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Vol. 69. Issue 12.
Pages 1230-1232 (December 2016)
Scientific letter
DOI: 10.1016/j.rec.2016.09.007
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Relaxin Concentrations in Acute Heart Failure Patients: Kinetics and Clinical Determinants
Concentración de relaxina en pacientes con insuficiencia cardiaca aguda: comportamiento y determinantes clínicos
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Jorge Martínez Solanoa, Juan José Santos Mateob, Jesús Sánchez-Másc, Juan Sánchezb, Mari Carmen Asensio Lópezc, Domingo Pascual Figala,b,c,
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dpascual@um.es

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a Departamento de Medicina, Facultad de Medicina, Universidad de Murcia, Murcia, Spain
b Servicio de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain
c Instituto Murciano de Investigación Biomédica, IMIB, Murcia, Spain
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Table. Characteristics of the Total Population and According to Relaxin Concentrations Upon Arrival at the Emergency Room Below or Above the Median
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To the Editor,

In recent decades, animal experiments have shown numerous cardiovascular benefits for the hormone relaxin, traditionally known for its effects during pregnancy1. Relaxin lowers peripheral vascular resistance, reduces pulmonary congestion, improves cardiac output, and increases renal flow. By increasing nitric oxide, it produces vasodilating, anti-inflammatory, antiplatelet, and antioxidant effects. In addition, there have been descriptions of relaxin cardiac receptors and release in atria and ventricles2. Serelaxin, a recombinant form of endogenous relaxin, has emerged as a therapeutic option in acute heart failure (AHF) and shows promising results in the RELAX-AHF trial3. However, the role of relaxin in the pathophysiology of AHF has not been established, and there are only a few published clinical studies4–6. To date, it has not been shown that endogenous relaxin production is an important compensatory mechanism, a useful biomarker, or a hormone with prognostic value in patients with AHF.

The aim of our study was to analyze the role of relaxin as a neurohormonal mediator in patients with AHF. To conduct the research, we selected 43 consecutive patients (age, 69.8±9.4 years; men, 63%) who had been hospitalized with a diagnosis of AHF. Plasma relaxin concentrations were determined upon arrival at the emergency room and at 30 days after discharge and in stable condition. All concentrations were measured using a previously validated enzyme-linked immunoassay (Immunodiagnostik; Bensheim, Germany)2,4–6. The patients’ clinical, analytical, and echocardiographic variables were retrospectively collected from their medical history.

On arrival at the emergency room, relaxin was undetectable in 3 patients (7%); the median for all other patients was 14.3 [interquartile range, 5.8-48.0] (range, 1.5-878) pg/mL. Table lists the characteristics for the entire study population and according to median concentration. No significant associations were found with any clinical variables, including age, sex, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, echocardiographic variables, and New York Heart Association functional class. After the acute event, relaxin concentration at 30 days had a median of 26.5 [11.4-47.3] (0.85-1031) pg/mL and strongly correlated with concentration on admission (rs=0.536; P<.001). The repeated measures analysis showed no significant change between measurements in the emergency room and at 30 days (P=.204, Wilcoxon test) or a uniform pattern of kinetics (Figure). During follow-up (median, 654 [332-932] days), 8 of 21 patients above and 8 of 22 below the relaxin median died or were readmitted for heart failure (P=.91).

Table.

Characteristics of the Total Population and According to Relaxin Concentrations Upon Arrival at the Emergency Room Below or Above the Median

  Total population, n=43  Relaxin<14.3 (n=22)  Relaxin>14.3 (n=21)  P 
Age, y  69.8±9.4  70.6±9.7  68.8±9.02  .518a 
Sex, female  16 (37.2)  10 (45.5)  5 (28.6)  .258b 
BMI  28.9±4.5  29.1±4.5  28.7±4.6  .819a 
HT  31 (72.1)  16 (72.7)  15 (71.4)  .925b 
Diabetes mellitus  18 (41.9)  11 (50)  7 (33.3)  .274b 
Dyslipidemia  16 (38.1)  8 (36.4)  8 (40)  .811b 
History of stroke  6 (14)  5 (22.7)  1 (4.8)  .093b 
Previous NYHA  2 (1-2.2)  2 (1-2.7)  2 (1-2.2)  .473c 
Hospitalizations for previous HFs  15 (37.5)  5 (25)  10 (50)  .107b 
Ischemic heart disease  14 (32.6)  7 (31.8)  7 (33.3)  .917b 
AMI  6 (14)  3 (13.6)  3 (14.3)  .952b 
Revascularization  6 (14)  1 (4.5)  5 (23.8)  .072b 
ICD or CRT user  1 (2.3)  0 (0)  1 (4.8)  .306b 
APE  20 (46.5)  8 (36.4)  12 (57.1)  .177b 
SBP, mmHg  138.9±33.4  135±29  142±37.5  .494a 
DBP, mmHg  77±17.4  75±12.9  78.7±21.2  .527a 
HR, bpm  88±27.4  88±23  87±31  .937a 
NMV  7 (16.7)  2 (9.5)  5 (23.8)  .220b 
Dopamine IV  3 (7)  2 (9.1)  1 (4.8)  .582b 
Dobutamine IV  1 (2.3)  0 (0)  1 (4.8)  .306b 
Nitrates IV  10 (24.4)  4 (19)  6 (30)  .420b 
Sinus rhythm  22 (51.2)  11 (50)  11 (52.4)  .877b 
Creatinine, mg/dL  1.1 (0.9-1.4)  1 (0.89-1.3)  1.1 (0.95-1.43)  .381c 
Urea, mg/dL  45 (39-57)  45 (37-55)  49.5 (4-67.2)  .433c 
Cystatin C, mg/L  1.37 (1.2-1.9)  1.53 (1.12-2.27)  1.33 (1.26-1.91)  .744c 
Sodium, mEq/L  140 (137-142)  139 (135-142)  140 (137-141)  .855c 
Potassium, mEq/L  4.3±0.5  4.2±0.5  4.3±0.4  .780a 
Hemoglobin, g/dL  12.8±12.5±1.9  13±.454a 
NT-proBNP, pg/mL  3932 (172-8149)  3609 (1619-8152)  4573 (1726-5600)  .911c 
Troponin T, pg/mL  25 (16-46.3)  23 (15.5-32)  32.2 (16.1-49.8)  .338c 
LVEF, %  40.3±17  40.6±17.9  39.8±16.3  .890a 
LV mass, g/m2  131.9±47.5  119±43.8  144±48.9  .112a 
LVEDV, mL/m2  70.6±29.1  67.8±25.3  73.5±33.24  .567a 
LVEDD, mm/m2  52±11.2  51±8.4  53±13.5  .596a 
SPAP, mmHg  44.8±13.8  48.7±16  40±9.2  .128a 
LA, mm  45.5±8.44  45.6±6.5  45.5±10  .959a 

AMI, acute myocardial infarction; APE, acute pulmonary edema; BMI, body mass index; CRT, cardiac resynchronization therapy; DBP, diastolic blood pressure; HF, heart failure; HR, heart rate; HT, hypertension; ICD, implantable cardioverter defibrillator; IV, intravenous; LA, anteroposterior diameter of left atrium; LV, left ventricle; LVEDD, left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; NMV, noninvasive mechanical ventilation; NT-proBNP, N-terminal pro-brain natriuretic peptide; NYHA: New York Heart Association functional class; SBP, systolic blood pressure; SPAP, systolic pulmonary artery pressure.

a

Student t test.

b

Chi-square test.

c

Nonparametric Mann-Whitney U test.

Figure.

Changes in relaxin concentrations on arrival to the emergency room and at 30 days (A) and enlargement of the area between 0 and 200 (pg/mL) (B).

(0.24MB).

Our study is the first to investigate relaxin kinetics in patients with AHF and its relationship with a broad set of variables related to the disease. Relaxin concentrations showed considerable variability, as observed in the few published studies, with variations between 600 and 900 (pg/mL)4–6, similar to those of our population (878-1031 pg/mL). These studies included patients with chronic heart failure, with reduced5,6 or preserved6 left ventricular ejection fraction, and after discharge following an episode of AHF4. The lack of an association with clinical variables plus the fact that hormone concentrations do not depend on the time point, whether the patient is in the emergency room with AHF or stabilized at 30 days, indicates that relaxin, as an endogenous hormone, does not actively participate in the pathophysiology of AHF. Once the patient has arrived at the emergency room, sample collection at different time points should have no influence, given the correlation with 30-day fasting values and the lack of a circadian effect on relaxin in previous studies. The results of our study are consistent with the those of series that found similar relaxin concentrations in patients with chronic heart failure and healthy controls5,6 and found no relationship with N-terminal pro-brain natriuretic peptide or prognosis at discharge following an AHF episode4. Only 1 study has observed this relationship, finding that concentrations correlated with ventricular filling pressures and cardiac index and dropped after 48 hours of intravenous nitroprusside in 14 patients with AHF and reduced left ventricular ejection fraction2; however, the decrease was not observed in 13 patients with moderate heart failure. This discrepancy in the findings does not seem to be explained by objective data, such as the type of patient or the clinical picture.

In conclusion, our study shows that relaxin can be detected in the peripheral blood of patients with AHF on arrival at the emergency room, but that relaxin concentrations were highly variable, did not correlate with clinical variables, and showed no significant change after clinical improvement (30 days). These data, along with other publications, indicate that relaxin, as an endogenously produced hormone, has no compensatory role in the pathophysiology of AHF. However, because only a few studies with small numbers of patients have been published, new studies should be conducted to confirm the role of relaxin as a biomarker in heart failure.

FUNDING

This work was funded by the national Cardiovascular Research Network (Red Nacional de Investigación Cardiovascular [RIC]), Ministry of Health and Consumer Affairs, Madrid, Spain [RD12/0042/0049].

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Copyright © 2016. Sociedad Española de Cardiología
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