SUPPLEMENTARY MATERIAL

Dynamic Trajectories of Left Ventricular Ejection Fraction in Heart Failure

Supplementary Table 1. Demographic and clinical characteristics of patients included in the study and

those excluded due to lack of 2 echocardiograms

INCLUDED EXCLUDED

N=1160 N=270 P

Age, years 64.9 ± 12.3 66.7 ± 13.6 0.04

Male 887 (76.5) 194 (71.9) 0.11

White 1153 (99.4) 264 (97.8) 0.03

Etiology 0.82

Ischaemic heart disease 662 (57.1) 149 (55.2)

Dilated cardiomyopathy 160 (13.8) 44 (16.3)

Hypertensive 82 (7.1) 22 (8.1)

Alcohol 68 (5.9) 11 (4.1)

Drugs 35 (3.0) 7 (2.6)

Valvular 70 (6.0) 17 (6.3)

Other 83 (7.2) 20 (7.4)

HF duration, months 6 (1–40) 10 (2–48) 0.09

NYHA class

I 60 (5.2) 60 (5.2)

II 817 (70.4) 817 (70.4)

III 277 (23.9) 277 (23.9)

IV 6 (0.5) 6 (0.5)

LVEF, % 30.4 ± 8.4 30.2 ± 8.9 0.76

LV end-diastolic diameter, mm 61.4 ± 8.3 62.3 ± 8.6 0.16

LV end-systolic diameter, mm 49.3 ± 9.5 49.9 ± 10.5 0.42

Diabetes 461 (40.0) 118 (43.7) 0.23

Hypertension 713 (61.5) 166 (61.5) 1.00

Anemia* 497 (43.0) 120 (44.8) 0.61

Renal insufficiency† 471 (41.0) 134 (50.6) 0.02

Atrial fibrillation/flutter 203 (17.5) 50 (18.5) 0.69

LBBB 155 (13.4) 50 (18.5) 0.03

Heart rate 70.7 ± 14.6 72.8 ± 15.1 0.03

Blood pressure 125.5 ± 21.7 126.2 ± 21.3 0.71

BMI, Kg/m2 27.0 (24.3-30.3) 26.9 (24.0-29.9) 0.68

NTproBNP, ng/L‡ 1623 (709–3709) 1741 (785–4400) 0.12

Data in mean ± SD, median (IQR) or n (%)

*According to W.H.O. criteria (<13 g/dl in men and <12 g/dl in women)

†eGFR (CKD-EPI equation) < 60 ml/min/1.73 m2

‡ Available in 904 patients

BMI: body mass index; F-U: follow-up; HF: heart failure; LBBB: left bundle branch block.

LVEF: left ventricular ejection fraction; NYHA: New York Heart Association; NTproBNP: N-

terminal pro-brain natriuretic peptide.

Supplementary Table 2. Causes of death of the studied cohort during the 15-year follow-up.

AMI: acute myocardial infarction; CV: cardiovascular

Cause of death N %

Unknown 37 3.2

Heart failure 146 12.6

Sudden death 78 6.7

AMI 25 2.2

Stroke 7 0.6

CV procedure 8 0.7

Non-CV 202 17.4

Other CV 33 2.8

Total dead 536 46.2

Supplementary Table 3. Paired wise means data analysis

LVEF Mean change p-value N

Pair 1Baseline 30.3 ± 8.4 1024

1 year 38.3 ± 11.9 +7.9 ± 11.6 <0.001

Pair 21 year 39.3 ± 11.9 683

3 years 41.2 ± 12.5 +1.8 ± 8.1 <0.001

Pair 33 years 41.6 ± 12.2 436

5 years 42 ± 12 +0.40 ± 7.5 0.26

Pair 45 years 41.8 ± 11.8 264

7 years 43.1 ±12.4 +1.3 ± 6.8 0.002

Pair 57 years 43.3 ± 12.2 157

9 years 43.2 ± 11.6 -0.07 ± 7.2 0.90

Pair 69 years 42.3 ± 11 107

11 years 41.5 ± 11.8 -0.73 ± 6.8 0.27

Pair 711 years 41.7 ± 10.8 65

13 years 41.5 ± 10.2 -0.24 ± 5.1 0.71

Pair 813 years 42.3 ± 9.7 34

15 years 41.1 ± 9.2 -1.2 ± 5.5 0.21

Supplementary Figure 1. Title: Schedule of the study.

Caption: Upper part: scheduled doctors' (blue) and nurses' (red) visits along follow-up. Lower

part: scheduled and actual echocardiograms performed along follow-up. Base= Baseline

Supplementary Figure 2. Title: Flow-chart of the study

Caption: Screened, excluded and included patients

Supplementary Figure 3. Title: Distribution of the number of echocardiograms

performed per patient.

Caption: Number of echocardiograms per patient ranged from 2 (minimum

inclusion criteria) to 9 (patients with all the per protocol pre-specified

echocardiograms).

Supplementary Figure 4. Title: Survival curves related to ischemic vs. non-ischemic

etiology

Caption: Patients of ischemic etiology (soft orange) showed worse prognosis

than patients of non-ischemic etiology (dark blue)

Supplementary Figure 5: Title: Loess splines curves of long-term LVEF trajectories

relative to HF hospitalization in the precedent year.

Caption: HF hospitalization in the precedent year (orange) vs. No HF

hospitalization in the precedent year (blue). P for trajectory changes on LVEF

<0.001 for both subgroups. P for comparison between groups <0.001. Shaded

regions displayed around curves represent the confidence interval at level =

0.95.

Supplementary Figure 6: Title: Loess splines curves of long-term LVEF trajectories

relative to vital status through follow-up.

Caption: Alive patients at 15 years of follow-up (blue); patients that died during follow-up

(red); whole cohort (orange).