bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time for a new paradigm shift from STE/non-STEMI to ACO/non-ACOMI?
Authors: Aslanger E , Yildirimturk O.Y , Simsek B , Bozbeyoglu E , Simsek M , Karabay C.Y , Degertekin M 
Published: November 2020

Abstract

Introduction
Although ST-segment elevation (STE) has been used synonymously with acute coronary occlusion (ACO), current STE criteria miss nearly one-third of ACO and cause a substantial amount of false catheterization laboratory activations.

Purpose
We sought whether a new ACO/non-ACO myocardial infarction (MI) paradigm would result in better identification of the patients who need acute reperfusion therapy.

Methods
A total of 3000 patients were enrolled in STEMI, non-STEMI and control groups. A combined ACO endpoint was composed of peak troponin level, troponin rise within the first 24 hours and angiographic appearance.

Results
In non-STEMI group, 282 patients were re-classified as having ACO. This subgroup had a higher ACO frequency and myocardial damage compared to NSTEMI group. More importantly, in-hospital and long-term mortality rates was similar to STEMI patients. The ECG reviewers prospectively classified 35.6% of ECGs as STEMI and 35.5% of ECGs as ACOMI; 25.6% being shared in the both definitions. Both unweighted and weighted diagnostic accuracy of STEMI/non-STEMI and ACOMI/non-ACOMI approaches for ACO and long-term mortality were presented in Table 1. The diagnostic accuracy of the ACOMI/non-ACOMI approach was superior to the STEMI/non-STEMI approach in three out of four comparisons. We also sought to compare ECG subtypes according to early (ECG-to-PCI time&lt;120 min) and late (ECG-to-PCI time over 120 min) coronary intervention (Figure 1).

Conclusions
We believe that it is time for a new paradigm shift from the STEMI/non-STEMI to the ACOMI/non-ACOMI in the acute management of MI.
Figure 1

Funding Acknowledgement
Type of funding source: None
Left atrial dynamics in the hemodynamic response during exercise in patients with asymptomatic severe aortic stenosis: a cardiopulmonary imaging study
Authors: Sugimoto T , Bandera F , Barletta M , Alfonzetti E , Guazzi M 
Published: November 2020

Abstract

Background
The hemodynamic impact of left atrial (LA) dynamics in aortic stenosis (AS) in relation to cardiopulmonary response to exercise has never been studied. We aimed at investigating the link between LA function vs valvulo-arterial impedance (Zva) and right ventricular (RV)-to-pulmonary circulation (PC) coupling in asymptomatic severe AS patients.

Methods
A total of 94 patients: 64 asymptomatic severe AS patients (aortic valve area (AVA) &lt;1.0 cm2 or AVA index &lt;0.6 cm2/m2) with ejection fraction &gt;50% and 30 gender-matched control subjects underwent cardiopulmonary exercise testing combined with Echo-Doppler with assessment of LA strain and RV-to-PC coupling (tricuspid annular peak systolic excursion (TAPSE)/ pulmonary arterial systolic pressure (PASP) ratio). AS patients were divided into 3 groups according to peak aortic jet velocity (PV), mean pressure gradient (MPG) and stroke volume index (SVI). Zva was assessed using (MPG + systolic blood pressure)/ SVI ratio.

Results
Paradoxical low-flow low-gradient AS (PLFLG: PV &lt;4 m/s and MPG &lt;40 mmHg, SVI ≤35ml/m2, N=18, AVA 0.77±0.16 cm2), Normal-flow low-gradient AS (NFLG: PV &lt;4 m/s and MPG &lt;40 mmHg, SVI &gt;35ml/m2, N=23, AVA 0.85±0.16 cm2) and High-gradient AS (HG: PV ≥4 m/s or MPG ≥40 mmHg, N=20, AVA 0.62±0.17 cm2) had a higher LA volume index than Control (Control 22±6, PLFLG 33±11*, NFLG 38±12* and HG 33±9* ml/m2, *P&lt;0.05 vs Control). There was no significant difference in peak VO2 (17±5 ml/min/kg) and VE/VCO2 slope (28±3) among 3 AS groups although PLFLG had lower peak cardiac output (7.0±2.4 L/min) compared to NFLG (9.0±2.3 L/min) and HG (9.2±3.3 L/min). In PLFLG and NFLG AS, LA strain at rest (21±9 and 26±13%) and during exercise (26±12 and 31±14%) were decreased compared to Control (37±8% at rest, 43±11% during exercise) but maintained some reserve during exercise (P&lt;0.001). HG AS had no increase in LA strain (31±15% at rest, 28±15% during exercise) (Figure A). In AS groups, no significant correlation at rest was observed between LA strain and Zva, whereas a negative correlation was observed during exercise (R=−0.4, P=0.003, Figure B). LA strain was also correlated with TAPSE/PASP at rest and exercise (R=0.44 and 0.47, P&lt;0.01, respectively, Figure C).

Conclusions
In asymptomatic severe AS, the study of LA functional adaptation to exercise plays a key role in the hemodynamic unfavorable cascade from AS-related left ventricular afterload to RV-to-PC uncoupling.

Funding Acknowledgement
Type of funding source: None
Effect of hypokintic transformation on the clinical phenotype and functional capacity in hypertrophic cardiomyopathy
Authors: Wasserstrum Y , Itelman E , Barriales-Villa R , Fernandez-Fernandez X , Adler Y , Lotan D , Klempfner R , Shlomo N , Sabbag A , Freimark D , Monserrat L , Arad M 
Published: November 2020

Abstract

Background
Advanced hypertrophic cardiomyopathy (HCM) may be complicated by a dilated hypokinetic transformation. Reduced left ventricular ejection fraction (HFrEF) has been described in terms of specific risks of morbidity and mortality, and specifically in terms of increased risk for fatal arrhythmias. Nevertheless, recent publications have casted doubt regarding the role of arrhythmia in non-ischemic HFrEF and questioned the role of primary prevention strategies in these cases.

Methods
We've reviewed clinical characteristics of 883 patients age ≥40, diagnosed with HCM who were evaluated in the cardiomyopathy clinic in two tertiary medical centers in Israel and Spain.

Results
Forty-five patients (5%) suffered from hypokinetic transformation. They were younger at diagnosis (median 32 [IQR 24–55] vs. 49 [35–60], p&lt;0.001), had a lower body-mass index (28.4 [±4.7] vs. 26.0 [±3.9], p&lt;0.001), and suffered more from strokes (19% vs 6%, p&lt;0.001). They had lower had a lower NYHA class (p=0.001) and lower exercise capacity (7.3 [4.5–10.8] vs. 9.6 [6.7–12.0] METS, p&lt;0.001). Patients with hypokinetic HCM had higher rates of pacemaker and implanted defibrillator (ICD) implantations (41% vs 11%, p&lt;0.001) and (43% vs 13%, p&lt;0.001) respectively. These patients had a higher incidence of sustained ventricular tachyarrhythmias (14% vs 2%, p&lt;0.001). Among patients who had an ICD, patients suffering from hypokinetic transformation had received more appropriate ICD therapy (27% vs 12%, p&lt;0.001). These patients received more heart transplantations (13% vs 1%, p&lt;0.001), and had a trend for higher incidence rate of Sudden cardiac death (6% vs 2% p=0.06) and a higher 5-year mortality rates (21% vs. 5%, p&lt;0.001).

Conclusions
HCM patients suffering from hypokinetic transformation have lower functional and exercise capacities, are more likely to suffer from ventricular tachyarrhythmias and experience appropriate ICD therapy, and undergo heart transplantation. They also have a significantly lower 5-year survival.
Five-year survival

Funding Acknowledgement
Type of funding source: None
Hereditary transthyretin amyloidosis: predictors of conduction disease
Authors: Dias De Frias A.F , Rodrigues P , Trepa M , Fontes-Oliveira M , Costa R , Campinas A , Hipolito-Reis A , Torres S 
Published: November 2020

Abstract

Introduction
Pacemakers are frequently needed due to a high prevalence of conduction disease in mutated ATTR amyloidosis (mATTR). We aimed to identify the variables associated with the need of pacemaker implantation in this population.

Methods
We retrospectively studied 255 patients with suspicion of heart involvement of mATTR observed at our cardiology clinic during the last year. Clinical and outcome data were retrieved by chart review. We have defined the need for pacemaker implantation as: 1) the formal guidelines indications or 2) Ventricular pacing &gt;10% in patients who had prophylactic pacemaker implantation prior to liver transplantation (LT). This way, we have defined 3 different groups: group 1: patients with no evidence of conduction disease; group 2: patients with conduction disease, but no formal indication for pacemaker implantation; and group 3: patients with formal indication for pacemaker implantation or ventricular pacing &gt;10% in patients who had prophylactic pacemaker implantation prior to hepatic transplantation.

Results
We included 255 patients (50±14 years, 53% male, 52.5% treated with tafamidis and 27% had prior LT, and 10% with atrial fibrillation), 43.3% with no evidence of conduction disease, 32.3% with conduction disease, but no formal indication for pacemaker implantation and 24.4% with formal indication for pacemaker implantation. Patients with formal indication for pacemaker implantation were older, with longer duration of neurologic manifestations, with higher concentration of both Troponin T and NT-proBNP and with higher number of organs affected. In multivariate analysis, longer duration of neurologic manifestations (OR 1.090 – 95% IC: 1.036–1.145, p-value 0.001), Left ventricular (LV) maximal wall thickness (OR 1.230 – 95% CI: 1.070–1.414, p-value 0.004), neurologic staging (OR 3.420 – 95% CI: 1.443–8.104, p-value 0.005) and higher number of organs affected (OR 1.719 – 95% CI: 1.218–2.424, p-value 0.002) all showed to be independent predictors of the need for pacemaker implantation, in contrast to LV ejection fraction and serum concentration of Troponin T and NT-proBNP. We've also found a statistical significant association between conduction disease and ophthalmic manifestations.

Conclusions
Our findings suggest that the need for pacemaker implantation in patients with mATTR is closer linked to the duration, severity and affected number of organs than to cardiac biomarkers or echocardiographic findings.

Funding Acknowledgement
Type of funding source: None
Progressive electrocardiographic changes in parallel with cardiac magnetic resonance findings in fabry disease
Authors: Figliozzi S , Camporeale A , Pieroni M , Pieruzzi F , Namdar M , Lusardi P , Spada M , Mignani R , Burlina A , Scolari F , Carrubbi F , Battaglia Y , Graziani F , Boveri S , Lombardi M 
Published: November 2020

Abstract

Background
Cardiac Magnetic Resonance (CMR) allows to detect progressive stages of cardiac involvement in Fabry Disease (FD). A systematic description of electrocardiographic (ECG) alterations occurring in FD is currently missing.

Purpose
To explore ECG changes in progressive stages of FD cardiomyopathy.

Methods
71 FD patients and 17 healthy controls underwent CMR with T1 mapping and 12-lead ECG. ECG analysis included the duration of the P-wave and the interval between the end of P-wave and the beginning of QRS (PendQ). FD patients in the test cohort were divided into 3 groups with increasing severity of cardiac involvement: A) normal T1, no LVH; B) low T1, no LVH; C) low T1, LVH.

Results
An increase of Pwave/PendQ ratio was observed in Group A compared to Controls (1.08 vs. 0.75, p&lt;0.0001). Higher Pwave/PendQ ratio (1.50 vs. 1.08, p&lt;0.0001), shorter PQc interval (127.9 vs. 159.5, p=0.0007), increased Sokolow-Lyon Index (SLI) (3.2 vs. 2.4, p&lt;0,001) and T wave amplitude (0.6 vs. 0.4 mV, p=0.002) characterized Group B in comparison with Group A. A higher prevalence of left bundle branch blocks (13.6% vs. 0%, p=0.03) and repolarization abnormalities (77.3% vs. 5.7%), wider QRS (120 vs 95 msec, p&lt;0.0001) and QT (460 vs 400 msec, p=0.003) intervals were found in Group C compared to Group B. SLI (AUC 0.769), Pwave/PendQ (AUC 0.778), QRS (AUC 0.703) and QT (AUC 0.769) durations resulted to be independent predictors of low T1 values on CMR at stepwise multivariate analysis.

Conclusion
FD is characterized by progressive ECG changes. The identification of ECG parameters able to predict a lowering of myocardial T1 values on CMR may promote early detection of cardiac involvement, helping to target the therapeutic approach.
Progressive ECG and CMR changes in FD

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): This study was partially supported by Ricerca Corrente funding from the Italian Ministry of Health to IRCCS Policlinico San Donato.
Suppression of myocardial HIF-1 by pubertal insulin resistance compromises metabolic adaptation and impairs cardiac function in patients with cyanotic congenital heart disease
Authors: Liu Y , Luo Q , Su Z , Xing J , Wu J , Xiang L , Huang Y , Pan H , Wu X , Zhang X , Li J , Yan F , Zhang H 
Published: November 2020

Abstract

Background
Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). A proportion of CCHD patients are unoperated due to various reasons. These patients remain CH all their lives and are at increased risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulation of hypoxia-inducible factor 1α (HIF-1α).

Purpose
The aim of this study was to determine the effect of CH on cardiac metabolism and function in CCHD patients and how it relates with age. The mechanistic role of HIF-1α in this process was investigated and potential therapeutic targets were explored.

Methods
CCHD patients (n=20) were evaluated for cardiac metabolism and function by positron-emission tomography/computed tomography and magnetic resonance imaging. Heart tissues collected during surgical intervention were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated using genetically modified animals and isotope-labeled metabolomic-pathway tracing studies.

Results
Prepubertal CCHD patients had glucose-dominant cardiac metabolism and normal cardiac function. By comparison, among patients who had entered puberty, the level of myocardial glucose uptake and glycolytic intermediates were significantly lower, but fatty acids were significantly higher, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients and animals with CH, myocardial HIF-1α was upregulated prior to puberty, but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α-knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, leading to inhibition of ATP production and impairment of cardiac function. Increased insulin resistance (IR) suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation under CH during puberty. Pioglitazone significantly reduced myocardial IR, restored glucose metabolism, and improved cardiac function in pubertal animals.

Conclusions
In CCHD patients, maladaptation of cardiac metabolism occurred during puberty, impairing cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation under CH but its expression was suppressed by pubertal IR. The use of pioglitazone during puberty might help improve cardiac function in these patients.
Metabolic maladaptation in CCHD patients

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China (81525002, 31971048) and Shanghai Outstanding Medical Academic Leader
Validation of serial echocardiographic versus mri functional assessments in patients with a systemic right ventricle
Authors: Zandstra T.E , Jongbloed M.R.M , Widya R.L , Ten Harkel A.D.J , Holman E.R , Vliegen H.W , Egorova A.D , Schalij M.J , Kies P 
Published: November 2020

Abstract

Background
Inherent to its geometry, echocardiographic imaging of the systemic right ventricle (sRV) may not always be feasible and/or reproducible in daily clinical practice. Here, we aim to validate the usefulness of all published echocardiographic measurements of systemic RV function in a longitudinal cohort by serial assessment of their correlations with cardiac magnetic resonance (CMR)-derived sRV ejection fraction (sRVEF).

Methods
A single-center, retrospective cohort study was performed. Adult patients with a sRV who underwent both CMR and echocardiography, at two different points in time, were included. Offline analysis of echocardiographic images was blinded to offline CMR analysis and vice versa. Measurements were repeated by a second observer blinded to the results of the first observer. Correlations between echocardiographic and CMR measures were assessed with Pearson's correlation coefficient and inter-observer variability was quantified with intraclass-correlation coefficients.

Results
Fourteen patients were included, of which 4 with congenitally corrected transposition of the great arteries (TGA) and 10 patients with TGA late after atrial switch. Eight patients (57%) were female. There was a mean of 8 years between the first and second imaging assessment. The average CMR-derived sRVEF was 39±6% at t=1. Only global systemic RV function (r=−0.77, p=0.002 at t=1, r=−0.63, p=0.024 at t=2), fractional area change (FAC; r=0.79, p=0.001 at t=1, r=0.67 and p=0.018 at t=2) and global longitudinal strain (GLS; r=−0.73 and p=0.005 at t=1 and r=−0.70 and p=0.011 at t=2) correlated consistently with CMR-sRVEF at both time points. The intraclass-correlation coefficient of GLS was consistently more favorable than that of FAC.

Conclusion
Out of the published echocardiographic parameters, GLS is the most robust measurement of sRV function in terms of feasibility, interobserver variability and correlation with CMR sRVEF.
Figure 1. Echocardiographic assessment

Funding Acknowledgement
Type of funding source: None
Sacubitil/valsartan in systemic right ventricular failure
Authors: Nederend M , Zandstra T.E , Kies P , Vliegen H.W , Jongbloed M.R.M , Schalij M.J , Egorova A.D 
Published: November 2020

Abstract

Background
In patients with heart failure with low ejection fraction (EF) (≤35%) sacubitril/valsartan is proven to be beneficial. We aimed to assess the effects of sacubitril/valsartan in adult congenital heart disease patients with failing systemic right ventricle (sRV) in the setting of congenitally corrected transposition of the great arteries (TGA) or TGA after atrial switch.

Purpose
To evaluate the feasibility and effect of treatment with sacubitril/valsartan in patients with heart failure in the setting of a sRV on optimal medical heart failure treatment.

Methods
Data of patients with sRV failure (estimated RVEF ≤35%) treated with sacubitril/valsartan were analyzed. Patients were clinically evaluated at baseline and at six months after initiation of the highest tolerated dose.

Results
Fourteen patients completed six-month follow-up thus far, of which 6 female (42.8%) and 2 (14.3%) with congenitally corrected transposition of the great arteries (TGA). After 6 months, 9 patients (64.3%) were using the highest dose (97/103 mg twice daily) of sacubitril/valsartan. NT-proBNP was significantly lower after 3 months and after 6 months compared with baseline (64% of baseline, p=0.006 and 53% of baseline, p=0.001, respectively). The kidney function did not change significantly (creatinine at baseline 83.6±12.0 and at 6 months 88.5±13.87, p=0.141) and serum potassium remained within normal limits (4.28±0.36 and 4.49±0.30, p=0.007). There was no significant decrease in systolic blood pressure (p=0.960). The echocardiographic sRV fractional area change (FAC) improved (p=0.002) and Global Longitudinal Strain (GLS) showed a trend towards improvement (p=0.058). During the 6 months of treatment, the exercise capacity remained stable, there was no increase in diuretic use, no serious adverse events and no heart failure related admissions occurred.

Conclusion
Treatment of sRV heart failure patients with sacubitril/valsartan leads to a significant reduction in NT-proBNP and significant increase in FAC. All patients remained clinically stable and no heart failure related admissions or serious adverse events occurred.
Changes after 6 months

Funding Acknowledgement
Type of funding source: None
Nerve growth factor receptor is involved in maintaining homeostasis of pulmonary arterial hypertension
Authors: Goten C , Usui S , Inoue O , Okada H , Takashima S , Sakata K , Kawashiri M , Takamura M 
Published: November 2020

Abstract

Introduction
Pulmonary arterial hypertension (PAH), characterized by vascular remodeling, is still disease with poor prognosis although many pulmonary vasodilators have been developed, and new mechanism of treatment for PAH is desired. Nerve growth factor receptor (Ngfr) is known to relate to inflammatory reaction and repair process in the damaged tissue. We have reported that Ngfr is associated to vascular remodeling in patients with acute coronary syndrome. However, it is unclear how Ngfr is involved in the pathogenesis of PAH.

Purpose
In this study, we investigated whether Ngfr relate to pathophysiology in PAH.

Methods
We estimated the frequency of Ngfr positive cells (% Ngfr+) in peripheral blood mononuclear cells obtained from PAH and non-PAH patients using flowcytometric analysis. In PAH patients, the hemodynamic parameters such as mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI) were obtained by right heart catheterization, and evaluated for correlation with the % Ngfr+.
Next, adult 8-week-old C57BL/6 (WT) mice and Ngfr knock out (KO) mice were exposed to chronic hypoxia (10% O2) or normoxia for 6 weeks. Then, mice were anesthetized and performed echocardiography and right heart catheterization. Then, mice were exsanguinated and blood sample was collected to evaluate the % Ngfr+ by flow cytometry. Right ventricular weight was measured and lung tissue was also collected for histological assessment and molecular pathway profiling.

Results
PAH (n=24) patients and non-PAH patients (n=17) were enrolled. The % Ngfr+ was significantly higher in PAH patients than that in non-PAH patients (0.056% versus 0.019%, p&lt;0.0001). In PAH patients, the % Ngfr+ was correlated with severity of hemodynamic parameters such as mPAP (R=0.64 p&lt;0.001), PVR (R=0.62 p&lt;0.005), and CI (R=−0.48 p&lt;0.05).
In WT mice, chronic hypoxia significantly increased the right ventricular systolic pressure and induced vascular medial thickness and fibrosis around the pulmonary artery. Flow cytometry analysis revealed that the % Ngfr+ was significantly increased in the hypoxia compared to that in the normoxia. Under hypoxic conditions, the right ventricular systolic pressure was significantly increased in Ngfr KO mice compared to that in WT mice. In histological analysis, hypoxia-induced peripheral vascular fibrosis and medial thickness was more severe in Ngfr KO than that in WT mice.

Conclusion
Circulating Ngfr-positive cells are associated with severity of PAH in patients. In the hypoxia-induced PH model, gene deletion of Ngfr shows the progression of the pathogenesis of PAH. These results suggest that circulating Ngfr-positive cells have an important role in the pathogenesis of PAH and may be a novel target for PAH therapy.

Funding Acknowledgement
Type of funding source: None