084 |
Serum chloride, mEq/L | 105 (101–108) | 101 (98–105)†,‡ | 105 (103–108)*,‡ | 107 (104–110)*,† | < 0.0001 |
NT-proBNP, ng/L | 3250 (1718–6430) | 2950 (1637–5281‡ | 2820 (1580–5292)‡ | 4805 (2108–10,010)*,† | < 0.0001 |
CRP, mg/dL | 0.53 (0.19–1.94) | 0.64 (0.21–2.43) | 0.46 (0.18–1.47) | 0.53 (0.20–2.00) | 0.0734 |
Glucose, mg/dL | 122 (103–161) | 118 (101–146)‡ | 117 (102–147)‡ | 133 (112–194)*,† | < 0.0001 |
PVS, % | 8.7 (− 0.4–16.8) | 8.3 (− 0.04–17.4) | 7.4 (− 1.1–15.6) | 9.8 (0.6–17.9) | 0.3156 |
Plasma osmolality, mOsm/kg | 297 (291–303) | 288 (283–291)†,‡ | 297 (295–299)*,‡ | 305 (303–309)*,† | < 0.0001 |
Echocardiographic variables on admission | |||||
LVDd, mm | 46 (42–51) | 46 (41–49)‡ | 46 (41–51) | 47 (43–51)* | 0.0066 |
LVEF, % | 60 (56–65) | 60 (56–67) | 61 (56–65) | 60 (55–65) | 0.8524 |
LAD, mm | 44 (40–50) | 44 (39–49) | 45 (40–51) | 45 (39–50) | 0.1973 |
E/A | 1.0 (0.7–1.5) | 1.1 (0.7–1.5) | 1.1 (0.7–1.7) | 0.9 (0.7–1.5) | 0.4369 |
E/e′ | 16 (12–21) | 16 (12–20)‡ | 16 (12–21) | 17 (13–22)* | 0.0311 |
TRPG, mmHg | 36 (28–45) | 36 (28–45) | 36 (29–45) | 36 (29–45) | 0.9959 |
IVC max, mm | 19 (15–22) | 18 (15–22) | 18 (15–22)‡ | 19 (16–22)† | 0.0548 |
IVC collapsibility | 0.44 (0.28–0.57) | 0.38 (0.23–0.55)† | 0.48 (0.30–0.59)* | 0.44 (0.29–0.56) | 0.0009 |
Acute phase treatment | |||||
NIPPV usage | 121 (13) | 36 (11)‡ | 26 (8)‡ | 59 (19)*,† | 0.0003 |
intubation | 16 (1.7) | 3 (0.9) | 2 (0.6)‡ | 11 (3)† | 0.0094 |
DOA (continuous injection) | 1 (0.1) | 0 (0) | 0 (0) | 1 (0.3) | 0.3663 |
DOB (continuous injection) | 17 (1.7) | 2 (0.6) | 7 (2) | 8 (3) | 0.1591 |
NAD (continuous injection) | 10 (1.0) | 3 (0.9) | 3 (0.9) | 4 (1.3) | 0.9018 |
PDE3I (continuous injection) | 3 (0.3) | 0 (0) | 2 (0.6) | 1 (0.3) | 0.3717 |
Carperitide (continuous injection) | 207 (22) | 54 (17)‡ | 66 (21) | 87 (27)* | 0.0063 |
nitrates (continuous injection) | 264 (28) | 85 (27) | 80 (25) | 99 (31) | 0.1989 |
Calcium channel blocker (continuous injection) | 77 (8) | 18 (6)‡ | 23 (7) | 36 (11)* | 0.0255 |
Nicorandil (continuous injection) | 6 (0.6) | 1 (0.3) | 3 (0.9) | 2 (0.6) | 0.6125 |
Diuretics (continuous injection) | 310 (32) | 103 (32) | 100 (31) | 107 (34) | 0.7970 |
Diuretics (bolus injection) | 549 (57) | 176 (55) | 178 (55) | 195 (61) | 0.2296 |
Prescription before admission | |||||
Antiplatelet | 292 (30) | 91 (29) | 95 (30) | 106 (33) | 0.4225 |
ACE inhibitor or ARB | 481 (50) | 149 (47) | 156 (48) | 176 (55) | 0.0924 |
Calcium channel blocker | 489 (51) | 148 (47) | 162 (50) | 179 (56) | 0.0575 |
β-blocker | 444 (46) | 136 (43) | 155 (48) | 153 (48) | 0.3031 |
Loop diuretics | 483 (50) | 133 (42)‡ | 165 (51) | 185 (58)* | 0.0003 |
Thiazide | 72 (8) | 33 (10)† | 13 (4)* | 26 (8) | 0.0085 |
Tolvaptan | 52 (5) | 14 (4) | 22 (7) | 16 (5) | 0.3667 |
Aldosterone antagonist | 204 (21) | 72 (23) | 68 (21) | 64 (20) | 0.7153 |
SGLT2 inhibitor | 15 (1.6) | 6 (1.9) | 2 (0.6) | 7 (2) | 0.2363 |
Anticoagulant | 424 (44) | 154 (48) | 145 (45) | 125 (39) | 0.0545 |
General condition at discharge | All patients (n = 960) | Q1 (n = 318) Osm < 293.2 | Q2 (n = 322) 293.2 ≤ Osm < 300.3 | Q3 (n = 320) 300.3 ≤ Osm | P-value |
---|---|---|---|---|---|
BMI, kg/m2 | 21.4 (18.9–24.2) | 21.1 (18.4–23.8)‡ | 21.2 (18.7–24.3) | 21.9 (19.4–24.6)* | 0.0150 |
SBP, mmHg | 118 (106–131) | 117 (106–128)‡ | 118 (106–130) | 122 (107–134)* | 0.0106 |
DBP, mmHg | 65 (58–73) | 65 (58–73) | 66 (58–74) | 65 (57–73) | 0.7041 |
Heart rate | 70 (61–80) | 70 (63–80) | 70 (61–80) | 70 (60–78) | 0.5914 |
AF | 365 (38) | 124 (39) | 131 (41) | 110 (34) | 0.2242 |
GNRI | 92 (85–99) | 91 (84–97) | 94 (85–101) | 92 (85–99) | 0.1277 |
6MWD, m | 260 (155–340) | 240 (150–333) | 270 (156–352) | 260 (160–338) | 0.5728 |
NYHA classification | 0.6460 | ||||
NYHA I | 340 (36) | 111 (36) | 106 (33) | 123 (39) | |
NYHA II | 538 (57) | 173 (55) | 193 (60) | 172 (54) | |
NYHA III | 67 (7) | 26 (8) | 20 (6) | 21 (7) | |
NYHA IV | 4 (0.4) | 2 (0.6) | 1 (0.3) | 1 (0.3) | |
Laboratory examination at discharge | |||||
Hemoglobin, g/dL | 11.3 (10.1–12.7) | 11.5 (10.3–12.7)‡ | 11.6 (10.4–13.1)‡ | 10.8 (9.5–12.2)*,† | < 0.0001 |
Hematocrit, % | 34 (31–39) | 35 (32–38)‡ | 35 (32–39)‡ | 33 (30–37)*,† | < 0.0001 |
Serum total protein, g/dL | 6.6 (6.2–7.1) | 6.8 (6.3–7.2)‡ | 6.8 (6.3–7.2)‡ | 6.5 (6.1–7.0)*,† | 0.0009 |
Serum albumin, g/dL | 3.4 (3.1–3.7) | 3.4 (3.1–3.7) | 3.4 (3.2–3.8)‡ | 3.3 (3.1–3.6)† | 0.0104 |
BUN, mg/dL | 25 (18–34) | 22 (16–28)†,‡ | 25 (18–33)*,‡ | 29 (21–42)*,† | < 0.0001 |
Creatinine, μmol/L | 1.1 (0.9–1.5) | 1.0 (0.8–1.2)†,‡ | 1.1 (0.9–1.5)*,‡ | 1.3 (1.0–2.1)*,† | < 0.0001 |
eGFR, mL/min/1.73m2 | 42 (30–55) | 50 (37–60)†,‡ | 42 (32–54)*,‡ | 33 (21–49)*,† | < 0.0001 |
Serum sodium, mEq/L | 139 (137–141) | 138 (135–140)†,‡ | 140 (138–141)*,‡ | 140 (138–142)* | < 0.0001 |
Serum potassium, mEq/L | 4.3 (3.9–4.6) | 4.3 (3.9–4.6) | 4.3 (4.0–4.6) | 4.3 (3.9–4.6) | 0.8271 |
Serum chloride, mEq/L | 103 (100–106) | 102 (99–105†,‡ | 103 (100–105)*,‡ | 104 (101–107)*,† | < 0.0001 |
NT–proBNP, ng/L | 1112 (478–2550) | 993 (497–2190)‡ | 952 (439–2025)‡ | 1437 (510–3770)*,† | 0.0010 |
CRP, mg/dL | 0.29 (0.11–0.90) | 0.34 (0.11–1.01) | 0.28 (0.11–0.77) | 0.26 (0.11–0.93) | 0.4804 |
Glucose, mg/dL | 98 (88–117) | 97 (87–114) | 98 (88–117) | 101 (89–120) | 0.3746 |
PVS, % | 11.5 (1.9–19.6) | 9.9 (1.9–20.0) | 9.6 (0.9–17.9)‡ | 13.4 (3.1–21.2)† | 0.0411 |
Plasma osmolality, mOsm/kg | 294 (289–299) | 290 (286–295)†,‡ | 294 (290–299)*,‡ | 297 (293–302)*,† | < 0.0001 |
Prescription at discharge | |||||
Antiplatelet | 278 (29) | 82 (26) | 93 (29) | 103 (32) | 0.1946 |
ACE inhibitor or ARB | 510 (53) | 157 (49) | 168 (52) | 185 (58) | 0.0935 |
Calcium channel blocker | 458 (48) | 135 (42)‡ | 149 (46) | 174 (55)* | 0.0076 |
β-blocker | 526 (55) | 167 (53) | 181 (56) | 178 (56) | 0.5896 |
Loop diuretics | 754 (79) | 243 (76) | 254 (79) | 257 (80) | 0.4793 |
Thiazide | 62 (6) | 18 (6) | 16 (5) | 28 (9) | 0.1165 |
Tolvaptan | 156 (16) | 39 (12)‡ | 54 (17) | 63 (20)* | 0.0377 |
Aldosterone antagonist | 383 (40) | 125 (39) | 141 (44) | 117 (37) | 0.1683 |
SGLT2 inhibitor | 50 (5) | 13 (4) | 12 (4) | 25 (8) | 0.0356 |
Anticoagulant | 571 (59) | 206 (65)‡ | 198 (61) | 167 (52)* | 0.0035 |
Plasma osmolality and prognosis
Unadjusted HR (95% CI) | P-value | |
---|---|---|
Composite endpoint | ||
Q2 versus Q1 | 1.13 (0.80–1.60) | 1.0000 |
Q3 versus Q1 | 1.61 (1.16–2.23) | 0.0120 |
Q3 versus Q2 | 1.42 (1.03–1.96) | 0.0954 |
Cardiac mortality | ||
Q2 versus Q1 | 0.85 (0.42–1.66) | 1.0000 |
Q3 versus Q1 | 1.59 (0.89–2.88) | 0.3531 |
Q3 versus Q2 | 1.88 (1.01–3.61) | 0.1338 |
HF re-admission | ||
Q2 versus Q1 | 1.12 (0.79–1.60) | 1.0000 |
Q3 versus Q1 | 1.50 (1.08–2.11) | 0.0504 |
Q3 versus Q2 | 1.34 (1.08–2.11) | 0.2454 |
Unadjusted HR (95% CI) | P-value | Adjusted HR (95% CI) | P-value | Adjusted HR (95% CI) | P-value | |
---|---|---|---|---|---|---|
Age | 5.86 (1.88–19.32) | 0.0019 | 5.67 (1.40–24.73) | 0.0143 | 5.98 (1.53–25.19) | 0.0093 |
Female | 1.20 (0.91–1.58) | 0.1897 | 1.19 (0.85–1.68) | 0.3120 | 1.18 (0.85–1.65) | 0.3356 |
AF | 0.96 (0.74–1.26) | 0.7902 | 1.15 (0.82–1.62) | 0.4163 | 1.11 (0.79–1.56) | 0.5309 |
HT | 0.94 (0.77–1.15) | 0.5207 | 0.87 (0.54–1.48) | 0.5952 | 0.89 (0.55–1.52) | 0.6637 |
Diabetes | 0.94 (0.80–1.10) | 0.4475 | 1.18 (0.83–1.67) | 0.3447 | 1.19 (0.84–1.68) | 0.3242 |
hematocrit | 0.28 (0.10–0.77) | 0.0139 | 1.08 (0.33–3.41) | 0.9028 | 0.84 (0.27–2.53) | 0.7555 |
eGFR | 0.15 (0.07–0.34) | < 0.0001 | 0.39 (0.12–1.24) | 0.1110 | ||
GNRI | 0.40 (0.10–1.57) | 0.1907 | 0.66 (0.19–2.36) | 0.5257 | 0.80 (0.23–2.72) | 0.7170 |
Log NT-proBNP | 15.04 (1.93–60.70) | 0.0139 | 1.73 (0.46–6.57) | 0.4196 | 2.69 (0.80–8.96) | 0.1077 |
E/e’ | 3.29 (1.25–7.84) | 0.0168 | 2.07 (0.61–6.38) | 0.2372 | 1.99 (0.59–6.09) | 0.2607 |
Plasma Osmolality | 7.29 (2.25–23.92) | 0.0009 | 3.51 (0.89–17.35) | 0.0730 | 5.47 (1.46–21.56) | 0.0113 |
BUN | 6.87 (3.36–13.52) | < 0.0001 | ||||
Serum sodium | 1.18 (0.39–3.81) | 0.7755 | ||||
Glucose | 1.58 (0.46–4.66) | 0.4447 |