614 Research letters

The derivation of LHFRS has been

.....................................................................................................................................................................
doi:10.1002/ejhf.1132
Online publish-ahead-of-print 22 December 2017 described in detail.2 Variables included
are hypertension history, myocardial infarc-
Larissa Heart Failure Risk tion history, and red cell distribution width
(RDW) at admission. Absence of hyper-
Score: a proposed simple tension history, presence of myocardial
score for risk stratification in infarction history, and admission RDW value
chronic heart failure ≥15% (median value) are assigned 2, 1, and 1
points, respectively. Patients with LHFRS = 0
have the best, whereas those with LHFRS = 4
Heart failure (HF) is a clinical syndrome with the worst score.
high morbidity and mortality.1 Although many Continuous variables exhibiting normal
prognostic models have been developed or non-normal distribution (Kolmogorov–
in HF, most require the use of calculators Smirnov test) are presented as mean ±
limiting their use in daily practice. We have standard deviation and median (interquartile
developed a simple score—the Larissa Heart range), respectively. Categorical variables are
Failure Risk Score (LHFRS)—that risk strati- presented as frequencies and percentages.
fies patients admitted with acute HF (AHF).2 Differences at baseline between events and
The purpose of this study was to examine non-events were assessed using the Student’s
ROC curves were the prognostic value of t-test, the Wilcoxon rank-sum test, and
LHFRS in ambulatory patients with chronic the Fisher’s exact test as appropriate. A
HF (CHF). visual assessment of LHFRS performance was
This is a retrospective study including made using a bar chart, depicting number of
454 consecutive ambulatory CHF patients events for each score value. Subsequently,
(age ≥ 18 years) followed up for 1 year. the LHFRS was inserted as the only variable
Patients with haemoglobin <10 g/dL, acute into a logistic regression model. A receiver
coronary syndromes (<3 months), sepsis, and operating characteristic (ROC) curve was
those who had received blood transfusions then produced and the area under the ROC
(the year preceding the inclusion in the study), curve (AUC) estimated. also constructed
had been hospitalized for AHF the month and compared for patients with HF with
preceding the clinical evaluation or had a his- preserved (HFpEF) or reduced ejection frac-
tory of malignancy were excluded. The study tion (HFrEF).3 P-values were two-sided and
endpoint was the 1-year all-cause death or those <0.05 were considered as statistically
hospitalization for HF (whichever occurred significant.
first). This study conforms to the principles of The baseline characteristics of the study
the Declaration of Helsinki and was approved population are depicted in Table 1. The study
by the local institutional review committees. composite endpoint occurred in 159 patients

A B
96.2%
100 (25/26)

90
71.7%
80
(43/60)
Percentage of events

70

60 44.8%
50 (30/67)

40 28.1%
(43/153)
30
12.2%
20 (18/148)
10

0
LHFRS=0 LHFRS=1 LHFRS=2 LHFRS=3 LHFRS=4

Figure 1 (A) Percentage of patients experiencing an event by Larissa Heart Failure Risk Score (LHFRS) value. (B) Receiver operating charac-
teristic (ROC) curve to assess the discrimination of LHFRS in the overall cohort (n = 454).

© 2017 The Authors

European Journal of Heart Failure © 2017 European Society of Cardiology
Research letters 615

......................................................................................................................................................................................................................................

......................................................................................................................................................................................................................................
Table 1 Baseline characteristics of the study population according to events
Overall Patients with events Patients without events P-value
(n = 454) (n = 159) (n = 295)
..........................................................................................................................................
Age (years), median [IQR] 74 [13.5] 74 [14] 74 [13] 0.7
Missing 2 – 2
Gender, male (%) 271 (60) 116 (73) 155 (53) <0.0001
Missing – – –
Systolic BP (mmHg), median [IQR] 120 [20] 110 [30] 120 [20] 0.007
Missing 122 61 61
Diastolic BP (mmHg), median [IQR] 70 [10] 70 [15] 70 [10] 0.16
Missing 122 61 61
Heart rate (b.p.m.), median [IQR] 75 [15] 75 [16] 74 [15] 0.03
Missing 104 53 51
Hypertension, yes (%) 342 (75) 77 (48) 265 (90) <0.0001
Missing – – –
Diabetes, yes (%) 152 (34) 64 (41) 88 (30) 0.03
Missing 3 1 2
Atrial fibrillation, yes (%) 198 (44) 86 (55) 112 (38) 0.001
Missing 6 2 4
Myocardial infarction, yes (%) 136 (30) 73 (46) 63 (21) <0.0001
Missing – – –
LVEF (%), median [IQR] 35 [25] 30 [20] 40 [25] <0.0001
≥50 (%) 146 (33) 26 (17) 120 (42) <0.0001
Missing 14 5 9
Haematocrit (%), median [IQR] 39 [6.5] 37.2 [6.9] 39.5 [5.6] 0.0003
Missing – – –
Haemoglobin (g/dL), median [IQR] 12.8 [2.3] 12.3 [2.5] 13 [2.1] 0.0008
Missing – – –
RDW (%), median [IQR] 14.8 [2.5] 15.3 [3] 14.4 [2.2] <0.0001
≥15 (%) 211 (46) 95 (60) 116 (39) <0.0001
Missing – – –
WBC (103 /mm3 ), median [IQR] 7.9 [3.1] 8.1 [2.9] 7.8 [3.2] 0.7
Missing – – –
PLTs (103 /mm3 ), median [IQR] 210 [78] 203 [82] 211 [76] 0.2
Missing – – –
Na+ (mmol/L), median [IQR] 139 [5] 138 [7] 139 [5] 0.01
Missing 81 34 47
K+ (mmol/L), median [IQR] 4.4 [0.7] 4.5 [0.7] 4.4 [0.7] 0.3
Missing 82 36 46
Urea (mg/dL), median [IQR] 49 [41] 56 [45] 45 [35.5] <0.0001
Missing 83 32 51
Creatinine (mg/dL), median [IQR] 1.1 [0.5] 1.2 [0.6] 1.1 [0.5] <0.0001
Missing 82 32 50
SGOT (IU/L), median [IQR] 23 [12] 23 [17] 22.5 [9.5] 0.2
Missing 84 33 51
SGPT (IU/L), median [IQR] 18 [13] 17 [13] 18 [13] 0.9
Missing 85 34 51
Beta-blockers, yes (%) 397 (88) 137 (87) 260 (88) 0.7
Missing 3 2 1
ACEIs, yes (%) 226 (50) 79 (50) 147 (50) 0.9
Missing 3 2 1
ARBs, yes (%) 124 (27) 28 (18) 96 (33) 0.001
Missing 3 2 1
MRAs, yes (%) 228 (51) 96 (61) 132 (45) 0.001
Missing 6 2 4
Loop diuretics, yes (%) 370 (82) 140 (89) 230 (79) 0.004
Missing 4 2 2
NYHA class <0.0001
I (%) 34 (7) 9 (6) 25 (9)
II (%) 270 (60) 69 (43) 201 (69)
III (%) 140 (31) 76 (48) 64 (21)
IV (%) 7 (2) 5 (3) 2 (1)
Missing 3 – 3

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BP, blood pressure; IQR, interquartile range; LVEF, left ventricular ejection fraction; MRA,
mineralocorticoid receptor antagonist; NYHA, New York Heart Association; PLT, platelet; RDW, red cell distribution width; SGOT, aspartate aminotransferase; SGPT, alanine
aminotransferase; WBC, white blood cells.

© 2017 The Authors

European Journal of Heart Failure © 2017 European Society of Cardiology
616 Research letters

(35%). An increasing trend was noted in Haralambos Karvounis4 , 26. doi: https://doi.org/10.1002/ejhf.989. [Epub

......................................................................................................................................................................................................................................

......................................................................................................................................................................................................................................
ahead of print]
the number of patients experiencing an Michael W. Kattan5 , John Skoularigis1 ,
8. van Kimmenade RR, Mohammed AA, Uthama-
event, from lower to higher LHFRS values John Parissis6 , Randall C. Starling2 , lingam S, van der Meer P, Felker GM, Januzzi JL
(Figure 1A). The obtained odds ratio was and Filippos Triposkiadis1∗ Jr. Red blood cell distribution width and 1-year
2.7 [95% confidence interval (CI) 2.2–3.4; mortality in acute heart failure. Eur J Heart Fail
1 2010;12:129–136.
P < 0.0001], meaning approximately three Department of Cardiology, University General
Hospital of Larissa, Larissa, Greece; 2 Department 9. Cohen-Solal A, Laribi S, Ishihara S, Vergaro G,
times higher odds of an event for every unit Baudet M, Logeart D, Mebazaa A, Gayat E,
of Cardiovascular Medicine, Heart and Vascular
increase of the LHFRS value. Furthermore, Vodovar N, Pascual-Figal DA, Seronde MF. Prog-
Institute, Kaufman Center for Heart Failure, nostic markers of acute decompensated heart
LHFRS discriminated patients who experi- Cleveland Clinic, Cleveland, OH, USA; failure: the emerging roles of cardiac biomark-
enced the study endpoint from those who 3
Independent Biostatistician, Athens, Greece; ers and prognostic scores. Arch Cardiovasc Dis
did not with an AUC of 0.78 (0.73–0.82) 4
First Cardiology Department, University General 2015;108:64–74.
(Figure 1B), and showed a similar good per- Hospital AHEPA, Thessaloniki, Greece; 10. Velazquez EJ, Francis GS, Armstrong PW, Ayl-
5
Department of Quantitative Health Sciences, ward PE, Diaz R, O’Connor CM, White HD,
formance in patients with HFrEF [AUC 0.76
Cleveland Clinic, Cleveland, OH, USA; and Henis M, Rittenhouse LM, Kilaru R, van Gilst
(0.71–0.82), n = 294] and HFpEF [AUC 0.77 6 Department of Cardiology, Athens University W, Ertl G, Maggioni AP, Spac J, Weaver WD,
(0.67–0.87), n = 146]. Rouleau JL, McMurray JJ, Pfeffer MA, Califf RM.
Hospital Attikon, Athens, Greece
These results indicate that LHFRS may An international perspective on heart failure and
*Email: ftriposkiadis@gmail.com left ventricular systolic dysfunction complicating
accurately stratify ambulatory CHF patients. myocardial infarction: the VALIANT registry. Eur
Three validated and commonly used scores in Heart J 2004;25:1911–1919.
CHF are the Seattle HF Risk Model, the MAG- References 11. Metra M, Torp-Pedersen C, Swedberg K, Cleland
GIC Risk Score and the MECKI score.4 – 7 1. Starling RC. The heart failure pandemic: changing JG, Di Lenarda A, Komajda M, Remme WJ,
patterns, costs, and treatment strategies. Cleve Clin Lutiger B, Scherhag A, Lukas MA, Charlesworth
The first consists of 14 continuous variables J Med 1998;65:351–358. A, Poole-Wilson PA. Influence of heart rate, blood
and 10 categorical values, the second includes 2. Xanthopoulos A, Giamouzis G, Tryposkiadis K, pressure, and beta-blocker dose on outcome and
13 variables, whereas the third encompasses Paraskevopoulou E, Paraskevopoulou P, Karagian- the differences in outcome between carvedilol
nis G, Patsilinakos S, Parissis J, Farmakis D, Butler and metoprolol tartrate in patients with chronic
six different variables. The vast majority of heart failure: results from the COMET trial. Eur
J, Skoularigis J, Triposkiadis F. A simple score for
scores used in acute HF do not perform well early risk stratification in acute heart failure. Int J Heart J 2005;26:2259–2268.
in CHF. Our model consists of only three Cardiol 2017;230:248–254. 12. Triposkiadis F, Giamouzis G, Parissis J, Starling
variables, all with proven prognostic ability 3. Hanley JA, McNeil BJ. The meaning and use of RC, Boudoulas H, Skoularigis J, Butler J, Filippatos
G. Reframing the association and significance of
both in acute and chronic HF.8 – 14 the area under a receiver operating characteristic
co-morbidities in heart failure. Eur J Heart Fail
(ROC) curve. Radiology 1982;143:29–36.
This study has several limitations. First, the 4. Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, 2016;18:744–758.
very small sample size deriving from only two Anker SD, Cropp AB, Anand I, Maggioni A, Bur- 13. Wu AH, Parsons L, Every NR, Bates ER; Second
ton P, Sullivan MD, Pitt B, Poole-Wilson PA, Mann National Registry of Myocardial Infarction. Hospi-
centres; second the retrospective nature of
DL, Packer M. The Seattle Heart Failure Model: tal outcomes in patients presenting with congestive
the data collection, although this is more rep- heart failure complicating acute myocardial infarc-
prediction of survival in heart failure. Circulation
resentative of ‘real-world patients’; third, the 2006;113:1424–1433. tion: a report from the Second National Registry
inclusion of ambulatory patients with CHF in 5. Pocock SJ, Ariti CA, McMurray JJ, Maggioni of Myocardial Infarction (NRMI-2). J Am Coll Cardiol
A, Kober L, Squire IB, Swedberg K, Dobson J, 2002;40:1389–1394.
New York Heart Association (NYHA) classes 14. Felker GM, Allen LA, Pocock SJ, Shaw LK, McMur-
Poppe KK, Whalley GA, Doughty RN. Predicting
II and III limiting the implementation of the survival in heart failure: a risk score based on ray JJ, Pfeffer MA, Swedberg K, Wang D, Yusuf S,
LHFRS in other NYHA classes; fourth, as 39 372 patients from 30 studies. Eur Heart J Michelson EL, Granger CB; CHARM Investigators.
Red cell distribution width as a novel prognostic
neurohumoral inhibitors are used both in 2013;34:1404–1413.
marker in heart failure: data from the CHARM
HF and hypertension, labelling some patients 6. Agostoni P, Corrà U, Cattadori G, Veglia F, La
Program and the Duke Databank. J Am Coll Cardiol
Gioia R, Scardovi AB, Emdin M, Metra M, Sinagra
hypertensive based on treatment may occa- G, Limongelli G, Raimondo R, Re F, Guazzi
2007;50:40–47.
sionally be problematic; fifth, our patient M, Belardinelli R, Parati G, Magrì D, Fiorentini
cohort included a Caucasian Greek popula- C, Mezzani A, Salvioni E, Scrutinio D, Ricci R,
Bettari L, Di Lenarda A, Pastormerlo LE, Pacileo
tion and the results may not be applicable to
G, Vaninetti R, Apostolo A, Iorio A, Paolillo S,
other ethnicities. Palermo P, Contini M, Confalonieri M, Giannuzzi
Regarding the therapeutic implications of P, Passantino A, Dei Cas L, Piepoli MF, Passino
the LHFRS, it is reasonable to assume that HF C. Metabolic exercise test data combined with
cardiac and kidney indexes, the MECKI score:
patients with high LHFRS should be treated
a multiparametric approach to heart failure
more aggressively compared to those with prognosis. Int J Cardiol 2013;167:2710–2718.
low LHFRS. In conclusion, LHFRS is a simple 7. Agostoni P, Paolillo S, Mapelli M, Gentile P,
prognostic score with substantial prognostic Salvioni E, Veglia F, Bonomi A, Corrà U, Lagioia
R, Limongelli G, Sinagra G, Cattadori G, Scardovi
ability in ambulatory CHF patients. However, AB, Metra M, Carubelli V, Scrutinio D, Raimondo
LHFRS should be further validated in larger R, Emdin M, Piepoli M, Magrì D, Parati G, Caravita
prospective studies. S, Re F, Cicoira M, Mina C, Correale M, Frigerio
Conflict of interest: none declared. M, Bussotti M, Oliva F, Battaia E, Belardinelli R,
Mezzani A, Pastormerlo L, Guazzi M, Badagliacca
R, Di Lenarda A, Passino C, Sciomer S, Zambon E,
Andrew Xanthopoulos1,2 , Pacileo G, Ricci R, Apostolo A, Palermo P, Contini
Konstantinos Tryposkiadis3 , M, Clemenza F, Marchese G, Gargiulo P, Binno
S, Lombardi C, Passantino A, Perrone Filardi P.
Gregory Giamouzis1 , Multiparametric prognostic scores in chronic
Dimitrios Konstantinou4 , heart failure with reduced ejection fraction: a
George Giannakoulas4 , long-term comparison. Eur J Heart Fail 2017 Sep

© 2017 The Authors

European Journal of Heart Failure © 2017 European Society of Cardiology