P6452Circulating human epididymis protein 4 is a novel prognostic predictor in ambulatory patients with non-ischemic dilated cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Okumura ◽  
H Oishi ◽  
T Kondo ◽  
Y Arao ◽  
H Kato ◽  
...  

Abstract Background Myofibroblasts, which are activated fibroblasts, play an important role in interstitial fibrosis in non-ischemic dilated cardiomyopathy (NIDCM). Recently, human epididymal body protein 4 (HE4) has attracted attention as a marker specific to myofibroblasts. However, the prognostic impact of HE-4 on cardiovascular events in NIDCM patients has not been reported. Purposes The purpose of this study was to investigate the impact of circulating serum HE4 on the prognosis in patients with NIDCM. Methods Forty-four NIDCM patients underwent echocardiography, laboratory measurements, cardiac catheterization, and endomyocardial biopsy within one week under stable heart failure condition. Patients with cancer were excluded from this study. We collected blood samples from peripheral vain, ascending aorta, and coronary sinus during cardiac catheterization and measured serum HE4 level. They were divided into two groups at the median of HE4 level: High-HE4 group (HE4 >69 pmol/L); n=22, Low-HE4 group (HE4 <69 pmol/L); n=22. Cardiac composite event was defined as cardiac related deaths and hospitalization due to worsening heart failure. Results The mean age, left ventricular ejection fraction (LVEF), and plasma brain natriuretic peptide level were 56 years, 32%, and 205 pg/mL. Between two groups, there were no significant differences in age, gender, LVEF, left ventricular end-diastolic diameter, cardiac index, and pulmonary capillary wedge pressure. However, estimated glomerular filtration rate was significantly lower in the High-HE4 group (p=0.025). Kaplan-Meier survival analysis revealed that the High-HE group had a higher rate of cardiac composite event (p=0.011, see Figure). However, as for the pathological analysis, not only the peripheral HE4 level but also HE4 value subtracting coronary sinus from ascending aorta did not significantly correlate with collagen volume fraction in biopsy samples. Circulating HE4 level and prognosis Conclusion Elevated circulating HE4 is associcated with poor prognosis in ambulatory patients with NIDCM.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hideo Oishi ◽  
TAKAHIRO OKUMURA ◽  
Koji Ohashi ◽  
Yuki Kimura ◽  
Shingo Kazama ◽  
...  

Introduction: Follistatin-like 1 (FSTL1) is secreted from various tissues including myocardium and could play a cardioprotective role against harmful stimuli. It has been shown that the expression of FSTL1 protein in patients with heart failure is higher than that in healthy subjects. However, little is known about the association between serum FSTL1 levels and the cardiac prognosis. Hypothesis: We hypothesized that the transcardiac gradient of FSTL1 reflect myocardial FSTL1 and is useful for predicting prognosis in patients with non-ischemic dilated cardiomyopathy (NIDCM). Methods: Thirty-two NIDCM patients were enrolled. Blood samples were simultaneously collected from the aortic root (Ao), coronary sinus (CS) as well as peripheral vein during cardiac catheterization. The transcardiac gradient of FSTL1 was calculated by the difference between serum FSTL1 levels of CS and Ao (FSTL1 CS-Ao ). Patients were divided into two groups at the median of FSTL1 CS-Ao : Low FSTL1 CS-Ao group, <0 ng/mL; High- FSTL1 CS-Ao group, > 0 ng/mL. The primary endpoint of this study was the occurrence of a cardiac event, which was defined as a composite of cardiac deaths and unexpected hospitalizations for worsening heart failure. Results: The median plasma B type natriuretic levels and mean left ventricular ejection fraction in the Low and High FSTL1 CS-Ao groups were 91.9 (21.7 - 277.5) vs. 94.1 (59.1 - 236.5) pg/mL (P = 1.000) and 31.4 ± 6.5 vs. 30.5 ± 7.3 % (P = 0.714), respectively. FSTL1 CS-Ao was negatively correlated with pulmonary capillary wedge pressure (R = -0.400, P = 0.023), mean pulmonary artery pressure (R = -0.40, P = 0.023) and right atrial pressure (R = -0.41, P = 0.019). Kaplan-Meier analysis showed that event-free survival rate was significantly lower in the Low FSTL1 CS-Ao group (p=0.0126). Conclusions: Transcardiac gradient of FSTL1 is associated with hemodynamics and low transcardiac gradient of FSTL1 might be associated with poor prognosis in NIDCM patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helen Sjöland ◽  
Jonas Silverdal ◽  
Entela Bollano ◽  
Aldina Pivodic ◽  
Ulf Dahlström ◽  
...  

Abstract Background Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003–2015. Methods DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003–2007 (Period 1, n = 2029), 2008–2011 (Period 2, n = 3363), 2012–2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. Results Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). Conclusions From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Naoaki Kano ◽  
Takahiro Okumura ◽  
Akinori Sawamura ◽  
Naoki Watanabe ◽  
Hiroaki Mori ◽  
...  

Background: It has been reported that mechanical dispersion of myocardial contraction is increased in failing myocardium. However little is known about the association between contractile entropy evaluated by myocardial scintigraphy and prognosis in patients with non-ischemic dilated cardiomyopathy (NIDCM). Purpose: We aimed to investigate the prognostic value of contractile entropy in patients with NIDCM. Methods: Forty-seven patients (38 male, 55.1 years) with NIDCM were performed gated 99mTc-sestamibi myocardial perfusion SPECT (GMPS) and endomyocardial biopsy. Entropy was automatically calculated as a result of contractile phase analysis for each myocardial sampling point from GMPS, and it reflects a dispersion of global mechanical contraction. All patients were allocated into two groups based on the median of entropy; HE-group: entropy≥0.61 and LE-group: entropy<0.61. All patients were followed up at the mean of 2.8 years. Results: The mean QRS duration, left ventricular ejection fraction (LVEF) and plasma brain natriuretic peptide (BNP) levels were 114 msec, 35% and 225 pg/mL, respectively. Although there were no significant differences in QRS duration and plasma BNP levels between the two groups, LVEF was lower in the HE-group than in the LE-group (31.1% vs 39.8%, p=0.002). In Kaplan-Meier survival analysis, cardiac event rate was significantly higher in the HE-group (Figure). Cox proportional hazard analysis revealed that the HE-group was a significant determinant of cardiac events (Hazard Ratio: 7.66; 95%CI: 0.070-2.532; p=0.033). The mRNA expression level of sarcoplasmic endoplasmic reticulum Ca2+ ATPase (SERCA2a) in biopsy specimens was significantly lower in the LE-group (p=0.015). Conclusion: Contractile entropy, reflecting an impairment of global left ventricular contraction, might be useful to predict a poor prognosis in patients with NIDCM.


Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 27
Author(s):  
Vaida Baltrūnienė ◽  
Ieva Rinkūnaitė ◽  
Julius Bogomolovas ◽  
Daiva Bironaitė ◽  
Ieva Kažukauskienė ◽  
...  

Background and objectives: T-cadherin (T-cad) is one of the adiponectin receptors abundantly expressed in the heart and blood vessels. Experimental studies show that T-cad sequesters adiponectin in cardiovascular tissues and is critical for adiponectin-mediated cardio-protection. However, there are no data connecting cardiac T-cad levels with human chronic heart failure (HF). The aim of this study was to assess whether myocardial T-cad concentration is associated with chronic HF severity and whether the T-cad levels in human heart tissue might predict outcomes in patients with non-ischemic dilated cardiomyopathy (NI-DCM). Materials and Methods: 29 patients with chronic NI-DCM and advanced HF were enrolled. Patients underwent regular laboratory investigations, echocardiography, coronary angiography, and right heart catheterization. TNF-α and IL6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, endomyocardial biopsies were obtained, and the levels of T-cad were assessed by ELISA and CD3, CD45Ro, CD68, and CD4- immunohistochemically. Mean pulmonary capillary wedge pressure (PCWP) was used as a marker of HF severity, subdividing patients into two groups: mean PCWP > 19 mmHg vs. mean PCWP < 19 mmHg. Patients were followed-up for 5 years. The study outcome was composite: left ventricular assist device implantation, heart transplantation, or death from cardiovascular causes. Results: T-cad shows an inverse correlation with the mean PCWP (rho = −0.397, p = 0.037). There is a tendency towards a lower T-cad concentration in patients with more severe HF, as indicated by the mean PCWP > 19 mmHg compared to those with mean PCWP ≤ 19 mmHg (p = 0.058). Cardiac T-cad levels correlate negatively with myocardial CD3 cell count (rho = −0.423, p = 0.028). Conclusions: Univariate Cox regression analysis did not prove T-cad to be an outcome predictor (HR = 1, p = 0.349). However, decreased T-cad levels in human myocardium can be an additional indicator of HF severity. T-cad in human myocardium has an anti-inflammatory role. More studies are needed to extend the role of T-cad in the outcome prediction of patients with NI-DCM.


Author(s):  
Yiyu Zhang ◽  
Guoqing Huang ◽  
Zhaohu Yuan ◽  
Yonggang Zhang ◽  
Rong Chang

Dilated cardiomyopathy (DCM) is a type of heart disease delimited by enlargement and dilation of one or both of the ventricles along with damaged contractility, which is often accompanied by the left ventricular ejection fraction (LVEF) less than 40%. DCM is progressive and always leads to heart failure. Circular RNAs (circRNAs) are unique species of noncoding RNAs featuring high cell-type specificity and long-lasting conservation, which normally are involved in the regulation of heart failure and DCM recently. So far, a landscape of various single gene or polygene mutations, which can cause complex human cardiac disorders, has been investigated by human-induced pluripotent stem cell (hiPSC) technology. Furthermore, DCM has been modeled as well, providing new perspectives on the disease study at a cellular level. In addition, current genome editing methods can not only repair defects of some genes, but also rescue the disease phenotype in patient-derived iPSCs, even introduce pathological-related mutations into wild-type strains. In this review, we gather up the aspects of the circRNA expression and mechanism in the DCM disease scenario, facilitating understanding in DCM development and pathophysiology in the molecular level. Also, we offer an update on the most relevant scientific progress in iPSC modeling of gene mutation–induced DCM.


2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
A Vera Sainz ◽  
A Cecconi ◽  
P Martinez-Vives ◽  
MJ Olivera ◽  
S Hernandez ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background In patients admitted for heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and a concomitant high-rate supraventricular tachyarrhythmia (SVT) it is challenging to predict LVEF recovery after heart rate control and distinguish tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DC). The role of cardiac magnetic resonance (CMR) and the electrocardiogram (ECG) in this setting remains unsettled. Methods Forty-three consecutive patients admitted for HF due to high-rate SVT and LVEF &lt;50% undergoing CMR in the acute phase were retrospectively included. Those who had LVEF &gt;50% at follow up were classified as TIC and those with LVEF &lt;50% were classified as DC. Clinical, laboratory, CMR and ECG findings were analyzed to predict LVEF recovery. Results Twenty-five (58%) patients were classified as TIC. Patients with DC had wider QRS (121.2 ± 26 vs 97.7 ± 17.35 ms; p = 0.003). On CRM the TIC group presented with higher LVEF (33.4 ± 11 vs 26.9 ± 6.4% p = 0.019) whereas late gadolinium enhancement (LGE) was more frequent in DC group (61 vs 16% p = 0.004). On multivariate analysis, QRS duration ≥100 ms (p = 0.027), LVEF &lt; 40% on CMR (p = 0.047) and presence of LGE (p = 0.03) were identified as independent predictors of lack of LVEF recovery. Furthermore, during clinical follow-up (median 60 months) DC patients were admitted more frequently for HF (44% vs 0%; p &lt; 0.001) than TIC patients (Figure 1). Conclusion In patients with reduced LVEF admitted for HF due to high-rate SVT, QRS duration ≥100 ms, LVEF &lt;40% on CMR and presence of LGE are independently associated with lack of LVEF recovery and worse clinical outcome.


Heart ◽  
2019 ◽  
Vol 105 (16) ◽  
pp. 1252-1259 ◽  
Author(s):  
Hanna Fröhlich ◽  
Niklas Rosenfeld ◽  
Tobias Täger ◽  
Kevin Goode ◽  
Syed Kazmi ◽  
...  

ObjectiveTo describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries.MethodsWe identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995–2005 vs period 2: 2006–2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses.ResultsAmong 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33–105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics.ConclusionAmbulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.


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