bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5703The anterior interventricular crux: anatomic basis for ablation below the left sinus of valsalva (LSOV) of varied ECG morphology PVCs
Authors: Mehra N , Kapa S , Deshmukh A , Asirvatham S 
Published: October 2019

Abstract

Background
Outflow tract premature ventricular complexes (PVCs) may be ablated at sites where the local electrogram is early. We describe ablation of PVCs of varying morphology at a cruciate structure extending from the inflection of the great cardiac vein to the junction of the distal RVOT and from the left ventricular (LV) inflow myocardium through the aortic mitral continuity (AMC) to the right coronary sinus of Valsalva centered below LSOV, termed the LV crux.

Purpose
Evaluate a novel target for ablation of PVCs with varied QRS morphologies.

Methods
A series of 51 patients undergoing ablation for PVCs between 2013–2018 was identified. In all cases, ICE-guided ablation occurred at the center of the LV crux.

Results
All patients had high PVC burden >20% (28±8%); EF<50% in 40/51 (78%). QRS morphology of PVCs is summarized in Table 1. 50% had prior ablation attempted at early sites. Mapping and ICE-guided ablation at the LV crux (Figure 1 A-B) revealed early activation with near-field ventricular or fascicular signal in 31 (61%), while others had early sites at extensions of the crux. PVCs were eliminated in 50/51 (98%) with continued suppression at 3-months. EF normalized in all 51.
Table 1. ECG charactaeristics ECG characteristics Number of patients (%) Inferior morphology 51/51 (100%) Lead I morphology   Monophasic R 8/51 (16%)   Rs 9/51 (18%)   rS 34/51 (66%) Precordial transition   Positive across precordium 40 (78%)   V2 transition 7 (14%)   V3 transition 4 (8%) Maximum deflection index   <0.55 37 (73%)   >0.55 14 (27%)
Figure 1. Mapping and ablation

Conclusions
A cruciate interventricular multidimensional crux centered below the LSOV is a site for successful ablation of varied PVC morphologies and should be considered for detailed mapping and ablation, particularly when multiple morphologies are present or prior ablation at early sites is unsuccessful. Ventricular myocardial architecture along with conduction system remnants may be the basis for this phenomenon.
P5709External validation of the ACEF II operative risk model in a cardiac surgery population: an interim evaluation
Authors: Georgievska M , Saiti R , Popevski D , Gramosli T , Stoicovski E , Vuckova D , Neziri D , Marinkovic S , Ugurov P , Klincheva M , Idoski E , Hristov N , Milojevik P , Mitrev Z K , Rosalia R A 
Published: October 2019

Abstract

Background
The ACEF II score has been proposed as a parsimonious, alternative, operative mortality risk prediction model for cardiac surgery. External validation is warranted to establish its use.

Aim
The primary goal was to evaluate the ACEF II model performance for cardiac surgery mortality risk stratification. We also tested the discriminatory power to classify patients in need of prolonged postoperative respiratory support and hospitalisation.

Methods
We evaluated 743 Cardiac Surgery patients – median age 65 (range 20–80 years), 27.4% females - operated between November 2017 and October 2018.
Receiver Operating Curves (ROC) were generated based on a dichotomous outcome, “yes/no”, for intrahospital mortality, prolonged mechanical ventilation time (>24 hours), ICU length-of-stay (>48 hours) and postoperative hospitalisation (>7 days).
The ACEF II was compared to the ACEF I and the EuroSCORE II (ESII).
The DeLong method was used to test the statistical significance of the difference between the areas under different dependent ROC curves.

Results
The median ACEF II scores for low risk (= ESII <2%), medium risk (= ESII ≥2–≤5%) and high-risk patients (= ESII >5%) were 1.24 (IQR 1.05–1.505), 1.48 (IQR 1.28–1.928) and 2.240 (IQR 1.560–2.933), respectively.
The observed mortality for low risk, medium risk and high-risk patients were 1.48% (5/337), 3.26% (9/275) and 19.23% (25/130), respectively.
ACEF II outperformed the ACEF I but was similar to the EuroSCORE II in discriminating intrahospital mortality cases and patients in need of prolonged mechanical ventilation (Table 1).
All risk models lacked sufficient power to classify patients requiring prolonged ICU-LOS and postoperative hospitalisation time (AUC <0.7).
Table 1. Pairwise comparison of ROC Risk Score Model AUC + CI95% – Intrahospital Mortality Area difference when compared to ACEF II AUC + CI95% p-value ACEF II 0.766 [0.733 to 0.796] ACEF I 0.645 [0.609 to 0.679] 0.121 [0.0288 to 0.212] 0.0100 EuroSCORE II 0.809 [0.778 to 0.836] 0.0429 [−0.0431 to 0.129] 0.3284 AUC + CI95% – Prolonged MVT Area difference when compared to ACEF II AUC + CI95% p-value ACEF II 0.721 [0.687 to 0.753] ACEF I 0.632 [0.596 to 0.667] 0.0891 [0.0224 to 0.156] 0.0088 EuroSCORE II 0.721 [0.687 to 0.753] 0.000128 [−0.0732 to 0.0735] 0.9973 AUC = Area Under the Curve, DeLong et al., 1988 – Binomial exact CI95% for the AUC, MVT = Mechanical Ventilation time.

Conclusion
The ACEF II risk model has a fair discriminative capacity to classify intrahospital mortality cases and patients who will require prolonged mechanical respiratory support following cardiac surgery.

Acknowledgement/Funding
None
P5729Restricted mean survival time analysis to assess efficacy and safety of intensive vs standard blood pressure treatment goals as a function of age: insights from the SPRINT trial
Authors: Krishnaswami A , Peterson E , Kim D , Rich M 
Published: October 2019

Abstract

Background
Blood pressure (BP) treatment targets in older adults (≥75 years) remain controversial. Restricted mean survival time (RMST) analysis is an alternative to hazard ratios (decreased reliance on proportional hazards assumption) with an intuitive interpretation of a gain or loss in event-free days. This may be valuable when assessing effectiveness and safety of BP treatment as a function of age.

Purpose
Determine differences in event-free time (days) between intensive (≤120 mm Hg) and conservative (≤140 mm Hg) BP treatment stratified by age categories.

Methods
Post hoc analysis to estimate RMST using publicly available SPRINT trial dataset for the primary SPRINT composite cardiovascular outcome and a 6-point secondary safety outcome (hypotension, syncope, bradycardia, electrolyte abnormality, injurious falls, or acute kidney injury) that resulted in emergency department visits or serious adverse events.

Results
In 9,361 participants the average age was 67.9±9.4 years (≤64 years: n=4,216; 65–74 years: n=2794, ≥75 years: n=2351). Over 5 years, participants in the intensive arm had an extra 13.8 cardiovascular event-free days [(3.9 to 23.6), p=0.006]; this increased to 28.6 days [(3.6 to 53.7), p=0.025] in those ≥75 years. For the 6-point composite safety outcome, participants in the intensive arm had on average significantly fewer safety event-free days compared to the control arm [−37.6 days (−54.2 to −21.1)], p<0.0001; this decreased to −8.6 days [(−43.2 to 26.1), p=0.63] in those ≥75 years.
Restricted Mean Survival Time Age Category RMST (Intensive) RMST (Control) RMST (Intensive-Control Difference) P-value (Days, 95% CI) (Days, 95% CI) (Days, 95% CI) Primary SPRINT MACE Outcome   All Ages 1441.9 (1435.3 to 1448.5) 1428.1 (1420.9 to 1435.3) 13.8 (3.9 to 23.6) 0.006   <65 years 1411.9 (1404.9 to 1419.0) 1401.8 (1393.4 to 1410.1) 10.2 (−0.7 to 21.1) 0.07   65–74 years 1375.2 (1363.9 to 1386.5) 1369.5 (1358.1 to 1380.9) 5.7 (−10.4 to 21.8) 0.49   ≥75 years 1393.7 (1376.9 to 1410.5) 1365.1 (1346.5 to 1383.7) 28.6 (3.6 to 53.7) 0.025 Primary Composite Safety Outcome   All Ages 1370.9 (1358.7 to 1383.3) 1408.6 (1397.5 to 1419.7) −37.6 (−54.2 to−21.1) <0.0001   <65 years 1396.9 (1380.7 to 1413.1) 1439.2 (1425.6 to 1452.8) −42.2 (−63.4 to −21.1) <0.0001   65–74 years 1299.7 (1279.7 to 1319.7) 1347.5 (1330.5 to 1364.5) −47.8 (−74.0 to −21.5) <0.0001   ≥75 years 1187.6 (1162.8 to 1212.4) 1196.2 (1171.9 to 1220.4) −8.6 (−43.2 to 26.1) 0.63 RMST = restricted mean survival time; MAC = major adverse cardiovascular events.

Conclusions
Compared to controls, intensively treated older adults ≥75 years had larger gains in the primary cardiovascular outcome with similar losses in the composite safety outcome.

Acknowledgement/Funding
None
P5737Use of the IMPELLA mechanical support device in patients with acute myocardial infarction complicated by cardiogenic shock - Results of the CULPRIT-SHOCK trial
Authors: Zeymer U , Desch S , Akin I , Ouarrak T , De Waha-Thiele S , Montalescot G , Piek J J , Zahn R , Thiele H 
Published: October 2019

Abstract

Background
Mortality in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is still high despite the use of early revascularization therapy. While IABP support has been shown not improve outcome more effective mechanical support devices such as the IMPELLA are increasingly used. We sought to study the use of the IMPELLA device in patients with multivessel coronary artery disease and CS.

Methods
The CULPRIT-SHOCK shock trial included 686 patients with AMI complicated by cardiogenic shock and multivessel coronary artery disease treated with early PCI. Patients were randomized to immediate multivessel PCI or culprit lesion only PCI. In the current subanalysis, we investigated the patients treated with an IMPELLA support device compared these to patients without IMPELLA.

Results
Of the 686 patients 82 (12%) were treated with an IMPELLA device, 32 (39%) with IMPELLA 2.5 and 50 (61%) with IMPELLA CP. The device has been implanted in 34 patients before and 48 patients after PCI. The table shows the baseline characteristics of the patients with and without IMPELLA. In an unadjusted analysis mortality was higher with IMPELLA (63% versus 45.5%). Patients with IMPELLA CP had somewhat lower mortality than IMPELLA 2.5 (59.2% versus 68.8%), while there was no difference for pre- and post-PCI implantation.
IMPELLA (n=82) No IMPELLA (n=606) p-value Age (years) 70 68 0.17 Women 22.2% 23.3% 0.88 Diabetes 37.7% 31.8% 0.30 Triple vessel disease 66.7% 62.9% 0.13 Left main disease 28.4% 14.1% 0.001 LV-EF 31% 34% 0.18 Lactate on admission 20 mmol/l 8 mmol/l 0.0001 Multivessel PCI 50.6% 51.1% 0.9 Mechanical ventilation 88.9% 80.2% 0.06 SAPS-2 score 65 55 0.0008

Conclusion
Currently the IMPELLA support device is used primarily in patients with higher risk indicated by a higher incidence of left main disease, higher lactate on admission and higher SAPS II scores. This is associated with a higher mortality. Therefore randomized trials are needed to determine the effect of IMPELLA on outcome in patients with cardiogenic shock.
P5740ACE2 activity level is associated with embolic stroke of undetermined source
Authors: Sajeev J , Burrell L M , Dewey H , Kalman J M , Chou B , Frost T , Patel S K , Roberts L , Cooke J C , Gould M , Ngoh J , Koshy A N , Denver R , Teh A W 
Published: October 2019

Abstract

Background
ACE2 activity levels correlate with adverse left atrial remodelling in patients with atrial fibrillation (AF). Several biochemical and structural markers have been associated with embolic stroke of undetermined source (ESUS). The relationship between ACE2 activity and ESUS is unknown.

Purpose
Randomised controlled trials failed to demonstrate a clear benefit of oral anticoagulation in an unselected ESUS population. As selective use of oral anticoagulation guided by biomarker risk-profiling may benefit these patients, we evaluated the association between ACE2 activity and ESUS.

Methods
This prospective case control study compared patients with ESUS against a control group matched for vascular risk factors. ESUS was diagnosed following cerebral vascular imaging and 24 hours of cardiac monitoring to exclude AF. Blood samples were collected for measurement of ACE2 activity, D-Dimer and high sensitivity troponin T (hsTnT).

Results
A total of 51 patients in the ESUS group were compared with 47 patients in the Control group. ACE2 activity and D-Dimer levels were significantly higher in the ESUS group. There was a significant but weak positive correlation between ACE2 activity and hsTnT (r=0.20, p<0.05). Left atrial volume index (LAVI) on echocardiography was significantly higher in the ESUS group. On regression modelling adjusting for LAVI, only ACE2 activity remained significant for ESUS, with a 20% rise in odds for every 4 unit increase in ACE2 activity (OR 1.20; 95% CI: 1.01 - 1.36, p=0.04).
Participant characteristics Control (n=47) ESUS (n=51) P value Age (years) 65.65±6.78 67.20±6.89 0.26 Female gender 22 (45.8) 19 (38.0) 0.43 Hypertension 22 (45.8) 24 (48.0) 0.83 Diabetes mellitus 9 (18.8) 12 (24.0) 0.53 CHA2DS2VASc score 2 (1–3) 2 (1–3) 0.50 LA size & Biomarkers   LA volume index (ml/m2) 36.5 (32.6–42.5) 39.1 (36.2–46.0) 0.04   ACE2 (pmol/ml/min) 7.24 (2.66–14.64) 10.16 (4.54–18.80) 0.04   D-Dimer (mg/L) 0.35 (0.3–0.5) 0.40 (0.30–0.60) 0.02   hsTroponin T (ng/L) 7.0 (5–10) 9.00 (6.0–13.5) 0.05 Values are expressed as mean ± standard deviation, median (IQR), or n (%).
Median ACE2 activity

Conclusion(s)
ACE2 activity is associated with ESUS independent of left atrial volume and correlate with elevated Troponin. Further studies are warranted to investigate the utility of ACE2 activity in identifying ESUS patients that may benefit from oral anticoagulation.

Acknowledgement/Funding
This study received project funding from the Eastern Health Foundation
P5977Predicting significant ventricular arrhythmias in STEMI patients: never-ending challenge, still more place for myocardial deformation imaging?
Authors: Krljanac G , Trifunovic D , Asanin M , Savic Spasic L , Aleksandric S , Dudic J , Cucic L , Sulovic V , Mrdovic I 
Published: October 2019

Abstract

Background
Malignant ventricular arrhythmias in STEMI patients carry ominous prognosis including sudden cardiac death (SCD). According to the current guidelines only EF<35%, 40 days after STEMI, is indication for ICD implantation. Recently, index of myocardial dispersion (IMD) estimated by myocardial deformation imaging (speckle tracking echocardiography) was documented to provide better risk stratification.

Aim
To define whether quantification of myocardial mechanics early after pPCI using modern echocardiography offers information more to predict malignant arrhythmias during the first year after STEMI.

Methods
In the 226 consecutive STEMI patients (pts) 57.8±10.4yr, 71.7% males, in PREDICT-VT study (NCT03263949) treated with pPCI early echo (5±2 days) was done including conventional parameters and comprehensive speckle tracking LV deformation analysis with longitudinal (L), circumferential (C) strain (S;%) and strain rate (SR, 1/sec) and rotational LV mechanics. ROC analysis was performed to identify the best parameters to predict composite end-point defined as secondary VF, sustained/non-sustained VT and SCD, 48h after pPCI and during the first year of follow up.

Results
Twenty two patients (9.7%) reached the end-point. Classical parameters of LV systolic function, including LVEF, wall motion score index; global, systolic LS, CS and parameters of diastolic dysfunction were not significant predictors of the malignant arrhythmias. Early L SR, systolic C SR, IMD of global rotation and late rotation rate predicted the primary end-point (table).
Parameter ROC area 95% CI p Cutt-off Sens Spec Longirudinal mechanics   SR E (1/sec) 0.687 0.577–0.796 0.019 0.69 64 65   IMD S (ms) 0.752 0.666–0.838 0.002 66.1 71 72 Circumferencial mechanics   SR S (1/sec) 0.732 0.613–0.852 0.002 −1.22 71 67 Rotational mechanics   Global IMD (ms) 0.329 0.177–0.481 0.036 82.9 63 62   Late rotation rate IMD (ms) 0.318 0.196–0.442 0.026 41.1 65 64

Conclusion
Myocardial deformation imaging offers deeper insight into complex mechanical abnormalities during LV contraction and relaxation in longitudinal, circumferential and rotational directions (impaired and asynchronous deformations) in STEMI patients and predicts serious arrhythmic events.
P5995A novel biased S1P1 agonist improves renal and cardiac functions in ZSF1 rats, a model of metabolic syndrome-associated Heart Failure with preserved Ejection Fraction
Authors: Evaristi M F , Poirier B , Gillot F , Beeske S , Pruniaux M P , Janiak P , Parkar A 
Published: October 2019

Abstract

Background/Introduction
Heart Failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide with currently no approved treatment. Diastolic dysfunction, dyspnea, intolerance to effort, high cardiac filling pressure, and lung congestion coexist with normal ejection fraction in this clinical syndrome. Ageing, obesity, type 2 diabetes, hypertension and renal dysfunction are the main comorbidities found in this heterogeneous group of patients. Microvascular endothelial dysfunction, driven by these risk factors, may be a common link with other aspects of the HFpEF pathogenesis that include oxidative stress, inflammation, cardiomyocyte stiffness/hypertrophy, and myofibroblast accumulation. Sphingosine-1-phosphate type-1 receptor (S1P1), a G protein–coupled receptor highly expressed in endothelial cells, regulates vascular integrity, vascular development and immune cell trafficking. Compound A is a novel G protein-biased S1P1 agonist that lacks functional antagonism and has endothelial-protective properties.

Purpose
S1P1 activation could promote phosphorylation of endothelial nitric oxide synthase, restoration of endothelial structure and function, and thus diminish cardiac and vascular stiffness, hypertrophy and fibrosis. The aim of this study was to investigate if compound A could improve renal and cardiac functions in a rat model of HFpEF with metabolic syndrome.

Methods
65-week-old obese ZSF1 rats were fed a chow diet containing compound A (8 mg/kg/day) or no compound for 4 weeks. Lean ZSF1 and Wistar rats were included in the study as control groups. Urinary protein/creatinine ratio was measured as an index of glomerular injury. Cardiac hypertrophy and function were assessed by two-dimensional and Doppler echocardiography. Total cardiac and atrial weights and pulmonary edema were assessed.

Results
The obese ZSF1 rat was confirmed as a relevant model of HFpEF with advanced renal dysfunction. These rats showed severe glomerular filtration impairment, left ventricular and atrial hypertrophy and pulmonary edema. Cardiac systolic function, cardiac output and chamber volumes were preserved, diastolic function was impaired, and left ventricular posterior walls and septal thicknesses were increased compared to control groups. Four weeks of compound A treatment reduced urinary protein/creatinine ratio, blunted cardiac and atrial hypertrophy, and partially restored diastolic function. Circulating lymphocytes were not reduced by compound A, confirming that these pharmacological effects were not associated with S1P1 desensitization.

Conclusion
Compound A, a novel S1P1 agonist with endothelial properties, improves cardiac and renal functions in a rat model of metabolic syndrome-associated HFpEF. Sustained S1P1 activation with compound A may be a promising strategy for HFpEF treatment.
P5996HDAC inhibition improves myofibrillar relaxation and metabolism in a feline model of HFpEF
Authors: Wallner M , Eaton D , Berretta R , Wu J , Jeong M , Zhao H , Rainer P , Blass S , Von Lewinski D , Zuegner E , Zirlik A , Graier W , McKinsey T , Wolfson M , Houser S 
Published: October 2019

Abstract

Background
Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for about 50% of all cases of HF and there are currently no effective therapies.

Purpose
To assess the effects of histone deacetylase (HDAC) inhibition on cardiac and mitochondrial function and the plasma metabolome in a large mammalian model of slow-progressive pressure overload with features of HFpEF.

Methods
Male domestic short hair cats (n=26, aged 2mo), underwent either sham (S) procedures (n=5) or aortic constriction with a customized pre-shaped band (n=21), resulting in slow progressive pressure overload during growth. 2 months post-banding, animals were treated daily with either 10mg/kg suberoylanilide hydroxamic acid (b+SAHA) (n=8), a pan-HDAC inhibitor, or vehicle (b+veh) (n=8) for 2 months. Serial in-vivo cardiopulmonary phenotyping was performed monthly, and invasive hemodynamic and gas exchange parameters were evaluated 4 months post-banding. Ex-vivo myofibril mechanical studies and blood-based metabolomic profiling were performed. Data is presented as mean±SEM.

Results
Echocardiography at 4-months post-banding revealed that b+SAHA animals had a significant reduction in left ventricular hypertrophy (LVH) and LA size vs. b+veh animals. Left ventricular end-diastolic pressure (LVEDP) and mean pulmonary arterial pressure (mPAP) were significantly lower in b+SAHA vs. b+veh. SAHA treatment also improved ex-vivo myofibril relaxation independent of LVH and this effect correlated with in-vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, and improved lung compliance and oxygenation, reflected by a decrease in alveolar-capillary wall thickness and intrapulmonary shunt. SAHA treatment also reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar-capillary stress failure. Treatment with SAHA caused an increase in both oxygen consumption in-vivo and the percentage of type 1 skeletal muscle fibers (higher oxidative capacity). SAHA also increased mRNA levels of coactivators that regulate mitochondrial function and induced metabolic reprogramming towards mitochondrial oxidation preferentially utilizing fatty acids. SAHA treated HeLa cells showed a significant increase in oxidative phosphorylation and ATP production.
Effects of SAHA

Conclusion
These results show that slow-progressive pressure overload mimics critical features of HFpEF. SAHA can improve cardiac, pulmonary, and metabolic derangements caused by chronic pressure overload. Therefore, HDAC inhibition may be an interesting therapeutic strategy to treat the ever growing HFpEF population.

Acknowledgement/Funding
NIH [HL33921 to S.R.H, HL116848, HL127240 to T.A.M]; AHA [16SFRN31400013 to T.A.M.]; Medical University of Graz [M.W.], Stadt Graz [M.W.]