- Academic Editors
†These authors contributed equally.
Background: The present study investigated the predictors of adverse
outcomes in young adult patients with dilated cardiomyopathy (DCM) who underwent
heart transplantation (HTx). Methods: Twenty-four young adult
patients (aged 18–45 years) with DCM who underwent HTx in our hospital from
January 2012 to December 2022 were included in this retrospective analysis. Pre-
and post-HTx data were collected for echocardiography, N-terminal pro-brain
natriuretic peptide (NT-proBNP), and uric acid (UA). Data collected at the time
of DCM diagnosis were designated as baseline data. Post-HTx assessments were
conducted at 1 week and 3, 6, 12, and 36 months post-HTx. The primary endpoint
was defined as any adverse event, including left ventricular ejection fraction
(LVEF)
Dilated cardiomyopathy (DCM) is characterized by left ventricular (LV) chamber enlargement and systolic dysfunction in the absence of known abnormal loading conditions or significant coronary artery disease. The estimated prevalence of DCM is 1:2500 in the general population, which constitutes the third most common type of heart failure and the most frequent cause of heart transplantation (HTx) [1]. Up to 50% of patients diagnosed with DCM as children either die or undergo HTx within 5 years of the diagnosis [2].
HTx offers the best survival benefit for patients with DCM, and DCM accounts for 50% of HTx cases in Europe and the United States. Notably, DCM constitutes as much as 73.9% of HTx cases in China [3]. New York Heart Association functional class I or II could be achieved in more than 90% of patients at 1 to 3 years post-HTx [4]. Post-transplant survival has improved over time. The median survival after adult heart transplants performed between 2002 and 2009 is 12.5 years, extending to 14.8 years among 1-year survivors [5]. According to recent data from the International Society of Heart and Lung Transplantation (ISHLT) in 2014, the 1-year survival rate in heart transplant recipients is 84.5%, and the 5-year rate is 72.5% [6, 7].
Although HTx has shown satisfactory long-term outcomes, its success is hindered by challenges such as the limited availability of donor hearts and the potential for donor heart dysfunction or rejection. Notably, significant risk factors for mortality in the initial five years post-HTx encompass recipient and donor ages, pulmonary vascular resistance, donor body mass index, and the donor/recipient weight ratio [8].
Limited data exist on the use of biomarkers, such as the brain natriuretic peptide and N-terminal-pro brain natriuretic peptide (NT-proBNP), to identify adverse recipient outcomes in adults following HTx [9]. Research on echocardiographic measures and outcomes post-HTx remains underexplored. Left ventricular hypertrophy, defined by echocardiography, has been commonly observed at 1-year post-HTx and is a robust and independent predictor of increased mortality [10]. Similarly, Raichlin et al. [11] reported the importance of assessing LV mass by echocardiography in heart transplant recipients as a crucial prognostic indicator associated with mortality post-HTx. The research on changes in left ventricular ejection fraction (LVEF) and ventricular chamber remodeling over time post-HTx is currently limited. Furthermore, the clinical significance and related risk factors of these indicators post-HTx are poorly characterized, especially for young adult patients (aged 18–45 years) with DCM.
To address the aforementioned knowledge gap, the present study comprehensively
assessed the pre- and post-HTx clinical and echocardiographic characteristics of
young adult patients with DCM. Serial changes in echocardiographic measurements
and important laboratory data were analyzed post-HTx over 36 months. The study
aimed to identify predictors of adverse events, defined as a decrease in LVEF
(
This retrospective study comprised a cohort of 24 young adult patients diagnosed with DCM who underwent HTx. The study population was derived from a dataset of consecutive DCM patients (n = 67) referred to our hospital between January 2012 and December 2022. DCM was defined by the presence of LV or biventricular dilatation and systolic dysfunction, excluding coronary artery disease or valve disease sufficient to cause global systolic impairment. The age range of the participants was from 18 to 45 years. Exclusion criteria were applied to patients with ischemic or valvular etiologies of LV dysfunction, as confirmed by coronary angiography and echocardiography. Additionally, patients with identifiable contributors to systolic dysfunction, such as alcohol abuse, chemotoxicity, congenital heart disease, neuromuscular disease, or systemic conditions capable of transiently impairing systolic function, were excluded. The 24 enrolled DCM patients exhibited insufficient responses to an average 2-year pharmacological treatment, characterized by a persistent decline in LVEF. Consequently, these patients were referred to our hospital for HTx.
As outlined previously, echocardiographic parameters were assessed in all
patients using two-dimensional echocardiography at the initial hospital admission
and during follow-up, adhering to the American Society of Echocardiography
guidelines and the European Association of Cardiovascular Imaging [12]. In
summary, LVEF was determined in the LV apical 4- and 2-chamber views using the
Simpson biplane method. Measurements of end-diastolic left ventricular diameter
(LVD) and end-systolic left atrial anterior–posterior diameter (LAD) were taken
in the LV long-axis view. End-diastolic right ventricular middle diameter (RVD),
along with end-systolic right atrial long-axis diameter (RAD1) and short-axis
diameter (RAD2), were measured from a right ventricular focused apical 4-chamber
view. Pulmonary systolic artery pressure (PASP) was derived from the peak
tricuspid regurgitation (TR) jet velocity using the simplified Bernoulli equation
in combination with an estimated right atrial pressure (RAP): PASP = 4V
We conducted a retrospective collection of clinical, laboratory, and echocardiographic data for HTx patients. The pre-HTx data included information collected at the time of DCM diagnosis, identified as baseline data, as well as data from the follow-up period after an average of 2-year pharmacological treatment before HTx (Fig. 1). Patients were administered standard HTx medical treatments post-HTx, according to the related guideline of the European Society of Cardiology [13]. The post-HTx assessments were scheduled at 1 week, 3 months, 6 months, 12 months, and 36 months post-HTx (Fig. 1). The collected follow-up data post-HTx included cardiac morphology and functional measures detected by echocardiography as well as the NT-proBNP and uric acid (UA) levels.
Study flowchart. DCM, dilated cardiomyopathy; HTx, heart transplantation.
The primary endpoint was defined as a composite of adverse events, including
LVEF
Continuous variables are expressed as the mean
The mean age of the entire HTx cohort was 32
As shown in Table 1, baseline NT-proBNP (11279 (8378–17882) vs. 3907
(2889–8912) pg/mL, p = 0.014) and UA (775 (611–828) vs. 429
(360–762) µmol/L, p = 0.012) were significantly higher in
the adverse-event group than those in the non-adverse-event group. Following an
average of 2-year pharmacological treatments, HTx patients demonstrated an LVEF
of 23.0
Total | Non-adverse-event group | Adverse-event group | p value | |||
(n = 24) | (n = 12) | (n = 12) | ||||
Baseline data (collected at the time of DCM diagnosis) | ||||||
Age (years) | 32 |
33 |
31 |
0.680 | ||
Male (n (%)) | 15 (62.5) | 7 (58.3) | 8 (66.7) | 1.000 | ||
Body mass index (kg/m²) | 23.3 |
22.8 |
23.9 |
0.610 | ||
Hypertension (n (%)) | 10 (41.7) | 4 (33.3) | 6 (50.0) | 0.408 | ||
Diabetes (n (%)) | 0 (0.0) | 0 (0.0) | 0 (0.0) | – | ||
Hypercholesterolemia (n (%)) | 1 (4.2) | 1 (8.3) | 0 (0.0) | 1.000 | ||
Chronic kidney disease (n (%)) | 0 (0.0) | 0 (0.0) | 0 (0.0) | – | ||
Smoking (n (%)) | 9 (37.5) | 4 (33.3) | 5 (41.7) | 1.000 | ||
Drinking (n (%)) | 3 (12.5) | 1 (8.3) | 2 (16.7) | 1.000 | ||
Medications (n (%)) | ||||||
Furosemide | 23 (95.8) | 11 (91.7) | 12 (100) | 1.000 | ||
Spironolactone | 23 (95.8) | 11 (91.7) | 12 (100) | 1.000 | ||
Sacubiril/valsartan | 3 (12.5) | 1 (8.3) | 2 (16.7) | 1.000 | ||
Beta blocker | 24 (100) | 12 (100) | 12 (100) | – | ||
ACEI | 7 (29.2) | 5 (41.7) | 2 (16.7) | 0.371 | ||
Digoxin | 20 (83.3) | 12 (100) | 8 (66.7) | 0.093 | ||
Laboratory data | ||||||
NT-proBNP (pg/mL) | 8645 (3846–14,186) | 3907 (2889–8912) | 11,279 (8378–17,882) | 0.014 | ||
14 (58.3) | 3 (25.0) | 11 (91.7) | 0.003 | |||
cTNI (ng/mL) | 0.02 (0.01–0.03) | 0.02 (0.01–0.03) | 0.01 (0.01–0.03) | 0.410 | ||
CRP (mg/L) | 4.90 (3.24–11.96) | 9.52 (3.45–18.24) | 4.35 (2.53–5.62) | 0.052 | ||
AST (U/L) | 22.0 (17.3–28.8) | 20.0 (14.5–23.0) | 24.0 (21.3–31.3) | 0.060 | ||
ALT (U/L) | 22.5 (19.0–28.5) | 21.0 (17.5–23.8) | 22.5 (19.5–39.8) | 0.219 | ||
Cr (µmol/L) | 70.0 (54.3–89.5) | 80.5 (61.3–91.5) | 64.0 (52.3–72.8) | 0.128 | ||
TG (mmol/L) | 1.22 (0.81–1.65) | 1.39 (0.75–2.65) | 1.11 (0.83–1.53) | 0.378 | ||
TC (mmol/L) | 4.12 (3.32–6.61) | 3.81 (3.22–6.03) | 4.75 (3.69–7.04) | 0.143 | ||
LDL-C (mmol/L) | 2.91 (2.07–3.89) | 2.80 (2.07–3.84) | 3.09 (1.92–4.32) | 0.671 | ||
UA (µmol/L) | 658 (422–820) | 429 (360–762) | 775 (611–828) | 0.012 | ||
15 (62.5) | 4 (33.3) | 11 (91.7) | 0.009 | |||
Echocardiography | ||||||
LVEF (%) | 24.9 |
23.1 |
26.7 |
0.096 | ||
LVD (mm) | 68.1 |
67.1 |
69.1 |
0.328 | ||
RVD (mm) | 45.6 |
46.8 |
44.4 |
0.668 | ||
LAD (mm) | 50.5 |
50.7 |
50.3 |
0.926 | ||
RAD1 (mm) | 59.0 |
58.0 |
60.1 |
0.570 | ||
RAD2 (mm) | 46.4 |
45.2 |
47.7 |
0.342 | ||
PASP (mmHg) | 46.7 |
45.0 |
48.4 |
0.477 | ||
Pre-HTx data (collected over a 2-year pharmacological treatment before HTx) | ||||||
Echocardiography | ||||||
LVEF (%) | 23.0 |
22.8 |
23.3 |
0.827 | ||
LVD (mm) | 73.5 |
72.9 |
74.0 |
0.504 | ||
RVD (mm) | 52.2 |
56.1 |
48.3 |
0.222 | ||
LAD (mm) | 53.5 |
54.8 |
52.3 |
0.514 | ||
RAD1 (mm) | 62.7 |
61.8 |
63.6 |
0.638 | ||
RAD2 (mm) | 49.2 |
48.0 |
50.3 |
0.372 | ||
PASP (mmHg) | 55.0 |
56.0 |
54.1 |
0.807 | ||
NT-proBNP (pg/mL) | 8511 (3528–17,593) | 4239 (2487–16,422) | 10,710 (8388–17,593) | 0.045 | ||
13 (54.2) | 3 (25.0) | 10 (83.3) | 0.004 | |||
UA (µmol/L) | 598 (431–650) | 470 (324–632) | 609 (563–682) | 0.060 | ||
Change (∆) and percentage change in parameters over the 2-year pharmacological treatment before HTx | ||||||
∆ LVEF (%) | –2.00 (–3.75 to 1.00) | 0.50 (–2.00 to 2.00) | –3.00 (–6.50 to –1.25) | 0.024 | ||
percentage change | –8.0 (–13.5 to 4.9) | 2.4 (–8.5 to 11.1) | –12.0 (–22.1 to –5.7) | 0.028 | ||
∆ LVD (mm) | 5.00 (2.00 to 8.00) | 6.00 (2.00 to 8.00) | 5.00 (2.00 to 7.50) | 0.551 | ||
percentage change | 7.6 (2.8 to 11.5) | 8.9 (3.0 to 12.5) | 7.2 (2.8 to 10.8) | 0.378 | ||
∆ RVD (mm) | 3.50 (1.00 to 8.00) | 5.50 (1.25 to 10.75) | 2.00 (1.00 to 6.75) | 0.347 | ||
percentage change | 9.3 (2.4 to 18.0) | 12.0 (1.7 to 24.7) | 6.2 (2.5 to 16.1) | 0.410 | ||
∆ LAD (mm) | 4.00 (1.25 to 5.00) | 4.00 (2.25 to 5.75) | 2.50 (–0.75 to 5.00) | 0.198 | ||
percentage change | 7.5 (2.1 to 10.4) | 8.8 (4.3 to 12.0) | 4.7 (–1.3 to 9.5) | 0.128 | ||
∆ RAD1 (mm) | 4.00 (–0.75 to 8.00) | 2.50 (–0.75 to 9.00) | 4.00 (–0.50 to 10.25) | 1.000 | ||
percentage change | 6.8 (–0.9 to 13.6) | 4.2 (–0.9 to 16.5) | 7.7 (–3.2 to 13.6) | 1.000 | ||
∆ RAD2 (mm) | 2.50 (–0.75 to 6.00) | 2.50 (0.25 to 5.50) | 2.00 (–3.25 to 8.25) | 0.887 | ||
percentage change | 5.2 (–1.7 to 16.9) | 5.2 (0.5 to 13.1) | 4.3 (6.0 to 19.4) | 0.932 | ||
∆ PASP (mmHg) | 6.00 (–0.50 to 15.75) | 9.50 (–5.75 to 22.50) | 3.00 (–0.50 to 10.25) | 0.266 | ||
percentage change | 17.7 (–0.4 to 34.0) | 23.7 (–10.1 to 49.6) | 6.6 (–0.4 to 19.5) | 0.143 | ||
∆ NT-proBNP (pg/mL) | –86.5 (–4030.7 to 2341.5) | –86.5 (–1473.0 to 673.7) | –1696.0 (–8830.7 to 7082.5) | 0.755 | ||
percentage change | –1.8 (–39.8 to 25.2) | –1.8 (–32.8 to 25.2) | –9.9 (–51.9 to 56.6) | 0.514 | ||
∆ UA (µmol/L) | –82.5 (–181.7 to –3.2) | –51.0 (–133.5 to 32.5) | –94.5 (–197.2 to –39.0) | 0.052 | ||
percentage change | –12.3 (–22.7 to –0.7) | –9.1 (–22.0 to 10.3) | –12.9 (–23.0 to –6.1) | 0.198 |
Adverse events were defined as left ventricular systolic function worsening
(LVEF, n = 3), cardiac chambers enlargement (50% increase in RVD/LVD over time,
n = 12), or death (n = 2) during follow-up.
ACEI, angiotensin converting enzyme inhibitors; ALT, alanine aminotransferase;
AST, aspartate aminotransferase; CRP, C-reactive protein; cTNI, cardiac troponin
I; Cr, serum creatinine; DCM, dilated cardiomyopathy; HTx, heart transplantation;
LAD, end-systolic left atrial anterior–posterior diameter; LDL-C, low-density
lipoprotein cholesterol; LVD, end-diastolic left ventricular diameter; LVEF, left
ventricular ejection fraction; NT-proBNP, N-terminal pro-brain natriuretic
peptide; PASP, pulmonary artery systolic pressure; RAD1, end-systolic right
atrial long-axis diameter; RAD2, end-systolic right atrial short-axis diameter;
RVD, end-diastolic right ventricular middle diameter; TC, total cholesterol; TG,
triglyceride; UA, uric acid.
Table 2 illustrates the sequential changes in echocardiographic measures, NT-proBNP, and UA for the entire HTx cohort. Notably, LVD and RVD at 36 months post-HTx exhibited a significant increase compared to measurements at 3 months post-HTx. The most notable enlargement occurred in RVD (T1: 32.0 mm vs. T2: 32.3 mm vs. T3: 36.3 mm vs. T4: 42.3 mm, p = 0.002). LVEF and PASP exhibited a slight reduction over time, while RA dimensions remained unchanged over the observation period. Serum NT-proBNP levels were slightly reduced, while UA levels remained constant.
T0 | T1 | T2 | T3 | T4 | p value | |
7 days | 3 months | 6 months | 12 months | 36 months | ||
post-HTx | post-HTx | post-HTx | post-HTx | post-HTx | ||
Mean | Estimated marginal mean (95% CI) | Estimated marginal mean (95% CI) | Estimated marginal mean (95% CI) | Estimated marginal mean (95% CI) | ||
LVEF (%) | 62.7 | 60.8 (60.2–61.5) | 60.9 (59.1–62.7) | 59.8 (57.3–62.3) | 57.6 (54.1–61.1)‡ | 0.028 |
LVD (mm) | 43.1 | 42.9 (41.7–44.0) | 43.1 (41.8–44.5) | 44.7 (42.8–46.6) | 46.7 (43.8–49.6)* | 0.051 |
RVD (mm) | 30.9 | 32.0 (29.8–34.2) | 32.3 (29.8–34.8) | 36.3 (32.6–39.9)† | 42.3 (37.2–47.4)*†‡ | 0.002 |
LAD (mm) | 38.3 | 39.4 (36.8–42.0) | 38.9 (37.6–40.2) | 38.5 (37.0–40.0) | 40.9 (38.4–43.4)‡ | 0.047 |
RAD1 (mm) | 45.4 | 44.3 (43.1–45.5) | 44.4 (43.1–45.6) | 43.9 (41.8–46.1) | 45.2 (42.8–47.6) | 0.161 |
RAD2 (mm) | 35.4 | 34.0 (32.6–35.4) | 34.0 (32.5–35.4) | 33.5 (31.7–35.2) | 35.2 (33.2–37.3) | 0.235 |
PASP (mmHg) | 33.0 | 32.1 (29.8–34.3) | 31.4 (29.4–33.4) | 29.7 (27.9–31.6) | 30.6 (28.4–32.7) | 0.088 |
Ln NT-proBNP | 6.86 | 5.76 (5.54–6.00) | 5.31 (4.86–5.75) | 4.79 (4.15–5.44)* | 4.86 (4.03–5.70) | 0.053 |
UA (µmol/L) | 482 | 467 (435–499) | 460 (421–499) | 461 (425–497) | 440 (403–476) | 0.283 |
One-way repeated measures analysis of variance (ANOVA) was conducted using the
general linear model, with measures at 7 days post-HTx (T0) as covariates
appearing in the models.
* p
As depicted in Fig. 2, HTx patients in the adverse-event group exhibited a notable decrease in LVEF, a significant increase in RVD, and a sustained NT-proBNP level. Conversely, HTx patients in the non-adverse-event group demonstrated stable LVEF, LVD, and RVD, coupled with a significant reduction in NT-proBNP levels.
Bar plots with estimated marginal mean
Figs. 3,4 depict the chronological alterations in echocardiographic measures, NT-proBNP, and UA for individual patients and the percentage variations in these parameters. When observing the overall trends, LVEF showed a gradual decrease (–9%), and NT-proBNP exhibited a consistent decline (–30%), while RVD increased (52%) and LVD showed a gradual rise (11%) over time post-HTx.
Dynamic changes and percentage variations (%, mean
Dynamic changes and percentage variations (%, mean
Modified Poisson Log-linear models were employed to identify the independent
prognostic significance of baseline NT-proBNP, UA level, and LVEF deterioration
during pharmacological treatment prior to HTx for adverse events post-HTx (Table 3). After adjusting for age, sex, and baseline LVEF, HTx patients with baseline
NT-proBNP levels
Event rates (%) | p value | Age, sex, and baseline LVEF adjusted RR (95% CI) | p value | |
Baseline NT-proBNP |
78.6 vs. 10.0 | 0.003 | 7.412 (1.034–53.132) | 0.046 |
Baseline UA |
73.3 vs. 11.1 | 0.009 | 8.838 (1.541–50.694) | 0.014 |
LVEF reduction |
33.3 vs. 0.0 | 0.118 | 3.252 (1.240–8.532) | 0.017 |
Modified Poisson Log-linear models were employed to identify independent risk factors linked to adverse outcomes. 95% CI, 95% confidence interval; HTx, heart transplantation; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-brain natriuretic peptide; RR, relative risk; UA, uric acid.
The present study demonstrates that elevated baseline levels of NT-proBNP
(
To the best of our knowledge, this is the first clinical report delineating independent risk factors preceding HTx for adverse ventricular remodeling in young adult patients with DCM post-HTx. Although the precise pathophysiological mechanisms remain unclear, our data suggest a potential association between higher baseline levels of NT-proBNP and UA and adverse ventricular remodeling post-HTx in young adults with DCM.
Numerous studies on DCM have consistently revealed a positive correlation
between the decrease in LVEF and adverse outcomes, such as all-cause mortality,
HTx, sudden cardiac death, and major ventricular arrhythmias [14, 15]. Existing
data indicate that a dynamic decline in LVEF among DCM patients, even with
optimal medication, is associated with an increased risk of cardiac events,
encompassing death, HTx, or major ventricular arrhythmias [16, 17, 18]. Gentile
et al. [16] observed a significantly higher risk of long-term major
events in patients with mid-range ejection fraction (HFmrEF, LVEF 40–49%)
transitioning to reduced ejection fraction (HFrEF, LVEF
Despite the wealth of data on the impact of LVEF changes in DCM patients, there is limited information on how pre-HTx LVEF changes influence post-HTx outcomes in this population. Our study fills this gap by revealing that LVEF reduction over a 2-year pharmacological treatment period before HTx is associated with a higher likelihood of adverse outcomes in young adult DCM patients post-HTx. The observed association between LVEF deterioration before HTx and worse outcomes in HTx patients may be indicative of an advanced stage of DCM with heightened myocardial damage. The subsequent compromised cardiac function could pose challenges in adapting to the stresses of the transplantation procedure. A recent study utilizing the Spanish National Heart Transplant Registry revealed that recipients categorized as the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 (critical cardiogenic shock) and profile 2 (progressive clinical decline despite inotrope treatment) faced elevated risks of primary graft failure, dialysis need, and in-hospital mortality [19]. The dynamic decline in LVEF may also indicate inherent myocardial vulnerabilities, increasing susceptibility to ischemic insults, immune reactions, or other post-transplant stressors. Although the underlying mechanism remains elusive, our findings emphasize the need for vigilant monitoring, especially in the postoperative period, for patients exhibiting dynamic LVEF decline before HTx.
Ventricular remodeling, a fundamental pathological process in heart failure following acute myocardial infarction (AMI) or DCM, substantially increases the risk of cardiac death [17, 20]. Prolonged remodeling negatively influences cardiac function, leading to notable morbidity and mortality. Serum NT-proBNP levels have been recognized as a sensitive marker for predicting ventricular remodeling in AMI and DCM patients [21, 22]. Several studies have demonstrated the independent predictive value of serum NT-proBNP in ventricular remodeling for heart failure (HF) following AMI [23] and in children with HF secondary to DCM [22]. NT-proBNP levels exceeding 1000 pg/mL can be used to identify symptomatic children. Additionally, Temporelli et al. [24] affirmed that preoperative NT-proBNP assessments (coronary artery bypass grafting) aid in evaluating postoperative LVEF and ventricular remodeling.
The clinical utility of NT-proBNP in HTx remains inadequately documented and has yielded controversial conclusions. Previous investigations into the relationship between NT-proBNP concentrations and survival post-HTx have presented mixed findings. Combining NT-proBNP and C-reactive protein as markers of acute rejection can significantly enhance their predictive value for developing cardiac allograft vasculopathy (CAV) and all-cause mortality during the first year post-HTx [25]. Moreover, research by Avello et al. [26] suggests that serial measurements of NT-proBNP are crucial for the proper follow-up of HTx patients. In fact, all patients exhibiting rejection showed a significant increase in NT-proBNP concentration compared to their previous values. The authors propose a serum NT-proBNP concentration of 1000 ng/L as a potential cutoff value for classifying patients at risk of death during the year following the analysis. However, a recent systematic review and meta-analysis by Zhu et al. [9] cast doubt on the reliability of serum BNP and NT-proBNP, suggesting insufficient sensitivity and specificity for predicting adverse outcomes following HTx.
Our study revealed that patients experiencing adverse events more frequently
exhibited elevated baseline NT-proBNP levels compared to those in the
non-adverse-event group. Baseline NT-proBNP levels
Previous research has consistently demonstrated a robust association between elevated UA concentrations and ventricular remodeling [28, 29]. Liu et al. [28] found that high levels of serum UA were associated with an increased risk of LV hypertrophy, end-diastolic LV internal diameter enlargement, and LVEF reduction in patients with coronary heart disease. Elevated UA levels are known to stimulate excessive production of oxygen free radicals within cells, leading to endothelial injury. Moreover, high serum UA levels can activate the renin–angiotensin system, contributing to vascular endothelial dysfunction [30, 31]. These changes may persist and contribute to the adverse outcomes observed in our patients. Supporting this hypothesis, Chen et al. [29] demonstrated that elevated serum UA levels were associated with unfavorable ventricular remodeling, and increased myocardial oxidative stress might promote the development of adverse ventricular remodeling, potentially through a superoxide and endothelin-1-dependent pathway.
Previous study has highlighted the prognostic significance of UA in patients post-HTx. Kittleson et al. [32] reported that elevated baseline UA levels were linked to an increased risk of CAV among heart transplant recipients during a median follow-up of 5 years post-HTx. Similarly, Asleh et al. [33] suggested that baseline UA levels independently predicted the incidence of CAV post-HTx. Consistent with these findings, our study observed a correlation between baseline UA levels and adverse outcomes in young DCM patients post-HTx.
Notably, LVEF, baseline serum levels of NT-proBNP and UA are integral components in Heart Failure Prognosis Scores used in the HTx listing criteria [34]. Our study reveals that these key indicators, commonly employed for HTx eligibility assessments, may also hold value in evaluating the risk of adverse events post-HTx among young DCM patients.
Our study underscores the importance of intensified post-HTx monitoring for young DCM patients who present with elevated baseline levels of NT-proBNP and UA, along with a reduction in LVEF within the 2 years prior to HTx. These specific baseline features are crucial indicators for heightened vigilance during the post-HTx period. Developing and implementing targeted monitoring strategies tailored to these identified risk factors can significantly enhance the overall post-HTx outcomes for this patient cohort.
The current study has several limitations. It is a retrospective, non-randomized, and single-center study, potentially affecting the generalizability of the findings. Additionally, the patient cohort is relatively small, thereby limiting the statistical power of the study. Larger-scale studies are necessary to validate and strengthen our observed associations. Lastly, the precise pathophysiological mechanisms underlying the identified associations, particularly regarding baseline NT-proBNP, UA, and LVEF deterioration before HTx, remain largely unclear. Future investigations are crucial for a more in-depth understanding of these mechanisms and their impact on outcomes post-HTx.
In this study, conducted with a limited number of DCM patients, we found that
elevated baseline NT-proBNP (
ALT, alanine aminotransferase; AST, aspartate aminotransferase; AMI, acute myocardial infarction; BNP, natriuretic peptide B; CAV, cardiac allograft vasculopathy; CRP, C-reactive protein; cTNI, cardiac troponin I; Cr, serum creatinine; DCM, dilated cardiomyopathy; HTx, heart transplantation; ISHLT, International Society of Heart and Lung Transplantation; LAD, end-systolic left atrial anterior–posterior diameter; LDL-C, low-density lipoprotein cholesterol; LVD, end-diastolic left ventricular diameter; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-brain natriuretic peptide; PASP, pulmonary artery systolic pressure; RAD1, end-systolic right atrial long-axis diameter; RAD2, end-systolic right atrial short-axis diameter; RVD, end-diastolic right ventricular middle diameter; TC, total cholesterol; TG, triglyceride; UA, uric acid.
Data are available on reasonable request (contact the corresponding author Dr. Junhua Ge).
JG designed the research study. JL, SM and FY performed the research and involved in drafting the manuscript; MW, ML and QG made substantial contributions to acquisition of data, or analysis and interpretation of data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
The study was conducted in accordance with the declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University research (approval number: QYFY WZLL 28041), and all patients provided written informed consent for their participation, which was obtained from subjects or legally authorized representatives by verbally and written.
We would like to express our gratitude to all those who helped us during the writing of this manuscript. Thanks to all the peer reviewers for their opinions and suggestions.
This work was supported by research grants from the National Natural Science Foundation of China [NSFC 81200202, 81960083], Applied Basic Research Foundation of Qingdao Science and Technology Bureau [grant number 16-5-1-57-jch], The National Natural Science Foundation of Shandong Province [ZR 2023MH083].
The authors declare no conflict of interest.
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