bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating microRNA-122-5p is associated with a lack of improvement in left-ventricular function after TAVR and regulates viability of cardiomyocytes via extracellular vesicles
Authors: Hosen D R 
Published: October 2022

Abstract

Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis (AVS). However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Herein, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EV-miRNAs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes.
Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in aortic stenosis patients at day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day seven (r=−0.264 and p=0.015) and at six months (r=−0.328 and p=0.0018) after TAVR. At the three-year follow-up, patients with a higher level of miR-122-5p displayed significantly increased cardiovascular mortality (p=0.03). By utilization of patient-derived samples and a murine aortic-stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced aortic-valve-stenotic mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocytes dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells in comparison to cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes and regulates the viability of cardiomyocytes. Mechanistically, miR pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation confirmed that miR-122-5p interacts with the RNA-binding protein, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling into recipient cells, miR-122-5p reduces the expression of the anti-apoptotic gene BCL2, by binding to its 3' untranslated region to inhibit its translation, and thereby decreasing the viability of target cardiomyocytes.
Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. Extracellular vesicular shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): German Research Foundation (DFG)German Society of Cardiology (DGK)
Optimization of biventricular cardiac resynchronization improves cardiac power and atrial kinetics in patients with systolic heart failure with often hospitalizations for decompensation
Authors: Magkas N , Xydis P , Konstantinou K , Antoniou C , Chrysohoou C , Manolakou P , Dilaveris P , Tsioufis K 
Published: October 2022

Abstract

Cardiac resynchronization therapy (CRT) reduces symptoms and improves left ventricular function in patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. In this work the biochemical, clinical and echocardiographic outcome of optimizing CRT (optCRT) function by the optimal VTI value of left ventricular outflow track.

Methods
80 NYHA III patients (68±10 years; 75% men; 53% ischemic cardiomyopathy-ICM), under optimal tolerated medical therapy, with standard BVP indication, having been implanted with a CRT system. Echocardiographic measurements, including aortoventricular coupling (VAC) calculation, 6-min-walking-test and quality of life (MLHF questionnaire) were measured at baseline, 6 months on optCRT. Cardiac power (CP) was calculated according the equation: CP=Cardiac Output x Mean Aortic Pressure/451.

Results
End-systolic volume of left ventricle was reduced (p=0.001) in both ischemic and non-ICM; while max left atrial volume was reduced only in non-ICM patients (72.1±32 to 65.8±30, p=0.04). Global longitudinal strain was improved in non ICM patients (p=0.015). Systolic strain of right ventricle was improved in non-ICM (9.4±2.2 to 10.7±2.3 vs. 8.7±3 to 8.9±3.2, p=0.03 for non-ICM); while left atrial function and the ratio E to E TDI of mitral annulus were not improved in either group. Non-ICM patients improved VAC (baseline: 1,36±0,3; CRT: 1.11±0.2; p=0.01) and CP (baseline 660±160 to 782±260, p=0.001); while no significant improvement was detected to ICM patients. 6-min-walk test was improved up to 30% (p=0.05). NtproBNP levels were decreased only in non-ICM patients (1759±1060.9 to 1015±650 vs. 2063,8±1800 to 1950.7±2342, p=0.001). MLHFQ improved in non-ICM patients (p=0.015); while non-significant improvement was detected in ICM patients.

Conclusion
Optimization of cardiac resynchronization therapy based on stroke volume maximization benefits quality of life and exercise tolerance, mainly in non-ICM. GLPS and aorto-ventricular coupling was improved in non-ischemic patients, reflecting the better adaptation of CRT in this population. Thus, CRT optimization by echocardiographic evaluation may be useful in improve clinical status and quality of life in CRT non-responder patients.

Funding Acknowledgement
Type of funding sources: None.
Definition of left ventricular dilation in heart failure using cardiovascular magnetic resonance: prognostic implications of end-diastolic diameter and volume assessment
Authors: Kasa Yaglici G , Teis Soley A , Aimo A , Junca Puig G , Lupon Roses J , Domingo Teixidor M , Ferrer Sistach E , Vallejo Camazon N , Lopez Ayerbe J , Cediel Calderon G , Codina Verdaguer P , Bayes Genis A , Delgado Garcia V 
Published: October 2022

Abstract

Background
Patients with heart failure (HF) and reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) display variable grades of left ventricular (LV) dilation. LV end-diastolic diameter (LVEDD) and volume (LVEDV) may not be concomitantly increased. The respective prognostic implications of LV dilation have not been explored.

Purpose
To assess the prognostic implications of LVEDD and LVEDV index (LVEDVi) in HFrEF/HFmrEF.

Methods
Data from consecutive HF outpatients undergoing cardiovascular magnetic resonance (CMR) and with LV ejection fraction &lt;50% were analyzed. LVEDD was measured in a basal short axis slice. Established age- and gender-specific cut-offs for LVEDVi and a cut-off of 58 mm for LVEDD were used to define LV dilation. Patients were followed for the occurrence of the combined endpoint of cardiovascular death or HF hospitalization.

Results
A total of 564 patients (79% men, median age 65 years [56–73], ischaemic aetiology in 32%) were included. HFrEF was present in 85% of patients, and HFmrEF in 15%. Median values for LVEDD and LVEDVi were 63 mm (58–69) and 124 mL/m2 (104–149) respectively. LVEDD was significantly correlated with LVEDVi (r=0.804, p&lt;0.001). Sixty-nine percent of patients had concomitant dilation of LV based on LVEDD and LVEDVi. In contrast, 18% of patients did not have concordant definition of LV dilation based on LVEDVi and LVEDD, including 14% with small LVEDD and large LVEDVi. LV dilation based on LVEDVi was associated with a shorter survival free from CV death or HF hospitalization (log-rank 4.6, p=0.032), while LVEDD &gt;58 mm was not (p=0.278). There was a trend toward an independent association between LV dilation based on LVEDVi and outcome adjusting for HFrEF/HFmrEF status and ischaemic aetiology (hazard ratio 2.10, 95% confidence interval 1.00–4.41, p=0.050). An independent association was not found for LV dilation based on LVEDD. An LVEDD &gt;66 mm was associated with increased risk of CV death or HF hospitalization on spline curve analysis (Figure 11). All patients with an LVEDD &gt;66 mm had also LV dilation based on LVEDVi.

Conclusions
In patients with HFrEF and HFmrEF, LV dilation based on LVEDVi does not always coincide with a dilated LVEDD. The cut-off value of LVEDD associated with an excess of the combined endpoint is much larger than the value used in clinical practice. However, in patients with dilated LV based on LVEDVi, LVEDD does not add to the risk stratification.

Funding Acknowledgement
Type of funding sources: None.
Prognostic value of left ventricular contractile reserve and heart rate reserve in dilated cardiomyopathy
Authors: Ciampi Q , Cortigiani L , Zagatina A , Wierzbowska-Drabik K , Rigo F , Djordjevic-Dikic A , Amor M , Merli E , Arbucci R , Celutkiene J , Gaibazzi N , Bartolacelli Y , De Nes M , Pepi M , Picano E 
Published: October 2022

Abstract

Background
Stress echocardiography (SE) allows to assess simultaneously left ventricular contractile reserve (LVCR) and heart rate reserve (HRR) in dilated cardiomyopathy (DCM).

Aim
To assess the prognostic value of LVCR and HRR in DCM patients

Methods
We prospectively enrolled 395 DCM patients with ejection fraction ≤40% (age 62±27 years, 270 males, 68%; ejection fraction 35±9%) referred from 9 certified laboratories, 264 with nonischemic DCM (67%) and 131 (33%) with ischemic DCM. All patients underwent clinically indicated SE. The employed stress modality was exercise (n=63), or pharmacological stress (n=332, with vasodilator, n=232; or dobutamine, n=100). LVCR was present with a rest-stress decrease ≥0.20 in wall motion score index. HRR was normal with a peak-rest value ≥1.80 with exercise or dobutamine and ≥1.22 with dipyridamole or adenosine stress.

Results
New regional wall motion abnormality was present in 46 (12%), LVCR in 131 (33%) and abnormal HRR in 275 (70%) DCM patients. During a median follow-up of 950 days (interquartile range: 360–1187 days) 71 deaths occurred. Annual mortality was 10.5%/year in DCM patients with abnormal HRR (HRR−) and absence of LVCR (LVCR−), 5.4%/year in patients with either abnormal HRR or absent LVCR, and 2.5%/year in patients with normal HRR and presence of LVCR (Figure 1). At multivariable analysis, only abnormal HRR (HR: 2.952, 95% CI: 1.547–5.630, p=0.001) but not absence of LVCR (HR: 1.545, 95% CI: 0.929–2.568, p=0.094), was independent predictors of survival.

Conclusion
Abnormal HRR predicts adverse prognosis in DCM patients, in addition to the presence of LV CR.

Funding Acknowledgement
Type of funding sources: None.
Impact of age on the utility of CardioMEMs device to guide heart failure therapy: analysis of the National Readmissions Database
Authors: Malik A , Gupta R , Maitz T , Bandyopadhyay D , Lanier G , Briasoulis A 
Published: October 2022

Abstract

Background
Weeks before patients exhibit signs and symptoms of HF, intracardiac and pulmonary artery pressures increase, offering a potential target for early intervention. The CardioMEMs device is an implantable hemodynamic device placed directly into a branch of the pulmonary artery (PA) which allows remote PA pressure monitoring. The aim of our analysis is to compare outcomes of patients admitted with HF receiving implanted CardioMEMs based on their age.

Methods
Data from the National Inpatient Sample (NIS) database from 2014–2019 was used to identify hospitalizations with International Classification of diseases – 9th Revision and International classification of Diseases – 10th Revision procedural codes of patients with heart failure and CardioMEMs implantation. The outcome of interest was readmission rates at 30 days and complications associated with device implantation.

Results
We identified 1841 hospitalizations: 708 (38.5%) for patients &lt;65 years-old (mean age 53.6) and 1,113 (60.1%) for patients &gt;65 years-old (mean age 79.5). Gender was similar between the two age cohorts with females representing 36.6% vs 37.7% of the patients (&lt;65 and &gt;65 years old respectively). The cohort of patients &gt;65 years of age had a higher rate of comorbidities including hypertension (87.9% vs 80.2%; p=0.003), prior CABG (20.3% vs 8.5%; p = &lt;0.001), atrial fibrillation (59.2% vs 38.4%; p = &lt;0.001), PPM (10.9%% vs 2.3%; p = &lt;0.001), and ESRD (56.1% vs 47.3%; p=0.015. The presence of LVAD prior to device implantation was higher in the &lt;65-year-old group at 2.8% vs 1.2% (p=0.065). Diabetes, prior PCI, PVD, pulmonary disease, anemia, cancer, and oxygen dependence were similar among the two cohorts and not statistically significant. Complications including acute kidney injury requiring dialysis, stroke, and transplant post CardioMEMs implantation were similar among the two groups. The patients who survived the index hospitalization, readmission rates were significantly improved in the cardioMEMs arm patients who were &lt;65 years of age (13.8% vs 21.9%) compared to those 65 and above (19.6% vs 20.5%), p for interaction &lt;0.001, Figure 1.

Conclusion
The CardioMEMS device is more effective in a younger patient population to reduce HF admissions.

Funding Acknowledgement
Type of funding sources: None.
Differences in chronic heart failure treatment between patients with and without obesity in a large real-world heart failure population
Authors: Aga Y , Radhoe S P , Aydin D , Linssen G C M , Moons A H M , Pronk A C B , Engelen D J M , Van Tooren R M , Brunner-La-Rocca H P , Dalen B M , Brugts J J 
Published: October 2022

Abstract

Background
Obesity is a well-established risk factor for the development of heart failure (HF). Numerous studies have demonstrated that HF patients with obesity have better prognosis and clinical outcomes compared to non-obese HF patients, a phenomenon commonly known as the obesity paradox. One of the proposed reasons for this paradox is that HF patients with obesity use more cardioprotective medication for the treatment of HF compared to HF patients without obesity. However, studies investigating treatment differences between HF patients with and without obesity are lacking.

Purpose
The aim of this study was to assess differences in HF treatment between patients with and without obesity in a large contemporary real-world cohort.

Methods
Patients with chronic HF with a left ventricular ejection fraction (LVEF) &lt;50% and available information on body mass index (BMI) were selected from the CHECK-HF registry, which included chronic heart failure patients between 2013 and 2016 in 34 Dutch outpatient HF clinics. Patients were divided into those with BMI ≥30 kg/m2 and those with BMI &lt;30 kg/m2. Detailed information on heart failure therapy prescription and dosage were recorded.

Results
A total of 7671 patients, of whom 1899 were obese (24.8%), were included in this analysis. Patients with obesity were younger, more often female and in NYHA class III/IV, and hypertension and diabetes were more prevalent in the obesity group. HF patients with obesity more often received beta-blockers (83.1% vs. 79.6%, p=0.001), renin-angiotensin system (RAS) inhibitors (84.8% vs. 80.8%, p&lt;0.001), mineralocorticoid receptor antagonists (MRAs) (56.9% vs. 51.5%, p&lt;0.001), and diuretics (87.4% vs. 82.8%, p&lt;0.001) compared to HF patients without obesity. Furthermore, guideline-recommended doses of beta-blockers (23.5% vs. 16.4%, p&lt;0.001), RAS-inhibitors (51.5% vs. 40.9%, p&lt;0.001), and MRAs (57.9% vs. 49.2%, p&lt;0.001) were significantly more often prescribed in patients with obesity (Figure 1). In multivariable logistic regression analysis, obesity was significantly associated with a higher likelihood to receive beta-blockers (OR 1.18 (1.02–1.38)), RAS-inhibitors (OR 1.25 (1.06–1.47)), MRAs (OR 1.15 (1.02–1.29)), and diuretics (OR 1.59 (1.34–1.89)).

Conclusion
In this large real-world HF registry, guideline recommended HF drugs were more frequently prescribed and at higher dose in patients with obesity as compared to HF patients without obesity.

Funding Acknowledgement
Type of funding sources: None.
Effects of sacubitril-valsartan on clinical, echocardiographic and polygraphic parameters in patients affected by heart failure with reduced ejection fraction and sleep apnea
Authors: Armentaro G , Pelaia C , Volpentesta M , Mancuso L , Cassano V , Severini G , Pastura C A , Francica M , Barbara K , Miceli S , Maio R , Caroleo B , Perticone M , Sesti G , Sciacqua A 
Published: October 2022

Abstract

Background
Heart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in clinical practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril–valsartan (sac/val) association has been proven to be effective in reducing disease progression and all-cause mortality in HFrEF patients. Sac/val treatment can potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction of extracellular fluid overload, and decrease of sympathetic neural activity.

Purpose
The aim of this work is to evaluate the effects of a 6-month therapy with sac/val on hemodynamic and metabolic parameters, as well as on the occurrence of apnea/hypopnea and oxygen saturation in patients with HFrEF and SA, already treated with CPAP.

Methods
We recruited 132 patients affected by HFrEF and SA, already under treatment with continuous positive airway pressure (CPAP), which was discontinued 24 hours before the scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient at baseline and after a 6-month treatment with sac/val.

Results
After 6 months, sac/val induced statistically significant changes in clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine and uric acid), and echocardiographic parameters. In particular, cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during a temporary CPAP interruption, revealed a significant reduction in global apnea-hypopnea index (AHI) value (p&lt;0.0001), central AHI (p&lt;0.0001), obstructive AHI (p&lt;0.0001), oxygen desaturation index (ODI) (p&lt;0.0001), and percentage time of saturation below 90% (TC90) (p&lt;0.0001). The changes of CI, estimated glomerular filtration rate (eGFR), NT-proBNP and tricuspid annular plane excursion (TAPSE) contributed to 23.6%, 7.6%, 7.3% and 4.8% of AHI variability, respectively, and the whole model accounted for a 43.3% of AHI variation.

Conclusions
Our results suggest that treatment with sac/val is able to significantly improve the cardiorespiratory performance of patients with HFrEF and SA, integrating the positive impact of CPAP. Thus, both CPAP and sac/val therapy may synergistically contribute to lower the risks of both cardiac and pulmonary complications in HFrEF patients with SA.

Funding Acknowledgement
Type of funding sources: None.
Predictors of ICU admission in patients with peripartum cardiomyopathy
Authors: Shahin O , Shahin H , Heineke H , Biswas M 
Published: October 2022

Abstract

Background
Peripartum cardiomyopathy (PPCM) is a dilated cardiomyopathy that affects women in the peripartum period. The incidence of PPCM in the United States is 1,100 women per year. We studied the admission of women diagnosed with PPCM to the intensive care unit (ICU) with the goal of identifying factors that increase risk for adverse outcomes.

Methods
This was a retrospective study of 2,286 patients with a diagnosis of PPCM admitted to a private hospital system across the United States between the years 2017 and 2021. Logistical regression analysis was utilized to identify specific patient characteristics and risk factors that were associated with admission to the ICU.

Results
The average age of patients was 32.13 years. The patient cohort was 39.76% black, 39.15% white, and 13.12% Hispanic. The average length of stay was 3.35 days. Preeclampsia was present in 342 (14.96%) patients, cerebral infarction in 31 (1.36%) patients, eclampsia in 48 (2.10%) patients, myocardial infarction (MI) in 52 (2.27%) patients, and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in 24 (1.05%) patients. There was a total of 504 (22.05%) patients admitted to the ICU. Preeclampsia (adjusted odds ratio [adj. OR] 1.588, 95% confidence interval [CI] 1.215–2.074, p&lt;0.001), eclampsia (adj. OR 3.131, 95% CI 1.718–5.708, p&lt;0.001), cerebral infarction (adj. OR 4.381, 95% CI 2.028–9.463, p&lt;0.001), age (adj. OR 0.967, 95% CI 0.953–0.982, p&lt;0.001), MI (adj. OR 2.961, 95% CI 1.608–5.455, p&lt;0.001), and HELLP syndrome (adj. OR 4.655, 95% CI 1.926–11.256, p&lt;0.001) were all associated with increased odds of requiring ICU level of care. However, hypertension, d-dimer level, troponin level, active tobacco smoking, alcohol use, and diabetes mellitus were not associated with increased likelihood of admission to the ICU.

Conclusion
In our study of 2,286 women with PPCM, we found statistically significant predictors of ICU admission included age, HELLP syndrome, eclampsia, preeclampsia, MI, and cerebral infarction. This data may be useful for the early identification and triaging of patients with PPCM that require higher level of care. These results can be utilized in developing a risk score to assist in this goal.

Funding Acknowledgement
Type of funding sources: Private hospital(s). Main funding source(s): HCA-Riverside Community Hospital
The comparison of composite end-points between SGLT-2 inhibitors and placebo in diabetic patients with heart failure with mildly reduced ejection fraction: a meta-analysis of the literature
Authors: Saylik F , Cinar T , Selcuk M , Cicek V , Hayiroglu M I , Orhan A L 
Published: October 2022

Abstract

Background
Sodium–glucose cotransporter 2 (SGLT-2) inhibitors have been found to decrease the incidence and progression of heart failure (HF) with reduced ejection fraction (EF). In the classification of HF, there is a gray zone between HF with reduced EF (EF &lt;40%) and HF with preserved EF (EF &gt;50%), which is named as HF with mildly reduced EF (EF between 40–50%). The effect of SGLT-2 inhibitors in mildly reduced EF HF patients have not yet been well established. We aimed to compare the composite outcomes, including cardiac death and re-hospitalization, between SGLT-2 inhibitors and placebo in this meta-analysis.

Methods
We searched MEDLINE, Scopus, EMBASE, Google Scholar, and the Cochrane Library for eligible studies. Of 167 eligible studies, three studies that compared the outcomes between SGLT-2 inhibitors and placebo in mildly reduced EF HF diabetic patients were included in this meta-analysis (n=928) (Table 1). Heterogeneity was assessed using High's I2, Egger's test and prediction intervals. The pooled effect size was calculated with a fixed-effect model. Due to the total number of studies was lower than 10, we did not report publication bias by drawing Funnel plot.

Results
Two studies were randomized controlled trial compared Sotagliflozin and placebo, and one study was an observational study with propensity score matched that compared SGLT-2 inhibitors with placebo. Patients using SGLT-2 inhibitors had lower primary composite end-points, such as cardiac death and re-hospitalization, than patients using placebo (HR= 0.69, 95% confidence intervals = 0.49–0.98, p value = 0.03) (Figure 1). There was no heterogeneity between studies, which was determined with High's I2 (0%) and Egger's test (p&gt;0.05). Prediction interval was detected as a relatively wide that ranged between 0.30 and 1.58, which concluded that it could be expected to get the results within this range in future studies.

Conclusion
This meta-analysis indicated that the composite outcomes, including cardiac death and re-hospitalization, were lower in mildly reduced EF HF diabetic patients using SGLT-2 inhibitors when compared to placebo in such patients.

Funding Acknowledgement
Type of funding sources: None.