Introduction
Pericardial effusions in cardiac amyloidosis
Methods
Study population
Diagnosis of cardiac amyloidosis
Definitions of clinical endpoints
Baseline assessment and transthoracic echocardiography
Total population (n = 143) | No effusion (n = 65) | Pericardial and/or pleural effusion (n = 78) | p-value | |
---|---|---|---|---|
Clinical parameters | ||||
Age, years | 73.0 (66.0–78.0) | 78.0 (67.0–78.0) | 74.0 (63.0–80.0) | 0.697 |
Male sex | 107 (75) | 51 (79) | 56 (72) | 0.360 |
BMI, kg/m2 | 25.6 (23.2–28.4) | 26.0 (23.0–29.0) | 26.0 (23.0–28.0) | 0.680 |
Systolic BP, mmHg | 126.5 (113.0–140.0) | 125.0 (113.0–140.0) | 128.0 (113.0–139.0) | 0.654 |
Diastolic BP, mmHg | 75.0 (70.0–85.0) | 77.0 /70.0–87.0) | 74.0 (69.0–84.0) | 0.354 |
Heart rate, bpm | 75.0 (66.5–87.0) | 76.0 (68.0–87.0) | 74.0 (65.0–87.0) | 0.566 |
NYHA class | 0.018 | |||
NYHA I | 14 (9.8) | 10 (15.4) | 4 (5.1) | |
NYHA II | 61 (42.7) | 33 (50.8) | 28 (35.9) | |
NYHA III | 64 (44.8) | 21 (32.3) | 43 (55.2) | |
NYHA IV | 4 (2.7) | 1 (1.5) | 3 (3.8) | |
Comorbidities | ||||
Polyneuropathy | 56 (39.2) | 30 (46.2) | 26 (33.3) | 0.118 |
Diabetes mellitus | 20 (14.0) | 12 (18.5) | 8 (10.3) | 0.168 |
Atrial fibrillation | 65 (45.5) | 27 (41.5) | 38 (48.7) | 0.352 |
Coronary artery disease | 29 (20.3) | 11 (16.9) | 18 (23.1) | 0.362 |
Intracardiac device | 19 (23.3) | 8 (12.3) | 11 (14.1) | 0.753 |
Concomitant medication | ||||
AT II antagonist | 35 (24.5) | 19 (29.2) | 16 (20.5) | 0.227 |
ACE inhibitor | 37 (25.9) | 13 (20.0) | 24 (30.8) | 0.143 |
Beta-blocker | 76 (53.1) | 32 (49.2) | 44 (56.4) | 0.392 |
Aldosterone antagonist | 64 (44.8) | 20 (30.8) | 44 (56.4) | 0.002 |
Loop diuretics | 91(63.6) | 30 (46.2) | 61 (78.2) | < 0.001 |
Oral anticoagulant | 67 (46.9) | 29 (44.6) | 38 (48.7) | 0.624 |
Echocardiography parameters | ||||
LA length, mm | 61.0 (55.0–68.0) | 60.0 (55.0–66.0) | 63.0 (55.0–68.0) | 0.147 |
RA length, mm | 59.0 (53.0–64.3) | 58.0 (53.0–63.0) | 60.0 (52.0–66.0) | 0.236 |
LVEDD, mm | 41.0 (37.0–46.0) | 42.0 (38.0–47.0) | 41.0 (34.0–46.0) | 0.060 |
LVEF, % | 45.0 (46.0–64.3) | 52.0 (47.0–65.0) | 55.0 (46.0–64.0) | 0.993 |
LV-GLS, -% | 12.0 (15.0–9.0) | 13.7 (16.8–10.0) | 11.3 (13.8–8.6) | 0.007 |
IVS, mm | 19.0 (16.0–22.0) | 18.0 (16.0–22.0) | 20.0 (17.0–23.0) | 0.155 |
RVEDD, mm | 33.0 (28.0–38.0) | 34.0 (29.0–38.0) | 33.0 (28.0–38.0) | 0.496 |
RV-TDI, m/s | 0.11 (0.09–0.14) | 0.12 (0.09–0.14) | 0.11 (0.09–0.13) | 0.485 |
TAPSE, mm | 16.0 (13.0–19.0) | 17.0 (14.0–20.0) | 15.0 (12.0–18.0) | 0.055 |
RV-GLS, -% | 16.3 (20.7–11.3) | 17.7 (23.0–13.3) | 14.0 (18.5–10.0) | 0.004 |
TR velocity, m/s | 2.9 (2.6–3.3) | 2.9 (2.5–3.2) | 2.9 (2.7–3.3) | 0.446 |
sPAP, mmHg | 43.0 (37.0–58.0) | 43.0 (32.0–55.0) | 43.0 (38.0–58.0) | 0.528 |
IVC diameter, mm | 20.0 (17.0–23.0) | 19.0 (14.0–22.0) | 20.0 (18.0–24.0) | 0.237 |
Laboratory parameters | ||||
NT-pro BNP, pg/mL | 2815.0 (1412.0–7173.0) | 1635.0 (827.0–3549.0) | 4268.5 (2048.0–8866.0) | < 0.001 |
Troponin T, ng/L | 52.0 (31.0–96.5) | 38.0 (22.0–56.0) | 68.0 (43.5–118.0) | < 0.001 |
Hemoglobin, g/dL | 12.7 (11.3–14.2) | 12.9 (11.3–14.4) | 12.7 (11.1–14.1) | 0.377 |
Creatinine, mg/dL | 1.2 (1.0–1.6) | 1.3 (0.9–1.6) | 1.2 (1.0–1.6) | 0.813 |
eGFR, mL/min | 51.7 (38.3–63.1) | 52.3 (40.7–72.4) | 51.0 (37.9–59.1) | 0.327 |
ASAT, U/L | 28.0 (22.0–34.0) | 27.0 (22.0–33.0) | 29.0 (23.0–35.0) | 0.102 |
ALAT, U/L | 24.0 (17.0–33.0) | 23.0 (17.0–29.0) | 24.0 (17.0–35.0) | 0.424 |
Albumin, g/L | 40.5 (35.0–44.1) | 43.3 (38.3–45.2) | 38.7 (33.0–42.4) | 0.002 |
GGT, U/L | 65.0 (32.0–137.0) | 42.0 (26.0–126.0) | 79.0 (46.0–140.0) | 0.033 |
LDH, U/L | 231.0 (197.0–282.0) | 224.0 (190.0–249.0) | 241.0 (206.0–292.5) | 0.017 |
CRP, mg/dL | 0.3 (0.1–1.1) | 0.2 (0.1–0.9) | 0.4 (0.1–1.1) | 0.060 |
Cardiac magnetic resonance imaging parameters | ||||
IVS, mm | 19.0 (15.5–22.0) | 18.0 (15.0–22.0) | 17.0 (19.0–22.0) | 0.197 |
LVEF, % | 57.0 (49.0–63.0) | 57.0 (45.0–65.0) | 57.0 (50.0–62.0) | 0.714 |
LV-ECV, % | 46.0 (40.0–55.5) | 45.0 (36.0–52.0) | 49.0 (41.0–58.0) | 0.090 |
RVEF, % | 49.5 (40.1–60.5) | 49.0 (42.0–61.0) | 51.0 (38.0–59.0) | 0.556 |
Statistical analysis
Results
Study cohort
Baseline characteristics and clinical presentation
Pericardial and pleural effusion
Total population (n = 143) | AL (n = 58) | ATTR (n = 85) | |
---|---|---|---|
No effusion | 65 (45.5) | 21 (36.2) | 44 (51.8) |
Isolated pleural effusion | 35 (24.5) | 16 (27.6) | 19 (22.4) |
Isolated pericardial effusion, | 24 (16.8) | 12 (20.7) | 12 (14.1) |
Pleural and pericardial effusion | 19 (13.3) | 9 (15.5) | 10 (11.8) |
Effusions in light chain amyloidosis
No pleural effusion (n = 33) | Pleural effusion (n = 25) | p-value | |
---|---|---|---|
Echocardiography parameters | |||
LA length mm | 60.0 (56.0–67.0) | 60.0 (52.0–64.0) | 0.665 |
LVEDD, mm | 46.0 (43.0–48.0) | 35.0 (32.0–46.0) | < 0.001 |
LVEF, % | 61.0 (51.0–70.0) | 56.0 (46.0–65.0) | 0.626 |
LV-GLS, -% | 14.8 (19.10–14.0) | 11.3 (14.8–8.3) | 0.003 |
IVS, mm | 16.0 (14.0–18.0) | 19.0 (16.0–22.0) | 0.170 |
RV diameter, mm | 34.0 (30.0–37.0) | 30.0 (26.0–36.0) | 0.044 |
RA length, mm | 59.0 (51.0–64.0) | 58.0 (52.0–61.0) | 0.826 |
RV strain basal, -% | 16.5 (20.0–14.0) | 13.0 (18.0–11.0) | 0.009 |
RV strain mid, -% | 18.0 (21.0–15.0) | 14.0 (17.0–11.0) | 0.007 |
RV strain apical, -% | 19.0 (23.0–15.0) | 14.0 (18.0–12.0) | 0.013 |
RV- GLS, -% | 18.0 (21.3–15.0) | 14.0 (17.7–11.0) | 0.007 |
RV- TDI, m/s | 0.14 (0.13–0.16) | 0.11 (0.09–0.12) | 0.009 |
TAPSE, mm | 18.0 (15.0–22.0) | 14.0 (13.0–16.0) | 0.001 |
TR velocity, m/s | 3.0 (2.6–3.7) | 2.8 (2.6–3.1) | 0.251 |
sPAP, mmHg | 51.0 (35.0–67.0) | 42.5 (39.0–50.0) | 0.354 |
IVC diameter, mm | 19.0 (14.0–25.0) | 19.0 (18.0–23.0) | 0.594 |
Laboratory parameters | |||
NT-pro BNP, pg/mL | 2292.0 (1121.0–4118.0) | 8866.0 (4751.0–17,103.0) | < 0.001 |
Troponin T, ng/L | 41.0 (21.0–73.5) | 112.0 (65.0–232.0) | 0.001 |
Gamma GT, U/L | 36.0 (21.0–77.0) | 117.0 (56.0–194.0) | < 0.001 |
ASAT, U/L | 23.0 (18.0–28.0) | 27.0 (20.0–43.0) | 0.094 |
ALAT, U/L | 21.0 (17.0–26.0) | 22.0 (15.0–43.0) | 0.994 |
Albumin, U/L | 39.2 (30.6–42.6) | 33.9 (28.5–40.3) | 0.253 |
CRP, mg/dl | 0.2 (0.1–1.0) | 0.9 (0.3–1.9) | 0.021 |
eGFR, mL/min/1.73m2 | 47.8 (33.3–61.5) | 40.5 (22.7–55.9) | 0.316 |
Cardiac magnetic resonance imaging parameters | |||
IVS, mm | 14.0 (12.0–26.0) | 19.0 (15.0–21.0) | 0.005 |
LVEF, % | 63.0 (53.0–66.0) | 61.0 (57.0–65.0) | 0.572 |
LV-ECV, % | 40.0 (32.0–43.0) | 48.0 (41.0–59.0) | 0.003 |
RVEF, % | 57.0 (48.0–62.0) | 56.0 (45.0–5620) | 0.405 |
Effusions in transthyretin amyloidosis
No pleural effusion (n = 56) | Pleural effusion (n = 29) | p-value | |
---|---|---|---|
Echocardiography parameters | |||
LA length, mm | 60.0 (54.0–63.0) | 66.0 (60.0–71.0) | 0.036 |
LVEDD, mm | 40.0 (38.0–44.0) | 42.0 (38.0–45.0) | 0.110 |
LVEF, % | 52.0 (46.0–62.0) | 54.0 (45.0–63.0) | 0.516 |
LV-GLS, -% | 12.1 (15.3–8.9) | 11.2 (13.1–8.6) | 0.052 |
IVS, mm | 20.0 (17.0–23.0) | 20.0 (17.0–24.0) | 0.790 |
RV diameter, mm | 32.0 (28.0–37.0) | 36.0 (31.0–42.0) | 0.401 |
RA length, mm | 58.0 (53.0–63.0) | 63.0 (59.0–68.0) | 0.017 |
RV strain basal, -% | 17.0 (21.0–11.5) | 12.5 (19.5–10.0) | 0.242 |
RV strain mid, -% | 17.0 (21.0–12.0) | 14.0 (19.0–10.0) | 0.308 |
RV strain apical, -% | 17.0 (21.0–12.0) | 16.5 (20.5–10.5) | 0.795 |
RV- GLS, -% | 17.0 (20.8–12.0) | 13.8 (19.5–10.2) | 0.399 |
RV- TDI, m/s | 0.10 (0.08–0.13) | 0.10 (0.09–0.12) | 0.965 |
TAPSE, mm | 16.0 (12.0–19.0) | 16.0 (11.0–20.0) | 0.892 |
TR velocity, m/s | 2.9 (2.6–3.2) | 2.9 (2.6–3.3) | 0.783 |
sPAP, mmHg | 42.0 (35.0–55.0) | 50.0 (37.0–61.0) | 0.343 |
IVC diameter, mm | 18.0 (15.0–22.0) | 22.0 (20.0–25.0) | 0.010 |
Laboratory parameters | |||
NT-pro BNP, pg/mL | 1574.5 (846.4–3367.0) | 3908.0 (2048.0–7173.0) | < 0.001 |
Troponin T, ng/L | 39.0 (29.0–64.0) | 68.0 (40.0–79.0) | 0.049 |
Gamma GT, U/L | 66.0 (28.5–140.0) | 72.0 (45.0–140.0) | 0.384 |
ASAT, U/L | 30.0 (24.0–34.0) | 31.0 (25.0–35.0) | 0.366 |
ALAT, U/L | 25.5 (20.0–33.0) | 23.0 (17.0–35.0) | 0.450 |
Albumin, U/L | 43.6 (40.4–46.3) | 38.7 (35.9–42.9) | 0.003 |
CRP, mg/dl | 0.2 (0.1–0.7) | 0.3 (0.2–1.2) | 0.096 |
eGFR, mL/min/1.73m2 | 56.0 (45.7–74.7) | 47.5 (40.6–56.9) | 0.092 |
Cardiac magnetic resonance imaging parameters | |||
IVS, mm | 18.0 (15.0–22.0) | 20.0 (18.0–23.0) | 0.667 |
LVEF, % | 55.0 (42.0–60.0) | 51.0 (46.0–57.0) | 0.098 |
LV-ECV, % | 49.0 (43.0–56.0) | 51.0 (42.0–57.0) | 0.173 |
RVEF, % | 47.0 (39.0–60.0) | 48.0 (37.0–55.0) | 0.474 |
Left and right heart function in patients with AL versus ATTR
Outcomes according to presence and localization of effusion
Univariable HR (95%CI) | p-value | Multivariable HR (95%CI) | p-value | |
---|---|---|---|---|
Clinical variables | ||||
Age, years | 0.999 (0.997–1.001) | 0.270 | ||
Male sex | 0.465 (0.214–1.013) | 0.054 | ||
BMI, kg/cm2 | 0.986 (0.933–1.043) | 0.628 | ||
Systolic BP, mmHg | 0.995 (0.973–1.017) | 0.630 | ||
Diastolic BP, mmHg | 0.997 (0.972–1.022) | 0.815 | ||
Heart rate, bpm | 1.005 (0.983–1.029) | 0.651 | ||
NYHA class | 4.367 (2.186–8.723) | < 0.001 | 2.628 (1.613–4.282) | < 0.001 |
Pleural effusion | 5.604 (2.334–13.456) | < 0.001 | 0.810 (0.356–1.845) | 0.616 |
Pericardial effusion | 0.970 (0.432–2.180) | 0.942 | ||
Comorbidities | ||||
Diabetes mellitus | 1.235 (0.462–3.301) | 0.674 | ||
Atrial fibrillation | 0.685 (0.294–1.596) | 0.380 | ||
Coronary artery disease | 1.619 (0.551–4.756) | 0.381 | ||
Intracardiac device | 1.544 (0.530–4.494) | 0.426 | ||
Echocardiography parameters | ||||
LA length*, mm | 0.990 (0.951–1.030) | 0.609 | ||
RA length*, mm | 1.004 (0.963–1.047) | 0.854 | ||
LVEDD*, mm | 0.887 (0.838–0.939) | < 0.001 | 0.988 (0.911–1.071) | 0.767 |
LVEF, % | 1.010 (0.976–1.046) | 0.556 | ||
LV-GLS, -% | 1.113 (1.020–1.215) | 0.017 | 1.133 (1.018–1.261) | 0.022 |
IVS, mm | 1.115 (1.024–1.214) | 0.013 | 1.071 (0.943–1.215) | 0.291 |
RVEDD*, mm | 0.965 (0.880–1.057) | 0.441 | ||
RV-TDI, m/s | 0.528 (0.301–0.927) | 0.026 | 0.659 (0.328–1.326) | 0.243 |
TAPSE, mm | 0.947 (0.864–1.039) | 0.248 | ||
RV-GLS, -% | 1.080 (0.988–1.182) | 0.091 | ||
TR velocity, m/s | 1.232 (0.608–2.500) | 0.563 | ||
sPAP, mmHg | 1.011 (0.983–1.040) | 0.428 | ||
IVC, mm | 0.958 (0.877–1.046) | 0.335 | ||
Laboratory parameters | ||||
NT-pro BNP**pg/mL | 4.959 (2.023–12.158) | 0.005 | 7.212 (2.248–23.136) | 0.001 |
Troponin T**ng/L | 4.282 (1.667–11.003) | 0.003 | 2.916 (0.779–10.906) | 0.112 |
Hemoglobin, mg/dL | 0.996 (0.833–1.192) | 0.968 | ||
Creatinine, mg/dL | 0.866 (0.690–1.086) | 0.213 | ||
eGFR, mL/min | 0.992 (0.978–1.005) | 0.241 | ||
ASAT, U/L | 1.008 (0.997–1.020) | 0.154 | ||
ALAT, U/L | 1.010 (0.997–1.022) | 0.139 | ||
Albumin, g/L | 0.968 (0.930–1.008) | 0.113 | ||
GGT, U/L | 1.001 (1.000–1.002) | 0.172 | ||
LDH, U/L | 1.003 (1.000–1.006) | 0.080 | ||
CRP, mg/dL | 1.033 (0.898–1.187) | 0.653 |